SMCLK SJMC 08 2022

VOLUMEN 3 • BROJ 2 • JUN 2022.
VOLUME 3 • NUMBER 2 • JUNE 2022

ISSN 2737-971X
eISSN 2737-9752
SRPSKI MEDICINSKI ČASOPIS

LEKARSKE KOMORE
SERBIAN JOURNAL
OF THE MEDICAL CHAMBER
VOLUMEN 3 • BROJ 2 • JUN 2022.

VOLUME 3 • NUMBER 2 • JUNE 2022
OSNIVAČ, VLASNIK, IZDAVAČ FOUNDER, OWNER & PUBLISHER
Lekarska komora Srbije Serbian Medical Chamber
Kraljice Natalije 1-3 1-3 Kraljice Natalije Street
11000 Beograd, Srbija 11000 Belgrade, Serbia
REDAKCIJA EDITORIAL OFFICE
Glavni i odgovorni urednik Editor-in-Chief
Prof. dr Milena Šantrić Milićević Prof. Milena Šantrić Milićević, MD, PhD
Zamenik glavnog urednika Deputy Editor-in-Chief
Prof. dr Goran Tulić Prof. Goran Tulić, MD, PhD
Pomoćnici glavnog i odgovornog urednika Assistant Editor-in-Chief
Prof. dr Predrag Đurđević Prof. Predrag Đurđević, MD, PhD
Prof. dr Milena Todorović Balint Prof. Milena Todorović Balint, MD, PhD
Doc. dr Aleksandra Ilić Asst. Prof. Aleksandra Ilić, MD, PhD
Dr sci. med Mlađan Golubović Mlađan Golubović, MD
Doc. dr Bojan Zarić Asst. Prof. Bojan Zarić, MD, PhD
Tehnički urednik Technical Editor
Doc. dr Zoran Bukumirić Asst. Prof. Zoran Bukumirić, MD, PhD
Sekretar Secretary
Asist. dr Aleksandra Radovanović Spurnić TA Aleksandra Radovanović Spurnić, MD, PhD
Lektor i prevodilac za srpski i engleski jezik Serbian and English Language Editor
Biljana Vukčević Lacković, prof. engleskog jezika Biljana Vukčević Lacković, lecturer
IZDAVAČKI SAVET PUBLISHER’S ADVISORY BOARD

Predsednik President
Asist. dr Danilo Jeremić TA Danilo Jeremić, MD
Članovi Members
Dr med Milan Dinić Milan Dinić, MD
Prof. dr Olga Popović Prof. Olga Popović, MD, PhD
Prof. dr Boris Đinđić Prof. Boris Đinđić, MD, PhD
Mr sci. med. Slađana Ilić Slađana Ilić, MD, MSc
Prof. dr Dejan Sakač Prof. Dejan Sakač, MD, PhD
Spec. dr med Ksenija Turković Ksenija Turković, MD
Spec. dr med Jasmina Pavlović Jasmina Pavlović, MD
ADRESA UREDNIŠTVA EDITORIAL OFFICE

Makenzijeva 53 53 Mackenzie Street
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126 Jun 2022. | Volumen 3 / Broj 2 | Srpski medicinski časopis Lekarske komore
UREĐIVAČKI ODBOR EDITORIAL BOARD
Predsednik President
Prof. dr Ivan Paunović Prof. Ivan Paunović, MD, PhD
Članovi Members
Akademik dr Vladimir Kostić Academician Vladimir Kostić
Akademik dr Nebojša Lalić Academician Nebojša Lalić
Akademik dr Predrag Peško Academician Predrag Peško
Prof. dr Milena Šantrić Milićević Prof. Milena Šantrić Milićević, MD, PhD
Prof. dr Zoran Baščarević Prof. Zoran Baščarević, MD, PhD
Prof. dr Eleonora Gvozdenović Prof. Eleonora Gvozdenović, MD, PhD
Prof. dr Goran Tulić Prof. Goran Tulić, MD, PhD
Prof. dr Dejan Nešić Prof. Dejan Nešić, MD, PhD
Prof. dr Mirjana Šumarac-Dumanović Prof. Mirjana Šumarac-Dumanović, MD, PhD
Prof. dr Milena Todorović Prof. Milena Todorović , MD, PhD
Prof. dr Lazar Velicki Prof. Lazar Velicki, MD, PhD
Prof. dr Bojan Zarić Prof. Bojan Zarić, MD, PhD
Prof. dr Dejan Ćelić Prof. Dejan Ćelić, MD, PhD
Prof. dr Oto Barak Prof. Oto Barak, MD, PhD
Prof. dr Predrag Đurđević Prof. Predrag Đurđević, MD, PhD
Prof. dr Svetlana Radević Prof. Svetlana Radević, MD, PhD
Prof. dr Vladimir Jurišić Prof. Vladimir Jurišić, MD, PhD
Doc. dr Zoran Bukumirić Asst. Prof. Zoran Bukumirić, MD, PhD
Doc. dr Aleksandra Ilić Asst. Prof. Aleksandra Ilić, MD, PhD
Doc. dr Nemanja Slavković Asst. Prof. Nemanja Slavković, MD, PhD
Doc. dr Marija Zdravković Asst. Prof. Marija Zdravković, MD, PhD
Doc. dr Željko Živanović Asst. Prof. Željko Živanović, MD, PhD
Doc. dr Danijela Jovanović Asst. Prof. Danijela Jovanović, MD, PhD
Asist. dr Andrej Ilanković TA Andrej Ilanković, MD, PhD
Asist. dr Aleksandra Radovanović Spurnić TA Aleksandra Radovanović Spurnić, MD, PhD
Asist. dr Kristina Davidović TA Kristina Davidović, MD
Asist. dr Slađana Mihajlović TA Slađana Mihajlović, MD, PhD
Asist. dr Igor Spurnić TA Igor Spurnić, MD
Asist. dr Boris Gluščević TA Boris Gluščević, MD
Asist. dr Marko Petrović TA Marko Petrović, MD
Dr sci. med Olga Vasović Olga Vasović, MD, PhD
Spec. dr med. Ivana Topalović Ivana Topalović, MD
Dr sci. med Goran Čitlučanin Goran Čitlučanin, MD, PhD
Serbian Journal of the Medical Chamber | Volume 3 / No. 2 | June 2022 127
EDITORIJAL
Poštovane koleginice i kolege,
Imam veliku čast, i još veće zadovoljstvo, da se u svoje ime, i u ime uredništva, obratim svim poštovaocima
našeg Časopisa i da vam predstavim još jedan broj Srpskog medicinskog časopisa Lekarske komore.
Uskoro se navršavaju dve godine od objavljivanja prvog broja našeg Časopisa. Početni koraci, u svakom poslu,
sami po sebi, uvek su komplikovani i teški, a naši su dodatno bili usložnjeni specifičnim društveno-zdravstvenim
prilikama uzrokovanim pandemijom KOVID-19 oboljenja. Navedeni uslovi su značajno uticali na motivisanost
stručne javnosti u kreiranju stručno-naučnih članaka, koji pak predstavljaju kamen temeljac razvoja i unapre-
đenja doktrine naše profesije. Stiče se utisak da su brojne prepreke u izradi Časopisa uspešno savladane, a po
kvalitetu, sadržaju i formi, svaki novi broj Časopisa prevazilazi onu prethodnu, što pruža osnov za veru da smo na
najboljem putu da kreiramo respektabilno stručno-naučno glasilo. Nadamo se, da će uz vašu pomoć, kao kruna
pažljivog i marljivog rada, doći i do brze kategorizacije našeg Časopisa.
I u ovom broju, Časopis nudi atraktivne teme koje će nam nesumnjivo biti od velike koristi u budućem sva-
kodnevnom radu.
Izdvajamo pregledni rad „Matične ćelije – opšti pregled: od razvojnih hemobioloških koncepata do (auto)
grafting-a u kliničkoj praksi“, Bele Balinta i saradnika, u kome se rekapituliraju ključne razvojne mogućnosti u
oblasti matičnih ćelija i njihovoj upotrebi u "konvencionalnim" transplantacijama ili u regenerativnoj medicini, uz
kratku kritičku ocenu istraživanja samih autora u ovoj oblasti.
Pandemija KOVID-19 oboljenja dovela je do velikih promena u zdravstvenim sistemima širom sveta, a čini se
da je organizacija primarne zdravstvene zaštite bila od ključnog značaja za ishod i tok bolesti kod mnogih paci-
jenata. Promene u primarnoj zdravstvenoj zaštiti, kao odgovor na pandemiju KOVID-19 oboljenja, prikazani su u
originalnom naučnom radu Lidije Šćepanović i saradnika. Nesumnjivo je da će ovo iskustvo imati primenu u svim
budućim epidemijama koje bi se mogle javiti.
Originalni naučni rad „Migracija dijagnostički srodnih grupa kao pokazatelj potencijalno neefikasne medicin-
ske intervencije“ autorke Marine Topalović i saradnika, ispituju pojavu migracija dijagnostički srodnih grupa (DSG
migracija), bolničke troškove i dužinu hospitalizacije kod kolektomija. U sprovedenoj retrospektivnoj sekundar-
noj analizi podataka o DSG migraciji, za serije bolničkih epizoda pacijenata, u trogodišnjem periodu, pokazano je
da kolektomije sa komplikacijama, u Republici Srbiji, produžavaju dužinu hospitalizacije i podrazumevaju veću
potrošnju resursa. Analiza troškova lečenja u vezi sa DSG migracijom, po bolničkom danu i pacijentu, veoma je
korisna, jer može ukazati na neefikasnost medicinskih intervencija ali i ukazati na neophodnost određenih korek-
cija u lečenju.
Rad „Antibiotska profilaksa u abdominalnoj hirurgiji - usaglašenost preporuka i prakse“ autorke Jelene Velič-
ković i saradnika, pokazuje da je usaglašenost kliničke prakse sa preporukama iz vodiča za antibiotsku profilaksu
u abdominalnoj hirurgiji na niskom nivou, a da je potpuna usaglašenost sa preporukama za primenu antibiotske
EDITORIAL
Dear colleagues,
On my own behalf and on behalf of the editorial staff, I have the great honor and even greater pleasure of
addressing all of the supporters of our Journal and presenting another issue of the Serbian Journal of the Medical
Chamber.
It will soon be two full years since the publishing of the first issue of the Journal. The first steps in any under-
taking are always difficult, and ours were additionally complicated by the exceptional social and health context
created by the COVID-19 pandemic. The conditions in such a context influenced the motivation of researchers to
write professional and scientific papers, which are the steppingstone of the development and improvement of our
profession’s doctrine. The impression is, however, that the numerous obstacles in producing the Journal have been
overcome, and that each new issue of the Journal surpasses the previous one, in quality, content, and form, which
provides the foundation for our faith that we are on the right course towards creating a reputable professional and
scientific publication. We hope that, with your help, our Journal will soon be categorized, which would be the pin-
nacle of our meticulous and hard work.
As was the case in previous issues, in this issue the Journal again offers interesting topics which will undoubte-
dly be very useful to all of us in our future work.
We would like to highlight the review paper A stem cell overview – from evolving hemobiological concepts to
(auto)grafting in clinical practice, written by Bela Balint et al., which provides an overview of the key development
possibilities in the field of stem cell application in ‘conventional’ transplantations or in regenerative medicine, as
well as a short critical assessment of the research performed in this area by the authors themselves.
The COVID-19 pandemic led to great changes in healthcare systems all over the world, and it seems that the
organization of primary health care was of crucial importance for the outcome and course of the disease, in many
patients. The changes in primary health care, which happened in response to the COVID-19 pandemic, are pre-
sented in this original research paper written by Lidija Šćepanović et al. Undoubtedly, this experience will find its
application in any future epidemics that may occur.
The original research paper Diagnosis related group migration as an indicator of a potentially inefficient medical inter-
vention, written by Marina Topalović et al., investigates the occurrence of diagnosis related group migration (DRG mi-
gration), hospital expenses, and the length of hospital stay in colectomy. In the retrospective secondary analysis of data
on DRG migration, for a series of in-hospital patient episodes, over a three-year follow-up period, it was shown that, in
the Republic of Serbia, colectomies with complications prolong the duration of hospital stay and require a greater con-
sumption of resources. Cost analysis of DRG-related treatment, per patient and per day of hospital stay (patient day), is
very useful, as it can indicate inefficiency of medical interventions, but also the necessity of certain changes in treatment.
The paper Antibiotic prophylaxis in abdominal surgery – compliance with international guidelines, written by Jelena
Veličković et al., shows that the compliance of clinical practice with the guidelines is low, while full compliance with
the recommendations for antibiotic prophylaxis has been recorded only with regards to the route of antibiotic ad-
ministration. This original research paper confirms the need for constant education of clinicians on the application
of antibiotic therapy, with the aim of reducing antibiotic resistance and implementing the proper use of these drugs.
profilakse zabeležena samo po pitanju puta primene antibiotika. Ovaj originalni naučni rad potvrđuje potrebu za
stalnom edukacijom kliničara o primeni antibiotske terapije, kako bi se smanjila antibiotska rezistencija i savlada-
la pravilna upotreba ovih lekova.
Značaj multidetektorske kompjuterizovane tomografije (MDCT) u otkrivanju, praćenju i izboru terapije akut-
nog moždanog udara opisan je u radu Aleksandre Obreški. Prikazani su prednosti i nedostaci ranih MDCT pregle-
da u dijagnostici akutnog moždanog udara, na osnovu praćenja svih pacijenata koji su se u određenom vremen-
skom periodu javili službi Urgentnog centra, usled nastanka akutnog neurološkog deficita.
„Funkcionisanje, onesposobljenost i vežbe kod starih“ je rad Milene Kostadinović koji pokazuje da održavanje
fizičkog i mentalnog zdravlja, zajedno sa prevencijom i smanjenjem invaliditeta kod starije populacije, treba da
bude jedan od važnih aspekata kvalitetnog starenja. Autori naglašavaju da je, prilikom planiranja i sprovođenja fi-
zičke aktivnosti, posebno kod starije populacije, važna procena trajanja, učestalosti, intenziteta i režima vežbanja.
Revijalni rad Uroša Dabetića i saradnika „Principi lečenja preloma karlice kod politraumatizovanih pacijenata“
govori o jednom od najvećih izazova u ortopedskoj hirurgiji i traumatologiji, sa ciljem da proceni trenutne stan-
darde zbrinjavanja preloma karlice, kao i da ukaže na moguću strategiju poboljšanja krajnjeg ishoda lečenja.
U svom radu, Katarina Vukosavljević teorijski razmatra značaj multidisciplinarnog dijagnostičkog i terapijskog
pristupa sindromu bolne simfize sportista. Iako je u literaturi izneto više od 70 uzroka nastanka pubalgije, posta-
vljanje dijagnoze je teško, zbog složene anatomije i preklapanja simptoma među različitim povredama prepona.
Terapijski pristup je uslovljen složenošću povreda i dinamikom oporavka pacijenta. Kako kod nastanka pubalgije
dolazi do onesposobljavanja u sportskim aktivnostima u produženom periodu, neophodno je pažnju posvetiti
prevenciji nastajanja ovog bolnog sindroma.
Uvek atraktivni, poučni i zanimljivi prikazi retkih slučajeva, nalaze se i u ovoj svesci Časopisa.
Dejan Lazović i saradnici prikazuju redak i zanimljiv slučaj koronarno-kameralne fistule (koja predstavlja ano-
malnu vezu između koronarne arterije i srčane komore) kod pacijentkinje sa anginom pektoris. Autori u radu
razmatraju i daju preporuke za kliničko praćenje, ali i pristup lečenju kod ovih abnormalnih nalaza.
Milan Dokić i saradnici prikazuju ekstremno gojaznu pacijentkinju kod koje je zbog produženog vaginalnog
krvarenja i anemije učinjena totalna histerektomija laparoskopskom hirurgijom. Ovaj rad ističe značaj i sve češću
primenu laparoskopske hirurgije u praksi, čak i u najtežim kliničkim slučajevima i hitnim situacijama, stavljajući
akcenat na važnost stručno obučenog tima uz postojanje odgovarajuće tehničke opreme.
Primena kortikosteroidne terapije, posebno visokih doza, kod nekih hematoloških pacijenata, predstavlja te-
rapiju prvog izbora u cilju stabilizacije bolesti. Milica Apostolović Stojanović i saradnici prikazuju pacijentkinju sa
hroničnom limfocitnom leukemijom, kod koje je, nakon primene visoke doze intravenskog metilprednizolona,
došlo do kardiotoksičnosti, što se manifestovalo pojavom atrijalne fibrilacije. Pored različitih negativnih efekata
do kojih mogu da dovedu visoke doze kortikosteroida, kardiotoksičnost se mora razmatrati kod svakog pacijenta
ponaosob, jer može da dovede do akutnih i teških stanja, koja zahtevaju hitnu a nekada i vitalnu terapiju.
„Stečena hemofilija kod bolesnika na oralnoj antikoagulantnoj terapiji“ autorke Jelene Ljubičić, još jedan je u
nizu prikaza slučaja bolesnika u ovom broju Časopisa. Ovaj rad ima za cilj da pobudi sumnju kod kliničara da kod
bolesnika koji primaju oralnu antikoagulantnu terapiju, hemoragijski sindrom može biti različite etiologije, što je
veoma važno u daljem zabrinjavanju i lečenju ovih bolesnika.
Željko Garabinović i saradnici u svom radu prikazuju lečenje bilateralnog pneumotoraksa u trudnoći, uzro-
kovanog limfangioleiomiomatozom, minimalno invazivnom torakoskopskom hirurgijom, ukazujući na to da
prilikom lečenja pneumotoraksa u trudnoći treba primeniti adekvatnu terapijsku proceduru, vodeći računa o
bezbednosti trudnoće i porođaja.
Srpski medicinki časopis Lekarske komore je i u ovoj svesci, uz pomoć naših cenjenih kolega, opravdao sva
naša očekivanja. Sa istim entuzijazmom i u istom smeru nastavljamo dalje, sa verom da ćemo zajedničkim trudom
uspeti u promociji vrhunskih profesionalnih vrednosti.
S poštovanjem,
Kl. ass. dr sc. med. Aleksandra Radovanović Spurnić
Sekretar Srpskog medicinskog časopisa Lekarske komore
The importance of multidetector computed tomography (MDCT) in detecting, monitoring, and choosing the
treatment of acute stroke is described in the paper written by Aleksandra Obreški. The advantages and disadvanta-
ges of early MDCT examinations in the diagnostics of acute stroke, based on the monitoring of all patients who re-
ported to the Emergency Department during a certain period of time, due to the occurrence of acute neurological
deficit, are presented in this paper.
Functioning, disability and exercise in the elderly is a paper written by Milena Kostadinović, which shows that the
maintenance of physical and mental health, together with the reduction of disability in the elderly, should be one
of the important aspects of successful aging. The authors point out that in planning and implementing a physical
activity, especially in the older population, the important factors that need to be considered include duration, fre-
quency, intensity and mode.
The review article written by Uroš Dabetić et al. Principles of pelvic fracture treatment in polytrauma patients,
describes one of the greatest challenges in orthopedic surgery and traumatology, with the aim of evaluating the
current standards of treating pelvic fractures, as well as pointing out the possible strategy in improving the final
outcome of treatment.
In her paper, Katarina Vukosavljević theoretically analyzes the importance of a multidisciplinary diagnostic and
therapeutic approach to painful symphysis syndrome in athletes. Although more than 70 causes of pubalgia have
been described in literature, establishing a diagnosis is difficult, due to the complex anatomy and the overlapping
of symptoms among different groin injuries. The therapeutic approach depends on the complexity of the injuries
and the dynamics of the patient's recovery. Bearing in mind that the occurrence of pubalgia prevents the patients
from engaging in sports activities over a prolonged period, attention should be directed towards the prevention of
this painful syndrome.
The always interesting, instructive, and informative case reports of rare cases can be found in this issue of the
Journal, as well.
Dejan Lazović et al. present a rare and interesting case of coronary-cameral fistula (which is an anomalous con-
nection between a coronary artery and a cardiac chamber) in a patient with angina pectoris. In the paper, the authors
analyze and offer recommendations for clinical follow-up and the therapeutic approach in such abnormal findings.
Milan Dokić et al. describe the case of an extremely obese female patient, in whom total hysterectomy with
laparoscopic surgery was performed, due to prolonged vaginal bleeding and anemia. This paper stresses the im-
portance and the more and more frequent use of laparoscopic surgery in clinical practice, even in the most difficult
clinical cases and emergency situations, emphasizing the importance of a well-trained professional team and the
availability of appropriate equipment.
The application of corticosteroid therapy, especially high-dose therapy, is the treatment of choice in some he-
matological patients, for the purpose of stabilizing the disease. Milica Apostolović Stojanović et al. present the case
of a patient with chronic lymphocytic leukemia, in whom cardiotoxicity occurred and manifested in the form of
atrial fibrillation, after the administration of a high dose of intravenous methylprednisolone. In addition to different
adverse effects which can be caused by high doses of corticosteroids, cardiotoxicity must be considered in each
patient individually, as it can lead to acute and severe conditions, which may require urgent and sometimes life-su-
staining treatment.
Acquired hemophilia in patients on oral anticoagulant therapy, written by Jelena Ljubičić, is another in the series
of case reports in this issue of the Journal. This paper aims to alert clinicians to the fact that, in patients on oral
anticoagulant therapy, hemorrhagic syndrome can vary in its etiology, which is of great importance in further tre-
atment and care for the patient.
In their paper, Željko Garabinović et al. present the treatment of bilateral pneumothorax in pregnancy, caused
by lymphangioleiomyomatosis, with minimally invasive thoracoscopic surgery. At the same time, the authors emp-
hasize that, when treating pneumothorax in pregnancy, the appropriate therapeutic procedure should be applied,
taking into account the safety of the pregnancy and of the delivery.
With the help of our esteemed colleagues, the current issue of the Serbian Journal of the Medical Chamber has,
yet again, met all of our expectations. With the same enthusiasm and on the same course, we continue our work
convinced that, with your help, we will continue to promote the highest professional standards.
Sincerely,
TA Aleksandra Radovanović Spurnić, MD, PhD
Secretary of the Serbian Journal of the Medical Chamber
sadržaj
PO IZBORU UREDNIKA EDITOR’S CHOICE

Bela Balint, Mirjana Pavlović, Olivera Marković, Saša Borović, Milena Todorović
MATIČNE ĆELIJE – OPŠTI PREGLED: OD RAZVOJNIH HEMOBIOLOŠKIH KONCEPATA DO
(AUTO)GRAFTING-a U KLINIČKOJ PRAKSI
A STEM CELL OVERVIEW – FROM EVOLVING HEMOBIOLOGICAL CONCEPTS TO
(AUTO)GRAFTING IN CLINICAL PRACTICE........................................................................................................................................... 135
ORIGINALNI RADOVI ORIGINAL ARTICLES

Lidija Šćepanović, Nataša Terzić
PROMENE U PRIMARNOJ ZDRAVSTVENOJ ZAŠTITI KAO ODGOVOR NA PANDEMIJU
KOVID-19 OBOLJENJA U CRNOJ GORI
CHANGES IN PRIMARY HEALTH CARE IN RESPONSE TO
THE COVID-19 PANDEMIC IN MONTENEGRO ........................................................................................................................... 149
Marina Topalović, Mirjana Milošević, Zorica Terzić-Šupić, Jovana Todorović, Milena Šantrić Milićević
MIGRACIJA DIJAGNOSTIČKI SRODNIH GRUPA KAO POKAZATELJ
POTENCIJALNO NEEFIKASNE MEDICINSKE INTERVENCIJE
DIAGNOSIS RELATED GROUP MIGRATION AS AN INDICATOR OF A
POTENTIALLY INEFFICIENT MEDICAL INTERVENTION . ........................................................................................................ 159
Jelena Veličković, Suzana Sredić, Aleksandra Radovanović Spurnić, Igor Lazić, Ivan Palibrk, Vesna Mioljević, Slavenko Ostojić
ANTIBIOTSKA PROFILAKSA U ABDOMINALNOJ HIRURGIJI - USAGLAŠENOST PREPORUKA I PRAKSE
IANTIBIOTIC PROPHYLAXIS IN ABDOMINAL SURGERY – COMPLIANCE
WITH INTERNATIONAL GUIDELINES ............................................................................................................................................ 173
Aleksandra Obreški, Ana Papović, Jovo Paskaš, Ana Stanković, Danilo Jeremić, Kristina Davidović
ZNAČAJ MULTIDETEKTORSKE KOMPJUTERIZOVANE TOMOGRAFIJE U OTKRIVANJU,
PRAĆENJU I IZBORU TERAPIJE KOD AKUTNOG MOŽDANOG UDARA
THE IMPORTANCE OF MULTIDETECTOR COMPUTED TOMOGRAPHY
IN ACUTE STROKE DETECTION, MONITORING AND SELECTION OF THERAPY . ......................................................... 183
PREGLEDNI RADOVI REVIEW ARTICLES

Milena Kostadinović, Sunčica Dedović, Filip Milanović, Nikola Aksović, Dejan Nikolić
FUNKCIONISANJE, ONESPOSOBLJENOST I VEŽBE KOD STARIH
FUNCTIONING, DISABILITY AND EXERCISE IN THE ELDERLY ............................................................................................. 191
Uroš Dabetić, Danilo Golubović, Jovana Grupković, Marko Ilić, Dejan Aleksandrić, Goran Tulić
PRINCIPI LEČENJA PRELOMA KARLICE KOD POLITRAUMATIZOVANIH PACIJENATA
PRINCIPLES OF PELVIC FRACTURE TREATMENT IN POLYTRAUMA PATIENTS . ............................................................ 200
contents
STRUČNI RAD PROFESSIONAL ARTICLE

Katarina Vukosavljević, Miloš Bojović, Dragana Drljačić, Kristina Vukušić
ZNAČAJ MULTIDISCIPLINARNOG DIJAGNOSTIČKOG I TERAPIJSKOG PRISTUPA
SINDROMU BOLNE SIMFIZE SPORTISTA
THE IMPORTANCE OF A MULTIDISCIPLINARY DIAGNOSTIC AND THERAPEUTIC
APPROACH TO PAINFUL SYMPHYSIS SYNDROME IN ATHLETES ...................................................................................... 209
PRIKAZI SLUČAJEVA CASE REPORTS
Dejan M. Lazović, Mladen Kočica, Ivana Đurošev, Milica Kočica-Karadžić, Dragan Cvetković
ZANIMLJIV SLUČAJ KORONARNO-KAMERALNE FISTULE SA ANGINOM PEKTORIS
AN INTERESTING CASE OF CORONARY-CAMERAL FISTULA WITH ANGINA PECTORIS............................................ 220
Milan Dokić, Dragiša Šljivančanin, Sandra Babić, Branislav Milošević

EKSTREMNA GOJAZNOST I TOTALNA LAPAROSKOPSKA HISTEREKTOMIJA - PRIKAZ SLUČAJA
EXTREME OBESITY AND TOTAL LAPAROSCOPIC HYSTERECTOMY – CASE REPORT.................................................. 224
Milica Apostolović Stojanović, Milica Radojković, Aleksandar Stojanović, Vladan Vukomanović

KARDIOTOKSIČNOST VISOKE DOZE METILPREDNIZOLONA KOD BOLESNIKA SA
HRONIČNOM LIMFOCITNOM LEUKEMIJOM – PRIKAZ SLUČAJA
CARDIOTOXICITY OF HIGH-DOSE METHYLPREDNISOLONE IN PATIENTS WITH
CHRONIC LYMPHOCYTIC LEUKEMIA – A CASE REPORT....................................................................................................... 228
Jelena Ljubičić
STEČENA HEMOFILIJA KOD BOLESNIKA NA ORALNOJ ANTIKOAGULANTNOJ TERAPIJI - PRIKAZ SLUČAJA
ACQUIRED HEMOPHILIA IN PATIENTS ON ORAL ANTICOAGULANT THERAPY – CASE REPORT........................... 234
Željko Garabinović, Nikola Čolić, Jelena Vasić Madžarević, Milan Savić

MINIMALNO INVAZIVNA TORAKOSKOPSKA HIRURGIJA KAO DIJAGNOSTIČKI I TERAPIJSKI PRISTUP
KOD BILATERALNOG PNEUMOTORAKSA U TRUDNOĆI UZROKOVANOG LIMFANGIOLEIOMIOMATOZOM
– PRIKAZ SLUČAJA
MINIMALLY INVASIVE THORACOSCOPIC SURGERY AS A DIAGNOSTIC AND THERAPEUTIC
APPROACH IN BILATERAL PNEUMOTHORAX IN PREGNANCY CAUSED BY
LYMPHANGIOLEIOMYOMATOSIS – A CASE REPORT.............................................................................................................. 241
UPUTSTVO AUTORIMA INSTRUCTIONS FOR AUTHORS
MATIČNE ĆELIJE – OPŠTI PREGLED: OD RAZVOJNIH HEMOBIOLOŠKIH
KONCEPATA DO (AUTO)GRAFTING-a U KLINIČKOJ PRAKSI
PO IZBORU UREDNIKA EDITOR’S CHOICE
A STEM CELL OVERVIEW – FROM EVOLVING HEMOBIOLOGICAL

CONCEPTS TO (AUTO)GRAFTING IN CLINICAL PRACTICE
Bela Balint1,2, Mirjana Pavlović3, Olivera Marković4,5, Saša Borović2, Milena Todorovic5,6
1
Odeljenje medicinskih nauka, Srpska akademija nauka i 1
Department of Medical Sciences, Serbian Academy of Sciences
umetnosti and Arts
2
Institut za kardiovaskularne bolesti "Dedinje", Beograd, Srbija 2
Dedinje Cardiovascular Institute, Belgrade, Serbia
3
Department of Computer and Electrical Engineering and 3
Department of Computer and Electrical Engineering and
Computer Science, FAU, Boca Raton, USA Computer Science, Florida Atlantic University, Boca Raton, USA
4
Odeljenje za hematologiju sa onkohematologijom, Klinika za 4
Department of Hematology with Oncohematology, Clinic of
internu medicinu, Kliničko-bolnički centar "Bežanijska kosa", Internal Medicine, Clinical-Hospital Center "Bezanijska kosa",
Beograd, Srbija Belgrade, Serbia
5
Medicinski fakultet, Univerzitet u Beogradu, Srbija; 5
Faculty of Medicine, University of Belgrade, Serbia
6
Klinika za hematologiju, Univerzitetski klinički centar Srbije, 6
Clinic for Hematology, University Clinical Center of Serbia,
SAŽETAK ABSTRACT
Konvencionalna transplantacija matičnih ćelija hematopoeze (MĆH) je dobro poznat me- Conventional hematopoietic stem cell transplantation is a well-known treatment method
tod lečenja brojnih stečenih i urođenih poremećaja hematopoeze, poremećaja imunskog for numerous acquired and congenital hematopoietic disorders, disorders of the immune
sistema, kao i određenih metaboličkih oboljenja. Matične ćelije (MĆ) se mogu definisati system, as well as certain metabolic disorders. Stem cells (SCs) can be defined as cells ca-
kao ćelije koje imaju sposobnost samoobnavljanja i koje poseduju visoki proliferativni ka- pable of self-renewal with a high proliferative capacity and the potential to differentiate
pacitet, kao i potencijal da se diferentuju u funkcionalno kompetentne zrele ćelije. MĆ se into functionally competent mature cells. Stem cells can be divided into embryonic SCs
mogu podeliti na embrionalne MĆ (EMĆ) i tkivno operdeljene, odnosno adultne MĆ – kao (ESCs) and tissue-specific or adult SCs – such as bone marrow (BM) stem cells, peripheral
što su one iz kostne srži, periferne krvi i iz krvi pupčane vrpce, kao i druge ne-hematopoet- blood (PB) stem cells, and SCs derived from umbilical cord blood (UCB), as well as other
ske odnosno somatske ćelije. Kod odraslih, MĆ se obično smatraju ograničenim po pitanju non-hematopoietic or somatic SCs. SCs in adults are characteristically considered to be
njihovog regenerativnog potencijala i potencijala diferentovanja, dok su EMĆ „prave“ toti- restricted in their regenerative and differentiative potential, while embryonic stem cells
potentne/pluripotentne ćelije, jer imaju sposobnost da se razviju i u endoderm, ektoderm are ‘true’ totipotent/pluripotent cells, due to their ability to develop into endoderm, ec-
i mezoderm – tj. u sva tri tipa embrionalnog tkiva u ljudskom organizmu. Među MĆ koje se toderm, or mesoderm – all three embryonic tissue types in the human body. They are the
potencijalno mogu presaditi, ove ćelije predstavljaju vrstu koja najviše obećava, ali i koja most promising, but also the most controversial type of potentially transplantable SCs.
je i najkontroverznija. Manje zrele ili primitivnije MĆH imaju potencijal da se diferentuju, Immature hematopoietic SCs have the potential of differentiating, not only into all blood
ne samo u sve vrste ćelija krvi, već i u neke vrste somatskih ćelija (plastičnost MĆ). U razli- cells, but also into some somatic cell types (SC plasticity). In different clinical settings, the
čitim kliničkim uslovima, transplantacija nezrelih (primitivnih) MĆ dovodi do repopulacije transplantation of immature stem cells leads to the repopulation of recipient bone marrow,
kostne srži primaoca transplantata, uz kasniju potpunu, stabilnu i dugoročnu rekonstitu- with subsequent complete, stable, and long-term reconstitution of hematopoiesis. Given
ciju hematopoeze. Imajući u vidu da su primitivne ćelije takođe sposobne za ukalemljenje that immature stem cells are also capable of homing to different tissues, autologous
(homing) u različita tkiva, autologna implantacija MĆ u oštećeno i/ili ishemično područje stem cell implantation into a damaged and/or ischemic area induces their colonizing and
indukuje njihovo naseljavanje i sledstveno transdiferentovanje u ćelijske linije organa consecutive transdifferentiating into cell lineages of the host organ, including neovascu-
domaćina, uključujući i neovaskularizaciju. Stoga su one klinički primenljive u oblasti re- larization. Thus, they are clinically applicable in the field of regenerative medicine for the
generativne medicine, u lečenju tkivnih oštećenja miokarda, mozga, krvnih sudova, jetre, treatment of myocardial, brain, vascular, liver, pancreatic, and other tissue damage. The
pankreasa i drugih tkiva. Svrha ovog pregleda jeste rekapitulacija ključnih otkrića u oblasti purpose of this overview is to recapitulate the key developments in the rapidly evolving
istraživanja MĆ, koja je u fazi ubrzanog razvoja. U radu je dat i pregled primene MĆ u tzv. area of stem cell research, as well as to review the use of SCs in conventional transplan-
konvencionalnim transplantacijama i u regenerativnoj medicini. Uz to, dat je i sažet kritički tations and in regenerative medicine. Additionally, a brief critical evaluation of our own
osvrt na naša sopstvena istraživanja u oblasti MĆ. stem cell research will be summarized.
Ključne reči: matične ćelije, plastičnost matičnih ćelija, transplantacija, regenerativna Key words: stem cells, SC plasticity, transplantation, regenerative medicine
medicina
Autor za korespondenciju: Corresponding author:

Bela Balint Bela Balint
Srpska akademija nauka i umetnosti Serbian Academy Of Sciences And Arts
Kneza Mihaila 35, 11000 Beograd, Srbija 35 Kneza Mihaila Street, 11000 Belgrade, Serbia
Elektronska adresa: balintbela52@yahoo.com E-mail: balintbela52@yahoo.com
Primljeno • Received: March 17, 2022; Revidirano • Revised: April 21, 2022; Prihvaćeno • Accepted: April 28, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-37014
matične ćelije – opšti pregled: od razvojnih hemobioloških koncepata do (auto)grafting-a u kliničkoj praksi
Balint B. i sar.
a stem cell overview – from evolving hemobiological concepts to (auto)grafting in clinical practice
UVOD INTRODUCTION
Multiciklična i trajna citopoeza jeste proces razvoja Multicyclic and permanent cytopoiesis is the process
i ekspanzije velikog broja progenitora i prekursora, of cell development or expansion of a large number
kao i zrelih ćelija, iz malog broja nediferentovanih of progenitors and precursors, as well as mature cells,
(primitivnih) matičnih ćelija (MĆ), in vivo ili ex vivo from a small number of undifferentiated (immature)
[1–3]. Uopšteno gledano, MĆ obezbeđuju stabilnu stem cells (SCs), in vivo or ex vivo [1–3]. Generally,
homeostazu u svakom sistemu koji produkuje tki- SCs guarantee steady-state homeostasis in every tis-
va. Dugo se verovalo da su samo embrionalne MĆ sue-generating system. It has been believed for a long
(EMĆ) totipotentne/pluripotentne, pošto je plastič- time that only embryonic SCs (ESCs) are totipotent/
nost MĆ od ključnog značaja za rani razvoj. Stoga se pluripotent, since SC plasticity is essential in early de-
dugo vremena smatralo da ćelijsku totipotentnost/ velopment. Thus, for a long time, cellular totipotency/
pluripotentnost poseduju samo specifične EMĆ. No, pluripotency was considered a property of only specif-
najprimitivniji odeljci MĆ kod odraslih takođe imaju ic ESCs. However, the most primitive adult SC compart-
gotovo „neograničeni“ potencijal samoobnavljanja, ments also have comparatively ‘limitless’ self-renewal
kao i sposobnost da prelaze u druge ćelijske linije (in- potential, as well as the ability to ‘switch’ into other cell
ter-sistemska plastičnost) [2–6]. lineages (inter-systemic SC plasticity) [2–6].
Tokom citopoeze, odigravaju se uravnoteženi pro- During cytopoiesis, a complex system of interac-
cesi složenog sistema interaktivnih supstanci, citokina, tive substances, cytokines, growth factors, and inhib-
faktora rasta i inhibitora. Delimični ili potpuni gubitak itors is regulated and balanced. A partial or complete
uravnotežene regulacije može dovesti do nekontroli- loss of balanced control can lead to uncontrolled cell
sanog rasta ćelija ili njene smrti. Vremenom, odnosno growth or death. Over time, i.e., with ageing, SC activ-
starenjem, aktivnost MĆ opada, rezultujući manjim re- ity leads to gradual deterioration of the regenerative
generativnim potencijalom ćelija i tkiva, te redukcije i potential of cells and tissues and the decline of organ
sposobnosti obnavljanja organa, što se manifestuje u repair/renewal capacity, manifesting as disease and tis-
vidu bolesti odnosno defekata u tkivima, uključujući tu sue defects, including cancer [2–4].
i karcinome [2–4]. Hematopoiesis is a dynamic hemobiological process,
Hematopoeza je dinamički hemobiološki proces u wherein a large quantity of all the types of blood cells is
kojem se velika količina svih vrsta krvnih ćelija nasta- produced from very primitive hematopoietic SCs (HSCs).
je iz populacije primitivnih MĆ hematopoeze (MĆH). HCSs are distributed to different hematopoietic compart-
One se distribuiraju u različite hematopoetske odeljke ments throughout the body, during fetal development
u organizmu tokom fetalnog razvoja i adultnog života. and adult life. The bone marrow (BM) of adults, as a pri-
Kostna srž odraslih, kao primarna lokacija, ima visoki mary location, has a high potential of differentiation into
potencijal diferentovanja u pluripotentne i opredelje- pluripotent and committed progenitors, which finally
ne progenitore, koji se na kraju transformišu u različi- transform into various mature blood cells, necessary for
te zrele ćelije krvi, neophodnih za obnavljanje krvi i za blood turnover and the fight against infections [7–15].
borbu protiv infekcija [7–15]. Intrinsic genetic pathways control hematopoiesis.
Unutrašnji genetski putevi kontrolišu hematopo- Interactive extrinsic signals from the extracellular ma-
ezu. Osnovni genetički putevi regulišu interaktivne trix (ECM) and other signaling molecular pathways,
spoljašnje signale iz ekstracelularnog matriksa i osta- as well as the stromal cell microenvironment are reg-
le signalne molekularne puteve, kao i mikrosredinu ulated by basic genetic pathways [2,11–14]. The role
stromalnih ćelija [2,11–14]. Uloga stromalnih ćelija, of stromal cells, including macrophages, fibroblasts,
uključujući makrofage, fibroblaste, dendritske, endo- dendritic, endothelial, and other cells, is to stimulate
telske i druge ćelije, jeste da stimulišu MĆ. Naime, ove SCs. Namely, these stromal cells stimulate SCs by pro-
stromalne ćelije stimulišu MĆ oslobađanjem specifič- ducing specific growth factors, such as the Flt3-ligand,
nih faktora rasta, kao što su Flt3-ligand, c-kit-ligand ili c-kit-ligand or SC-factor, as well as interleukins, gran-
SC-factor, kao i interleukini, faktor stimulacije kolonije ulocyte-macrophage colony-stimulating factor and
granulocita-makrofaga (engl. granulocyte-macrophage granulocyte colony-stimulating factor (GM-CSF and
colony-stimulating factor – GM-CSF) i faktor stimulacije G-CSF). In addition to secreting cytokines, stromal cells
kolonija granulocita (engl. granulocyte colony-stimula- regulate the adhesion of SC molecules and allow them
ting factor – G-CSF). Uz lučenje citokina, stromalne će- to stay in the BM or migrate to the area where the re-
lije regulišu i adheziju molekula MĆ i omogućavaju im spective cell type is needed [14–19].
da ostanu u kostnoj srži ili da migriraju u ono područje Populations of HSCs, also named CD34+ cells, ex-
gde je dati tip ćelije potreban [14–19]. press the CD34 antigen. Namely, CD34 is the name
Balint B. et al.
Populacije MĆH, označene i kao CD34+ ćelije, iska- given to a transmembrane glycoprotein present on
zuju (ekspresija) antigen CD34. Naime, CD34 je ime the surface of HSCs and some stromal cells. Adult cells
koje je dato transmembranskom glikoproteinu, pri- expressing the CD34 antigen, obtained from BM or pe-
sutnom na površini MĆH, ali i nekih stromalnih ćelija. ripheral blood (PB), stimulate complete and long-term
Adultne ćelije koje eksprimuju CD34 antigena, a koje repopulation of the recipient's bone marrow (follow-
su poreklom iz kostne srži ili periferne krvi, omoguća- ing engraftment), with subsequent hematopoietic re-
vaju kompletnu i dugotrajnu repopulaciju kostne srži constitution [16–21].
primaoca (nakon prihvatanja kalema), sa sledstvenom Traditionally, SC transplantation involves intensive
rekonstitucijom hematopoeze [16–21]. radiochemotherapy (myeloablation) coupled with
Po pravilu, transplantacija MĆ uključuje intenzivnu infusion of collected cells, which is done in order to
radiohemoterapiju (mijeloablacija) uz infuziju priku- achieve the eradication of the underlying disease and/
pljenih ćelija, što se sprovodi da bi se postigla elimina- or eliminate certain disorders, as well as improve the
cija osnovne bolesti i/ili eliminisali određeni poreme- clinical status of the patient. Patients who are ineligible
ćaji, kao i da bi se poboljšalo kliničko stanje bolesnika. for high-dose radio-chemotherapy because of their
Kod bolesnika, kod kojih ne može biti primenjena vi- age or comorbidity, may be offered a similar procedure
sokodozna radiohemoterapija zbog starosti ili komor- with reduced-intensity conditioning (RIC) [1–3,8,9]. In
biditeta, može biti sprovedena procedura kondicioni- order to be administered immediately after harvesting
ranja smanjenog intenziteta (engl. reduced-intensity or after long-term storage in the frozen state – cryo-
conditioning – RIC) [1–3,8,9]. Kako bi mogle da se daju preservation [2–5], SCs can be collected in three ways
bolesniku odmah nakon prikupljanja ili nakon dugo- [8,17–22]:
ročnog čuvanja u zamrznutom stanju – krioprezerva- a) multiple aspirations from BM;
cija [2–5], MĆ se mogu prikupiti na tri načina [8,17–22]: b) harvesting from PB after mobilization with chemo-
a) višestrukom aspiracijom iz kostne srži; therapy and/or growth factors (rHuG-CSF);
b) prikupljanjem iz periferne krvi (engl. peripheral blo- c) processing from umbilical cord blood (UCB).
od – PB) nakon mobilizacije hemoterapijom i/ili fak-
Hematological diseases (mostly malignant) and
torima rasta (rHuG-CSF);
certain benign diseases (severe combined immunode-
c) izdvajanjem iz krvi pupčane vrpce (engl. umbilical
ficiency – SCID, severe aplastic anemia, and different
cord blood – UCB).
autoimmune or metabolic disorders) have thus far
Hematološka oboljenja (uglavnom maligna) kao i
been the most common indication for SC transplan-
određena benigna oboljenja (teška kombinovana imu-
tation. Nowadays, SC transplants derived from PB and
nodeficijencija – TKI, teška aplastična anemija i različita
BM are more common in adult allogeneic or autolo-
autoimunska ili metabolička oboljenja) do sada su bila
gous transplantation. UCB-derived SC transplantations
najčešća indikacija za transplantaciju MĆ. U današnje
have achieved encouraging results in the pediatric set-
vreme, transplantati MĆ prikupljeni iz periferne krvi ili
ting, mainly when a matched unrelated SC donor is not
kostne srži su češći kod adultne alogene ili autologne
available [2–4,8].
transplantacije. Transplantati MĆ izdvojeni iz krvi pup-
SC plasticity is a phenomenon of inter-systemic cell
čane vrpce pokazali su ohrabrujuće rezultate u pedi-
plasticity, which reflects the wide-ranging phenotypic
jatriji, uglavnom u slučajevima kada nije moguće naći
potential of very primitive SCs, capable of homing to
podudarnog nesrodnog davaoca MĆ [2–4,8].
different tissues during the implantation of autologous
Plastičnost MĆ je fenomen intersistemske ćelijske
SCs into the damaged area, with subsequent transdif-
plastičnosti, koji odslikava široki fenotipski potencijal
ferentiation into cell lineages of the host tissue/organ
vrlo primitivnih MĆ, sposobnih za ukalemljenje u razli-
and the development of therapeutic micro-angiogen-
čita tkiva tokom implantacije autolognih MĆ na ošte-
esis i.e., neovascularization stimulated by angiogenesis
ćeno mesto, uz sledstveno transdiferentovanje u ćelij-
growth factors [11–15,23–25].
ske linije tkiva/organa domaćina i razvoj terapeutske
Both the intensification of SC transplantations and
mikroangiogeneze (neovaskularizacije) podstaknute
the introduction of innovative cell-mediated restor-
faktorima angiogeneze [11–15,23–25].
ative or regenerative therapy, increase the need for SCs
Intenziviranjem transplantacija MĆ i uvođenjem
and for practical operating procedures and manipula-
inovativnih oblika regenerativne i restorativne ćelijske
tion methods in relation to these cells. Therefore, this
terapije, došlo je do povećanja potreba za MĆ kao i za
paper summarizes the SC hemobiology and the practi-
praktičnim operativnim procedurama i metodama ma-
cal aspects of the optimization of cell harvesting, puri-
nipulacije ovih ćelija. Stoga, ovaj rad sažima hemobio-
fication, and clinical use.
logiju MĆ i praktične aspekte optimizacije prikupljanja,
prečišćavanja i kliničke primene MĆ.
Balint B. i sar.
EMBRIONALNI NASPRAM ADULTNIH EMBRYONIC VERSUS ADULT STEM CELL

ODELJAKA MATIČNIH ĆELIJA COMPARTMENTS
Odeljci MĆ uključuju populacije ćelija koje su karakte- SC compartments include cell populations characteris-
ristične i za EMĆ i za adultno tkivo. Opšte uzev, samo tic of both ESCs and adult tissue. Generally, only ESCs
su EMĆ ćelije „prave“ totipotentne/pluripotentne ćeli- are ‘true’ totipotent/pluripotent cells, because the phe-
je, zato što je fenomen intersistemske plastičnosti MĆ nomenon of inter-systemic SC plasticity during early
tokom ranog razvoja živih bića od ključnog značaja. U development of living organisms is critical. It is the
pitanju je sposobnost EMĆ da se razviju u svaku od tri ability of ESCs to develop into all three embryonic tis-
vrste embrionalnog tkiva. Nasuprot tome, smatra se sue types. Conversely, SCs in adults are characteristical-
da su MĆ kod odraslih osoba po pravilu ograničene, i ly considered to be restricted, in their regenerative as
u regenerativnom potencijalu i u potencijalu diferen- well as their differentiative potential, to tissues where
tovanja, na tkiva koja „nastanjuju“ [6]. Stoga, hepatociti they reside [6]. Therefore, hepatocytes can proliferate
mogu da proliferiraju (i manje-više da se diferentuju) (and more or less differentiate) following partial hepa-
nakon delimične hepatektomije; MĆH mogu da rekon- tectomy; HSCs can reconstitute blood cells after BM
stituišu ćelije krvi nakon oštećenja kostne srži (usled damage (due to chemotherapy and/or irradiation); ke-
hemoterapije i/ili zračenja); progenitori keratinocita ratinocyte progenitors can participate in wound heal-
mogu da učestvuju u zarastanju rana; a određene „sa- ing; and certain ‘satellite’ cells can repair injured skele-
telitske“ ćelije“ mogu da obnove oštećene skeletne mi- tal muscles. In addition to their role in the regeneration
šiće. Uz ulogu u regeneraciji oštećenih tkiva, MĆ ima- of damaged tissues, SCs have an important function
ju važnu funkciju u održavanju homeostaze tkiva. Na in maintaining tissue homeostasis. For example, SCs
primer, MĆ imaju specifičnu ulogu u održavanju tkivne have a specific role in maintaining tissue homeostasis
homeostaze tokom celog života jedinke [2–6]. throughout the entire life of an individual [2–6].
Embrionalne matične ćelije Embryonic stem cells

Kao što je već navedeno, samo su EMĆ validne odno- As stated above, only ESCs are valid or ‘authentic’ toti-
sno „autentične“ totipotentne/pluripotentne MĆ, zbog potent/pluripotent SCs, due to their potential to differ-
njihovog potencijala da se diferentuju u bilo koju od entiate into any of the cell lineages, i.e., their ability to
ćelijskih linija, odnosno njihove sposobnosti da sazru mature into any of the three tissue types/germ layers
u bilo koji od tri tipa tkiva/germinativnih slojeva u ljud- in the human body – the endoderm, ectoderm, or me-
skom organizmu – endoderm, ektoderm ili mezoderm. soderm. Conversely, SCs in adults are considered limit-
Nasuprot tome, smatra se da su MĆ kod odraslih oso- ed in their developmental and regenerative potential,
ba, po pravilu, ograničene u svom razvojnom i regene- typically to the tissues where they reside, despite the
rativnom potencijalu na tkiva koja „nastanjuju“, uprkos current findings that some adult SCs have SC plastici-
određenim nalazima u današnje vreme koji ukazuju na ty, similar to the biological potential of ESCs. Namely,
to da neke adultne MĆ pokazuju plastičnost koja je slič- very primitive BM-derived cells, such as very small em-
na biološkom potencijalu EMĆ. Naime, vrlo primitivne bryonic-like SCs (VSELs), are also able to develop into a
ćelije potekle iz kostne srži, kao što su veoma male MĆ variety of somatic cells, due to the aforementioned SC
nalik embrionalnim (engl. very small embryonic-like SCs plasticity [2,26–34].
– VSELs), takođe imaju sposobnost da se razviju u razne The age of innovation in ESC physiology began at
somatske ćelije, zahvaljujući već spomenutoj plastič- the end of the last century, with the separation of cells,
nosti MĆ kojom se odlikuju [2,26–34]. which possess totipotency (the potential to differenti-
Doba inovacija u oblasti fiziologije embrionalnih ate into any of the cell lineages in the human body),
ćelija je započelo krajem prošlog veka izdvajanjem će- from human blastocysts and fetal tissue. Subsequently,
lija koje poseduju totipotentnost (potencijal da se di- researchers described the important hemobiological
ferentuju u bilo koju od ćelijskih linija u ljudskom telu), and molecular characteristics of these cells and im-
iz humanih blastocisti i fetalnog tkiva. Nakon toga, proved methods for their cultivation [2–6].
naučnici su opisali važne hemobiološke i molekularne Due to the highest degree of cell plasticity, the
karakteristike ovih ćelija i unapredili metode njihove zygote is considered to be the ‘authentic’ totipotent/
kultivacije [2–6]. pluripotent SC. By the end of the fifth or sixth day of
Usled najvišeg stepena ćelijske plastičnosti, zigot division, it further develops from the older cells of the
se smatra „autentičnom“ totipotentnom/pluripoten- blastocyte that initiate the expansion of the coding se-
tnom MĆ. Do kraja petog ili šestog dana deobe, nadalje quence for specific functions, which makes it possible
Balint B. et al.
se razvija iz starih ćelija blastocite koje podstiču širenje to isolate ESCs. Accumulation of fetal SCs in the fetal
kodne sekvence za specifične funkcije, čime postaje liver makes them hypothetically suitable to be extract-
moguće da se izoluju EMĆ. Akumulacija fetalnih MĆ ed from the blastocyte and to be cultured ex vivo into
u fetalnoj jetri čini ove ćelije hipotetički pogodnim za SCs. After their transplantation into an individual, the
ekstrakciju iz balstocite i kultivaciju ex vivo u MĆ. Posle possibility of rejection is reduced, since these SCs have
njihove transplantacije bolesnicima, smanjena je vero- little or no immunity-triggering proteins on their cell
vatnoća odbacivanja alotransplantata, pošto ove MĆ surface [2,3,5].
imaju vrlo malo ili nimalo proteina okidača imunskog Despite strong ethical arguments that ESC re-
sistema na svojoj površini [2,3,5]. search, and especially potential clinical use, border on
Uprkos jakoj etičkoj argumentaciji da se istraživa- negligent manslaughter [3,5], ESCs are the most prom-
nje EMĆ, a naročito njihova potencijalna klinička pri- ising potentially transplantable SCs. Namely, basic re-
mena, graniče sa ubistvom iz nehata [3,5], EMĆ najviše search and some preclinical investigations with ESCs
obećavaju kao ćelije koje se mogu potencijalno pre- have proven to be important for the development of
saditi, od svih ostalih MĆ. Naime, bazična istraživa- new cell-replacement methods and strategies to re-
nja i neka pretklinička ispitivanja EMĆ su se pokazala store damaged tissues and re-establish critical func-
kao značajna u razvoju novih metoda zamene ćelija i tions of the diseased human body [2,26–34].
strategija za regenerisanje oštećenih tkiva i ponovno
uspostavljanje ključnih funkcija u obolelom ljudskom Adult stem cells – concept and functionality
organizmu [2,26–34]. Adult SCs identified in various tissues/organs (BM, PB,
dental pulp, adipose tissue, fetal liver, blood vessels,
Pojam i funkcionalnost adultnih matičnih ćelija brain, heart, skeletal muscle, skin, pancreas, and the
Adultne MĆ identifikovane u raznim tkivima/organima gastrointestinal tract) are usually more mature than
(kostna srž, periferna krv, zubna pulpa, masno tkivo, ESCs [2–6]. Previously, adult SCs were considered ‘in-
fetalna jetra, krvni sudovi, mozak, srce, skeletni mišići, capable’ of producing cell lineages of the three above-
koža, gušterača, i gastrointestinalni trakt) obično su mentioned tissue types (endoderm, ectoderm and
zrelije od EMĆ [2–6]. Ranije se smatralo da su adultne mesoderm) because they could not be ‘rejuvenated’ (in
MĆ „nesposobne“ da proizvedu ćelijske linije tri već na- the earlier cell phase) by the process of cell dediffer-
vedena tipa tkiva (endoderm, ektoderm i mezoderm) entiation – accompanied by transdifferentiation. Adult
zato što ne mogu da se „podmlade“ (u ranijoj ćelijskoj SCs are capable of self-renewal, but divide more fre-
fazi) procesom diferentovanja ćelija – uz proces transdi- quently to produce progenitors and precursors, as well
ferentovanja. Adultne MĆ su sposobne da se samoob- as mature cells of specific cell lineages.
navljaju, ali se češće dele kako bi proizvele progenitore Figure 1 shows that only the combination of several
i prekursore, kao i zrele ćelije specifičnih ćelijskih linija. conditions can be used to confirm that some SCs, de-
Slika 1 pokazuje da samo kombinacija nekoliko rived from BM, have in fact transformed into somatic
uslova može da posluži kao potvrda da su se neke MĆ, cells (cells specific to solid organs) [2,4,23–25].
dobijene iz kostne srži, zaista transformisale u somatske HSCs are undoubtedly the most thoroughly un-
ćelije (ćelije specifične za solidne organe) [2,4,23–25]. derstood specific type of SCs in adults which have
MĆH su nesumnjivo najbolje proučeni specifični the potential to reconstitute all blood cells. Both
tip MĆ kod odraslih osoba koje imaju potencijal da re- identified classes of HSCs, short-term HSCs (ST-HSCs)
konstituišu sve ćelije krvi. Obe klase MĆH, kratkotrajno and long-term HSCs (LT-HSCs), can reconstitute
(engl. short-term HSCs – ST-HSCs) i dugotrajno koloni- the blood of experimental animals for one to two
šuće ćelije (engl. long-term HSCs – LT-HSCs), mogu da months, and more than 6 months, respectively [2,5].
rekonstituišu krv eksperimentalnih životinja – i to, na After homing, BM-derived SCs can undergo a mul-
jedan do dva meseca (ST-HSCs), odnosno na više od tistep process involving migration, conversion to
šest meseci (LT-HSCs) [2,5]. Nakon ukalemljenja, MĆ a new cellular phenotype, and expression of func-
dobijene iz kostne srži mogu da prođu proces koji se tions characteristic of the tissue where they reside
sastoji iz više faza, uključujući migraciju, konverziju u [4,23,24].
novi ćelijski fenotip, kao i ispoljavanje funkcija karakte- BM-derived SCs are a heterogeneous population
rističnih za tkiva koja „nastanjuju“ [4,23,24]. of cells with morphological and functional character-
MĆ dobijene iz kostne srži su heterogena popula- istics of tissue committed SCs (TCSCs). They may be in
cija sa morfološkim i funkcionalnim karakteristikama charge of healing minor tissue damage; their number
tkivno opredeljenih MĆ (engl. tissue committed SCs – among mononuclear cells (MNCs) is very low – approx-
TCSCs). Moguće je da su zadužene za reparaciju manjih imately one cell per 1,000 to 10,000 total nucleated
Balint B. i sar.
Slika 1. Pokazuje da samo kombinacija nekoliko uslova može da posluži kao Figure 1. Shows that only the combination of several conditions can be used to
potvrda da su se neke MĆ, dobijene iz kostne srži, zaista transformisale u so- confirm that some SCs, derived from BM, have in fact transformed into somatic
matske ćelije (ćelije specifične za solidne organe) [2,4,23–25] cells (cells specific to solid organs) [2,4,23–25]
oštećenja tkiva; njihov broj među mononuklearnim cells (TNCs) in BM [2,19]. However, in severe injuries
ćelijama (engl. mononuclear cells – MNCs) je veoma ni- (heart infarction or stroke), they have the possibility
zak – oko jedna ćelija na 1.000 do 10.000 od ukupnog to express their full therapeutic potential. The migra-
broj ćelija s jedrom (engl. total nucleated cells – TNCs) u tion of these cells to the damaged areas depends on
kostnoj srži [2,19]. Međutim, kod teških oštećenja (in- the ‘homing signal’, which might be inefficient in the
farkt miokarda ili moždani udar), oni imaju mogućnost presence of cytokines or proteolytic enzymes released
da ispolje svoj puni terapijski potencijal. Migracija ovih from injured leukocytes and/or macrophages [23].
ćelija u oštećene zone zavisi od „signala ukalemljenja“, Nonetheless, these cells while ‘captured’ or ‘encapsu-
koji može biti neefikasan u prisustvu citokina ili prote- lated’ in BM might be in a particular ‘latent stage’ – not
oliznih enzima, koje oslobađaju leukociti i/ili makrofa- fully functional, and in need of the appropriate activa-
gi oštećenog tkiva [23]. Ipak, dok su „zarobljene“ od- tion signals [2–4,23].
nosno „inkapsulirane“ u kostnoj srži, ove ćelije mogu
biti u posebnom „latentnom stadijumu“ – nisu u pot- Mesenchymal stem cells/stromal cells
punosti funkcionalne, te su im potrebni odgovarajući Compared to ESCs and induced pluripotent SCs (iP-
aktivacioni signali [2–4,23]. SCs), mesenchymal stem cells/stromal cells (MSCs)
have a high-quality therapeutic potential and safety
Mezenhimske matične ćelije/stromalne ćelije profile [2–6]. The molecular and functional character-
U poređenju sa EMĆ i indukovanim pluripotentnim MĆ istics of the dental pulp make it an important source
(engl. induced pluripotent SCs – iPSCs), mezenhimske/ of dental pulp SCs, including adult MSCs [2,34–38].
stromalne MĆ (engl. mesenchymal stem/stromal cells MSCs of ectomesenchymal origin located in the peri-
– MSCs) imaju terapijski potencijal i bezbednosni pro- vascular niche are considered highly proliferative, mul-
fil visokog kvaliteta [2–6]. Molekularne i funkcionalne tipotent, and similar to BM-derived SCs. Other dental
karakteristike zubne pulpe čine je važnim izvorom MĆ, pulp SCs (DPSCs), stem cells from human exfoliated de-
uključujući tu i adultne mezenhimske MĆ [2,34–38]. ciduous teeth (SHED), and immature dental pulp cells
Smatra se da su mezenhimske MĆ ektomezenhimskog (IDPC) can transdifferentiate into various cells, such as
Balint B. et al.
porekla, koje se nalaze u perivaskularnoj niši, visoko odontoblasts, chondrocytes, osteoblasts, adipocytes,
proliferativne, multipotentne i slične MĆ poteklim iz neuron/glial cells, smooth muscle cells, skeletal muscle
kostne srži. Druge MĆ iz zubne pulpe (engl. dental pulp cells, and other cells. Future research should provide us
SCs – DPSCs), MĆ iz „eksfoliranih“ humanih mlečnih with complex data on many human tissues, in addition
zuba (engl. stem cells from human exfoliated deciduo- to DPSCs, as potential sources of SCs responsible for
us teeth – SHED), kao i primitivne ćelije zubne pulpe tissue development/regeneration.
(engl. immature dental pulp cells – IDPC) mogu se tran-
sdiferentovati u različite ćelije, kao što su odontoblasti, The concept of very small embryonic-like stem
hondrociti, osteoblasti, adipociti, nervne/glijalne ćelije, cells (VSELs)
ćelije glatkih mišića, ćelije skeletnih mišića, i druge će- A specific type of cells, isolated initially from BM, look
lije. Buduća istraživanja trebalo bi da pruže, uz podatke like ESCs and appear to mimic their ability to trans-
o MĆ zubne pulpe, kompleksne podatke i o mnogim differentiate into other cell types. Furthermore, these
drugim humanim tkivima kao potencijalnim izvorima cells can transdifferentiate into novel cell lineages from
MĆ odgovornih za razvoj/regeneraciju tkiva. more than one germ layer – into nerve, heart, pancre-
atic and cells of other tissues/organs. Ratajczak et al.
Pojam veoma malih matičnih ćelija nalik
were the first to identify VSELs, a special type of SC that
embrionalnim (VSEL ćelije) acts differently than other SCs derived from adult BM
Specifični tip ćelija, koji je prvobitno izolovan iz kostne [26–30]. Although VSELs have basically very similar or
srži, liči na EMĆ i u stanju je da imitira njihovu sposob- the same ultrastructure and protein markers as ESCs
nost transdiferentovanja u druge tipove ćelija. Štaviše, [2,27–29], they are considered ‘contaminants’, which, in
ove ćelije mogu da se transdiferentuju u nove ćelijske fact, contribute to a positive regenerative clinical out-
linije iz više od jednog germinativnog sloja – u nervne, come [26–32]. Finally, there are data confirming that
ćelije srca, gušterače, kao i ćelije drugih tkiva odnosno VSELs regenerate, whereas MSCs rejuvenate diseased
organa. Retajčak i saradnici su bili prvi koji su identi- reproductive tissues [33]. However, the authors of such
fikovali VSEL ćelije, poseban tip ćelija koji se ponaša studies supposed that MSC implantation may simply
drugačije od ostalih MĆ dobijenih iz adultne kostne release growth factors or specific cytokines critical for
srži [26–30]. Iako su VSEL ćelije u suštini vrlo slične ili tissue-resident SCs to differentiate into sperm cells or
iste, po ultrastrukturi i proteinskim markerima, kao ova [33]. This is an interesting concept in regenerative
i EMĆ [2,27–29], one se smatraju „kontaminantima“, medicine, which should be seriously considered in fu-
koji zapravo doprinose pozitivnom regenerativnom ture research and preclinical studies on humans.
kliničkom ishodu [26–32]. Najzad, postoje podaci koji
potvrđuju da VSEL ćelije regenerišu, dok mezenhim- The concept and application of induced
ske MĆ podmlađuju, obolela reproduktivna tkiva [33]. pluripotent stem cells (iPSCs)
Međutim, autori ovakvih studija su izneli pretpostavku An incredible contribution to SC research and appli-
da implantacija MSC ćelija naprosto oslobađa faktore cation came from the Nobel prize awarded work of
rasta ili specifične citokine koji su od ključnog znača- John Gurdon and ShinyaYamanaka (2012), which has
ja u procesu diferentovanja MĆ „nastanjenih“ u tkivu, shown that, with the use of crucial molecules, mature
u spermatozoide ili jajne ćelije [33]. Ovo je zanimljiv adult cells/fibroblasts can dedifferentiate into pluripo-
koncept u regenerativnoj medicini koji bi trebalo da se tent SCs and transdifferentiate or convert into different
ozbiljno razmotri u budućim istraživanjima i pretklinič- mature cellular lines (e.g., cardiac muscle cells) [39]. Al-
kim ispitivanjima na ljudima. though limited in pluripotency and capable of induc-
ing malignant cells, these iPSCs are a potential source
Pojam i primena indukovanih pluripotentnih
with which clinicians can circumvent certain source-re-
matičnih ćelija (iPSC ćelije) lated problems. The future will show their implications
Izuzetan doprinos istraživanjima i primeni MĆ dali su and impact on SC therapy.
Džon Gurdon i Šinja Jamanaka svojim radom nagrađe-
nim Nobelovom nagradom, 2012. godine, koji je po- STEM CELL CATEGORY AND INFLUENCE
kazao da, uz primenu ključnih molekula, zrele adultne The traditional primary cell source for SC transplanta-
ćelije/fibroblasti mogu da se diferentuju u pluripoten- tion is the bone marrow. Approximately 1 – 3% of TNCs
tne MĆ i da se transdiferentuju, odnosno konvertuju u in BM express the CD34 antigen. The CD34+ cells have
različite zrele ćelijske linije (npr. ćelije srčanog mišića) been found in PB, but in an extremely small number
[39]. Iako su ograničene u pluripotentnosti i u stanju in steady-state hematopoiesis – only 0.01 – 0.05% of
da indukuju maligne ćelije, ove iPSC ćelije predstavljaju TNCs [2,19].
Balint B. i sar.
potencijalni izvor MĆ koji može pomoći kliničarima For transplantation, the SC quantity is a critical is-
da prevaziđu određene probleme u njihovom obez- sue. Different populations of TNCs and MNCs (includ-
beđivanju. Budućnost će pokazati implikacije koje su ing SCs) can be obtained by multiple aspirations from
skopčane sa iPSC ćelijama, kao i njihov uticaj na oblast BM, harvesting from PB after mobilization (chemo-
lečenja MĆ. therapy and/or rHuG-CSF), and processing from UCB.
These cells can be clinically applied (transplanted) im-
KATEGORIJA I UTICAJ MATIČNIH ĆELIJA mediately after collection or cryopreservation [1–4,10].
Tradicionalno, primarni izvor ćelija za transplantaciju When the donor is anesthetized, cells can be col-
MĆ jeste kostna srž. Oko 1 – 3% od ukupnog broja ćeli- lected by multiple aspirations from the posterior (sel-
ja sa jedrom (TNC) u kostnoj srži eksprimira CD34 anti- dom anterior) iliac crests, using the maximal target as-
gen. CD34+ ćelije su pronađene u kostnoj srži, ali u jako pirate volume of up to 15 ml/kg of body mass (kgbm) of
malom broju u stanju stabilne hematopoeze – svega the donor. Marrow aspirate must be filtered to remove
0,01 – 0,05% od ukupnog broja ćelija sa jedrom [2,19]. bone or lipid particles and cell aggregates. Citrate solu-
Za transplantaciju je od ključnog značaja količina tion and heparin diluted in saline (5,000 IU/500 ml) are
MĆ. Različite populacije TNC-a i MNC-a (uključujući i used for anticoagulation [2–5].
MĆ) mogu se dobiti višestrukim (ponovljenim) aspiraci- For ABO incompatible SC transplantations, red
jama iz kostne srži, prikupljanjem iz periferne krvi nakon blood cell (RBC) count and plasma quantity reduc-
mobilizacije (hemoterapija i/ili rHuG-CSF), ili obradom tion is required (by aspirate processing). Depletion of
iz krvi pupčane vrpce. Ove ćelije se mogu klinički pri- T-cells is achieved by ex vivo purging (positive or neg-
meniti (može se izvršiti njihova transplantacija) odmah ative immune-magnetic cell selection). Procedures of
nakon prikupljanja odnosno krioprezervacije [1–4,10]. processing and purging SCs enable the reduction of
Kada se davalac anestezira, ćelije se mogu prikupiti RBC total quantity by 90% as well as T-cell depletion
višestrukim aspiracijama iz zadnjih grebena bedrene by 3 – 4 Log10 [2–5].
kosti (ređe prednjih grebena), primenom maksimal- Nowadays, the number of patients treated with
nog ciljnog volumena aspirirane kostne srži do 15 ml/ PB-derived SCs is constantly growing, and PB-derived
kg telesne mase (engl. kg of body mass – kgbm) dava- SCs are used for about 80% of allogeneic and practical-
oca. Aspirat iz kostne srži mora se filtrirati da bi se od- ly for all autologous transplants. The characteristics of
stranile partikule kosti ili lipida kao i agregati ćelija. Ra- SC transplantations are the following [2–5,19]:
stvor citrata i heparin razblažen u fiziološkom rastvoru a) minimally invasive cell harvesting method and ab-
(5.000 IU/500 ml) koriste se kao antikoagulansi [2–5]. sence of general anesthesia risks;
Kod ABO nekompatibilnih transplantacija MĆ, po- b) small harvesting volume (250 ml) with a better yield
trebna je redukcija broja crvenih krvnih zrnaca i koli- of CD34+;
čine plazme (obradom aspirata). Redukcija T ćelija se c) high engraftment rate (rapid hematopoietic recon-
postiže ex vivo prečišćavanjem (pozitivna ili negativna struction) and low transplant-related morbidity
imuno-magnetna selekcija ćelija). Procedure obrade (TRM).
i prečišćavanja MĆ omogućavaju redukciju ukupnog Regarding the timing of stem cell harvesting, the
broja crvenih krvnih zrnaca za 90%, kao i redukciju T CD34+ cell count in the circulation is maximal, i.e., it
ćelija za 3 – 4 Log10 [2–5]. peaks on the 5th day of rHuG-CSF administration (5 –
U današnje vreme, broj bolesnika lečenih MĆ dobi- 10 μg/kgbm per day for allogeneic donors). However,
jenim iz kostne srži neprestano raste, a MĆ dobijene iz the optimal timing of autologous SC harvesting is more
kostne srži se koriste za oko 80% alogenih i za praktič- complex, and these patients receive a higher rHuG-CSF
no sve autologne transplantacije. Karakteristike tran- dose (12 – 16 μg/kgbm or more, daily) combined with
splantacija MĆ su sledeće [2–5,19]: chemotherapy [2–5]. It is important that the count of
a) minimalno invazivni metod prikupljanja ćelija i od- circulating CD34+ cells should correlate with a high
sustvo rizika opšte anestezije; CD34+ yield in the graft. It is estimated that when the
b) mali volumen afereznog produkta (250 ml) sa ve- number of CD34+ cells in PB is higher than 40/μl, the
ćom količinom prikupljenih CD34+ ćelija; possibility of obtaining CD34+ ≥ 2.5x106 per kgbm in
c) visoka stopa prihvatanja kalema (brza rekonstituci- the recipient is 60%, after performing one large-vol-
ja hematopoeze) i nizak nivo morbiditeta uzrokova- ume leukapheresis (LVL) [2–5,21].
nog transplantacijom (engl. transplant-related mor- An innovative harvesting protocol uses plerixa-
bidity – TRM). for (mozobil) to obtain a sufficient SC quantity from
Kada je u pitanju planiranje vremena prikupljanja ‘poor-mobilizers’. The stromal derived factor 1 (SDF-1)
MĆ, ukupan broj CD34+ ćelija u cirkulaciji je maksimalan retains SCs in the BM due to its physiological interaction
Balint B. et al.
petog dana nakon primene rHuG-CSF (5 – 10 μg/kgbm, with chemokine receptor CXCR. Plerixafor is a potent
na dan, za alogene davaoce). Međutim, planiranje antagonist of the alpha chemokine receptor CXCR4 as it
optimalnog vremena autolognog prikupljanja MĆ je effectively inhibits CXCR4 – SDF-1 interaction. There are
ipak kompleksnije, te ovi bolesnici primaju višu dozu data on an improved mobilizing regimen which uses
rHuG-CSF (12 – 16 μg/kgbm ili više, na dan) u kombina- plerixafor with rHuG-CSF on account of a higher imma-
ciji sa hemoterapijom [2–5]. Važno je da ukupan broj ture SC count in the circulation and a high CD34+ yield
CD34+ ćelija u cirkulaciji korelira sa visokim brojem pri- in the graft [2–4,20]. A successful transplantation can be
kupljenih CD34+ ćelija u graftu. Procenjuje se da, kada expected when the target: CD34+ cells ≥ 2–4x106/kgbm
je broj CD34+ ćelija u kostnoj srži viši od 40/μl, moguć- of the recipient, is achieved. Our preclinical investiga-
nost dobijanja CD34+≥ 2,5x106 po kgbm kod primao- tion has confirmed that the relative frequency of the
ca iznosi 60%, nakon leukapareze velikog volumena very primitive SC subset (CD34+/CD90+) in circulation
(engl. large-volume leukapheresis – LVL) [2–5,21]. could be a practical and potentially objective mobiliza-
Jedan inovativni protokol prikupljanja ćelija po- tion predictive factor for optimized timing of cell har-
drazumeva upotrebu pleriksafora (mozobila) kako bi vesting and a predictor of the harvest quality [1–5,20].
se dobila dovoljna količina MĆ od „loših mobilizera“. A possibility ≤ 30% (for related donors) and ≤ 85%
Faktor poreklom iz strome 1 (engl. stromal derived fa- (for unrelated donors) of finding an adult allogeneic
ctor 1 – SDF-1), zadržava MĆ u kostnoj srži usled svo- donor, indicates limited donor availability [2–5,18]. In
je fiziološke interakcije sa hemokinskim receptorom the previous decades, UCB has been used as a viable
CXCR. Pleriksafor je potentan antagonist alfa hemokin- alternative source of 1HLA-typed (matching) SCs for al-
skog receptora CXCR4, jer uspešno inhibira interakciju logeneic transplantation [2–5,17].
CXCR4 – SDF-1. Postoje podaci o unapređenom režimu Neonatal SCs are obtained from UCB, immediately
mobilizacije koji primenjuje pleriksafor sa rHuG-CSF, after birth, by a painless and non-invasive method of col-
zbog većeg broja nezrelih MĆ u cirkulaciji i većeg bro- lection. These cells are less mature than those in BM. The
ja prikupljenih CD34+ ćelija u graftu [2–4,20]. Uspešna ‘naïve’ nature of UCB lymphocytes allows the use of par-
transplantacija se može očekivati kada se postigne cilj: tially HLA-mismatched SC grafts without an increased
CD34+ ćelije ≥2–4x106/kgbm kod primaoca. Naša pret- risk of severe graft versus host disease (GvHD), as com-
klinička istraživanja su potvrdila da relativna učestalost pared to BM transplantation from a completely matched
jedne vrlo primitivne podgrupe MĆ (CD34+/CD90+) u unrelated donor [2–5,17]. Due to a limited number of
cirkulaciji može biti praktičan i potencijalno objektivan SCs, the UCB is a cell source accepted for pediatric pa-
prediktivni faktor mobilizacije kod planiranja optimal- tients and patients for whom a matched unrelated SC
nog vremena za prikupljanje MĆ, kao i prediktor kvali- donor is unavailable. Unfortunately, children weighing
teta prikupljenog uzorka [1–5,20]. ≥ 45 kgbm have a higher risk of graft failure [2–5,17].
Mogućnost pronalaženja odraslog alogenog dava- More recently, SC transplantation from haploiden-
oca ≤ 30% (za srodne davaoce) i ≤ 85% (za nesrodne tical donors for the treatment of patients who do not
davaoce), ukazuje na ograničenu dostupnost davao- have HLA-matched donors has continued to increase
ca [2–5,18]. Tokom proteklih decenija, krv iz pupčane [40,41].
vrpce korišćena je kao održivi alternativni izvor 1HLA-ti-
piziranih (podudarnih) MĆ za alogenu transplantaciju CLINICAL PRACTICE: STEM CELL
[2–5,17]. TRANSPLANTATIONS VERSUS REGENERATIVE
Neonatalne MĆ dobijaju se iz krvi pupčane vrpce, MEDICINE
odmah nakon porođaja, bezbolnom i neinvazivnom The standard treatment for hematological malignan-
metodom prikupljanja. Ove ćelije su manje zrele nego cies and certain benign disorders is the infusion of al-
ćelije iz kostne srži. „Naivna“ priroda limfocita iz krvi logeneic or autologous SCs, collected for the hemato-
pupčane vrpce omogućava upotrebu HLA-delimično poietic and clinical recovery of patients after high-dose
podudarnih graftova MĆ, bez povećanog rizika teškog radio-chemotherapy. A similar procedure with RIC may
oblika bolesti kalema protiv domaćina (engl. graft ver- be offered to patients who are ineligible for high dose
sus host disease – GvHD), u poređenju sa transplantaci- conditioning due to age or comorbidity. The idea of
jom iz kostne srži dobijene od potpuno podudarnog treating immune-mediated diseases, such as multiple
nesrodnog davaoca [2–5,17]. Zbog ograničenog bro- sclerosis and immune-mediated enteropathy, by using
ja MĆ, krv pupčane vrpce je izvor koji je prihvatljiv za SC transplants, is based on the principle that immu-
pedijatrijske bolesnike kao i bolesnike kod kojih nije noablative treatment can destroy the patient’s anti-self
moguće obezbediti podudarnog nesrodnog davaoca. lymphocytes [2–5].
1 engl. HLA – human leukocyte antigens 1 HLA – human leukocyte antigens
Balint B. i sar.
Nažalost, kod dece čija je težina ≥ 45 kgbm postoji veći Table 1 presents the most common indications
rizik da dođe do neprihvatanja kalema [2–5,17]. for SC transplantation, such as hematological diseas-
U novije vreme, u porastu je transplantacija MĆ does and certain immune-mediated disorders [1–5,11–
bijenih od haploidentičnih davaoca za lečenje bolesni- 15,18–22].
ka koji nemaju HLA-podudarne donore [40,41]. In our Center, we use SC transplantations to treat
patients with acute leukemia (lymphoblastic and
KLINIČKA PRAKSA: TRANSPLANTACIJE non-lymphoblastic), chronic myeloid leukemia, multi-
MATIČNIH ĆELIJA NASPRAM REGENERATIVNE ple myeloma, Hodgkin and non-Hodgkin lymphoma, as
MEDICINE well as patients with breast and ovarian cancer, extrag-
Standardno lečenje hematoloških maligniteta i odre- onadal non-seminal germ cell tumors, severe aplastic
đenih benignih oboljenja jeste infuzija alogenih ili anemia, and severe multiple sclerosis [2–5,20-22].
autolognih MĆ, prikupljenih u cilju hematopoetskog However, specific clinical aspects of SC transplan-
i kliničkog oporavka bolesnika nakon visokodozne ra- tation in the treatment of various hemato-oncological
diohemoterapije. Slična procedura – uz primenu RIC – and other disorders, such as optimal transplantation
se izvodi kod bolesnika kojima nije moguće primeniti
Tabela 1. Uobičajene i relativne indikacije za transplantaciju matičnih ćelija
visokodozno kondicioniranje, zbog uzrasta ili komor-
biditeta. Tretman oboljenja uzrokovanih poremećajem Table 1. Common and relative indications for SC transplantation
imunskog sistema (kao što su multipla skleroza i auto-
Hematološka oboljenja / Hematological diseases
imunska enteropatija) transplantacijom MĆ, zasnovan
je na principu da imunoablativna terapija može uništiti Akutna leukemija / Acute leukemia
bolesnikove autodestruktivne limfocite [2–5]. − Akutna mijeloidna leukemija / Acute myeloid leukemia
Tabela 1 prikazuje najčešće indikacije za transplan- − Akutna limfoblastna leukemija / Acute lymphoblastic leukemia
taciju MĆ, kao što su hematološka oboljenja i određe- Mijelodisplazija / Myelodysplasia
na oboljenja uzrokovana poremećajem imunskog si-
Mijeloproliferativni poremećaji / Myeloproliferative disorders
stema [1–5,11–15,18–22].
Transplantacije MĆ kod nas su izvedene u lečenju − Hronična mijeloidna leukemija (retko) / Chronic myeloid leukemia (seldom)
bolesnika sa akutnim leukemijama, hroničnom mijelo- − Ostali mijeloproliferativni poremećaji / Other myeloproliferative disorders
idnom leukemijom, multiplim mijelomom, limfomima, Hronične limfoproliferativne bolesti / Chronic lymphoproliferative diseases
kao i bolesnika sa pojedinim karcinomima, ekstrago- − Hočkinov limfom / Hodgkin lymphoma
nadalnim neseminomskim tumorom germinativnih
− Ne-Hočkinov limfom / Non-Hodgkin lymphoma
ćelija, teškim oblikom aplastične anemije i multiplom
sklerozom [2–5,20–22]. - Visoko agresivni ne-Hočkinov limfom /
High grade non-Hodgkin lymphoma
Specifični klinički aspekti transplantacije MĆ u le-
čenju različitih hematoonkoloških i drugih oboljenja, - Nisko agresivni ne-Hočkinov limfom /
Low grade non-Hodgkin lymphoma
kao što su optimalno vreme transplantacije, terapijska
efikasnost i komplikacije, neće biti detaljno opisani i − Multipli mijelom / Multiple myeloma
analizirani u ovom radu. Ukratko, efikasnost transplan- Aplastična anemija / Aplastic anemia
tacije MĆ zavisila je od vrste bolesti, stadijuma bolesti, Ostali poremećaji /Other disorders
njene osetljivosti na hemoterapiju, kao i od uzrasta bo- Teška kombinovana imunodeficijencija /
lesnika, njegovog opšteg zdravstvenog stanja, te ste- Severe combined immunodeficiency (SCID)
pena podudaranja u sistemu HLA [2–4,20–22].
Stečene imunodeficijencije / Acquired immune deficiencies
Opšte poznati efekti alogene transplantacije u he-
matoonkologiji se tek od nedavno koriste za precizno Talasemija / Thalassemia
izučavanje sistema koji jasno odvaja pozitivne efekte Metabolički poremećaji / Metabolic deficiencies
fenomena kalem protiv leukemije (engl. graft versus Autoimunska oboljenja (nrp. multipla skleroza – MS) /
leukemia – GvL) od negativnih efekata GvHD. Uz opšte Autoimmune disorders (e.g., multiple sclerosis – MS)
poznate pozitivne rezultate u lečenju bolesnika sa mul- Ne-hematološki maligniteti / Nonhematological malignancies
tiplim mijelomom i leukemijom [2,42], kod nas je usta- Neuroblastom / Neuroblastoma
novljeno da je infuzija donor specifičnih limfocita (engl.
Vilmsov tumor / Wilms’ tumor
donor-specific lymphocyte infusion – DLI) efikasna bila u
lečenju bolesnika sa Filadelfija hromozom-pozitivnom Rabadomiosarkom / Rhabdomyosarcoma
hroničnom mijeloidnom leukemijom (engl. Philadelp- Juingov sarkom / Ewing sarcoma
hia chromosome-positive CML) (za vreme relapsa nakon Karcinom dojke, jajnika, testisa / Breast, ovarian, testicular cancer
Balint B. et al.
transplantacije MĆ). Uz to, uveden je originalni in vi- timing, therapeutic efficacy, and complications, are not
tro test, označen kao „Test mešanih progenitora“ radi described and discussed in this paper in detail. In brief,
predviđanja kliničkog ishoda terapije primenom DLI the efficacy of SC transplantations depends on the
[2,5,42]. Iako su TRM i mortalitet radikalno smanjeni, type of disease, its stage, its sensitivity to chemothera-
transplantacije MĆ mogu rezultovati brojnim kompli- py, the patient’s age, and their general health status, as
kacijama, uključujući i one najčešće – neuspešno pri- well as the degree of HLA-matching [2–4,20–22].
hvatanje kalema, virusne ili oportunističke infekcije, te The well-known beneficial effects of allogeneic
akutni ili hronični GvHD [1–5]. SC transplantation in hemato-oncology have only re-
U oblasti regenerativne medicine, intersistemska cently been applied in designing a system that sepa-
plastičnost MĆ opravdava upotrebu primitivnih MĆ u rates the positive effects of graft versus leukemia (GvL)
lečenju bolesnika sa oštećenjima srca, jetre, pankreasa from the negative effects of graft versus host disease
i drugih organa ili tkiva. Rezultati kliničkih studija uka- (GvHD). In addition to the already known favorable
zuju na transdiferentovanje MĆ u kardiomiocite nakon results in the treatment of patients with multiple my-
primene i ukalemljenja (homing) u oštećenoj, odnosno eloma and leukemia [2,42], we have also found do-
ishemijskoj zoni miokarda. Kostna srž je najčešće kori- nor-specific lymphocyte infusion (DLI) to be effective
šćen izvor ćelija koje se koriste za postizanje kliničkog in patients with Philadelphia chromosome-positive
oporavka miokarda zbog sadržaja mešavine različitih CML (relapsed after SC transplantation), and we have
populacija progenitora – uključujući MĆH, ali i brojne introduced an original in vitro test, the so called ‘Test
ne-hematopoetske ćelije (npr. TCSC, MSC i VSEL ćelija), of Mixed Progenitors’, to predict the clinical outcome
koje mogu da se transdiferentuju u različite ćelijske li- of DLI treatment [2,5,42]. Although TRM and mortality
nije [14,23,43–45]. have been radically reduced, SC transplantations can
Naš Centar za regenerativnu medicinu počeo je sa involve a number of complications, including the most
intrakoronarnom aplikacijom (u kardiologiji) i intramio- common ones – engrafting failure, viral or opportunis-
kardnom implantacijom (u kardiohirurgiji) mononukleu- tic infections, and acute or chronic GvHD [1–5].
snih ćelija (sa prisutnim MĆ – MNĆ/MĆ) 2003, odnosno In the field of regenerative medicine, intersystem-
2006. godine [14,23–25]. Preliminarni rezultati pokazali ic SC plasticity provides a rationale for the use of im-
su da je lečenje akutnog infarkta miokarda sa ST elevaci- mature SCs in the treatment of patients with damage
jom (engl. ST-elevation myocardial infarction – STEMI) po- to the heart, liver, pancreas, and other organs/tissues.
moću intrakoronarne injekcije (petog dana od infarkta) Findings from clinical studies indicate transdifferenti-
autolognih MNC/SC-a, prikupljenih iz aktivirane kostne ation in cardiomyocytes after the administration and
srži (kostna srž aktivirana pomoću G-CSF-a u jednoj dozi; homing of SCs in the damaged or ischemic region of
3 – 5 mg/kgbm), bilo delotvorno i bezbedno. Ejekciona the myocardium. BM was the most frequently used
frakcija leve komore (engl. left ventricular ejection fracti- source of cells for clinical cardiac repair, due to its com-
on – LVEF) se popravila (povećanje = 5,5 ± 6,6%; četvoro- plex mixture of progenitors, including HSCs, but also
mesečni period praćenja), a veličina infarktne zone (engl. different non-hematopoietic cells (e.g., TCSCs, MSCs
infarction size – IS) se smanjila (smanjenje = 6,2 ± 5,0%). and VSELs) which can transdifferentiate into various
Dugoročni pozitivni LVEF/IS efekti su bili umereni. Nisu cell lineages [14,23,43–45].
registrovani kardiovaskularni mortalitet, ponovljeni in- Our Center of Regenerative Medicine began applying
farkt, klinički manifestna srčana insuficijencija, maligna intracoronary injection (cardiology) and intramyocardial
aritmija ili drugi neželjeni događaji [14,23,24]. implantation (cardiac surgery) of MNC/SCs in 2003 and
Naši prvobitni rezultati u domenu hirurške reva- 2006, respectively [14,23–25]. Preliminary results have
skularizacije srca ili koronarne bajpas hirurgije (engl. shown that treatment of acute ST-elevation myocardial
coronary artery bypass grafting – CABG) udružene in- infarction (STEMI) with intracoronary injection (on the
tramiokardnom implantacijom MNĆ/MĆ (grupa: CABG 5th day upon infarction) of autologous MNC/SCs, collect-
plus MNĆ/MĆ) pokazali su nedvosmislenu superior- ed from primed/activated BM (BM activated by G-CSF,
nost ove metode. LVEF se značajno popravila (poveća- single dose; 3 – 5 mg/kgbm), was effective and safe. The
nje = 5,0 ± 4,2) kod ovih bolesnika. Takođe je potvrđen left ventricular ejection fraction (LVEF) improved (in-
značajno poboljšani funkcionalni kapacitet (p < 0,001) crease = 5.5 ± 6.6%; 4-month follow-up period) and the
pomoću šestominutnog testa hodanja (engl. 6-mi- infarction size (IS) decreased (decrease = 6.2 ± 5.0%). The
nute walk test – 6-MWT); (6-MWT; šestomesečni pe- long-term positive LVEF/IS effects were moderate. No
riod praćenja; p < 0,001) u grupi CABG plus MNĆ/MĆ cardiovascular mortality, reinfarction, clinically manifest
naspram kontrolne grupe (samo CABG). Ova terapija heart failure, malignant arrhythmia, or other adverse
se takođe pokazala kao bezbedan terapijski pristup events were detected [14,23,24].
Balint B. i sar.
– kardiovaskularni mortalitet je bio značajno niži (pe- Our initial results in coronary artery bypass grafting
togodišnji period praćenja; p = 0,049) kod bolesnika iz (CABG) followed by MNC/SC intramyocardial implan-
grupe CABG plus MNĆ/MĆ [2,25,45]. tation (the CABG plus MNC/SC group) showed the un-
doubted superiority of this method. LVEF significantly
ZAKLJUČAK improved (increase = 5.0 ± 4.2) in these patients. Also, a
Transplantacija MĆ je, bez sumnje, veoma efikasan significantly improved functional capacity (p < 0.001) was
modalitet lečenja hematoloških maligniteta i određe- confirmed with the 6-minute walk test (6-MWT; 6-months
nih bolesti nastalih zbog poremećaja imunskog siste- follow-up period; p < 0.001) in the CABG plus MNC/SC ver-
ma. Intenziviranje kliničke upotrebe terapije ćelijama sus the control (CABG alone) group. This treatment also
(transplantacija MĆ i regenerativna medicina) poveća- proved to be a safe therapeutic approach – cardiovascu-
la je potrebu za većim kvantitetom i boljim kvalitetom lar mortality was significantly lower (5-year follow-up pe-
suspenzije MĆ (veći prinos prikupljenih ćelija i bolja riod; p = 0.049) in CABG plus MNC/SC patients [2,25,45].
vijabilnost). Unapređeni protokoli prikupljanja, preči-
šćavanja i kriokonzervacije, kao i poboljšane extrakor-
CONCLUSION
poralne operativne procedure, svele su na minimum SC transplantation is undoubtedly an effective treat-
mehanička i termička oštećenja tokom ex vivo mani- ment for hematological malignancies and certain
pulacije ćelijama. Neophodno je raspolagati optimi- immune-mediated disorders. The intensification of
zovanim procedurama ekstrakorporalne manipulacije the clinical use of cell-mediated therapies (SC trans-
MĆ. Primena koncepta plastičnosti MĆ podstakla je plantation and regenerative medicine) has increased
sve širu terapijsku primenu primitivnih MĆ za obnav- the need for a higher quantity/quality of SCs (bet-
ljanje, odnosno regeneraciju organa. Neophodna su ter cell yields and viability). Improved SC collection,
buduća bazična istraživanja, kao i brojne randomizo- purification and cryopreservation protocols, as well
vane kontrolisane velike kliničke studije u oblastima as improved extracorporeal operating procedures,
transplantacijske i regenerativne primene MĆ, radi have minimized mechanical and thermal cell damage
bolje procene efikasnosti ove revolucionarne terapije during ex vivo manipulations. However, it is necessary
u lečenju ishemijske bolesti srca, ali i oštećenja drugih to have optimized SC extracorporeal manipulations.
tkiva, odnosno organa. The implementation of the concept of SC plasticity has
stimulated the ever-increasing therapeutic application
KRATAK PREGLED NAJVAŽNIJIH TEMA of immature SCs for organ regeneration/repair. We still
Primena konvencionalnih transplantacija MĆ je, bez need much more fundamental research and a greater
sumnje, delotvoran oblik lečenja hematoloških bolesni- number of randomized, controlled and larger clinical
ka. Opšte poznati efekti alogenih transplantacija u he- trials of SC transplantations, especially in the field of
matoonkologiji se koriste kako bi se razradio sistem koji regenerative medicine, in order to investigate the pos-
odvaja pozitivne efekte GvL, od negativnih efekata GvHD. sible role of this revolutionary therapy in treating isch-
Plastičnost MĆ je fenomen intersistemske ćelijske emic heart disease and other tissue/organ damage.
plastičnosti, koji omogućava široki fenotipski potenci-
jal vrlo primitivnih MĆ, sposobnih za ukalemljenje (ho-
HIGHLIGHTS
ming) u različita tkiva posle implantacije na oštećeno The use of conventional SC transplantations is undoubt-
mesto, uz sledstveno transdiferentovanje u ćelijske li- edly effective in the treatment of hematological pa-
nije tkiva/organa domaćina. tients. The well-known beneficial effects of allogeneic SC
Intersistemska plastičnost primitivnih MĆ opravda- transplantations in hemato-oncology have only recently
va njihovu primenu u lečenju bolesnika sa oštećenjima been used to design a system that separates the positive
na srcu, u jetri, pankreasu, i drugim organima ili tkivima. effects of GvL from the negative effects of GvHD.
SC plasticity is a phenomenon of inter-systemic cell
Sukob interesa: Nije prijavljen. plasticity, which represents a wide-ranging phenotyp-
ic potential of very primitive SCs capable of homing
to different tissues following implantation into a dam-
aged area, with a subsequent transdifferentiation into
the cell lineages of the host tissue/organ.
Intersystemic SC plasticity provides a rationale for the
use of immature SCs in the treatment of patients with dam-
age to the heart, liver, pancreas, and other organs/tissues.
Conflict of interest: None declared.
Balint B. et al.
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PROMENE U PRIMARNOJ ZDRAVSTVENOJ ZAŠTITI KAO ODGOVOR
NA PANDEMIJU KOVID-19 OBOLJENJA U CRNOJ GORI
ORIGINALNI RAD ORIGINAL ARTICLE
CHANGES IN PRIMARY HEALTH CARE IN RESPONSE TO

THE COVID-19 PANDEMIC IN MONTENEGRO
Lidija Šćepanović¹, Nataša Terzić¹
¹ Institut za javno zdravlje Crne Gore, Podgorica, Crna Gora ¹ Institute of Public Health of Montenegro, Podgorica, Montenegro
SAŽETAK ABSTRACT
Uvod: Primarna zdravstvena zaštita se smatra osnovom, ne samo za zadovolje- Introduction: Primary health care is considered the basis, not only for meeting
nje potreba za zdravstvenom zaštitom, već i za odgovor na krizne situacije, kakva healthcare needs, but also for responding to crisis situations, such as the crisis
je kriza uzrokovana izbijanjem pandemije KOVID-19 infekcije. caused by the outbreak of the COVID-19 pandemic.
Cilj: Cilj ove studije jeste da opiše promene u primarnoj zdravstvenoj zaštiti na- Aim: The aim of this study is to describe changes in primary health care caused
stale usled izbijanja KOVID-19 pandemije u Crnoj Gori, sa fokusom na organizaciju by the outbreak of COVID-19 in Montenegro, with a focus on the organization and
i pružanje zdravstvenih usluga. provision of health services.
Metode: Ovo je deskriptivna opservaciona studija u kojoj su glavne mere ishoda: Methods: This is a descriptive observational study with the following main out-
broj i način obavljenih poseta i usluga, uključujući e-servise, propisane antibi- come measures: number and manner of visits and services, including e-services,
otike i recepte po dijagnozi, na 1.000 stanovnika, u 2020. godini, u poređenju prescribed antibiotics and prescriptions according to the diagnosis, per 1,000 in-
sa istim parametrima u 2019. godini. Podaci su generisani iz zdravstveno-stati- habitants, in the year 2020, as compared to the same indicators in 2019. Data were
stičkog informacionog sistema Instituta za javno zdravlje Crne Gore. Korišćeni su generated from the health statistics information system of the Institute of Public
demografski podaci zvanične statistike. Health of Montenegro. Demographic data from official statistics were used.
Rezultati: Globalna pandemija promenila je način rada primarne zdravstvene Results: The global pandemic has changed the functioning of primary health care,
zaštite, a ad hoc rešenja su iznalažena u pogledu infrastrukture, zdravstvene and ad hoc solutions have been found, in terms of infrastructure, the health work-
radne snage i novih usluga e-zdravlja. U poređenju sa 2019. godinom, ukupne force, and new e-health services. As compared to 2019, in 2020, the total number of
posete na 1.000 stanovnika su, u 2020. godini, smanjene za 12%, dok su kućne visits per 1,000 inhabitants decreased by 12%, while home visits increased by 15%,
posete porasle za 15%, u trećem kvartalu. Elektronsko zakazivanje je bila najčeš- in the third quarter. Online scheduling (e-order) was the most commonly used e-ser-
će korišćena e-usluga (983.212 pristupa u 2020. godini). Propisani antibiotici nisu vice (accessed 983,212 times in 2020). The prescribed antibiotics did not exceed the
premašili mesečne stope iz 2019. godine (na 1.000 stanovnika). Broj propisanih monthly rates from 2019 (per 1,000 inhabitants). The number of prescriptions issued
recepata (na 1.000 stanovnika), u 2020. godini, porastao je za 8%, za dijagnoze za (per 1,000 inhabitants), in 2020, increased by 8% for the diagnoses for which doctors
koje su lekari propisivali najviše recepata (na 1.000 stanovnika). prescribed the most prescriptions (per 1,000 inhabitants).
Zaključak: Pandemija KOVID-19 oboljenja promenila je način rada primarne Conclusion: The COVID-19 pandemic has changed the functioning of primary health
zdravstvene zaštite, uz prelazak sa poseta u ambulanti na kućne posete, tele- care, with a transition from office visits to – home visits, telephone consultations,
fonske konsultacije i e-usluge, bez fizičkog kontakta. Međutim, ima prostora za and e-services, without physical contact. However, there is room for improvement
unapređenje u delu zadovoljenja potreba prevencije i lečenja drugih bolesti. in meeting health needs in the area of prevention and treatment of other diseases.
Ključne reči: primarna zdravstvena zaštita, posete, KOVID-19, Crna Gora Key words: primary health care, visits, COVID-19, Montenegro

Lidija Šćepanović Lidija Šćepanović
Institut za javno zdravlje Crne Gore, Podgorica, Crna Gora Institute of Public Health of Montenegro, Podgorica, Montenegro
Džona Džeksona bb, 81000 Podgorica, Crna Gora Džona Džeksona Street, 81000 Podgorica, Montenegro
Elektronska adresa: lidija.scepanovic@ijzcg.me E-mail: lidija.scepanovic@ijzcg.me
Primljeno • Received: May 6, 2022; Revidirano • Revised: May 10, 2022; Prihvaćeno • Accepted: June 5, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-37722
promene u primarnoj zdravstvenoj zaštiti kao odgovor na pandemiju kovid-19 oboljenja u crnoj gori
Šćepanović L. i sar.
changes in primary health care in response to the covid-19 pandemic in montenegro
UVOD INTRODUCTION
Primarna zdravstvena zaštita (PZZ), kao „kamen teme- Primary health care (PHC), as the “cornerstone of a sus-
ljac održivog zdravstvenog sistema“ [1], od suštinskog tainable health system“ [1], is essential for the response
je značaja za odgovor na pandemiju KOVID-19 infek- to the COVID-19 pandemic. Primary health care was ex-
cije. Od primarne zdravstvene zaštite se očekivalo da pected, not only to meet the ‘usual’ needs in health care,
zadovolji ne samo „uobičajene“ potrebe zdravstvene but also to respond to the crisis situation, as well as to
zaštite, već i da odgovori na kriznu situaciju i da se mo- adapt, in order to meet the needs of the patients with
difikuje kako bi zadovoljila potrebe pacijenata sa sum- suspected COVID-19, as well as the needs of the patients
njom na KOVID-19 infekciju, te testiranih i potvrđenih tested for COVID-19, and with a confirmed diagnosis of
obolelih pacijenata. PZZ je morala da iskoristi svoje the disease. PHC had to use its advantages in order to
prednosti kako bi razvila osnovnu strategiju za suo- develop a basic strategy for dealing with the COVID-19
čavanje sa pandemijom KOVID-19 oboljenja, a među pandemic, with these advantages being: familiarity be-
te prednosti spadaju: poznavanje lekara i pacijenata, tween the doctors and patients, a good relationship
njihovi dobri odnosi, pristup zdravstvenim uslugama, between the doctors and patients, access to healthcare
i drugo [2]. Upravljajući glavnim delom tereta pande- services, etc. [2]. In managing the best part of the bur-
mije KOVID-19 oboljenja, pri čemu je istaknuta njena den of the COVID-19 pandemic, wherein its role of the
uloga čuvara ulaznih tačaka u zdravstveni sistem i ulo- healthcare system gatekeeper, as well as its role in triage
ga u trijaži, PZZ je morala da zadrži fokus na zdravlju have been emphasized, PHC had to maintain focus on
zajednice u celini [3]. the health of the community as a whole [3].
Crna Gora je bila poslednja država u Evropi koja Montenegro was the last country in Europe to
je registrovala prve slučajeve KOVID-19 oboljenja, register its first cases of COVID-19, which provided the
što je crnogorskim vlastima omogućilo dodatno Montenegrin authorities with an opportunity to prepare
vreme da pripreme celokupni sistem za odgovor na the entire system for a response to the pandemic [4].
pandemiju [4]. Međutim, slično drugim zemljama However, similarly to other countries in Southeast
Jugoistočne Evrope (JIE), i Crna Gora se suočavala sa Europe (SEE), Montenegro also faced a number of
nizom različitih poteškoća (npr. nedostatak zaštitne different challenges (e.g., lack of personal protective
opreme) [5]. Pre prvih slučajeva, Institut za javno equipment) [5]. Before the first cases were registered,
zdravlje Crne Gore (IJZCG) predstavio je prvu verziju the Institute of Public Health of Montenegro (IPHM)
Nacionalnog akcionog plana za KOVID-19 u Crnoj Gori presented the first version of the National Action Plan for
[6]. Nakon izbijanja epidemije KOVID-19 oboljenja u COVID-19 in Montenegro (i.e., COVID-19: Preparedness
Italiji [7], i nakon što su potvrđeni prvi slučajevi u Crnoj and Response Plan Montenegro) [6]. After the COVID-19
Gori (17. marta 2020. godine), PZZ je bila prva ulazna epidemic broke out in Italy [7], and after the first cases
tačka za osobe sa simptomima KOVID-19 infekcije, of the disease were confirmed in Montenegro (March
koja se suočila sa potrebom da se transformiše, 17, 2020), PHC was the first entry point for persons
kako bi mogla da odgovori na izazove pandemije. with symptoms of the COVID-19 infection, and it was
To je uključivalo, ne samo promene u organizaciji, faced with the necessity to transform, in order to be
menadžmentu, komunikaciji i radu, već i stalno able to respond to the challenges of the pandemic. This
menjanje i prilagođavanje novim načinima rada i included, not just changes in organization, management,
pružanja zdravstvenih usluga. Pored opšteg strateškog communication, and work, but also constant changing
plana, koji je usvojila Vlada, Klinika za infektivne bolesti and adapting to the new modes of operation and new
je izdala i nacionalne preporuke za lečenje KOVID-19 ways of providing health services. In addition to the
oboljenja, uključujući smernice za lečenje i mere general strategic plan, adopted by the Government,
podrške. Druge nacionalne smernice za primarnu the Clinic for Infectious Diseases also issued national
zdravstvenu zaštitu u vezi sa KOVID-19 infekcijom, koje recommendations for treating COVID-19, including
bi podržale centre primarne zdravstvene zaštite, kao guidelines for treatment and support measures. Other
odgovor na pandemiju ovog oboljenja, nisu razvijene. national guidelines for PHC, in relation to COVID-19,
Odluke na nacionalnom nivou je donosio ad hoc tim which would provide additional support for the primary
Nacionalnog koordinacionog tela (NKT). healthcare centers, as a response to the pandemic of
Cilj rada je da opiše promene primarne zdravstvene the new disease, were not developed. Decisions at the
zaštite nakon izbijanja epidemije KOVID-19 oboljenja u national level were made by the ad hoc team of the
Crnoj Gori, sa fokusom na organizaciju i nekoliko mera National Coordinating Body (NCB).
ishoda. The aim of this paper is to describe the changes in
primary health care, occurring after the outbreak of the
Šćepanović L. et al.
PRIMARNA ZDRAVSTVENA ZAŠTITA U CRNOJ COVID-19 epidemic in Montenegro, with a focus on the
GORI organizational aspect, as well as on several measures
of outcomes.
Primarna zdravstvena zaštita u Crnoj Gori je organizo-
vana dominantno u javnom vlasništvu. Reformisana je PRIMARY HEALTH CARE IN MONTENEGRO
u poslednjih dvadeset godina, kako bi se zadovoljio
najveći deo potreba stanovništva za zdravstvenom za- Primary health care in Montenegro is predominantly
štitom. Zadaci i organizacija primarne zdravstvene za- organized within publicly owned institutions. In the
štite su precizno definisani zakonskim okvirom, sa fo- last 20 years, it has undergone reforms, in order to meet
kusom na porodičnu medicinu [8]. PZZ obuhvata širok most of the healthcare needs of the population. The
spektar usluga koje se pružaju odraslima, deci i mladi- responsibilities and the organization of primary health
ma, ženama (u pogledu reproduktivnog zdravlja), a u care are precisely defined within the legal framework,
primarnu zdravstvenu zaštitu spadaju i stomatološke with a focus on family medicine [8]. PHC encompass-
usluge, usluge u oblasti mentalnog zdravlja, hitne po- es a wide array of services offered to adults, children
moći, i druge. PZZ je prioritet u razvoju zdravstvenog and youths, and women (in the field of reproductive
sistema Crne Gore i pruža se u 18 domova zdravlja, koji health). Primary health care also includes dental health
imaju jedinice na različitim gradskim i prigradskim lo- services, services in the area of mental health, emer-
kacijama. Dom zdravlja ima tri osnovne jedinice: (i) am- gency services, and other. PHC is a priority in the de-
bulante izabranih lekara (pedijatri za decu do 15 go- velopment of the healthcare system of Montenegro.
dina, lekari za odrasle i ginekolozi); (ii) centre podrške Its services are provided within 18 community health-
izabranim lekarima, organizovane na lokalnom i regio- care centers, which have units at different urban and
nalnom nivou (plućne bolesti, dijagnostika, mentalno suburban locations. The community healthcare center
zdravlje, prevencija, i drugo); (iii) jedinice za: patronažu, has three basic types of units: (i) offices of the ‘selected
primarni nivo fizikalne terapije i medicinski transport. physicians’ (i.e., primary care physicians/family doctors)
Prema podacima posljednjeg popisa iz 2011. – pediatricians for children up to the age of 15, GPs for
godine, Crna Gora ima 620.029 stanovnika, sa adults, as well as gynecologists for women; (ii) support
tendencijama postepenog starenja stanovništva (pad centers for the primary care physicians, organized at
nataliteta, fertiliteta i prirodnog priraštaja) i porasta the local and regional levels (pulmonary diseases, di-
stope mortaliteta [9]. Izabrani lekari posećuju one koji agnostics, mental health, prevention, other); (iii) units
ne mogu da posete lekara u prostorijama primarne for home and domiciliary visits, primary-level physical
zdravstvene zaštite. Pored toga, patronažni timovi therapy, and medical transport.
vrše kućne posete u cilju pružanja preventivnih ili According to the data from the latest census
kurativnih usluga za najugroženiju populaciju (posete (2011), the population of Montenegro is 620,029, with
u trudnoći, posete novorođenčadi i maloj deci, posete tendencies of gradual population ageing (decreasing
starima). Služba koja pruža zdravstvene usluge deci van birthrate, fertility rate, and population growth) and
radnog vremena je obezbeđena u jedinici primarne mortality rate increase [9]. Primary care physicians
zdravstvene zaštite koja je dežurna, a za odrasle, visit those patients who are unable to visit the doctor’s
u jedinicama hitne pomoći primarne zdravstvene office in the primary health care facilities. Additionally,
zaštite, tokom 24 časa. Pristup primarnoj zdravstvenoj teams for home and domiciliary visits carry out
zaštiti je moguć putem zakazanih poseta, poseta bez home visits with the aim of providing preventive and
zakazivanja, u slučaju hitne potrebe, kao i putem treatment services for the most vulnerable groups
telefonskih konsultacija. Centri za mentalno zdravlje (visits during pregnancy, home visits for newborns
su organizovani na bazi ambulanti. PZZ ima pozivni and small children, home visits for the elderly). A unit
(„kol“) centar za opšte informacije i zakazivanje. providing out-of-hours services to children operates
within the primary health care unit that is on-call/on-
MATERIJALI I METODE duty at the time, while adults receive out-of-hours care
in emergency units within the PHC, which are on-duty
Ova studija je osmišljena kao komparativna opserva-
24 h. Access to PHC is possible via scheduled visits,
ciona analiza broja i načina obavljenih poseta i uslu-
unscheduled visits, in case of an emergency, as well as
ga, uključujući tu i e-servise, propisane antibiotike i
via telephone consultations. Mental health centers are
recepte po dijagnozi, na 1.000 stanovnika Crne Gore,
organized as clinics/outpatient facilities. PHC has a call
tokom prve godine pandemije (2020. godina) i u go-
center for issuing general information and scheduling
dini pre pandemije (2019. godina). Korišćeni podaci
appointments.
su generisani iz zdravstveno-statističkog sistema In-
stituta za javno zdravlje Crne Gore (IJZCG). Među njih MATERIALS AND METHODS
spadaju: broj poseta primarnoj zdravstvenoj zaštiti;
This study is designed as a comparative observational
način obavljanja konsultacija (poseta u ambulanti/ku-
analysis of the number and method of provided visits
ćna poseta); broj recepata za najčešće dijagnoze pre-
and services. These services include e-services, pre-
ma Desetoj reviziji Međunarodne klasifikacije bolesti
scribed antibiotics, and prescriptions issued on the basis
(MKB-10), kao što su: hipertenzija (I10), dijabetes (E11),
of registered diagnoses, per 1,000 population, in Mon-
hronična opstruktivna bolest pluća (J44), astma (J45),
tenegro, during the first year of the COVID-19 pandem-
dispepsija (K30), angina pectoris (I20), kardiomiopati-
ic (2020), and in the year before the pandemic (2019).
ja (I42), i akutni bronhitis (J20), za koje su propisivani
The data used was generated from the health statistics
lekovi i antibiotici za grupu J01 (antibakterijski lekovi
information system of the Institute of Public Health of
za sistemsku primenu), na 1.000 stanovnika. Podaci
Montenegro (IPHM). These data include: number of vis-
se odnose na period januar – septembar, 2019. i 2020.
its to PHC; method of performing consultations (visit to
godine. Takođe, podaci o e-servisima su dobijeni od
the doctor’s office/home visit); number of issued pre-
Fonda zdravstvenog osiguranja Crne Gore, za period
scriptions for the most common diagnoses, according
januar – septembar 2019. i 2020. godine. Korišćeni su
to the Tenth Revision of the International Classification
demografski podaci zvanične statistike za izračunava-
of Diseases (ICD-10), such as: hypertension (I10), diabe-
nje stopa. Analiza podataka je bila deskriptivna i anali-
tes (E11), chronic obstructive pulmonary disease (J44),
tička, sa fokusom na promene u načinu rada, obavlja-
asthma (J45), dyspepsia (K30), angina pectoris (I20), car-
nju konsultacija, i pružanju zdravstvenih usluga, nakon
diomyopathy (I42), and acute bronchitis (J20), for which
izbijanja epidemije KOVID-19 infekcije u Crnoj Gori.
drugs and antibiotics were prescribed, belonging to
REZULTATI the J01 group (antibacterial drugs for systemic use), per
1,000 population. The data relate to the period January
Nakon izbijanja epidemije KOVID-19 oboljenja u Crnoj – September of 2019 and 2020. Additionally, data on
Gori, pripremljen je strateški plan pripravnosti kao od- e-services, pertaining to the period January – Septem-
govor na krizu, koji je, međutim, više bio fokusiran na ber of 2019 and 2020, were obtained from the Health
organizaciju bolničkih kapaciteta u zemlji [6,10]. PZZ je Insurance Fund of Montenegro. Demographic data of
shodno tome morala da napravi sopstvenu organizaci- the official statistics for calculating rates were used. Data
ju i način rada, kao odgovor na krizu. Prvo je uspostav- analysis was descriptive and analytical, with a focus on
ljena trijaža na ulazu u ustanove primarne zdravstvene changes in the mode of operation, changes in perform-
zaštite, dok je pacijentima savetovano da izbegavaju ing consultations, as well as changes in providing health
posete. Pacijentima, za koje se sumnjalo da su obole- services, after the COVID-19 outbreak in Montenegro.
li od oboljenja KOVID-19, savetovano je da telefonom
kontaktiraju ambulante primarne zdravstvene zaštite. RESULTS
Telefonske linije u ambulantama za KOVID-19 bile su
After the outbreak of the COVID-19 epidemic in Mon-
otvorene za zakazivanje na dnevnom nivou, kao i za
tenegro, in response to the crisis, a strategic prepared-
dobijanje rezultata testova, informacija i kratkih medi-
ness and response plan was prepared, which was,
cinskih saveta. PZZ je vršila nadzor nad osobama koje
however, more focused on the organization of the
su bile u karantinu i izolaciji, pri čemu je poseban iza-
country’s in-patient hospital capacities [6,10]. Conse-
zov bilo brzo reagovanje i prepoznavanje ranih znako-
quently, PHC had to manage its own organization and
va pogoršanja zdravstvenog stanja, koje zahteva bol-
mode of operation, in response to the crisis. First, triage
ničko lečenje. Prioritet je bilo zbrinjavanje pacijenata
was established at the entrances of the primary health
sa oboljenjem KOVID-19, nauštrb potreba za redovnim
care facilities, while patients were advised to avoid vis-
zdravstvenim uslugama u domovima zdravlja. Takođe,
its. Also, patients in whom COVID-19 was suspected
patronažni timovi su prvenstveno obavljali kućne po-
were advised to contact primary health care clinics by
sete pacijentima sa simptomima KOVID-19 infekcije.
phone. The telephone lines in COVID-19 clinics were
Domovi zdravlja su podeljeni na dve celine: deo
open for scheduling appointments, obtaining test re-
za pacijente sa sumnjom na KOVID-19 oboljenje i deo
sults, getting information and short medical advice, on
za pacijente koji nisu zaraženi ovom infekcijom, u koju
a daily basis. PHC monitored persons who were in iso-
svrhu su otvarani novi ili korišćeni privremeni montažni
lation and quarantine, wherein a particular challenge
objekti. Rukovodstvo domova zdravlja je moralo da iz
was providing a quick response and recognizing the
postojeće zdravstvene radne snage obezbedi kadar i
early signs of deterioration in the health status of the
za KOVID-19 ambulante. Ad hoc rešenja za proširenje
patient requiring in-hospital treatment and care. The
kapaciteta radne snage bila su: izmena rasporeda
priority was taking care of COVID-19 patients, at the
rada, izmena radnog vremena i uvođenje dežurstava cost of regular health care services that are normally
sa dodatnim satima. KOVID-19 timovi su deo svog provided at the community health care centers. Also,
radnog vremena provodili u kućnim posetama. the teams for home and domiciliary visits primarily vis-
Zdravstveni radnici koji su bili uključeni u testiranje ited patients with COVID-19 symptoms.
i lečenje obolelih od KOVID-19 infekcije, dobijali su, The community health care centers were divided
u više navrata, novčane podsticaje. Upućivanje na into two separate subdivisions: the division with
testiranje je vršeno preko ambulanti domova zdravlja patients with suspected COVID-19 and the division for
i preko pozivnog centra u IJZCG-u. Testiranje je bilo non-COVID-19 patients. To this end, new facilities were
centralizovano u referentnoj ustanovi koja vrši PCR built, or temporary prefabricated buildings were used.
testiranja na nacionalnom nivou – IJZCG. Uzorci za The management of the community health care centers
ispitivanje su dopremani svakodnevno iz svih gradova had to provide staff for the COVID-19 clinics from its
u IJZCG, a rezultati su, u većini slučajeva, dobijani u existing pool of health workers. The ad hoc solutions
roku od 24 sata. for providing increased working capacities were, as
follows: changes in the work schedules, changes in
ELEKTRONSKI SERVISI working hours, and introducing on-duty shifts with
Veb portal „E-zdravlje“ [11] integrisao je postojeće e-us- additional working hours. The COVID-19 teams spent
luge (npr. e-zakazivanje, e-recept, e-rezultati analize) i a part of their shift in house visits. Health workers who
nove e-usluge, koje su postale dostupne korisnicima took part in testing and treating COVID-19 patients
(Grafikon 1). Elektronsko zakazivanje je bila najčešće were awarded financial incentives, on a number of
korišćena e-usluga (983.212 pristupa u 2020. godini), occasions. Patients were referred for testing through
koja je upotrebljena 3,7 puta više nego prethodne go- the COVID-19 clinics at the community health care
dine. Nova e-usluga – KOVID-19, posebno je razvijena centers and through the IPHM call center. The testing
tokom pandemije, u svrhu dobijanja povratnih infor- process was centralized at the reference institution
macija o rezultatima testova (više od 600.000 pristupa performing PCR testing at the national level – the
u 2020. godini). E-recept je bio među veoma intenziv- IPHM. Samples were delivered to the IPHM for testing
no korišćenim e-aplikacijama (243.378 pristupa). from all towns in Montenegro, on a daily basis, and the
test results were, in most cases, issued within 24 hours.
POSETE U AMBULANTI, KUĆNE I UKUPNE
POSETE E-SERVICES
Ukupne posete na 1.000 stanovnika u 2020. godini The web portal E-zdravlje (E-health) [11] integrated the
(Tabela 1) smanjile su se za 12% (po kvartalima: -4,5%; existing e-services (e.g., e-order, e-prescription, e-test
results) and new e-services, which also became avail-
* podaci za prva tri kvartala *data for the first three quarters
Grafikon 1. Upotreba e-servisa u 2019. godini naspram 2020. godine. Izvor: Figure 1. Use of e-services in 2019 vs 2020; Source: Institute of Public Health
Institut za javno zdravlje Crne Gore, 2020. of Montenegro, 2020
Tabela 1. Broj poseta (ukupne, kućne i u ambulanti) u ustanovama na primar- Table 1. Number of visits (total, home and office visits) in primary health care
nom nivou zdravstvene zaštite u Crnoj Gori, na 1.000 stanovnika, u periodu ja- institutions, in Montenegro, per 1,000 inhabitants, in the period January –
nuar – septembar; 2019. godina naspram 2020. godine September; year 2019 vs year 2020
Godina / Year 2019. 2020.

Kvartal / Quarter I II III I II III
Ukupne posete na 1.000 stanovnika / Total
1.725 1.595 1.611 1.648 1.293 1.413
visits per 1,000 population
Kućne posete na 1.000 stanovnika / Home

5,64 5,51 5,28 4,57 3,62 6,09
visits per 1,000 population
Posete u ambulanti na 1.000 stanovnika /

1.720 1.589 1.605 1.644 1.290 1.407
Office visits per 1,000 population
-18,9%; -12,2%), što važi i za udeo poseta u ambulanti able to users (Figure 1). Electronic scheduling (e-or-
(-4,42; -18,84; -12,34), dok su se kućne posete timova der) was the most frequently used e-service (accessed
primarne zdravstvene zaštite takođe smanjile u prvom 983,212 times in 2020) and was used 3.7 times more
i drugom kvartalu (-19,09%; -34,27%), a porasle u tre- than the previous year. The new e-service – COVID-19,
ćem kvartalu (+15,36%). was specially developed during the pandemic, for the
purpose of obtaining feed-back on test results (ac-
PROPISANI ANTIBIOTICI: JANUAR – SEPTEMBAR cessed more than 600,000 times in 2020). E-prescrip-
2019. GODINE I JANUAR- SEPTEMBAR 2020. tion was amongst the very frequently used e-applica-
GODINE tions (accessed 243,378 times).
Broj propisanih antibiotika, u periodu januar – septem- OFFICE VISITS, HOME VISITS, TOTAL NUMBER
bar 2020. godine, bio je 23% manji, prema ukupnom
OF VISITS
broju recepata, nego u istom periodu 2019. godine.
Propisani antibiotici na 1.000 stanovnika u 2020. go- The total number of visits per 1,000 population in
dini nisu premašili stopu iz 2019. godine (Grafikon 2). 2020 (Table 1) decreased by 12% (by quarters: -4.5%;
Stopa je bila najniža u aprilu, nakon čega je porasla, ali -18.9%; -12.2%), which is also true for office visits (-4.42;
je ipak ostala niža nego 2019. godine. -18.84; -12.34), while home visits of the PHC teams also
Grafikon 2. Broj propisanih recepata za ATC grupu J01 – Antibiotici za Figure 2. Number of prescriptions for ATC group J01 – Antibiotics for systemic
sistemsku upotrebu, na 1.000 stanovnika, u periodu januar – septembar; 2019. use, per 1,000 population, in the period January – September; years 2019 and
i 2020. godina, u Crnoj Gori; Izvor: Institut za javno zdravlje Crne Gore, 2020. 2020, in Montenegro; Source: Institute of Public Health of Montenegro, 2020
Kada se uporedi deset dijagnoza (MKB-10) za decreased in the first and second quarters (-19.09%;
koje su lekari propisali najviše recepata (na 1.000 -34.27%) and increased in the third quarter (+15.36%).
stanovnika), broj recepata (na 1.000 stanovnika) je
porastao za 8% u 2020. godini u odnosu na 2019. PRESCRIBED ANTIBIOTICS: JANUARY – SEPTEMBER
godinu (Grafikon 3). Najveći rast, od 24,4%, imali su 2019 AND JANUARY – SEPTEMBER 2020
recepti za bolesti cirkulatornog sistema. The number of prescribed antibiotics in the period Jan-
uary – September 2020 decreased by 23%, regarding
DISKUSIJA
the total number of prescriptions, as compared to the
Ova studija stavlja akcenat na transformaciju i prome- same period in 2019. The prescribed antibiotics per
ne primarne zdravstvene zaštite, do kojih je došlo u 1,000 population in 2020 did not surpass the rate from
prvim talasima epidemije KOVID-19 oboljenja u Crnoj 2019 (Figure 2). The rate was the lowest in April, upon
Gori. PZZ se suočila sa izazovima u sprovođenju tzv. which it increased but still remained lower than in 2019.
„dvostrukog koloseka“ u pružanju zdravstvenih uslu- When the 10 diagnoses (ICD-10) for which doctors
ga i pacijentima sa KOVID-19 oboljenjem i onima koji prescribed the highest number of prescriptions (per
Grafikon 3. Deset dijagnoza (MKB-10) za koje su doktori propisivali lekove (na Figure 3. Ten diagnoses (ICD-10) for which doctors prescribed medication (per
1.000 stanovnika), u 2020. i 2019. godini; Izvor: Institut za javno zdravlje Crne 1,000 population), in the years 2020 and 2019; Source: Institute of Public He-
Gore, 2020. alth of Montenegro, 2020
nisu oboleli od ove bolesti, što je bilo neophodno za 1,000 population) are compared, it transpires that
uspostavljanje bezbednog okruženja u zdravstvenim the number of prescriptions (per 1,000 population)
ustanovama. Ova studija je pokazala da je PZZ, u Cr- increased by 8% in 2020, as compared to 2019 (Figure 3).
noj Gori, brzo prilagodila fizičku infrastrukturu (novi The greatest increase, amounting to 24.4%, was noted
objekti ili transformisani postojeći kapaciteti) omogu- amongst the prescriptions for cardiovascular diseases.
ćivši da pacijenti, za koje se sumnjalo da su oboleli od
KOVID-19 infekcije, budu pregledani i praćeni, te da je DISCUSSION
izvršila promene u upravljanju ljudskim resursima (mo- This study emphasizes the transformation and chang-
difikacija rasporeda rada, uvođenje dodatnih radnih es in primary health care, which occurred in the first
sati, finansijski podsticaji, uređenje uslova rada). Neko- waves of the COVID-19 epidemic in Montenegro. PHC
liko evropskih zemalja (Belgija, Holandija, Irska) orga- faced the challenges of implementing a parallel system
nizovalo je usluge na sličan način, u KOVID-19 ambu- in providing health services both to COVID-19 and non-
lantama (hub-ovima), kako bi se obezbedilo bezbedno COVID-19 patients, which needed to be established, in
zbrinjavanje pacijenata [12]. order to provide a safe environment in the healthcare
Naši podaci su pokazali da je, uprkos smanjenju units. This study has shown that, in Montenegro, PHC
poseta u okviru primarne zdravstvene zaštite (posete quickly adapted its physical infrastructure (by build-
pacijenata u ambulantama i kućne posete lekara), u ing new buildings or transforming existing facilities),
prvim mesecima nakon izbijanja pandemije KOVID-19 thus enabling the examining and follow-up of patients
oboljenja, došlo do povećanja broja kontakata sa with suspected COVID-19, and that it also implement-
primarnom zdravstvenom zaštitom. Zanimljivo je i to ed changes in human resources management (modi-
da bi porast kućnih poseta u trećem kvartalu 2020. fications to the work schedule, introducing additional
godine, mogao biti rezultat organizovanja kućnih working hours, financial incentives, improving/orga-
poseta patronažnih timova primarne zdravstvene nizing work conditions). Several European countries
zaštite za praćenje pacijenata sa simptomima KOVID-19 (Belgium, the Netherlands, Ireland) organized services
infekcije. Mnogo zemalja je takođe prijavilo da je, kao in a similar way, within COVID-19 clinics (hubs), in order
indirektni rezultat izbijanja KOVID-19 pandemije, to provide safe environments for patient care [12].
došlo do drastičnog pada obima poseta primarnoj Our data have shown that, despite a decrease in
zdravstvenoj zaštiti [15]. Pružanje zdravstvenih usluga visits within PHC (office visits and home visits), the
na daljinu, putem telefonskih linija i veb portala number of contacts with PHC increased, in the first
„E-zdravlje“, povećalo je, u velikoj meri, broj kontakata months after the outbreak of the COVID-19 pandemic.
sa primarnom zdravstvenom zaštitom, nakon izbijanja It is also interesting that the increase in home visits
epidemije KOVID-19 infekcije u Crnoj Gori. Veliki broj in the third quarter of 2020 could be the result of
evropskih zemalja je smatralo da je prelazak na pružanje organized home visits by PHC teams for the purpose
zdravstvenih usluga na daljinu bilo neophodno [13]. of monitoring patients with COVID-19 symptoms.
E-usluge su omogućile pacijentima da korišćenjem Many countries also reported that, as an indirect
svojih uređaja (računar, pametni telefon, tablet, itd.) result of the COVID-19 pandemic outbreak, a drastic
dobiju propisane lekove. Lekari primarne zdravstvene decrease in the scope of PHC visits was registered [15].
zaštite su mogli da propišu lek bez fizičkog kontakta, Providing remote health services, via telephone lines
odnosno posle telefonske konsultacije, što je bilo and the web portal E-zdravlje, increased, to a great
veoma pogodno za određene pacijente (npr. za starije extent, the number of contacts with primary health
osobe, osobe sa hroničnim ili drugim bolestima). Pored care, upon the outbreak of the COVID-19 epidemic in
toga, e-usluge, kao što su e-rezultati zdravstvenih Montenegro. A large number of European countries
analiza ili e-prava, bile su pogodne za dobijanje felt that the transition to remote health services was
rezultata laboratorijskih testova ili dokumentacije i necessary [13]. E-services enabled the patients to
drugih sertifikata, koje obično izdaje PZZ (npr. sertifikati obtain their prescription medication through the use
za vrtić ili bolovanje), bez napuštanja kuće. of their electronic devices (computer, smartphone,
Smanjenje poseta u okviru primarne zdravstvene tablet, etc.) Primary healthcare physicians could
zaštite (posete pacijenata u ambulantama i kućne prescribe medication without physical contact, i.e.,
posete lekara) praćeno je smanjenjem broja propisanih after a telephone consultation, which was very helpful
antibiotika (januar – septembar 2020. godine u to certain patients (e.g., elderly patients, patients with
odnosu na januar – septembar 2019. godine), na 1.000 chronic and other diseases). Also, e-services, such as
stanovnika. Studija sprovedena u drugoj maloj zemlji e-results of health tests or e-rights, were appropriate for
je otkrila da je pandemija KOVID-19 oboljenja imala obtaining lab test results or documents and certificates
mali uticaj na propisivanje antibiotika [13]. Međutim, customarily issued by PHC (health certificates for
u drugim slučajevima, ograničen pristup zdravstvenoj preschool attendance or sick-leave certificates) without
zaštiti zbog pandemije KOVID-19 oboljenja doveo je do any need for the patient to leave their home.
povećanog propisivanja antibiotika [14]. Naša studija The decrease in the number of visits within PHC
je pokazala da je broj propisanih antibiotika u trećem (office visits and home visits) was followed by the
kvartalu 2020. godine porastao, te skoro dostigao nivo iz decrease in the number of prescribed antibiotics
2019. godine. Moguće je da je na povećanje propisivanja (January – September 2020 as compared to January –
lekova uticalo enormno povećanje usluge e-recepta. September 2019), per 1,000 population. A study from
Što se tiče 10 vodećih dijagnoza iz MKB-10 another small country revealed that the COVID-19
klasifikacije, za koje su lekari propisivali lekove (na 1.000 pandemic had a small impact on the prescribing of
stanovnika), najviše je porastao broj recepata za bolesti antibiotics [13]. However, in other cases, the limited
sistema krvotoka, koje su vodeći uzrok oboljevanja i access to primary health care resulting from the
smrti u Crnoj Gori. Očekivano, vodećih 10 dijagnoza COVID-19 pandemic, led to the increased prescribing
MKB-10 klasifikacije, za koje su lekari propisivali lekove of antibiotics [14]. Our study has shown that the
(na 1.000 stanovnika) u pandemiji bile su uobičajene number of prescribed antibiotics increased in the third
dijagnoze: hipertenzija (I10), dijabetes (E11), hronična quarter of 2020, almost reaching the level of 2019. It is
opstruktivna bolest pluća (J44), astma (J45), dispepsija possible that the increase in the prescribing of drugs
(K30), angina pectoris (I20) i kardiomiopatija (I42). was influenced by the enormous increase in the use of
Iznenađujuće, dijagnoza akutnog bronhitisa (J20) nije the e-prescription service.
bila među 10 vodećih uzroka za koje su lekari propisivali Regarding the 10 leading diagnoses from the ICD-
lekove tokom pandemije. Ukupan porast broja recepata 10, for which doctors prescribed medication (per 1,000
za 10 vodećih dijagnoza MKB-10 klasifikacije ukazuje na population), the number of prescriptions increased the
to da je PZZ bila relativno dostupna tokom pandemije. most for circulatory system diseases, which are, indeed, the
Naša studija ima nekoliko ograničenja. Korišćeni leading cause of morbidity and mortality in Montenegro.
podaci su generisani iz izveštaja primarne zdravstvene As expected, the 10 leading ICD-10 diagnoses for which
zaštite u državnom vlasništvu i nisu uključili podatke doctors prescribed medication (per 1,000 population)
o uslugama pružanim u privatnim ambulantama during the pandemic, were the usual diagnoses:
(propisani lekovi, posete, itd.). Osim što opisuje hypertension (I10), diabetes (E11), chronic obstructive
promene u primarnoj zdravstvenoj zaštiti i nekoliko pulmonary disease (J44), asthma (J45), dyspepsia (K30),
ishoda, našoj studiji nedostaju zaključci u pogledu angina pectoris (I20), and cardiomyopathy (I42). What
efikasnosti i kvaliteta nege. Promene primarne is surprising is that the diagnosis of acute bronchitis
zdravstvene zaštite koje su se desile nisu praćene (J20) was not amongst the 10 leading causes for which
trenutnim promenama u informacionom sistemu i doctors prescribed medication during the pandemic.
izveštavanju, što se odrazilo na kvalitet dostupnih The total increase of the number of prescriptions for
podataka. Nisu ispitane posledice koje je odlaganje the 10 leading ICD-10 diagnoses indicates that PHC was
redovnih poseta ustanovama primarne zdravstvene relatively accessible during the pandemic.
zaštite imalo na zdravlje pacijenata. Vremenski period Our study has several limitations. The data used in
koji je obuhvatila ova studija je relativno kratak, tako the study were generated from the reports pertaining
da je preporuka da se nastavi detaljnije istraživanje to state-owned PHC and did not include data on health
odgovora primarne zdravstvene zaštite na pandemiju services provided at privately owned clinics (prescribed
KOVID-19 oboljenja. medication, visits, etc.). While the study describes the
changes in primary health care and several outcomes,
ZAKLJUČAK it lacks conclusions with respect to the efficiency and
U Crnoj Gori, primarna zdravstvena zaštita se suočila quality of care. The changes in PHC that occurred
sa naglim promenama, nakon izbijanja pandemije KO- were not followed by changes in the information and
VID-19 oboljenja, što je rezultiralo transformacijom na- reporting system, which has had impact on the quality of
čina pružanja usluga i upravljanja. Prelaskom sa poseta available data. The effect that the postponing of regular
u ordinaciji na – kućne posete, telefonske konsultacije visits to PHC clinics has had on the health of patients
i e-usluge, bez fizičkog kontakta, omogućen je pristup has not been investigated and analyzed. The time
zdravstvenim uslugama. Ukupan porast broja recepa- period covered by this study is relatively short, which
ta za 10 vodećih dijagnoza (MKB-10) ukazuje da je PZZ is why the recommendation is that a more detailed
bila relativno dostupna tokom pandemije. Propisiva- analysis should be performed regarding the response
nje antibiotika pratilo je povećanje korišćenja usluga of primary health care to the COVID-19 pandemic.
e-zdravstva, ali nije premašilo broj recepata iz 2019. CONCLUSION

godine. Iako je PZZ uspela da se delom transformiše,
In Montenegro, primary health care faced abrupt
ima prostora za unapređenje u delu zadovoljenja po-
changes after the COVID-19 outbreak, which resulted
treba prevencije i lečenja drugih bolesti.
in the transformation of the method of management
SPISAK SKRAĆENICA and providing services. With the transition from office
visits to – home visits, telephone consultations, and
ATC – Anatomsko-terapijsko-hemijska klasifikacija (engl. Anatomical e-services, without physical contact, access to PHC was
Therapeutic Chemical Classification System) made possible. The overall increase in the number of
IJZCG – Institut za javno zdravlje Crne Gore prescriptions issued for the 10 leading diagnoses (ICD-
JIE – Jugoistočna Evropa 10) indicates that PHC was relatively accessible during
MKB-10 – Međunarodna klasifikacija bolesti, 10 revizija the pandemic. The prescribing of antibiotics followed
NKT – Nacionalno koordinaciono telo the increase in the use of e-health services, but it did
PZZ – primarna zdravstvena zaštita not surpass the number of prescriptions issued in
PCR – lančana reakcija polimeraze (engl. polymerase chain reaction) 2019. Although PHC was, in part, transformed, there is
still room for improvement in meeting health needs in
Sukob interesa: Nije prijavljen.
the area of prevention and treatment of other diseases.
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tory.who.int/monitors/hsrm/hsrm-countries/hsrm/montenegro
MIGRACIJA DIJAGNOSTIČKI SRODNIH GRUPA KAO POKAZATELJ
POTENCIJALNO NEEFIKASNE MEDICINSKE INTERVENCIJE
DIAGNOSIS RELATED GROUP MIGRATION AS AN INDICATOR

OF A POTENTIALLY INEFFICIENT MEDICAL INTERVENTION
Marina Topalović1, Mirjana Milošević1, Zorica Terzić-Šupić2, Jovana Todorović2, Milena Šantrić Milićević2
1
Ministarstvo zdravlja Republike Srbije, Drugi projekat razvoja Ministry of Health of Republic Serbia, Second Serbia Health
1
zdravstva Srbije Project

2
Univerzitet u Beogradu, Medicinski fakultet, Institut za socijalnu University of Belgrade, Faculty of Medicine, Institute of Social
2
medicinu, Beograd, Srbija Medicine, Belgrade, Serbia
SAŽETAK ABSTRACT
Uvod: Migracija dijagnostički srodnih grupa (DSG) je pojava u kodiranju hospi- Introduction: Diagnosis related group migration (DRG) is a phenomenon in cod-
talizacija, kojom se označava da je pacijent, nakon epizode bolničkog lečenja, ing hospitalizations that indicates that a patient has been transferred from one
iz jedne grupe prebačen u drugu, skuplju grupu, isključivo zbog komplikacija ili group to a different, more costly group, after an episode of hospital treatment,
komorbiditeta koji su nastali tokom bolničkog lečenja ili medicinske intervencije. solely because of complications or comorbidities that occurred during hospital
Cilj rada: Cilj rada je bio da se ispitaju: pojava DSG migracija, bolnički troškovi i treatment or medical intervention.
dužina hospitalizacije kod kolektomija. Objective: The objective of the study was to examine the following: occurrence
Metod: Sprovedena je retrospektivna sekundarna analiza podataka o dijagno- of DRG migrations, hospital costs, and length of hospitalization for colectomies.
stički srodnim grupama (DSG), za serije bolničkih epizoda pacijenata (n = 4.939), Methods: A retrospective secondary analysis of DRG data was conducted for a
starosti 18 i više godina, koji su podvrgnuti proceduri kolektomije, u 49 bolnica u series of episodes of hospital treatment (n = 4,939) in patients aged 18 and above,
Republici Srbiji, u periodu od 2018. do 2020. godine, a čije su epizode bolničkog who underwent colectomy in 49 hospitals in the Republic of Serbia, in the period
lečenja grupisane u tri dijagnostički srodne grupe: G02A grupu, izdvojenu G02A between 2018 and 2020, and whose episodes of hospital treatment were grouped
grupu sa T81-T88 dijagnozama za komplikacije hirurškog lečenja, i G02B grupu. into three diagnosis related groups: the G02A group, a separate G02A group with
Rezultati: U posmatranom trogodišnjem periodu, incidencija DSG migracije je T81-T88 diagnoses for surgical treatment complications, and the G02B group.
iznosila 7,4%. Bolničko lečenje pacijenata svrstanih u dijagnostičku grupu G02A Results: In the observed three-year period, the incidence of DRG migration was
(T81-T88), koja predstavlja DSG migraciju, bilo je statistički značajno skuplje, a ovi 7.4%. Inpatient treatment of patients classified in the diagnostic group G02A
pacijenti su statistički značajno duže bili hospitalizovani. Ukupan iznos fakture, (T81-T88), which represents DRG migration, was statistically significantly more
za dijagnostičku grupu G02A (T81-T88), bio je 509.651,7 dinara (cca 4.320 €), a costly and these patients had a statistically significantly longer hospital stay. The
prosečna dužina epizode bolničkog lečenja je bila 23 dana. U grupi G02B ukupan total invoice amount for the diagnostic group G02A (T81-T88) was 509,651.7 dinars
iznos fakture je bio 231.989,0 dinara (cca 1.960 €), uz prosečnu dužinu hospitali- (approximately 4,320 euros), and the average length of an episode of hospital treat-
zacije od 11 dana. ment was 23 days. In group G02B, the total invoice amount was 231,989.0 dinars
Zaključak: Kolektomije sa komplikacijama produžavaju dužinu hospitalizacije i (approximately 1,960 euros) with an average length of hospital stay of 11 days.
podrazumevaju veću potrošnju resursa u Republici Srbiji. Analiza troškova u vezi Conclusion: Colectomies with complications prolong the length of hospitaliza-
sa DSG migracijama, po bolničkom danu i pacijentu, može ukazati na neefika- tion and imply a higher consumption of resources in the Republic of Serbia. Cost
snost medicinskih intervencija. analysis related to DRG migration, per patient day and patient, may indicate the
ineffectiveness of medical interventions.
Ključne reči: DSG migracija, kolektomija, trošak, hospitalizacija, Srbija
Keywords: DRG migration, colectomy, cost, hospitalization, Serbia

Marina Topalović Marina Topalović
Ministarstvo zdravlja Republike Srbije Ministry of Health of Republic Serbia
Pasterova 1, 11000 Beograd, Srbija 1 Pasterova Street, 1000 Belgrade, Serbia
Elektronska adresa: topalovicmmarina@gmail.com E-mail: topalovicmmarina@gmail.com
Primljeno • Received: January 19, 2022; Revidirano • Revised: February 11, 2022; Prihvaćeno • Accepted: February 15, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-35960
migracija dijagnostički srodnih grupa kao pokazatelj potencijalno neefikasne medicinske intervencije
Topalović M. i sar.
diagnosis related group migration as an indicator of a potentially inefficient medical intervention
UVOD INTRODUCTION
Sistem dijagnostički srodnih grupa (DSG) predstavlja The system of diagnosis related groups (DRG) is a mod-
moderan sistem klasifikacije bolnički lečenih pacije- ern system for classifying patients treated in hospital
nata u grupe kojima se opisuju različite kombinacije (inpatients) into groups which describe different com-
slučajeva kod pacijenata (engl. casemix). Ovaj sistem se binations of cases in patients – casemix. This system is
primenjuje širom sveta u cilju unapređivanja modela fi- being used all over the world with the aim of improv-
nansiranja, kontrole resursa i plaćanja bolničkih usluga. ing financing models, resource control, and hospital
Casemix je izraz međunarodne terminologije kojim se services payment. Casemix is an international term
opisuje konzistentna metodologija za klasifikaciju pa- describing the consistent methodology for classifying
cijenata, epizoda bolničkog lečenja i ukupnih troškova, patients, episodes of hospital treatment (patient epi-
na osnovu: 1) potrošnje bolničkih resursa zbog lečenja sodes), and overall costs (consumption), on the basis of
pacijenta i 2) kliničkih manifestacija bolesti pacijenta. the following: 1) the consumption of hospital resources
Svaka epizoda bolničkog lečenja, odnosno pacijent, for patient treatment and 2) clinical manifestations of a
svrstava se u jednu od dijagnostički srodnih grupa. U disease in a patient. Each episode of hospital treatment,
okviru svake DSG, objedinjuju se sve zdravstvene us- i.e., each patient, is classified into one of the diagnosis
luge, lekovi i materijal koji su tokom epizode lečenja related groups. All health services, drugs, and materi-
potrošeni za lečenje jednog pacijenta [1], tako da se als spent during a single episode of hospital treatment
bolnički troškovi mogu analizirati po dijagnostički srod- of one patient are integrated within each DRG [1], in
nim grupama. Bolnice koje primenjuju plaćanje po DSG such a way as to enable the analysis of hospital costs by
sistemu mogu biti podstaknute da smanjuju troškove DRGs. Hospitals implementing payment on the basis of
putem skraćivanja dužine hospitalizacije, preusmerava- the DRG system, may be stimulated to reduce costs by
nja na lečenje u dnevnoj bolnici, i smanjivanja broja di- shortening hospital stay, redirecting patient treatment
jagnostičkih i terapijskih procedura [2]. Sa druge strane, to day hospitals, and reducing the number of diagnos-
primena DSG sistema povlači rizik da bolnice postanu tic and treatment procedures [2]. On the other hand,
previše orijentisane ka štednji, što rezultira prevreme- the application of the DRG system carries the risk of
nim otpustom pacijenata, uštedama na lekovima i pa- hospitals becoming excessively oriented towards cut-
ketu usluga, a čime se dovodi u pitanje kvalitet lečenja ting costs, which consequently means premature pa-
[2]. Stoga je analiziranje DSG migracija višestruko važ- tient discharge and saving on medication and service
no. Na primer, na individualnom nivou, može rasvetliti packages, thus jeopardizing the quality of treatment
proces bolničkog lečenja svakog pacijenta; na nivou [2]. Therefore, analyzing DRG migrations is important
bolnice, doprinosi detaljnom praćenju njenog poslo- for a number of reasons. For instance, at the individual
vanja; na nivou bolničke zdravstvene zaštite, olakšava level, it helps in clarifying the hospital treatment pro-
upoređivanje rada bolnica; a sa aspekta finansiranja, cess of each patient; at the level of the hospital, it con-
može da podstakne pravičnu raspodelu sredstava tributes to detailed monitoring of the hospital’s oper-
među bolnicama i unutrašnji nadzor troškova lečenja, a ation and management; at the level of hospital health
naročito spoljašnji nadzor i kontrolu troškova. care, it facilitates the comparison of the mode of opera-
tion between hospitals; and at the financial level, it may
G 02 A
Prvi simbol označava glavnu Drugi i treći simboli su numerički i označavaju kojem Četvrti simbol označava stepen potrošnje resursa.
dijagnostičku kategoriju. / odeljku pripada grupa. / The second and third symbols are / The fourth symbol designates the level of resource
The first symbol designates the numerical, and they designate the partition that the group consumption.
main diagnostic category. belongs in.
А - najveća / А - highest
G - Bolesti i poremećaji 01 - 39 hirurški / 01 - 39 surgical B - nešto manja / B - second highest
digestivnog sistema / C - još manja / C - third highest
G - Diseases and disorders of the 40 - 59 invazivno-nehirurški / 40 - 59 invasive - nonsurgical D - minimalna / D - minimal
digestive system Z - nema gradacije u potrošnji / Z - no split for the DRG
60 - 99 konzervativni / 60 - 99 conservative
Slika 1. Simboli DSG grupe G02A – Velike procedure na tankom i debelom cre- Figure 1. Symbols of the DRG G02A – Major small and large bowel procedures,
vu, sa vrlo teškim komplikacijama i komorbiditetima major complexity and comorbidity
Topalović M. et al.
G02А - težinski koeficijent = 6,80 / G02А - Cost weight = 6.80
G02B - težinski koeficijent = 3,51 / G02B - Cost weight = 3.51
Slika 2. Težinski koeficijenti grupe G02A – Velike procedure na tankom i debelom Figure 2. Cost weight of the G02A group – Major small and large bowel proce-
crevu, sa vrlo teškim komplikacijama i komorbiditetima i grupe G02B – Velike pro- dures, major complexity and comorbidity; cost weight of the G02B group – Ma-
cedure na tankom i debelom crevu, bez vrlo teških komplikacija i komorbiditeta jor small and large bowel procedures, intermediate complexity and comorbidity
Metodologija sistema DSG grupisanja je izuzetno stimulate an equitable distribution of funds amongst
sofisticirana i zavisi od kvaliteta korišćenih podataka. hospitals, as well as internal control of treatment costs,
Zato je kvalitet bolničke medicinske dokumentacije od and, especially, external monitoring and control of
presudnog značaja da pokaže da li stepen potrošnje costs.
resursa kod hirurških i konzervativnih epizoda lečenja The methodology of the system of DRG grouping is
korelira sa težinom kliničke slike pacijenta, odnosno highly sophisticated and depends on the quality of the
stepenom složenosti komorbiditeta i/ili komplikacija. data that is used. This is why the quality of hospital med-
Ove informacije se dobijaju iz četvoromesne alfanu- ical records is of vital importance in showing whether
meričke šifre svake DSG (Slika 1). the degree of resource consumption in episodes of sur-
Svaka DSG, u skladu sa pripadajućom kategorijom, gical and of conservative treatment corelate with the
odeljkom i stepenom potrošnje, ima definisan težinski severity of patient presentation, i.e., with the level of
koeficijent, na osnovu kojeg se računa i monetarna complexity of the comorbidities and/or complications.
vrednost grupe (Slika 2). This information is obtained from the four alphanumeric
Na prijemu u bolnicu, pacijent se svrstava u odgo- characters comprising the code for each DRG (Figure 1).
varajuću dijagnostički srodnu grupu, prema glavnoj Each DRG, in keeping with the corresponding cat-
dijagnozi zbog koje je pacijent hospitalizovan, a uz egory, the partition, and the level of consumption, has
pomoć posebne funkcije DSG softvera za grupisanje – a defined cost weight, which is used as the basis for
„Gruper” (engl. Grouper), koji koristi niz algoritama za calculating the monetary value of the group (Figure 2).
obradu podataka o pacijentu, kliničkom stanju i leče- At hospital admission, the patient is classified into
nju. Na kraju epizode bolničkog lečenja, „Gruper” pro- the appropriate diagnosis related group, according to
verava podatke o intervencijama/procedurama u toku the main diagnosis which was the cause for hospital-
epizode lečenja, kako bi svrstao epizodu, ili u hirurški ization. This is done with the aid of the special function
odeljak, ili u invazivno nehirurški odeljak, ili u konzer- of the DRG grouping software – Grouper, which uses a
vativni odeljak; proverava starost i pol pacijenta, prate- series of algorithms for processing patient data, the pa-
će dijagnoze, ishod lečenja, te utvrđuje dužinu trajanja tient’s clinical state of health, and the treatment received
epizode bolničkog lečenja. DSG migracija podrazume- by the patient. At the end of the episode of hospital treat-
va da se pacijent, odnosno epizoda bolničkog lečenja, ment, the Grouper checks data on procedures within the
svrsta, ne u istu već u drugu, skuplju grupu, isključivo episode, in order to categorize the episode, either in the
zbog komplikacija koje su se dogodile tokom lečenja ili surgical partition, the invasive nonsurgical partition, or
operativne procedure. To znači da je lečenje dovelo do the conservative partition. The Grouper checks the age
određenog pogoršanja stanja pacijenta, kao i do po- and sex of the patient, the underlying diagnoses, and
većane potrošnje resursa. Zato se DSG migracija u jed- the treatment outcome, and it determines the length of
noj zdravstvenoj ustanovi (ili pojedinačnom odeljenju) the episode of hospital treatment. DRG migration means
može koristiti kao pokazatelj za sagledavanje efikasno- that the patient, i.e., the episode of hospital treatment
sti i kvaliteta zdravstvene zaštite koja se pruža. Ovo je becomes categorized, not in the same, but in a differ-
posebno značajno za hirurške grane medicine, koje su ent, more costly group, exclusively due to complications
skupe, i neretko zahtevaju dug period oporavka u bol- occurring during treatment or surgical procedure. This
ničkim uslovima, kao i značajna finansijska sredstva [4].
U nekim bolnicama, postoje zaposleni koje se bave means that treatment has led to a certain level of deteri-
DSG kodiranjem i kontrolom pre predaje dokumen- oration of the patient’s health status, as well as to an in-
tacije osiguravajućim kućama [3]. U Republici Srbiji, crease in resource consumption. This is why DRG migra-
Republički fond za zdravstveno osiguranje (RFZO) je tion in a healthcare facility (or an individual department)
dominantni kupac usluga bolnica u javnoj svojini. Od may be used as an indicator of the efficiency and quality
1. januara 2019. godine, RFZO primenjuje model plaća- of health care being provided. This is especially import-
nja po dijagnostički srodnim grupama, uz linijsko (na- ant for surgical branches of medicine, which are costly,
mensko) budžetiranje – budžet se ugovara na osnovu and often require a long period of recovery in hospital,
ugovora iz prethodne godine, a eventualno ušteđena as well as significant funds [4].
sredstva se vraćaju RFZO-u. Trenutno se 95% predraču- In some hospitals, there are employees who deal
nom definisanih finansijskih sredstava svakog meseca with DRG coding and control before the records and
prenosi zdravstvenim ustanovama po namenama, dok documentation are handed over to the insurance com-
je preostalih 5% finansijskih sredstava varijabilni deo panies [3]. In the Republic of Serbia, the National Health
budžeta i njegova isplata zavisi od DSG učinka [5]. Za Insurance Fund of the Republic of Serbia (RFZO) is pre-
procenu DSG učinka, koristi se verzija 6.0 Australijske dominantly the buyer of services provided by the state-
DSG klasifikacije, koja ima i prateći softver za grupi- owned hospitals. As of January 1, 2019, the RFZO has
sanje podataka. U periodu od 2018. do 2020. godine, been applying the payment model based on DRGs,
prema procenama Drugog projekta razvoja zdravstva along with line item (dedicated) budgeting – the budget
Srbije, godišnje se izdvajalo, u proseku, oko 142 mili- is negotiated based on last year’s contracts, while any
jarde dinara (cca 1,21 milijarda €) za ustanove na se- remaining funds are returned to the RFZO. At the mo-
kundarnom i tercijarnom nivou zdravstvene zaštite, od ment, 95% of funds are defined by estimate and trans-
čega za bolnice, više od jedne trećine (oko 44,8 milijar- ferred every month to healthcare institutions, by budget
di dinara godišnje), a za hirurška odeljenja, u proseku, lines, while the remaining 5% of funds are the variable
32% ukupnog budžeta zdravstvene ustanove, dok je u part of the budget whose payment depends on DRG
nekim bolnicama to iznosilo i preko 90% [6]. performance [5]. DRG performance is assessed with the
Prema našim saznanjima, DSG migracija i analiza Australian Refined Diagnosis Related Groups Version 6.0,
troškova operativnih procedura, sa i bez komplikacija, which also has software for data grouping. According to
do sada nisu bile predmet naučnih istraživanja u Repu- the assessment of the Second Serbia Health Project, in
blici Srbiji. Po ugledu na razvijene zemlje, potrebno je the period between 2018 and 2020, the amount of ap-
da se naučno i stručno argumentuju troškovi najsku- proximately 142 billion RSD (approximately 1.2 billion
pljeg lečenja, kao što je bolničko, posebno u situacija- euros) was designated annually for health institutions
ma kada su planirane velike investicije u stacionarne at the secondary and tertiary levels of health care. Of
kapacitete [7]. Aktuelno je da se pažnja profesionalaca this sum, more than one third (around 44.8 billion RSD
i javnosti usmerava na sagledavanje razlike u troškovi- a year) was designated for hospitals, while, on average,
ma kolektomija, lečenja uz pomoć laparoskopskih pro- 32% of the budget of an individual hospital was allocat-
cedura i otvorenih operacija na debelom crevu [8,9], ed to surgical departments, with this percentage run-
kao i na praćenje troškova u primeni najsavremenije ning as high as 90% or above, in some hospitals [6].
tehnologije i robotike [10]. Međunarodne publikacije To the best of our knowledge, DRG migration and
pokazuju da se i DSG migracija koristi kao jedan od ala- the cost analysis of surgical procedures, with and with-
ta za procenu kvaliteta i efikasnosti rada, kako na nivou out complications, have as yet not been the subject of
odeljenja ili bolnice, tako i na nacionalnom nivou [5]. scientific research in the Republic of Serbia. In line with
Kolektomija, kao hirurška intervencija, koristi se u the practice of developed countries, it is necessary to
lečenju drugih oboljenja creva, pored karcinoma de- scientifically and professionally justify the costs of the
belog creva, ali imajući u vidu da je karcinom kolona most expensive forms of treatment, such as hospital
jedna od tri najčešće maligne bolesti u svetskoj popu- treatment, especially in situations when large invest-
laciji, jasno je da se ove procedure neretko obavljaju. ments are planned for inpatient facilities [7]. Current-
Prema dostupnim podacima, na listi vodećih lokaliza- ly, the attention of the professional circles as well as
cija u oboljevanju od karcinoma u opštoj populaciji u of the public is being directed towards determining
Republici Srbiji, karcinom debelog creva se nalazi na the difference in costs among colectomies, treatment
drugom mestu (11,2%) a na listi vodećih lokalizacija with laparoscopic procedures, and open surgery of the
u umiranju od maligniteta, karcinom kolona je takođe colon [8,9], as well as towards monitoring costs of the
na drugom mestu (12%) [11]. Stoga je cilj ovog rada use of cutting-edge technology and robotics [10]. In-
da se ispitaju: pojava DSG migracije kod kolektomija, ternational publications have demonstrated that DRG
odnosno svrstavanje epizode lečenja pacijenta u DSG migration is used as one of the tools for assessing the
grupu koja se potencijalno odlikuje većim troškovima quality and efficiency of work, both at the department
lečenja; bolnički troškovi; dužina hospitalizacije. and hospital levels, as well as at the national level [5].
Colectomy, as a surgical procedure, is used in treat-
MATERIJALI I METODE ing diseases of the colon other than colon cancer.
Sprovedena je retrospektivna sekundarna analiza po- However, bearing in mind that that colon cancer is one
dataka o DSG, za serije bolničkih epizoda pacijenata of the three most common malignant diseases in the
(n = 4.939), starosti 18 i više godina, koji su podvrgnu- world population, it is clear that this procedure is per-
ti proceduri kolektomije, u 49 bolnica iz Plana mreže formed rather frequently. According to available data,
zdravstvenih ustanova u Republici Srbiji [12,13], u pe- colon cancer is second (11.2%) on the list of leading
riodu od 2018. do 2020. godine, čije su epizode bolnič- localizations of cancer-related morbidity in the gener-
kog lečenja grupisane u tri dijagnostički srodne grupe: al population of the Republic of Serbia, and it is also
1. G02A – Velike procedure na tankom i debelom cre- second (12%) on the list of leading localizations of ma-
vu, sa vrlo teškim komplikacijama i komorbiditetima lignancy-related mortality [11]. Therefore, the aim of
(težinski koeficijent 6,8); this paper is to investigate the following: occurrence
2. G02A (T81-T88) – Velike procedure na tankom i de- of DRG migration in colectomies, i.e., categorizing the
belom crevu, sa vrlo teškim komplikcijama i komor- patient episode into the DRG group which is potential-
biditetima (težinski koeficijent 6,8) – posebno izdvo- ly characterized by a higher treatment cost; hospital
jene grupe sa dijagnozama koje mogu predstavljati costs; length of hospital stay.
komplikacije hirurškog lečenja koje su prouzrokova-
le DSG migraciju;
MATERIALS AND METHODS
3. G02B – Velike procedure na tankom i debelom cre- A retrospective secondary analysis of data on DRG was
vu, bez vrlo teških komplikacija i komorbiditeta (te- performed, for series of episodes of hospital treatment
žinski koeficijent 3,51). (n = 4,939), in patients aged 18 and above, who had
undergone colectomy, in 49 hospitals belonging to
Izvor podataka korišćen u ovoj studiji jeste baza
the Plan of the Republic of Serbia Healthcare Institu-
Drugog projekta razvoja zdravstva Srbije koju sprovo-
tions Network [12,13], in the period between 2018 and
di Ministarstvo zdravlja [6] u kojoj se generišu i dalje
2020, and whose episodes of hospital treatment were
analiziraju svi podaci dobijeni od javnih zdravstvenih
grouped into three DRGs:
ustanova posredstvom elektronskog fakturisanja. Za
1. G02A – Major small and large bowel procedures, ma-
ovu analizu su izdvojeni podaci za period 1. 1. 2018.
jor complexity and comorbidity (cost weight = 6.8)
godine – 31. 12. 2020. godine.
2. G02A (T81-T88) – Major small and large bowel
U pogledu kolektomija, definisano je 12 različitih
procedures, major complexity and comorbidity
hirurških procedura sa odgovarajućim šiframa [14]:
(cost weight = 6.8) – separate associated diagno-
1. 32003-00 Parcijalna resekcija debelog creva sa ana-
ses, which may represent complications of surgical
stomozom
treatment that were the cause of DRG migration
2. 32000-00 Parcijalna resekcija debelog creva sa for-
3. G02B – Major small and large bowel procedures,
miranjem stome
intermediate complexity and comorbidity (cost
3. 32003-01 Desna hemikolektomija sa anastomozom
weight = 3.51).
4. 32000-01 Desna hemikolektomija sa formiranjem
stome The data source used for the study is the database
5. 32005-01 Proširena desna hemikolektomija sa ana- of the Second Serbia Health Project implemented by the
stomozom Ministry of Health [6], which generates and further anal-
6. 32004-01 Proširena desna hemikolektomija sa for- yses all data obtained from public healthcare institutions
miranjem stome through electronic billing. For the purpose of this analy-
7. 32006-00 Leva hemikolektomija sa anastomozom sis, data for the period between January 1, 2018 and De-
8. 32006-01 Leva hemikolektomija sa formiranjem stome cember 31, 2020 were taken from the database.
9. 32005-00 Subtotalna kolektomija sa anastomozom With respect to colectomies, 12 different surgical
10. 32004-00 Subtotalna kolektomija sa formiranjem procedures have been defined, with associated codes
stome [14]:
11. 32012-00 Totalna kolektomija sa ileorektalnom ana- 1. 32003-00 Limited excision of large intestine with
stomozom anastomosis
12. 32009-00 Totalna kolektomija sa ileostomom. 2. 32000-00 Limited excision of large intestine with for-
mation of stoma
Vodeći se naučnim radovima u ovoj oblasti [8,9], 3. 32003-01 Right hemicolectomy with anastomosis
uzete su dijagnoze koje mogu predstavljati komplika- 4. 32000-01 Right hemicolectomy with formation of
cije hirurškog lečenja i koje su omogućile pretpostavku stoma
DSG migracije u grupu G02A (T81-T88), a to su: 5. 32005-01 Extended right hemicolectomy with anas-
1. T88.8 – Druge označene komplikacije hirurške i me- tomosis
dicinske nege, neklasifikovane na drugom mestu 6. 32004-01 Extended right hemicolectomy with for-
2. T81.0 – Krvarenje i krvni podliv kao komplikacije me- mation of stoma
dicinskog postupka, neklasifikovani na drugom mestu 7. 32006-00 Left hemicolectomy with anastomosis
3. T81.3 – Poremećaj operativne rane, neklasifikovan 8. 32006-01 Left hemicolectomy with formation of stoma
na drugom mestu 9. 32005-00 Subtotal colectomy with anastomosis
4. T81.4 – Infekcija nakon medicinske intervencije, ne- 10. 32004-00 Subtotal colectomy with formation of stoma
klasifikovana na drugom mestu 11. 32012-00 Total colectomy with ileorectal anastomosis
5. T81.5 – Strano telo u operativnoj rani 12. 32009-00 Total colectomy with ileostomy.
6. T81.8 – Druge komplikacije medicinskih intervenci-
Guided by scientific studies in this field [8,9], the
ja, neklasifikovane na drugom mestu
following diagnoses, which may present complications
7. T81.9 – Neoznačena komplikacija medicinske inter-
of surgical treatment, and which provide the supposi-
vencije.
tion of DRG migration to the group G02A (T81-T88),
Varijable uključene u analizu DSG (G02A, G02A were taken:
(T81-T88) i G02B) su: 1. T88.8 – Other complications of surgical and medical
1. Zastupljenost različitih dijagnoza koje predstavljaju care, not elsewhere classified
osnovni uzrok hospitalizacije (OUH) 2. T81.0 – Hemorrhage and hematoma complicating a
2. Starost pacijenta, izražena kao aritmetička sredina i procedure, not elsewhere classified
standardna devijacija (SD) 3. T81.3 – Disruption of operation wound, not else-
3. Pol pacijenta where classified
4. Dužina hospitalizacije (broj dana) 4. T81.4 – Infection following a procedure, not else-
5. Troškovi bolničkog lečenja – sedam vrsta troškova where classified
koji su izraženi kao medijana (25. i 75. percentil), 5. T81.5 – Foreign body accidentally left in body cavity
uključuju: or operation wound following a procedure
• Vrednost pruženih usluga bez vrednosti bolnič- 6. T81.8 – Other complications of procedures, not else-
kog dana (B.O. dan) where classified
• Vrednost ostvarenih B.O. dana 7. T81.9 – Unspecified complication of procedure.
• Vrednost utroška za lekove
The variables included in DRG (G02A, G02A
• Vrednost utroška za krv i produkte krvi
(T81-T88) and G02B) analysis, are as follows:
• Vrednost utroška za potrošni medicinski materijal
1. The predominance of different diagnoses which
• Ukupan iznos po fakturi.
represent the basic cause of hospitalization (BCH)
6. Srbija, ukupno i regioni: Grad Beograd, Istočna Srbi-
2. Patient age, expressed as the mean and as standard
ja, Južna Srbija, Centralna Srbija, Vojvodina, i Zapad-
deviation (SD)
na Srbija.
3. Patient sex
U posmatranom periodu od tri godine, bilo je uku- 4. Length of hospital stay (number of days)
pno 4.939 ispitivanih grupa, od čega je najzastupljenija 5. Hospital treatment costs – seven types of costs ex-
bila grupa G02B, sa udelom od 70,5%. pressed as the median (25th and 75th percentile), in-
clude the following:
Statistička analiza podataka • Total value of services rendered (without pa-
Podaci su analizirani metodama deskriptivne i ana- tient days)
litičke statistike. Od metoda deskriptivne statistike, • Total value of billed patient days
korišćene su mere centralne tendencije (aritmetička • Total cost of medication
sredina, medijana), mere varijabiliteta (standardna • Total cost of blood and blood products
devijacija i percentili), apsolutni i relativni brojevi. Nor- • Total cost of disposable medical supplies
malnost raspodele je testirana grafičkim i matematič- • Total invoice amount.
kim metodama. Za poređenje statistički značajne ra- 6. Serbia, in total, and by regions – City of Belgrade,
zlike između ispitivanih grupa, korišćen je ANOVA test East Serbia, South Serbia, Central Serbia, Autono-
(ili Kraskal-Volisov test), odnosno t-test (ili Man-Vitnijev mous Province of Vojvodina, and West Serbia.
test), za numeričke podatke, te χ2 test (ili Fišerov test), In the observed three-year period, there was a total
za nominalne podatke. Statistička značajnost je prihva- of 4,939 observed groups, amongst which group G02B
ćena na nivou 0,05. Rezultati su prikazani tabelarno. Za was predominant, with a prevalence of 70.5%.
obradu podataka korišćen je softverski paket SPSS 21.0.
Statistical data analysis
REZULTATI Data were analyzed with the use of descriptive and
U periodu između 2018. i 2020. godine, u 49 bolni- analytical statistics methods. The following descriptive
ca Srbije, dijagnoze koje su bile najzastupljenije, kao statistics methods were used: measures of central ten-
osnovni uzrok hospitalizacije, u grupama G02A i G02B, dency (mean, median), measures of variability (standard
bile su C18.7 – Zloćudni tumor sigmoidnog dela de- deviation and percentiles), absolute and relative num-
belog creva i C18.2 – Zloćudni tumor uzlaznog dela bers. Normality of distribution was tested with graphic
debelog creva, nakon kojih sledi C18.0 – Zloćudni tu- and mathematical methods. For the comparison of sta-
mor slepog creva (Tabela 1). U grupi G02A (T81-T88), tistically significant difference amongst the analyzed
najviše je bilo pacijenata sa osnovnim uzrokom hos- groups, the ANOVA test (or the Kruskal-Wallis test) was
pitalizacije K56.7 – Zavezano crevo, neoznačeno, used, i.e., the t-test (or the Mann-Whitney test), for nu-
K56.6 – Drugo zavezano crevo, neoznačeno i C18.0 – meric data, and the χ2 test (or Fisher’s test), for nominal
Zloćudni tumor slepog creva. data. Statistical significance was accepted at the level of
U posmatranom periodu, u dijagnostičkoj gru- 0.05. The results have been presented in tables. The SPSS
pi G02A, bilo je ukupno 1.349 pacijenata, prosečne 21.0 software package was used for data processing.
Tabela 1. Najzastupljenije dijagnoze kao osnovni uzrok hospitalizacije i broj Table 1. The most prevalent diagnoses as the basic cause of hospitalization and
epizoda lečenja, po dijagnostički srodnim grupama, za velike procedure na the number of treatment episodes, by DRGs, for major small and large bowel
tankom i debelom crevu, Srbija, 2018 -2020. godina procedures, Serbia, 2018 - 2020
Epizode lečenja
Najzastupljenije dijagnoze kao osnovni uzrok hospitalizacije (MKB-10 klasifikacija) / n (%) /
DSG grupa / DRG group
Most prevalent diagnoses as the basic cause of hospitalization (ICD-10 classification) Treatment
episodes n (%)
UKUPNO / TOTAL 4,939 (100%)
C18.7 Zloćudni tumor sigmoidnog dela debelog creva / C18.0 Malignant neoplasm of the appendix 157 (11.6%)
G02А - Velike procedure na C18.2 Zloćudni tumor uzlaznog dela debelog creva / C18.2 Malignant neoplasm of the ascending colon 157 (11.6%)
tankom i debelom crevu sa
C18.0 Zloćudni tumor slepog creva / C18.0 Malignant neoplasm of the appendix 123 (9.1%)
vrlo teškim komplikacijama i
komorbiditetima / K56.7 Zavezano crevo, neoznačeno / K56.7 Ileus, unspecified 95 (7%)
G02А - Major small and large bowel C18.4 Zloćudni tumor poprečnog dela debelog creva / C18.4 Malignant neoplasm of the transverse colon 90 (6.7%)
procedures, major complexity and
comorbidity Ostale dijagnoze / Other diagnoses 727 (54%)
Ukupno / Total 1,349 (100%)
G02A - (T81-T88) Velike procedure K56.7 Zavezano crevo, neoznačeno / K56.7 Ileus, unspecified 10 (9.3%)
na tankom i debelom crevu sa K56.6 Drugo zavezano crevo, neoznačeno / K56.6 Other and unspecified intestinal obstruction 10 (9.3%)
vrlo teškim komplikacijama i
C18.0 Zloćudni tumor slepog creva / C18.0 Malignant neoplasm of the appendix 10 (9.3%)
komorbiditetima, sa izdvojenim
pratećim dijagnozama / C18.2 Zloćudni tumor uzlaznog dela debelog creva / C18.2 Malignant neoplasm of the ascending colon 9 (8.3%)
G02A - (T81-T88) Major small and
C18.4 Zloćudni tumor poprečnog dela debelog creva / C18.4 Malignant neoplasm of the transverse colon 6 (5.6%)
large bowel procedures, major
complexity and comorbidity, with Ostale dijagnoze / Other diagnoses 63 (58.3%)
separate associated diagnoses Ukupno / Total 108 (100%)
C18.7 Zloćudni tumor sigmoidnog dela debelog creva / C18.7 Malignant neoplasm of the sigmoid colon 475 (13,6%)
G02B - Velike procedure na C18.2 Zloćudni tumor uzlaznog dela debelog creva / C18.2 Malignant neoplasm of the ascending colon 451 (13%)
tankom i debelom crevu bez
C18.0 Zloćudni tumor slepog creva / C18.0 Malignant neoplasm of the appendix 396 (11,4%)
vrlo teških komplikacija i
komorbiditeta / C18.4 Zloćudni tumor poprečnog dela debelog creva / C18.4 Malignant neoplasm of the transverse colon 186 (5,3%)
G02B - Major small and large
C18.3 Zloćudni tumor jetrinske krivine debelog creva / C18.3 Malignant neoplasm of hepatic flexure 182 (5,2%)
bowel procedures, intermediate
complexity and comorbidity Ostale dijagnoze / Other diagnoses 1.792 (51,5%)
Ukupno / Total 3.482 (100%)
starosti 69,8 godina, a u grupi G02B dva i po puta više RESULTS

pacijenata (3.482), prosečne starosti 64,9 godina. Iz
In the period between 2018 and 2020, in 49 hospitals in
G02B grupe je u izdvojenu grupu G02A (T81-T88) mi-
Serbia, the diagnoses that were the most prevalent as
griralo ukupno 108 (7,4%) pacijenata, kod kojih je regi-
the basic cause of hospitalization, in groups G02A and
strovana neka komplikacija nakon hirurške intervenci-
G02B, were C18.7 – Malignant neoplasm of the sigmoid
je, a koji su bili prosečne starosti 70,6 godina. U sve tri
colon and C18.2 – Malignant neoplasm of the ascending
grupe, većina pacijenata je bila muškog pola. Utvrđene
colon, followed by C18.0 – Malignant neoplasm of the
su statistički značajne razlike u svim posmatranim troš-
appendix (Table 1). In the group G02A (T81-T88), the ma-
kovima i u dužini hospitalizacije, prema posmatranim
jority of the patients had, as the basic cause of hospital-
dijagnostički srodnim grupama (Tabela 2).
ization, the following diagnoses: K56.7 – Ileus, unspec-
Za razliku od strukture po polu, u pogledu staro-
ified, K56.6 – Other and unspecified intestinal obstruc-
sti pacijenata, razlika između tri grupe je bila statistički
tion, and C18.0 – Malignant neoplasm of the appendix.
značajna, a najstariji pacijenti su pripadali grupi G02A
In the observed period, in the diagnostic group G02A,
(T81-T88) (Tabela 2). Post hoc analizom je utvrđeno da
there were, in total, 1,349 patients. Their average age was
je razlika u starosti bila značajna između grupe G02A i
69.8 years. At the same time, in group G02B, the number
grupe G02B, kao i između grupa G02A (T81-T88) i G02B,
of patients was 2.5 times greater (3,482), and their aver-
ali ne i između grupa G02A (T81-T88) i G02A (Tabela 3).
age age was 64.9 years. A total of 108 (7.4%) patients, in
Ukupan iznos fakture za grupu G02A je bio 290.702,9
whom some complication was registered upon surgery
dinara (cca 2.460 €), a pacijenti sa ovom grupom hos-
and whose average age was 70.6 years, migrated from
pitalizovani su u proseku 13 dana. Ukupan iznos fak-
the G02B group to the separate group G02A (T81-T88).
ture za grupu G02A (T81-T88) je bio 509.651,7 dinara
In all three groups, a majority of the patients were male.
(cca 4.320 €), a prosečna dužina epizode bolničkog leče-
Statistically significant differences were determined in all
nja je bila 23 dana, dok je ukupan iznos fakture za grupu
the observed costs and in the length of hospital stay, in
G02B bio 231.989 dinara (cca 1.970 €), uz prosečnu duži-
relation to all the observed DRGs (Table 2).
nu hospitalizacije od 11 dana (Tabela 2).
As opposed to the group structure pertaining to
Vrednost pruženih usluga bez B.O. dana, ukupna
the sex of the patients, with regards to the age of the
vrednost B.O. dana, ukupni troškovi za lekove, kao i
patients, the difference amongst the groups was sta-
troškovi krvi, bili su najviši u grupi G02A (T81-T88), a
tistically significant, with the oldest patients belonging
Tabela 2. Razlike u karakteristikama bolesnika, troškovima i dužini hospitalizacije, Table 2. The differences in patient characteristics, costs and length of hospital stay,
prema posmatranim dijagnostički srodnim grupama, Srbija, 2018 - 2020. godina by observed DRGs, Serbia 2018 - 2020
Varijable / Variables G021 G02A (T81-T88) G02B p

Starost u godinama /
69.8 ± 11.7 70.6 ± 10.8 64.9 ± 13 < 0.001
Age in years (mean ± SD)
Pol muški n (%) / Male sex n (%) 778 (57.7%) 64 (59.3%) 1,921 (55.2%)
0.227
Pol ženski n (%) / Female sex n (%) 571 (42.3%) 44 (40.7%) 1,561 (44.8%)
Vrednost pruženih usluga bez B.O. dana* / 162,391 267,729.3 128,448.1
< 0.001
Value of services rendered (without patient days)* (119,179.8 – 232,246.7) (176,277.1 – 395,510.8) (101,621.1 – 165,716.1)
28,747.2 50,923.9 24,049.9
Vrednost B.O. dana* / Value of patient days* < 0.001
(19,533.8 – 42,000.2) (30,292.6 – 75,034.9) (17,493.9 – 33,142.8)
40,036.9 78,587.1 25,130.6
Ukupan trošak za lekove* / Total cost of medication* < 0.001
(21,857.9 – 77,065.1) (39,679.7 – 159,813.1) (15,897.6 – 44,899.4)
Ukupan trošak za krv i labilne produkte od krvi* / 14,134.5 22,440.4 11,928.6
< 0.001
Total cost of blood and labile blood products* (7,067.2 – 28,622.3) (9,060 – 41,932.3) (7,067.2 – 21,201.7)
Ukupan trošak za potrošni medicinski materijal* / 34,876.5 45,187.4 32,586.1
< 0.001
Total cost of disposable medical supplies* (19,743.7 – 61,637.4) (30,277.1 – 78,191.5) (18,727.1 – 64,725.3)
Ukupan iznos naplaćene participacije* / 32,970.5 48,724.5 29,677.5
0.116
Total amount of patient participation* (15,495.1 – 62,544.3) (21,265.2 – 85,313.9) (13,542.9 – 54,755.7)
290,702.9 509,651.7 231,989
Ukupan iznos fakture* / Total invoice amount* < 0.001
(213,227.8 – 415,879.4) (312,222 – 677,846.7) (184,692.9 – 298,871.3)
Broj dana / Number of days of hospital stay 13 (9 – 20) 23 (16 – 35.5) 11 (8 – 15) < 0.001
* dinari, medijana (25. i 75. percentil) / RSD (dinars), median (25th and 75th percentile)
Tabela 3. Post hoc analiza karakteristika bolesnika, troškova i dužine hospitalizacije, Table 3. Post hoc analysis of patient characteristics, costs, and length of hospital
prema posmatranim dijagnostički srodnim grupama, Srbija, 2018 – 2020. godina stay, according to the observed DRGs, Serbia, 2018 – 2020
G02A (T81/T88) naspram G02A / G02A naspram G02B / G02A (T81-T88) naspram G02B /
Varijable / Variables
G02A (T81/T88) versus G02A G02A versus G02B G02A (T81-T88) versus G02B
Starost u godinama (aritmetička sredina ± SD) /
0.482 < 0.001 < 0.001
Age in years
Vrednost pruženih usluga bez vrednosti B.O. dana* /
< 0.001 < 0.001 < 0.001
Total value of services rendered (without patient days)*
Vrednost B.O. dana* / Total cost of medication* < 0.001 < 0.001 < 0.001
Ukupan trošak za lekove* /
< 0.001 < 0.001 < 0.001
Value of services rendered (without patient days)*
Ukupan trošak za krv i labilne produkte krvi* /
0.007 < 0.001 < 0.001
Total cost of blood and labile blood products*
Ukupan trošak za potrošni medicinski materijal* /
0.001 0.210 < 0.001
Total cost of disposable medical supplies*
Ukupan iznos fakture* / Total invoice amount* < 0.001 < 0.001 < 0.001
Broj dana hospitalizacije / Number of days of hospital stay < 0.001 < 0.001 < 0.001
* dinari, medijana (25. i 75. percentil) / RSD (dinars), median (25th and 75th percentile)
za pacijente te grupe hospitalizacija je bila najduža. to the group G02A (T81-T88) (Table 2). Post hoc anal-
Post hoc analizom je utvrđeno da su razlike u vrednosti ysis determined a statistically significant difference
pruženih usluga bez B.O. dana, ukupnoj vrednosti B.O. between groups G02A and G02B, as well as between
dana, ukupnim troškovima lekova, kao i u broju dana groups G02A (T81-T88) and G02B, but not between
hospitalizacije, statistički značajne između grupa G02A groups G02A (T81-T88) and G02A (Table 3).
(T81-T88) i G20A, zatim između grupa G02A i G02B, kao The total invoice amount for group G02A was
i između grupa G02A (T81-T88) i G02B (Tabela 3). Po- 290,702.9 RSD (approximately 2,460 euros), and the av-
smatrano u svim regionima, statistička značajnost ovih erage hospital stay was 13 days. The total invoice amount
razlika u troškovima je potvrđena (Tabela 4). for group G02A (T81-T88) was 509,651.7 RSD (approxi-
U svim regionima, osim u Zapadnoj Srbiji, ukupni mately 4,320 euros), while the average episode of hos-
iznos fakture je bio najviši za grupu G02A (T81-T88) pital treatment was 23 days. The total invoice amount
(p < 0,001) i bio je u opsegu od 390.048 dinara (cca for group G02B was 231,989 RSD (approximately 1,970
3.300 €), u Centralnoj Srbiji, do čak 581.338,8 dinara euros), with an average hospital stay of 11 days (Table 2).
(cca 4.930 €), u regionu Južne Srbije. Prosečna najduža The value of services rendered without patient days,
hospitalizacija je zabeležena za grupu G02A (T81-T88) the total value of patient days, the total cost of medica-
i bila je u opsegu od 21 dana, u Gradu Beogradu, do tion, as well as the cost of blood and blood products,
31 dana, u regionu Centralne Srbije, dok je u regio- were the highest in group G02A (T81-T88), and for these
nu Zapadne Srbije bila najmanja (u proseku 11 dana) patients, hospital stay was the longest. Post hoc analy-
(p < 0,001) (Tabela 4). sis has determined that the differences in the values of
services rendered without patient days, in the total val-
DISKUSIJA ue of patient days, the total medication costs, as well as
Tokom posmatranog trogodišnjeg perioda, DSG mi- in the number of patient days, were statistically signifi-
gracija je zabeležena kod 108 (7,4%) epizoda bolnič- cant between group G02A (T81-T88) and group G20A,
kog lečenja, što znači da su pacijenti usled komplika- between groups G02A and G02B, as well as between
cija (dijagnoze T81-T88) nastalih u toku hospitalizacije groups G02A (T81-T88) and G02B (Table 3). The statis-
svrstani u drugu dijagnostički srodnu grupu, sa većim tical significance of these differences in costs has been
koeficijentom. Međutim, ovaj podatak se mora uzeti sa confirmed at the level of all the regions (Table 4).
rezervom, s obzirom na to da u procesu analize poda- In all the regions, except West Serbia, the total in-
taka nisu mogle biti izdvojene sve komplikacije koje voice amount was the highest for group G02A (T81-T88)
potencijalno dovode do DSG migracije. Naime, najče- (p < 0.001) and ranged between 390,048 RSD (approx-
šće komplikacije nakon resekcije debelog creva jesu imately 3.300 euros), in Central Serbia, to as much as
različite infekcije rane i unutrašnjih organa, a slede ih 581,338.8 RSD (approximately 4,930 euros), in the South
gastrointestinalne komplikacije motiliteta, uključuju- Serbia region. The longest average hospital stay was
ći ileus i opstrukciju creva [14]. Me]utim, za navedene registered for group G02A (T81-T88) and ranged from
Tabela 4. Razlike u karakteristikama bolesnika, troškovima i dužini hospitalizacije, Table 4. The differences in patient characteristics, costs and length of hospital stay,
prema posmatranim dijagnostički srodnim grupama, Srbija, 2018 - 2020. godina by observed DRGs, Serbia 2018 - 2020
Region /
Varijable / Variables G02A G02A (T81-T88) G02B p
Region
Grad Beograd / 292,397.8 451,224.8 244,222.7

Ukupan iznos fakture / Total invoice amount < 0.001
The City of (224,873.6–434,404.8) (271,906.4 –822,026.1) (195,514.7 –311,865.3)
Belgrade Broj dana hospitalizacije / Number of days of hospital stay 12 (9 – 20) 21 (12 – 32) 11(8 – 14) < 0.001
280,336.5 512,103.2 271,696.4
Istočna Srbija / Ukupan iznos fakture / Total invoice amount < 0.001
(231,734.8 – 384,200.4) (373,152.7 – 626,516.5) (216,759.2 – 351,204.8)
East Serbia
Broj dana hospitalizacije / Number of days of hospital stay 12 (8 – 20) 29.5 (25 – 39) 14 (11 – 19) < 0.001
258,989.8 581,338.8 203,086.9
Južna Srbija/ Ukupan iznos fakture / Total invoice amount < 0.001
(186,943.4 – 404,702.4) (264,184.6 – 893,674) (159,515.1 – 255,794.9)
South Serbia
Broj dana hospitalizacije / Number of days of hospital stay 11 (8 – 16) 26.5 (16.5 – 37) 10 (8 – 14) < 0.001
Centralna 307,995 390,048 234,968.6
Srbija / (217,097.7 – 428,826.4) (249,080.9 – 700,264.9) (184,884.6 – 306,681.4)
Central Serbia Broj dana hospitalizacije / Number of days of hospital stay 13 (8 – 19) 31 (16.5 – 40.5) 12 (8 – 16) < 0.001
AP Vojvodina / 302,596.1 561,971.3 214,990.3
Autonomous (213,808.2 – 411,959.1) (368,837.8 – 669,199) (179,504.8 – 275,306.4)
Province of
Vojvodina Broj dana hospitalizacije / Number of days of hospital stay 14 (9 – 21) 23.5 (18 – 36) 10 (8 – 13) < 0.001
274,765.7 218,098.1 256,400.4

Zapadna Srbija / Ukupan iznos fakture / Total invoice amount 0.051
(196,785.6 – 410,079.4) (214,042 – 234,916) (187,771.2 – 330,216.6)
West Serbia
Broj dana hospitalizacije / Number of days of hospital stay 14 (10 – 21) 11 (8 – 13) 12 (9 – 16) 0.004
dijagnoze se ne može sa sigurnošću reći kada su na- 21 days, in the City of Belgrade, to 31 days, in the region
stale i u kom periodu hospitalizacije – pre, za vreme ili of Central Serbia, while it was the shortest in the region
nakon hirurške intervencije, za razliku od posmatranih of West Serbia (11 days on average) (p < 0.001) (Table 4).
dijagnoza u analizi T81-T88, čiji naziv jasno ukazuje na
komplikacije nastale kao posledica hirurške interven- DISCUSSION
cije ili lečenja. Ovaj problem je posledica načina izve- During the observed three-year period, DRG migra-
štavanja o radu zdravstvenih ustanova ka RFZO-u, jer tion was registered in 108 (7.4%) episodes of hospital
elektronska faktura sadrži osnovni uzrok hospitalizaci- treatment, which means that patients, due to complica-
je i sve prateće dijagnoze koje su bile značajne za epi- tions (diagnoses T81-T88) which had developed during
zodu lečenja, ali one nisu razvrstane na komorbiditete hospital stay were categorized into another DRG, with
sa kojima je pacijent primljen i komplikacije koje su se a greater cost weight. However, this data must be con-
desile tokom bolničkog lečenja. sidered with certain reservations, since not all compli-
Za razliku od razvijenijih zemalja, u kojima se prime- cations potentially leading to DRG migration could be
njuje neki od modela plaćanja po učinku, u Republici identified in the process of data analysis. Namely, the
Srbiji, ni pružaoci ni ugovarač zdravstvenih usluga nisu most frequent complications following large intestine
u potpunosti prihvatili značaj detaljnog prikazivanja excision are different wound infections and infections
slučajeva i dokumentacije kojom se pravdaju sredstva of internal organs, followed by gastrointestinal motility
utrošena za lečenje. Razlog za to je što se novac zdrav- complications, including ileus and bowel obstruction
stvenim ustanovama, još uvek, u najvećoj meri (95%) [14]. However, for the said diagnoses, it cannot be de-
prenosi po namenama na osnovu predračunom ugo- termined with certainty when they developed and in
vorenih sredstava, dok se preostali, varijabilni deo od which part of the patient’s hospital stay – before, during
5%, obračunava na osnovu zbira težinskih koeficijenata or after the surgical procedure, as opposed to the ob-
DSG. Tek po određivanju baznog koeficijenta, može se served diagnoses in the analysis of T81-T88, whose name
doći i do cena DSG grupa, nakon čega se može smatrati clearly indicates complications occurring as the result of
da je potpuno završena implementacija modela plaća- a surgical procedure or treatment. This problem is the
nja po DSG sistemu. Kada se zdravstvenim ustanova- result of the method used for reporting on the function-
ma bude definisao budžet na osnovu vrednosti njiho- ing of healthcare institutions to the RFZO. Namely, the
vih DSG grupa, onda će se povećati značaj ispravnog electronic invoice does state the basic cause of hospital-
izveštavanja, kako za bolnice, tako i za RFZO, naravno ization and all the underlying diagnoses that were sig-
iz dijametralno suprotnih razloga. Interes zdravstvene nificant for the episode of hospital treatment, but these
ustanove je da opravda finansijska ulaganja, dok je in- are not further classified to show which comorbidities
teres RFZO-a da racionalizuje potrošnju sredstava. the patient had been admitted with and which compli-
Kada se posmatra distribucija grupa G02A, G02A cations occurred during hospital treatment.
(T81-T88) i G02B, od ukupno 4.939 grupa pacijenata, As opposed to the more developed countries,
koliko ih je zabeleženo u periodu od 1. 1. 2018. do 21. where one of the performance-related payment models
12. 2020. godine, 2.779 njih, odnosno 56,26%, su bile is applied, in the Republic of Serbia, neither the service
grupe pacijenata lečenih u jedanaest od ukupno 49 provider nor the service contractor have completely ac-
bolnica koje izvode kolektomije. Svih jedanaest zdrav- cepted the significance of more detailed case reports
stvenih ustanova pripada tercijarnom nivou zdravstve- and files whose purpose is to account for the funds
ne zaštite, što je i očekivano, imajući u vidu komplek- spent on treatment. The reason for this is that money
snost samih procedura i težinu kliničke slike pacijenata is still mostly (95%) allocated to healthcare institutions,
koja zahteva izvođenje kolektomije. U pogledu DSG by dedicated budget lines, based on funds contracted
migracije, trećina (33 od 108) grupa G02A (T81-T88) pri- on the basis of estimate, while the remaining, variable
padala je pomenutim tercijarnim ustanovama, a DSG part, amounting to 5%, is calculated based on the sum
migracija je iznosila samo 1,58%. Kako se DSG migracija of DRG cost weights. Only after the base rate is deter-
može posmatrati kao mera kvaliteta rada zdravstvene mined can the costs of each DRG group be defined,
ustanove, ustanove tercijarnog nivoa koje imaju najbo- upon which the implementation of the payment model
lju medicinsku opremu i najobučeniji subspecijalistički based on the DRG system can be considered complete-
kadar imaju i najmanju DSG migraciju [15,16]. ly finished. When the practice of defining the budget
Međunarodna praksa je pokazala da je kod tzv. of healthcare institutions on the basis of the value of
otvorenih operacija veći rizik od nastajanja komplika- their DRG groups becomes prevalent, the significance
cija, a samim tim je i duži period oporavka pacijenta, of proper reporting will increase, both for the hospitals,
odnosno veći je rizik od produžavanja hospitalizacije. but also for the RFZO, naturally, for opposing reasons.
Prelazak na minimalno invazivne, odnosno laparo- The interest of the healthcare institution is to justify fi-
skopske kolektomije bi u ovom slučaju imao pozitivan nancial investment, while the interest of the RFZO is to
efekat na ishode i uštede [17]. Međutim, ono što bi bilo rationalize the consumption of resources.
najvažnije jeste redovno merenje ovog pokazatelja When the distribution of groups G02A, G02A
efikasnosti zdravstvene zaštite i inkorporiranje ekono- (T81-T88) and G02B is observed, out of a total of 4,939
metrije u zdravstvenu politiku, jer je merenje troškova, patient groups recorded in the period between Janu-
koje u sistemu generišu komplikacije, i to na način koji ary 1, 2018 and December 31, 2020, 2,779 groups, i.e.,
je zasnovan na dokazima, kao što je prikazano u ovom 56.26%, were groups of patients treated at 11 out of a
istraživanju, od velikog značaja [18]. Pojedine studije total of 49 hospitals, where colectomies are performed.
pokazuju da određene komplikacije kolektomija mogu All of the eleven healthcare institutions are at the tertia-
iznositi i preko 8% ukupnih bolničkih troškova [19]. ry level of health care, which is to be expected, bearing
Redovnim praćenjem troškova i pokazatelja kva- in mind the complexity of the procedures themselves as
liteta rada bolnica mogu se detektovati one ustano- well as the severity of patient presentation requiring col-
ve koje predstavljaju centre izuzetnosti za određenu ectomy. With regards to DRG migration, a third (33 out
patologiju. Prepoznavanje centara izuzetnosti je ve- of 108) of the G02A (T81-T88) groups belonged to the
oma značajno, s obzirom da se pacijenti onda mogu abovementioned tertiary healthcare institutions, and
usmeravati na lečenje tamo gde je volumen određene DRG migration was only 1.58%. As DRG migration can be
patologije značajan, a međunarodna praksa pokazuje considered a measure of the quality of work of a health-
da je u tom slučaju procenat neželjenih događaja sma- care facility, the tertiary-level institutions with the best
njen, kvalitet zdravstvene zaštite bolji i troškovi lečenja medical equipment and the best trained subspecialists
manji [20]. To sugeriše i potrebu da donosioci odluka also have the lowest DRG migration [15,16].
razmotre model organizacije pružanja usluga u kojem International practice has shown that in, so called,
bi se slučajevi kolektomije uspešnije rešavali u terci- open surgery procedures the risk of complications is high-
jarnim ustanovama i još nekoliko referentnih centara, er, and thereby the recovery period for the patient is lon-
koji imaju najbolju medicinsku opremu i najobučeniji ger, i.e. the risk of prolonged hospital stay is higher. Tran-
subspecijalistički kadar, i stoga i manju DSG migraciju. sitioning to minimally invasive, i.e., laparoscopic colecto-
U pogledu procedura kolektomije, prosečna po- mies would, in this case, have a positive effect on both
trošnja na ove intervencije u periodu 2018 – 2020. outcomes and cost reduction [17]. However, what would
bila je oko 488,8 miliona dinara (cca 4,2 miliona €) po be most important is performing regular measuring of this
godini. Rezultati dobijeni u ovom radu pokazuju sta- indicator of health care efficiency and incorporating eco-
tistički značajne razlike u iznosima faktura. Oni takođe nometry into health policy, since measuring costs, which
pokazuju da su, u proseku, najskuplje bile fakture za are generated in the system by complications, particular-
grupu G02A (T81-T88). Isto tako, najduže hospitalizaci- ly evidence-based measuring – as shown in this study, is
je se vezuju za ovu grupu. Kada je stopa DSG migraci- of great significance [18]. Individual studies have shown
je od 7,4% ekstrapolirana na sve pacijente kojima je u that certain complications of colectomies may amount to
Republici Srbiji u posmatranom periodu od tri godine more than 8% of overall hospital costs [19].
urađena procedura kolektomije, dobijeno je povećanje Regular monitoring of indicators of hospital costs
ukupnog iznosa faktura za 2,6% (12,5 miliona dinara, and work quality enables the detection of those hospi-
odnosno cca 106.500 €), kao i povećanje broja B.O. tals which are centers of excellence for certain pathol-
dana za 1.771 dan [18]. To praktično znači da postoji ogies. Identifying centers of excellence is very import-
povećanje od oko 590 B.O. na godišnjem nivou, odno- ant, since patients can then be referred for treatment to
sno skoro dva zauzeta kreveta tokom cele godine na those facilities where the volume of a certain pathology
račun komplikacija iz spektra T81-T88, samo kod izvo- is significant – and international experience has shown
đenja procedure kolektomije. Zato je praćenje DSG that, in such cases, the percentage of adverse effects de-
migracija vrlo dobar indikator za detekciju neefikasnih creases, the quality of health care improves, and treat-
medicinskih intervencija. ment costs drop [20]. This suggest the need for decision
Procenat komplikacija tokom bolničkog lečenja makers to consider an organizational model of service
je jedan od pokazatelja kvaliteta zdravstvene zaštite, provision wherein colectomy cases would be more suc-
a praćenje DSG migracija usled komplikacija nastalih cessfully resolved at tertiary healthcare institutions and
u toku procedura obavljenih tokom hospitalizacije at several referral centers, which have the best medical
preciznije ukazuje na kvalitet rada u bolnicama. U equipment and the best trained subspecialists, and
Republici Srbiji, praćenje kvaliteta zdravstvene zašti- therefore lesser DRG migration.
te je definisano posebnim Pravilnikom [21]. Kompli- Regarding colectomies, the average expenditure
kacije definisane dijagnozama T81-T88 su pre svega for these procedures, in the period 2018 – 2020, was
različite infekcije u vezi sa hirurškom intervencijom, around 488.8 million RSD (approximately 4.2 million
o kojima su zdravstvene ustanove u obavezi da izve- euros), per year. The results obtained in this study show
štaju u okviru pokazatelja bezbednosti pacijenata statistically significant differences in invoice amounts.
na hirurškim odeljenjima. Prema poslednjem javno They also show that the costliest invoices were for group
dostupnom Izveštaju o unapređenju kvaliteta rada u G02A (T81-T88). Also, the longest hospital stays are re-
zdravstvenim ustanovama Republike Srbije [22], sto- lated to this group. When the rate of DRG migration of
pa incidencije infekcije operativnog mesta je oko 1%. 7.4% was extrapolated to all the patients in the Repub-
Međutim, još uvek ne postoji svest institucija o važ- lic of Serbia who had undergone colectomy in the ob-
nosti evidentiranja ovih neželjenih događaja, kao ni o served three-year period, the result was an increase in
njihovom značaju, ne samo za zdravlje pacijenata, već the total invoice amount of 2.6% (12.5 million RSD, i.e.,
i za sveukupne troškove u sistemu zdravstvene zašti- approximately 106,500 euros), as well as an increase in
te, na šta ukazuje ovo istraživanje. the number of patient days by 1,771 days [18]. This prac-
Prednosti ovog istraživanja ogledaju se u tome tically means that there is an increase of around 590 pa-
što je ono pružilo uvid u parametre kao što su: dis- tient days a year, i.e., almost two occupied beds during
tribucija pacijenata kojima je urađena procedura the entire year resulting from complications from the
kolekotomije po posmatranim grupama, prosečan T81-T88 spectrum, in colectomy procedures alone. This
trošak i prosečna dužina hospitalizacije za svaku od is why monitoring DRG migrations is a very good indica-
dijagnostički srodnih grupa, te procenat DSG migraci- tor for detecting inefficient medical procedures.
ja, na osnovu izdvojenih komplikacija. S druge strane, The percentage of complications during hospital
imajući u vidu da nedostaci u procesu prikupljanja treatment is one of the indicators of the quality of health
podataka u Republici Srbiji dovode do nekompletnih care, while the monitoring of DRG migrations occurring
ili nepreciznih podataka o svim mogućim komplika- as the result of complications developing during proce-
cijama nakon resekcije debelog creva (već pomenute dures performed in the course of hospitalization more
infekcije rane i unutrašnjih organa, komplikacije mo- specifically indicate the work quality in hospitals. In the
tiliteta, ileus i opstrukcija creva), kroz ovu analizu nisu Republic of Serbia, the control of the quality of health
mogli biti obuhvaćeni i analizirani svi potencijalni slu- care is defined by a special Rulebook [21]. The compli-
čajevi DSG migracije. cations defined by the diagnoses T81-T88 are primarily
ZAKLJUČAK different infections related to surgical procedures, which

healthcare institutions are obliged to report on, within
Na nacionalnom nivou, i na skoro svim regionalnim ni-
the indicators of patient safety in surgical wards. Accord-
voima u Republici Srbiji, statistički značajno stariji od
ing to the latest available Report on the Improvement of
ostalih jesu pacijenti koji su izdvojeni u dijagnostičku
Work Quality in Healthcare Institutions of the Republic of
grupu G02A (T81-T88), koja predstavlja DSG migraciju,
Serbia [22], the incidence rate of surgical site infection is
i njihovo lečenje je statistički značajno duže i skuplje,
around 1%. However, awareness in the institutions on the
u pogledu vrednosti pruženih usluga, vrednosti B.O.
importance of recording these adverse effects is still lack-
dana, vrednosti lekova, vrednosti krvi i produkata krvi,
ing, as is the awareness of their importance, not only for
kao i ukupne vrednosti fakture. Kolektomije sa kompli-
the health of the patient, but also for the overall health-
kacijama, kao posledicama bolničkog lečenja ili medi-
care system costs, as shown in this study.
cinske intervencije, dovode do svrstavanja date epizo-
The advantages of this study are reflected in the
de bolničkog lečenja u dijagnostički srodnu grupu koja
fact that it has offered insight into parameters, such
podrazumeva veću potrošnju resursa i veću dužinu
as: distribution of patients who had undergone colec-
hospitalizacije. DSG migracija kao pokazatelj efikasno-
tomy by groups, average cost and average length of
sti i kvaliteta pružene zdravstvene zaštite može biti
hospital stay for each of the diagnosis related groups,
valjan signal za kontrolu i upravljanje procesima i kva-
as well as the percentage of DRG migration, based on
litetom rada u jednoj zdravstvenoj ustanovi ili njenoj
the separate complications. On the other hand, bearing
organizacionoj jedinici.
in mind that the drawbacks in the process of data col-
Sukob interesa: Nije prijavljen. lection in the Republic of Serbia lead to the generation
of incomplete and imprecise data on all the possible
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ANTIBIOTSKA PROFILAKSA U ABDOMINALNOJ HIRURGIJI
- USAGLAŠENOST PREPORUKA I PRAKSE
ANTIBIOTIC PROPHYLAXIS IN ABDOMINAL SURGERY –

COMPLIANCE WITH INTERNATIONAL GUIDELINES
Jelena Veličković1,2, Suzana Sredić1, Aleksandra Radovanović Spurnić1,3, Igor Lazić2, Ivan Palibrk1,2,
Vesna Mioljević4, Slavenko Ostojić1,5
1
Univerzitet u Beogradu, Medicinski fakultet, Beograd, Srbija 1
University of Belgrade, Faculty of Medicine, Belgrade, Serbia
2
Univerzitetski klinički centar Srbije, Centar za anesteziju, 2
University Clinical Center of Serbia, Belgrade, Center for Anesthesia,
Beograd, Srbija Serbia
3
Univerzitetski klinički centar Srbije, Beograd, Klinika za 3
University Clinical Center of Serbia, Clinic for Infectious and
infektivne i tropske bolesti, Srbija Tropical Diseases, Belgrade, Serbia
4
Univerzitetski klinički centar Srbije, Služba za bolničku 4
University Clinical Center of Serbia, Department for Hospital
epidemiologiju i higijenu ishrane, Beograd, Srbija Epidemiology and Dietetics, Belgrade, Serbia
5
Univerzitetski klinički centar Srbije, Klinika za digestivnu 5
University Clinical Center of Serbia, Clinic for Digestive Surgery –
hirurgiju – Prva hirurška klinika, Beograd, Srbija First Surgical Clinic, Belgrade, Serbia
SAŽETAK ABSTRACT
Uvod: Antibiotska profilaksa (AP) u hirurgiji predstavlja značajnu meru za sma- Introduction. Antibiotic prophylaxis (AP) in surgery is an important measure
njenje incidencije nastanka infekcija operativnog mesta. Međunarodne smerni- that contributes to the prevention of surgical site infection. International and
ce i Nacionalni vodič daju jasne preporuke za pravilno sprovođenje antibiotske national guidelines provide clear recommendations for the proper implementa-
profilakse, međutim podaci u literaturi ukazuju na nedovoljno poštovanje ovih tion of antibiotic prophylaxis. However, many studies indicate poor compliance in
smernica u mnogim zdravstvenim ustanovama. many health care centers.
Cilj: Cilj naše studije je bio da se ispita stepen usaglašenosti prakse u primeni antibiot- Aim: Our study aimed to determine the level of compliance in the application of
ske profilakse u adbominalnoj hirurgiji sa međunarodnim i nacionalnim smernicama. antibiotic prophylaxis in abdominal surgery with the guidelines.
Materijali i metode: Retrospektivnom studijom su obuhvaćeni svi bolesnici operi- Materials and methods: The retrospective study included all patients which
sani na Klinici za digestivnu hirurgiju Univerzitetskog kliničkog centra Srbije (UKCS), were operated on at the Clinic for Digestive Surgery of the University Clinical
u periodu januar – mart 2019. godine (270 pacijenata). Iz medicinske dokumentacije Center of Serbia (UCCS), during the period January - March 2019 (270 patients).
dobijeni su podaci koji se odnose na vrstu operacije, primenjenu antibiotsku profilak- Medical records provided information about the type of surgery, the choice of an-
su, vreme primene prve doze, način primene, potrebu za redoziranjem, kao i na duži- tibiotic, the time of application, the route of administration, the need for redos-
nu primene profilakse i postojanje alergije na lekove. Prikupljeni podaci su analizirani ing, the duration of antibiotic prophylaxis administration, as well as the presence
metodama deskriptivne i analitičke statistike (χ2 test). of drug allergies. The collected data were analyzed by descriptive and analytical
Rezultati: Tokom perioda ispitivanja, na Klinici za digestivnu hirurgiju je ope- statistics (χ2 test).
risano 270 bolesnika, od kojih je antibiotsku profilaksu primilo 227 (84,1%) bo- Results: During the study period, 270 patients were operated on at the Clinic for Di-
lesnika. Cefazolin, koji je preporučen za većinu operacija u digestivnoj hirurgiji, gestive Surgery, of whom 227 (84.1%) received antibiotic prophylaxis. Cefazolin, an
primilo je 17 (6,3%) bolesnika. Najveći broj bolesnika (64,4%) je profilaksu primi- antibiotic recommended for most abdominal surgeries, was administered to only
lo unutar 30 minuta po započinjanju operacije. Trajanje profilakse do 24 sata od 17 (6.3%) patients. The majority of patients (64.4%) received antibiotic prophylaxis
operacije sprovedeno je kod 13.1% operisanih bolesnika. within 30 minutes of the beginning of surgery. The duration of antibiotic prophylax-
Zaključak: Usaglašenost kliničke prakse sa preporukama iz vodiča za antibiotsku is of up to 24 hours after the operation was applied in 13.1% of patients.
profilaksu u abdominalnoj hirurgiji je bila na niskom nivou. Potpuna usaglašenost Conclusion: Compliance with the guidelines was low, while full compliance with
sa preporukama za primenu antibiotske profilakse je zabeležena samo po pitanju the recommendations for antibiotic prophylaxis was achieved only with regards
puta primene antibiotika. to the route of antibiotic administration.
Ključne reči: antibiotska profilaksa, abdominalna hirurgija, infekcija hirurškog mesta Keywords: antibiotic prophylaxis, abdominal surgery, surgical site infection

Jelena Veličković Jelena Veličković
Medicinski fakultet, Univerzitet u Beogradu Faculty of Medicine, University of Belgrade, Serbia
Dr Subotića 8, 11000 Beograd, Srbija 8 Dr Subotića Street, 11000 Belgrade, Serbia
Elektronska adresa: lelavelickovic@gmail.com E-mail: lelavelickovic@gmail.com
Primljeno • Received: January 17, 2022; Revidirano • Revised: March 6, 2022; Prihvaćeno • Accepted: May 17, 2022; Online first: June 25, 2022
10.5937/smclk3-35917
antibiotska profilaksa u abdominalnoj hirurgiji - usaglašenost preporuka i prakse
Veličković J. i sar.
antibiotic prophylaxis in abdominal surgery – compliance with international guidelines
UVOD INTRODUCTION
Antibiotska profilaksa (AP) u hirurgiji predstavlja efika- Antibiotic prophylaxis (AP) in surgery is an efficient
san metod za prevenciju i smanjenje rizika od nastanka method for preventing and reducing the risk of surgi-
infekcija operativnog mesta. Prema podacima Centra cal site infection. According to the Centers for Disease
za kontrolu i prevenciju bolesti u Atlanti (engl. Cen- Control and Prevention (CDC), surgical site infections
ters for Disease Control and Prevention - CDC), infekcije are considered an important global problem [1]. They
operativnog mesta se smatraju važnim globalnim pro- are connected with a longer duration of treatment, the
blemom [1]. Infekcije operativnog mesta su povezane need for additional surgical procedures, and a higher
sa dužim trajanjem lečenja, potrebom za dodatnim mortality rate [2]. International guidelines and the Ser-
hirurškim procedurama, i većom stopom mortaliteta bian National Good Clinical Practice Guideline provide
[2]. Međunarodne smernice i Nacionalni vodič kliničke clear recommendations for the proper implementation
prakse daju jasne preporuke za pravilno sprovođenje of antibiotic prophylaxis in surgery [3,4]. However, data
antibiotske profilakse u hirurgiji [3,4]. Međutim, poda- from literature indicate insufficient compliance with
ci u literaturi ukazuju na nedovoljno poštovanje ovih these guidelines, in many healthcare institutions [5,6].
smernica u mnogim zdravstvenim ustanovama [5,6]. Irrational and inadequate use of antibiotics represents
Neracionalna i neadekvatna upotreba antibiotika pred- one of the main drivers of bacterial resistance develop-
stavlja jedan od glavnih pokretača razvoja rezistencije ment and may be accompanied by the occurrence of
bakterija, a može biti udružena sa pojavom brojnih ne- many adverse effects of antibiotics and increased over-
željenih efekata antibiotika i povećanim ukupnim troš- all treatment costs [1,2].
kovima lečenja [1,2]. The choice of the antibiotic mostly depends on the
Izbor antibiotika najviše zavisi od područja na kome region of the body where the surgical procedure is per-
se izvodi hirurški zahvat, ali na osnovu najvećeg broja formed. However, based on the majority of recommen-
preporuka iz međunarodnih smernica i vodiča kliničke dations from international guidelines and clinical prac-
prakse, cefalosporini prve generacije (cefazolin) su leko- tice guides, first generation cephalosporins (cefazolin)
vi prvog izbora u prevenciji infekcija operativnog mesta are the medicaments of first choice in the prevention
u abdominalnoj hirurgiji. Preporučuje se intravenska of surgical site infections in abdominal surgery. Intrave-
primena antibiotika. Za većinu antibiotika u hirurškoj nous administration of antibiotics is recommended. For
antibiotskoj profilaksi, adekvatnim se smatra primena most antibiotics in surgical antibiotic prophylaxis, the
antibiotika unutar 60 minuta pre početka operacije [3]. application of antibiotics within 60 minutes of the be-
Uvek treba razmotriti davanje još jedne doze antibioti- ginning of the surgical procedure is considered appro-
ka kod procedura koje su trajale duže od dva poluvre- priate [3]. Administering one more dose of the antibi-
mena eliminacije leka, kao i u slučaju gubitka više od otic should always be considered in procedures lasting
1.500 ml krvi. Kod pacijenata sa dokazanom alergijom longer than two drug elimination half-lives, as well as
na penicilin, treba izbegavati davanje beta-laktamskih in cases where there was more than 1,500 ml of blood
antibiotika, i u tom slučaju se koristi alternativni antibi- loss. In patients with proven penicillin allergy, admin-
otik naveden u smernicama. Smatra se da je jedna doza istration of beta-lactam antibiotics should be avoided.
antibiotika dovoljna za efikasnu antibiotsku profilaksu In such cases, the alternative antibiotic proposed in the
kod najvećeg broja hirurških zahvata, te da je treba za- guidelines should be administered. It is believed that a
vršiti unutar 24 sata [3,4]. single dose of antibiotic is sufficient for effective antibi-
Cilj naše studije je bio da se ispita stepen usagla- otic prophylaxis in most surgical procedures and that it
šenosti prakse u primeni antibiotske profilakse u ab- should be completed within 24 hours [3,4].
dominalnoj hirurgiji sa međunarodnim smernicama i The aim of our study was to investigate the level of
preporukama Nacionalnog vodiča. compliance of antibiotic prophylaxis application in ab-
dominal surgery with international guidelines and the
MATERIJALI I METODE recommendations from the National Guide.
Retrospektivna studija načina primene antibiotske MATERIALS AND METHODS
profilakse u abdominalnoj hirurgiji je obuhvatila 270
bolesnika operisanih na Klinici za digestivnu hirurgiju This retrospective study of the method of antibiotic pro-
Univerzitetskog kliničkog centra Srbije (UKCS), u peri- phylaxis application in abdominal surgery included 270
odu januar - mart 2019. godine. Pacijenti podvrgnuti patients, who were surgically treated at the Clinic for Di-
hitnoj operaciji, oni sa prethodno dokazanom infekci- gestive Surgery of the University Clinical Center of Ser-
jom kod kojih je antibiotska terapija u toku, i pacijenti bia (UCCS), in the period January – March 2019. Patients
undergoing emergency surgery, those with a previously
Veličković J. et al.
podvrgnuti invazivnim dijagnostičkim procedurama proven infection who had already been on antibiotic
bili su isključeni iz ispitivanja (56 bolesnika). Podaci o therapy, as well as patients undergoing invasive diag-
primenjenoj antibiotskoj profilaksi, vrsti antibiotika, nostic procedures were excluded from the study (56 pa-
načinu primene, vremenu davanja prve doze, potrebi tients). Data on applied antibiotic prophylaxis, the type
za redoziranjem, dužini primene antibiotika i postoja- of antibiotic, the mode of administration, the time of
nju alergije na lekove, dobijeni su iz medicinske doku- administration of the first dose, the need for redosing,
mentacije (liste anestezije i terapijske liste). the length of antibiotic application, and the presence of
Podaci su analizirani metodama deskriptivne i ana- drug allergies, were obtained from medical records (an-
litičke statistike. U zavisnosti od vrste obeležja posma- esthesia records and hospital medication charts).
tranja, podaci su prikazani kao medijana (interkvartilni The data were analyzed using the methods of de-
opseg) ili broj (procenat). Usaglašenost dobijenih rezul- scriptive and analytical statistics. Depending on the type
tata sa preporukama je ispitana u odnosu na Nacional- of marker being observed, the data have been present-
ni vodič dobre kliničke prakse – Racionalna upotreba ed as the median (interquartile range) or number (per-
antibiotika i Vodič za antimikrobnu profilaksu u hirur- centage). The compliance of the obtained results with
giji Američkog udruženja bolničkih farmaceuta (engl. the recommendations was tested in relation to the Ser-
ASHP Therapeutic Guidelines on Antimicrobial Prop- bian National Good Clinical Practice Guideline for Ratio-
hylaxis in Surgery; American Society of Health-System nal Antibiotic Use and the ASHP Therapeutic Guidelines
Pharmacists - AHSP) (Tabela 1). on Antimicrobial Prophylaxis in Surgery of the American
U kreiranju baze i obradi podataka korišćen je sof- Society of Health-System Pharmacists (AHSP) (Table 1).
tver IBM SPSS Statistics for Windows, Version 22.0 (IBM In creating the database and in data processing,
Corp., Armonk, NY). the software – IBM SPSS Statistics for Windows, Version
22.0 (IBM Corp., Armonk, NY), was used.
Tabela 1. Preporuke za antibiotsku profilaksu u abdominalnoj hirurgiji odraslih [3, 4]
Put Trajanje
Tip procedure Preporučeni antibiotik Alternativa Redoziranje
primene profilakse
Cefazolin 2 - 3 g, i.v.; Kod operacija dužeg trajanja: nakon 4 h za 1 doza ili

Klindamicin 900 mg, i.v.;
Ezofagektomija ampicilin/sulbaktam i.v. cefazolin, nakon 2 h za ampicilin/sulbaktam; završiti unutar
vankomicin 15 mg/kg
3 g, i.v. nakon 6 h za klindamicin 24 h
Cefazolin 2 - 3 g, i.v.; Klindamicin 900 mg, i.v.; Kod operacija dužeg trajanja: nakon 4 h za 1 doza ili
Operacija sa ulaskom u
ampicilin/sulbaktam vankomicin 15 mg/kg + aminoglikozid i.v. cefazolin, nakon 2 h za ampicilin/sulbaktam; završiti unutar
lumen GIT-a
3 g, i.v. ili hinolon nakon 6 h za klindamicin 24 h
Klindamicin 900 mg, i.v.; Kod operacija dužeg trajanja: nakon 4 h za 1 doza ili
Operacija bez ulaska u
Cefazolin 2 - 3 g, i.v. vankomicin 15 mg/kg + aminoglikozid i.v. cefazolin, nakon 2 h za ampicilin/sulbaktam; završiti unutar
lumen GIT
ili hinolon nakon 6 h za klindamicin 24 h
Elektivna laparoskopija
- - - - -
niskog rizika
Cefazolin 2 - 3 g, i.v.; Klindamicin 900 mg, i.v.;

Kod operacija dužeg trajanja: nakon 4 h za 1 doza ili
Elektivna laparoskopija ampicilin/sulbaktam vankomicin 15 mg/kg + aminoglikozid ili
i.v. cefazolin, nakon 2 h za ampicilin/sulbaktam; završiti unutar
visokog rizika 3 g, i.v.; ceftriakson hinolon ili
nakon 6 h za klindamicin * 24 h
2 g, i.v. metronidazol 500 mg + aminoglikozid
1 doza ili
Klindamicin 900 mg, i.v.; i.v. Kod operacija dužeg trajanja: nakon 4 h za
Operacija hernije Cefazolin 2 - 3 g i.v. završiti unutar
vankomicin 15 mg/kg cefazolin; nakon 6 h za klindamicin
24 h
Cefazolin 2 - 3 g +
metroniodazol 1g ili
Klindamicin Kod operacija dužeg trajanja: nakon 4 h za 1 doza ili
ampicilin/sulbaktam
Kolorektalna operacija 900 mg + aminoglikozid ili metronidazol i.v. cefazolin, nakon 2 h za ampicilin/sulbaktam; završiti unutar
3 g ili ceftriakson 2 g
+ aminoglikozid ili hinolon nakon 6 h za klindamicin ** 24 h
+ metronidazol 1 g, ili
ertapenem 1 g
* Redoziranje nije potrebno za većinu operacija za ceftriakson, metronidazol, vankomicin, aminoglikozid i hinolone.
** Ertapenem nije potrebno redozirati.
Table 1. Recommendations for antibiotic prophylaxis in abdominal surgery in adults [3, 4]
Route of Duration of
Type of procedure Recommended antibiotic(s) Alternative antibiotic(s) Redosing
administration prophylaxis
Clindamycin 900 mg, IV; In prolonged surgery: after 4 hours for 1 dose or to be
Cefazolin 2 - 3 g, IV; ampicillin/
Esophagectomy vancomycin IV cefazoline; after 2 hours for ampicillin/ completed within
sulbactam 3 g, IV
15 mg/kg, IV sulbactam; after 6 hours for clindamycin 24 hours
Surgery with GIT Cefazolin 2 - 3 g, IV; ampicillin/
vancomycin 15 mg/kg + IV cefazoline; after 2 hours for ampicillin/ completed within
involvement sulbactam 3 g, IV
aminoglycoside or a quinolone sulbactam; after 6 hours for clindamycin 24 hours
Surgery without GIT IV
Cefazolin 2 - 3 g, IV vancomycin 15 mg/kg + cefazoline; after 2 hours for ampicillin/ completed within
involvement
aminoglycoside or a quinolone sulbactam; after 6 hours for clindamycin 24 hours
Low-risk elective
laparoscopic - - - - -
cholecystectomy
Clindamycin 900 mg, IV;
vancomycin In prolonged surgery: after 4 hours for 1 dose or to be
High-risk elective Cefazolin 2 - 3 g, IV; ampicillin/
15 mg/kg + aminoglycoside cefazoline, after 2 hours for ampicillin/ completed within
laparoscopic sulbactam 3 g, IV; ceftriaxone IV
or a quinolone or sulbactam; after 6 hours for clindamycin* 24 hours
cholecystectomy 2 g, IV
metronidazole 500 mg +
aminoglycoside
1 dose or to be
Clindamycin 900 mg, IV; In prolonged surgery: after 4 hours for
IV completed within
Hernia repair Cefazolin 2 - 3 g, IV vancomycin cefazoline; after 6 hours for clindamycin
24 hours
15 mg/kg, IV
Cefazolin 2 - 3 g + metronidazole Clindamycin 900 mg In prolonged surgery: after 4 hours 1 dose or to be

1 g or ampicillin/sulbactam 3 g or + aminoglycoside for cefazoline; after 2 hours for completed within
Colorectal surgery IV
ceftriaxone 2 g + metronidazole or metronidazole + ampicillin/sulbactam; after 6 hours for 24 hours
1 g or ertapenem 1 g aminoglycoside or quinolone clindamycin**
* Redosing not required for a majority of the surgical procedures for ceftriaxone, metronidazole, vancomycin, aminoglycoside, and quinolones
** Redosing not required for ertapenem
REZULTATI RESULTS
U toku perioda ispitivanja, na Klinici za digestivnu hi- Within the study period, at the Clinic for Digestive Sur-
rurgiju je operisano 270 bolesnika, čije su operacije gery, 270 patients were surgically treated; their oper-
grupisane u 13 grupa, a koje su bile prosečnog traja- ations were grouped into 13 groups; the average du-
nja od 100 (60 – 160) minuta. Antibiotsku profilaksu je ration of the operations was 100 (60 – 160) minutes.
primilo 227 (84,1%) bolesnika. Vrsta primenjene anti- In total, 227 (84.1%) patients received antibiotic pro-
biotske profilakse (lekovi i njihove kombinacije) prika- phylaxis. The type of administered antibiotic prophy-
zani su u Grafikonu 1. Cefazolin, antibiotik preporučen laxis (the drugs and their combinations) are presented
za većinu operacija u digestivnoj hirurgiji, primilo je 17 in Graph 1. Cefazolin, the antibiotic recommended for
(6,3%) bolesnika. Svi bolesnici su antibiotsku profilaksu most surgical procedures in digestive surgery, was ad-
primili intravenskim putem. Od bolesnika koji su primili ministered to 17 (6.3%) patients. All of the patients re-
profilaksu, 24 (8,9%) pacijenta je primilo antibiotik više ceived AP intravenously. Of the patients who received
od jedan sat pre operacije, 8 (3%) bolesnika ju je pri- AP, 24 (8.9%) patients were given the antibiotic more
milo unutar 60 minuta pre početka operacije, 19 (7%) than an hour prior to surgery, 8 (3%) patients got their
pacijenata je primilo antibiotsku profilaksu nakon više AP in the space of 60 minutes prior to the beginning
od 30 minuta od početka operacije, dok je većina, 174 of the operation, 19 (7%) patients received AP more
(64,4%) bolesnika, antibiotik primila unutar 30 minu- than 30 minutes after the start of the surgical proce-
ta po započinjanju operacije. Potreba za redoziranjem dure, while most of the patients, i.e., 174 (64.4%) of
antibiotika zbog trajanja operacije ili masivnog krvare- them, were given the antibiotic within 30 minutes of
nja postojala je kod 27 (10%) bolesnika. Među njima, the beginning of the operation. The need for antibiot-
antibiotik je redoziran kod 5 (18,5%) bolesnika. Prime- ic redosing due to the duration of the surgical proce-
na antibiotika u profilaktičke svrhe završena je unutar dure or because of massive bleeding arose in 27 (10%)
24 sata kod 30 (13,1%) bolesnika. Podatak o alergiji patients. Amongst them, the antibiotic was redosed
Grafikon 1. Distribucija vrsta antibiotika primenjenih za antimikrobnu profilaksu Figure 1. Distribution of drugs administered for antibiotic prophylaxis
Tabela 2. Usaglašenost prakse u primeni antibiotske profilakse sa smernicama, prema vrsti hirurgije
Trajanje operacije Vreme davanja Lek redoziran Trajanje

Antibiotik dat; Vrsta antibiotika; Put primene;
Vrsta operacije (min); medijana leka; ukoliko je profilakse;
n/N* (%) n/N (%) n/N (%)
[IKO**] n/N (%) potrebno; n/N(%) n/N (%)
85 36/52 2/52 36/36 2/52 6/36
Hernioplastika -
[70 – 110] (69.2%) (3.8%) (100.0%) (3.8%) (16.6%)
Laparospkopska 80 41/47 10/47 41/41 2/47 1/41
-
holecistektomija [70 – 110] (87.2%) (21.3%) (100.0%) (4.3%) (2.4%)
460 4/4 0/4 4/4 0/4 2/4 0/4
Ezofagektomija
[430 – 535] (100.0%) (0.0%) (100.0%) (0.0%) (50.0%) (0.0%)
Laparospkopska 145 6/8 0/9 6/6 0/8 1/6
-
antirefluks operacija [120 – 160] (75.0%) (0.0%) (100.0%) (0.0%) (16.6%)
240 11/12 2/12 11/11 0/12 0/5 1/11
Gastrektomija
[190 – 320] (91.7%) (16.7%) (100.0%) (0.0%) (0.0%) (9.1%)
180 23/24 1/24 24/24 1/24 0/10 0/23
Hepatobilijarna hirurgija
[120 – 345] (95.8%) (4.2%) (100.0%) (4.2%) (4.2%) (0.0%)
220 6/7 1/7 6/6 1/7 2/3 1/6
Resekcija pankreasa
[140 – 410] (85.7%) (14.3%) (100.0%) (14.3%) (28.6%) (16.6%)
Kolorektalna 120 47/53 35/53 47/47 2/53 0/2 18/47
hirurgija [80 – 180] (88.7%) (66.0%) (100.0%) (3.8%) (3.8%) (38.3%)
Proktološka 23/26 0/23 23/23 0/26 0/23
30 [30 – 45] -
intervencija (88.5%) (0.0%) (100.0%) (0.0%) (0.0%)
120 4/5 0/4 4/4 0/5 1/4
Operacija tankog creva -
[50 – 165] (80.0%) (0.0%) (100.0%) (0.0%) (25.0%)
220 3/3 2/3 3/3 0/3 1/1 0/3
Multiorganska resekcija
[120 – 360] (100.0%) (66.6%) (100.0%) (0.0%) (100.0%) (0.0%)
Splenektomija 160 3/3 1/3 3/3 0/3 0/3
-
[160 – 160] (100.0%) (33.3%) (100.0%) (0.0%) (0.0%)
85 21/26 7/26 21/21 0/21 0/2 0/21
Ostale operacije
[50 – 120] (80.8%) (26.9%) (100.0%) (0.0%) (0.0%) (0.0%)
100 227/270 61/270 227/227 8/270 5/27 30/227
Ukupno
[60 – 160] (84.1%) (22.6%) (100.0%) (3.0%) (18.5%) (13.1%)
Izvor preporuka: reference 3 i 4
n – Broj bolesnika koji je profilaksu dobio u skladu sa preporukama; N – Broj bolesnika koji je dobio profilaksu; IQR – Interkvartilni opseg;
Table 2. Compliance of clinical practice of antibiotic prophylaxis with recommendations according to the type of abdominal surgery
Drug
Operation length Antibiotic Type of Route of Timing of drug Duration of
Type of the re-dosed if
(min); Median administered; antibiotic; administration; administration; prophylaxis;
operation necessary;
[IQR] n/N (%) n/N (%) n/N (%) n/N (%) n/N (%)
n/N (%)
85 36/52 2/52 36/36 2/52 6/36
Hernioplasty -
[70 – 110] (69.2%) (3.8%) (100.0%) (3.8%) (16.6%)
Laparoscopic 80 41/47 10/47 41/41 2/47 1/41
-
cholecystectomy [70 – 110] (87.2%) (21.3%) (100.0%) (4.3%) (2.4%)
460 4/4 0/4 4/4 0/4 2/4 0/4
Esophagectomy
[430 – 535] (100.0%) (0.0%) (100.0%) (0.0%) (50.0%) (0.0%)
Antireflux 145 6/8 0/9 6/6 0/8 1/6
-
surgery [120 – 160] (75.0%) (0.0%) (100.0%) (0.0%) (16.6%)
240 11/12 2/12 11/11 0/12 0/5 1/11
Gastrectomy
[190 – 320] (91.7%) (16.7%) (100.0%) (0.0%) (0.0%) (9.1%)
Hepatobiliary 180 23/24 1/24 24/24 1/24 0/10 0/23
surgery [120 – 345] (95.8%) (4.2%) (100.0%) (4.2%) (4.2%) (0.0%)
Pancreas 220 6/7 1/7 6/6 1/7 2/3 1/6
resection [140 – 410] (85.7%) (14.3%) (100.0%) (14.3%) (28.6%) (16.6%)
Colorectal 120 47/53 35/53 47/47 2/53 0/2 18/47
surgery [80 – 180] (88.7%) (66.0%) (100.0%) (3.8%) (3.8%) (38.3%)
Proctological 23/26 0/23 23/23 0/26 0/23
30 [30 – 45] -
procedures (88.5%) (0.0%) (100.0%) (0.0%) (0.0%)
Small intestine 120 4/5 0/4 4/4 0/5 1/4
-
surgery [50 – 165] (80.0%) (0.0%) (100.0%) (0.0%) (25.0%)
Multiorgan 220 3/3 2/3 3/3 0/3 1/1 0/3
resection [120 – 360] (100.0%) (66.6%) (100.0%) (0.0%) (100.0%) (0.0%)
160 3/3 1/3 3/3 0/3 0/3
Splenectomy -
[160 – 160] (100.0%) (33.3%) (100.0%) (0.0%) (0.0%)
Other surgical 85 21/26 7/26 21/21 0/21 0/2 0/21
procedures [50 – 120] (80.8%) (26.9%) (100.0%) (0.0%) (0.0%) (0.0%)
100 227/270 61/270 227/227 8/270 5/27 30/227
Total
[60 – 160] (84.1%) (22.6%) (100.0%) (3.0%) (18.5%) (13.1%)
Source of recommendations: references 3 and 4
n – Number of patients in whom prophylaxis was administered according to guidelines; N – Number of patients who were given prophylaxis; IQR – Interquartile range
na penicilin dalo je 20 (7,4%) bolesnika, od kojih je 6 in (18.5%) patients. The application of antibiotic pro-
(30%) pacijenata primilo beta-laktamski antibiotik kao phylaxis was completed within 24 hours in 30 (13.1%)
profilaksu. Bolesnici bez prijavljene alergije na penici- patients. In total, 20 (74%) patients declared an aller-
lin su statistički značajno češće dobijali cefalosporine gy to penicillin, of whom 6 (30%) patients received a
kao profilaksu (145 (58%) naspram 6 (30%); χ2 = 5,89; beta-lactam antibiotic as prophylaxis. Patients without
p = 0,019). Usaglašenost prakse u primeni antibiotske a reported allergy to penicillin statistically more sig-
profilakse sa smernicama, prema vrstama hirurgije, pri- nificantly received cephalosporins as prophylaxis (145
kazana je u Tabeli 2. Način primene antibiotske profi- (58%) versus 6 (30%); χ2 = 5.89; p = 0.019). The compli-
lakse je prikazan u Tabeli 3. ance of clinical practice in the application of antibiotic
prophylaxis with the guidelines, by type of surgery, is
DISKUSIJA presented in Table 2. The method of administering an-
Rezultati ove studije ukazuju na veoma nisku usagla- tibiotic prophylaxis is presented in Table 3.
šenost kliničke prakse sa Nacionalnim vodičem i me-
đunarodnim smernicama, u tercijarnoj ustanovi koja se
DISCUSSION
bavi abdominalnom hirurgijom. AP je primenjena kod The results of this study indicate a very low level of com-
84,1% bolesnika u našoj studiji, što potvrđuje procene pliance of clinical practice with the National Guide and
da je profilaktička primena zastupljena sa 30 – 50%, international guidelines, in the tertiary health institution
u ukupnoj potrošnji antibiotika u bolničkim uslovima involved in abdominal surgery observed in the study.
Table 3. Characteristics of patients and surgeries and the pattern of antibiotic

Tabela 3. Karakteristike bolesnika i operacija i način primene antibiotske profilakse
prophylaxis
Varijabla / Variable
Vrsta hirurgije / Type of surgery
Hernioplastika / Hernioplasty 52 (19.3%)
Laparoskopska holecistektomija / Laparoscopic cholecystectomy 47 (17.5%)
Ezofagektomija / Esophagectomy 4 (1.5%)
Laparoskopska antirefluks operacija / Laparoscopic anti-reflux surgery 8 (3.0%)
Gastrektomija / Gastrectomy 12 (4.4%)
Hepatobilijarma hirurgija / Hepatobiliary surgery 24 (8.9%)
Pankreasna hirurgija / Pancreatic resection 7 (2.6%)
Kolorektalna hirurgija / Colorectal surgery 53 (19.6%)
Proktološka intervencija / Proctological surgery 26 (9.6%)
Operacija tankog creva / Small intestine surgery 5 (1.8%)
Multiorganska resekcija / Multiorgan resection 3 (1.1%)
Splenektomija / Splenectomy 3 (1.1%)
Ostalo / Other 26 (9.6%)
Trajanje operacije (min) / Length of surgery (min) 100 [60 – 160]
Alergije / Allergies
Beta-laktamski antibiotik / Beta-lactam antibiotic 20 (7.4%)
Ostalo / Other 16 (5.9%)
Profilaksa primenjena / Prophylaxis administered 227 (84.1%)
Vreme primene profilakse / Timing of prophylaxis
Više od 1 h pre operacije / More than 1 h before the beginning of surgery 24 (8.9%)
Unutar 1 h pre početka operacije / Within 1 h before the beginning of surgery 8 (3.0%)
Unutar 30 min od početka operacije / Within 30 min after the beginning of surgery 174 (64.4%)
Nakon 30 min od početka operacije / 30 min after the beginning of surgery 19 (7.0%)
Intravenski put primene antibiotika / Intravenous route of administration 227 (100.0%)
Potreba za redoziranjem / Redosing required 27 (10.0%)
Dužina profilakse (dani) / Duration of prophylaxis (days) 4 [2 – 6]
Podaci su prikazani kao broj (procenat) i kao medijana [interkvartilni opseg] Data are presented as number (percentage) and median [interquartile range]
[7]. Podaci iz literature ukazuju da je obuhvat hirurških AP was applied in 84.1% patients, which confirms the
bolesnika antibiotskom profilaksom u većini razvijenih estimations that prophylactic administration accounts
zemalja visok i iznosi preko 95% [8]. for 30% – 50% of the overall intrahospital antibiotic
U našoj studiji, antibiotik kao profilaksa je najma- consumption [7]. Data found in literature indicate that
nje primenjivan u grupi bolesnika podvrgnutih opera- the coverage of surgical patients with AP is very high in
ciji hernije (69,2%). Elektivna operacija preponske kile most developed countries, amounting to over 95% [8].
je tipičan predstavnik „čiste“ hirurgije za koju AP nije In our study, antibiotics, as prophylaxis, were least
potrebna. Iako rezultati randomizovanih studija ne used in the group of patients who underwent hernia
daju jasan zaključak po pitanju efikasnosti antibiotske repair surgery (69.2%). Elective inguinal hernia surgery
profilakse u smanjenju učestalosti infekcije rane, vodi- is a typical example of ‘clean’ surgery, which does not
či preporučuju da se antibiotik primeni kao profilaksa require AP. Although results of randomized studies do
kada se planira ugradnja protetskog materijala (mreži- not offer a clear conclusion regarding the efficiency of
ca) kao i za reparaciju kompleksnih hernija, posebno antibiotic prophylaxis in the decrease of wound infec-
u centrima sa manje iskustva u ovoj vrsti hirurgije [9]. tion frequency, guides recommend that the antibiotic
Laparoskopija niskog rizika ne predstavlja indikaci- should be applied as prophylaxis when prosthetic ma-
ju za profilaktičku primenu antibiotika, prema prepo- terial (mesh) implantation is planned, as well as in cases
rukama domaćeg i međunarodnog vodiča. Činjenica of complex hernia repair, especially in medical centers
da je nekada teško preoperativno definisati rizik kod where there is less experience in this type of surgery [9].
laparoskopije, verovatno je uslovila relativno veliki Low-risk laparoscopy does not indicate prophylac-
obuhvat profilaksom kod bolesnika podvrgnutih lapa- tic antibiotic use, according to the recommendations
roskopskoj holecistektomiji (87,2%). of the national and international guides. The fact that
U našoj studiji, pokazano je ogromno varira- it is sometimes difficult to preoperatively define the
nje u izboru antibiotika ili antibiotskih kombinacija risk in laparoscopy has probably resulted in a relatively
primenjenih za profilaksu. Iako preporuke sugerišu pri- wide coverage of patients undergoing laparoscopic
menu cefazolina za većinu operacija u abdominalnoj cholecystectomy with AP (87.2%).
hirurgiji, ovaj lek je bio tek na petom mestu po učesta- In our study, a huge variability in the selection of an-
losti primene, a dobilo ga je 17 (6,3%) bolesnika. Najče- tibiotics or combinations of antibiotics used as prophy-
šće primenjivani antibiotski režimi bili su: ceftriakson i laxis has been shown. Although recommendations sug-
metronidazol (24,8%), ceftriakson (21,9%), metronida- gest the application of cefazolin for most operations in
zol (13,7%) i ciprofloksacin (10,7%). Kao AP, primenjeno abdominal surgery, this drug was only the fifth most fre-
je ukupno 14 različitih antibiotskih režima. quent drug used and was administered to only 17 (6.3%)
Istraživanje sprovedeno u 14 bolnica u Nemačkoj, patients. The most frequently applied antibiotic regi-
pokazalo je da je kao AP korišćeno čak 29 antibiotskih mens were the following: ceftriaxone and metronidazole
režima, a da je variranje u praksi i odstupanje od pre- (24.8%), ceftriaxone (21.9%), metronidazole (13.7%), and
poruka bilo posebno izraženo u abdominalnoj hirurgiji ciprofloxacin (10.7%). Fourteen different antibiotic regi-
[10]. Ta studija je pokazala i značajnu zastupljenost an- mens were applied as antibiotic prophylaxis.
tibiotika širokog spektra i tzv. rezervnih antibiotika, što A study including 14 hospitals in Germany has shown
je bio slučaj i u našem istraživanju. Iznenađujuće je da that as many as 29 antibiotic regimens were used as anti-
je u našoj sredini ciprofloksacin bio veoma zastupljen biotic prophylaxis, and that variations in clinical practice
izbor, i pored preporuke da se hinoloni, zbog neželje- and deviation from recommendations was especially
nih efekata, koriste samo za lečenje životno ugrožava- prominent in abdominal surgery [10]. This study showed
jućih infekcija. significant use of broad-spectrum antibiotics and of so-
Razlozi za nisku usaglašenost izbora antibiotske called reserve antibiotics, which was also the case in our
profilakse sa preporukama iz vodiča nisu sasvim po- study. It is surprising that in our environment ciprofloxa-
znati. Moguće je da je tome doprinela i relativno veli- cin was used to a great extent, despite the recommenda-
ka učestalost samoprijavljenih alergija na antibiotike. tion that quinolones, due to adverse effects, should be
Prethodno istraživanje sprovedeno u ovom centru je used only for treating life-threatening infections.
pokazalo da gotovo 40% pacijenata pre operacije pri- The reasons for poor compliance of the choice of
javi alergiju na neki lek, pri čemu je navodna alergija na AP with recommendations offered in the guides have
penicilin najčešća [11]. Ipak, ni u jednom slučaju kao not completely been elucidated. It is possible that a
AP nije primenjen klindamicin, kao prva preporučena relatively high frequency of self-reported allergies to
alternativa cefazolinu, kod alergičnih na beta-laktam- antibiotics has contributed to this state of affairs. A pre-
ske antibiotike, pa je ukupna usaglašenost sa vodičima vious study carried out in this health center has shown
po pitanju izbora antibiotika iznosila svega 22,6% . that almost 40% of patients report a drug allergy prior
Svi bolesnici u našoj studiji dobili su antibiotik in- to surgery, wherein the alleged allergy to penicillin is
travenskim putem, što je u skladu sa smernicama. Slič- the one most commonly reported [11]. Yet, clindamy-
ne rezultate prikazuju i drugi autori, posebno kada je u cin was not used as AP in a single case, even though it
pitanju abdominalna hirurgija [12]. is the first recommended alternative for cefazoline in
Vreme davanja antibiotika za hiruršku profilaksu je patients allergic to beta-lactam antibiotics, and there-
od značaja, jer je cilj da se postigne najviša koncentra- fore, the overall compliance with the guidelines with
cija leka u plazmi u vreme najveće izloženosti potenci- respect to antibiotic choice was a only 22.6%.
jalnim uzročnicima infekcije rane. Ovaj aspekt primene All of the patients in our study received the antibi-
antibiotske profilakse imao je najnižu usaglašenost sa otic intravenously, which is in keeping with the guide-
smernicama u našem istraživanju, jer je kod samo 8 lines. Other authors have reported similar results, espe-
(3,0%) bolesnika ispoštovana satnica za davanje doze cially in the domain of abdominal surgery [12].
antibiotika. To je neuporedivo niže u odnosu na rezul- The timing of antibiotic administration for surgical
tate drugih autora, gde je 45% do 94% slučajeva anti- prophylaxis is significant, since the goal is to achieve
biotske profilakse bilo primenjeno u pravilno vreme, u the highest concentration of the drug in the blood at
skladu sa preporukama [13]. Mogući uzroci ovako niske the time of the greatest exposure to potential causative
usaglašenosti sa smernicama u našem istraživanju leže agents of wound infection. In our study, this aspect of
u organizacionim razlozima, jer operacioni blok na Kli- AP application had the lowest compliance with the
nici za digestivnu hirurgiju nema prostor u kome bi bo- guidelines, since the timeline for antibiotic application
lesnici mogli da dobiju lek venskim putem. Takođe, če- was observed in only 8 (3.0%) patients. This is far low-
ste izmene programa otežavaju da bolesnik dobije lek er than the results reported by other authors, where in
pravovremeno na odeljenju, već se sa ordiniranim an- 45% to 94% of the cases, AP was applied at the appro-
tibiotikom upućuje u operacionu salu gde procedure priate time, as recommended by the guidelines [13].
oko uvođenja u anesteziju često imaju prioritet. Zato The possible causes of such a low compliance with the
je najveći broj bolesnika (174; 64,4%) antibiotsku pro- guidelines, in our study, may be attributed to organi-
filaksu primio unutar 30 minuta od početka operacije. zational issues, since the surgical suite at the Clinic for
Produženo trajanje antibiotske profilakse je jedna Digestive Surgery does not have a space/room where
od čestih grešaka u mnogim ustanovama. Iako vodiči the patients could receive the antibiotic intravenously.
jasno ističu da je potrebno dati jednu dozu ili završiti Also, frequent changes in the operating schedule make
sa primenom antibiotika unutar 24 h, u studijama se it more difficult for the patient to receive the antibiotic
navodi da se to primenjuje u 5,8% – 91,4% slučajeva in a timely fashion while still on the ward, rather the pa-
[14]. Činjenica da je adekvatno trajanje profilakse u tients are prescribed the antibiotic and then transferred
našoj studiji bilo ostvareno u 13,1% slučajeva, može to the operating theatre, where anesthesia procedures
se objasniti strahom hirurga od razvoja infekcije rane are often given priority. This is why the greatest num-
nakon velikih, čistih-kontaminiranih operacija, u situa- ber of patients in our study (174; 64.4%) received AP
ciji u kojoj se drenovi zadržavaju više dana. Ostaje ne- within 30 minutes of the beginning of the operation.
jasno zašto je dužina profilakse ispoštovana kod samo Prolonged antibiotic prophylaxis is one of the fre-
jednog bolesnika podvrgnutog laparoskopskoj holeci- quent mistakes made in many healthcare facilities. Al-
stektomiji, za koju davanje antibiotika, u najvećem bro- though guides clearly emphasize that only one dose
ju slučajeva, nije potrebno. should be administered or that antibiotic application
Moguće je da se uslovi za dobru praksu u prime- should be finished within 24 hours, studies report that
ni antibiotske profilakse stiču usvajanjem znanja iz te this recommendation is observed in 5.8% – 91.4% cas-
oblasti, u toku studija medicine. Istraživanje sprovede- es [14]. The fact that the appropriate duration of pro-
no u bolnici u Kataru je pokazalo da je 51% specijali- phylaxis was achieved in 13.1% of the cases may be ex-
zanata hirurgije, koji su samostalno izvodili operacije, plained by the surgeons’ concern that infections may
bilo upoznato sa principima primene antibiotske pro- develop after major, clean-contaminated surgeries, in
filakse [15]. Kliničku praksu, osim poznavanja teorije, situations when drains remain in place for a number of
oblikuju i neki drugi faktori, koji nisu bili predmet ovog days. It remains unclear, why the length of prophylaxis
istraživanja. Rezultati ranijih istraživanja ukazuju na was observed only in one patient who underwent lap-
značajnu pomoć povratne informacije o primeni an- aroscopic cholecystectomy, for which, in most cases,
tibiotika putem zdravstvenog informacionog sistema, antibiotic prophylaxis is unnecessary.
kao i periodičnih unutrašnjih stručnih nadzora, u po- It is possible that the conditions for good clinical
boljšanju usaglašenosti prakse sa vodičima za primenu practice in the application of antibiotic prophylaxis are
antibiotske profilakse [16,17]. developed during medical studies, when knowledge
and understanding in this area is obtained. A study
ZAKLJUČAK carried out in a hospital in Qatar showed that 51% of
Usaglašenost prakse sa preporukama vodiča za AP surgical residents, who were performing surgery inde-
u abdominalnoj hirurgiji je bila na niskom nivou u ter- pendently, were aware of the principles of antibiotic
cijarnoj ustanovi za abdominalnu hirurgiju. Činjenica prophylaxis application [15]. Aside from theoretical
da se nalazimo u eri ekspanzivnog razvoja hirurgije, ali knowledge, clinical practice is shaped by other factors
i razvoja multirezistentnosti bakterija prouzrokovača as well, which were not the subject of this study. The
bolničkih infekcija, nameće potrebu za izvesnim mera- results from earlier studies indicate the importance of
ma i postupcima, u cilju racionalnije primene antibio- feedback related to the application of antibiotics, ob-
tika. Potrebno je preduzeti mere na institucionalnom tained through the health information system, as well
nivou, u cilju povećanja svesti kliničara o značaju ovog as the importance of periodical internal professional
problema; podržati timove za upravljanje antibiotici- supervision, for improving the compliance of clinical
ma u bolnicama; uvesti liste za proveru, kako bi se vršio practice with AP application guides [16,17].
nadzor nad različitim aspektima primene antibiotske
profilakse; te unaprediti nastavu na studijama medici-
CONCLUSION
ne, kako bi se naglasio značaj ove teme. Promovisanje The compliance of clinical practice with recommenda-
Nacionalnog vodiča i izrada lokalnih preporuka su tations from guides on AP in abdominal surgery was poor
kođe neke od mera koje bi mogle doprineti efikasnijoj at the tertiary health institution for abdominal surgery
primeni i sprovođenju antibiotske profilakse u hirurgiji. observed in our study. The fact that this is the era of
extensive surgery development, but also the develop-
Sukob interesa: Nije prijavljen. ment of multi-drug resistance in bacteria causing in-
trahospital infections, necessitates the need for certain
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ZNAČAJ MULTIDETEKTORSKE KOMPJUTERIZOVANE
TOMOGRAFIJE U OTKRIVANJU, PRAĆENJU I IZBORU
TERAPIJE KOD AKUTNOG MOŽDANOG UDARA
THE IMPORTANCE OF MULTIDETECTOR COMPUTED
TOMOGRAPHY IN ACUTE STROKE DETECTION,
MONITORING AND SELECTION OF THERAPY
Aleksandra Obreški1, Ana Papović1, Jovo Paskaš1, Ana Stanković1, Danilo Jeremić2, Kristina Davidović1,2
1
Univerzitetski klinički centar Srbije, Centar za radiologiju i 1
University Clinical Center of Serbia, Center for Radiology and
magnetnu rezonancu, Beograd, Srbija Magnetic Resonance Imaging, Belgrade, Serbia
2
Univerzitet u Beogradu, Medicinski fakultet, Srbija 2
University of Belgrade, Faculty of Medicine, Serbia
SAŽETAK ABSTRACT
Uvod: Moždani udar označava naglo nastali, fokalni nekonvulzivni neurološki Introduction: A stroke is a sudden, focal nonconvulsive neurological dysfunc-
poremećaj, do kojeg dolazi usled vaskularnog oštećenja. tion which occurs due to vascular damage.
Cilj: Cilj studije bilo je praćenje svih pacijenata koji su se u određenom vremenskom Aim: The aim of the study was monitoring all patients who reported to the Emer-
periodu javili službi Urgentnog centra, usled nastanka nekog neurološkog deficita. gency Center due to some neurological deficit, within a particular period of time.
Materijali i metode: U periodu od mesec dana, pratili smo 123 pacijenta koji su Materials and methods: For a period of one month, we monitored 123 patients
primljeni na Odeljenje urgentne dijagnostike sa nekim neurološkim deficitom, a who were admitted to the Department of Emergency Diagnostics with some
urađen im je nativni CT i/ili angiografski pregled endokranijuma. Svi pregledi su form of neurological deficit and who underwent a native computed tomography
rađeni na 16-slajsnom CT aparatu – GE BrightSpeed, USA. Nakon inicijalne nativne (CT) scan and/or angiographic examination of the endocranium. All examinations
CT dijagnostike, u zavisnosti od nalaza, pregled se ili prekidao, ili se administriralo were performed with the GE BrightSpeed 16 Slice CT scanner (USA). After initial
kontrastno sredstvo i rađen je postkontrastni pregled ili CT angiografija. native CT diagnostics, depending on the finding, the examination was either
Rezultati: Najveći broj pacijenata sa vaskularnim neurološkim deficitom je bio stopped, or the contrast dye was administered and postcontrast examination
životnog doba između 50 i 59 godina, dok je najmanji broj pacijenta registrovan was performed or CT angiography was carried out.
u grupi osoba životnog doba ispod 40 godina. Najveći broj pacijenata ženskog Results: Most of the patients with vascular neurological deficit were between 50 and
pola bio je uzrasta od 50 do 59 godina, dok je najveći broj pacijenata muškog pola 59 years old, while a smaller number of patients was registered in the age group of
bio starosti od 40 do 49 godina. Od 94 pacijenta koji su razvili moždani udar, 78 persons younger than 40 years. Most of the female patients were in the 50 – 59 age
(83%) pacijenata je imalo ishemijski moždani udar, dok je 16 (17%) pacijenata group, while most of the male patients were between 40 and 49 years old. Of the
imalo hemoragijski moždani udar. Ne postoji statistički značajna razlika u javlja- 94 patients who developed stroke, 78 (83%) patients had ischemic stroke, while 16
nju intracerebralne hemoragije i subarahnoidalne hemoragije među polovima. (17%) patients suffered hemorrhagic stroke. There is no statistically significant differ-
Lokalizacija ishemijskog infarkta mozga nalazila se u zoni vaskularizacije prednje ence in the occurrence of intracerebral hemorrhage and subarachnoid hemorrhage
moždane arterije (ACA) – u 3,2% slučajeva, srednje moždane arterije (MCA) – u between the sexes. The localization of ischemic brain infarction was in the vascular
38,9% slučajeva, unutrašnje karotidne arterije – (ICA) kod 8,4% pacijenata, bazi- territory of the anterior cerebral artery (ACA) – 3.2% of the cases, the middle cerebral
larne arterije (BA) – u 13,7% slučajeva, zadnje moždane arterije – kod 7,4% paci- artery (MCA) – in 38.9% of the cases, the internal carotid artery (ICA) – in 8.4% of the
jenata, vertebralne arterije – u 9,5% slučajeva, i u watershed supratentorijalnim patients, the basilar artery (BA) – in 13.7% of the cases, the posterior cerebral artery
zonama arterijske irigacije – kod 11,7% pacijenata. (PCA) – in 7.4% of the patients, the vertebral artery (VA) – 9.5% of the cases, and the
Zaključak: Nativni CT pregled je zlatni standard za trijažu pacijenata sa akutnim supratentorial watershed areas of arterial irrigation – in 11.7% of the patients.
moždanim udarom. Prednosti CT skeniranja u proceni pacijenata sa akutni mož- Conclusion: Native CT examination is the golden standard for the triage of pa-
danim udarom su praktičnost, preciznost, brzina i dostupnost CT uređaja. Takođe, tients with acute stroke. The advantages of using a CT scan in the assessment of
CT skeniranje ima i prognostičku vrednost jer može predvideti i odgovor na pri- patients with acute stroke are that it is practical, precise, quick and available. CT
menjenu trombolitičku terapiju. imaging has prognostic value as well, as it can predict the response to the admin-
Ključne reči: kompjuterizovana tomografija, ishemijski moždani udar, hemora- istered thrombolytic therapy.
gijski moždani udar Key words: computed tomography, ischemic stroke, hemorrhagic stroke

Kristina Davidović Kristina Davidović
Centar za radiologiju i magnetnu rezonancu, Univerzitetski Klinički centar Center for Radiology and Magnetic Resonance Imaging, University Clinical
Srbije Center of Serbia
Elektronska adresa: dr.kristina.davidovic@gmail.com E-mail: dr.kristina.davidovic@gmail.com
Primljeno • Received: February 22, 2021; Revidirano • Revised: May 04, 2022; Prihvaćeno • Accepted: May 10, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-31003
značaj multidetektorske kompjuterizovane tomografije u otkrivanju, praćenju i izboru terapije kod akutnog moždanog udara
Obreški A. i sar.
the importance of multidetector computed tomography in acute stroke detection, monitoring and selection of therapy
UVOD INTRODUCTION
Akutni moždani udar je drugi uzrok smrtnosti u svetu Acute stroke is the second most common cause of
i prvi uzrok invaliditeta u razvijenim zemljama sveta. death in the world and the first most common cause
Procenjuje se da na svakih 45 sekundi jedna osoba do- of disability in developed countries. It is estimated that
živi, a svakih tri minuta jedna osoba umire od posle- one person suffers stroke every 45 seconds, while there
dica akutnog moždanog udara. Incidencija moždanog is one death related to acute stroke every three min-
udara u razvijenim zemljama je 100 – 150 slučajeva utes, in the world. The incidence of stroke in developed
na 100.000 osoba godišnje, dok je u Srbiji ona znatno countries is 100 – 150 cases per 100,000 population,
češća i procenjuje se na 300 slučajeva na 100.000 ljudi per year. In Serbia, however, it is significantly higher
godišnje. Samo oko polovina preživelih u daljem toku and is estimated at 300 cases per 100,000 population,
života bude nezavisna, dok preko 30% nije sposobno per year. Only around a half of the surviving patients
za preživljavanje bez tuđe pomoći. Značajan broj bo- remain independent after stroke, while 30% are inca-
lesnika, oko 20%, doživljava ponovni moždani udar [1]. pable of living without assistance. A significant number
Moždani udar označava naglo nastali, fokalni ne- of patients, around 20%, suffer a repeated stroke [1].
konvulzivni neurološki poremećaj, do koga dolazi A stroke is a sudden, focal nonconvulsive neurological
usled vaskularnog oštećenja. Osnovna karakteristika dysfunction which occurs due to vascular damage. The
nastanka moždanog udara je nagli početak neurološ- basic characteristic of stroke is sudden onset of neurolog-
kih simptoma, ali se neurovizuelizacionim metodama ical symptoms. However, neuro-visualization techniques
(CT; NMR – nuklearna magnetna rezonanca) otkrivaju i (CT – computed tomography; MRI – magnetic resonance
tzv. „nemi infarkti“, koji su se razvili bez jasnih kliničkih imaging) can also reveal so called “silent brain infarcts”,
manifestacija. which develop without clear clinical manifestation.
Moždani udar se klasifikuje prema patologiji koja Stroke is classified according to the pathology which
je u osnovi fokalnog oštećenja mozga, pa razlikujemo is at the core of the focal brain damage. Therefore, we rec-
ishemijski i hemoragijski moždani udar [2]. Pojava gla- ognize two types of stroke – ischemic and hemorrhagic
vobolje, povraćanja, epileptičkih napada ili kome, sa stroke [2]. The occurrence of a headache, vomiting, epi-
većom verovatnoćom ukazuje da je razlog moždanog leptic seizures, or coma, indicate, with a higher degree of
udara krvarenje, ali jedini pouzdan način utvrđivanja certainty, that the cause of stroke is hemorrhage, howev-
vrste moždanog udara jeste snimanje glave CT apara- er, the only reliable method of definitively determining
tom (engl. computed tomography). the type of stroke is scanning the head with a CT scanner.
Savremeni koncept moždanog udara kao urgen- The contemporary concept of stroke as an emer-
tnog stanja, zahteva brzu, usmerenu i tačnu dijagno- gency, requires a fast, focused, and precise diagnosis,
zu, od koje zavisi, ne samo vrsta terapijskog pristupa, on which not only the type of therapeutic approach is
već i prognoza bolesti. Preporučena metoda i metoda dependent, but also the prognosis of the illness. The
izbora u hitnim neurološkim stanjima je nativni CT gla- recommended method and the method of choice in
ve, koji omogućava isključivanje drugih, nevaskularnih emergency neurological states is the native CT scan,
uzroka neurološkog deficita, kao i odabir bolesnika po- which enables the exclusion of other, nonvascular
godnih za različite urgentne terapijske procedure (npr. causes of neurological deficit and the selection of pa-
primena trombolitičke i drugih reperfuzionih terapija, tients eligible for different emergency therapeutic pro-
izvođenje urgentnih endovaskularnih intervencija) [3]. cedures (e.g., administering thrombolytic and other
Cilj studije bilo je praćenje svih pacijenata koji su reperfusion therapy options, performing emergency
se u određenom vremenskom periodu javili službi Ur- endovascular procedures) [3].
gentnog centra usled nastanka nekog neurološkog The aim of the study was monitoring all patients
deficita. Na osnovu dobijenih rezultata, zaključujemo who reported to the Emergency Center due to some
o prednostima i nedostacima ranih pregleda putem neurological deficit, within a particular period of time.
multidetektorske kompjuterizovane tomografije (engl. Based on the obtained results, we can draw conclu-
multidetector computed tomography – MDCT) u dija- sions on the advantages and disadvantages of early
gnostici akutnog moždanog udara. multidetector computed tomography (MDCT) exam-
ination within the diagnostics of acute stroke.
MATERIJALI I METODE
U periodu od 1. decembra 2017. godine do 1. januara
MATERIALS AND METHODS
2018. godine, pratili smo 123 pacijenta, koji su primlje- During the period between December 1, 2017 and Janu-
ni u Urgentni centar Univerzitetskog kliničkog centra ary 1, 2018, we monitored 123 patients who were admit-
Srbije sa nekim neurološkim deficitom, a urađen im je ted to the Department of Emergency Diagnostics of the
Obreški A. et al.
nativni CT i/ili angiografski pregled endokranijuma. Svi University Clinical Center of Serbia with some form of neu-
pregledi su rađeni na 16-slajsnom CT aparatu – GE, Bri- rological deficit and who underwent a native computed
ghtspeed, USA. Nakon inicijalne nativne CT dijagnosti- tomography (CT) scan and/or angiographic examination
ke, u zavisnosti od nalaza, pregled se ili prekidao, ili se of the endocranium. All examinations were performed
administriralo kontrastno sredstvo i rađen je postkon- with the GE BrightSpeed 16 Slice CT scanner (USA). After
trastni pregled, ili je rađena CT angiografija. initial native CT diagnostics, depending on the finding,
Rezultati su obrađeni metodama deskriptivne the examination was either stopped, or the contrast dye
(srednja vrednost, medijana, modus) i analitičke (X2 was administered and postcontrast examination was per-
test) statistike. formed or CT angiography was carried out.
The results were processed with methods of de-
REZULTATI scriptive (mean, median, mode) and analytical (X2 test)
U periodu od 1. 10. 2017. godine do 1. 2. 2018. godine, statistics.
u Urgentni centar Univerzitetskog kliničkog centra Sr-
bije je primljeno 123 pacijenta sa nekim neurološkim
RESULTS
deficitom. Od ukupno 123 pacijenta, 20 pacijenata je During the period between December 1, 2017 and
na nativnoj CT dijagnosti imalo nevaskularnu patologi- January 1, 2018, 123 patients were admitted to the De-
ju. Kao što se vidi na Slici 1, ženski pol je bio dominan- partment of Emergency Diagnostics of the University
tan, u odnosu 1,5:1 (Slika 1). Clinical Center of Serbia with some form of neurolog-
ical deficit. Of the 123 patients, in 20 patients nonvas-
cular pathology was discovered on the CT scan. As pre-
sented in Figure 1, the female sex was dominant, at a
ratio of 1.5:1 (Figure 1).
The youngest patient was 35 years old, while the
oldest patient was 94 years old. It has been observed
that the greatest number of patients were in the 50 –
59 age group, followed by patients in their forties, and
then those in their seventies and their sixties, with a
similar frequency amongst the said groups, while the
smallest number of patients was registered in the
group of patients younger than 40 years (Figure 2).
The greatest number of female patients was in the
age group 50 – 59 years, while the greatest number of
male patients belonged to the age group 40 – 49 years
(Figure 3).
Of the 103 patients with a neurological deficit of
Grafikon 1. Broj pacijenata sa simptomima moždanog udara, po polu vascular etiology, 94 (91%) patients developed stroke.
Figure 1. Number of patients with symptoms of stroke, by sex
Najmlađi pacijent je imao 35 godina, a najstariji 94

godine. Konstatovano je da je najveći broj pacijenata
bio životnog doba između 50 i 59 godina, zatim slede
osobe u petoj, a potom u osmoj i sedmoj deceniji živo-
ta, sa međusobno sličnom učestalošću, dok je najma-
nji broj pacijenta registrovan u grupi osoba životnog
doba ispod 40 godina (Slika 2).
Najveći broj pacijenata ženskog pola bio je uzrasta
od 50 do 59 godina, dok je najveći broj pacijenata muš-
kog pola imao između 40 i 49 godina (Slika 3).
Od 103 pacijenta sa neurološkim deficitom vasku-
larne etiologije, 94 (91%) bolesnika je razvilo moždani
udar. U preostalih 9%, u pitanju je bio tranzitorni ishe- Grafikon 2. Broj pacijenta po uzrasnim grupama
mijski atak (TIA) (Slika 4). Figure 2. Number of patients, by age groups
Obreški A. i sar.
Grafikon 3. Broj pacijenta po uzrasnim grupama u odnosu na pol

Grafikon 4. Broj pacijenata sa neurološkim simptomima vaskularne etiologije
Figure 3. Number of patients, by age groups, in relation to sex
Figure 4. Number of patients with neurological symptoms with a vascular etiology
Od 94 pacijenta, koji su razvili moždani udar, 78 In the remaining 9%, the deficit in question was tran-
(83%) bolesnika je imalo ishemijski moždani udar, dok sient ischemic attack (TIA) (Figure 4).
je 16 (17%) pacijenata imalo hemoragijski moždani Of the 94 patients who suffered stroke, 78 (83%)
udar (Slika 5). patients sustained ischemic stroke, while 16 (17%) pa-
Od 16 pacijenata sa hemoragijskim moždanim tients had hemorrhagic stroke (Figure 5).
udarom, njih 10 (62,5%) su bile žene, dok je 6 (37,5%) Of the 16 patients with hemorrhagic stroke, there
bolesnika bilo muškog pola. Intracerebralnu hemo- were 10 (62.5%) women, while 6 (37.5%) patients were
ragiju (ICH) je imalo 7 (43,75%) bolesnika, od toga 3 men. Intracerebral hemorrhage (ICH) was found in 7
žene i 4 muškarca, dok je subarahnoidalnu hemoragiju (43.75%) patients, of whom 3 were women, while 4
(SAH) imalo 9 (56,25%) pacijenta – 7 žena i 2 muškarca were men. A total of 9 (56.25%) patients suffered sub-
(Tabela 1). Nije postojala statistički značajna razlika u arachnoid hemorrhage (SAH) – 7 women and 2 men
javljanju ICH-a i SAH-a među polovima, p = 0,152. (Table 1). There was no statistically significant differ-
Od ukupnog boja primljenih pacijenata sa vasku- ence in the occurrence of ICH or SAH between the sex-
larnom etiologijom, kod 24 (23,3%) osobe je ordinirana es, p = 0.152.
trombolitička terapija, dok je 79 (76,7%) osoba imalo Of all the patients with vascular etiology, thrombo-
kontraindikacije za primenu ove terapije. Najčešće lytic therapy was administered in 24 (23.3%) persons,
kontraindikacije su bile razvijena zona ishemije na CT-u while 79 (76.7%) patients had contraindications for the
(kod 30,4% pacijenata), zatim izražena leukoarajoza na application of this therapy. The most frequent contra-
CT-u (u 25,3% slučajeva) i intracerebralna hemoragija indications were a developed ischemic zone visible
na CT-u (u 20,3% slučajeva). Nakon intravenske pri- on CT (in 25.3% of the cases) and intracerebral hem-
mene trombolitičke terapije, kod 5 (0,2%) pacijenata orrhage visible on CT (in 20.3% of the cases). After
se razvila intracerebralna hemoragija sa posledičnim intravenous administration of thrombolytic therapy,
smrtnim ishodom (Slika 6). intracerebral hemorrhage with a consequent lethal
outcome developed in 5 (0.2%) patients (Figure 6).
The localization of ischemic brain infarction was
in the vascular territory of the anterior cerebral artery
(ACA) – 3.2% of the cases, the middle cerebral artery
(MCA) – in 38.9% of the cases, the internal carotid artery
Žene / Women Muškarci / Men Ukupno / Total
ICH 3 4 7
SAH 7 2 9
Total 10 6 16
Grafikon 5. Odnos pacijenata sa ishemijskim i hemoragijskim moždanim udarom
Tabela 1. Učestalost tipova hemoragijskog moždanog udara po polu.
Figure 5. Ratio of patients with ischemic stroke vs. patients with hemorrhagic stroke Table 1. Frequency of the occurrence of the types of hemorrhagic stroke, by sex
Obreški A. et al.
Grafikon 6. Broj pacijenta u odnosu na uzroke kontraindikacija za primenu Figure 6. Number of patients in relation to the causes of contraindications for the
trombolitičke terapije application of thrombolytic therapy
Lokalizacija ishemijskog infarkta mozga nalazila se (ICA) – in 8.4% of the patients, the basilar artery (BA) – in
u zoni vaskularizacije prednje moždane arterije (engl. 13.7% of the cases, the posterior cerebral artery (PCA) –
anterior cerebral artery – ACA) – u 3,2% slučajeva, sred- in 7.4% of the patients, the vertebral artery (VA) – 9.5%
nje moždane arterije – u 38,9% slučajeva, unutrašnje of the cases, and the supratentorial watershed areas of
karotidne arterije – (engl. internal carotid artery – ICA) arterial irrigation – in 11.7% of the patients (Figure 7).
kod 8,4% pacijenata, bazilarne arterije (engl. basilar ar- DISCUSSION
tery – BA) – u 13,7% slučajeva, zadnje moždane arterije
(engl. posterior cerebral artery – PCA) – kod 7,4% pacije- Of the 123 patients with some form of neurological
nata, vertebralne arterije (engl. vertebral artery – VA) – u deficit who were included in the study, 103 patients
9,5% slučajeva, i u watershed supratentorijalnim zona- had a deficit of a vascular origin. Of those 103 patients,
ma arterijske irigacije – kod 11,7% pacijenata (Slika 7). 61% were female. Appelros et al. showed the opposite
results in their study [1,2,3]. The greatest number of fe-
Grafikon 7. Broj pacijenta u odnosu na lokalizaciju ishemijskog moždanog udara Figure 7. Number of patients in relation to the localization of ischemic stroke
Obreški A. i sar.
DISKUSIJA male patients was in the age group between 50 and 59

years, followed by patients in their sixties and those in
Od 123 pacijenta sa neurološkim deficitom koji su bili
their seventies, while the percentage of female patients
obuhvaćeni istraživanjem, njih 103 je imalo deficit va-
who were younger than 50 and suffering from some
skularne geneze. Od ta 103 pacijenta, 61% su bile osobe
form of neurological deficit was significantly lower.
ženskog pola. Apelros i saradnici su u svom istraživanju
pokazali suprotno [1,2,3]. Najveći broj pacijenata žen- This can be explained by the fact that women in meno-
skog pola bio je uzrasta od 50 do 59 godina, iza kojih pause are at a higher risk of developing cardiovascular
su bili pacijenti u sedmoj i osmoj deceniji života, dok disease [4]. Also, in women, 10 years after the onset of
su pacijentkinje mlađe od pedeset godina oboljevale menopause, the risk of stroke doubles. The decerase in
u znatno nižem procentu. Ovo se može objasniti činje- the level of endogenous estrogen by 60% leads to an
nicom da su žene u menopauzi pod većim rizikom od excess of androgens, which may lead to increased risk
dobijanja kardiovaskularnih oboljenja [4]. Pored toga, factors for the development of cardiovascular diseases.
deset godina nakon menopauze, rizik od moždanog On the other hand, the greatest number of male pa-
udara se udvostručuje kod žena. Pad nivoa endogenog tients was in the age group 40 – 49 years, which may
estrogena za oko 60% dovodi do viška androgenih indicate risk factors related to lifestyle, which include
hormona, što može da dovede do povećanih faktora smoking, excess alcohol intake, drug abuse, physical
rizika za nastanak kardiovaskularnih oboljenja. S dru- inactivity and obesity, an unhealthy diet, and stress [5].
ge strane, najveći broj pacijenata muškog pola je bio Also, hypertension, elevated cholesterol levels, diabe-
od 40 do 49 godina, što može ukazati na faktore rizika tes, and cardiac diseases, lead to stroke.
koji su povezani sa načinom života. To su pušenje, pre- Acute ischemic stroke (AIS) occurs as the result of
komerno konzumiranje alkohola, zloupotreba droga, blood vessel occlusion, either by a thrombus or em-
fizička neaktivnost i gojaznost, nezdrava ishrana i stres bolus. This type of stroke is significantly more frequent
[5]. Takođe, hipertenzija, povišeni holesterol, šećerna and is diagnosed in 83% of patients, while acute hem-
bolest i srčane bolesti dovode do moždanog udara. orrhagic stroke, which can have two types – intracere-
Akutni ishemijski moždni udar (AIMU) nastaje kao bral hemorrhage (ICH) and subarachnoid hemorrhage
posledica okluzije krvnog suda, bilo trombom ili em- (SAH), is diagnosed in the remaining 17% of patients.
bolusom. Ovaj udar je značajno češći i dijagnostikuje se According to the latest studies, ischemic stroke in-
u 83% bolesnika, dok se akutni hemoragijski moždani cludes thrombosis, emboli, venous thrombosis, and
udar, koji po tipu može biti intracerebralna hemoragija systemic hypoperfusion. The most frequent shared risk
(ICH) ili subarahnoidalna hemoragija (SAH), dijagnosti- factor for ICH and SAH are hypertension, smoking and
kuje u preostalih 17% bolesnika. Prema novijim istraži- alcohol abuse [6].
vanjima, ishemijski moždani udar obuhvata trombozu, The present study included 37.5% of men and
emboluse, vensku trombozu i sistemsku hipoperfuziju. 62.5% of women with hemorrhagic stroke, but we
Najčešći zajednički faktori rizika za ICH i SAH su: hiper- did not find a highly statistically significant difference
tenzija, pušenje i zloupotreba alkohola [6]. in the occurrence of ICH and SAH between the sexes.
U ovom istraživanju je bilo 37,5% muškaraca i 62,5% Other studies state that the distribution by gender in
žena sa hemoragijskim udarom, ali nismo pronašli viso- hemorrhagic stroke is similar, however, probably due
kostatistički značajnu razliku u javljanju ICH-a i SAH-a to the link between the occurrence of SAH and ICH and
među polovima. U drugim istraživanjima se navodi da pregnancy and puerperium, but also with the use of
je polna zastupljenost kod hemoragijskog moždanog oral contraceptives, most studies report a higher fre-
udara približna, ali da se verovatno zbog povezanosti quency of these entities in female patients [7]. Some
javljanja SAH-a i ICH-a sa trudnoćom i puerperijumom, authors, however, report between 1.4 and 2.0 times
ali sa uzimanjem kontraceptiva, u većini izveštaja po- more frequent cerebral hemorrhage in men [6].
tvrđuje veća učestalost ovih entiteta kod osoba žen- The obtained results indicate a higher frequency
skog pola [7]. Neki autori opet navode 1,4 – 2,0 puta of ischemic infarction in the watershed area of the ca-
češće moždano krvarenje kod muškaraca [6]. rotid artery vascular territory (54.7%), as compared to
Dobijeni rezultati ukazuju na to da postoji veća the arteries in the watershed area of the vertebrobas-
učestalosti ishemijskih infarkta u zoni vaskularizacije ilar territory (45,3%). Infarctions in the vascular terri-
karotidnog sliva (54,7%) u odnosu na arterije verte- tory of the middle cerebral artery (MCA) are the most
bro-bazilarnog sliva (45,3%). Infarkti u regiji vaskulari- common type of stroke, which has been demonstrat-
zacije srednje moždane arterije (engl. middle cerebral ed in this study. They may be superficial (involving the
artery – MCA) su najčešći tip moždanog udara, što je cortex and white matter), deep (involving the basal
pokazano i u ovom istraživanju. Oni mogu biti površni ganglia, internal capsule, and deep white matter), and
Obreški A. et al.
(uključuju korteks i belu masu), duboki (uključuju ba- combined [8]. These infarctions are most commonly
zalne ganglije, kapsulu internu i duboku belu masu) i caused by cardioembolism, thrombosis of the internal
kombinovani [8]. Ovi infarkti su najčešće uzrokovani carotid artery (ICA), dissection, or embolism.
kardioembolizmom, trombozom unutrašnje karotidne All 24 candidates for thrombolytic therapy had
arterije (ICA), disekcijom ili embolijom. thrombotic masses present in the large arteries of the
Svih 24 kandidata za trombolitičku terapiju su brain, while in 11 candidates for thrombolytic therapy,
imala prisustvo trombotične mase u velikim arterija- who had a positive sign of hyperdense artery on the
ma mozga, dok je kod 11 kandidata za trombolitičku native CT scan, angiographic examination revealed
terapiju, koji su imali pozitivan znak hiperdenzne arte- the presence of a thrombus, i.e., a filling defect. The
rije na nativnom CT pregledu, na angiografskom pre- main clinical role of CT angiography in acute stroke is
gledu potvrđeno prisustvo tromba, odnosno uočen excluding thrombolytic therapy in patients with em-
je defekt u punjenju kontrastnim sredstvom. Glavna bolic stroke who do not have large occlusions of the
klinička uloga CT angiografije u akutnom moždanom blood vessels, as is the case in lacunar infarct, transient
udaru je isključivanje trombolitičke terapije kod paci- ischemic attack (TIA), migraines, hypoglycemia. Com-
jenata sa embolijskim moždanim udarom, koji nema- puted tomography angiography (CTA) is very precise
ju velike okluzije krvnog suda, kao što je to slučaj kod in diagnosing intracranial thrombi. In a study including
lakunarnog infarkta, tranzitornog ishemijskog ataka 44 candidates for thrombolysis, who had undergone
(TIA), migrenske glavobolje, hipoglikemije. CT angio- both CTA and digital subtraction angiography (DSA)
grafija (engl. computed tomography angiography – CTA) within the diagnostic algorithm, CTA showed high
je veoma precizna u dijagnostikovanju intrakranijalnih sensitivity (98.4%) and specificity (98.4%) in detecting
trombova. U studiji, koja je obuhvatila 44 kandidata za large thrombi in large blood vessels [9]. Additionally,
trombolizu, koji su u dijagnostičkom algoritmu prošli the degree and level of occlusion are important factors
i CTA i DSA (engl. digital subtraction angiography), CTA in planning the treatment in acute stroke. CTA is also
je pokazala visoku senzitivnost (98,4%) i specifičnost used for serial follow-up of patients with proven occlu-
(98,4%) za detekciju velikih trombova u velikim krvnim sions of the internal carotid artery (ICA).
sudovima [9]. Takođe, stepen i nivo okluzije su važan
faktor u planiranju terapije akutnog moždanog udara. CONCLUSION
CTA se koristi i za serijsko praćenje pacijenata sa doka-
zanim okluzijama unutrašnje karotidne arterije (ICA). Stroke occurs as the result of changes developing in
the blood vessels of the brain. Around 80% of strokes
ZAKLJUČAK are the result of the interruption of blood supply to the
Moždani udar je posledica promena na krvnim sudo- brain (ischemic stroke), while around 20% of strokes
vima mozga. Oko 80% moždanih udara je posledica occur due to hemorrhage in the brain (hemorrhagic
onemogućenog snabdevanja mozga krvlju (ishemijski stroke).
udar), a oko 20% njih je posledica krvarenja u mozgu Despite new technological advances in neuroimag-
(hemoragijski moždani udar). ing techniques and protocols for the assessment and
Uprkos novim tehnološkim dostignućima u neuroi- treatment of patients with cerebrovascular diseases,
maging tehnikama i protokolima za procenu i tretman native CT remains the golden standard for the tirage of
bolesnika sa cerebrovaskularnim bolestima, nativni CT patients with acute stroke. The advantages of using a
ostaje zlatni standard za trijažu pacijenata sa akutnim CT scan in the assessment of patients with acute stroke
moždanim udarom. Prednosti CT skeniranja u proceni are that it is practical, precise, quick and available. CT
pacijenata sa akutni moždanim udarom jesu praktičnost, imaging has prognostic value as well, as it can predict
preciznost, brzina i dostupnost CT uređaja. Takođe, CT the response to the administered thrombolytic thera-
skeniranje ima i prognostičku vrednost, jer može pred- py. CT angiography is precise in diagnosing intracra-
videti i odgovor na primenjenu trombolitičku terapiju. nial vascular occlusion in patients with symptoms of
CT angiografija je precizna za dijagnozu intrakranijalne stroke, within the first 6 hours. Data obtained with CT
vaskularne okluzije kod pacijenata sa simptomima mož- angiographic examination are valuable, as they enable
danog udara u prvih 6 sati. Podaci dobijeni CT angiograf- quick diagnostics and appropriate treatment within a
skim pregledom su dragoceni, jer omogućavaju brzu di- short period of time. CTA is a quick, simple, and pre-
jagnostiku i adekvatnu terapiju u kratkom vremenskom cise diagnostic method, which provides enough infor-
periodu. CTA je brza, jednostavna i tačna dijagnostička mation to the neurologist with regards to the vascular
metoda, koja daje dovoljno informacija neurologu u vezi passability of the affected artery.
sa vaskularnom prohodnošću zahvaćene arterije.
Obreški A. i sar.
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FUNKCIONISANJE, ONESPOSOBLJENOST I VEŽBE KOD STARIH
PREGLEDNI RAD REVIEW ARTICLE
FUNCTIONING, DISABILITY AND EXERCISE IN THE ELDERLY
Milena Kostadinović1, Sunčica Dedović2, Filip Milanović3, Nikola Aksović4, Dejan Nikolić5,6
1
Univerzitetski klinički centar Srbije, Beograd, Srbija 1
University Clinical Center of Serbia, Belgrade, Serbia
2
IQVIA, Beograd, Srbija 2
IQVIA, Belgrade, Serbia
3
Univerzitetska dečija klinika, Služba dečije hirurgije, Beograd, 3
University Children’s Hospital, Department of Pediatric Surgery,
Srbija Belgrade, Serbia
4
Univerzitet u Nišu, Fakultet sporta i fizičkog vaspitanja, Niš, Srbija 4
University of Niš, Faculty of Sport and Physical Education, Niš,
Serbia
5
Univerzitet u Beogradu, Medicinski fakultet, Beograd, Srbija
5
6
Univerzitetska dečija klinika, Beograd, Služba fizikalne medicine i
rehabilitacije, Srbija 6
University Children’s Hospital, Department of Physical Medicine
and Rehabilitation, Belgrade, Serbia
SAŽETAK ABSTRACT
Starost stanovništva širom sveta je u porastu, tako da postaje sve veći problem The age of the population is increasing worldwide and is becoming an emerging
u društvu. Održavanje fizičkog i mentalnog zdravlja zajedno sa prevencijom i problem in society. Maintaining physical as well as mental health, together with
smanjenjem invaliditeta, posebno kod starije populacije, treba da bude jedan od preventing and reducing disability, particularly in the older population, should be
važnih aspekata kvalitetnog starenja. Stoga, ciljevi zdravstvenih programa treba one of the most important aspects of successful aging. Thus, the goals of health
da budu usmereni na promociju kvalitetnog, aktivnog i zdravog starenja. Stariji programs should be the promotion of successful, active, and healthy aging. El-
pacijenti su obično povezani sa višestrukim komorbiditetima, koje treba multi- derly patients are usually associated with multiple medical conditions, which
disciplinarno procenjivati, imajući u vidu potrebe ove grupe pojedinaca. Iako se should be evaluated in a multidisciplinary fashion, bearing in mind the needs of
pretpostavlja da je starenje povezano sa opadanjem funkcionisanja i samim tim this group of individuals. Even though it is assumed that aging is associated with
smanjenjem funkcionalnog kapaciteta kod starijih osoba, važno je identifikova- a decline in functioning and, therefore, with reduced functional capacity in the
ti faktore koji igraju specifične uloge u zdravom i aktivnom starenju. Posebnu elderly, it is important to identify the factors which play specific roles in healthy
pažnju treba posvetiti i kognitivnom funkcionisanju. Štaviše, starije osobe su u and active aging. Special consideration should be given to cognitive functioning.
opasnosti, usled životnih navika karakterističnih za neaktivni način života. Upr- Furthermore, the elderly are at risk, due to habits characteristic of a sedentary
kos pozitivnim efektima fizičke aktivnosti, posebno u domenu prevencije i odla- lifestyle. Despite the positive effects of physical activity, particularly in the pre-
ganja hroničnih bolesti i stanja, ali i u domenu smanjenja rizika od prerane smrti vention and delay of chronic diseases and conditions, as well as in reducing the
i u domenu podrške pozitivnom mentalnom zdravlju i zdravom starenju, starija risk of premature death and in supporting positive mental health and healthy
populacija se može suočiti sa preprekama, u smislu ograničenog prostora za bez- aging, the elderly population may face obstacles in terms of limited space for
bedno obavljanje aktivnosti i nedostatka odgovarajućeg znanja o tome kako da the safe execution of activities and the lack of proper knowledge on how to be
se bude aktivan a da se pri tom uzmu u obzir sopstvena fizička ograničenja. Pri- active while taking into account one’s physical limitations. When planning and
likom planiranja i sprovođenja fizičke aktivnosti, posebno kod starije populacije, implementing a physical activity, especially in the older population, the import-
faktori koje je važno uzeti u obzir uključuju: trajanje, učestalost, intenzitet i režim. ant factors that need to be considered include duration, frequency, intensity and
Treba naglasiti da programi vežbanja kod starijih osoba treba da uključuju aerob- mode. It should be stressed that exercise programs for the elderly should include
ni trening, trening otpora, trening fleksibilnosti i trening ravnoteže. aerobic, resistance, flexibility, and balance training.
Ključne reči: stare osobe, funkcionisanje, onesposobljenost, vežbe Keywords: the elderly, functioning, disability, exercise

Milena Kostadinović Milena Kostadinović
Univerzitetski klinički centar Srbije, Beograd, Srbija University Clinical Center of Serbia, Belgrade, Serbia
Elektronska adresa: milena8250@gmail.com E-mail: milena8250@gmail.com
Primljeno • Received: April 20, 2022; Revidirano • Revised: April 22, 2022; Prihvaćeno • Accepted: May 17, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-37528
funkcionisanje, onesposobljenost i vežbe kod starih
Kostadinović M. i sar.
functioning, disability and exercise in the elderly
UVOD INTRODUCTION
Starost stanovništva širom sveta je u porastu, tako da The age of the population is increasing worldwide and
postaje sve veći problem u društvu. Tokom pedeseto- is becoming an emerging problem in society. During
godišnjeg perioda, između 1900. i 1950. godine, popu- the 50-year period between 1900 and 1950, the elderly
lacija starih ljudi se udvostručila u Sjedinjenim Američ- population doubled in number in the United States of
kim Državama (SAD), gde su, 1900. godine, ljudi stariji America (USA) – people over the age of 65 years com-
od 65 godina činili 4,1% stanovništva, dok su 1950. go- prised 4.1% of the US population in 1900 and more
dine činili više od 8% stanovništva [1]. Ovaj trend je na- than 8% of the US population in 1950 [1]. This trend
stavljen, pa je 2000. godine ovaj procenat bio 12, 6%. continued, and in 2000 the percentage was 12.6%. It
Procenjuje se da će 2050. godine, u zemljama sa niskim is estimated that in 2050, around 80% of the popula-
i srednjim primanjima, oko 80% populacije biti starija tion of low and middle-income countries will be older
lica [2]. Pregledni rad koji su objavili Arai i saradnici people [2]. The review by Arai et al. states that develop-
navodi da su dostignuća u medicini zajedno sa unap- ments in medicine together with improvement in hy-
ređenjima u higijeni i snabdevanju hranom uticali na giene and food supply have influenced life expectancy
očekivano trajanje života u Japanu, zemlji sa najdužim in Japan, which is the country with the longest life ex-
očekivanim trajanjem života u svetu [3]. pectancy in the world [3].
Starenju i starosti se može pristupiti sa tačke gledi- Aging and old age can be approached from the mi-
šta mikro nivoa (iskustvo pojedinca) ili tačke gledišta cro-level perspective (individual experience) and the
makro nivoa (iskustva starijih pojedinaca unutar druš- macro-level perspective (experience of older individ-
tva kao i društvene implikacije starenja populacije) [4]. uals within the society as well as societal implications
Održavanje fizičkog ali i mentalnog zdravlja, zajedno sa of population aging) [4]. Maintaining physical as well as
prevencijom i smanjenjem onesposobljenosti, naročito mental health, together with preventing and reducing
u starijoj populaciji, trebalo bi da bude jedan od naj- disability, particularly in the older population, should be
važnijih aspekata kvalitetnog starenja [4]. Stoga, ciljevi one of the most important aspects of successful aging
zdravstvenih programa treba da budu usmereni na pro- [4]. Thus, the goals of health programs should be the
movisanje kvalitetnog, aktivnog i zdravog starenja [5]. promotion of successful, active, and healthy aging [5].
FAKTORI POVEZANI SA STARENJEM I ZDRAVIM FACTORS ASSOCIATED WITH AGING AND

STARENJEM HEALTHY AGING
Postoje brojni faktori koji su povezani sa povećanim sta- There are numerous factors associated with the in-
renjem populacije: Među njima su i produženo očekiva- creased age of the population. Among them are in-
no trajanje života i smanjenje stope plodnosti u popula- creased life expectancy and the decreasing fertility
ciji [6]. Takođe, postoje faktori koji utiču na zdravo stare- rate in the population [6]. Additionally, there are fac-
nje. Na takve faktore je potrebno usredsrediti posebnu tors that influence healthy aging. Such factors should
pažnju i promovisati ih na takav način da se dopre do be given special attention and they need to be pro-
svih nivoa društva. Ovo treba učiniti putem odgovaraju- moted in such a way as to reach every level of society.
ćih obrazovnih programa. Rasna pripadnost, materijalni This should be done through appropriate educational
status, i obrazovanje se smatraju društvenim faktorima programs. Race, income, and education are consid-
koji potencijalno mogu uticati na zdravo starenje. U po- ered to be social factors that may potentially influence
slednje vreme, proučavaju se i drugi faktori, uključujući healthy aging. Recently, other social factors have also
tu i naselja u kojima ljudi žive kao i različite vrste siste- been studied, including neighborhoods and different
ma, npr. zdravstveni sistem [7]. U studiji koju su obja- systems, such as the healthcare system [7]. In the study
vili Liu i Su, navodi se da obrazovni i materijalni status, by Liu and Su, the authors state that educational and
zdravstveno ponašanje i učešće u društvenom životu economic status, health behavior, and social partici-
takođe mogu biti faktori koji predviđaju zdravo starenje pation may also be factors predicting healthy aging
[8]. Među zdravstvenim ponašanjima, fizička aktivnost [8]. Among health behaviors, physical activity and
i način ishrane su veoma značajni [9,10]. Ustanovljeno diet are very important [9,10]. It has been established
je da fizička aktivnost ima brojne povoljne efekte, uk- that physical activity has numerous favorable effects,
ljučujući i prevenciju padova, sarkopenije, osteoporoze, including the prevention of falls, sarcopenia, osteopo-
i kognitivnog oštećenja [9]. Ishrana se može smatrati rosis, and cognitive impairment [9]. Diet might be con-
potencijalno promenljivim faktorom u prevenciji bo- sidered as a potential modifiable factor in preventing
lesti vezanih za starost [10]. Ovo jasno ukazuje na to age-related diseases [10]. This clearly demonstrates
da je kvalitetno starenje multidimenzionlno, te da je
Kostadinović M. et al.
povezano sa fizičkim, društvenim, psihološkim i duhov- that successful aging is multidimensional and is linked
nim aspektima pojedinca, ali i sa socijalnim aspektima, to physical, social, psychological and spiritual aspects
kao što su kultura i sredina u kojoj pojedinac živi [11]. of the individual, as well as to the cultural and environ-
mental aspects of the society [11].
STARENJE I KOMORBIDITETI
Kod starijih pacijenata je obično prisutno više AGING AND COMORBIDITIES
zdravstvenih problema, koje treba proceniti multidis- Elderly patients are usually associated with multiple
ciplinarnim pristupom, imajući u vidu potrebe ove gru- medical conditions, which should be evaluated in a
pacije pacijenata. Značaj ranog otkrivanja i blagovre- multidisciplinary fashion, bearing in mind the needs
menog lečenja istovremeno prisutnih oboljenja i sta- of this group of individuals. The importance of early
nja, naročito kod starijih osoba, odnosi se na činjenicu detection and timely treatment of comorbid condi-
da su komorbiditeti, sami po sebi, povezani sa složenim tions, particularly in the elderly, relates to the fact that
medicinskim tretmanom, nepovoljnijim zdravstvenim comorbidity itself is associated with complex medical
ishodima i uvećanim troškovima po zdravstveni sistem, management, less favorable health outcomes, and in-
što može predstavljati značajno opterećenje [12]. creased healthcare costs that could represent a signifi-
Komorbiditeti mogu biti povezani sa samim proce- cant burden [12].
som starenja, usled produženog očekivanog trajanja ži- Comorbidities can be associated with the aging
vota i, usled toga, produženog izlaganja brojnim fakto- process itself, due to increased life expectancy and,
rima rizika [13]. Do sada su opisani brojni komorbiditeti, therefore, prolonged exposure to numerous risk fac-
u koje spadaju kardio-vaskularna oboljenja (uključujući tors [13]. So far, numerous comorbidities have been
hipertenziju, srčanu insuficijenciju, stabilnu anginu described, some of them being cardiovascular diseas-
pektoris, i druga kardio-vaskularna oboljenja), dijabe- es (including hypertension, heart failure, stable angina,
tes, hronična opstruktivna bolest pluća (HOBP), osteo- and other cardiovascular conditions), diabetes, chronic
artritis, delirijum, slabljenje čula, te druga oboljenja i obstructive pulmonary disease (COPD), osteoarthritis,
stanja [13,14]. U svojoj studiji, Fan i saradnici navode da delirium, sensory impairment, and other diseases and
su dva najčešće istovremeno prisutna stanja hiperten- conditions [13,14]. In their study, Fan et al. state that
zija i dislipidemija, dok su tri stanja najčešće prisutna u the two most frequent conditions present at the same
isto vreme hipertenzija, dislipidemija i dijabetes [14]. time are hypertension and dyslipidemia, while the
three most frequent conditions present simultaneous-
FUNKCIONISANJE KOD STARIH OSOBA ly are hypertension, dyslipidemia, and diabetes [14].
Iako je pretpostavka da je starenje povezano sa funk-
cionalnim propadanjem, a samim tim i sa smanjenjem FUNCTIONING IN THE ELDERLY
funkcionalnih kapaciteta starih lica, važno je identifiko- Even though it is assumed that aging is associated with
vati faktore koji igraju određene uloge u zdravom i ak- a decline in functioning and, therefore, with reduced
tivnom starenju. Utvrđeno je da funkcionalni kapacitet functional capacity in the elderly, it is important to
predstavlja jedan od vitalnih pokazatelja zdravstvenog identify the factors which play specific roles in healthy
stanja u populaciji starih lica, te da je tesno povezan and active aging. It has been noted that functional
sa kvalitetom života u ovoj grupaciji [15]. Funkcionalno capacity presents one of the vital indicators of health
oštećenje može biti na pojedinačnom nivou (nemo- status in the elderly population and relates closely
gućnost nezavisnog obavljanja svakodnevnih aktivno- to the quality of life in this group of individuals [15].
sti i gubitak samostalnosti) i na nivou populacije [15]. Functional impairment can be on the individual level
Potrebno je obratiti posebnu pažnju na funkcioni- (inability to perform everyday activities independently
sanje na kognitivnom nivou. Prethodno je uočeno da se and personal autonomy loss) and on the populational
opadanje kognitivne funkcije može uočiti kod starijih level [15].
lica, te da je kognitivna sposobnost povezana sa broj- Special consideration should be given to cogni-
nim varijablama, među kojima su socioekonomski fak- tive functioning. It has been previously noted that
tori, zdravstveno stanje, društveni kapital i zdravstveno cognitive decline can be detected in older individuals
ponašanje [16]. Takođe, opadanje kognitivne funkcije and that cognitive performance is associated with nu-
može se povezati sa demencijom, upotrebom lekova, merous variables, which include socioeconomic fac-
promenama raspoloženja i drugim činiocima [17]. tors, health status, social capital, and health behavior
Među najproučavanijim aspektima fizičke kondicije i [16]. Additionally, cognitive decline might be associ-
funkcije jesu telesna konstitucija i kardio-vaskularna utre- ated with dementia, medication use, mood shifts, and
niranost [18]. Stoga, promene u mišićnoj i koštanoj masi other [17].
kao i u mišićno-skeletnoj i neuromotornoj funkciji mogu Among the most studied health related aspects
biti povezane sa funkcionalnim propadanjem [18] kod sta- of physical fitness and function are body composition
rih lica, što vodi do različitih stepena onesposobljenosti. and cardiovascular fitness [18]. Muscle and bone mass
as well as musculoskeletal and neuromotor function
ONESPOSOBLJENOST I STARA LICA changes might be associated with functional decline
Povećanje udela starih lica u sveukupnoj populaciji, na [18] in the elderly, leading to various degrees of dis-
svetskom nivou, povećanje funkcionalne onesposoblje- ability.
nosti, kao i povećanje socijalnih, medicinskih i ekonom-
skih opterećenja, postaje sve relevantnije i relevantnije.
DISABILITY AND THE ELDERLY
Važan aspekt onesposobljenosti jeste da ona može biti The increase in the proportion of the elderly in the
dinamična tokom vremena, napredujući do težeg oblika. overall population worldwide, the increase in func-
Prema definiciji Svetske zdravstvene organizaci- tional disability, as well as in the social, medical, and
je (SZO), staračka onesposobljenost jeste poteškoća u economic burden, are becoming more and more rele-
obavljanju jedne ili više aktivnosti osnovne brige o sebi vant. An important aspect of disability is that it can be
ili svakodnevnih fizičkih aktivnosti (SFA) ili poteškoća u dynamic over time, progressing to a more severe state.
obavljanju jedne ili više svakodnevnih instrumentalnih According to the World Health Organization
aktivnosti (SIA) [19]. Finski centar za interdisciplinarnu (WHO), old age disability can be defined as difficul-
gerontologiju Univerziteta Jiveskile (engl. Finnish Cen- ty in performing one or more basic self-care tasks or
tre for Interdisciplinary Gerontology of the University of physical activities of daily living (PADL) or difficulty in
Jyväskylä) definiše onesposobljenost kao jaz između performing one or more instrumental activities of daily
sposobnosti neke osobe i zahteva koje pred tu osobu living (IADL) [19]. The Finnish Centre for Interdisciplin-
postavlja okruženje [20]. Štaviše, procenjuje se da otpri- ary Gerontology of the University of Jyväskylä defines
like svaka peta osoba stara 70 godina i više, te svaka dru- disability as a mismatch between a person’s abilities
ga osoba starosti 85 godina i više prijavljuje poteškoće u and environmental requirements [20]. Furthermore, it
obavljanju svakodnevnih fizičkih aktivnosti, uključujući is estimated that approximately every fifth individual
tu i kupanje, oblačenje, odlazak u toalet, održavanje lič- aged 70 years and above and every second individu-
ne higijene, kontinenciju, obedovanje, i prebacivanje iz al aged 85 years and above reports a difficulty in per-
stolice u krevet [19,20]. Treba napomenuti da su poteš- forming PADLs, including bathing, dressing, going to
koće pri obavljanju svakodnevnih instrumentalnih ak- the toilet, maintaining personal hygiene, maintaining
tivnosti takođe uobičajene, uključujući tu i upotrebu te- bowel and bladder control, feeding, and transferring
lefona, aktivnosti u domaćinstvu, pranje i sušenje veša, from chair to bed [19,20]. It should also be mentioned
korišćenje javnog prevoza, uzimanje lekova, i vođenje fi- that IADL difficulties are common, including the use
nansija [20]. Značaj ranog otkrivanja postojeće onespo- of the phone, housekeeping, doing the laundry, using
sobljenosti u populaciji starih, kao i uvođenja programa public transportation, taking medication, and finance
prevencije, u vezi je sa činjenicom da onesposobljenost, handling [20]. The importance of the early detection
sama po sebi, povećava zavisnost onesposobljenog lica of existing disability in the elderly population, as well
od drugih kao i rizik od prevremene smrti, istovremeno as the introduction of preventive programs, has to do
umanjujući kvalitet života onesposobljenog lica. with the fact that disability itself increases dependency
Onesposobljenost može biti povezana sa smanje- on others, as well as the risk of premature death, at the
nom mobilnošću, što uključuje poteškoće u hodanju, same time reducing a person’s quality of life.
penjanju uz stepenice, i premeštanju iz stolice u krevet, Disability can be related to reduced mobility, which
iz kreveta u stolicu i sl.; može se odnositi na sopstvenu includes difficulty walking, climbing stairs, and per-
negu, što uključuje poteškoće u obavljanju aktivnosti forming transfers; it can be related to self-care, which
koje se odnose na uzimanje obroka, oblačenje, odla- includes difficulty in performing activities related to
zak u toalet, održavanje lične higijene, i kupanje; može eating, getting dressed, going to the toilet, maintain-
se odnositi i na aktivnosti u domaćinstvu, što uključu- ing personal hygiene, and bathing; it can also be re-
je poteškoće u pripremi obroka, nabavci namirnica, lated to household activities, which includes difficulty
obavljanju kućnih poslova, vožnji, uzimanju lekova, in preparing meals, shopping for groceries, performing
upotrebi telefona, i raspolaganju novcem [21]. housework, driving, taking medication, using the tele-
U populaciji starih, postoje određeni faktori rizika phone, and managing money [21].
u vezi sa onesposobljenošću, koje je potrebno identifi- There are certain risk factors of disability in the el-
kovati. Mogu se grupisati kao nepromenljivi faktori ri- derly population that should be identified. They can be
zika (starost, pol i genetski faktori) i promenljivi faktori categorized as non-modifiable risk factors (age, gender,
rizika, koji se mogu dalje podeliti na faktore koji se od- and genetic factors) and modifiable risk factors, which
nose na pojedinca (bolesti povezane sa starosnim do- can be subdivided into factors related to the individu-
bom, nepovoljna zdravstvena ponašanja, funkcionalna al (age-related diseases, unfavorable health behaviors,
ograničenja, i sl.) i karakteristike okruženja [20]. functional limitations, etc.) and characteristics of the
Pokazano je da demencija kod stanovništva Japana, environment [20].
posebno kod ljudi starijih od 75 godina, predstavlja naj- It has been shown that dementia in the Japanese
češći uzrok funkcionalne onesposobljenosti, nevezano population, particularly in those above 75 years of life,
od pola [22]. Slični rezultati su dobijeni u studiji ura- is the most frequent cause of functional disability, irre-
đenoj na švedskom stanovništvu [23]. Oštećenje vida spective of gender [22]. Similar findings were obtained
i/ili sluha takođe doprinose pojavi onesposobljenosti in a study on the Swedish population [23]. Vision and/or
kod starije populacije. Kod onih sa oslabljenim vidom, hearing impairment also contribute to the presence of
uz potencijalne poteškoće u obavljanju svakodnevnih disability in the older population. Those with impaired
aktivnosti, povećana je i incidencija padova, društve- vision, aside from potential difficulties in performing ev-
ne izolacije i zavisnosti od drugih [24]. Oštećenje sluha eryday tasks, have a higher incidence of falls, social isola-
može uticati na govor i čujenje, što samim tim ima uti- tion, and dependency on others [24]. Talking and hear-
caja na socijalizaciju osoba sa oslabljenim sluhom [24]. ing may be affected in those with hearing impairment,
which, therefore, has an impact on socialization [24].
FIZIČKA AKTIVNOST I REKREACIJA
Smatra se da je fizička neaktivnost četvrti po redu vode-
PHYSICAL ACTIVITY AND EXERCISE
ći faktor globalnog mortaliteta i značajan faktor rizika Physical inactivity is considered to be the fourth lead-
za razvoj nezaraznih bolesti i hroničnih stanja, kao i za ing risk factor for global mortality and an important
uvećanje telesne mase [25]. Stara lica su pod rizikom da risk factor for the development of non-communicable
steknu navike karakteristične za neaktivni način života, diseases and chronic conditions, as well as for increase
pri čemu se raspon fizičke neaktivnosti kod osoba sta- in body weight [25]. The elderly are at risk of develop-
rijih od 55 godina u Evropi kreće od 5% u Švedskoj do ing habits characteristic of a sedentary lifestyle, with
29% u Portugalu [26]. Uprkos pozitivnim efektima fizič- a range of physical inactivity in individuals above the
ke aktivnosti, posebno u prevenciji i odlaganju hronič- age of 55 years in Europe spanning from 5% in Sweden
nih bolesti i stanja, kao i u smanjenju rizika od prevre- to 29% in Portugal [26]. Despite the positive effects
mene smrti i u podršci pozitivnom mentalnom zdravlju of physical activity, particularly in the prevention and
i zdravom starenju, populacija starih može biti suočena delay of chronic diseases and conditions, as well as in
sa preprekama, u smislu ograničenog prostora za bez- reducing the risk of premature death and in support-
bedno izvođenje aktivnosti, kao i nedostatka odgova- ing positive mental health and healthy aging, the el-
rajućeg znanja o tome kako biti aktivan, istovremeno derly population may face obstacles in terms of limited
uzimajući u obzir sopstvena fizička ograničenja [27,28]. space for the safe execution of activities and the lack
Prilikom planiranja i sprovođenja fizičke aktivnosti, of proper knowledge on how to be active while taking
posebno kod starije populacije, faktori koje je važno into account one’s physical limitations [27,28].
uzeti u obzir uključuju: trajanje, učestalost, intenzitet When planning and implementing a physical ac-
i režim [29]. Prema smernicama koje se tiču fizičke ak- tivity, especially in the older population, the import-
tivnosti i neaktivnog ponašanja, koje je objavila SZO ant factors that need to be considered include dura-
2020. godine, preporučuje se da osobe od 65 godina tion, frequency, intensity and mode [29]. According to
i starije treba da sprovode fizičke aktivnosti odnosno the WHO 2020 guidelines regarding physical activity
vežbe umerenog intenziteta u trajanju od 150 – 300 and sedentary behavior, it is recommended that indi-
minuta, ili fizičke aktivnosti jačeg intenziteta u traja- viduals 65 years of age and above should be involved
nju od 75 – 150 minuta, ili da sprovode ekvivalentnu in 150 – 300 minutes of moderate-intensity exercise
kombinaciju ove dve vrste aktivnosti, svake sedmice, or 75 – 150 minutes of vigorous-intensity physical ac-
te da da treba da rade vežbe za jačanje mišića dva ili tivity or an equivalent combination of these two, each
više puta nedeljno [30]. Kopenhaško saopštenje o kon- week, and should perform muscle strengthening ex-
senzusu na temu fizičke aktivnosti i starenja iz 2019. ercises twice or more times a week [30]. The Copen-
godine (engl. Copenhagen Consensus statement 2019: hagen Consensus statement 2019: physical activity and
physical activity and ageing) navodi da sve više nauč- ageing states that emerging evidence suggests that
nih dokaza ide u prilog tome da se pozitivni efekti kod beneficial effects can be achieved for older adults at a
starijih ljudi mogu postići pri manjem volumenu i ni- lower volume and lower intensity of physical activity
žem intenzitetu fizičke aktivnosti nego što se postiže than the recommended 150 minutes of moderate to
preporučenim umerenim do jakim intenzitetom fizičke vigorous intensity physical activity [31]. It should be
aktivnosti u trajanju od 150 minuta sedmično [31]. Po- stressed that exercise programs for the elderly should
trebno je naglasiti da programi vežbanja za stare treba include aerobic, resistance, flexibility, and balance
da uključuju aerobni trening, vežbe otpornosti, vežbe training [32].
fleksibilnosti-pokretljivosti i vežbe ravnoteže [32].
AEROBIC TRAINING
AEROBNI TRENING The elderly population is associated with a decline in
Populacija starih lica povezuje se sa opadanjem kardi- cardiorespiratory capacity, which is associated primari-
orespiratornog kapaciteta, što je, pre svega, povezano ly with a decline in maximal cardiac output and chang-
sa opadanjem maksimalnog minutnog volumena srca es in arteriovenous difference [33]. Aerobic training
i promenama u arteriovenskoj razlici pritiska [33]. Ae- can modulate such alterations by inducing central and
robni trening može da modifikuje ovakve promene peripheral adaptations [33]. Such modulations are low-
podsticanjem centralnih i perifernih adaptacija [33]. U ering of the heart rate at rest and during submaximal
ove modifikacije spadaju smanjenje srčane frekvencije exercise, smaller increases in blood pressure, whole
u mirovanju kao i tokom submaksimalne fizičke aktiv- body insulin action improvement, and plasma lipid
nosti, manja povećanja u krvnom pritisku, poboljšanje concentration reduction [32].
dejstva insulina na nivou celog organizma i smanjenje During aerobic exercise, large muscles of the body
koncentracije lipida u plazmi [32]. rhythmically move for sustained periods of time and
Tokom aerobnog treninga, veliki mišići tela vrše ri- energy is used through the oxidative metabolism [32].
tmične pokrete u dužem vremenskom periodu, pri čemu The following aerobic exercises in the elderly can be
se energija koristi putem oksidativnog metabolizma [32]. considered: walking, treadmill walking, climbing stairs,
Mogu se uzeti u obzir sledeće aerobne vežbe kod starijih stationary cycling [33], with individually designed mo-
osoba: hodanje, hodanje na traci, penjanje uz stepenice, dalities that take into consideration the preferences,
vežbanje na sobnom biciklu [33], uz individualno osmi- physical capacities, and comorbidities of the elderly
šljene modalitete koji uzimaju u obzir afinitete, fizičke ka- individual. For example, those with lower back pain or
pacitete i komorbiditete određenog starog lica. Na primer, poor balance may be advised stationary recumbent cy-
licima sa bolom u krstima ili sa lošom ravnotežom može cling [32].
se sugerisati vežbanje na ležećem sobnom biciklu [32].
RESISTANCE TRAINING
TRENING OTPORNOSTI Resistance training is beneficial for the elderly who are
Trening otpornosti (otpora) koristan je kod starih lica severely frail [33]. This type of training improves muscle
koja su izuzetno krhka [33]. Ova vrsta treninga po- mass, strength, and function, and includes static (iso-
boljšava mišićnu masu, snagu i funkciju, a uključuje metric) and dynamic (concentric and eccentric) types
statične (izometrijske) i dinamične (koncentrične i eks- of exercises [32]. Additionally, this type of training pro-
centrične) vrste vežbi [32]. Takođe, ova vrsta treninga motes neuronal adaptation (intermuscular and intra-
pospešuje neurološku adaptaciju (međumišićna i unu- muscular coordination) [34] and improves bone den-
tarmišićna koordinacija) [34] i unapređuje gustinu ko- sity and metabolic health [35]. Furthermore, resistance
stiju i metaboličko zdravlje [35]. Nadalje, vežbe otpor- training is used in the treatment of various symptoms
nosti se koriste u terapiji različitih simptoma i stanja, and conditions, including but not limited to, osteopo-
koja uključuju osteoporozu i degenerativna oboljenja rosis and degenerative joint disorders [34]. For elderly
zglobova, ali i druga stanja i tegobe [34]. Za stara lica sa adults with existing pain, isometric strengthening ex-
prisutnim bolom, preporučuju se izometrijske vežbe za ercises are advised, while for those with poor balance
jačanje, dok se kod onih sa lošom ravnotežom i stanji- and conditions that may limit weight bearing activity,
ma koja mogu ograničavati sposobnost nošenja tereta, aquatic resistance exercises are advised [32].
savetuje sprovođenje treninga otpornosti u vodi [32].
FLEXIBILITY TRAINING
TRENING FLEKSIBILNOSTI-POKRETLJIVOSTI It has been hypothesized that flexibility or range of
Postoji hipoteza koja kaže da fleksibilnost odnosno op- motion (ROM) in a joint or group of joints declines af-
seg pokreta (engl. range of motion – ROM) u zglobu ili ter the age of 70 years, especially in women [32]. Sig-
grupi zglobova opada nakon 70. godine, naročito kod nificant decline in the flexibility of hip and shoulder
žena [32]. Značajan pad pokretljivosti kukova i rame- joints in the population of adults aged above 70 years
nih zglobova u populaciji starih iznad 70 godina zapa- was observed in a study by Stathokostas et al. [36]. In
žen je u studiji koju su sproveli Statokostas i saradnici the elderly population, the goal of flexibility training
[36]. U populaciji starih, cilj programa za trening flek- programs is to improve ROM in the muscle-tendon
sibilnosti jeste unapređenje opsega pokreta u grupa- groups, so as to enable the individual to perform func-
ma mišića i tetiva, kako bi se omogućilo staroj osobi tional everyday activities [37]. The flexibility exercises
da sprovodi svakodnevne funkcionalne aktivnosti [37]. that can improve ROM include dynamic stretching,
Vežbe pokretljivosti koje mogu da unaprede opseg static stretching, proprioceptive neuromuscular facil-
pokreta uključuju: dinamičko istezanje, statičko isteza- itation, and ballistic methods, which are usually not
nje, proprioceptivnu neuromišićnu stabilizaciju (engl. recommended for everyday exercise [32].
proprioceptive neuromuscular facilitation – PNF) i bali-
stičke metode, koje se ne preporučuju pri svakodnev- BALANCE TRAINING
nom vežbanju [32]. In the elderly population, there is a decline in balance
control, which affects the individual’s ability to move
TRENING RAVNOTEŽE and function independently [38]. Thus, impaired bal-
U populaciji starih lica, dolazi do opadanja kontrole ance might be a major risk for falls in this population
ravnoteže, što utiče na sposobnost pojedinca da se group [38]. When performing everyday activities, both
kreće i nezavisno funkcioniše [38]. Stoga, oštećena rav- static and dynamic balance are susceptible to change
noteža kod ove grupacije može predstavljati ozbiljan [39]. Therefore, balance relies on the proper function-
rizik za padove [38]. Prilikom obavljanja svakodnevnih ing of the visual, vestibular, proprioceptive and tac-
aktivnosti, i statička i dinamička ravnoteža su podlož- tile senses along with an adequate functioning of the
ne promenama [39]. Stoga se ravnoteža oslanja na neuromuscular system [39]. The recommended exer-
pravilno funkcionisanje čula vida, kao i vestibularnog, cises include progressively difficult postures, dynamic
proprioceptivnog i čula dodira, uz adekvatno funkcio- movement, stressing postural muscle groups, and sen-
nisanje nervno-mišićnog sistema [39]. Preporučene ve- sory input reduction (standing with eyes closed) [32].
žbe uključuju progresivno teže položaje tela, dinamič- Examples of exercises include tandem walking, stand-
ke pokrete, opterećivanje posturalnih mišićnih grupa i ing on one leg, stepping over objects, climbing slowly
redukciju senzornih inputa (stajanje sa zatvorenim oči- up and down steps, turning, maintaining balance in a
ma) [32]. Primeri ovih vežbi uključuju: tandem hodanje, moving vehicle [33].
stajanje na jednoj nozi, prekoračivanje predmeta, laga-
no penjanje uz stepenice i silaženje niz stepenice, okre- CONCLUSION
tanje, održavanje ravnoteže u vozilu u pokretu [33]. The elderly population presents a fragile group of in-
dividuals with an increased likelihood of functional
ZAKLJUČAK decline in performing everyday activities, which ulti-
Populacija starih predstavlja fragilnu grupaciju kod mately reduces their independence and increases the
koje su povećani izgledi da će doći do funkcionalnog need for the care of these individuals, at the family and
propadanja u obavljanju svakodnevnih aktivnosti, što community levels. Special attention should be focused
na kraju umanjuje njihovu samostalnost i povećava on multimorbidity and the increased needs of these in-
potrebu za staranje o ovim licima, na nivou porodice dividuals, in order to prevent premature death, reduce
i na nivou zajednice. Posebnu pažnju treba posveti- hospitalizations, and favor positive lifestyle habits and
ti višestrukom morbiditetu i povećanim potrebama healthy aging. Therefore, preventive measures, imple-
ovih osoba, kako bi se prevenirala prevremena smrt, mented at healthcare centers and at the level of the
smanjio broj hospitalizacija, te promovisale navike po- community, are of great importance. Educational pro-
zitivnog načina života i zdravog starenja. Stoga su od grams and awareness raising regarding the impact of
velikog značaja mere prevencije koje se sprovode u health habits are vital in the elderly population, while
zdravstvenim centrima i na nivou zajednice. Obrazovni the timely identification of comorbidities and func-
programi i podizanje svesti o uticaju zdravstvenih national deterioration, as well as a multidisciplinary ap-
vika, od vitalnog su značaja za populaciju starih, dok proach are important for achieving a more favorable
su blagovremena identifikacija komorbiditeta i funk- outcome in the treatment and follow-up of this popu-
cionalnog propadanja, kao i multidisciplinarni pristup, lation. Finally, a healthy and active elderly population
značajni za postizanje povoljnijeg ishoda u lečenju i poses a lesser burden to the medical system and the
praćenju ove populacije. Najzad, zdrava i aktivna po- community.
pulacija starih lica predstavlja manje opterećenje za
medicinski sistem i društvenu zajednicu. Conflict of interest: None declared.
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PRINCIPI LEČENJA PRELOMA KARLICE KOD
POLITRAUMATIZOVANIH PACIJENATA
PREGLEDNI RAD REVIEW ARTICLE
PRINCIPLES OF PELVIC FRACTURE TREATMENT

IN POLYTRAUMA PATIENTS
Uroš Dabetić1, Danilo Golubović2, Jovana Grupković1, Marko Ilić1,3, Dejan Aleksandrić4, Goran Tulić1,3
1
Univerzitetski klinički centar Srbije, Klinika za ortopedsku University Clinical Center of Serbia, Clinic for Orthopedic Surgery
1
hirurgiju i traumatologiju, Beograd, Srbija and Traumatology, Belgrade, Serbia

2
Gradski zavod za hitnu medicinsku pomoć Beograd, Beograd, City Medical Emergency Department, Belgrade, Serbia
2
Srbija
3
3
Univerzitet u Beogradu, Medicinski fakultet, Beograd, Srbija
Institute for Orthopedic Surgery "Banjica", Belgrade, Serbia
4
4
Institut za ortopediju „Banjica“, Beograd, Srbija
SAŽETAK ABSTRACT
Uvod: Lečenje preloma karlice predstavlja jedan od najvećih izazova u ortoped- Introduction: The treatment of pelvic fractures is one of the biggest challenges
skoj hirurgiji i traumatologiji. Radi se o povredama čiji mortalitet dostiže i do in orthopedic surgery and traumatology. Mortality from these injuries can be as
21%, te je od velike važnosti prepoznavanje i adekvatno lečenje. Najčešći uzrok high as 21%, which is why recognizing them and providing adequate treatment
smrtnog ishoda u prva 24 sata od povrede je krvarenje. Prelomi karlice variraju is of great importance. The most common cause of death in the first 24 hours
od jednostavnih preloma do kompleksnih fraktura sa posledičnom hemodinam- following injury is bleeding. Pelvic fractures range from simple to complex frac-
skom nestabilnošću. Cilj ove studije je da proceni trenutne standarde zbrinjavanja tures with consequent hemodynamic instability. The aim of this study is to assess
preloma karlice, kao i da ukaže na moguću strategiju poboljšanja krajnjeg ishoda current standards of pelvic fracture care, as well as to indicate a possible strategy
lečenja. to improve the final outcome of treatment.
Rezultati: Kada protokol ne postoji, dežurni tim se vodi smernicama koje su Results: When there is no established protocol, the on-duty team of doctors is
im dostupne. U novije vreme DCR se smatra vodećim principom u zbrinjavanju guided by the guidelines available to them. More recently, DCR has been consid-
politraumatizovanih pacijenata. Primarno je uspostaviti kontrolu krvarenja – ered a guiding principle in the care of polytraumatized patients. It is of primary
primenom PPP-a, angiografskom embolizacijom ili REBOA metodom. U literaturi importance to establish bleeding control – using PPP, angiographic embolization
se primena karličnih poveski preporučuje kao primarni vid zbrinjavanja povreda or the REBOA method. The use of pelvic bandages is recommended in literature as
karlice od strane službe hitne pomoći ili obučenog lica u predbolničkim uslovima. the primary form of care for pelvic injuries by the emergency service or by a trained
Spoljašnja fiksacija nestabilnih preloma karlice je jedan od ključnih koraka u sklo- person in pre-hospital conditions. External fixation of unstable pelvic fractures is
pu DCR protokola. ORIF preloma karlice je definitivan tip fiksacije preloma, ali je one of the key steps in the DCR protocol. ORIF of pelvic fracture is a definite type
indikovan kod hemodinamski stabilnog pacijenta. of fracture fixation, but it is performed only in hemodynamically stable patients.
Zaključak: S obzirom na anatomske karakteristike karlične duplje, povrede kar- Conclusion: Due to the anatomical characteristics of the pelvic cavity, pelvic
ličnog prstena predstavljaju samo deo spektra politraume, tako da se lečenje u ring injuries represent only a part of the spectrum of polytrauma, therefore the
početku bazira na hemodinamskoj stabilizaciji pacijenta (DCR protokol). Lečenje treatment is initially based on the hemodynamic stabilization of the patient (DCR
ovakvih pacijenata zahteva multidisciplinarni pristup. Plasiranje spoljašnjeg fik- protocol). The treatment of such patients requires a multidisciplinary approach.
satora u sklopu DCO protokola ima ulogu u kontroli krvarenja, te je to metoda Placement of an external fixator as part of the DCO protocol has a role in bleed-
izbora kod hemodinamski nestabilnih pacijenata. Definitivna fiksacija preloma ing control and is the method of choice in hemodynamically unstable patients.
karlice (ORIF) se sprovodi kod stabilnih pacijenata, koji nisu životno ugroženi. Definitive pelvic fracture fixation (ORIF) is performed in hemodynamically stable
Ključne reči: prelom karlice, politrauma, krvarenje, DCO patients, who are not in life-threatening condition.
Key words: pelvic fracture, polytrauma, bleeding, DCO

Uroš Dabetić Uroš Dabetić
Klinika za ortopedsku hirurgiju i traumatologiju, Univerzitetski klinički Clinic for Orthopedic Surgery and Traumatology, University Clinical Center of
centar Srbije Serbia
Elektronska adresa: urosdabetic1983@gmail.com E-mail: urosdabetic1983@gmail.com
Primljeno • Received: January 25, 2022; Revidirano • Revised: February 14, 2022; Prihvaćeno • Accepted: February 15, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-36072
principi lečenja preloma karlice kod politraumatizovanih pacijenata
Dabetić U. et al.
principles of pelvic fracture treatment in polytrauma patients
UVOD INTRODUCTION
Lečenje preloma karlice predstavlja jedan od najvećih Treating pelvic fracture is one of the greatest chal-
izazova u ortopedskoj hirurgiji i traumatologiji. Ovi lenges in orthopedic surgery and traumatology. Pelvic
prelomi nastaju usled dejstva jake sile, i to u saobraćaj- fractures occur as the result of powerful force, primar-
nim udesima (60%), prilikom pada sa visine (30%), kao ily in traffic accidents (60%), in falls from height (30%),
i pri ustrelnim i industrijskim nezgodama [1]. Kod ma- as well as in shooting and industrial accidents [1]. In a
njeg broja starijih pacijenata, mogu nastati usled pada small number of elderly patients, pelvic fracture may
sa sopstvene visine, a usled osteodistrofičnih prome- occur as the result of the patient falling from standing
na koštano-zglobnog sistema. S obzirom da se radi o height, due to osteodystrophic changes in the bone
povredama čiji mortalitet dostiže i 21% [2], od velike joint system. Bearing in mind that mortality in these
važnosti su, kako prepoznavanje, tako i pravovremeno injuries can be as high as 21% [2], it is of great impor-
i adekvatno lečenje. Krvarenje je najčešći uzrok smrt- tance that they should be recognized and treated ad-
nog ishoda u prva 24 sata od povrede. equately and on time. Bleeding is the most common
Prelomi karlice variraju od jednostavnih preloma cause of death in the first 24 hours following injury.
do kompleksnih višestrukih fraktura sa posledičnom Pelvic fractures vary from simple fractures to com-
hemodinamskom nestabilnošću. Kod politraumatizo- plex multiple fractures with consequent hemodynamic
vanih pacijenata, prelomi karlice su zastupljeni u čak instability. In polytraumatized patients, pelvic fractures
20% slučajeva [3]. Kod zbrinjavanja ovakvih pacijenata, are present in as many as 20% of cases [3]. In treating
neophodan je multidisciplinarni pristup lečenju – tim these patients, a multidisciplinary approach is neces-
sastavljen od iskusnih ortopedskih i opštih hirurga, kao sary – a team made up of experienced orthopedic and
i interventnog radiologa i anesteziologa. general surgeons, including also an interventional ra-
U nekoliko objavljenih studija je zapaženo da je u diologist and anesthesiologist.
centrima u kojima je napravljen i primenjen algoritam In several studies published so far, it has been not-
za zbrinjavanje preloma karlice kod hemodinamski need that, in those centers where an algorithm for treat-
stabilnih pacijenata došlo da značajnog opadanja mor- ing pelvic fracture in hemodynamically unstable pa-
taliteta [4–7]. tients has been designed and put into use, a significant
Cilj ove studije je da proceni trenutne standarde drop in mortality has occurred [4–7].
zbrinjavanja preloma karlice, kao i da ukaže na mogu- The aim of this study is to assess the current stan-
ću strategiju poboljšanja krajnjeg ishoda lečenja. dards of pelvic fracture treatment, as well as to indicate
the possible strategy for improving the final outcome
POLITRAUMA of treatment.
Politrauma, prema novoj Berlinskoj definiciji, podra-
zumeva slučajeve sa skorom na skali povreda (engl.
POLYTRAUMA
Abbreviated Injury Scale – AIS) ≥ 3, za najmanje dva ana- According to the new Berlin Definition, polytrauma
tomska regiona tela, i sa jednim od sledećih pet fizi- indicates cases with an Abbreviated Injury Scale (AIS)
oloških parametara, odnosno sa kombinacijom dva ili score ≥ 3, for at least two anatomical regions of the
više navedena parametra: body, and with one of the following five physiological
1. Hipotenzija (sistolni pritisak ≤ 90 mmHg) parameters, or with a combination of two or more of
2. Gubitak svesti (Glazgovska skala kome - Glasgow these parameters:
Coma Scale ≤ 8) 1. Hypotension (systolic blood pressure ≤ 90 mmHg)
3. Acidoza 2. Loss of consciousness (Glasgow Coma Scale ≤ 8)
4. Koagulopatija (parcijalno tromboplastinsko vreme 3. Acidosis
≥ 40 s) 4. Coagulopathy (partial thromboplastin time ≥ 40 s)
5. Starost pacijenta (≥ 70 godina) [8]. 5. Patient age (≥ 70 years) [8].
Kod politraumatizovanog pacijenta, barem jedna, In a polytraumatized patient, at least one of two or
od dve ili više povreda, ugrožava njegov život. more injuries is life-threatening.
PRVI KORAK U ZBRINJAVANJU PRELOMA FIRST STEP IN TREATING PELVIC FRACTURE

KARLICE The protocol for treating pelvic fracture varies from
Protokol za zbrinjavanje preloma karlice varira od usta- hospital to hospital. When there is no established pro-
nove do ustanove. Kada protokol ne postoji, dežurni tocol, the on-duty team of doctors are guided by avail-
tim se vodi smernicama koje su im dostupne. U novije able guidelines. As of late, damage control resuscitation
Dabetić U. i sar.
vreme, DCR (engl. damage control resuscitation) se sma- (DCR) has been considered the leading principle in treat-
tra vodećim principom u zbrinjavanju politraumatizo- ing polytraumatized patients. DCR is a strategy whose
vanih pacijenata. DCR je strategija koja za cilj ima da aim is to stop bleeding, as well as to prevent or reverse
zaustavi krvarenje, kao i da spreči ili preokrene razvoj the development of the components of the trauma tri-
komponenti letalnog traumatskog trijasa - hipotermi- ad of death – hypothermia, acidosis, and coagulopathy,
je, acidoze i kogaulopatije, kroz niz kombinovanih te- through a series of combined therapeutic protocols [9].
rapijskih protokola [9]. However, the implementation of this strategy de-
Međutim, primena ove strategije zavisi od mnoš- pends on a number of factors – the capacities of the
tva faktora – kapaciteta same bolnice, opremljenosti, hospital, equipment, the capability of the surgical
osposobljenosti hirurškog tima za damage control hi- team to perform damage control surgery, as well as the
rurgiju, kao i mogućnosti izvođenja hitne angiografije possibility of performing urgent angiography (blood
(embolizacije krvnih sudova). vessel embolization).
Nezavisno od izbora strategije, neophodno je ura- Regardless of the choice of strategy, it is necessary
diti dijagnostiku (klinički pregled, laboratorijske anali- to perform the following: requisite diagnostics (clinical
ze, RTG, EHO, MSCT), napraviti procenu težine povre- examination, laboratory analyses, X-ray, ECHO, MSCT),
da, procenu potrebe za neinvazivnom/invazivnom assessment of the severity of the injuries, assessment
stabilizacijom karlice, procenu eventualnih povreda of the need for noninvasive/invasive pelvic stabiliza-
abdomena, te doneti odluku o potrebi za hirurškim le- tion, assessment of possible abdominal injuries, and
čenjem i angiografijom [10]. then reach a decision on the need for surgical treat-
ment and angiography [10].
IZVORI KRVARENJA
Mogući izvori krvarenja su arterije, vene i spongiozne
SOURCES OF BLEEDING
kosti [11]. Neophodno je utvrditi izvor i uspostaviti The possible sources of bleeding are arteries, veins,
kontrolu krvarenja. Vefls i saradnici su u svojoj studiji and cancellous bones [11]. It is necessary to determine
naveli da je, kod hemodinamski nestabilnih pacijenata the source and establish control of the bleeding. In
sa povredom karlice i hipotenzijom otpornom na rea- their study, Wijffels et al. stated that in 70 % of cases
nimaciju, u 70% slučajeva bilo prisutno arterijsko krva- of hemodynamically unstable patients with pelvic in-
renje [12]. jury and hypotension resistant to resuscitation, arterial
Takođe, određeni tipovi preloma su u korelaciji sa bleeding was present [12].
povredom određenih krvnih sudova – prelomi pubič- Also, certain types of fractures correlate with injury
nih kostiju koreliraju sa povredom obturatornih krvnih of certain blood vessels – pubic bone fractures correlate
sudova; dislokacija sakroilijačnog zgloba (povreda po with injury to obturator blood vessels; dislocation of the
tipu smicanja) korelira sa venskim krvarenjem, i to iz sacroiliac joint (shear injury) correlates with venous bleed-
glutealnih i hipogastričnih grana. ing, primarily from gluteal and hypogastric branches.
KARLIČNE POVESKE ABDOMINAL-PELVIC TOURNIQUETS

Primena karličnih poveski se u literaturi preporučuje The application of abdominal-pelvic tourniquets is rec-
kao primarni vid zbrinjavanja povreda karlice od strane ommended in literature as the primary method of taking
službe hitne pomoći ili obučenog lica u predbolničkim care of pelvic injuries by the emergency services or by
uslovima. Karlične poveske predstavljaju neinvazivni a trained person, in prehospital care. Abdominal-pelvic
vid spoljašnje kompresije, koji se pokazao koristan u tourniquets are a noninvasive form of external compres-
kontroli krvarenja i privremenoj stabilizaciji karličnog sion, which has proven useful in the control of bleeding
prstena [10]. and for temporarily stabilizing the pelvic ring [10].
Karlične poveske treba pozicionirati oko velikih tro- Abdominal-pelvic tourniquets should be posi-
hantera i pubične simfize, kako bi primenjeni pritisak tioned around the great trochanters and the pubic
doveo do privremene stabilizacije preloma karlice, ad- symphysis, so that the pressure applied would lead to
dukcije nogu i smanjenja unutrašnje zapremine karlič- temporary stabilization of pelvic fracture, leg adduc-
ne duplje. tion, and a decrease of the internal volume of the pel-
vic cavity.
SPOLJAŠNJA FIKSACIJA PRELOMA KARLICE
Spoljašnja perkutana fiksacija mehanički nestabilne
EXTERNAL PELVIC FRACTURE FIXATION
karlice predstavlja jedan od ključnih koraka u sklo- External percutaneous fixation of a mechanically un-
pu DCR protokola politraumatizovanih pacijenata sa stable pelvis is one of the key steps in the DCR protocol
Dabetić U. et al.
prelomom karlice. Osim što se stabilizuje karlični pr- for polytraumatized patients with pelvic fracture. In ad-
sten, cilj primene ove metode je i smanjenje volumena dition to stabilizing the pelvic ring, the goal in apply-
karlične duplje, kako bi došlo do tamponade venskog ing this method is also to decrease the volume of the
krvarenja [13]. pelvic cavity, in order to bring about the tamponade of
U literaturi su opisana dva glavna principa spoljaš- venous hemorrhage [13].
nje fiksacije, u zavisnosti od vrste preloma karlice. Za Two main principles of external fixation, depending
rotaciono nestabilne, antero-posteriorne kompresiv- on the type of pelvic fracture, have been described in lit-
ne i lateralne kompresivne prelome, metoda izbora je erature. For rotationally unstable, anteroposterior com-
prednja spoljašnja fiksacija. Zadnja spoljašnja fiksacija pression fractures and lateral compression fractures, the
(C clamp) je pristup koji se preporučuje kod vertikalno method of choice is anterior external fixation. Posterior
nestabilnih preloma karlice, kako bi se postigla stabil- external fixation (C clamp) is the approach recommend-
nost posteriornih segmenata karlice [10,14]. ed in vertically unstable pelvic fractures, in order to
Spoljašnja fiksacija se u najvećem broju slučajeva achieve stability of posterior pelvic segments [10,14].
sprovodi u sklopu DCR protokola i predstavlja privre- In most cases, external fixation is carried out within
menu metodu stabilizacije preloma i kontrole krva- the DCR protocol and represents a temporary method
renja, koja, međutim, u određenom broju slučajeva, for stabilizing the fracture and establishing control of
može biti i definitivna metoda fiksacije [15]. Tada imo- the bleeding, which, however, in a certain number of
bilizacija preloma spoljašnjim fiksatorom traje 6 – 12 cases, may be the definitive method of fixation [15]. In
nedelja, sve dok se ne pojave klinički i radiografski zna- such cases, immobilization of the fracture with an ex-
ci zarastanja preloma. ternal fixator lasts 6 – 12 weeks, until clinical and radio-
Kod primene ove metode, neophodno je da hirurg graphic signs of fracture healing are registered.
bude iskusan i upoznat sa principima spoljašnje fiksa- In the application of this method, it is necessary that
cije karlice, s obzirom na moguće komplikacije, u smi- the surgeon is experienced and familiar with the prin-
slu povreda neurovaskularnih struktura neadekvatnim ciples of external pelvic fixation, due to the possibility
pozicioniranjem klinova, potom popuštanja fiksacije i of the development of complications, such as injury to
pojave ponovne nestabilnosti, kao i u smislu razvoja the neurovascular structures caused by inappropriate
infekcija na mestu plasiranih šrafova. positioning of the pins, loosening of the fixation and
renewed instability, as well as the development of infec-
PREPERITONEALNO TAMPONIRANJE KARLICE tion at the placement site of the pins.
(PPP)
PREPERITONEAL PELVIC PACKING (PPP)
Glavni izvor akutnog retroperitonealnog krvarenja kod
hemodinamski nestabilnih pacijenata sa povredama The primary source of acute retroperitoneal bleeding
karličnog prstena pripisuje se venskom krvarenju, u in hemodynamically unstable patients with pelvic ring
80% – 90% svih slučajeva, a potiču iz presakralnog i injury is attributed to venous bleeding, in 80% – 90% of
paravezikularnog venskog pleksusa, kao i od krvarenja all cases, and it originates from the presacral and para-
spongioznih kostiju, usled ilijačnih i sakralnih fraktura i vesical venous plexus, as well as from bleeding from
prekida sakroilijačnog zgloba, dok je 10% – 20% arte- the cancellous bones, due to iliac and sacral fractures
rijskog porijekla [16]. and the disruption of the sacroiliac joint, while in 10% –
Koncept „direktnog” preperitonealnog karličnog 20% of cases the bleeding is of arterial origin [16].
tamponiranja (engl. preperitoneal pelvic packing – PPP), The concept of ‘direct’ preperitoneal pelvic pack-
opisanog u Denveru, predstavlja posebnu hiruršku ing (PPP), as described in Denver, is a special surgical
metodu, prilikom koje se pravi suprapubična incizija, method, wherein a suprapubic incision is made, en-
koja omogućava direktni retroperitonealni pristup, na- abling direct retroperitoneal access, upon which pack-
kon čega se vrši tamponiranje [17]. ing is performed [17].
Modifikovana PPP metoda omogućava efikasnije The modified PPP method enables more efficient
tamponiranje unutar skrivenog retroperitonealnog packing within the hidden retroperitoneal space,
prostora, pri čemu se tri jastučića za laparotomiju po- wherein three laparotomy pads are placed on each side
stavljaju sa svake strane mokraćne bešike, tako da of the urinary bladder, in such a way as to be packed
budu upakovani ispod oboda karlice a prema ilijačnim below the rim of the pelvis and towards the iliac blood
krvnim sudovima, bez potrebe eksponiranja retroperi- vessels, without there being any need to expose the
tonealnog prostora [10]. Ovom tehnikom, laparotomi- retroperitoneal space [10]. Using this technique, mid-
ja na srednjoj liniji se može izvesti kroz odvojeni rez, line laparotomy can be executed through a separate in-
proksimalno od suprapubičnog pristupa, ako postoje cision, proximally to the suprapubic access, if there are
Dabetić U. i sar.
pridružene intraabdominalne povrede [18]. Ova meto- associated intraabdominal injuries [18]. This method is
da se preporučuje zajedno sa spoljašnjom fiksacijom recommended along with external fixation in hemo-
kod hemodinamski i mehanički nestabilnih pacijenata. dynamically and mechanically unstable patients. The
Nedostaci ove tehnike ogledaju se u tome što ona zah- drawbacks of this method are reflected in the follow-
teva dodatnu operaciju radi uklanjanja obloga - jastu- ing: it requires additional surgery, which is necessary to
čića, neefikasna je za arterijsko krvarenje i može kom- remove the pads; it is inefficient for arterial bleeding; it
promitovati buduće hirurške intervencije [11]. may compromise future surgical procedures [11].
ANGIOGRAFSKA EMBOLIZACIJA ANGIOGRAPHIC EMBOLIZATION

Angiografska embolizacija je tehnika kojom se u arte- Angiographic embolization is a technique whereby syn-
rijski krvni sud kateterom plasiraju sintetički materijali, thetic materials, called embolic agents, are injected into
koji se nazivaju embolički agensi, i na taj način se bloki- an artery via catheter, which results in blood flow block-
ra tok krvi u datom području tela. Arterijsko krvarenje ing in the given region of the body. Arterial bleeding oc-
se javlja u oko 10% – 15% svih krvarenja kod hemo- curs in approximately 10% – 15% of all hemorrhages in
dinamski nestabilnih karličnih povreda, što je obično hemodynamically unstable pelvic injuries, which is usu-
praćeno hipotenzijom, koja je otporna na reanimaciju ally accompanied by hypotension, resistant to resuscita-
i mehaničku stabilizaciju [19]. Arterijske povrede imaju tion or mechanical stabilization [19]. Arterial injuries have
lošu prognozu, posebno kada su zahvaćeni veći krvni an unfavorable prognosis, especially when larger blood
sudovi. Unutrašnja ilijačna arterija predstavlja glavni vessels are involved. The internal iliac artery is the main
izvor arterijskog krvarenja u karlici (86%), sa najvećim source of arterial bleeding in the pelvis (86%), with the
brojem lezija na njenoj glavnoj grani [11]. Indikacije za greatest number of lesions occurring on its main branch
angiografiju su sledeće: hemodinamska nestabilnost [11]. Indications for angiography are as follows: hemo-
otporna na reanimaciju, delimično responzivni paci- dynamic instability resistant to reanimation, partially re-
jenti sa kontrastnom ekstravazacijom na CT-u, kao i sponsive patients with CT contrast extravasation, as well
progresivni pad nivoa hemoglobina, koji zahteva četiri as a progressive fall of the hemoglobin level, requiring
ili više jedinica krvi [11]. the transfusion of four or more units of blood [11].
REANIMACIJSKA ENDOVASKULARNA RESUSCITATIVE ENDOVASCULAR BALLOON

BALONSKA OKLUZIJA AORTE (REBOA) OCCLUSION OF THE AORTA (REBOA)
Reanimacijska endovaskularna balonska okluzija aorte Resuscitative endovascular balloon occlusion of the
(engl. resuscitative endovascular balloon occlusion of the aorta (REBOA) is a percutaneous transfemoral proce-
aorta – REBOA) predstavlja perkutanu transfemoralnu dure, which includes the placement of an endovascu-
proceduru, koja uključuje postavljanje endovaskular- lar balloon into the aorta, for the purpose of controlling
nog balona u aortu, u cilju kontrole arterijskog krvare- arterial bleeding and temporarily maintaining blood
nja i privremenog održavanja krvnog pritiska kod trau- pressure in traumatic hemorrhagic shock [11,20]. This
matskog hemoragičnog šoka [11,20]. Visoko je zavisna procedure is highly dependent on a functional ap-
od funkcionalnog pristupa femoralnoj arteriji, a rano proach to the femoral artery, and early implementa-
formiranje ovog pristupa je od velikog značaja. Ova tion of this approach is of the utmost importance. This
metoda je poslednjih godina postala alternativa za ur- method has become the alternative for emergency
gentnu torakotomiju kod hemodinamski nestabilnih thoracotomy in hemodynamically unstable polytrau-
politraumatizovanih pacijenata. matized patients.
REBOA se može sprovesti u Zoni 1 (supracelijačna REBOA can be performed in Zone 1 (supraceliac
aorta ili descedentna aorta), Zoni 2 (pararenalna aor- aorta or descendant aorta), Zone 2 (pararenal aorta),
ta) ili Zoni 3 (infrarenalna aorta). Zona 2 se uglavnom or Zone 3 (infrarenal aorta). Zone 2 is usually avoided,
izbegava, zbog moguće ishemije visceralnih organa. due to possible visceral organ ischemia. Zone 3 is the
Zona 3 je optimalna kod krvarenja u karlici, zato što se optimal approach in pelvic hemorrhage, as it prevents
prevenira ishemija visceralnih organa a istovremeno visceral organ ischemia, at the same time enabling a
omogućava dugo vreme okluzije (4 – 6 h) [21]. long occlusion time (4 – 6 h) [21].
REBOA je samo privremeno rešenje, a definitivna REBOA is just a temporary solution, while definitive
kontrola krvarenja se mora postići. Jedan od glavnih hemorrhage control still needs to be achieved. One of
nedostataka ove tehnike je pojava ishemijskih ošteće- the main limitations of this technique is the occurrence
nja organa i tkiva koja mogu dovesti i do višestrukog of ischemic organ and tissue damage, which may lead
otkazivanja organa (engl. multiple organ dysfunction to multiple organ dysfunction syndrome (MODS), due
Dabetić U. et al.
syndrome – MODS) usled ishemijsko – reperfuzijske to ischemia-reperfusion injury. This problem is pre-
reakcije. Ovaj problem se prevenira kratkotrajnom vented by applying short REBOA, intermittent REBOA
REBOA procedurom, intermitentnom REBOA proce- (iREBOA), Zone 3 REBOA, and partial REBOA [22,23].
durom (iREBOA), Zona 3 REBOA procedurom i parcijal-
nom REBOA procedurom [22,23]. DCO AS A PART OF DCR
After severe trauma, the following three major factors
DCO U SKLOPU DCR-A determine the development of clinical presentation:
Nakon teške traume, razvoj kliničke slike određuju tri 1. Initial degree of injury ("first hit" – burden of trauma)
glavna faktora: 2. Individual biological response of the injured pa-
1. Inicijalni stepen povrede („first hit’’ – opterećenje tient’s body
traumom) 3. Type of treatment ("second hit" – burden of sur-
2. Individualni biološki odgovor organizma povređenog gery) [24].
3. Vrsta lečenja („second hit’’ – opterećenje operaci- Within the DCR protocol, damage control orthope-
jom) [24]. dics (DCO) also has its place.
U sklopu DCR protokola, svoje mesto ima i damage
control orthopedics – DCO. DCO is a surgical strategy focused on the following:
1. establishing control of the bleeding – the ABCDE (air-
DCO je hirurška strategija koja se fokusira na:
way, breathing, circulation, disability, exposure) ap-
1. postizanje kontrole krvarenja – ABCDE pristup (engl.
proach, except in conditions of catastrophic bleed-
airway, breathing, circulation, disability, exposure – AB-
ing, when component C is primarily focused on;
CDE approach), osim u uslovima katastrofalnog krva-
2. prevention of soft tissue contamination – wound
renja kada se primarno zbrinjava komponenta C;
debridement;
2. sprečavanje kontaminacije mekog tkiva – debrid-
3. early temporary stabilization of the fracture – pri-
man rane;
marily with external fixation, which is the method
3. ranu privremenu stabilizaciju preloma – uglavnom
of choice as it is expedient and minimally invasive,
spoljašnjom fiksacijom, što je metoda izbora jer je
but also with simpler procedures, such as traction
ekspeditivna i minimalno invazivna, ali i jednostav-
and plaster;
nijim procedurama, kao što su trakcija i gips;
4. stabilization of the patient – requires good com-
4. stabilizaciju pacijenta – zahteva dobru komunika-
munication between the surgical team and the
ciju hirurškog tima sa anesteziologom, s obzirom
anesthesiologist, as it is the anesthesiologist who
da anesteziolog ima najbolju sliku o opštem sta-
has the best understanding of the general status
nju pacijenta; sve terapijske procedure su usme-
of the patient; all treatment procedures are aimed
rene na dostizanje željenih vrednosti – srednji ar-
at achieving the desired values – median arterial
terijski pritisak > 60 mmHg, puls < 100, diureza =
pressure > 60 mmHg, pulse < 100, urine output =
0,5 – 1,0 ml/kg/h, serumski laktati < 2,5 i normalan
0.5 – 1.0 ml/kg/h, serum lactates < 2.5, and normal
bazni deficit ( -2 do +2);
base deficit ( -2 to +2);
5. izbegavanje „second hit“ i letalne trijade [9].
5. avoiding ‘second hit’ and the trauma triad of death [9].
Ovakav pristup minimalizuje operativno vreme i
Such an approach minimalizes the duration of the
gubitak krvi, a istovremeno olakšava negu bolesnika i
procedure and blood loss; at the same time, it makes
omogućava raniju i bolju pokretljivost pacijenta [25].
patient care easier and provides earlier and better mo-
Smatra se da je to najkorisniji pristup za pacijente sa
bility of the patient [25]. It is believed to be the most
udruženom traumom glave i grudnog koša, visokim
useful approach for patients with associated head and
skorom ozbiljnosti povrede (engl. injury severity sco-
chest trauma, patients with a high injury severity score
re – ISS), predispozicijama za razvoj postoperativnih
(ISS), patients with a predisposition for the develop-
komplikacija, kao i za „borderline“ pacijente [16]. Kod
ment of postoperative complications, as well as for
ovakvih politraumatizovanih pacijenata, izlaganje hi-
‘borderline’ patients [16]. In such polytraumatized pa-
rurškoj intervenciji povećava rizik od postoperativnih
tients, undergoing surgery increases the risk of postop-
komplikacija [26]. Ovaj pristup je proizašao iz primera
erative complications [26]. This approach stems from
zbrinjavanja pacijenata sa abdominalnom i karličnom
examples of patient care in cases with abdominal and
traumom, gde se pokazalo da primarno zaustavljanje
pelvic trauma, where it has transpired that the strate-
krvarenja i sekundarna revizija, u cilju definitivnog
gy of primary bleeding control and secondary revision
zbrinjavanja pacijenta, poboljšava postoperativni tok i
surgery, with the aim of definitive patient treatment,
oporavak [27].
improves the course of postoperative recovery [27].
Dabetić U. i sar.
Kod primene DCO-a, umesto rane potpune fiksa- In DCO, instead of early complete fixation (< 24
cije (< 24 – 36 časova posle povrede), ortoped privre- – 36 hours after injury), the orthopedic surgeon tem-
meno stabilizuje prelom pomoću trakcije ili eksterne porarily stabilizes the fracture by means of traction or
fiksacije, kod „borderline“ visokorizičnih pacijenata [28]. external fixation, in ‘borderline’ high-risk patients [28].
Za pacijente sa teškim povredama, koagulopatijom, For patients with severe injuries, coagulopathy, hypo-
hipotermijom, kao i pacijente koji su u šoku, ovo je me- thermia, as well as patients in a state of shock, this is
toda prvog izbora. the method of first choice.
Kada se lečenje sprovodi po principima DCO-a, važ- When treatment is carried out according to the
no pitanje jeste u kom je trenutku optimalno izvesti se- principles of DCO, an important issue to consider is the
kundarnu hiruršku intervenciju. optimal moment for carrying out the secondary pro-
Smatra se da period od 2 – 4 dana nakon povrede cedure.
nije pogodan za sekundarnu intervenciju. U ovo vreme, It is believed that the period of 2 – 4 days following
imunološke promene su još uvek u toku [29], a genera- injury is not favorable for the second procedure. In this
lizovani edem tkiva se još nije povukao [30]. Rezultati period, immunological changes are still ongoing [29]
velikog istraživanja, kojim je obuhvaćeno 4.314 pacije- and generalized edema has as yet not subsided [30]. The
nata, pokazali su da tajming sekundarne operacije, koja results of a large study, which included 4,314 patients,
traje duže od tri sata, može biti povezan sa razvojem or- showed that the timing of the secondary operation,
ganske disfunkcije. Pacijenti su podeljeni u odnosu na which normally lasts more than three hours, may be as-
prisustvo ili odsustvo sindroma disfunkcije više organa – sociated with the development of organ dysfunction. Pa-
MODS. Kod pacijenata koji su operisani 2 – 4 dana nakon tients were divided according to the presence or absence
traume, došlo je do otkazivanja organa, dok kod pacije- of MODS. In patients surgically treated 2 – 4 days follow-
nata koji su sekundarno operisani između 6. i 8. dana, ing trauma, organ failure did occur, while in patients
nije došlo do razvoja disfunkcije organa (p < 0,0001) which had a secondary operation between day 6 and
[31]. Takođe, istraživanje je pokazalo da je, kod pacije- day 8, organ dysfunction did not develop (p < 0,0001)
nata koji su ranije operisani, došlo do razvoja jače infla- [31]. Also, the study showed that, in patients who were
macije, u odnosu na pacijente koji su operisani kasnije. operated on earlier, more severe inflammation devel-
Stoga, nakon DCO-a, trebalo bi da postoji period čekanja oped, as compared to patients who were operated on
od nekoliko dana pre sekundarne definitivne operacije. later. Therefore, after DCO, there should be a waiting pe-
riod of several days before secondary definitive surgery.
OTVORENA REPOZICIJA I UNUTRAŠNJA
FIKSACIJA (ORIF) OPEN REDUCTION AND INTERNAL FIXATION
Otvorena repozicija i unutrašnja fiksacija (engl. open
(ORIF)
reduction and internal fixation – ORIF) preloma karlice Open reduction and internal fixation (ORIF) of pelvic
jeste jedna od najkompleksnijih ortopedskih operacija fracture is one of the most complex orthopedic surgical
i predstavlja definitivan tip fiksacije preloma. Kod poli- procedures and represents a definitive type of fracture
traumatizovanih pacijenata, otvorena repozicija i unu- fixation. In polytraumatized patients, open reduction
trašnja fiksacija preloma realizuje se najčešće u dru- and internal fracture fixation is most often carried out
gom aktu, nakon potpune stabilizacije pacijenta, a u as a second step, after the patient has been completely
cilju omogućavanja najboljeg funkcionalnog oporavka stabilized, with the aim of providing the best possible
i minimalizovanja poremećaja kvaliteta života i poten- functional recovery and minimizing the disruption in
cijalne stope invaliditeta, u slučaju nelečenog preloma the quality of life, as well as minimizing potential inva-
karlice [32,33]. Za vreme stabilizacije pacijenta od stra- lidity, in case of untreated pelvic fracture [32,33]. While
ne intenzivista, prelom karlice ostaje stabilizovan spo- the patient is being stabilized in intensive care, the pel-
ljašnjim fiksatorom. vic fracture remains stabilized with an external fixator.
U odnosu na vrstu preloma, adekvatnim pristu- Depending on the type of fracture, the site of the
pom se dolazi do mesta preloma, te se učini otvorena fracture is accessed using the appropriate approach,
repozicija prelomnih fragmenata, koji se potom fiksi- open reduction of the fractured fragments is per-
raju odgovarajućim implantacionim materijalom – u formed, and the fractures are then fixed with the ap-
najvećem broju slučajeva, kompresivnim zavrtnjima, propriate implantation material – in most cases, with
anatomskom pločicom i pripadajućim zavrtnjima. U lag screws and with plates. As compared to external
poređenju sa spoljašnjom fiksacijom, ORIF obezbeđuje fixation, ORIF provides anatomical reduction of frac-
anatomsku repoziciju prelomnih fragmenata i superi- tured fragments and more superior biomechanical sta-
orniju biomehaničku stabilnost, kao i brži oporavak. bility, as well as faster recovery.
Dabetić U. et al.
ZAKLJUČAK CONCLUSION
Povrede karličnog prstena uglavnom nastaju dejstvom Pelvic ring injuries mainly occur as the result of pow-
jakih sila, usled čega dolazi do oštećenja, kako skelet- erful force, resulting in injury, not only to the skeletal,
nog, tako i drugih organskih sistema. To su retko izolo- but to other body systems as well. These are rarely iso-
vane povrede (kod starijih pacijenata, nisko energetske lated injuries (in elderly patients, low-energy injuries),
povrede), te u najvećem broju slučajeva postoje udru- and, in most cases, associated injuries of the bone joint
žene povrede koštano-zglobnog sistema, grudnog system, thorax, abdomen, and/or head are also pres-
koša, abdomena i/ili glave. To znači da je pravovreme- ent. This means that timely and appropriate treatment
no i adekvatno zbrinjavanje ovih povreda od ključnog of these injuries is of vital importance, both at the site
značaja, kako na mestu pružanja prve pomoći, tako i of first aid and at trauma centers. Bearing in mind the
u trauma centrima. S obzirom na anatomske karakteri- anatomical features of the pelvic cavity, injuries to the
stike karlične duplje, povrede karličnog prstena pred- pelvic ring are only one segment of polytrauma, which
stavljaju samo deo spektra politraume, tako da se leče- is why treatment is initially focused on hemodynamic
nje u početku fokusira na hemodinamsku stabilizaciju stabilization of the patient (DCR protocol). The treat-
pacijenta (DCR protokol). Lečenje ovakvih pacijenata ment of such patients requires a multidisciplinary ap-
zahteva multidisciplinarni pristup (hemodinamska proach (hemodynamic stabilization, PPP, REBOA). Only
stabilizacija, PPP, REBOA). Tek kada se osiguraju vitalne when vital functions are stabilized, can doctors pro-
funkcije, može se pristupiti lečenju drugih poremećaja, ceed to treat other medical issues, which do not pri-
koji primarno ne ugrožavaju život pacijenta. marily threaten the life of the patient.
Plasiranje spoljašnjeg fiksatora, u sklopu DCO pro- Placement of an external fixator, within the DCO
tokola, ima ulogu u kontroli krvarenja, te je to metoda protocol, has a role in bleeding control, which makes
izbora kod hemodinamski nestabilnih pacijenata. it the method of choice in hemodynamically unstable
Definitivna fiksacija preloma karlice (ORIF) se ini- patients.
cijalno sprovodi kod stabilnih pacijenata, koji nisu ži- Definitive fixation of pelvic fracture (ORIF) is carried
votno ugroženi, ili po stabilizaciji politraumatizovanih out initially in stable patients, whose life is not in dan-
pacijenata. Predstavlja nezamenjiv način lečenja, u po- ger, or in polytraumatized patients, upon their stabili-
gledu funkcionalnog oporavka pacijenta i smanjenja zation. It is an indispensable method of treatment with
stope invaliditeta. respect to functional recovery and decreasing the rate
Iako je stopa mortaliteta kod ovih pacijenata i dalje of invalidity.
visoka, pravovremenim pružanjem pomoći i ispravnim Although the mortality rate in these patients is still
odabirom i primenom terapijskih metoda, pomenuta high, timely medical assistance and the correct choice
stopa se uspešno smanjuje. and application of treatment methods, reduce the said
rate effectively.
SPISAK SKRAĆENICA KORIŠĆENIH U TEKSTU
ABCDE – pristup koji se koristi za kontrolu krvarenja (engl. airway,
LIST OF ABBREVIATIONS AND ACRONYMS
breathing, circulation, disability, exposure – ABCDE approach) ABCDE –airway, breathing, circulation, disability, exposure – ABCDE
DCO – engl. damage control orthopedics approach; approach used in bleeding control
DCR – protokol za hemodinamsku stabilizaciju pacijenta (engl. damage
DCO – damage control orthopedics
control resuscitation)
ISS – skor ozbiljnosti povrede (engl. injury severity score) DCR – damage control resuscitation; protocol used for hemodynamic
MODS – sindrom disfunkcije više organa (engl. multiple organ dysfunction stabilization of the patient
syndrome) ISS – injury severity score
ORIF - otvorena repozicija i unutrašnja fiksacija (engl. open reduction and MODS – multiple organ dysfunction syndrome
internal fixation) ORIF – open reduction and internal fixation
PPP – preperitonealno karlično tamponiranje (engl. preperitoneal pelvic
PPP – preperitoneal pelvic packing
packing)
REBOA – reanimacijska endovaskularna balonska okluzija aorte (engl. REBOA – resuscitative endovascular balloon occlusion of the aorta
resuscitative endovascular balloon occlusion of the aorta)
Sukob interesa: Nije prijavljen. Conflict of interest: None declared.
Dabetić U. i sar.
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ZNAČAJ MULTIDISCIPLINARNOG DIJAGNOSTIČKOG I TERAPIJSKOG
PRISTUPA SINDROMU BOLNE SIMFIZE SPORTISTA
STRUČNI RAD PROFESSIONAL ARTICLE
THE IMPORTANCE OF A MULTIDISCIPLINARY
DIAGNOSTIC AND THERAPEUTIC APPROACH TO
PAINFUL SYMPHYSIS SYNDROME IN ATHLETES
Katarina Vukosavljević1,2, Miloš Bojović2, Dragana Drljačić2, Kristina Vukušić2
1
2
Visoka sportska i zdravstvena škola, Beograd, Srbija 2
College of Sports and Health, Belgrade, Serbia
SAŽETAK ABSTRACT
Sindrom bolne simfize sportista (pubalgija) je specifična povreda, bolno stanje Painful symphysis syndrome (pubalgia) in athletes is a particular injury, a painful
i disfunkcija femoro-ingvinalne regije, koje nastaje usled disproporcije snage condition, and dysfunction of the femoroinguinal region, which occurs due to the
mišića trbušnog zida i mišića donjih ekstremiteta. Cilj ovog rada jeste da se te- disproportion in strength between the abdominal wall muscles and the muscles
orijski razmotri značaj multidisciplinarnog dijagnostičkog i terapijskog pristupa of the lower extremities. This study aims to theoretically analyze the importance
sindromu bolne simfize sportista. U literaturi je izneto više od 70 uzroka nastanka of a multidisciplinary diagnostic and therapeutic approach to painful symphysis
pubalgije, pri čemu su oni koji su uslovljeni sportskim činiocima najzastupljeniji. syndrome in athletes. More than seventy causes of pubalgia have been present-
Aktivnosti koje uključuju ponavljajuće snažne udarce nogama, pokrete rotacije, ed in literature, most commonly linked to sports factors. Activities that include
cirkumdukcije i torzije predstavljaju faktore rizika. Sindrom je najpre registro- repetitive strong kicks, rotational movements, circumduction, and torsion, are
van kod fudbalera, a uglavnom se javlja kod sportista muškog pola, mlađih od risk factors. The syndrome was first registered in football players, and it mostly
40 godina. Postavljanje dijagnoze je teško zbog složene anatomije i preklapanja occurs in male athletes under the age of forty. Establishing a diagnosis is difficult,
simptoma među različitim povredama prepona. Terapijski pristup je uslovljen due to the complex anatomy and the overlapping of symptoms between different
složenošću povreda i dinamikom oporavka pacijenta. Podrazumeva poštovanje groin injuries. The therapeutic approach depends on the complexity of the inju-
principa započinjanja lečenja minimalno invazivnim modalitetima, pri čemu je za ries and the dynamics of the patient's recovery. It entails observing the principles
krajnji terapijski pristup rezervisan operativni tretman, nakon kog je neophodno of initiating treatment with minimally invasive modalities and reserving surgical
sprovesti odgovarajući rehabilitacioni program, u skladu sa bolom i dinamikom treatment as the final therapeutic option, after which it is necessary to conduct
oporavka. Najveći broj sportista se nakon dva do tri meseca vraća na teren, pri an appropriate rehabilitation program, tailored to the pain and the dynamics of
čemu recidivi nakon operativnog lečenja praktično nisu registrovani. No, s ob- recovery. Most athletes resume their sports activities after two to three months,
zirom na to da kod nastanka pubalgije dolazi do onesposobljavanja u sportskim with no recurrence of pubalgia after surgical treatment. However, bearing in
aktivnostima u prolongiranom periodu, posebnu pažnju treba posvetiti preven- mind that the occurrence of pubalgia prevents the patients from engaging in
ciji nastajanja ovog bolnog sindroma. S tim u vezi, s prevencijom treba započeti sports activities over a prolonged period, special attention should be directed
u najranijim uzrastima, sprovođenjem svakodnevnog programa vežbi jačanja towards the prevention of this painful syndrome. Taking this into consideration,
mišića prednjeg trbušnog zida, s posebnim akcentom na kose i poprečne trbušne prevention should begin at the earliest age, through a daily program of exercises
mišiće. for strengthening the muscles of the anterior abdominal wall, with special em-
phasis on the oblique and transverse abdominal muscles.
Ključne reči: pubalgija, sportske aktivnosti, povreda, rehabilitacija.
Key words: pubalgia, sports activities, injury, rehabilitation.

Katarina Vukosavljević Katarina Vukosavljević
Visoka sportska i zdravstvena škola College of Sports and Health
Toše Jovanovića 11, 11030 Beograd, Srbija 11 Toše Jovanovića Street, 11030 Belgrade, Serbia
Elektronska adresa: katarina.vukosavljevic@vss.edu.rs E-mail: katarina.vukosavljevic@vss.edu.rs
Primljeno • Received: September 27, 2021; Revidirano • Revised: February 27, 2022; Prihvaćeno • Accepted: March 15, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-34160
značaj multidisciplinarnog dijagnostičkog i terapijskog pristupa sindromu bolne simfize sportista
Vukosavljević K. i sar.
the importance of a multidisciplinary diagnostic and therapeutic approach to painful symphysis syndrome in athletes
UVOD INTRODUCTION
Sindrom bolne simfize sportista prvi put je detaljno Painful symphysis syndrome in athletes was, in detail,
opisao Spineli, 1932. godine, ali se u literaturi pronala- first described by Spinelli, in 1932, but literature also
zi i da ga je Gilmor, 90-ih godina 20. veka, nazvao Gil- shows that, in the 1990s, Gilmore named this syndrome
morove prepone. Sinonimi koji se u literaturi još mogu Gilmore’s groin. Other synonymous names for the con-
sresti su i: bol u preponama, sindrom simfize, pubalgi- dition, also found in literature, are as follows: symphysis
ja, atletska pubalgija, sindrom stidne ingvinalne boli, syndrome, pubalgia, athletic pubalgia, pubic inguinal
prepona sportista, kompleksna povreda prepona fud- pain syndrome, sports-men’s groin, footballers groin
balera, sindrom hokejaša, atletska kila i preponski ras- injury complex, hockey player’s syndrome, athletic her-
cep [1]. nia, and inguinal disruption [1].
Atletska pubalgija je specifična anatomska povre- Athletic pubalgia is a particular anatomical injury,
da, a ne široka kategorija nalaza, te treba naglasiti da and not a broad category of findings, which is why it
patološka dijagnoza, poput ingvinalne kile, ne isključu- must be emphasized that a pathological diagnosis, such
je prisustvo ovog sindroma. Izrazi kao što su sportska as inguinal hernia, does not exclude the presence of this
kila ili hernija sportista, danas često korišćeni u profesi- syndrome. Terms such as athletic hernia or sports-men’s
onalnim krugovima, dovode do problema u razlikova- hernia, used customarily in professional circles today,
nju anatomskih obrazaca povreda i nalaza pri dijagno- cause problems in distinguishing amongst anatomical
stici. Sindrom je prvo zabeležen kod fudbalera (poznat injury patterns and findings in the diagnostic process.
kao „fudbalerske prepone“), a vremenom je opisan i The syndrome was first registered in footballers (known
kod ostalih sportista, naročito kod onih čije aktivnosti as ‘footballers groin’) and, with time, it was described in
podrazumevaju prekomernu upotrebu mišića donjeg other athletes, especially in those whose activities re-
dela trbuha i proksimalne muskulature donjih ekstre- quire the excess use of the lower abdominal wall muscles
miteta. and the proximal musculature of the lower extremities.
Razmatrajući pubalgiju sa kliničko-anatomskog as- Viewing pubalgia from the clinical and anatomical
pekta, do izražaja dolazi značaj koštano-mišićne ana- aspect, the significance of the skeleto-muscular anato-
tomije ove regije. Pored kostiju (oba femura, sakralne my of this region becomes evident. In addition to the
i kokcigealne kosti) u anatomski značajan obrazac bones (both femoral bones, the sacral and coccygeal
uvršteni su i prednje bočni trbušni mišići (m. obliquus bones), the muscles of the anterolateral abdominal wall
externus abdominis, m. obliquus internus abdominis, (m. obliquus externus abdominis, m. obliquus internus ab-
m. transversus abdominis, m. rectus abdominis), kao i dominis, m. transversus abdominis, m. rectus abdominis)
unutrašnji mišići buta – primicači buta, (m. pectineus, as well as the inner thigh muscles – the adductors (m.
m. gracilis, m. adductor longus, m. adductor brevis, m. pectineus, m. gracilis, m. adductor longus, m. adductor
adductor magnus). Svi ovi mišići imaju svoje pripoje na brevis, m. adductor magnus) are also a part of the an-
preponskoj kosti i pubičnoj simfizi, dok su od najvećeg atomically significant framework. All of these muscles
značaja za održavanje stabilnosti karlice u sagitalnoj have their insertions on the pubic bone and the pubic
ravni m. rectus abdominis i m. adductor magnus [2,3]. symphysis, while the m. rectus abdominis and m. adduc-
Imajući u vidu da su povrede prepona česta pojava tor magnus have the greatest importance in maintain-
kod sportista i da one čine 6% svih sportskih povreda ing the stability of the pelvis in the sagittal plane [2,3].
[4], a ujedno uzimajući u obzir i činjenicu da su neret- Bearing in mind that groin injuries are a frequent
ko i pogrešno interpretirane, cilj ovog rada jeste teorij- occurrence in athletes, as well as the fact that they ac-
sko razmatranje značaja multidisciplinarnog dijagno- count for 6% of all sports injuries [4], and, at the same
stičkog i terapijskog pristupa sindromu bolne simfize time, taking into account the fact that these injuries
sportista. are relatively frequently misinterpreted, the aim of this
paper is the theoretical analysis of the significance of a
ETIOLOGIJA I ETIOPATOGENEZA multidisciplinary diagnostic and therapeutic approach
U literaturi je opisano više od 70 uzroka pubalgije. Na to the painful symphysis syndrome in athletes.
osnovu klasifikacije, koju je, 1999. godine, predložio
Benaco (Benazzo), uzroci pubalgije mogu se donekle
ETIOLOGY AND ETIOPATHOGENESIS
proizvoljno grupisati, prateći koristan metodološki pri- More than 70 causes of pubalgia have been described
stup, počevši od pubalgije uzrokovane preoptereće- in literature. Based on the classification proposed
njem pubične simfize (engl. rectus adductor symphysis by Benazzo, in 1999, the causes of pubalgia may be
syndrome), čija učestalost iznosi približno 40%. Nada- grouped, somewhat arbitrarily, by applying a use-
lje slede pubalgije uzrokovane parietoabdominalnom ful methodological approach, starting with pubalgia
Vukosavljević K. et al.
slabošću (sportska kila), sa učestalošću od oko 40% i, caused by pubic symphysis overstraining, i.e., rectus
konačno, pubalgije uzrokovane patološkim procesima, adductor symphysis syndrome, occurring in 40% of the
koje zahvataju susedne organe (karlicu i urogenitalni cases; followed by pubalgia caused by parietoabdom-
trakt), koje čine oko 20% slučajeva [5]. Sportski uzroci inal weakness (sports hernia), occurring in 40% of the
su najzastupljeniji u etiologiji ovog sindroma. Kod fud- cases; and finally, pubalgia caused by pathological pro-
balera, sindrom se javlja zbog ponavljanih napornih cesses, which involve the surrounding organs (pelvis
treninga, utakmica i nemogućnosti dobre restitucije. and urogenital tract), and which account for 20% of cas-
Zastupljen je i kod igrača hokeja na ledu, igrača ragbi- es [5]. Sports causes are the most frequent in the etiolo-
ja, trkača na duge staze, igrača australijskog fudbala, gy of this syndrome. In footballers, the syndrome occurs
igrača kriketa, itd. Navedeni sportovi podrazumevaju as the result of repeated strenuous workout and train-
ponovljene snažne udarce nogom, pokrete rotacije, ing sessions and football matches, as well as the play-
cirkumdukcije, torzije, i sl. Svi navedeni pokreti pred- ers’ inability to have sufficient rest and recuperation in
stavljaju faktore rizika za pojavu sindroma bolne sim- between these activities. The syndrome is also present
fize [6]. in ice hockey players, rugby players, long-distance run-
Sportisti sa dijagnozom sindroma bolne simfize su ners, players of Australian football, cricket players, etc.
uglavnom muškarci mlađi od 40 godina. Uopšteno, to The above-mentioned sports include repeated strong
se može objasniti činjenicom da se pripadnici muškog kicks, rotation, circumduction and torsion movements,
pola češće bave gore nabrojanim sportovima, koji nose etc. All of these movements represent risk factors for the
veći rizik za nastanak ovog bolnog sindroma. Drugi ra- development of painful symphysis syndrome [6].
zlozi leže u anatomskim razlikama između muške i žen- Athletes with the diagnosis of painful symphysis
ske karlice. Žene uglavnom imaju veći i robusniji kau- syndrome are mainly men under the age of 40. Gen-
dalni m. rectus abdominis na stidnoj simfizi, karlica im erally speaking, this can be explained by the fact that
je šira i ima veći potpubični ugao, što može rezultirati men more often engage in the sports listed above than
boljim usmeravanjem sila dalje od pubične regije. Sto- women, and these sports carry a greater risk for the de-
ga, anatomskim i biomehaničkim razlikama u strukturi velopment of this painful syndrome than other sports.
ženske karlice mogla bi se objasniti bolja stabilizacija Other reasons originate from the anatomical differenc-
stidne regije i smanjeni rizik od pubalgije, u žena [3]. es between the male and female pelvis. Women usually
Načelno gledano, do bola pri ovom sindromu do- have a larger and more robust caudal m. rectus abdom-
lazi zbog disproporcije snage mišića trbušnog zida i inis on the pubic symphysis, their pelvis is wider, and it
mišića donjih ekstremiteta, kao i elastičnosti pubične has a wider subpubic angle, which may result in better
simfize, koja joj omogućava kretanje do 2 milimetra i transfer of forces away from the pubic region. There-
rotaciju do 3 stepena [3]. Ova neravnoteža dovodi do fore, the anatomical and biomechanical differences in
osećaja bola u dubini prepona. Na temelju toga, ovaj the structure of the female pelvis may be the explana-
bi se entitet mogao preimenovati u „sindrom mišićne tion regarding the better stabilization of the pubic re-
neravnoteže prepona“, a sportska kila mogla bi se sma- gion and the decreased risk of pubalgia in women [3].
trati nalazom uključenim u ovaj sindrom [7]. Mehani- Generally speaking, the pain occurring in this syn-
zam nastanka simptoma se objašnjava stalnim silovi- drome, occurs due to a disproportion between the
tim kontrakcijama koje se prenose na pripoje mišića strength of the abdominal wall muscles and the mus-
u ovim regijama, stvarajući oštećenje subhondralne cles of the lower extremities, as well as the elasticity of
vaskularizacije u predelu pubične kosti, što potenci- the pubic symphysis, which enables movement of up
jalno posledično uslovljava nastanak njene aseptične to 2 mm and rotation of up to 3 degrees [3]. This imbal-
nerkoze. Ovaj proces, u daljem toku, izaziva nespecifič- ance leads to the sensation of pain, deep in the groin.
no zapaljenje, pre svega na insercijama mišića. Opisani Based on the above stated, this entity could be re-
mehanizam uslovljava i patološki proces na pripojima named as ‘muscular groin imbalance syndrome’, while
mišića na pubisu, dok je u kasnijoj fazi primećeno ra- athletic hernia could be considered as a finding includ-
zvijanje osteoporoze pubičnih kostiju [8]. ed in this syndrome [7]. The mechanism of the develop-
ment of symptoms is explained by constant powerful
SIMPTOMI I KLINIČKI ZNACI contractions, which radiate to the muscular insertions
Većina bolesnika sa pubalgijom ima simptome meseci- in these regions, creating damage to the subchondral
ma ili godinama pre postavljanja prave dijagnoze. Prvi vascularization in the area of the pubic bone, which
simptomi se obično javljaju nakon izvesnog napora i potentially causes the consequential development of
naknadnog odmora bolne regije. Bol se uglavnom ma- its aseptic necrosis. This process further causes nonspe-
nifestuje prilikom hoda po strmim terenima. Sportista, cific inflammation, primarily in the muscular insertions.
pri takvoj vrsti hoda, zauzima prinudan antalgičan stav, The described mechanism also brings about the patho-
sa kukovima u fleksiji. Bol u predelu simfize se može logical process in the muscular insertions on the pubis,
javiti i/ili pogoršati aktom defekacije, kijanja i kašljanja. while, in the later phase, the development of pubic
Bolovi su u početku u najvećoj meri podnošljivi, dok u bone osteoporosis has been noticed [8].
daljem toku mogu u potpunosti da onesposobe igra-
če. Pacijenti se obično žale na jednostrani dubok i oštar SYMPTOMS AND CLINICAL SIGNS
bol u donjem delu trbuha i prednjem delu prepona. Most patients with pubalgia experience symptoms for
Bol može zračiti proksimalno na bedra, krsta, ali i u mi- months or even years before they get the correct diag-
šiće donjeg dela trbuha, perineum ili skrotum [9]. Više nosis. The first symptoms usually occur after a certain
studija je pokazalo da je najveći broj igrača pre pojave amount of strain and subsequent rest of the painful
bola odigrao tri do četiri zahtevna meča u toku nedelje, region. The pain mainly manifests when walking on
bez dovoljno vremena za oporavak između njih. Nakon steep terrains. The athlete, when walking in such a
intenzivnog treninga ili meča, sportista ima poteškoće way, is forced to assume the antalgic gait, with hips in
u hodanju, posebno pri penjanju uz stepenice. U kre- flexion. The pain in the symphysis area may occur and/
vetu obično leži sa strane, savijenih kukova i kolena, uz or become worse upon defecation, sneezing or cough-
poremećen ritam sna. Ustajanje sa stolice i iz kreveta je ing. In the beginning, the pain is mostly tolerable,
veoma bolno [10]. while as the condition develops, it may completely in-
capacitate the player. The patients usually complain of
DIJAGNOSTIČKI KRITERIJUMI unilateral deep and sharp pain in the lower abdomen
Dijagnoza pubalgije je teška zbog složene anatomije and in the frontal part of the groin. The pain may radi-
i preklapanja simptoma različitih povreda prepona. ate proximally to the thighs, lower back, but also to the
Klinički pregled i istorija bolesti su od najveće važ- muscles of the lower abdomen, to the perineum, or the
nosti. Kliničar mora uzeti u obzir činjenicu da sportisti scrotum [9]. A number of studies have shown that, pri-
sa bolovima u preponama mogu imati više od jedne or to the occurrence of pain, most players had played
dijagnoze, dok prisutnost jedne od ovih povezanih di- in three to four challenging games in one week, with-
jagnoza ne isključuje dijagnozu pubalgije. Preporuka out enough time to rest in between these matches.
je da se ovom entitetu pristupi sa multidisciplinarnog After an intense game or training session, the athlete
aspekta, s obzirom na to da dosadašnja literatura ne has difficulty walking, especially when climbing stairs.
pruža odgovarajuće dijagnostičke studije i preporuke When in bed, the athlete usually lies on their side, with
za ispravno lečenje, koje bi trebalo sprovesti kod ovih hips flexed and knees bent, with a disturbed sleeping
pacijenata [7]. Predložena je klasifikacija simptoma na rhythm. Standing up from a chair or from the bed is
nivou prepona u tri velike kategorije kliničkih sindro- very painful [10].
ma (Slika 1) [11].
Prvi korak u postavljanju dijagnoze jeste uzimanje DIAGNOSTIC CRITERIA
adekvatne i detaljne anamneze o bolu (kada se javlja, Diagnosing pubalgia is difficult due to the complex anat-
koliko traje, tačna lokalizacija bola, propagacija, jačina, omy and the overlapping of symptoms of different groin
pridruženi simptomi, i slično). Fizikalni pregled atletske injuries. The clinical examination and the medical history
pubalgije, kao sledeći bitni korak u dijagnostikovanju are of the utmost importance. The physician must take
sindroma, započinje palpacijom potencijalnih mesta into account the fact that athletes with groin pain may
povrede. Pregledom se može pronaći palpatorna bol- have more than one diagnosis and that the presence of
na osetljivost na mestu pripoja aduktora natkolenice, one of these related diagnoses does not necessarily ex-
na pripoju Pupartovog ligamenta, kao i na mestu spoja clude pubalgia. The recommendation is to approach this
dve pubične kosti. U ingvinumu se mogu napipati i lim- entity from a multidisciplinary aspect, since literature so
fne žlezde koje su izrazito bolne na dodir. Tokom kon- far does not offer the appropriate diagnostic studies and
trakcije trbušnog zida, u stojećem ili ležećem položaju, recommendations for the proper treatment to be ap-
moguće je uočiti znak slabosti kosih i poprečnih mišića plied in these patients [7]. A classification of symptoms
trbušnog zida i njegove aponeuroze – Malgenjijev ka- pertaining to the groin area into three major categories
pitalni znak. Ovaj znak predstavlja pojavu vretenastog of clinical syndromes has been proposed (Figure 1) [11].
izbočenja koje se proteže od pubisa do prednje-gor- The first step in establishing the diagnosis is taking
nje bedrene bodlje (lat. spina iliaca anterior superior). the appropriate and detailed anamnesis on the report-
Istovremeno, ovaj znak pokazuje slabost i atoniju po- ed pain (when it occurs, how long it lasts, the exact lo-
prečnih mišićnih vlakana prednjeg trbušnog zida [8]. calization of the pain, pain propagation, pain intensity,
Abdukcija kuka je ograničena bolovima nastalim usled associated symptoms, etc.). The physical examination of
POREMEĆAJI PREPONSKE REGIJE / DISORDERS OF THE GROIN
KLASIČNA HERNIJA / OKULTNE POVREDE PREPONA / OSTALI DIJAGNOSTIČKI KRITERIJUMI /

CLASSIC HERNIAS OCCULT GROIN INJURIES OTHER DIAGNOSTIC ENTITIES
Atletska pubalgija / Sportska hernija / Osteitis pubis / • Poremećaji kuka / Hip disorders
• Ingvinalna hernija /
Athletic Pubalgia Sports Hernia Osteitis Pubis • Avaskularna nekroza / Avascular Necrosis
Inguinal Hernia
− direktna / Direct • Škljocajući kuk / Snapping Hip
− indirektna / Femoral • Sindrom atletske pubalgije / Athletic • Stres frakture / Stress Fractures
• Hernija sportska /
Hernia Pubalgia Syndrome • Karlice / Pelvis
Sportmans Hernia
• Femoralna hernija / • Gilmorove prepone / Gilmores Groin • Kuka / Hip
Femoral Hernia • Sindrom pimfize / Symphysis • Atletska hernija / • Tumori/Maligniteti / Tumors/Malignancies
• Obturatorna hernija / Syndrome Athletic Hernia • Kompresivne neuropatije / Nerve Entrapment disorders
Obturator Hernia • Sindrom hokejaških prepona / Hockey • Poremećaji kičme / Spinal disorders
• Početna hernija /
Groin Syndrome • Sedalnopreponski burzitis / Ischiopectineal Bursitis
Incipient Hernia
• Sindrom hokejaškog golmana • Gastrointestinalni/Urogenitalni/Ginekološki poremećaji
- bejzbool igrača / Hockey Goalie - • Okultna ingvinalna / Gastro/ urogenital/ Ginecological disorders
Baseball Pitcher Syndrome hernija / Oculte • Duboki glutealni sindrom (sindrom piriformisa) / Deep
• Sindrom aduktora / Adductor Inguinal Hernia Gluteal Syndrome (Pyriformis Syndrome)
Syndrome • Avulzione povrede (adolescentne apofizijalne povrede) /
• Tendonitis m. adduktor longus-a / Avulsion injuries (adolescent apophysea injuries)
Adductor Longus Tendonitis • Akutna mišićno/ tetiva istegnuća / Acute muscule/
• Sindrom m. adduktor gracilis-a / tendon strains
Adductor Gracilis Syndrome
Slika 1. Klasifikacija simptoma poremećaja preponske regije (modifikovano Figure 1. Classification of symptoms of inguinal region disorders (modified ac-
prema: Gerhardt, Brown, Giza) [11] cording to Gerhardt, Brown, Giza) [11]
istezanja aduktora. Adukcija i abdukcija u kuku su bol- athletic pubalgia, as the next important step in the diag-
ne. Aktivno podizanje noge u spoljašnjoj rotaciji sa nosis of the syndrome, begins with the palpation of the
kolenom u punoj ekstenziji vrlo je bolno i obično nije potential injury sites. Palpatory painful sensitivity ca be
izvodljivo [10]. detected through physical examination at the site of the
Opisani su i specifični testovi provokacije za mišiće insertion of the adductors of the thigh, at the insertion
aduktore i mišiće prednjeg trbušnog zida. Test aduktora of Poupart’s ligament, as well as at the meeting point of
je od velike važnosti za fizikalni pregled. Pri ovom testu, the two pubic bones. In the ingenium, lymph nodes can
pacijent leži na leđima sa kukovima u abdukciji i u flek- also be palpated and they are extremely painful to the
siji od 80 stepeni. Test je pozitivan ako pacijent, dok po- touch. During the contraction of the abdominal wall,
kušava da povuče noge protiv otpora (koje lekar pruža) when the patient is standing or lying down, it is pos-
u suprotnom smeru, oseća oštar bol u preponama [12]. sible to note the signs of weakness of the oblique and
Sa druge strane, Kačingve i saradnici su klasifikovali pet transverse abdominal wall muscles as well as of the ab-
kliničkih znakova koji mogu ukazati na atletsku pubal- dominal wall aponeurosis – Malgaigne's sign. This sign is
giju: 1) subjektivna nelagodnost zbog bolova duboko represented by the presence of a spindle shaped buldge
u preponama /bolova u donjem delu trbuha; 2) bol se extending from the pubis to the anterior superior iliac
pogoršava povećanjem napora (sprint, “trbušnjaci”) a spine (lat. spina iliaca anterior superior). At the same time,
ublažava se odmorom; 3) palpatorna osetljivost pubič- this sign indicates the weakness and atonia of the trans-
nog ramusa na mestu pripoja m. rectus abdominisa i/ili verse muscle fibers of the anterior abdominal wall [8].
pripojne tetive; 4) bol pri otporu prilikom adukcije kuka The abduction of the hip joint is limited by the pain aris-
uz fleksiju od 45 i/ili 90 stepeni; 5) bol prilikom pružanja ing from the stretching of the adductors. The adduction
otpora tokom rotacije abdomena [13,14]. and abduction of the hip are painful. Active lifting of the
Regionalni pregled je od izuzetne važnosti u suža- leg in external rotation with the knee in full extension is
vanju diferencijalne dijagnoze. Lumbalni deo kičme- very painful and usually not possible for the patient [10].
nog stuba, sakroilijačni zglobovi i zglobovi kukova mo- Particular muscle provocation tests for adductors
raju se funkcionalno ispitati. Istovremeno, simfiza se is- of the anterior abdominal wall have been described.
pituje u pravcu nestabilnosti i osetljivosti, jer je osteitis The testing of the adductors is of great importance
pubične kosti relativno čest nalaz u atletskoj popula- for the physical examination. In this test, the patient
ciji. Pripoji mišića (uključujući aduktore, kao i m. rectus is lying supine with the hips in abduction and flexed
femoris, m. sartorius, rectus abdominis) palpiraju se na at 80 degrees. The test is positive if the patient, while
bolnu osetljivost. U pokušaju provociranja simptoma, attempting to pull the legs against the resistance in
isti mišići se testiraju i na otpor. Pacijent se pregleda the other direction (exerted by the doctor), feels sharp
i u stojećem i u ležećem stavu kako bi se utvrdilo pri- pain in the groin [12]. On the other hand, Kachingwe et
sustvo ingvinalne ili femoralne kile. Kod pacijentkinja al. made a classification comprising the following five
može biti potreban i ginekološki pregled [15]. clinical signs that may indicate athletic pubalgia: 1) sub-
Kineziološkom analizom, kod svih pacijenata je jective discomfort caused by pain deep in the groin/
ustanovljena slabost prednjeg trbušnog zida (i to spe- pain in the lower abdomen; 2) pain which increases
cijalno kosih trbušnih mišića) sa ocenom, po manuel- with the increase of exertion (sprinting, crunches/sit-
nom mišićnom testu, dva od pet (MMT = 2/5). Aduktori ups) and decreases with rest; 3) palpatory sensitivity of
kuka su takođe oslabljeni kod ovih pacijenata, ali pre the pubic ramus at the insertion site of the m. rectus
svega zbog neaktivnosti [8]. abdominis and/or the insertion tendon; 4) pain when
Zbog svega do sada navedenog, kao i zbog specifič- resistance is exerted in hip adduction with a flexion of
ne kliničke slike i preklapajućih simptoma između pu- 45 and/or 90 degrees; 5) pain when offering resistance
balgije i ostalih bolova u preponama, korisno je uraditi during the rotation of the abdomen [13,14].
neku od vizualizacionih dijagnostičkih tehnika, kako bi The regional examination is exceptionally import-
se isključili drugi uzroci bola [4,16]. Mogu biti od kori- ant in narrowing down the differential diagnosis. The
stiti sledeće tehnike: radiografija, ultrazvuk, magnetna lumbar segment of the spinal column, the sacroiliac
rezonanca (MR), kao i kompjuterizovana tomografija joints, and the hip joints must be functionally tested.
(CT). Na radiografskom nalazu se kod ovog sindroma At the same time, the symphysis is tested for instabil-
može uočiti sledeća evolucija koštanih promena: proli- ity and sensitivity, as pubic bone osteitis is a relatively
feracija kostiju na jednoj ili obe strane, erozije na rubo- frequent finding in the population of athletes. Muscle
vima pubičnih kostiju, dijastaza simfize (razdvojenost insertions (including adductors, as well as m. rectus
pubičnih kostiju), asimetrija simfize, hipertrofija stid- femoris, m. sartorius, rectus abdominis) show painful
nih grebenova, pojava regionalnih slobodnih koštanih sensitivity to palpation. In order to elicit symptoms,
tela, zone demineralizacije i kondenzacije. the same muscles are tested for resistance. The patient
Progresijom bolesti, evolucija znakova je jasnija, lako is examined both in the standing position and when
se otkrivaju i u korelaciji su sa simptomima i nalazom lying down, in order to determine the presence of in-
prilikom pregleda. Radiografski nalaz je sličan onome guinal or femoral hernia. In female patients a gyneco-
koji se uočava kod avaskularne nekroze kostiju [10]. Ul- logical examination may be necessary as well [15].
trazvuk je sa izvesnošću od 92% pouzdan u pronalaže- Kinesiological analysis has found, in all patients, a
nju sigurnih znakova preponske kile i omogućava dobar weakness of the anterior abdominal wall (especially
uvid u očuvanost mekih tikva, prisustvo burzi, kalcifika- oblique abdominal muscle weakness), with a manual
cija ili nekih tumefakcija. Kompjuterizovana tomografija muscle test score of two out of five (MMT = 2/5). Hip
pomaže u identifikaciji nedostataka zadnjeg zida ingvi- adductors are also weakened in these patients, but pri-
nalnog kanala i prisustva kile [7]. Magnetna rezonanca marily due to the lack of activity [8].
ima izvrstan dijagnostički potencijal za atletsku kilu i Due to all that has been stated so far, but also due
može ukazati na abnormalnosti u mišićno-fascijalnim to the particular clinical presentation and the overlap-
slojevima trbušnog zida, koje usko koreliraju sa nalazom ping of the symptoms of pubalgia and the symptoms
hirurga prilikom pregleda. Takođe, pruža i mogućnost vi- of other conditions involving groin pain, it is useful to
zualizacije edema uzrokovanog neuravnoteženom kon- carry out one of the diagnostic imaging techniques, in
trakcijom mišića i njihovih pripoja na pubičnoj simfizi order to exclude other causes of pain [4,16]. The follow-
[15]. Pored navedenih, pouzdana ali invazivna dijagno- ing techniques may be useful: radiography, ultrasound,
stička procedura jeste laparoskopija, koja objedinjuje sli- magnetic resonance imaging (MR), as well as comput-
ku unutrašnjosti abdomena i mogućnost istovremenog ed tomography (CT). The following evolution of bone
hirurškog lečenja uočenog problema [13]. change can be detected on radiographic images: unilat-
eral or bilateral bone proliferation, erosion on the rims
DIFERENCIJALNA DIJAGNOZA of the pubic bones, diastasis symphysis pubis (pubic
Iako se pod pojmom sportiste najčešće podrazumeva symphysis separation), symphysis asymmetry, hyper-
zdrava mlada osoba, ne treba zanemariti ozbiljna sta- trophy of the pubic crest, the presence of regional loose
nja koja pokazuju sličnu simptomatologiju (aneurizma bodies, demineralization and condensation zones.
abdominalne aorte, diskus hernija u nivou L2 kičmenog With the progression of the disease, the evolution of
pršljenja, koja daje iradirajući bol u prepone, rak prosta- the signs becomes clearer, they are more easily detected
te, metastatske promene na strukturama male karlice, and are in correlation with the symptoms and the findings
ciste na jajnicima, vanmaterična trudnoća, kompresiv- established during the examination. The radiographic
ne frakture slabinskih pršljenskih tela, itd.). Postavljanje image is similar to the one which can be seen in avascu-
tačne dijagnoze je bitno iz više razloga. Prvi i najvažniji lar necrosis of the bone [10]. Ultrasound is 92% reliable in
je da, ukoliko je reč o ozbiljnoj dijagnozi (poput ma- detecting definitive evidence of inguinal hernia and pro-
ligniteta ili aneurizme abdominalne aorte) osoba ne vides good insight into the condition of the soft tissues,
izgubi dragoceno vreme, već da se odmah pristupi as well as into the presence of bursae, calcifications, or tu-
lečenju. Budući da simptomi deluju bezazleno i najče- mefactions. Computed tomography helps in identifying
šće podnošljivo, sportisti ne žele da gube vreme pro- the defects in the posterior wall of the inguinal canal and
puštajući važna takmičenja i treninge. Međutim, zbog the presence of hernia [7]. Magnetic resonance imaging
svega navedenog, nikako ne treba žuriti sa dijagnozom has excellent diagnostic potential in relation to athletic
i preskakati određene procedure, jer posledice pogreš- hernia and may reveal abnormalities in the musculo-fas-
nog terapijskog pristupa mogu biti nepopravljive. U cial layers of the abdominal wall, which closely correlate
okvirima diferencijalne dijagnoze mogu se razmatrati with the surgeon’s finding on examination. Also, it offers
i sledeća oboljenja/stanja: osteitis pubis, osteomijelitis, the opportunity of visualizing the edema caused by un-
osteom, osteohondrom, tuberkuloza, sarkoidoza, he- even contractions of the muscles and their insertions on
mohromatoza, reumatska bolest, traumatska povreda the pubic symphysis [15]. In addition to the described
simfize, intraartikularna/ekstraartikularna patologija techniques, a reliable but also invasive procedure is lap-
kuka i intraabdominalnog prostora, femoroacetabular- aroscopy, which unites the imaging of the inside of the
ni impindžment (FAI), cepanje labruma acetabuluma, abdomen with the possibility of surgically treating the
povrede mišića aduktora, i drugo [10,17]. detected problem at the same time [13].
TERAPIJSKI PRINCIPI DIFFERENTIAL DIAGNOSIS

Tek nakon postavljanja sigurne dijagnoze, pribegava Although athletes are most commonly young healthy
se terapiji, koja ima dva pristupa – konzervativni i ope- individuals, serious conditions displaying similar symp-
rativni. U okvirima konzervativne terapije, u lečenju toms (abdominal aortic aneurism; discus hernia at the
ovog bolnog sindroma je na prvom mestu mirovanje, level of the L2 vertebra, which produces pain that irra-
odnosno prekid treninga. Ova mera može trajati od 3 diates into the groin; prostate cancer; metastatic lesions
do 12 meseci, zavisno od težine povrede i dinamike in the structures of the lesser pelvis; ovarian cysts; ecto-
oporavka. Za lečenja inflamacije i bolova, primenjuje pic pregnancy; compressive fractures of the bodies of
se lokalna i sistematska farmakološka terapija u kom- the lumbar vertebrae, etc.) mustn’t be overlooked. Es-
binaciji sa fizikalnom terapijom. tablishing the precise diagnosis is important for several
reasons. The first and most important one is that, if the
FIZIKALNA TERAPIJA I REHABILITACIONI diagnosis is serious (such as malignancies or abdominal
PROGRAM aortic aneurism) the patient should not waste precious
Postupna fizikalna terapija u kombinaciji s farmako- time but be treated immediately. As the symptoms usu-
terapijom (antiinflamatorni lekovi i miorelaksansi) ally seem harmless and usually bearable at the start,
jeste delotvorna u većini slučajeva. Rehabilitacija je athletes do not want to waste time and miss out on im-
prvi izbor lečenja za većinu pacijenata iz ove grupe. portant competitions and training sessions. However,
Najčešće podrazumeva fizikalne agense poput ma- due to all the above stated, the diagnosis must not be
gnetoterapije, ultrazvuka, transkutane električne rushed, nor should certain procedures be omitted, as the
nervne stimulacije, laseroterapije, galvanske struje, consequences of the wrong therapeutic approach may
neuromuskularnog tejpinga, akupunkture i kinezi- be irreparable. As a part of the differential diagnosis, the
terapijskog tretmana (kada bol i funkcionalni status following diseases/conditions may be considered: oste-
pacijenta to dozvole). Međutim, tretman treba da itis pubis, osteomyelitis, osteoma, osteochondroma, tu-
bude individualan i zasnovan na nivou utreniranosti berculosis, sarcoidosis, hemochromatosis, rheumatic dis-
svakog sportiste, vremenskom periodu neophodnom ease, traumatic injury to the symphysis, intraarticular/ex-
da se sportista vrati u igru, kao i trajanju sportske se- traarticular pathology of the hip and the intraabdominal
zone. Tretman se najpre sastoji od odmora, aktivne space, femoroacetabular impingement (FAI), acetabular
mobilizacije mekog tkiva u slučaju zatezanja mišića, labral tear, injury to the adductor muscles, etc. [10,17].
kao i zglobne manipulacije karličnog, sakroilijačnog
zgloba i zgloba kuka, koje mogu biti korisne u sma- TREATMENT PRINCIPLES
njenju bola povezanog sa disfunkcijom [13,18]. Tera-
Only after establishing a definitive diagnosis can treat-
pijski ultrazvučni tretmani, hladne kade i duboka ma-
ment be started. There are two treatment approach-
saža prepona takođe mogu biti korisni.
es – conservative treatment and surgical treatment.
Jedan od prvih ciljeva nakon smanjenja bola jeste
Within conservative treatment, resting, i.e., cessation
rad na opravku i poboljšanju obima pokreta. Nakon
of training is the most important. This measure can last
toga, terapija se sastoji od vežbi za jačanje centralne
from 3 to 12 months, depending on the severity of the
muskulature, koje su pre svega usmerene na abdomen,
injury and the rate of recovery. Localized and systemic
lumbalnu kičmu i kukove. Uključuju se vežbe istezanja
pharmacotherapy combined with physical therapy is
i jačanja mišića aduktora, mišića trbušnog zida, m. ili-
applied to treat the inflammation and pain.
opsoas-a, m. quadriceps femoris-a i pripadajućih tetiva.
Cilj terapije jeste uspostavljanje ravnoteže stabilizatora PHYSICAL THERAPY AND REHABILITATION
mišića kuka i karlice. PROGRAM
Sledeći presudni deo rehabilitacije jeste nervno-mi-
šićna reedukacija usredsređena na aduktore i trbušne Gradual physical therapy in combination with pharma-
mišiće, koja započinje kontrolisanim kontrakcijama m. cotherapy (antiinflammation drugs and myorelaxants)
transversus abdominis-a. Uz ove vežbe, dodaju se i vež- is effective in most cases. Rehabilitation is the treatment
be za mišiće karlice i gluteusa, kao i za m. multifidus (po- of first choice for most of the patients in this group.
sturalni stabilizator). Izuzetno je važno trenirati adukto- It most commonly involves physical agents such as
re u zatvorenom i otvorenom kinetičkom lancu, pobolj- magnetotherapy, ultrasound, transcutaneous electri-
šavajući propriocepciju, kao i izvođenje ko-kontrakcija cal nerve stimulation, laser therapy, galvanic currents,
posturalnih mišića, kako bi se uspostavila ravnoteža. neuromuscular taping, acupuncture, and kinesitherapy
Autogeno istezanje ima dvostruku funkciju: opuštanje (when pain and the functional status of the patient al-
uskih mišića i pomoć u propriocepciji [13,14,18]. Koor- low it). However, treatment needs to be individualized
dinacija i stabilizacija su od vitalnog značaja za reinte- and based on the level of fitness of each athlete, the
graciju pacijenta u sportske i svakodnevne aktivnosti time period necessary for the athlete to return to their
[18]. Ukoliko ove mere ne daju željeni efekat, treba raz- sports activities, as well as the duration of the sports
misliti o mogućnostima infiltracije lokalnih anestetika season. The treatment primarily comprises of rest, ac-
i kortikosteroida na bolno mesto. Svi navedeni vidovi tive mobilization of the soft tissue in case of muscle
terapije se mogu primenjivati u vidu monoterapije ili tightening, as well as of articular manipulations of the
se mogu kombinovati prema nalogu lekara. U literatu- pelvic, sacroiliac, and hip joints, which can be useful
ri zabeležen algoritam terapije pubalgije kod sportista in the alleviation of pain linked to dysfunction [13,18].
(Slika 2) upućuje u kom smeru treba razmišljati kada je Therapeutic ultrasound treatment, cold tubs, and deep
terapijski pristup ovom sindromu u pitanju [19]. tissue massage of the groin can also be useful.
Ukoliko nijedna od konzervativnih procedura na- Next to pain alleviation, one of the first goals is work-
kon najmanje tri meseca ne da odgovarajući efekat, ing on the recovery and improvement of the scope of
treba razmisliti o najinvazivnijem terapijskom pristu- movement. Following this, treatment consists of exer-
pu – hirurškom [20]. Postoje različite tehnike ovakvog cises for strengthening central musculature, which are
lečenja, pri čemu većina ima zebeležene zadovolja- primarily directed towards the abdomen, lumbar spine
vajuće rezultate. Principi operativnog lečenja uklju- and hips. Exercises of stretching and strengthening the
čuju procedure ojačavanja zadnjeg zida i fiksaciju m. adductor muscles, the muscles of the abdominal wall,
rectus abdominis-a ili njegove pripojne tetive. Druga the m. iliopsoas and m. quadriceps femoris, and of the
vrsta hirurškog lečenja je laparoskopska hirurgija (po- associated tendons are included. The aim of the treat-
stavljanje totalne ekstraperitonealne mreže iza stidne ment is establishing a balance amongst the stabilizer
kosti i/ili zadnjeg zida ingvinalnog kanala). Pajanen i muscles of the hip and pelvis.
saradnici, predočili su da je, u njihovoj studiji, laparo- The next crucial part of rehabilitation is neuromus-
skopska hirurgija pubalgije kod sportista bila efikasnija cular reeducation, focused on the adductors and ab-
od neoperativnog lečenja [21]. Nakon operacije, bol se dominal muscles. It starts with controlled contractions
smanjio nakon jednog meseca, dok se 90% operisanih of the m. transversus abdominis. Along with these, exer-
sportista u potpunosti vratilo sportskim aktivnostima, cises for pelvic and gluteal muscles are added, as well
nakon tri meseca. as exercises for the m. multifidus (postural stabilizer).
Operativno lečenje neophodno je sprovesti po It is exceptionally important to train the adductors
principu što ranije intervencije, jer su rezultati u tom in the open and closed kinetic chain, thus improving
Razmotriti mogućnost operacije

/ Symptoms resolve, return to
Za vreme sezone Rehabilitacija / sport
Sportista sa akutnim stanjem
bola u donjem delu stomaka / In season Rehabilitation
/ Athlete with acute event with Razmotriti mogućnost operacije
lower abdominal groin pain Razmotriti mogućnost ako se bol održava i 3-4 nedelje
Van sezone / Off season operacije nakon rehabilitacije
/ Consider Surgery / Consider surgery if conitnued
pain after 3-4 weeks rehabilitation
Istorija, znaci i simptomi
atletske pubalgije
Sportista sa poodmaklim Simptomi rešeni, povratak sportu
/ History, signs and
bolovima u donjem delu / Symptoms resolve, return to sport
symptoms of athletic Rehabilitacija /
pubalgia prepona Rehabilitation
/ Athlete with insidous onset Razmotriti mogućnost operacije ako se bol
lower abdominal groin pain održava i 3-4 nedelje nakon rehabilitacije
/ Consider surgery if conitnued pain after 3-4
weeks rehabilitation
Osoba koja nije sportista Rehabilitacija /

/ Non Athlete Rehabilitation
Slika 2. Terapijski algoritam atletske pubalgije (modifikovano prema: Cohen, Figure 2. Therapeutic algorithm of athletic pubalgia (modified according to Co-
Kleinhenz, Schiller, Tabaddor) [19] hen, Kleinhenz, Schiller, Tabaddor) [19]
proprioception, as well as to train the execution of
slučaju povoljniji. Kod operativnog lečenja, potrebno
co-contractions of the postural muscles, in order to
je ujednačiti sile obe mišićne regije, što je poznato
establish an equilibrium. Autogenous stretching has a
kao metoda mišićno-aponeurotične terapije, kojom
twofold function – relaxation of narrow muscles and
se ojačava trbušni zid i rasterećuju pripoji na pubisu.
support in proprioception [13,14,18]. Coordination
Jedna od najpoznatijih tehnika operativnog lečenja
and stabilization are of vital importance for enabling
sprovodi se po metodi Plastica telmentis abdominalis
the patient to resume sports and everyday activities
et canalis inguinalis secundum Bassini cum modificati-
[18]. If these measures do not produce the desired ef-
one Nešović, koja omogućava usklađivanje snage pe-
fect, infiltrating local anesthetics and corticosteroids
lvifemoralne lože mišića, posebno aduktora, i mišića
at the site of the pain should be considered. All of the
prednjeg trbušnog zida. Ovu tehniku je, 1967. godine,
described forms of treatment may be applied in the
uspešno predstavio dr Branislav Nešović (Beograd, Sr-
form of monotherapy, or they may be combined as per
bija) modifikujući do tada poznatu klasičnu tehniku
the doctor’s instructions. The therapeutic algorithm
operacije ingvinalne kile po Basiniju [8]. Pri operaci-
for pubalgia in athletes, recorded in literature (Figure
ji je potrebno zatvaranje ingvinalnog kanala i prav-
2), indicates the different therapeutic approaches that
ljenje novih prolaza za neurovaskularne elemente u
should be considered regarding this syndrome [19].
ovoj regiji [21].
If none of the conservative procedures, applied for
POSTOPERATIVNA REHABILITACIJA at least three months, does not yield the appropriate
effect, the most invasive therapeutic approach – sur-
Rehabilitacija nakon hirurškog zahvata podrazume- gery, should be considered [20]. There are different sur-
va postepenu vertikalizaciju i jačanje ciljnih mišićnih gical techniques for treating pubalgia, and for most of
grupa. Ukoliko oporavak ide po planu, fudbaleri se naj- them satisfactory results have been recorded. The prin-
češće vraćaju na teren nakon pet nedelja, pri čemu je ciples of surgical treatment include the procedures of
najbolji pokazatelj oporavka izostanak bola. Recidivi strengthening the posterior wall and the fixation of the
nakon operativnog lečenja praktično nisu registrovani, m. rectus abdominis or its insertion tendon. Another
tako da se postignuti rezultati mogu smatrati potpu- type of surgical treatment is laparoscopic surgery (fix-
nim uspehom u lečenju bolnog sindroma u regiji simfi- ation of a total extraperitoneal mesh behind the pubic
ze [10]. Za svakog pacijenta, posebno za sportistu, važ- bone and/or the posterior wall of the inguinal canal).
no je da kardiovaskularna izdržljivost ostane na istom Paajanen et al. reported that, in their study, laparoscop-
nivou ili da ona bude u poboljšanju nakon ponovnog ic surgery of pubalgia in athletes was more efficient
testiranja. Shodno tome, svaka sesija treba da započ- than non-operative treatment [21]. After the surgery,
ne određenim kardiovaskularnim vežbama. Program the pain decreased after a month, while 90% of all the
aktivnog treninga superioran je u fizioterapijskom le- surgically treated athletes completely returned to their
čenju [14]. sports activities, after three months.
It is necessary to carry out surgical treatment act-
PREVENCIJA ing on the principle of the earliest possible interven-
Zbog uvida u složenost terapijskog pristupa sindro- tion, as the results are, in such cases, more favorable. In
mu bolne simfize, neophodno je sprovoditi prevenciju surgical treatment, it is necessary to balance the forces
već u najranijim sportskim uzrastima. Ona se ogleda u exerted by both muscular regions, which is known as
sprovođenju vežbi jačanja mišića prednjeg trbušnog the method of musculoaponeurotic treatment, used to
zida i to po programu svakodnevnog treninga, uz po- strengthen the abdominal wall and relieve the inser-
seban akcenat na vežbe za kose i poprečne trbušne tions on the pubis. One of the best-known techniques
mišiće. Veoma su značajne i kontrakcije mišića bez op- of surgical treatment is carried out in keeping with the
terećenja. Ukoliko dođe do pojave bolnog sindroma, method – Plastica telmentis abdominalis et canalis in-
potrebno je što ranije započeti konzervativnu terapiju guinalis secundum Bassini cum modificatione Nešović,
uz odgovarajući fizikalni tretman. which enables the balancing of the strength of the pel-
vifemoral muscles, especially the adductors, and the
ZAKLJUČAK strength of the anterior abdominal wall muscles. This
Sindrom bolne simfize je značajno kliničko stanje za technique was successfully presented by Dr. Branislav
sportiste, sa posebnim akcentom na igrače fudbala. Nešović (Belgrade, Serbia), in 1967, who modified the
Etiologija razvoja bolova u preponama leži u sukobu classical Bassini technique of inguinal hernia surgery
između nejednakih mišićnih snaga susednih regija – [8]. During the surgery it is necessary to close the ingui-
prednjeg trbušnog zida i donjih ekstremiteta, te nejed- nal canal and create new passageways for neurovascu-
nakog opterećenja između svih pripoja u regiji simfize. lar elements in this region [21].
Kod nastanka pubalgije, dolazi do onesposobljavanja POSTOPERATIVE REHABILITATION
sportiste za sportske aktivnosti u prolongiranom peri-
odu. Da bi se takvo stanje izbeglo i da bi se sportisti Rehabilitation after surgery requires gradual patient
omogućilo adekvatno aktivno učešće u treninzima i verticalization and strengthening of the target muscle
utakmicama, mora se imati u vidu prevencija, kao os- groups. If recovery goes according to plan, football play-
nova i temelj zaštite sportista od ovog bolnog stanja, ers return to the football pitch, and the best indicator of
na duže staze. No, ako i uprkos tome dođe do pojave recovery is the absence of pain. Recurrence of the syn-
bola, treba imati na umu značaj pravovremene i speci- drome after surgery has practically never been registered,
fične dijagnostike, koja lekara upućuje na najefektniji which is why the results achieved can be considered as
terapijski pristup. complete success in the treatment of painful symphysis
syndrome [10]. For each patient, especially for an athlete,
Sukob interesa: Nije prijavljen. it is important that cardiovascular endurance remains at
the same level or that it improves after repeated testing.
LITERATURA / REFERENCES To that effect, each session needs to begin with certain
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10.1016/j.surg.2011.02.016.
ZANIMLJIV SLUČAJ KORONARNO-KAMERALNE
FISTULE SA ANGINOM PEKTORIS
PRIKAZ SLUČAJA CASE REPORT
AN INTERESTING CASE OF CORONARY-CAMERAL

FISTULA WITH ANGINA PECTORIS
Dejan M. Lazović1,2, Mladen Kočica1, Ivana Đurošev1, Milica Kočica-Karadžić2,3, Dragan Cvetković1,2
1
Univerzitetski klinički centar Srbije, Klinika za kardiohirurgiju, University Clinical Center of Serbia, Clinic for Cardiac Surgery,
1

2
Univerzitet u Beogradu, Medicinski fakultet, Beograd, Srbija University of Belgrade, Faculty of Medicine, Belgrade, Serbia
2
3
Univerzitetski klinički centar Srbije, Centar za anesteziju, Beograd, University Clinical Center of Serbia, Center for Anesthesia,
3
Srbija Belgrade, Serbia
SAŽETAK ABSTRACT
Uvod: Koronarno-kameralna fistula (KKF) predstavlja anomalnu vezu između Introduction: Coronary-cameral fistula (CCF) is an anomalous connection
koronarne arterije i srčane komore. Većina KKF-a se otkrije slučajno, tokom an- between a coronary artery and a cardiac chamber. Most CCFs are discovered
giografske evaluacije koronarnih vaskularnih poremećaja. Prikazujemo slučaj incidentally during angiographic evaluation of coronary vascular disorders. We
KKF-a sa anginom pektoris. report a case of CCF with angina pectoris.
Prikaz slučaja: Žena, stara 67 godina, imala je bolove u grudima i dispneju pri Case report: A 67-year-old woman presented with chest pain and dyspnea upon
naporu. Koronarna angiografija je pokazala aterosklerotske lezije u dve glavne exertion. Coronary angiography showed atherosclerotic lesions in the two major
koronarne arterije, ali i postojanje komunikacije između tri arterije i šupljine de- coronary arteries, but also communication between three arteries and the cav-
sne komore kroz mnoge male, difuzne fistule. Angiografija je takođe pokazala ity of the right ventricle (RV) through many small, diffuse fistulas. Angiography
fistulu između proksimalnog dela leve prednje silazne arterije (prve septalne also showed a fistula between the proximal left anterior descending artery (LAD)
grane) i desne komore, i između proksimalnog dela desne srčane arterije (akutna (first septal branch) and the right ventricle, as well as between the proximal right
marginalna grana) i desne komore. Kod pacijentkinje je postojala indikacija za coronary artery (RCA) (acute marginal branch) and the right ventricle. The patient
hiruršku revaskularizaciju miokarda (CABG) i hirurško zatvaranje fistula, te je, na qualified to undergo coronary artery bypass graft surgery (CABG) and surgical
kucajućem srcu, učinjena CABG intervencija, sa dva autovenska grafta – između closing of the fistulas, which is why we performed, on a beating heart, double
uzlazne aorte i desne srčane arterije, i između uzlazne aorte i leve prednje silazne vessel revascularization by autovein graft between the ascending aorta and the
arterije, kao i zatvaranje fistula hemoklipsevima i polipropilenskim šavom, sa RCA and between the ascending aorta and the LAD, as well as closing of the fistu-
teflonskim pledžetom. las with hemoclips and polypropylene suture, with a teflon pledget.
Zaključak: Hemodinamski beznačajne fistule, koje su klinički neme i nisu pove- Conclusion: Hemodynamically insignificant fistulas, which are clinically silent
zane sa drugim abnormalnim nalazima, najčešće ne zahtevaju dalje lečenje. Ve- and not associated with other abnormal findings, most commonly do not re-
like, hemodinamski značajne fistule treba ligirati. Ipak, kako manje fistule imaju quire further treatment. Large, hemodynamically significant fistulas should be
tendenciju da se uvećavaju sa godinama, preporučuje se i njihovo rano elektivno closed by ligation. However, smaller fistulas tend to get larger with age and it is
zatvaranje, u slučajevima kada su one simptomatske, ali i onda kada su asimp- recommended that early elective closure is performed in patients experiencing
tomatske, uz prisutan kontinuirani šum ili sistolni šum sa ranom dijastolnom symptoms or in asymptomatic patients with a continuous murmur or a systolic
komponentom. murmur with an early diastolic component.
Ključne reči: fistule koronarne arterije, koronarna angiografija Key words: coronary artery fistulas, coronary angiography

Dejan Lazović Dejan Lazović
Klinika za kardiohirurgiju, Univerzitetski klinički centar Srbije Clinic for Cardiac Surgery, University Clinical Center of Serbia
Elektronska adresa: lazovic.dejan88@gmail.com E-mail: lazovic.dejan88@gmail.com
Primljeno • Received: April 30, 2022; Revidirano • Revised: May 10, 2022; Prihvaćeno • Accepted: May 18, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-37639
zanimljiv slučaj koronarno-kameralne fistule sa anginom pektoris
Lazović M. D. et al.
an interesting case of coronary-cameral fistula with angina pectoris
UVOD INTRODUCTION
Koronarno-kameralna fistula (KKF) predstavlja anomal- Coronary-cameral fistula (CCF) is an anomalous con-
nu vezu između koronarne arterije i srčane komore. Ve- nection between a coronary artery and a cardiac
ćina KKF-a se otkrije slučajno tokom angiografske eva- chamber. Most CCFs are discovered incidentally during
luacije koronarnih vaskularnih poremećaja. Nekada se angiographic evaluation of coronary vascular disor-
smatralo da je koronarno-kameralna fistula, koju je prvi ders. It was previously believed that coronary-cam-
put opisao Krause, 1865. godine, retka anomalija srčanih eral fistula, first described by Krause in 1865, is a rare
arterija [1]. Prikazujemo slučaj koronarno-kameralne fi- anomaly of the coronary arteries [1]. We present a case
stule sa anginom pektoris. Selektivnom koronarnom of coronary-cameral fistula with angina pectoris. Selec-
angiografijom je otkrivena difuzna KKF, koja uključuje tive coronary angiography revealed diffuse CCF, which
desnu srčanu arteriju (engl. right coronary artery – RCA) included the right coronary artery (RCA) (Figure 1) and
(Slika 1) i levu prednju silaznu arteriju (engl. left anterior the left anterior descending artery (LAD) (Figure 2),
descending artery – LAD) (Slika 2), koje se prazne u desnu voiding into the right ventricle (RV), as well as double
komoru (DK), kao i dvosudovna koronarna bolest. coronary vessel disease.
PRIKAZ BOLESNIKA CASE PRESENTATION

Žena stara 67 godina, bez poznatih faktora rizika za sr- A 67-year-old woman, without known risk factors for cor-
čana oboljenja, imala je bolove u grudima i dispneju onary disease, presented with chest pain and dyspnea
pri naporu. Vitalni znaci su bili normalni. Ehokardio- upon exertion. Her vital signs were normal. Echocardio-
grafski pregled je pokazao očuvanu ejekcionu frakciju graphic examination showed preserved ejection fraction
leve komore (LK) – 60%, te odsustvo valvularnog obo- of the left ventricle (LV) – 60%, and absence of valvular
ljenja, ali je uočena umerena hipertrofija leve komore heart disease, however moderate hypertrophy of the left
sa dijastolnom disfunkcijom. ventricle with diastolic dysfunction was observed.
Koronarna angiografija je pokazala aterosklerotske Coronary angiography showed atherosclerotic le-
lezije u dve glavne srčane arterije, a otkriveno je i da su sions in the two main coronary arteries, and it was also dis-
tri srčane arterije bile u komunikaciji sa šupljinom desne covered that three coronary arteries were in communica-
komore kroz mnoge male, difuzne fistule (Slika 1 i Slika 2), tion with the right ventricular cavity through many small,
što je za posledicu imalo potpuno zamućenje kontrasta diffuse fistulas (Figure 1 and Figure 2), which resulted in
Slika 1. Selektivna koronarna angiografija pokazuje lavirint finih krvnih sudova, Slika 2. Selektivna koronarna angiografija pokazuje višestruke fistule koje na-
koji nastaju iz desne srčane arterije (proksimalno i distalno), i u komunikaciji su staju iz proksimalne leve prednje silazne srčane arterije – prve septalne grane, a
sa šupljinom desne komore koje su u komunikaciji sa šupljinom desne komore
Figure 1. Selective coronary angiography showing a maze of fine vessels arising Figure 2. Selective coronary angiography showing multiple fistulas arising from
from the right coronary artery (proximal and distal) and communicating with the the proximal left anterior descending coronary artery - first septal branch and
right ventricular cavity communicating with the right ventricular cavity
Lazović D. M. i sar.
Slika 3. Identifikovan ostijum fistuloznog kanala između RCA-e i DK Slika 4. Ligirana i prešivena fistula, bajpas od aorte ka desnoj srčanoj arteriji
Figure 3. The ostium of the fistula between the RCA and the RV Figure 4. Ligated and sutured fistula, by pass from the aorta to the right coronary
artery
u desnoj komori. Koronarni sinus je bio normalne veli- complete contrast opacification in the right ventricle. The
čine. Selektivna koronarografija otkrila je stenozu od 90 coronary sinus was normal in size. Selective coronarog-
– 99% u distalnom delu desne srčane arterije (RCA) i ste- raphy revealed a 90 – 99% stenosis in the distal segment
nozu od 80% u kratkom segmentu leve prednje silazne of the right coronary artery (RCA) and an 80% stenosis in
arterije (LAD), koja se širila u drugu dijagonalnu granu. the short segment of the left anterior descending artery
Angiografija je takođe pokazala fistulu između (LAD), spreading into the other, diagonal branch.
proksimalnog dela leve prednje silazne arterije (prve Angiography also showed a fistula between the
septalne grane) i desne komore, i između proksimal- proximal left anterior descending artery (LAD) (first
nog dela desne srčane arterije (akutna marginalna gra- septal branch) and the right ventricle, as well as be-
na) i desne komore. tween the proximal right coronary artery (RCA) (acute
Transtorakalni, dvodimenzionalni ehokardiogram marginal branch) and the right ventricle.
pokazao je normalne prečnike srčanih komora. Sta- Two-dimensional transthoracic echocardiography
blo plućne arterije bilo je prepunjeno krvlju. Sistolni showed normal diameters of the cardiac ventricles.
pritisak desne komore bio je umereno povećan – do The trunk of the pulmonary artery was overflown with
vrednosti od 32 mmHg. Kolor dopler ehokardiografski blood. The systolic pressure of the right ventricle was
pregled ukazao je na prisustvo fistule srčane arterije. moderately elevated – up to the value of 32 mmHg.
Pacijentkinja nije bila prethodno podvrgnuta nekoj in- Color doppler echocardiographic examination indicat-
vazivnoj kardiološkoj dijagnostičko-terapijskoj proce- ed the presence of coronary artery fistula. The patient
duri koja bi mogla da se dovede u vezu sa KKF-om, a had not previously undergone any invasive cardiolog-
u porodičnoj anamnezi je negirala postojanje koronar- ical diagnostic or therapeutic procedure that could be
no-kameralne fistule. connected with CCF, and in her family anamnesis, she
Kod pacijentkinje je postojala indikacija za hiruršku negated the existence of coronary-cameral fistula.
revaskularizaciju miokarda (engl. coronary artery bypa- The patient’s condition indicated the need for sur-
ss graft surgery – CABG) i hirurško zatvaranje fistule. gical revascularization of the myocardium (coronary
U slučaju naše pacijentkinje, na kucajućem srcu, artery bypass graft surgery – CABG) and surgical clos-
učinjena je hirurška revaskularizacija miokarda, sa dva ing of the fistula.
autovenska grafta – između uzlazne aorte i desne sr- In the case of our patient, we performed, on a beating
čane arterije, te između uzlazne aorte i leve prednje heart, double vessel revascularization by autovein graft
silazne arterije. Fistulozni trakt je osiguran sa dva he- between the ascending aorta and the RCA, and between
moklipsa i polipropilenskim šavom 4-0 sa teflonskim the ascending aorta and the LAD. The fistulas were se-
pledžetom (Slika 3 i Slika 4). Pacijentkinja je otpuštena cured with two hemoclips and polypropylene suture 4-0,
kući u dobrom kliničkom stanju. with a teflon pledget (Figure 3 and Figure 4). The patient
was discharged from hospital in good general condition.
DISKUSIJA
DISCUSSION
Fistula koronarne arterije predstavlja postojanje abnor-
malne direktne veze između srčane arterije i srčane ko- Coronary artery fistula is an abnormal direct connection
more (koronarno-kameralna fistula) ili vene (koronarna between a coronary artery and a cardiac chamber (cor-
onary-cameral fistula) or vein (coronary arteriovenous
Lazović M. D. et al.
arteriovenska fistula). Fistule srčane arterije se javljaju fistula). Coronary artery fistulas occur with an incidence
sa incidencijom od 0,1%. Retko, mogu izazvati ishemi- of 0.1%. Rarely, they may cause myocardial ischemia,
ju miokarda, usled sindroma koronarne krađe, srčane due to coronary steal syndrome, cardiac insufficiency, or
insuficijencije ili spontane intraperikardne rupture [2]. spontaneous intrapericardial rupture [2]. Sixty percent
Šezdeset procenata ovih fistula nastaje iz desne sr- of these fistulas originate from the right coronary ar-
čane arterije, a 90% se završava na desnoj strani srca. tery, while 90% end on the right side of the heart. Coro-
Koronarno-kameralne fistule, iz sve tri glavne srčane nary-cameral fistulas, from all three major coronary arter-
arterije, a koje se završavaju u desnoj komori, retka su ies, which end in the right ventricle, are a rare occurrence.
pojava. Coronary-cameral fistulas are most commonly con-
Koronarno-kameralne fistule su najčešće urođene genital and may be connected to the normally occur-
i mogu biti u vezi sa normalno prisutnim Tebezijevim ring Thebesian veins, which drain blood from the coro-
venama, koje dreniraju krv srčanih arterija nakon nje- nary arteries after it passes through the capillaries into
nog prolaska kroz kapilare u srčane komore [3]. One the cardiac ventricles [3]. They are usually clinically in-
obično nemaju klinički značaj niti daju kliničke simpto- significant, and do not result in clinical symptoms and
me i znake. U zavisnosti od veličine i lokalizacije fistula, signs. Depending on the size and localization of the
u nekim slučajevima, mogu se izvesti epikardijalno i fistulas, in some cases, surgical ligation, epicardially or
endokardijalno hirurško ligiranje ili perkutana endolu- endocardially, or a percutaneous endoluminal proce-
minalna procedura (embolizacija). Intervencija je teška dure (embolization) may be performed. The procedure
ili nemoguća kada su fistule difuzne. Stoga, uprkos is- is difficult or impossible when the fistulas are diffuse.
hemiji, kod naše pacijentkinje, takva intervencija nije Therefore, despite ischemia, such a procedure was not
razmatrana [4]. contemplated in our patient [4].
Jamanaka i Hobs su pronašli fistule malih srčanih Yamanaka and Hobbs found fistulas of small cor-
arterija kod 0,18% od 126.595 pacijenata podvrgnutih onary arteries in 0.18% of 126,595 patients who had
kateterizaciji srca [2]. Fistule ovog tipa obično nasta- undergone cardiac catheterization [2]. Fistulas of this
ju iz jedne grane srčane arterije i dreniraju se u jednu type usually develop from one coronary artery branch
od srčanih komora ili u jedan krvni sud, i najčešće nisu and drain into one of the cardiac ventricles or into
povezane sa kliničkim simptomima i znacima [6]. Ipak, one blood vessel, and are most commonly not asso-
velike fistule sa značajnim šantom daju znake kao što ciated with clinical signs and symptoms [6]. Never-
je prisustvo kontinuiranog šuma i simptome poput theless, large fistulas with a significant shunt result in
dispneje pri naporu, intolerancije fizičke aktivnosti ili signs such as the presence of a persistent murmur and
kongestivne srčane insuficijencije, i tada ih treba hirur- symptoms such as dyspnea upon exertion, exercise
ški korigovati [5,6,7]. Glavna mesta nastanka fistula su intolerance, or congestive heart failure, which is when
desna srčana arterija (55%), leva srčana arterija (35%) i surgical treatment is necessary [5,6,7]. The main sites
obe srčane arterije (5%). Glavna mesta drenaže fistula of fistula development are the right coronary artery
su desna komora (40%), desna pretkomora (26%), pluć- (55%), the left coronary artery (35%), and both coro-
ne arterije (17%) i ređe gornja šuplja vena ili koronarni nary arteries (5%). The main sites where fistulas most
sinus, a najređe leva pretkomora i leva komora [8]. commonly drain are the right ventricle (40%), the right
atrium (26%), pulmonary arteries (17%), less frequently
Sukob interesa: Nije prijavljen. the superior vena cava or the coronary sinus, and least
frequently the left atrium and the left ventricle [8].
1. Krause W. Ueber den Ursprung einer akzessorischen A. coronaria aus der A.
pulmonalis. Z Ratl Med 1965; 24:225-9.
6. Kaplan JD, Redberg RF. Coronary to pulmonary artery fistula detected by
2. Yamanaka O, Hobbs RE. Coronary artery anomalies in 126,595 patients under- transthoracic echocardiography. Am Heart J. 1995 Apr;129(4):839-40. doi:
going coronary arteriography. Cathet Cardiovasc Diagn. 1990 Sep;21(1):28- 10.1016/0002-8703(95)90343-7.
40. doi: 10.1002/ccd.1810210110.
7. Kidawa M, Peruga JZ, Foryś J, Krzemińska-Pakuła M, Kasprzak JD. Acute co-
3. Iadanza A, del Pasqua A, Fineschi M, Pierli C. Three-vessel left-ventricu- ronary syndrome or steal phenomenon - a case of right coronary to right
lar microfistulization syndrome: a rare case of angina. Int J Cardiol. 2004 ventricle fistula. Kardiol Pol. 2009 Mar;67(3):287-90.
Jul;96(1):109-11. doi: 10.1016/j.ijcard.2003.04.052.
8. Funabashi N, Komuro I. Aberrant fistula arteries from the left main branch
4. Iyisoy A, Arslan Z, Ozmen N, Kursaklioglu H, Amasyali B, Demirtas E. Double and right coronary artery to the left pulmonary arterial sinus demonstrated
coronary fistulas between coronary artery and left ventricle: a case report [in by multislice computed tomography. Int J Cardiol. 2006 Jan 26;106(3):428-
Turkish]. Gulhane Tip Dergisi 2003;45:203-5. 30. doi: 10.1016/j.ijcard.2005.01.036.
5. Alkhulaifi AM, Horner SM, Pugsley WB, Swanton RH. Coronary artery fistulas
presenting with bacterial endocarditis. Ann Thorac Surg. 1995 Jul;60(1):202-4.
EKSTREMNA GOJAZNOST I TOTALNA LAPAROSKOPSKA
HISTEREKTOMIJA - PRIKAZ SLUČAJA
EXTREME OBESITY AND TOTAL LAPAROSCOPIC

HYSTERECTOMY – CASE REPORT
Milan Dokić1,2, Dragiša Šljivančanin1,2, Sandra Babić1, Branislav Milošević1,2
1
Univerzitetski klinički centar Srbije, Klinika za ginekologiju i 1
University Clinical Center of Serbia, Clinic for Gynecology and
akušerstvo, Beograd, Srbija Obstetrics, Belgrade, Serbia
2
SAŽETAK ABSTRACT
Uvod: Laparoskopski pristup se ranije nije razmatrao za gojazne osobe, upravo Introduction: Previously, the laparoscopic approach was not considered for
zbog povećanog rizika od operativnih i postoperativnih komplikacija. Poslednjih obese people, because of the increased risk of operative and postoperative
godina, međutim, pristup se promenio u korist minimalno invazivnih procedura complications. In recent years, however, the approach has changed in favor of
kojima se izbegava laparotomija, koja je kod gojaznih osoba najčešći uzrok kom- minimally invasive procedures that avoid laparotomy, which, in obese people, is
plikacija, u vidu sporijeg i otežanog zarastanja rana, krvarenja i infekcija na mestu the most common cause of complications, in the form of slower and aggravated
laparotomije. I dalje je, u hitnim situacijama, ekstremna gojaznost praćena više- wound healing, bleeding, and infections at the laparotomy site. In emergency
strukim komorbiditetima pravi izazov za endoskopsku hirurgiju, endoskopskog situations, extreme obesity accompanied by multiple comorbidities still remains
hirurga i kompletan hirurški i anesteziološki tim. a real challenge for endoscopic surgery, the surgeon and the entire surgical and
Prikaz slučaja: Predstavljamo slučaj šezdesetjednogodišnje, ekstremno goja- anesthesiology team.
zne pacijentkinje, koja je hitno primljena u bolnicu, zbog produženog vaginalnog Case report: We present a case of a 61-year-old, extremely obese patient, who
krvarenja i anemije. Nakon preoperativne pripreme, pacijentkinja je operisana was admitted to hospital as an emergency case, due to prolonged vaginal bleed-
– izvršena je totalna laparoskopska histerektomija sa bilateralnom salpingoofo- ing and anemia. After preoperative preparation, the patient underwent surgery
rektomijom. – laparoscopic total hysterectomy with bilateral salpingo-oophorectomy.
Zaključak: Gojaznost je veliki problem u savremenom društvu. Osim što direk- Conclusion: Obesity is a major problem in modern society. In addition to directly
tno utiče na zdravlje, prekomerna telesna masa kod pacijenata veoma otežava affecting health, excessive body weight in a patient makes it very difficult to per-
izvođenje hirurških zahvata. Debljina trbušnog zida i prateći zdravstveni proble- form surgical procedures. The thickness of the abdominal wall and accompanying
mi predstavljaju kontraindikaciju za laparoskopske operacije. U ovakvim slučaje- health problems are a contraindication for laparoscopic operations. In such cases,
vima, za izvođenje hirurških operacija, posebno laparoskopskih, potrebno je ima- performing surgery, especially laparoscopic procedures, requires a trained team
ti stručno obučen tim i odgovarajuću tehničku opremu. Laparoskopska hirurgija of professionals and appropriate equipment. Laparoscopic surgery is more and
ima sve veću zastupljenost, čak i u najtežim slučajevima. Prikazom ovog slučaja more present, even in the most difficult cases. In presenting this case, we aimed
želeli smo da pokažemo da je moguće uspešno uraditi totalnu laparoskopsku to demonstrate that it is possible to successfully perform total laparoscopic hys-
histerektomiju kod ekstremno gojaznih pacijentkinja sa brojnim komorbiditeti- terectomy in extremely obese patients with associated health problems, even in
ma, čak i u hitnim situacijama. emergency situations.
Ključne reči: ekstremna gojaznost, histerektomija, endoskopska hirurgija Keywords: extreme obesity, hysterectomy, endoscopic surgery

Branislav Milošević Branislav Milošević
Klinika za ginekologiju i akušerstvo, Univerzitetski klinički centar Srbije Clinic for Gynecology and Obstetrics, Clinical Center of Serbia
Koste Todorovića 26, 11000 Beograd, Srbija 26 Koste Todorovića Street, 11000 Belgrade, Serbia
Elektronska adresa: drbanemilosevic@gmail.com E-mail: drbanemilosevic@gmail.com
Primljeno • Received: May 10, 2022; Revidirano • Revised: May 17, 2022; Prihvaćeno • Accepted: May 19, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-37790
ekstremna gojaznost i totalna laparoskopska histerektomija – prikaz slučaja
Dokić M. et al.
extreme obesity and total laparoscopic hysterectomy – case report
UVOD INTRODUCTION
Gojaznost je ozbiljan zdravstveni problem modernog Obesity is a serious health problem of modern society.
društva. Gojazne žene su pod većim rizikom od određe- Obese women are at higher risk of developing certain
nih ginekoloških oboljenja, uključujući tu i hiperplaziju gynecological diseases including endometrial hyper-
endometrijuma i karcinom endometrijuma [1]. Takođe, plasia and endometrial carcinoma [1]. In addition, ex-
prekomerna telesna masa otežava izvođenje operativ- cessive body weight makes it difficult to perform sur-
nih zahvata kod ovakvih pacijenata, te predstavlja ne- gical procedures in such patients and represents an
posredni izvor povećanog rizika od komplikacija, i to- immediate source of increased risk of complications
kom operacije, ali i kasnije, u postoperativnom toku [2]. during surgery and later, during postoperative recov-
Normalan indeks telesne mase (engl. body mass index ery [2]. Normal body mass index (BMI) values range
- BMI) kreće se u rasponu od 25 – 29,9 kg/m2. Vrednost from 25 - 29.9 kg/m2. A BMI over 30 kg/m2 is an indi-
BMI iznad 30 kg/m2 predstavlja indeksprekomerne tele- cation of excess body weight. Obesity is a chronic dis-
sne mase. Gojaznost je hronična bolest, koja je snažno ease, which is also strongly associated with an increase
povezana sa povećanjem mortaliteta i morbiditeta, uk- in mortality and morbidity, including diabetes mellitus,
ljučujući dijabetes melitus, hipertenziju, kardiovaskular- hypertension, cardiovascular disease, disability, stroke,
na oboljenja, invalidnost, moždani udar, i ostala hronič- and other chronic diseases [3]. All these conditions, es-
na oboljenja [3]. Sva ova stanja, posebno insulin zavisni pecially insulin dependent diabetes mellitus (IDDM),
dijabetes melitus (engl. insulin dependent diabetes melli- are also associated with a higher risk of intraoperative
tus – IDDM), takođe su povezana sa povećanim rizikom and postoperative complications [4,5].
od intraoperativnih i postoperativnih komplikacija [4,5]. Until recently, the laparoscopic approach was con-
Do nedavno, laparoskopski pristup se smatrao po- sidered only for slender people, precisely because of
godnim samo za vitke ljude, baš zbog povećanog rizika the increased safety risk [6]. In recent years, however,
[6]. Poslednjih godina, međutim, došlo je do promene the approach has changed in favor of minimally inva-
stava u korist minimalno invazivnih hirurških zahvata sive procedures that avoid laparotomy, which, in obese
kojima se izbegava laparotomija, koja kod gojaznih people, is the most common cause of complications,
ljudi predstavlja najčešći uzrok komplikacija, u obliku in the form of slower and aggravated wound healing,
sporijeg i otežanog zarastanja rane, krvarenja, te infek- bleeding, and infections at the laparotomy site [7].
cija na mestu hirurškog reza [7]. Nevertheless, extreme obesity accompanied by
Ipak, ekstremna gojaznost udružena sa višestrukim multiple comorbidities remains a real challenge for
komorbiditetima i dalje predstavlja ozbiljan izazov u endoscopic surgery, the endoscopic surgeon and the
endoskopskoj hirurgiji, kako za hirurga tako i za ceo hi- entire surgical and anesthesiology team, especially in
rurški i anesteziološki tim, posebno u hitnim stanjima. emergency situations.

Šezdesetjednogodišnja pacijentkinja primljena je u A 61-year-old patient was admitted to hospital, as an
bolnicu, kao hitan slučaj, usled dugotrajnog vaginal- emergency case, due to prolonged vaginal bleeding
nog krvarenja i teške anemije. Dva meseca pre toga, and severe anemia. Endometrial polypectomy and
kod ove pacijentkinje su uspešno izvedene endometri- fractional curettage procedures had successfully been
jalna polipektomija i frakcionisana eksplorativna kire- performed two months previously. The histopatholog-
taža. Histopatološki nalaz je ukazao na endometrijalnu ical finding indicated endometrial hyperplasia with
hiperplaziju sa atipijom. Ova pacijentkinja je ujedno atypia. This was a cardiovascular patient with insu-
imala i kardiovaskularne probleme, insulin zavisni dija- lin-dependent diabetes mellitus and hypothyroidism.
betes melitus i hipotiroidizam. On admission, the patient’s body weight was 132 kg,
Na prijemu, njena telesna masa je bila 132 kg, dok je while her height was 172 cm (BMI = 44.62 kg/m2); her
njena visina bila 172 cm (BMI = 44,62 kg/m2); krvni priti- blood pressure was 170/90 mmHg; her glycemia was
sak je iznosio 170/90 mmHg; glikemija je bila 4,2 mmol/l. 4.2 mmol/l. Laboratory blood test results confirmed
Rezultati laboratorije su potvrdili tešku anemiju: broj eri- severe anemia: red blood cell count = 2.4 x 106; hemo-
trocita = 2,4 x 106; hemoglobin = 61,0 g/l; Hct =18,7. globin = 61.0 g/l; HCT =18.7.
Anemija je kod pacijentkinje korigovana transfuzija- The patient’s anemia was corrected with blood
ma krvi (3 doze). Učinjene su pripreme za hirurško leče- transfusions (3 doses). Preparations were made for sur-
nje. Pre operacije, nakon što je pacijentkinja provela tri gical treatment. Before the operation, after spending
dana u našoj bolnici, njen internistički status se popra- three days in our hospital, the patient’s overall status
vio – krvni pritisak je bio 140/80 mmHg, dok su rezultati was improved – her blood pressure was 140/80 mmHg,
Dokić M. i sar.
laboratorije krvi bili značajno bolji: broj eritrocita = 4,06 while the blood test results were significantly better:
x 106; Ht = 32,5; hemoglobin = 104,0 g/l. Međutim, vagi- red blood cell count = 4.06 x 106; HCT = 32.5; hemo-
nalno krvarenje se održavalo, uz promenljivi intenzitet. globin = 104.0 g/l. However, the vaginal bleeding re-
Pacijentkinja je podvrgnuta hitnoj operaciji – total- mained constant, with varying intensity.
na laparoskopska histerektomija sa bilateralnom sal- The patient underwent emergency surgery – lapa-
pingooforektomijom. Operacija je prošla bez kompli- roscopic total hysterectomy with bilateral salpingo-oo-
kacija, trajala je 110 minuta, uz gubitak krvi od 152,7 ml. phorectomy. The procedure was without complica-
Postoperativno, pacijentkinja je nastavila da prima tions, lasting 110 minutes, with a blood loss of 152.7 ml.
internističku terapiju, kao i antibiotike. Finalni histopa- Postoperatively, the patient continued to receive
tološki nalaz je bio – atipična endometrijalna hiperpla- the necessary therapy, including antibiotics. The final
zija. Pacijentkinja se oporavila bez komplikacija i otpu- histopathological finding was – atypical endometrial
štena je iz bolnice trećeg postoperativnog dana. hyperplasia. The patient recovered without experienc-
ing any complications and was dismissed on the third
DISKUSIJA postoperative day.
Gojaznost je ozbiljan, rastući problem, koji pogađa
zdravlje ljudi širom sveta. Broj žena čiji je BMI iznad 40
DISCUSSION
dostigao je skoro 7,5% u Sjedinjenim Američkim Država- Obesity is a major and increasing problem that affects
ma [8]. Osim što direktno utiče na zdravlje, prekomerna people’s health worldwide. The number of women with
telesna masa kod pacijenata značajno otežava izvođenje a BMI over 40 has increased to nearly 7.5% in the United
hirurških zahvata. Debljina trbušnog zida i prateći zdrav- States [8]. In addition to directly affecting health, exces-
stveni problemi predstavljaju kontraindikaciju za lapa- sive body weight in the patient makes it very difficult to
roskopske operacije [6]. Takođe, morbidna gojaznost perform surgical procedures. The thickness of the ab-
predstavlja ozbiljan problem kada je u pitanju ventilaci- dominal wall and accompanying health problems are
ja, pošto smanjuje respiratornu komplijansu, povećava a contraindication for laparoscopic operations [6]. Also,
pritisak u disajnim putevima, i slabi srčanu funkciju [9]. morbid obesity is a significant challenge with respect to
U ovom trenutku, hirurzi su još uvek nedovoljno ventilation, as it decreases respiratory compliance, in-
upoznati sa laparoskopskim operacijama na pacijenti- creases airway pressure, and impairs cardiac function [9].
ma čiji je BMI > 40, možda zbog inicijalnog ulaza tro- At present, surgeons are still unfamiliar with lap-
kara, plasmana porta, kontrole hiperkapnije ili zbog aroscopic operations on patients with a BMI > 40,
više stope konverzije u otvorenu operaciju. Ipak, lapa- possibly due to initial trocar entry, port placement,
roskopske operacije su sve prisutnije čak i u najtežim management of hypercarbia or a higher rate of lapa-
slučajevima [10]. Podrazumeva se da je za izvođenje rotomy conversions. Nevertheless, laparoscopic sur-
hirurških operacija, posebno laparoskopskih, potreb- gery is more and more present even in the most se-
no imati stručno obučen tim i odgovarajuću tehničku vere cases [10]. It goes without saying that surgery,
opremu. Vreme trajanja naše operacije, kao i gubitak especially laparoscopic procedures, requires a trained
krvi kod pacijentkinje, komparabilni su sa podacima iz team of professionals and appropriate equipment. Our
literature koji se odnose na gojazne ali i na pacijente operation time and blood loss were comparable with
normalne telesne mase [10]. Pacijentkinja je otpuštena literature data for obese as well as for normal weight
iz bolnice trećeg postoperativnog dana, što je za je- patients [10]. The patient was discharged on the third
dan do dva dana duža hospitalizacija od standardnog postoperative day, which is a day or two longer than
protokola za pacijentkinje sa normalnom telesnom the standard protocol for normal weight patients un-
masom koje se podvrgavaju totalnoj laparoskopskoj dergoing total laparoscopic hysterectomy. However,
histerektomiji. Međutim, u obzir se moraju uzeti i brojni the patient’s numerous comorbidities and significant
komorbiditeti, te ozbiljna anemija koja je bila prisutna anemia before the operation also need to be taken into
kod pacijentkinje. Na koncu, pacijentkinja je otpuštena consideration. Ultimately, the discharge was four days
iz bolnice četiri dana ranije nego što bi to bio slučaj da earlier than it would have been if open surgery had
je izvršena otvorena operacija, a sama intervencija je been performed, and the procedure was performed
prošla bez ikakvih postoperativnih komplikacija. without any postoperative complications.
Prikazom ovog slučaja želeli smo da pokažemo da In presenting this case, we aimed to demonstrate
je moguće uspešno izvesti laparoskopske operacije that it is possible to successfully perform laparoscopic
kod ekstremno gojaznih pacijenata sa brojnim komor- procedures in extremely obese patients with multiple
biditetima, čak i u hitnim situacijama. comorbidities, even in emergency situations.
Sukob interesa: Nije prijavljen. Conflict of interest: None declared.
Dokić M. et al.
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KARDIOTOKSIČNOST VISOKE DOZE METILPREDNIZOLONA
KOD BOLESNIKA SA HRONIČNOM LIMFOCITNOM
LEUKEMIJOM – PRIKAZ SLUČAJA
CARDIOTOXICITY OF HIGH-DOSE METHYLPREDNISOLONE IN PATIENTS

WITH CHRONIC LYMPHOCYTIC LEUKEMIA – A CASE REPORT
Milica Apostolović Stojanović1, Milica Radojković1,2, Aleksandar Stojanović3, Vladan Vukomanović1
1
Kliničko-bolnički centar „Dr Dragiša Mišović”, Beograd, Srbija 1
Clinical Hospital Center "Dr Dragiša Mišović", Belgrade, Serbia
2
3
Institut za ortopediju „Banjica”, Beograd, Srbija 3
Institute for Orthopedic Surgery "Banjica", Belgrade, Serbia
SAŽETAK ABSTRACT
Uvod: Nekoliko klasa lekova mogu izazvati atrijalnu fibrilaciju (AF) kod bole- Introduction: Several classes of drugs can cause atrial fibrillation (AF) in pa-
snika koji nemaju oboljenje srca, kao i pojavu atrijalne fibrilacije kod postoje- tients without heart disease, as well as the occurrence of AF in pre-existing heart
ćeg srčanog oboljenja. AF izazvana lekovima se najčešće klinički manifestuje u disease. Drug-induced AF is most often clinically manifested in the form of par-
vidu paroksizma. Visoke doze intravenskog metilprednizolona (VDMP) u lečenju oxysms. High doses of intravenous methylprednisolone (HDMP) in the treatment
hronične limfocitne leukemije (HLL) povezane su sa pojavom različitih neželje- of chronic lymphocytic leukemia (CLL) have been associated with the occurrence
nih efekata, uključujući i pojavu atrijalne fibrilacije. Tačan mehanizam atrijalne of various adverse effects, including AF. The exact mechanism of HDMP-induced
fibrialcije indukovane VDMP-om nije poznat. AF is unknown.
Prikaz slučaja: Prikazujemo slučaj bolesnika sa HLL-om, kod koga je, nakon Case presentation: We present the case of a patient with CLL in whom AF oc-
primene visoke doze intravenskog metilprednizolona, došlo do pojave atrijalne curred after the administration of a high dose of intravenous methylpredniso-
fibrilacije. lone.
Zaključak: Lekari bi trebalo da budu upoznati sa posebnim okolnostima u le- Conclusion: Physicians should be aware of the special circumstances in the
čenju hronične limfocitne leukemije, jer AF izazvana lekom može biti neželjeni treatment of CLL, because drug-induced AF can be a side effect that limits further
efekat koji ograničava dalju terapiju. therapy.
Ključne reči: hronična limfocitna leukemija, atrijalna fibrilacija izazvana lekovi- Key words: chronic lymphocytic leukemia, drug-induced atrial fibrillation, high
ma, visoke doze metilprednizolona doses of methylprednisolone

Milica Apostolović Stojanović Milica Apostolović Stojanović
Kliničko-bolnički centar „Dr Dragiša Mišović” Clinical Hospital Center "Dr Dragiša Mišović"
Heroja Milana Tepića 1, 11000 Beograd, Srbija 1 Heroja Milana Tepića Street, 11000 Belgrade, Serbia
Elektronska adresa: apostolovic.ncrc@gmail.com E-mail: apostolovic.ncrc@gmail.com
Primljeno • Received: February 27, 2022; Revidirano • Revised: April 20, 2022; Prihvaćeno • Accepted: May 12, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-36683
kardiotoksičnost visoke doze metilprednizolona kod bolesnika sa hroničnom limfocitnom leukemijom - prikaz slučaja Apostolović Stojanović M. et al.
cardiotoxicity of high-dose methylprednisolone in patients with chronic lymphocytic leukemia – a case report
UVOD INTRODUCTION
Atrijalna fibrilacija (AF) predstavlja najčešći poremećaj Atrial fibrillation (AF) is the most frequent cardiac
srčanog ritma u kliničkoj praksi i najčešće je udružena rhythm disturbance in clinical practice and is most com-
sa koronarnom bolešću i hipertenzijom. Iz literature je monly associated with coronary disease and hyperten-
poznato da nekoliko klasa lekova (simpatikomimetici, sion. It is known, from relevant literature, that several
parasimpatikomimetici i njihovi inhibitori) mogu da classes of drugs (sympathomimetics, parasympathomi-
izazovu atrijalnu fibrilaciju kod bolesnika koji nemaju metics, and their inhibitors) may cause atrial fibrillation
oboljenje srca [1–3]. AF izazvana lekovima povećava in patients who do not suffer from heart disease [1–3].
broj hospitalizacija i incidenciju ishemijskog možda- Drug-induced AF increases the number of hospitaliza-
nog udara. tions and the incidence of ischemic stroke.
Visoka doza intravenskog metilprednizolona High-dose intravenous methylprednisolone thera-
(VDMP) predstavlja standardnu terapiju kod velikog py (HDMT) is the standard therapy in a large number
broja autoimunih i hematoloških oboljenja (autoimu- of autoimmune and hematological diseases (autoim-
na trombocitopenija, hronična limfocitna leukemija mune thrombocytopenia, chronic lymphocytic leuke-
(HLL) i druge bolesti) [4–7]. mia (CLL), and other diseases) [4–7].
Pojava atrijalne fibrilacije indukovane metilpred- The occurrence of methylprednisolone-induced
nizolonom opisana je u literaturi kod nekoliko različitih atrial fibrillation has been described in literature in sev-
bolesti (multipla skleroza, reumatoidni artritis, membra- eral different diseases (multiple sclerosis, rheumatoid
nozni proliferativni glomerulonefritis). Upotreba korti- arthritis, membranoproliferative glomerulonephritis).
kosteroida udružena je sa pojavom različitih neželjenih The use of corticosteroids is associated with different
efekata. Takođe, zabeleženi su i primeri pojave atrijalne adverse effects. Cases of atrial fibrillation have also
fibrilacije [8–14]. Kao najčešća neželjena dejstva visokih been documented [8–14]. The following have been
doza kortikosteroida, zabeležene su sledeće pojave: iz- registered as the most frequently occurring adverse ef-
menjeno čulo ukusa (61%), crvenilo lica (61%), nesanica fects of high doses of corticosteroids: altered sense of
(44%) i poremećaj raspoloženja (36%) [15]. taste (61%), facial redness (61%), insomnia (44%), and
Elektrofiziološki efekti u pretkomori koji dovode do mood disorders (36%) [15].
atrijalne fibrilacije mogu biti uzrokovani ili pokrenuti Electrophysiological effects in the atrium, leading
fiziološkim procesima, kao što su adrenergička ili va- to atrial fibrillation, may be induced or triggered by
galna stimulacija, metaboličkim ili elektrolitnim pore- physiological processes, such as adrenergic or vagus
mećajima, kao i efektima određenih lekova ili agenasa nerve stimulation, by metabolic or electrolyte disor-
[16]. Patofiziološki, lekovi koji povećavaju ili smanjuju ders, as well as by the effects of certain drugs or agents
adrenergičku ili vagalnu aktivnost, kao što su simpati- [16]. Pathophysiologically, drugs increasing or decreas-
komimetici, parasimpatikomimetici i njihovi inhibito- ing adrenergic or vagal activity, such as sympathomi-
ri, mogu da izazovu atrijalnu fibrilaciju, posebno kod metics, parasympathomimetics, and their inhibitors,
kardiovaskularnih pacijenata (bolest je supstrat, lek je may cause atrial fibrillation, especially in cardiovascu-
pokretač), ali i kod, naizgled, zdravih pacijenata [3]. Me- lar patients (the disease is the substrate, the drug is
hanizam atrijalne fibrilacije izazvane lekovima nije tač- the trigger), but also in seemingly healthy patients. [3].
no poznat. Fudžimoto i saradnici su pronašli da efluks The mechanism of drug-induced atrial fibrillation is not
kalijuma iz ćelije, koji je uzrokovan direktnim dejstvom precisely known. Fujimoto et al. found that the efflux of
metilprednizolona na ćelijsku membranu, može dove- potassium from the cell, caused by the direct action of
sti do poremećaja srčanog ritma [12]. methylprednisolone on the cell membrane, may lead
Prikazujemo slučaj bolesnika sa HLL-om, kod koga to cardiac rhythm disturbance [12].
je, nakon primene visoke doze intravenskog metilpred- We present the case of a patient with CLL, in whom,
nizolona, došlo do pojave AF. after the administering of high-dose intravenous
methylprednisolone, AF occurred.
PRIKAZ SLUČAJA
Bolesnik, starosti 69 godina, imao je dijagnozu hro-
CASE REPORT
nične limfocitne leukemije, koja je postavljena 1992. A 69-year-old patient had the diagnosis of chronic lym-
godine, u kliničkom stadijumu (engl. clinical stage – phocytic leukemia, established in 1992 – clinical stage
CS) 0. Anamneza je bila bez drugih hroničnih bolesti. (CS) 0. Anamnesis showed no other chronic diseases. The
Redovno je kontrolisan, bez terapije do februara 2019. patient had regular follow-up; he received no treatment
godine, kada dolazi do progresije bolesti, sa pojavom until February 2019, when the disease started to prog-
opštih simptoma i splenomegalije. Laboratorijske ress and general symptoms, as well as splenomegaly,
kardiotoksičnost visoke doze metilprednizolona kod bolesnika sa hroničnom limfocitnom leukemijom - prikaz slučaja
Apostolović Stojanović M. i sar.
analize krvi su pokazale: leukocitozu (47,1 x 109/l) sa developed. Laboratory blood test results showed the
80% limfocita, anemiju sa hemoglobinom od 115 g/l, following: leukocytosis (47.1 x 109/l) with 80% of lym-
trombocitopeniju (132 x 109/l), te normalne vrednosti phocytes, anemia with a hemoglobin level of 115 g/l,
laktat dehidrogenaze (194 IJ/L), parametara bubrežne thrombocytopenia (132 x 109/l), as well as normal levels
funkcije i hepatograma. Citogenetska analiza – fluores- of lactate dehydrogenase (194 IJ/L), renal function pa-
centna in situ hibridizacija (FISH) otkrila je deleciju 13q rameters, and hepatogram. Cytogenetic analysis – fluo-
u 80% jedara i deleciju 17p u 20% jedara. rescence in situ hybridization (FISH) discovered 3q dele-
Lečenje je započeto primenom VDMP-a (1.500 mg tion in 80% of nuclei and 17p deletion in 20% of nuclei.
dnevno, IV, tokom 5 dana, u ciklusima od 4 nedelje). Treatment started with the application of HDMP
Trećeg dana drugog ciklusa, nakon primene VDMP-a, (1,500 mg per day, IV, for 5 days, in four-week cycles).
bolesnik prijavljuje osećaj lupanja srca. Na elektrokar- On the third day of the second cycle, after the applica-
diogramu (EKG) registrovane su pojedinačne ekstra- tion of HDMP, the patient reported feeling palpitations.
sistole, a zatim i pojava atrijalne fibrilacije, sa komor- The electrocardiogram (ECG) registered individual ex-
skom frekvencom od oko 140/min, bez promena u ST trasystoles, and then the occurrence of atrial fibrilla-
segmentu. Bolesnik je bio normotenzivan. Troponin tion, with a ventricular frequency of around 140/min,
(engl. high sensitivity troponin I assay – hsTnI), krea- without changes in the ST segment. The patient was
tin-kinaza (engl. creatine kinase – CK), kreatin-kinaza normotensive. Troponin (high sensitivity troponin I as-
izoenzim (engl. creatine kinase isoenzyme – CK-MB), say – hsTnI), creatine kinase (CK), creatine kinase isoen-
proBNP (engl. pro b-type natriuretic peptide) (100 pg/ zyme (CK-MB), pro b-type natriuretic peptide (proBNP)
ml) i tiroidni status (engl. thyroid stimulating hormone – (100 pg/ml), and thyroid status (thyroid stimulating
TSH) (1,66 mU/l) bili su u referentnom opsegu (hsTnI < hormone – TSH) (1.66 mU/l) were within the reference
34 ng/L; CK = 29 - 168 IJ/L; CK-MB = 7 – 25 IJ/L: proBNP range (hsTnI < 34 ng/L; CK = 29 - 168 IJ/L; CK-MB = 7 –
< 450 pg/ml; TSH = 0,35 – 4,94 mU/L). Ehokardiograf- 25 IJ/L: proBNP < 450 pg/ml; TSH = 0.35 – 4.94 mU/L).
ski, leva pretkomora je bila normalnih dimenzija, bez Echocardiographically, the left atrium had normal
spontanog eho kontrasta i trombnih masa; registro- dimensions, without spontaneous echo contrast or
vana je normalna sistolna i dijastolna funkcija leve ko- thrombotic masses; normal systolic and diastolic func-
more (ejekciona frakcija = 55%). Koronarografijom nije tion of the left ventricle (ejection fraction = 55%) was
utvrđeno postojanje koronarne bolesti srca. registered. Coronarography did not establish the pres-
Nakon 48 sati terapije antiaritmikom klase III (amjo- ence of coronary heart disease.
daron), došlo je do konverzije u sinusni ritam, koji se odr- After 48 hours of treatment with a class III antiar-
žavao, što je potvrđeno i 24-časovnim Holter EKG-om. rhythmic (amiodarone), conversion into normal sinus
Bolesnik je, pored amjodarona, bio i na niskoj dozi be- rhythm occurred; the normal sinus rhythm persisted,
ta-blokatora, kada je primenjen sledeći ciklus VDMP-a, which was confirmed with 24-hour Holter ECG. In addi-
a po čijem završetku, tokom 48-časovnog Holter-EKG-a, tion to amiodarone, the patient was also on a low dose
nije registrovan paroksizam atrijalne fibrilacije. of beta-blockers when the next cycle of HDMP was
administered, upon whose completion, after 48-hour
DISKUSIJA Holter monitoring, paroxysmal atrial fibrillation was
Atrijalna fibrilacija izazvana lekovima javlja se kod pa- not registered.
cijenata bez prethodne pojave atrijalne fibrilacije ili
strukturnih srčanih oboljenja. Očekivani rizik od pojave
DISCUSSION
atrijalne fibrilacije izazvane lekovima povećan je kod Drug-induced atrial fibrillation occurs in patients with-
starijih osoba i pacijenata sa kardiovaskularnim komor- out previous episodes of atrial fibrillation or structural
biditetima. [3,17]. Mehanizam nastanka aritmija nakon heart disease. The expected risk of drug-induced atrial
visokih doza kortikosteroida nije jasan. Predloženo je fibrillation is increased in elderly patients and patients
nekoliko mehanizama: direktno povećanje efluksa kali- with cardiovascular comorbidities [3,17]. The mecha-
juma, efekat mineralkortikosteroida, koji dovodi do za- nism of the development of arrythmias after high doses
državanja natrijuma i tečnosti, povećanja leve pretko- of corticosteroids is not clear. Several possible mecha-
more i kongestivne srčane insuficijencije, kao i razvoj nisms have been proposed: direct increase in the efflux
kasnih potencijala i izražen periferni vazodilatatorni of potassium, the effect of mineralocorticoids, which
odgovor [3,12,18,19]. leads to the retention of sodium and fluids, increase of
U literaturi je opisano nekoliko slučajeva atrijalne the left atrium and congestive heart failure, as well as
fibrilacije nakon terapije visokim dozama kortikostero- the development of late potentials and pronounced
ida [10,11,13,19-22]. Studija van der Hufta i saradnika peripheral vasodilator response [3,12,18,19].
je pokazala da je upotreba visokih doza kortikosteroi- Several cases of atrial fibrillation developing after
da povezana sa povećanim rizikom od razvoja atrijalne high-dose corticosteroid treatment have been de-
fibrilacije [18]. scribed in literature [10,11,13,19-22]. A study by van
U nekim radovima, kortikosteroidi su dovođeni u der Hooft et al. has shown that the application of high
vezu sa pojavom atrijalne fibrilacije, nezavisno od puta doses of corticosteroids is connected with increased
primene leka. Pojava atrijalne fibrilacije je zabeležena risk of atrial fibrillation development [18].
tokom primene visokih pulsnih doza metilprednizolo- In some studies, corticosteroids have been con-
na [5–9,14], kod primene nižih doza intravenske terapi- nected to the occurrence of atrial fibrillation, inde-
je metilprednizolonom, kao i nakon primene inhalator- pendently of the method of drug administration. The
nih oblika kortikosteroida [5,23,24]. occurrence of atrial fibrillation was recorded during the
U literaturi je opisano da se atrijalna fibrilacija javila application of high-dose methylprednisolone pulse
tokom ili ubrzo nakon završetka infuzije VDMP-a [11] ili therapy [5–9,14], in the application of lower doses of in-
u roku od 24 – 48 sati od završetka terapije VDMP-om travenous methylprednisolone therapy, as well as after
[5,21,22]. Takođe, nekoliko objavljenih slučajeva je po- the application of inhalation corticosteroids [5,23,24].
kazalo da je pojava atrijalne fibrilacije registrovana u Reports of atrial fibrillation occurring during or
roku od 24 do 48 sati od završetka terapije VDMP-om. soon after IV administration of HDMP [11] or with-
Kod našeg bolesnika vreme pojave atrijalne fibrilacije in 24 – 48 hours of the completion of HDMP therapy
je bilo u skladu sa prethodnim zapažanjima. [5,21,22] can be found in literature. Also, several pub-
Moreti i saradnici su opisali slučaj pedesetdeveto- lished cases have shown that the occurrence of atrial
godišnjeg muškarca sa dijagnozom primarno progre- fibrillation was registered within 24 to 48 hours since
sivne multiple skleroze, koji je lečen visokim dozama the completion of HDMP therapy. In our patient, the
metilprednizolona. Posle treće doze metilprednizolona time of atrial fibrillation occurrence was in keeping
(1 g, IV, tokom 2 h) na EKG-u je viđena AF. Nakon što je with previous reports.
dva dana lečen digoksinom i propafenonom, AF je me- Moretti et al. described the case of a fifty-nine-year-
dikamentozno konvertovana u sinusni ritam [9]. old man diagnosed with primary progressive multiple
Početak atrijalne fibrilacije indukovane lekovima je sclerosis, who was treated with high doses of methyl-
prilično varijabilan, u zavisnosti od leka, u rasponu od prednisolone. After the third dose of methylprednisolone
nekoliko sekundi/minuta nakon intravenozne primene (1 g, IV, for 2 hours) ECG showed AF. After being treated
leka kratkog poluživota, do nekoliko dana, u slučaju ne- for two days with digoxin and propafenone, AF was con-
kih hemoterapijskih agenasa. Ponekad se AF induko- verted to normal sinus rhythm with medication [9].
vana lekovima pojavljuje, ne tokom prvog, već nakon The onset of drug-induced atrial fibrillation is rather
ponovljenog izlaganja leku. Trajanje atrijalne fibrilacije variable, depending on the drug, ranging from several
izazvane lekovima je takođe promenljivo – opisano je seconds/minutes after intravenous application of a drug
trajanje od nekoliko sekundi do nekoliko sati [25]. with a short half-life, to several days after application, in
Naš bolesnik nije imao istoriju prethodnog možda- the case of some chemotherapeutic agents. Sometimes,
nog udara, niti istoriju hipertireoze, koronarne bolesti, drug-induced AF occurs, not during the first, but after
kao ni implantirane srčane uređaje, prethodne opera- repeated exposure to a drug. The duration of drug-in-
cije na otvorenom srcu ili prethodno zabeleženu poja- duced atrial fibrillation is also variable – the duration of
vu atrijalne fibrilacije. EKG, pre primene VDMP-a, poka- several seconds to several hours has been described [25].
zao je normalni srčani ritam. Kao i u većini slučajeva, i Our patient did not have a history of previous stroke,
u našem slučaju, AF je bila paroksizmalna i završila se or a history of hyperthyreosis, coronary disease, nor im-
nakon nekoliko sati. planted cardiac devices, previous open-heart surgeries
Do danas nisu identifikovani nikakvi faktori pomo- or previously registered episodes of atrial fibrillation.
ću kojih bi se mogla predvideti pojava atrijalne fibri- The ECG, before HDMP application, showed normal car-
lacije. U prethodno objavljenim studijama, tzv. global diac rhythm. As in most cases, in the case of our patient
strain i strain rate leve pretkomore bili su značajno sma- as well, AF was paroxysmal and ended after a few hours.
njeni kod pacijenata sa paroksizmalnom atrijalnom fi- To date, no factors have been identified that would
brilacijom, u poređenju sa normalnim vrednostima u help predict the occurrence of atrial fibrillation. In pre-
kontrolnoj grupi [26,27,28,29]. viously published studies, the so-called global strain
Zanimljiva je činjenica da su trajanje P talasa i dis- and strain rate of the left atrium were significantly de-
perzija P talasa takođe povezani sa povećanim rizikom creased in patients with paroxysmal atrial fibrillation,
za pojavu atrijalne fibrilacije i mogu se koristiti kao as compared to the normal values found in the control
elektrokardiografski markeri [30]. Takođe, natriuretski group [26,27,28,29].
kardiotoksičnost visoke doze metilprednizolona kod bolesnika sa hroničnom limfocitnom leukemijom - prikaz slučaja
Apostolović Stojanović M. i sar.
peptidi su statistički značajno povezani sa inciden- It is interesting that P-wave duration and P-wave
tnom atrijalnom fibrilacijom [31]. Kod našeg bolesnika dispersion are also connected with the increased risk
proBNP je bio u referentnom opsegu. of atrial fibrillation occurrence, and they can be used
Pojava atrijalne fibrilacije je takođe opisana i kod as electrocardiographic markers [30]. Also, natriuretic
primene inhibitora tirozin kinaze (ibrutinib) kod bole- peptides are statistically significantly connected with
snika sa HLL-om, u 6 – 16% slučajeva [32,33]. incident AF [31]. In our patient, proBNP was within the
reference range.
ZAKLJUČAK The occurrence of atrial fibrillation has also been
Atrijalna fibrilacija indukovana lekovima predstavlja reported in the application of tyrosine kinase inhibitors
neželjeni efekat terapije, koji može biti ograničavaju- (ibrutinib) in patients with CLL, in 6 – 16% cases [32,33].
ći faktor za nastavak lečenja osnovne bolesti. Klinički
pregled i elektrokardiografsko praćenje, tokom i nakon
CONCLUSION
terapije visokim dozama kortikosteroida, mogu pove- Drug-induced atrial fibrillation is a side effect of treat-
ćati šanse za raniju dijagnozu atrijalne fibrilacije. Neop- ment, which may be a limiting factor for the continua-
hodna su dalja istraživanja radi otkrivanja prediktivnih tion of underlying disease treatment. Clinical examina-
faktora za pojavu atrijalne fibrilacije, pre davanja speci- tion and electrocardiographic monitoring, during and
fične terapije. after high-dose corticosteroid treatment, may increase
Sukob interesa: Nije prijavljen. the chances of earlier diagnosis of atrial fibrillation.
Further research and investigation are necessary in
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STEČENA HEMOFILIJA KOD BOLESNIKA NA ORALNOJ
ANTIKOAGULANTNOJ TERAPIJI - PRIKAZ SLUČAJA
ACQUIRED HEMOPHILIA IN PATIENTS ON ORAL

ANTICOAGULANT THERAPY – CASE REPORT
Jelena Ljubičić
Opšta bolnica „Studenica“, Kraljevo, Srbija General hospital "Studenica", Kraljevo, Serbia
SAŽETAK ABSTRACT
Uvod: Stečena hemofilija je teško, nekada i fatalno stanje poremećene koagula- Introduction: Acquired hemophilia is a severe, sometimes even fatal condition
cije. Najčešće dovodi do teških mukokutanih, gastrointestinalnih, urinarnih, retko of impaired coagulation. It most often leads to severe mucocutaneous, gastroin-
i intrakranijalnih krvarenja. Razlog ovakvog poremećaja je stvaranje antitela na testinal, urinary, and, rarely, intracranial bleeding. This disorder occurs due to the
faktor VIII koagulacije (F VIII), što ometa njegovu normalnu funkciju. U laborato- production of antibodies against clotting factor VIII (F VIII), which interfere with
rijskim analizama se uočava produženo aktivirano parcijalno tromboplastinsko its normal function. In laboratory analyses, prolonged activated partial thrombo-
vreme (engl. activated partial thromboplastin time – aPTT), koje se ne može nor- plastin time (aPTT), which cannot be normalized after being mixed with pooled
malizovati ni posle mešanja sa plazmom zdrave osobe. normal plasma, is noticeable.
Prikaz bolesnika: U ovom radu prikazan je klinički tok kod bolesnika sa ste- Case report: In this article, the clinical course of the disease is described in a
čenom hemofilijom, koji je bio na oralnoj antikoagulantnoj terapiji, a inicijalno patient with acquired hemophilia, who was treated with oral anticoagulant
je imao i produženo protrombinsko vreme, izraženo jedinicama međunarodnog therapy, and who initially also had prolonged prothrombin time, measured in
normalizovanog odnosa (engl. International normalized ratio - INR), koji se prora- international normalized ratio (INR) units, which measure how long it takes for
čunava na osnovu vremena potrebnog da se formira ugrušak u uzorku krvi. He- a clot to form in a blood sample. Hemorrhagic syndrome was explained by iatro-
moragijski sindrom je tumačen jatrogenim efektom, a kako se krvarenje nastavilo genic effect. However, since bleeding continued after INR normalization, it was
i nakon normalizacije INR-a, posumnjano je na drugi uzrok hemoragijskog sin- suspected that there was a different cause of hemorrhagic syndrome. The aPTT
droma. Urađen je test mešanja plazme bolesnika i plazme zdrave osobe (mešanje mixing test was performed (mixing an equal volume of the patient's plasma and
jednake zapremine pacijentove plazme i plazme zdrave osobe, te ponavljanje normal pooled plasma (NPP) and repeating the aPTT test immediately and after
aPTT testa odmah, i jedan sat nakon inkubacije), posle čega je aPTT ostalo produ- one-hour incubation), after which the aPTT remained prolonged. This proved
ženo. Ovo je bio dokaz postojanja inhibitora koagulacije, koji je pobudio sumnju the presence of coagulation inhibitors, which is why acquired hemophilia was
na stečenu hemofiliju. Bolesnik je upućen u tercijarnu ustanovu gde je dalje spro- suspected. The patient was referred to a tertiary medical institution for further
vedena dijagnostika i lečenje. diagnostics and treatment.
Zaključak: Cilj ovog prikaza slučaja je da se pokaže da bolesnici sa hemoragij- Conclusion: The objective of this case report is to show that patients with hem-
skim sindromom koji sa na terapiji antikoagulansima mogu da razviju hemoragij- orrhagic syndrome, who are on anticoagulant therapy, may develop hemorrhagic
ski sindrom i iz drugog, nejatrogenog razloga. Svrha rada je da se skrene pažnja syndrome for a different, non-iatrogenic reason. The purpose of the study is to
lekara na različite uzroke hemoragijskog sindroma kod bolesnika na antikoagu- draw the attention of medical doctors to various causes of hemorrhagic syn-
lantnoj terapiji. drome in patients receiving anticoagulant therapy.
Ključne reči: stečena hemofilija, oralna antikoagulantna terapija, produženo Key words: acquired hemophilia, oral anticoagulant therapy, prolonged activat-
aktivirano parcijalno protrombinsko vreme, hemoragijski sindrom ed partial thromboplastin time, hemorrhagic syndrome

Jelena Ljubičić Jelena Ljubičić
Opšta bolnica „Studenica“ General hospital "Studenica"
Jug Bogdanova 2, 36000 Kraljevo, Srbija 2 Jug Bogdanova Street, 36000 Kraljevo, Serbia
Elektronska adresa: jeljub1408@gmail.com E-mail: jeljub1408@gmail.com
Primljeno • Received: November 28, 2021; Revidirano • Revised: December 26, 2021; Prihvaćeno • Accepted: April 20, 2022; Online first: June 25, 2022
DOI: 10.5937/smclk3-35121
stečena hemofilija kod bolesnika na oralnoj antikoagulantnoj terapiji - prikaz slučaja
Ljubičić J.
acquired hemophilia in patients on oral anticoagulant therapy – case report
UVOD INTRODUCTION
Stečena hemofilija je retko stanje poremećene koa- Acquired hemophilia is a rare condition of impaired co-
gulacije sa incidencijom od oko 0,2 do 1 slučaja na agulation with a yearly incidence of around 0.2 to 1 case
1.000.000 stanovnika godišnje. Uzrok bolesti je pojava per 1,000,000 population. The cause of the disease is the
antitela na esencijalni protein zgrušavanja krvi, tako- presence of antibodies to an essential blood-clotting
zvani faktor koagulacije VIII (F VIII), poznat kao antihe- protein, the so-called factor VIII (F VIII), also known as an-
mofilni faktor. Stvaranje antitela na F VIII dovodi do po- tihemophilic factor VIII. The production of antibodies to
remećaja u zgrušavanju [1-7]. Javlja se kod osoba koje F VIII leads to clotting inefficiency [1-7]. It occurs in indi-
prethodno nisu imale poremećaj koagulacije. Inciden- viduals who had previously not had any bleeding disor-
cija je slična kod oba pola, sa bifazičnom krivom dis- der. The incidence is similar in both genders, with a bi-
tribucije incidencije između 20 i 40 godina (češće kod phasic incidence distribution curve, between 20 and 40
žena) i između 60 i 80 godina (češće kod muškaraca). years (more common in women) and between 60 and 80
Sama antitela su najčešće poliklonski IgG4. U oko 50% years (more common in men). The most commonly oc-
slučajeva uzrok bolesti je idiopatski, a u 50% slučajeva, curring antibodies are polyclonal IgG4. In about 50% of
uzrok je povezan sa različitim stanjima [1-4]. cases, the cause of the disease is idiopathic, and in 50%
Kao najčešeći uzročnici pojave antitela na faktor of cases it is associated with various conditions [1-4].
VIII, u okviru stečene hemofilije, navode se autoimune The conditions that are referred to as the most com-
bolesti (reumatoidni artritis, sistemski eritemski lupus, mon causes of the presence of antibodies against fac-
Sjogrenov sindrom, miastenija gravis, multipla sklero- tor VIII within acquired hemophilia are the following:
za, autoimuni hipotireoidizam, Grejvsova bolest), za- autoimmune diseases (rheumatoid arthritis, systemic
paljenske bolesti creva, astma, bolest kalema protiv lupus erythematosus, Sjogren syndrome, myasthenia
domaćina (engl. graft versus host disease – GVHD) posle gravis, multiple sclerosis, autoimmune hypothyroidism,
alogene transplantacije koštane srži, trudnoća, kao i Graves’ disease), inflammatory bowel diseases, asthma,
period od 4 meseca do godinu dana posle porođaja. graft versus host disease (GVHD) after bone marrow
Sekundarni uzroci su maligniteti – hematološki mali- transplantation, pregnancy, as well as the period of 4
gniteti (limfoproliferativne bolesti, osteomijelofibro- months to one year after delivery. The secondary cause
za, eritroleukemija) i solidni tumori (tumori prostate, are malignancies - hematological malignancies (lymph-
dojke, bubrega, gastrointestinalnog trakta, pankreasa, proliferative diseases, osteomyelofibrosis, erythroleuke-
melanom). Nekada se antitela zadržavaju i nakon što mia) and solid tumors (prostate, breast, renal, gastroin-
je tumor uklonjen. Neki lekovi utiču na protrombinsko testinal, pancreatic, melanoma). Sometimes antibodies
vreme, na primer penicilin, sulfonamidi, hinoloni, hlo- are retained even after the tumor has been removed.
ramfenikol, fludarabin, fenitoin, klopidogrel, levodopa, Drugs that affect prothrombin time are the following:
kao i BCG vakcina. U vodičima za dobru kliničku praksu penicillin, sulfonamides, quinolones, chloramphenicol,
postoje opisane mogućnosti udruženosti sa direktnim fludarabine, phenytoin, clopidogrel, levodopa, as well
oralnim antikoagulansima kao i sa hirurškim interven- as the BCG vaccine. Cases associated with direct oral
cijama [1-5,8,9]. anticoagulants, as well as surgical procedures, have also
Klinička slika se obično manifestuje teškim muko- been described in good clinical practice guides [1-5,8,9].
kutanim krvarenjem, krvarenjem u mekim tkivima (uz The clinical manifestation is usually severe mucocu-
pojavu kompartment sindroma), gastrointestinalnim taneous bleeding, as well as soft tissue bleeding (with
i urogenitalnim krvarenjem, a ponekad i intrakrani- the development of the compartment syndrome), gas-
jalnim krvaranjem. Za razliku od nasledne hemofilije, trointestinal and urogenital bleeding, sometimes even
ovde su krvarenja u zglobovima jako retka [2,3,5]. U la- intracranial bleeding. Unlike congenital hemophilia,
boratorijskim nalazima, hemoglobin može biti snižen, bleeding in the joints is very rare [2,3,5]. The laboratory
dok su broj trombocita, protrombinsko vreme (INR) i fi- results may show reduced levels of hemoglobin, while
brinogen uredni, ali je aktivirano parcijalno trombopla- the platelet count, prothrombin time (INR), and fibrin-
stinsko vreme (aPTT) produženo. Prisustvo antitela se ogen remain within the normal range. However, acti-
dokazuje testom mešanja sa normalnom plazmom. vated partial thromboplastin time (aPTT) is prolonged.
Lako izvodljiv test mešanja plazme bolesnika i plazme The presence of antibodies is proven by the mixing test.
zdrave osobe na temperaturi 37 °C u trajanju od 2 sata, An easily performed mixing test of the patient’s plasma
pri čemu se aPTT bolesnika ne normalizuje, ukazuje and the plasma of a healthy person at 37 °C for 2 hours,
na prisustvo inhibitora faktora koagulacije i na steče- wherein the patient's aPTT is not normalized, indicates
nu hemofiliju [6,10-11]. Nakon pozitivnog testa radi the presence of coagulation factor inhibitors as well as
se određivanje nivoa F VIII i nivoa inhibitora na F VIII, the presence of acquired hemophilia [6,10-11]. After
Ljubičić J.
izraženog u Bethesda jedinicama. Lečenje podrazume- a positive test is established, the Bethesda method is
va kontrolu krvarenja i terapiju koja će smanjiti nivo used to determine the level of clotting factor VIII and
inhibitora. U cilju zaustavljanja krvarenja, neophodna the level of F VIII inhibitors. Treatment involves bleed-
je terapija bypassing sredstvima, kao što su rekombi- ing control and therapy aimed at reducing the level of
nantni faktor VII (rVII NovoSeven) ili aktivirani protrom- inhibitors. In order to stop the bleeding, treatment with
binski kompleks FEIBA (Factor Eight Inhibitor Bypassing bypassing agents, such as recombinant factor VII (rVII
Activity) – ako je nivo inhibitora veći od 5 Bethesda je- NovoSeven) or the activated prothrombin complex FEI-
dinica. Ako je nivo inhibitora manji od 5 Bethesda jedi- BA (factor eight inhibitor bypassing activity) is neces-
nica, ordinira se koncentrat faktora VIII ili DDAVP (dez- sary – if the level of inhibitors is higher than 5 Bethesda
mopresin) [1,6,8]. units. If the level of inhibitors is lower than 5 Bethesda
Istovremeno se uvodi i terapija kortikosteroidima units, clotting factor VIII concentrate or DDAVP (desmo-
ili čak ciklofosfamidom, čiji je cilj smanjenje sinteze in- pressin) is prescribed [1,6,8].
hibitora koagulacije, a u rezistentnim oblicima može se At the same time, treatment with corticosteroids or
ordinirati i rituksimab, takrolimus, ciklosporin i mikofe- even cyclophosphamide, aimed at reducing the synthe-
nolat mofetil, kao i primeniti procedura ekstrakorporal- sis of coagulation inhibitors, is introduced. In resistant
ne plazmafereze sa imunoadsorpcijom. Obično se nivo forms, rituximab, tacrolimus, cyclosporine, and myco-
inhibitora postepeno smanjuje tokom više narednih phenolat mofetil may be administered, and extracorpo-
meseci [6,8,10-11]. Kod bolesnika koji su na oralnoj an- real plasmapheresis and immunoadsorption may be ap-
tikoagulantnoj terapiji a imaju hemoragijski sindrom plied. Usually, the level of inhibitors gradually decreases
ovo stanje se može prevideti, jer se obično kontroliše over the following months [6,8,10-11]. In patients on
samo protrombinsko vreme [12–15]. oral anticoagulant therapy who have hemorrhagic syn-
Cilj ovog prikaza slučaja jeste da se pokaže da bo- drome, this condition can be overlooked, since, usually,
lesnici sa hemoragijskim sindromom koji sa na terapiji only the prothrombin time is monitored [12–15].
antikoagulansima mogu da razviju hemoragijski sin- The aim of this case report is to show that patients
drom i iz drugog, nejatrogenog razloga. Na takvu mo- with hemorrhagic syndrome who are on oral antico-
gućnost posebno treba misliti kada se, i pored korekci- agulant therapy can develop hemorrhagic syndrome
je vrednosti INR-a, hemoragijski sindrom klinički i dalje for a different, non-iatrogenic, reason. Such a possibil-
održava [15]. ity should be especially considered when, despite the
correction of INR, hemorrhagic syndrome still persists,
PRIKAZ SLUČAJA clinically [15].
Prikazan je bolesnik starosti 66 godina, koji se dve
godine unazad lečio od dilatativne kardiomiopatije
CASE PRESENTATION
(ejekciona frakcija = 30%, mitralna regurgitacija = 3+, We present a 66-year-old patient who had previous-
end-dijastolni dijametar leve komore = 71 mm), a kome ly been treated for dilated cardiomyopathy for two
je zbog postojanja perzistentne atrijalne fibrilacije uve- years (ejection fraction = 30%, mitral regurgitation =
dena oralna antikoagulantna terapija kumarinskim de- 3+, left ventricular end-diastolic diameter = 71 mm).
rivatom. Tokom dve godine, pacijent je redovno pra- Due to the presence of persistent atrial fibrillation, oral
ćen ambulantno, bez hemoragijskog sindroma i bez anticoagulant therapy with coumarin derivatives was
značajnog povećanja protrombinskog vremena (engl. introduced. He was regularly monitored for two years
prothrombin time – PT). Oko 4 nedelje pre prezentacije with no sign of hemorrhagic syndrome and without
opisane u ovom radu, bolesnik je primetio pojavu sve- a significant increase in prothrombin time (PT). Four
že krvi u stolici, uz bolove u donjem delu trbuha. weeks before the presentation described in this paper,
Pacijent je hospitalizovan na odeljenju hirurgi- the patient noticed fresh blood in his stool with pain
je, sa sledećim vrednostima: INR = 4,84 (0,70 - 1,20), in the lower abdomen. He was hospitalized in the sur-
aPTT = 83,9 s (26.00 s – 36.00 s). Primio je tri jedinice gery department with the following laboratory results:
sveže smrznute plazme, INR je nakon toga bio 2,8, aPTT INR = 4.84 (0.70 – 1.2), aPTT = 83.9 s (26.00 s – 36.00 s).
nije ponavljano, krvarenje se zaustavilo, nije bilo pada The patient received three units of fresh frozen plas-
vrednosti hemoglobina. Zakazana je kolonoskopija i ma, upon which INR was 2.8, aPTT was not repeated,
pacijent je pušten na kućno lečenje. bleeding was stopped, and there was no decrease in
U daljem toku, pacijent se javio u tercijarnu usta- the hemoglobin level. Colonoscopy was scheduled for
novu na zakazanu koronarografiju ali je ista odložena the patient, and he was released to recover at home.
zbog povišenog C reaktivnog proteina, koji je iznosio When the patient came in for coronary angiog-
30 mg/L. Pacijent je ponovo hospitalizovan, sada na raphy, scheduled at a tertiary healthcare facility, he
Ljubičić J.
internom odeljenju, radi daljeg ispitivanja. Zbog loše had an elevated C reactive protein level of 30 mg/L.
saniranih zuba pregledan je od strane maksilofacijal- Coronary angiography was, therefore, postponed
nog hirurga, a zbog prethodne pojave krvi u stolici ura- and he was again hospitalized for further examina-
đena je i gastroskopija. U tom trenutku je laboratorijska tion, this time at the internal medicine department.
analiza pokazivala da je INR bio u terapijskom opsegu, Due to the poor condition of his teeth, the patient
aPTT nije rađeno, dok su svi ostali parametri bili uredni, was examined by a maxillofacial surgeon. Due to pre-
uključujući i nivo hemoglobina. Trećeg dana hospita- viously registered blood in his stool, gastroscopy was
lizacije, uočena je pojava hematoma na levoj natko- also performed. At that point, the INR level was with-
lenici; bolesnik je naveo da je prethodno ambulantno in the normal therapeutic range, while aPTT was not
primio intramuskularnu injekciju. Ukinuta je oralna an- tested, and all other parameters were normal, includ-
tikoagulantna terapija i pacijent je preveden na nisko ing the hemoglobin level. On the third day of hos-
molekularni heparin (engl. low molecular weight he- pitalization, a hematoma was registered on the left
parin – LMWH). U laboratorijskom nalazu, INR je bio u thigh, and the patient stated that he had previously
fiziološkim okvirima, a aPTT vrednost nije određivana. received an intramuscular injection. Oral anticoagu-
Četvrtog dana hospitalizacije, na levoj podlaktici, na lant therapy was discontinued and replaced with low
mestu gde je bila plasirana braunila, dolazi do pojave molecular weight heparin (LMWH). The INR level was
intenzivnog krvarenja koje se moralo hirurški zaustavi- within the normal range, while aPTT was not tested.
ti. Bolesnik se naredna dva dana žalio na progresivno On the fourth day of the patient’s hospital stay, there
otežano gutanje. Pet dana posle gastroskopije, uočava was copious bleeding at the site where a cannula had
se gotovo nemoguće gutanje, stridorozno disanje, kao been placed on the patient’s left forearm. The bleed-
i ogroman hematom prednjeg zida vrata, poda usne ing had to be surgically stopped. Over the next two
duplje i jezika (Slike 1a, 1b). Ultrazvuk vrata ukazao je days, the patient complained of progressively greater
na izrazito edematozno izmenjeno tkivo praktično and greater difficulty swallowing. Five days after gas-
svih regija vrata. Kompjuterizovana tomografija vra- troscopy, it was evident that it was almost impossible
ta opisala je supraglotično, na zadnjem zidu vrata, sa for the patient to swallow, stridor was present, as well
propagacijom desno, nepravilnu formaciju (hematom) as a massive hematoma of the front wall of the neck,
dijametra 25 x 20 mm, koja je gotovo u potpunosti su- floor of the oral cavity, and tongue (Figures 1a, 1b).
žavala vazdušni stub opisane regije. Obe submandibu- Ultrasound of the neck revealed extremely edema-
larne žlezde su bile otečene, uvećane, heterodenzne, tous tissue of virtually all compartments of the neck.
komprimujući okolne mekotkivne strukture i mišićne The CT of the neck showed – supraglottically, on the
strukture od kojih su se teško diferencirale, sužavajući posterior wall of the neck, with propagation to the
lumen vazdušnog stuba na tom nivou. Tada je u labo- right – an irregular formation (hematoma), 25 x 20
ratoriji zabeležen pad vrednosti hemoglobina za 30 g, mm in diameter, which almost completely narrowed
INR je bio normalan, a po prvi put je urađeno i aPTT, the airway in the described region. Both subman-
koje je bilo 58,3 s (26,00 s – 36,00 s). Urađen je test me- dibular glands were swollen, enlarged, heterodense,
šanja sa normalnom plazmom, posle čega je aPTT i da- compressing the surrounding soft tissue structures
lje bilo produženo, što je bio razlog da se posumnja na and muscular structures. It was difficult to differenti-
postojanje inhibitora koagulacije u plazmi bolesnika. ate the glands from the surrounding tissue and they
S obzirom na preporučeno lečenje, kao i nemoguć- were narrowing the lumen of the airway. Laboratory
nost dalje dijagnostike (određivanje nivoa F VIII i nivoa test results showed a drop in the level of hemoglobin
inhibitora Bethesda metodom), bolesnik je upućen u by 30 g, the INR value was normal, aPTT was tested for
tercijarnu ustanovu, gde je ustanovljen snižen nivo F the first time, and was 58.3 s (26.00 s – 36.00 s). The
VIII, kao i povišen nivo inhibitora F VIII od 9 Bethesda mixing test with normal plasma was then performed
jedinica. Ordinirana je FEIBA terapija uz istovremeno showing that aPTT was still prolonged, which led to
započinjanje terapije pronisonom i ciklofosfamidom. the suspicion that coagulation inhibitors were pres-
Detaljnim kliničkim i imunološkim analizama nije usta- ent in the patient’s plasma.
novljeno sekundarno stanje koje bi moglo biti uzrok Given the recommended treatment, as well as the
stečene hemofilije. S obzirom na perzistentnu atrijalnu fact that it was not possible to perform further diag-
fibrilaciju, bolesniku je, po normalizaciji nivoa F VIII na- nostics (determining F VIII levels and inhibitor levels
kon primenjene navedene terapije, nastavljena oralna with the Bethesda method) within the facility that the
antikoagulantna terapija, oko 6 nedelja od početka le- patient was hospitalized in, the patient was referred
čenja. to a tertiary medical facility, where a decreased level
of F VIII was found, as well as an increased level of F
Ljubičić J.
Slika 1. Hemoragijski sindrom kod bolesnika sa stečenom hemofilijom Figure 1. Hemorrhagic syndrome in a patient with acquired hemophilia
a) Hematom podvilične regije a) Hematoma of the submandibular region
b) Hemoragijska bula desne strane jezika b) Hemorrhagic bulla of the right side of the tongue
DISKUSIJA VIII inhibitors, measuring 9 Bethesda units. FEIBA was

administered and the patient was also started on pred-
Poznato je da kumarinski derivati produžavaju INR i nisone and cyclophosphamide at the same time. De-
aPTT zbog zajedničkog efekta na nivo faktora koagu- tailed clinical and immunological examinations and
lacije IX [6,10-11]. U literaturi se navode slučajevi bole- analyses could not identify a secondary condition that
snika sa hemoragijskim sindromom koji su na oralnoj could be the cause of acquired hemophilia. Due to per-
antikoagulantnoj terapiji kumarinskim derivatima, kod sistent atrial fibrillation, the patient continued with oral
kojih se i INR i aPTT obično kontrolišu samo pri prezen- anticoagulant therapy after the normalization of F VIII
taciji bolesti, dok se nadalje prati samo INR. [15–18]. levels, about 6 weeks after the beginning of treatment.
Ako je krvarenje značajnije, ordinira se sveža smrznuta
plazma ili vitamin K, obično samo uz kontrolu INR-a u DISCUSSION
daljem toku bolesti. S obzirom na veliki broj pacijenata
Coumarin derivatives are known to prolong INR and
na ovoj terapiji i relativno retku pojavu drugih uzroka
aPTT due to their combined effect on coagulation fac-
krvarenja, posebno stečene hemofilije, drugi razlozi
tor IX levels. [6,10-11]. Cases have been reported of
hemoragijskog sindroma se retko razmatraju.
hemorrhagic syndrome occurring in patients on oral
Međutim, u situacijama kada se hemoragijski sin-
anticoagulant therapy in the form of coumarin deriv-
drom i dalje održava po normalizaciji INR-a, potrebno
atives, in whom both INR and aPTT are usually moni-
je posumnjati na neki drugi uzrok ovakvog stanja i
tored only on presentation of the disease, while only
Ljubičić J.
naložiti ponovno testiranje celokupnog koagulacio- INR is further monitored on follow-up [15–18]. If the
nog statusa. Produženo aPTT, uz normalizaciju INR-a, bleeding is significant, fresh frozen plasma or vitamin
uvek ukazuje na stečeni poremećaj koagulacije, po- K is prescribed, with usually only INR being controlled
sebno kod starijih bolesnika sa komorbiditetima koji in the further course of the disease. Given the large
imaju opsežna mukokutana krvarenja i krvarenja u number of patients on this therapy and the relatively
mekim tkivima [5]. Kod bolesnika kojeg smo prikazali, rare occurrence of other causes of bleeding, especial-
a koji je imao krvarenje iz digestivnog trakta i opsežno ly acquired hemophilia, other causes of hemorrhagic
mukokutano krvarenje, posebno u predelu orofarink- syndrome are rarely considered.
sa, inicijalno značajno produženo aPTT je shvaćeno However, in situations where hemorrhagic syn-
kao posledica oralne antikoagulantne terapije. Iako je drome continues to persist after the normalization of
bolesnik gotovo svo vreme bio pod kontrolom lekara, INR, it is necessary to suspect a different cause of this
sumnja da se radi o nekom pridruženom poremećaju condition and order re-testing of the overall coagula-
koagulacije je postavljena tek nakon 5 nedelja od prve tion status. Prolonged aPTT, with normalized INR, al-
manifestacije bolesti. U trenutku kada je postavljena ways indicates an acquired coagulation disorder, espe-
dijagnoza, bolesnik je imao po život opasno krvarenje cially in elderly patients with comorbidities who have
u orofarinksu, koje je bilo isprovocirano gastroskopi- extensive mucocutaneous bleeding and soft tissue
jom. I u literaturnim podacima se navodi kašnjenje u bleeding [5]. In the patient we have presented, who
dijagnozi stečene hemofilijie kod bolesnika na oralnoj had digestive tract bleeding and extensive mucocu-
antikoagulantnoj terapiji, što dovodi do često fatalnih taneous bleeding, particularly in the oropharynx, the
krvarenja [13–15]. Svaka invazivna dijagnostika ili hi- initial significantly prolonged aPTT was understood as
rurška intervencija kod bolesnika sa neprepoznatom an effect of oral anticoagulant therapy. Although the
stečenom hemofilijom može isprovocirati obilna krva- patient was under medical supervision almost all the
renja, kao što je bio slučaj kod našeg bolesnika [6,8,18]. time, the suspicion that it was an associated coagula-
Važno je istaći da antiagregacioni lek klopidogrel tion disorder was established only 5 weeks after the
može dovesti do razvoja stečene hemofilije [20-22]. S first manifestation of the disease. At the time of diag-
obzirom da stečena hemofilija uglavnom daje muko- nosis, the patient had life-threatening bleeding in the
kutana krvarenja, ovakvo krvarenje se lako može pri- oropharynx, which was provoked by gastroscopy. De-
pisati jatrogenom efektu klopidogrela, posebno ako je lays in the diagnosis of acquired hemophilia leading
u kombinaciji sa acetilsalicilnom kiselinom. I kod ovih to frequently fatal bleeding, in patients on oral antico-
bolesnika se kasno postavlja dijagnoza stečene hemo- agulant therapy, have also been reported in literature
filije [18]. [13–15]. Any invasive diagnostics or surgical procedure
U današnje vreme, kada je sve veća upotreba novih in patients with unrecognized acquired hemophilia
oralnih antikoagulantnih lekova (engl. novel oral anti- can provoke heavy bleeding, as was the case with our
coagulants – NOACs) – dabigatran, rivaroksaban, apik- patient [6,8,18].
saban, važno je napomenuti da su i kod upotrebe ovih It is important to point out that the antiplatelet
lekova opisani slučajevi stečene hemofilije [16,17]. Pri- drug clopidogrel can lead to the development of ac-
likom ordiniranja NOAC-a obično se ne kontroliše koa- quired hemophilia [20–22]. Since acquired hemophilia
gulacioni status, ali je značajno naglasiti da vrednosti mainly causes mucocutaneous bleeding, such bleed-
INR-a i aPTT-a, takođe mogu biti u manjoj meri izme- ing can easily be attributed to the iatrogenic effect of
njeni [5-17,23]. Stoga, svaku pojavu krvarenja, poseb- clopidogrel, especially if it is combined with acetylsal-
no mukokutanog, kod bolesnika na terapiji NOAC-ima icylic acid. Diagnosis of acquired hemophilia in these
treba propratiti novim analizama INR-a i aPTT-a. patients is also delayed. [18].
Nowadays, when the use of new oral anticoagulant
ZAKLJUČAK drugs (NOAC) is increasing (dabigatran, rivaroxaban,
U zaključku, iako je stečena hemofilija retko stanje, apixaban), it is important to note that cases of acquired
treba biti oprezan u kliničkoj praksi kod teških spon- hemophilia have also been described with the use of
tanih, obično mukokutanih krvarenja, kod bolesnika these drugs [16,17]. Coagulation status is not usually
(posebno starijih) na oralnoj antikoagulantnoj terapiji monitored with the administration of NOAC, but it is
koji imaju neadekvatno produženo aPTT [11,13,15,18]. important to note that INR and aPTT values may also
Uvek treba imati na umu da se u svakoj medicinskoj be altered to a lesser degree [5-17,23]. Therefore, any
biohemijskoj laboratoriji može izvesti lako dostupan occurrence of hemorrhagic, especially mucocutaneous
test mešanja plazme i tako dokazati prisustvo inhibi- bleeding, in patients on NOAC therapy should be ac-
tora koagulacije i posumnjati na stečenu hemofiliju companied by new INR and aPTT analyses.
Ljubičić J.
[6-7,10-11,15]. Ovakvo stanje zahteva neodložnu tera- CONCLUSION

piju specifičnim agensima i zato je važno blagovreme-
In conclusion, although acquired hemophilia is a rare
no postaviti dijagnozu.
condition, caution should be exercised in clinical prac-
Sukob interesa: Nije prijavljen. tice in severe spontaneous, usually mucocutaneous
bleeding, in patients (especially elderly patients) on
oral anticoagulant therapy who have excessively pro-
longed aPTT [11,13,15,18]. It should always be remem-
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MINIMALNO INVAZIVNA TORAKOSKOPSKA HIRURGIJA KAO DIJAGNOSTIČKI
I TERAPIJSKI PRISTUP KOD BILATERALNOG PNEUMOTORAKSA U TRUDNOĆI
UZROKOVANOG LIMFANGIOLEIOMIOMATOZOM – PRIKAZ SLUČAJA
MINIMALLY INVASIVE THORACOSCOPIC SURGERY AS A DIAGNOSTIC AND
THERAPEUTIC APPROACH IN BILATERAL PNEUMOTHORAX IN PREGNANCY
CAUSED BY LYMPHANGIOLEIOMYOMATOSIS – A CASE REPORT
Željko Garabinović1, Nikola Čolić2, Jelena Vasić Madžarević1, Milan Savić1,3
1
Univerzitetski klinički centar Srbije, Klinika za grudnu hirurgiju, University Clinical Center of Serbia, Clinic for Thoracic Surgery,
1

2
Univerzitetski klinički centar Srbije, Centar za radiologiju i University Clinical Center of Serbia, Center for Radiology and
2
magnetnu rezonancu, Beograd, Srbija Magnetic Resonance Imaging, Belgrade, Serbia

3
Univerzitet u Beogradu, Medicinski fakultet, Beograd, Srbija University of Belgrade, Faculty of Medicine, Belgrade, Serbia
3
SAŽETAK ABSTRACT
Uvod: Limfangioleiomiomatoza (LAM) je retka bolest i uglavnom se javlja kod Introduction: Lymphangioleiomyomatosis (LAM) is a rare disease which mainly
žena u generativnom periodu, kao i tokom trudnoće, dok je kod muškaraca opi- occurs in women in the generative period, as well as during pregnancy, while
sano samo nekoliko pojedinačnih slučajeva. Javlja se u vidu sporadičnog oblika only a few individual cases have been described in men. It occurs in sporadic form
ili je povezana sa kompleksom tuberozne skleroze. Dijagnoza se može postaviti or is associated with tuberous sclerosis complex. The diagnosis can be made on
na osnovu nalaza kompjuterizovane tomografije grudnog koša visoke rezolucije the basis of high-resolution computed tomography (HRCT) findings, or histo-
(HRCT), ili je potrebna histopatološka analiza. U kliničke manifestacije bolesti pathological analysis is required. Clinical manifestations of the disease include
spadaju: progresivna dispneja pri naporu, recidivantni pneumotoraks, hilotoraks, the following: progressive dyspnea on exertion, recurrent pneumothorax, chy-
angiomiolipomi i limfangiomiomi. lothorax, angiomyolipomas and lymphangiomyomas.
Prikaz slučaja: Pacijentkinja stara 32 godine, u trećem tromesečju trudnoće, Case report: A 32-year-old female patient was admitted to our clinic, in her third
primljena je na našu kliniku nakon levostranog pneumotoraksa, verifikovanog trimester of pregnancy, after a left-sided pneumothorax was verified on chest
na rendgenu grudnog koša. Početni tretman je uključivao eksuflaciju, a potom X-ray. Initial treatment included needle aspiration, followed by thoracic drainage
torakalnu drenažu levog pleuralnog kavuma. Zbog produženog gubitka vazduha of the left pleural cavity. Due to the prolonged air leak through the thoracic drain
kroz torakalni dren i poodmakle trudnoće, urađen je carski rez. Nakon porođa- and the advanced stage of the pregnancy, a caesarean section was performed.
ja, rendgenom grudnog koša, utvrđen je kompletni desnostrani pneumotoraks, After delivery, chest X-ray revealed complete right-sided pneumothorax, which
koji je zahtevao torakalnu drenažu, kao i nedovoljno reekspandirano levo plućno required thoracic drainage, as well as an insufficiently reexpanded left lung.
krilo. Na učinjenom HRCT snimku zabeležene su cistično-bulozne promene u plu- HRCT was performed and cystic bullous changes in the lungs were noted; LAM
ćima, te je najpre sa leve, a potom i sa desne strane, torakohirurškim minimalno was histopathologically verified through a minimally invasive thoraco-surgical
invazivnim pristupom, histopatološki verifikovana LAM, uz hirurško lečenje obo- approach, first on the left and then on the right side, while bilateral pneumotho-
stranog pneumotoraksa. rax was surgically treated.
Zaključak: Pneumotoraks je česta komplikacija limfangioleiomiomatoze. Zbog Conclusion: Pneumothorax is a common complication of LAM. Due to the high
visoke stope recidiva, treba izvršiti definitivnu ranu hiruršku intervenciju. Tre- recurrence rate, definitive early surgical intervention should be performed.
nutne smernice preporučuju hemijsku pleurodezu i operaciju, za prvu epizodu Current guidelines recommend chemical pleurodesis and surgery for the first
pneumotoraksa. Prilikom lečenja pneumotoraksa u trudnoći treba primeniti ade- pneumothorax. When treating pneumothorax in pregnancy, the appropriate
kvatnu terapijska proceduru, vodeći računa o bezbednosti trudnoće i porođaja. therapeutic procedure should be applied, taking into account the safety of the
Ključne reči: pneumotoraks, trudnoća, limfangioleiomiomatoza pregnancy and of the delivery.
Key words: pneumothorax, pregnancy, lymphangioleiomyomatosis

Željko Garabinović Željko Garabinović
Klinika za grudnu hirurgiju, Univerzitetski klinički centar Srbije Clinic for Thoracic Surgery, University Clinical Center of Serbia
Koste Todorovića 26, 11000 Beograd, Srbija 26 Koste Todorovića Street, 11000 Belgrade, Serbia
Elektronska adresa: zeljkogarabinovic@gmail.com E-mail: zeljkogarabinovic@gmail.com
Primljeno • Received: April 27, 2022; Revidirano • Revised: May 11, 2022; Prihvaćeno • Accepted: May 17, 2022; Online first: May 25, 2022
10.5937/smclk3-37604
minimalno invazivna torakoskopska hirurgija kao dijagnostički i terapijski pristup kod bilateralnog pneumotoraksa u trudnoći
uzrokovanog limfangioleiomiomatozom – prikaz slučaja
Garabinović Ž. i sar.
minimally invasive thoracoscopic surgery as a diagnostic and therapeutic approach in bilateral pneumothorax in pregnancy
caused by lymphangioleiomyomatosis – a case report
UVOD INTRODUCTION
Limfangioleiomiomatoza (LAM) je progresivna, retka, Lymphangioleiomyomatosis (LAM) is a progressive and
multisistemska bolest nepoznate etiologije, koja se rare multisystem disease of unknown etiology, which
pretežno javlja kod žena, pri čemu uzrokuje oštećenje predominantly affects women, causing damage to the
plućne funkcije [1]. Epidemiološka studija, sprove- function of the lungs [1]. An epidemiological study, car-
dena u sedam zemalja, pokazala je da je incidencija ried out in seven countries, showed the incidence of
limfangioleiomiomatoze 3,4 – 7,8 slučajeva na milion LAM to be 3.4 – 7.8 cases per one million women [2].
žena [2]. LAM se uglavnom manifestuje u vidu cistič- LAM mainly manifests in the form of cystic destruction of
ne destrukcije plućnog parenhima, kao i ekstrapul- the lung parenchyma, as well as in the form of extrapul-
monalne bolesti, koja se sastoji od angiomiolipoma, monary disease, consisting of angiomyolipoma, lymph
limfnih tumora (limfangioleiomioma) i hiloznih izliva tumors (lymphangioleiomyoma) and chylous effusions
[3]. Limfangioleiomiomatoza je retka u opštoj popu- [3]. Lymphangioleiomyomatosis is rare in the general
laciji, ali je česta kod žena sa kompleksom tuberozne population but is frequent in women with tuberous scle-
skleroze (engl. tuberous sclerosis complex – TSC). Javlja rosis complex (TSC). It occurs in 30 – 40% of cases (TSC-
se u 30 – 40% slučajeva (TSC-LAM) [4]. Prisutna je kod LAM) [4]. It is present in women between menarche and
žena između menarhe i menopauze, prosečne starosti menopause, of the average age of 34 years [5].
od 34 godine [5]. A significant number of patients with LAM devel-
Značajan broj pacijentkinja sa LAM-om razvija svo- ops initial symptoms during pregnancy. It has been re-
je početne simptome tokom trudnoće. Zabeleženo je corded that pregnancy in cases of lymphangioleiomy-
da je trudnoća kod limfangioleiomiomatoze poveza- omatosis is linked to an increased incidence of pneu-
na sa povećanom incidencijom pneumotoraksa, iako mothorax, although some of the patients have an un-
neke pacijentkinje imaju nekomplikovanu trudnoću complicated pregnancy [6]. Most frequently, patients
[6]. Najčešće, pacijenti imaju kratak dah, kašalj i pneu- have shortness of breath, coughing, and pneumotho-
motoraks. Ređe su prisutni hilozni pleuralni izlivi i he- rax. Less frequently, there are chylous pleural effusions
moptizije [7,8]. and hemoptysis are present [7,8].
Cilj ovog rada jeste da se prikaže slučaj trudnice The aim of this paper is to present the case of a preg-
koja je razvila spontani bilateralni pneumotoraks to- nant woman who developed spontaneous bilateral
kom trećeg tromesečja trudnoće i odmah nakon po- pneumothorax during the third trimester of her preg-
rođaja, ali i da se ukaže na značaj minimalno invaziv- nancy and immediately after childbirth, as well as to
nog video-asistiranog torakohirurškog pristupa (engl. point out the importance of minimally invasive video-as-
video-assisted thoracoscopic surgery – VATS) u dijagno- sisted thoracoscopic surgery (VATS) in the diagnosis of
stici limfangioleiomiomatoze i lečenju pneumotoraksa LAM and in treating pneumothorax caused by LAM.
izazvanog limfangioleiomiomatozom.
CASE REPORT
PRIKAZ SLUČAJA A thirty-two-year-old female patient was admitted to
Tridesetdvogodišnja pacijentkinja je primljena na našu our hospital in the 36th week of gestation of her second
kliniku, u 36. nedelji gestacije druge trudnoće, dva pregnancy, two days after experiencing sudden pain in
dana nakon pojave iznenadnog bola u levom hemito- the left hemithorax, which was followed by acute short-
raksu, praćenog akutnom kratkoćom daha. Pacijentki- ness of breath. The patient had no previous history of
nja nije imala istoriju ranijih hroničnih plućnih bolesti chronic pulmonary disease or other comorbidities. Her
ili drugih komorbiditeta. Njena prethodna trudnoća je first pregnancy was without complications. On physi-
protekla bez komplikacija. Prilikom fizikalnog pregle- cal examination, she displayed tachypnea, tachycardia,
da, imala je tahipneju, tahikardiju i hiperrezonantni and hyperresonance with percussion of the chest, with
perkusioni zvuk, sa smanjenim disajnim pokretima reduced breathing movements of the left hemithorax.
levog hemitoraksa. Pregledima kardiovaskularnog si- Examination of the cardiovascular system did not yield
stema nije zabeležen patološki nalaz niti je verifikova- a pathological finding nor was organomegaly verified.
na organomegalija. Rezultati krvne slike, kao i testovi The blood count results, as well as the test of liver func-
funkcije jetre i bubrega bili su normalni. Radiografski tion and kidney function were normal. The radiograph-
snimak grudnog koša potvrdio je prisustvo komplet- ic image of the thorax confirmed the presence of com-
nog levostranog pneumotoraksa (Slika 1). plete left-sided pneumothorax (Figure 1).
Početni tretman je podrazumevao eksuflaciju le- Initial treatment included exsufflation of the left
vog pleuralnog kavuma, a nakon učinjene navedene pleural cavity, and after this procedure yielded no im-
intervencije i nalaza bez poboljšanja, učinjena je tora- provement, thoracic drainage of the left pleural cavity
Garabinović Ž. et al.
Slika 1. Radiografija grudnog koša na prijemu na kliniku na kojoj se verifikuje Slika 2. Radiografija grudnog koša nakon porođaja na kojoj se verifikuje de-
levostrani pneumotoraks snostrani pneumotoraks, uz prethodno plasirani torakalni dren – levo
Figure 1. Chest X-ray at hospital admission verifying left-sided pneumothorax Figure 2. Chest X-ray after delivery verifying right-sided pneumothorax, with a
previously placed thoracic drain – left ax
kalna drenaža levog pleuralnog kavuma, sa torakalnim using under water sealed drainage (UWSD). Since re-
drenom povezanim na podvodnu aspiraciju. S obzirom expansion of the left lung did not occur, the thoracic
da nije došlo do reekspanzije levog plućnog krila, tora- drain was subsequently connected to active aspiration.
kalni dren je naknadno priključen na aktivnu aspiraciju. Due to prolonged air loss via the thoracic drain and the
Zbog produženog gubitka vazduha kroz torakalni dren advanced stage of pregnancy (37th week of gestation),
i poodmakle trudnoće (37. nedelja gestacije), urađen je a C-section was performed and a girl weighing 3,130
carski rez. Rođena je devojčica od 3.130 grama sa do- grams with a good Apgar score (9) was born.
brim Apgar skorom (9). After the delivery, an X-ray of the patient’s chest
Nakon porođaja, radiografijom grudnog koša, utvr- revealed complete right-sided pneumothorax, which
đen je kompletni desnostrani pneumotoraks, koji je za- required thoracic drainage, in addition to the thoracic
htevao torakalnu drenažu, uz prethodno plasirani tora- drain previously placed due to left-sided pneumotho-
kalni dren, zbog levostranog pneumotoraksa (Slika 2). rax (Figure 2).
Nalaz kompjuterizovane tomografije grudnog koša The high-resolution computed tomography (HRCT)
visoke rezolucije (engl. high-resolution computed tomo- chest scan showed bilateral multiple diffuse thin-walled
graphy HRCT) je pokazao bilateralne višestruke difuzne cystic lesions, scattered throughout the lung parenchy-
cistične promene tankih zidova, rasute po plućnom ma, which measured up to 22 mm in diameter (Figure
parenhimu, veličine do 22 milimetra (Slika 3). Kompju- 3). Computed tomography (CT) of the abdomen and
terizovana tomografija abdomena i male karlice nije the lesser pelvis showed no abnormalities.
pokazala abnormalnosti. In such circumstances, we decided on surgical
U ovim okolnostima odlučili smo se za hirurško le- treatment of the pneumothorax.
čenje pneumotoraksa.
Slika 3. Aksijalni i koronalni preseci HRCT snimaka grudnog koša na kojima se Figure 3. Axial and coronal sections of the HRCT images of the thorax verifying
verifikuju cistične difuzne bilateralne promene u plućnom parenhimu cystic diffuse bilateral lesions in the lung parenchyma
Inicijalno, sedmog dana nakon porođaja, izveli smo

levostrani VATS pristup. Intraoperativno su otkrivene
pleuralne adhezije u predelu levog gornjeg režnja.
Nakon razdvajanja pleuralnih adhezija, u gornjem i do-
njem režnju je nađeno više mehurića i bula, predomi-
nantno u lingularnom segmentu gornjeg režnja i api-
kalnom segmentu donjeg režnja (Slika 4). Endostaple-
rom smo učinili klinastu resekciju apikalnog segmenta
donjeg režnja i lingularnog segmenta gornjeg režnja.
Urađena je hemijska pleurodeza sa 30 ml pedesetopro-
centnog rastvora glukoze i mehanička pleurodeza sa
abrazijom kostalne parijetalne pleure.
Histopatološki nalaz je pokazao prošireni alveo-
larni prostor sa glatkim mišićnim tkivom u njegovim
zidovima, perivaskularnu proliferaciju glatkih mišića,
Slika 4. Intraoperativni nalaz difuznih cističnih promena u plućnom parenhimu
agregate limfoidnih ćelija i proširene limfne prostore.
Nije primećen granulom ili malignitet. Utvrđeno je da Figure 4. Intraoperative finding of diffuse cystic lesions in the lung parenchyma
su kultivisane ćelije glatkih mišića pozitivne na hu-
Initially, on the seventh day after delivery, we per-
mani melanomski blok-45 (HMB-45). Dakle, dijagnoza
formed left-sided VATS. Intraoperatively, pleural adhe-
limfangioleiomiomatoze je potvrđena.
sions were discovered in the region of the left superior
Hirurško lečenje desnostranog pneumotoraksa
lobe. After the separation of the pleural adhesions, a
VATS pristupom izvedeno je 15. dana nakon porođa-
number of blisters and bullae were found in the su-
ja. Intraoperativno smo primetili više mehurića i bula,
perior and inferior lobe, predominantly in the lingular
predominantno u srednjem režnju. Učinjena je klina-
segment of the superior lobe and the apical segment
sta resekcija srednjeg režnja endostaplerom, a zatim
of the inferior lobe (Figure 4). Using an endostapler, we
hemijska i mehanička pleurodeza, kao u prethodnoj
performed wedge resection of the apical segment of
operaciji. Histopatološki nalaz odgovarao je nalazu
the inferior lobe and the lingular segment of the su-
prethodne operacije.
perior lobe. Chemical pleurodesis was performed with
Postoperativni tok, nakon oba hirurška zahvata,
30 ml of 50% glucose solution, as well as mechanical
protekao je uredno, uz potpunu reekspanziju desnog i
pleurodesis with abrasion of the costal parietal pleura.
levog plućnog krila, koja se održavala nakon uklanjanja
The histopathological finding revealed enlarged
torakalnih drenova.
alveolar space with smooth muscle tissue in its walls,
Pacijentkinja je otpuštena iz bolnice 20. dana na-
perivascular proliferation of smooth muscles, aggre-
kon porođaja. Na dan otpusta iz bolnice, rendgenski
gates of lymphoid cells, and enlarged lymph spaces.
snimak grudnog koša je pokazao potpuno reekspandi-
Granuloma or malignancy was not found. The culti-
rano levo i desno plućno krilo.
vated cells of smooth muscle tissue proved positive to
Testiranje plućne funkcije tri, šest i dvanaest meseci
human melanoma block-45 (HMB-45). Thereby, the di-
nakon porođaja pokazalo je referentne vrednosti.
agnosis of lymphangioleiomyomatosis was confirmed.
Ponovljeni HRCT snimci abdomena i karlice, šest
Surgical treatment of the right-sided pneumothorax
meseci i godinu dana nakon porođaja, nisu pokazali
with the VATS approach was performed on the 15th day
abnormalnosti. Rendgen snimci grudnog koša, me-
after delivery. Intraoperatively, we detected a number
sec dana, tri meseca, šest meseci i godinu dana nakon
of blisters and bullae, predominantly in the middle lobe.
porođaja, pokazali su potpuno reekspandirano levo i
Wedge resection of the middle lobe was performed
desno plućno krilo. Ponovljeni HRCT snimci grudnog
with the use of the endostapler, followed by chemical
koša, šest meseci i godinu dana nakon porođaja, nisu
and mechanical pleurodesis, in the same way as in the
pokazali progresiju bolesti. I pacijentkinja i njeno dete
previous operation. The histopathological finding was
ostali su zdravi nakon godinu dana praćenja.
in keeping with the one from the previous surgery.
DISKUSIJA Postoperative recovery, after both surgeries, was
uneventful and full reexpansion of both the right and
Limfangioleiomiomatoza je progresivna, cistična bolest the left lung was achieved, with the reexpansion per-
pluća, koja se javlja pretežno kod žena u tridesetim go- sisting after the removal of the thoracic drains.
dinama života [1,5]. LAM se retko javlja u opštoj popula- The patient was discharged form hospital on the
ciji. Obično se javlja kod žena sa TSC-om (30 – 40% slu- 20th day after delivery. On the day of discharge, the
čajeva), ili se javlja kao sporadični oblik. Postoje speci- chest X-ray showed a completely reexpanded left and
fični kriterijumi za dijagnostikovanje TSC-a [9]. U slučaju right lung.
naše pacijentkinje, kriterijumi za TSC nisu ispunjeni. Pulmonary function tests performed three, six,
Pneumotoraks je čest kod pacijenata sa limfangi- and twelve months upon delivery, showed results that
oleiomiomatozom. Studija registra Nacionalnog insti- were within the reference range.
tuta za srce, pluća i krv (engl. National Heart, Lung, and Repeated HRCT scans of the abdomen and pelvis,
Blood Institute - NHLBI) u Sjedinjenim Američkim Drža- six and twelve months after delivery, showed no abnor-
vama, koja je obuhvatila 230 pacijenata sa limfangio- malities. X-rays of the chest made one, three, six, and
leiomiomatozom, zabeležila je pneumotoraks u 55,5% twelve months after delivery, showed a completely re-
slučajeva [10]. Druge studije su pokazale da je inciden- expanded left and right lung. Repeated HRCT scans of
cija pneumotoraksa kod limfangioleiomiomatoze 1.000 the chest, six and twelve months after delivery, showed
puta veća nego u opštoj ženskoj populaciji [11]. Štavi- no progression of the disease. Both the patient and her
še, 50 – 80% pacijenata će razviti pneumotoraks tokom child remained healthy after a year of follow-up.
bolesti. Pojava recidiva pneumotoraksa je česta, sa pro-
sečnim brojem pneumotoraksa od oko četiri [10–14]. DISCUSSION
Nespecifične kliničke karakteristike sa neupadlji- Lymphangioleiomyomatosis is a progressive cystic
vim rendgenskim snimcima grudnog koša na prezen- pulmonary disease, occurring mainly in women in their
taciji dovode do kašnjenja u dijagnozi ili netačne dija- thirties [1,5]. LAM rarely occurs in the general popula-
gnoze [7,8]. tion. It usually develops in women with TSC (30 – 40%
Komplikacije povezane sa limfangioleiomiomato- of cases), or it may occur as a sporadic form. There are
zom, uključujući pneumotoraks i hilotoraks, mogu se specific criteria for diagnosing TSC [9]. In the case of
javiti tokom trudnoće, a izražena je zabrinutost zbog our patient, the TSC criteria were not met.
moguće povezanosti trudnoće sa progresijom limfan- Pneumothorax is frequent in patients with lymph-
gioleiomiomatoze. Takođe je zabeleženo da žene sa angioleiomyomatosis. The study of the National Heart,
LAM-om imaju lošiji ishod trudnoće, uključujući i više Lung, and Blood Institute(NHLBI) registry (USA), involv-
prevremenih porođaja i abortusa [6,15,16]. ing 230 patients with LAM, registered pneumothorax
U literaturi je opisan pneumotoraks izazvan LAM- in 55.5% of cases [10]. Other studies have shown that
om, u poslednjem tromesečju trudnoće i ubrzo nakon the incidence of pneumothorax in LAM is 1,000 great-
porođaja. Ovaj fenomen se objašnjava činjenicom da er than in the general female population [11]. More-
hormonska stimulacija tokom trudnoće dovodi do over, 50 – 80% of patients will develop pneumothorax
povećanja cističnih struktura u plućima, te potom, na during the illness. The recurrence of pneumothorax is
kraju trudnoće ili ubrzo nakon porođaja, dolazi do opa- frequent, with the average number of pneumothorax
danja hormonske stimulacije i posledično do rupture episodes being around four [10–14].
neke od tankozidnih cističnih struktura i pojave pneu- Nonspecific clinical characteristics with unremark-
motoraksa. Ovo takođe objašnjava činjenicu da je LAM, able chest X-rays on presentation lead to delayed diag-
skoro tipično, ženska bolest [17,18]. nosis or misdiagnosis [7,8].
Ranije se pokazalo da je dispneja pri naporu, kao Complications connected to LAM, including pneu-
prisutni simptom, povezana sa povećanim mortalite- mothorax and chylothorax, may occur in pregnancy,
tom kod limfangioleiomiomatoze [19]. Nasuprot tome, and the possible connection between pregnancy and
prethodno se smatralo da pacijenti sa pneumotorak- the progression of LAM is cause for serious concern.
som imaju povoljniju prognozu [1]. Kasnije studije nisu Also, it has been recorded that women with LAM have
pokazale vezu između pneumotoraksa i dugoročnog a poorer outcome of pregnancy, including a greater
ishoda [20,21]. number of premature births and miscarriages [6,15,16].
Ako pacijent sa potvrđenom LAM-om ima pneu- Pneumothorax caused by LAM in the third trimes-
motoraks, treba ga lečiti u skladu sa standardnim smer- ter of pregnancy and shortly after delivery has been
nicama za lečenje sekundarnog pneumotoraksa [22]. described in literature. This phenomenon is explained
Lečenje pneumotoraksa u trudnoći zavisi od stepena i by the fact that hormone stimulation during pregnan-
faze progresije. Obično se koristi torakalna drenaža, sa cy leads to the increase in cystic structures in the lungs,
ili bez aktivne aspiracije [16]. U slučaju naše pacijentki- and subsequently, at the end of pregnancy or soon after
nje, dijagnoza limfangioleiomiomatoze nije bila pozna- delivery, hormone stimulation drops, and consequent-
ta prilikom donošenja odluke o inicijalnom zbrinjava- ly, some of the thin-walled cystic structures rupture,
nju pneumotoraksa, pa smo koristili preporuke zvanič- leading to pneumothorax. This also explains the fact
nih smernica za lečenje pneumotoraksa u trudnoći [23]. that LAM is, almost typically, a female disease [17,18].
Smernice Američkog torakalnog društva/Japan- It has been found earlier that dyspnea on exertion,
skog respiratornog društva (engl. American Thoracic as a symptom, is connected with increased mortality in
Society/Japanese Respiratory Society Clinical Practice LAM [19]. Conversely, it used to be believed that patients
Guidelines) podržavaju kliničku dijagnozu limfangiole- with pneumothorax had a more favorable prognosis
iomiomatoze zasnovanu na HRCT nalazima tipičnim za [1]. More recent studies have not shown a link between
limfangioleiomiomatozu (npr. ciste/mehurići difuzni, pneumothorax and the long-term outcome [20,21].
tankih zidova, okrugli) koji su praćeni bilo kojom od If a patient with confirmed LAM has pneumotho-
sledećih kliničkih karakteristika: TSC, angiomiolipom rax, this patient should be treated in keeping with the
bubrega, cistični limfangioleiomiom, ili hilozni izliv u standard guidelines for treating secondary pneumo-
grudnom košu i/ili abdomenu. Smernice daju snažnu thorax [22]. Treatment of pneumothorax in pregnancy
preporuku za korišćenje testa VEGF-D (vaskularni en- depends on the degree and phase of progression. Usu-
dotelni faktor rasta D; engl. vascular endothelial growth ally, thoracic drainage is used, but without active aspi-
factor D test) za postavljanje dijagnoze limfangioleio- ration [16]. In the case of our patient, the diagnosis of
miomatoze, pre razmatranja biopsije pluća, kod paci- LAM was not known at the time when the decision was
jenata sa cističnim abnormalnostima na HRCT nalazu, made on initial pneumothorax treatment, which is why
karakterističnim za LAM, ali bez drugih potvrdnih kli- we applied the recommendations of the official guide-
ničkih karakteristika [24]. lines for treating pneumothorax in pregnancy [23].
Histopatološka potvrda limfangioleiomiomatoze The American Thoracic Society/Japanese Respira-
može se dobiti na različite načine, uključujući tran- tory Society Clinical Practice Guidelines support the
sbronhijalnu, perkutanu ili VATS biopsiju. Rizik od pneu- clinical diagnosis of LAM based on HRCT findings that
motoraksa nakon transbronhijalne biopsije je 1 – 6 %, a are typical for lymphangioleiomyomatosis (e.g., dif-
čak je i veći nakon perkutane biopsije. Prednost VATS-a fuse, thin-walled, spheric cysts/blisters) accompanied
je minimalna hirurška trauma, kao i odgovarajući uzo- by any of the following characteristics: TSC, renal angi-
rak za patološku potvrdu, kada se radi bulektomija i omyolipoma, cystic lymphangioleiomyoma, or chylous
pleurodeza ili pleurektomija [25]. Neke retrospektivne effusion in the thorax and/or abdomen. The guidelines
serije sugerišu da transbronhijalna biopsija pluća može strongly recommend the use of the VEGF-D test (vas-
biti bezbedna i efikasna u delu pacijenata sa sumnjom cular endothelial growth factor D test) for establishing
na limfangioleiomiomatozu. U studiji koju su objavili the diagnosis of LAM, before considering lung biopsy
Meraj i saradnici, među 63 pacijenta koji su bili podvrg- in patients with cystic abnormalities characteristic of
nuti transbronhijalnoj biopsiji pluća, kada se prvobitno LAM present on the HRCT scan, but without other pos-
sumnjalo na limfangioleiomiomatozu, kod 35 pacije- itive clinical characteristics [24].
nata (56%) je ovim postupkom potvrđena LAM. Stopa Histopathological confirmation of LAM may be
prijavljenih komplikacija prilikom transbronhijalne bi- obtained in different ways, including transbronchial,
opsije bila je približno 14% (6% sa pneumotoraksom, percutaneous or VATS biopsy. The risk from pneumo-
4% sa krvarenjem, 2% sa bolom u grudima i 2% sa pne- thorax after transbronchial biopsy is 1 – 6 %, and it is
umonijom) [26]. even higher after percutaneous biopsy. The advantag-
Međutim, hirurška biopsija pluća primenom VATS es of VATS are reflected in minimal surgical trauma, as
pristupa se smatra zlatnim standardom za dobijanje well as in the fact that it enables the obtaining of an
histopatološke potvrde limfangioleiomiomatoze. Kada adequate sample for pathological confirmation, when
je potrebna definitivna dijagnoza kod pacijenata sa bullectomy and pleurodesis or pleurectomy are per-
parenhimskim cistama specifičnim za limfangioleio- formed [25]. Some retrospective studies suggest that
miomatozu prisutnim na HRCT nalazu, ali bez dodat- transbronchial lung biopsy may be safe and efficient
nih potvrdnih karakteristika limfangioleiomiomatoze, in some of the patients with suspected LAM. In a study
Smernice Američkog torakalnog društva/Japanskog by Meraj et al., amongst 63 patients who underwent
respiratornog društva predlažu dijagnostički pristup transbronchial lung biopsy at the time when LAM was
koji uključuje transbronhijalnu biopsiju pluća, pre hi- initially suspected, in 35 (56%) patients LAM was con-
rurške biopsije pluća [27]. U slučaju naše pacijentkinje, firmed in this way. The rate of reported complications
dijagnoza limfangioleiomiomatoze je postavljena VATS of transbronchial biopsy was approximately 14% (6%
pristupom, koji je ujedno predstavljao i terapijski po- with pneumothorax, 4% with bleeding, 2% with chest
stupak za rešavanje pneumotoraksa. pain, and 2% with pneumonia) [26].
Pošto je stopa recidiva visoka, trenutne smernice However, surgical biopsy of the lungs with the ap-
preporučuju pleurodezu u vreme prve epizode pne- plication of VATS is believed to be the golden standard
umotoraksa, kod pacijenata sa potvrđenom LAM-om for obtaining histopathological confirmation of LAM.
[22,27]. Međutim, pleurodeza kod pacijenata sa LAM- When a definitive diagnosis is necessary in patients
om ima ograničenu efikasnost, a zabeleženo je da se with parenchymal cysts characteristic of LAM present
stope recidiva pneumotoraksa kreću između 18% i 32% on the HRCT finding, but without additional positive
[27,28]. Nedostaju jasne smernice o tome da li je hemij- characteristics of LAM, the American Thoracic Society/
ska ili hirurška pleurodeza optimalna, ali je važno rano Japanese Respiratory Society Clinical Practice Guide-
uključiti grudne hirurge, jer će nekim pacijentima biti lines suggest a diagnostic approach which includes
potrebna transplantacija pluća, u dužem vremenskom transbronchial lung biopsy, before surgical lung bi-
roku. Smernice za dijagonzu i lečenje limfangioleiomio- opsy [27]. In our patient, the diagnosis of LAM was es-
matoze (LAM) Evropskog respiratornog društva (engl. tablished with the VATS approach, which was also the
European Respiratory Society Guidelines for the Diagnosis treatment procedure for pneumothorax.
and Management of Lymphangioleiomyomatosis – LAM) Since the recurrence rate is high, current guide-
i Smernice Američkog torakalnog društva/Japanskog lines recommend pleurodesis at the time of the first
respiratornog društva preporučuju hemijsku pleurode- episode of pneumothorax, in patients with confirmed
zu i operaciju, za prvi pneumotoraks [22,26]. U slučaju LAM [22,27]. However, pleurodesis in patients with
naše pacijentkinje, učinili smo hemijsku i mehaničku LAM has limited efficiency, and it has been recorded
pleurodezu. Prethodne pleuralne procedure nisu kon- that recurrence rates for pneumothorax range from
traindikacija za buduću transplantaciju pluća [29]. 18% to 32% [27,28]. Clear guidelines are lacking as to
whether chemical or mechanical pleurodesis is opti-
Sukob interesa: Nije prijavljen. mal, but it is definitively important to include thorac-
ic surgeons into the process early on, as some of the
patients will need a lung transplant, in the long-term.
European Respiratory Society Guidelines for the Diag-
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Consensus Conference. Pediatr Neurol. 2013 Oct;49(4):243-54. doi: 10.1016/j. 16. Shen L, Xu W, Gao J, Wang J, Huang J, Wang Y, He Y, Yang Y, Tian X, Xu KF. Pre-
pediatrneurol.2013.08.001. gnancy after the diagnosis of lymphangioleiomyomatosis (LAM). Orphanet J
10. Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT, et al.; NHLBI LAM Rare Dis. 2021 Mar 17;16(1):133. doi: 10.1186/s13023-021-01776-7.
Registry Group. The NHLBI lymphangioleiomyomatosis registry: characte- 17. Crawford TC, Grimm JC, Magruder JT, Stephens RS, Sciortino CM, Vaught AJ,
ristics of 230 patients at enrollment. Am J Respir Crit Care Med. 2006 Jan et al. A curious case of acute respiratory distress syndrome. J Surg Case Rep.
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18. Grzegorek I, Lenze D, Chabowski M, Janczak D, Szolkowska M, Langfort R, et 24. McCormack FX, Gupta N, Finlay GR, Young LR, Taveira-DaSilva AM, Glasgow
al. Immunohistochemical evaluation of pulmonary lymphangioleiomyoma- CG, et al.; ATS/JRS Committee on Lymphangioleiomyomatosis. Official Ame-
tosis. Anticancer Res. 2015 Jun;35(6):3353-60. rican Thoracic Society/Japanese Respiratory Society Clinical Practice Guide-
19. Hayashida M, Seyama K, Inoue Y, Fujimoto K, Kubo K; Respiratory Failure lines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir
Research Group of the Japanese Ministry of Health, Labor, and Welfare. Crit Care Med. 2016 Sep 15;194(6):748-61. doi: 10.1164/rccm.201607-1384ST.
The epidemiology of lymphangioleiomyomatosis in Japan: a nationwide 25. Tsai CF, Hsiao CH, Lee JM, Chen KC, Shieh MJ, Lai HS, et al. Video-assisted
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Radiologic Biomarkers Emerge From a 15-Year Prospective Longitudinal lity of transbronchial biopsy in the diagnosis of lymphangioleiomyomatosis.
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uputstvo autorima
instructions for authors
UPUTSTVO AUTORIMA ZA PRIPREMU RADOVA INSTRUCTIONS FOR AUTHORS

Srpski medicinski časopis Lekarske komore objavljuje do sada neobjavljene The Serbian Journal of the Medical Chamber publishes previously unpub-
originalne stručne i naučne radove, pregledne članke, kratka saopštenja, uvod- lished, original professional and scientific papers, reviews, short communications,
nike, pisma uredniku, meta-analize, prikaze slučajeva, aktuelne teme, prikaze editorials, letters to the editor, meta-analyses, case reports, current topics, book
knjiga, radove iz istorije medicine i drugo, iz svih oblasti medicine, farmacije i reviews, papers on the history of medicine and more, from all fields of medicine,
stomatologije, čime doprinosi promociji i razvoju struke i nauke. Časopis se objav- pharmacy and dentistry, therefore contributing to the promotion and develop-
ljuje u papirnom i elektronskom obliku četiri puta godišnje. ment of the profession and science. The journal is published in print and electronic
Da bi se rad razmatrao za publikovanje neophodno je da bude pripre- form four times per year.
mljen prema propozicijama ovog Časopisa. U suprotnom Urednik može da ga In order for a paper to be considered for publication, it is necessary to prepare
odbije, bez daljih objašnjenja. Objavljivanje radova se ne honorariše. Prilikom it according to the Journal’s guidelines, otherwise the editor may reject it without
prihvatanja rada za publikovanje svi autori prenose svoja autorska prava na further explanation. The publication of papers is not paid. When accepting a paper
izdavača časopisa. for publication, all authors transfer their copyrights to the Journal publisher.
Radovi se šalju elektronski. Adresa za prijavljivanje rada za časopis je Papers are submitted electronically. The web address for submitting papers is
https://aseestant.ceon.rs/index.php/smclk. Časopis koristi otvoren sistem https://aseestant.ceon.rs/index.php/smclk. The Journal uses an open access sys-
pristupa koji omogućava automatsko proveravanje plagijarizma i autoplagijariz- tem that allows automatic checking for plagiarism and autoplagiarism. Appropriate
ma. Uz rad se šalju i odgovarajuće potvrde (videti na kraju ovog uputstva). certificates should be provided with the paper (see at the end of these instructions).
OPŠTA UPUTSTVA GENERAL INSTRUCTIONS

Tekst rada treba da bude napisan latinicom u programu za obradu teksta Word, The paper should be submitted as a Microsoft Word document (.docx, .doc), using
fontom Times New Roman i veličinom slova 12 tačaka (12 pt). Sve četiri margine the Times New Roman font, size 12 pt. All four margins should be set to 25 mm and
treba podesiti na 25 mm, a veličinu stranice na format A4. Prored treba da bude the page size to A4. The line spacing should be 1.5, with left alignment and 10 mm
1,5, sa levim poravnanjem i uvlačenjem svakog pasusa za 10 mm. Ne treba da indentation of each paragraph. There should be no end-of-line hyphenation. The
bude podeljenih reči (hifenacije). Ne treba koristiti tabulatore i uzastopne prazne alignment tools should be used for aligning the text, not tabs or multiple spaces.
karaktere (spejsove) radi poravnanja teksta, već alatke za kontrolu poravnanja Only the page-break should be used for a new page in the document. A single space
u tulbaru. Za prelazak na novu stranu dokumenta koristi se isključivo Page bre- should follow each punctuation mark. If special characters (symbols) are used in
ak. Posle svakog znaka interpunkcije treba staviti samo jedan prazan karakter the text, use the font from the Symbol package. Use only generic names for drugs.
(spejs). Ako se u tekstu koriste specijalni znaci (simboli), koristite font iz paketa Devices (equipment) should be identified using factory names, and the name and
Symbol. Za nazive lekova koristiti isključivo generička imena. Uređaji (aparati) se location of the manufacturer should be indicated in parentheses. If the text uses
označavaju fabričkim nazivima, a ime i mesto proizvođača treba navesti u oblim labels that are a combination of letters and numbers, it is necessary to appropri-
zagradama. Ukoliko se u tekstu koriste oznake koje su spoj slova i brojeva potreb- ately write the number that appears in superscript or subscript (e.g. 99Tc, IL-6, O2,
no je precizno napisati broj koji se javlja u superskriptu ili supskriptu (na pr. 99Tc, B12, CD8, etc.). If something is typically written in italic, it should be written so
IL-6, O2, B12, CD8 itd.). Ukoliko se nešto uobičajeno piše kurzivom (italic) tako se (e.g. gene names). International System of Units (SI) units should be used, with the
i navodi (npr. nazivi gena). Neophodno je koristiti međunarodni sistem mernih exception of temperature (°C) and blood pressure (mmHg). If the paper is part of a
jedinica (SI), uz izuzetak temperature (°C) i krvnog pritiska (mmHg). Ukoliko je master’s thesis or doctoral dissertation, or was created within a scientific project,
rad deo magistarske teze, odnosno doktorske disertacije, ili je urađen u okviru this should be specifically indicated in the Notes section, at the end of the text.
naučnog projekta, to treba posebno naznačiti u Napomeni na kraju teksta. Graphics attachments should be created using standard graphics software
Za izradu grafičkih priloga koristite standardne grafičke programe za vin- for MS Windows, preferably from the MS Office suite (MS Excel, MS Word Graph).
dovs (Windows), najbolje iz programskih paketa mikrosoft ofisa (Excel, Word Use of colors should be avoided, especially gradients and shading.
Graph). Izbegavajte upotrebu boja, naročito prelaze boja i senčenje.
PREPARING THE PAPER
PRIPREMA RADA
The sections of the paper are: the cover page, the abstract and keywords, the text
Delovi rada su: naslovna strana, sažetak sa ključnim rečima, tekst rada, zahval- of the paper, acknowledgements (optional), literature, and attachments.
nost (po želji), literatura i prilozi. COVER PAGE (first page) should include the title of the paper, without ac-
NASLOVNA STRANA (prva strana) sadrži naslov rada bez skraćenica, ronyms, a suggested short title of the paper, the full names of the authors (with-
predlog kratkog naslova rada, puna imena i prezimena autora (bez titula) indek- out titles) indexed using numbers, the official name of the institutions where
sirana brojevima, zvaničan naziv ustanova u kojima autori rade, mesto i državu the authors work, place and country (in the order corresponding to the indexed
(redosledom koji odgovara indeksiranim brojevima autora). Na dnu stranice na- numbers of the authors). At the bottom of the page, provide the name, contact
vesti ime i prezime, adresu za kontakt, broj telefona, faksa i imejl adresu autora address, phone number, fax number and email address of the corresponding au-
zaduženog za korespondenciju. Naslovna strana treba da bude na spskom i en- thor. The cover page should be in Serbian and English language (second page).
gleskom jeziku (druga strana). ABSTRACT should be up to 250 words, including acronyms (third page).
SAŽETAK treba da ima do 250 reči, uključujući skraćenice (treća strana). Za For original papers, preliminary and short communications, meta-analyses and
originalne radove, prethodno i kratko saopštenje, meta-analize i pregledne rado- review papers, the abstract should have the following structure: Introduction,
ve, sažetak treba da ima sledeću strukturu: Uvod, Cilj, Metode, Rezultati, Zaključak. Aim, Methods, Results, Conclusion. Each of these segments should be written as
Svaki od navedenih segmenata treba da bude napisan kao poseban pasus. Za prika- a separate paragraph. For case report, the summary should have the following
ze slučajeva sažetak treba da ima sledeće delove: Uvod, Prikaz bolesnika, Zaključak. sections: Introduction, Case Report, Conclusion; each part should be written as a
Svaki deo, takođe, pisati kao poseban pasus. Za ostale vrste radova sažetak nema separate paragraph. For other types of papers, the abstract does not have a special
posebnu strukturu. Ispod Sažetka navesti od tri do šest ključnih reči ili izraza. Ne tre- structure. List three to six key words or phrases below the abstract. Words from the
uputstvo autorima
ba da se ponavljaju reči iz naslova, a ključne reči treba da budu relevantne i opisne. U title should not be repeated, and the key words should be relevant and descriptive.
izboru ključnih reči koristiti Medical Subject Headings – MeSH (http://www. nlm.nih. The Medical Subject Headings - MeSH thesaurus (http://www.nlm.nih.gov/mesh)
gov/mesh). Sažetak treba da bude napisan na srpskom i engleskom jeziku. should be used for selecting the key word. The abstract should be submitted in
Na četvrtoj strani treba da se nalazi prevod teksta koji je na trećoj strani both Serbian and English language.
(sažetak). Ova strana mora da ima identičnu strukturu trećoj strani. The fourth page should contain the translation of the text from the third
Od pete strane broji se broj strana predviđen za odgovarajuću strukturu rada. page (abstract). This page must have the identical structure as the third page.
STRUKTURA RADA. Svi podnaslovi se pišu velikim masnim slovima The number of pages provided for the appropriate structure of the paper is
(bold). Originalni rad, meta-analiza, prethodno i kratko saopštenje obavezno counted from the fifth page.
treba da imaju sledeće podnaslove: Uvod (Cilj rada navesti kao poslednji pasus STRUCTURE OF THE PAPER. Capital bold letters should be used for all sub-
Uvoda), Metode rada, Rezultati, Diskusija (koncizna, jasna, predstavlja tuma- headings. Original papers, meta-analyses, preliminary and short communications
čenje i poređenje rezultata studije sa relevantnim studijama koje su objavljene must have the following subheadings: Introduction (the objective of the paper
u domaćoj i međunarodnoj literaturi), Zaključak (mora proisteći isključivo iz should be stated in the last paragraph of the Introduction), Methodologies, Re-
rezultata istraživanja rada, Spisak skraćenica (ukoliko su korišćene u tekstu), sults, Discussion (concise and clear, it represents the interpretation and compari-
Zahvalnica, Literatura (navodi se arapskim brojevima redosledom kojim je u son of study results with relevant studies published in domestic and international
tekstu navedena u uglastim zagradama, vidi dalje). Struktura rada kod pregle- literature), Conclusion (it must derived solely from the results of the research), List
da literature sastoji se od Uvoda, Većeg broja podnaslova, Zaključka, Literature. of acronyms (if used in the text), Acknowledgment, and Literature (listed using
Autori preglednog rada treba da navedu bar tri rada (kao autori ili koautori) Arabic numerals, in the order in which they appear in the text, in square brackets,
publikovanih u časopisima s recenzijom. Struktura rada kod prikaza jednog ili see below). The structure of literature review papers should be: Introduction, a
više slučajeva čine: Uvod (Cilj rada navesti kao poslednji pasus Uvoda), Prikaz number of subheadings, Conclusion, and Literature. The authors of the reviews
bolesnika, Diskusija, Literatura. Ne treba koristiti imena bolesnika, inicijale, should list at least three papers (as authors or co-authors) published in peer-re-
niti brojeve istorija bolesti, naročito u ilustracijama. Prikazi slučajeva ne smeju viewed journals. The structure of the paper presenting one or more cases should
imati više od pet autora. consists of: Introduction (the objective of the paper should be given as the last
paragraph of the Introduction), Case Report, Discussion, and Literature. Patient
STATISTIČKE METODE, PRIKAZ I INTERPRETACIJA REZULTATA names, initials, and medical history numbers should not be used, especially in
Ukoliko je moguće, sve numeričke vrednosti zaokružiti na jedno decimalno me- illustrations. Case reviews should not have more than five authors.
sto. Ne duplirati prikaz rezultata u tabelama i grafikonima. Za prikaz rezultata u
STATISTICAL METHODS, PRESENTATION AND INTERPRETATION OF RESULTS
tabelama i tekstu preporuka je da se: numerički podaci sa normalnom raspode-
lom i bez ekstremnih vrednosti prikazuju kao aritmetička sredina ± standardna If possible, all numbers should be rounded to one decimal place. The display of
devijacija; numerički podaci čija raspodela odstupa od normalnosti ili kada po- results in tables and graphs should not be repeated. When presenting results in
stoje ekstremne vrednosti, i ordinalni podaci prikazuju kao medijana i opseg (mi- tables and text, it is recommended that numerical data with normal distribution
nimalna – maksimalna vrednost); nominalni podaci i ordinalni podaci sa malim and without extreme values be presented as arithmetic mean ± standard devia-
brojem kategorija prikazuju kao n (%). tion; that numerical data whose distribution deviates from normal distribution or
Prilikom opisa primenjenih statističkih metoda, prikaza i interpretacije re- when there are extreme values, and ordinal data, be presented as the median and
zultata u radu pridržavati se SAMPL Guidelines (Lang TA, Altman DG. Basic statisti- range (minimum–maximum value); that nominal data and ordinal data with a
cal reporting for articles published in biomedical journals: the “Statistical Analyses small number of categories be displayed as n (%).
and Methods in the Published Literature” or the SAMPL Guidelines. Int J Nurs Stud When describing the applied statistical methods, presentation and interpre-
2015;52(1):5-9.). Primenjene statističke metode treba opisati dovoljno detaljno da tation of results in the paper, follow the SAMPL Guidelines (Lang TA, Altman DG.
ih čitalac može ponoviti na svojim podacima. Navesti korišćeni statistički test i Basic statistical reporting for articles published in biomedical journals: The “Sta-
nivo značajnosti. Saopštiti tačnu p-vrednost na 3 decimalna mesta. tistical Analyses and Methods in the Published Literature” or the SAMPL Guide-
lines. Int J Nurs Stud 2015; 52(1):5-9.). The applied statistical methods should be
PRILOGE (tabele, grafikone, slike itd.) postaviti na kraj rukopisa, a u sa-
described in sufficient detail so that the reader may repeat them using own data.
mom tekstu jasno naznačiti mesto koje se odnosi na dati prilog. Krajnja pozicija
Indicate the statistical test used and the level of significance. Report the correct
priloga biće određena u toku pripreme rada za publikovanje.
p-value to the third decimal place.
SKRAĆENICE. Koristiti samo kada je neophodno, i to za veoma dugačke na- ATTACHMENTS (tables, graphs, pictures, etc.) should be placed at the end
zive hemijskih jedinjenja, odnosno nazive koji su kao skraćenice već prepoznatljivi of the manuscript, while clearly indicating in the text the place that refers to the
(standardne skraćenice, kao npr. DNK, sida, HIV). Za svaku skraćenicu pun termin given attachment. The final position of the attachment will be defined during the
treba navesti pri prvom navođenju u tekstu, sem ako nije standardna jedinica preparation of the paper for publication.
mere. U naslovi se ne koriste skraćenice. Izbegavati korišćenje skraćenica u sa-
ACRONYMS should be used only when necessary, i.e. for very long names
žetku, ali ako su neophodne, svaku skraćenicu objasniti pri prvom navođenju u
of chemical compounds and names that are already commonly used as acronyms
tekstu.
(standard acronyms, such as DNA, AIDS, HIV). For each acronym, the full term
DECIMALNI BROJEVI. U tekstu rada na engleskom jeziku, u tabelama, na should be given at the first appearance in the text, unless it is a standard unit of
grafikonima i drugim prilozima decimalne brojeve pisati sa tačkom (npr. 12.5 ± measure. Acronym should not be used in the title. Avoid using acronyms in the
3.8), a u tekstu na srpskom jeziku sa zarezom (npr. 12,5 ± 3,8). Kad god je to abstract, but if necessary, explain each acronym at the first appearance in the text.
moguće, broj zaokružiti na jednu decimalu. DECIMAL NUMBERS. In the English text of the paper, in tables, graphs and
JEDINICE MERA. Dužinu, visinu, težinu i zapreminu izražavati u metričkim other appendices decimal numbers are written with a point (e.g. 12.5 ± 3.8), and
jedinicama (metar – m, kilogram (gram) – kg (g), litar – l) ili njihovim delovima. in the text in Serbian with a comma (e.g. 12,5 ± 3,8). Whenever possible, round
Temperaturu izražavati u stepenima Celzijusa (°C), količinu supstance u molima the number to one decimal place.
uputstvo autorima
(mol), a pritisak krvi u milimetrima živinog stuba (mm Hg). Sve rezultate hema- UNITS OF MEASURE. Express length, weight and volume in metric units
toloških, kliničkih i biohemijskih merenja navoditi u metričkom sistemu prema (meter – m, kilogram (gram) – kg (g), liter – l) or their parts. Express temperature
Međunarodnom sistemu jedinica (SI). in degrees Celsius (°C), amount of substance in moles (mol), and blood pressure
in millimeters of mercury (mmHg). All results of hematological, clinical and bio-
PRILOZI su tabele, slike (fotografije, crteži, sheme, grafikoni), do šest po
chemical measurements should be reported using the metric system, according to
radu. Svaki prilog se dostavlja kao poseban dokument, obeležen na isti način kao
the International System of Units (SI).
u tekstu. Ako su tabele, grafikoni, sheme ili slike već objavljene, navesti originalni
izvor i priložiti pisano odobrenje autora za njihovo korišćenje ATTACHMENTS are tables, pictures (photographs, drawings, diagrams,
graphs), up to six per paper. Each attachment is submitted as a separate docu-
TABELE. Svaka tabela treba da bude sama po sebi lako razumljiva. Naslov ment, labeled the same way as it appears in the text. If tables, graphs, charts or
treba otkucati iznad tabele, a objašnjenja ispod nje. Tabele se označavaju arap- figures have already been published, the original source should be indicated, and
skim brojevima prema redosledu navođenja u tekstu. Tabele crtati isključivo u written consent for their use attached.
programu Word, kroz meni Table– Insert–Table, uz definisanje tačnog broja kolo-
TABLES. Tables should be easily comprehensible. The caption should be typed
na i redova koji će činiti mrežu tabele. Desnim klikom na mišu – pomoću opcija
above the table, with an explanation below it. Tables are labeled with Arabic numer-
Merge Cells i Split Cells – spajati, odnosno deliti ćelije. Kucati fontom Times New
als, according to the order of appearance in the text. Tables should be drawn only in
Roman, veličinom slova 12 pt, s jednostrukim proredom i bez uvlačenja teksta.
MS Word, using the Insert Table function, defining the exact number of columns and
Korišćene skraćenice u tabeli treba objasniti u legendi ispod tabele. Ukoliko je
rows that will form the table grid. Use Merge Cells and Split Cells options to merge or
rukopis na srpskom jeziku, priložiti nazive tabela i legendu na oba jezika. Takođe,
split cells. Use Times New Roman font, size 12 pt, with single spacing and no inden-
u jednu tabelu, u okviru iste ćelije, uneti i tekst na srpskom i tekst na engleskom
tation. The acronyms used in the table should be explained in the legend below the
jeziku (nikako ne praviti dve tabele na dva jezika!).
table. If the manuscript is in Serbian, attach the names of the tables and the legend
SLIKE. Slike su svi oblici grafičkih priloga. Objavljuju se fotografije, crteži, in both languages. Also, enter the Serbian text and English text in the same table,
sheme i grafikoni. Slike se označavaju arapskim brojevima prema redosledu na- within a single cell (never make two tables in two languages).
vođenja u tekstu. Primaju se isključivo digitalne fotografije (crno-bele ili u boji) IMAGES. All forms of graphic attachments are images. Photographs, drawings,
rezolucije najmanje 300 dpi i formata zapisa tiff ili jpg (male, mutne i slike lošeg diagrams and graphs can be published. Images are labeled using Arabic numerals,
kvaliteta neće se prihvatati za štampanje!). Ukoliko autori nemaju ili nisu u mo- according to the order of appearance in the text. Only digital photos (black-and-
gućnosti da dostave digitalne fotografije, onda originalne slike treba skenirati u white or color) of at least 300 dpi resolution, in TIFF or JPG format are accepted (small,
rezoluciji 300 dpi i u originalnoj veličini. Ukoliko je rad neophodno ilustrovati sa blurry and poor-quality images will not be accepted for print). If the authors do not
više slika, u radu će ih biti objavljeno nekoliko, a ostale će biti u e-verziji članka have or are not able to submit digital photos, then the original images should be
kao PowerPoint prezentacija (svaka slika mora biti numerisana i imati legendu). U scanned at a resolution of 300 dpi and in original size. If the paper requires multiple
legendi slika treba napisati korišćeno uveličanje okulara i objektiva mikroskopa. images for illustration, several will be published in the paper, and the rest will be
Svaka fotografija treba da ima vidljivu skalu. Potrebno je priložiti nazive slika i included in the e-version of the article, as a MS PowerPoint presentation (each image
legendu na srpskom i engleskom jeziku. must be numbered and include a legend). The used microscope magnification should
GRAFIKONI. Grafikoni treba da budu urađeni i dostavljeni u programu Ex- be noted in the image legend. Each photo should include the scale. The image names
cel, da bi se videle prateće vrednosti raspoređene po ćelijama. Iste grafikone pre- and the legend should be provided in both Serbian and English language.
kopirati i u Word-ov dokument. Grafikoni se označavaju arapskim brojevima pre- GRAPHS. Graphs should be provided and submitted in MS Excel, in order
ma redosledu navođenja u tekstu. Svi podaci na grafikonu kucaju se u fontu Times to show the accompanying values arranged by cell. The same graphs should be
New Roman. Korišćene skraćenice na grafikonu treba objasniti u legendi ispod copied into a MS Word document. Graphs are labeled with Arabic numerals, ac-
grafikona. Priložite nazive grafikona i legendu na srpskom i engleskom jeziku. cording to the order of appearance in the text. All data in the graphs should be
displayed using the Times New Roman font. Acronyms used on the graph should
SHEME I CRTEŽI. Crteži i sheme se dostavljaju u jpg ili tiff formatu. Svi po-
be explained in the legend below the graph. Include the names of the graphs and
daci na shemi kucaju se u fontu Times New Roman, veličina slova 10 pt. Korišćene
the legend in both Serbian and English language.
skraćenice na shemi treba objasniti u legendi ispod sheme. Ukoliko je rukopis na
srpskom jeziku, priložiti nazive shema i legendu na oba jezika. DIAGRAMS AND DRAWINGS. Diagrams and drawings can be submitted in
JPG or TIFF format. All data in the diagram should be displayed using the Times
ZAHVALNICA. Navesti sve saradnike koji su doprineli stvaranju rada a ne New Roman font, size 10 pt. The acronyms used in the diagram should be ex-
ispunjavaju kriterijume za autorstvo, kao što su osobe koje obezbeđuju tehničku plained in the legend below the diagram. If the manuscript is submitted in Serbi-
pomoć, pomoć u pisanju rada ili rukovode odeljenjem koje obezbeđuje opštu po- an, the names of the diagrams and the legends should be provided in both Serbian
dršku. Finansijska i materijalna pomoć, u obliku sponzorstva, stipendija, poklona, and English language.
opreme, lekova i drugo, treba takođe da budu navedene.
ACKNOWLEDGEMENTS. List all associates who contributed to the production
LITERATURA. Spisak referenci je odgovornost autora, a citirani članci treba of the paper but do not meet the authorship criteria, such as persons providing tech-
da budu lako pristupačni čitaocima časopisa. Reference numerisati rednim arap- nical assistance, assistance in writing the paper, or managing the department that
skim brojevima prema redosledu navođenja u tekstu. Broj referenci ne bi trebalo provided general support. Financial and material assistance, in the form of sponsor-
da bude veći od 30, osim u pregledu literature, u kojem je dozvoljeno da ih bude ships, scholarships, donations, equipment, medicine, etc., should also be listed.
do 50, a u meta-analizi do 100. LITERATURE. The list of references is the responsibility of the author, and
Broj citiranih originalnih radova mora biti najmanje 80% od ukupnog broja the cited articles should be easily accessible to the readers of the Journal. Ref-
referenci, odnosno broj citiranih knjiga, poglavlja u knjigama i preglednih čla- erences should be numbered using Arabic numerals, according to the order of
naka manji od 20%. Nije dozvoljeno citiranje apstrakata. Ukoliko je bitno ko- appearance in the text. The number of references should not exceed 30, except in
mentarisati rezultate koji su publikovani samo u vidu apstrakta, neophodno je the case of literature reviews, in which case it may be up to 50, and up to 100 in
to navesti u samom tekstu rada. Reference članaka koji su prihvaćeni za štampu, the case of meta-analyses.
uputstvo autorima
ali još nisu objavljeni, treba označiti sa in press i priložiti dokaz o prihvatanju Original papers must account for at least 80% of the total number of ref-
rada za objavljivanje. erences, i.e. the number of cited books, book chapters, and reviews must be less
Podaci o korišćenoj literaturi u tekstu označavaju se arapskim brojevima u than 20%. Citing abstracts is not permitted. If it is important to comment on re-
uglastim zagradama – npr. [1,2], i to redosledom kojim se pojavljuju u tekstu. sults that have been published only in the form of an abstract, it is necessary to
Reference se citiraju prema Vankuverskom stilu (uniformisanim zahtevima cite this in the text of the paper. References to articles that have been accepted for
za rukopise koji se predaju biomedicinskim časopisima), koji je uspostavio publication but have not yet been published should be marked “in press” and proof
Međunarodni komitet urednika medicinskih časopisa (http://www.icmje.org), of acceptance of the paper for publication should be attached.
čiji format koriste U.S. National Library of Medicine i baze naučnih publikaci- Information about the literature used in the paper is indicated in the text
ja. Primeri navođenja publikacija (članaka, knjiga i drugih monografija, elek- by Arabic numerals in square brackets, e.g. [1,2], in the order in which they ap-
tronskog, neobjavljenog i drugog objavljenog materijala) mogu se pronaći na pear in the text. References are cited according to the Vancouver style (Uniform
internet-stranici http://www.nlm.nih.gov/bsd/uniform_ requirements.html. Requirements for Manuscripts Submitted to Biomedical Journals), established by
Prilikom navođenja literature veoma je važno pridržavati se pomenutog stan- the International Committee of Medical Journal Editors (http://www.icmje.org),
darda, jer je to jedan od najbitnijih faktora za indeksiranje prilikom klasifikacije whose format is used by the U.S. National Library of Medicine and scientific publi-
naučnih časopisa. Podaci sa interneta citiraju se uz navođenje datuma pristupa cation databases. Examples of citations of publications (articles, books and other
tim podacima. monographs, electronic, unpublished and other published material) are available
Za citiranje literature preporučuje se Mendeley softver za upravljanje refe- at http://www.nlm.nih.gov/bsd/uniform_ requirements.html. When citing litera-
rencama. U okviru softvera preuzeti i aktivirati stil citiranja Vancouver (brackets) ture, it is very important to abide by the mentioned standard, because it is one of
koji uređuje sve reference u skladu sa propozicijama časopisa. the most important indexing factors when classifying scientific journals. Online
Uputstvo na srpskom jeziku za korišćenje Mendeley softvera za upravljanje data is cited with the date of access to that data.
referencama može se preuzeti sa sledećeg linka: The Mendeley Reference Manager software is recommended for managing
https://www.smj.rs/images/casopis/MENDELEY_-_uputstvo.pdf references. Within the software, download and activate the Vancouver (brackets)
style, which organizes all references in accordance with the Journal’s guidelines.
PREDVIĐEN BROJ STRANICA ZA RAD SA SVIM PRILOZIMA
NUMBER OF PAGES FOR THE PAPER (WITH ALL ATTACHMENTS)
1. Uvodnici – do 5 strana: mišljenja ili diskusiju o posebno značajnoj temi za
1. Editorials (up to 5 pages) present opinions or discussions on a particularly rele-
Časopis, kao i o podacima koji su štampani u ovom ili nekom drugom časopisu.
vant topic for the Journal, as well as on data published in this or other journals.
Obično ih piše jedan autor po pozivu.
They are usually written by one author, by invitation.
2. Originalni članci – do 12 strana. Predstavljaju rezultate istraživanja autora
2. Original articles (up to 12 pages) present the results of the research of the
rada i njihovo tumačenje. Istraživanje treba da bude obrađeno i izloženo na
authors of the paper and their interpretation. The research should be processed
način da se može ponoviti, a analiza rezultata i zaključci jasni da bi se mogli
and presented in a way that can be repeated, and the analysis of results and
proveriti.
conclusions should be clear so that they can be verified.
3. Pregledni članci – do 10 strana. Predstavljaju sistematsko, sveobuhvatno i
3. Reviews (up to 10 pages) represent the systematic, comprehensive and critical
kritičko izlaganje problema na osnovu analiziranih i diskutovanih podataka iz
presentation of a problem on the basis of analyzed and discussed data from
literature, a koji oslikavaju postojeću situaciju u određenom području istraži-
literature, which reflect the state of the science in a particular area of r esearch.
vanja. Literatura koja se koristi u radu mora da sadrži najmanje 5 radova autora
The literature used in the paper must contain at least 5 papers by the author of
članka iz uže naučne oblasti koja je opisana u radu.
the article from the specific scientific field addressed in the paper.
4. Prethodna ili kratka saopštenja – do 4 strane. Sadrže izuzetno važne na-
4. Preliminary and short communications (up to 4 pages) contain extremely
učne rezultate koje bi trebalo objaviti u što kraćem vremenu. Ne moraju da
important scientific results that should be published as soon as possible. They do
sadrže detaljan opis metodologije rada i rezultata, ali moraju da imaju sva
not have to contain a detailed description of the methodology and results, but
poglavlja kao originalni članci u sažetoj formi.
they must contain all the same sections as original articles, in a concise form.
5. Stručni članci – do 10 strana. Odnose se na proveru ili prikaz prethodnog
5. Professional articles (up to 10 pages) refer to the verification or presentation of
istraživanja i predstavljaju koristan izvor za širenje znanja i prilagođavanja ori-
previous research; they represent a useful means of disseminating knowledge and
ginalnog istraživanja potrebama postojeće nauke i prakse.
adapting original research to the needs of existing science and practice.
6. Prikazi slučajeva – do 6 strana. Opisuju retke slučajeve iz prakse. Slični su
6. Case report (up to 6 pages) describe rare cases from practice and are similar
stručnim člancima. U ovim radovima prikazuju se neuobičajeni oblici i tokovi
to professional articles. These papers present unusual forms and courses of dis-
oboljenja, neočekivane reakcije na primenjenu terapiju, primene novih dija-
ease, unexpected reactions to the applied therapy, application of new diagnos-
gnostičkih procedura ili retke i nove bolesti.
tic procedures, or rare and new diseases.
7. Članci iz istorije medicine – do 10 strana. Ovi članci opisuju događaje iz
7. History of medicine articles (up to 10 pages) describe developments from
prošlosti sa ciljem da omoguće očuvanje medicinske i zdravstvene kulture.
the past, with the aim of preserving medical and health culture. They have the
Imaju karakter stručnih članaka.
same form as professional articles.
8. Ostali članci – prikazi knjiga, izvodi iz strane literature, izveštaji sa kongresa
8. Other articles – book reviews, excerpts from foreign literature, reports from
i stručnih sastanaka, saopštenja o radu pojedinih zdravstvenih organizacija,
congresses and professional conferences, statements on the operation of health
podružnica i sekcija, saopštenja Uredništva, pisma Uredništvu, novosti u me-
organizations, branches and sections, editorial statements, letters to the edi-
dicini, pitanja i odgovori, stručne i naučne vesti i članci napisani u znak sećanja
torial board, medical news, questions and answers, professional and scientific
(In memoriam).
news and articles written in commemoration (in memoriam).
uputstvo autorima
U POSTUPKU PRIJAVE IN THE SUBMISSION PROCEDURE

U postupku prijave neophodno je da se naglasi kojoj kategoriji rad pripada: uvod- in the submission procedure it is necessary to point out which category the paper
nik, stručni rad, originalni rad, prethodna ili kratka saopštenja, pregledni članak, belongs to: editorial, professional paper, original paper, preliminary or short com-
prikaz slučaja, prikaz serije slučajeva, članak iz istorije medicine i drugo. munications, review article, case review, case series review, paper on the history
Uz rad neophodno je da se pošalje: of medicine, or other.
1) saglasnost svih autora, da rad nije delimično ili u celini objavljen, poslat ili pri- Together with the paper, it is necessary to include:
hvaćen za štampu u drugom časopisu, 1) singed statements of all the authors that the work has not been partially or
2) potpisana izjava svih autora da su rukopis pročitali i odobrili za objavljivanje u entirely published, sent or accepted for publication in another journal;
časopisu sa navođenjem njihovog doprinosa u realizaciji istraživanja i pisanja 2) signed statements of all authors that they have read the manuscript and ap-
rada, proved it for publication in the Journal, stating their contribution to the study
3) izjava o nepostojanju sukoba interesa. or the writing of the paper,
3) a declaration on absence of conflict of interest.
CIP - Каталогизација у публикацији
Народна библиотека Србије, Београд
61
Srpski medicinski časopis Lekarske komore = Serbian Journal of the Medical Chamber / glavni i odgovorni
urednik Milena Šantrić Milićević. - [Štampano izd.]. - Vol. 3, br. 2 (jun. 2022)- . - Beograd : Lekarska komora
Srbije, 2022- (Beograd : Donat Graf ). - 30 cm
Tromesečno. - Tekst na srp. i engl. jeziku. -

Drugo izdanje na drugom medijumu: Srpski medicinski časopis Lekarske komore (Online) = ISSN 2737-9752
ISSN 2737-971X = Srpski medicinski časopis Lekarske komore (Štampano izd.)
COBISS.SR-ID 19685641

SMCLK SJMC 08 2022

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VOLUMEN 3 • BROJ 2 • JUN 2022.

VOLUME 3 • NUMBER 2 • JUNE 2022

SRPSKI MEDICINSKI ČASOPIS

VOLUMEN 3 • BROJ 2 • JUN 2022.

IZDAVAČKI SAVET PUBLISHER’S ADVISORY BOARD

ADRESA UREDNIŠTVA EDITORIAL OFFICE

Poštovane koleginice i kolege,

PO IZBORU UREDNIKA EDITOR’S CHOICE

ORIGINALNI RADOVI ORIGINAL ARTICLES

PREGLEDNI RADOVI REVIEW ARTICLES

STRUČNI RAD PROFESSIONAL ARTICLE

PRIKAZI SLUČAJEVA CASE REPORTS

Milan Dokić, Dragiša Šljivančanin, Sandra Babić, Branislav Milošević

Milica Apostolović Stojanović, Milica Radojković, Aleksandar Stojanović, Vladan Vukomanović

Željko Garabinović, Nikola Čolić, Jelena Vasić Madžarević, Milan Savić

UPUTSTVO AUTORIMA INSTRUCTIONS FOR AUTHORS

A STEM CELL OVERVIEW – FROM EVOLVING HEMOBIOLOGICAL

Autor za korespondenciju: Corresponding author:

EMBRIONALNI NASPRAM ADULTNIH EMBRYONIC VERSUS ADULT STEM CELL

Embrionalne matične ćelije Embryonic stem cells

CHANGES IN PRIMARY HEALTH CARE IN RESPONSE TO

Lidija Šćepanović¹, Nataša Terzić¹

Autor za korespondenciju: Corresponding author:

Godina / Year 2019. 2020.

Kućne posete na 1.000 stanovnika / Home

Posete u ambulanti na 1.000 stanovnika /

e-zdravstva, ali nije premašilo broj recepata iz 2019. CONCLUSION

DIAGNOSIS RELATED GROUP MIGRATION AS AN INDICATOR

zdravstva Srbije Project

medicinu, Beograd, Srbija Medicine, Belgrade, Serbia

Autor za korespondenciju: Corresponding author:

G02А - težinski koeficijent = 6,80 / G02А - Cost weight = 6.80

G02B - težinski koeficijent = 3,51 / G02B - Cost weight = 3.51

starosti 69,8 godina, a u grupi G02B dva i po puta više RESULTS

Varijable / Variables G021 G02A (T81-T88) G02B p

Grad Beograd / 292,397.8 451,224.8 244,222.7

274,765.7 218,098.1 256,400.4

ZAKLJUČAK different infections related to surgical procedures, which

ANTIBIOTIC PROPHYLAXIS IN ABDOMINAL SURGERY –

Autor za korespondenciju: Corresponding author:

Tabela 1. Preporuke za antibiotsku profilaksu u abdominalnoj hirurgiji odraslih [3, 4]

Cefazolin 2 - 3 g, i.v.; Kod operacija dužeg trajanja: nakon 4 h za 1 doza ili

Cefazolin 2 - 3 g, i.v.; Klindamicin 900 mg, i.v.;

Table 1. Recommendations for antibiotic prophylaxis in abdominal surgery in adults [3, 4]

Cefazolin 2 - 3 g + metronidazole Clindamycin 900 mg In prolonged surgery: after 4 hours 1 dose or to be

Trajanje operacije Vreme davanja Lek redoziran Trajanje

Table 3. Characteristics of patients and surgeries and the pattern of antibiotic

LITERATURA / REFERENCES measures and procedures, with the aim of achieving a

Autor za korespondenciju: Corresponding author:

Najmlađi pacijent je imao 35 godina, a najstariji 94

Grafikon 3. Broj pacijenta po uzrasnim grupama u odnosu na pol

Žene / Women Muškarci / Men Ukupno / Total

DISKUSIJA male patients was in the age group between 50 and 59

PREGLEDNI RAD REVIEW ARTICLE

FUNCTIONING, DISABILITY AND EXERCISE IN THE ELDERLY

Autor za korespondenciju: Corresponding author:

FAKTORI POVEZANI SA STARENJEM I ZDRAVIM FACTORS ASSOCIATED WITH AGING AND

Sukob interesa: Nije prijavljen.

PRINCIPLES OF PELVIC FRACTURE TREATMENT

hirurgiju i traumatologiju, Beograd, Srbija and Traumatology, Belgrade, Serbia

Autor za korespondenciju: Corresponding author:

PRVI KORAK U ZBRINJAVANJU PRELOMA FIRST STEP IN TREATING PELVIC FRACTURE

KARLIČNE POVESKE ABDOMINAL-PELVIC TOURNIQUETS