PUBLIC HEALTH AND MANAGEMENT

ACTA MEDICA TRANSILVANICA March 26(1):1-5

DOI: 10.2478/amtsb-2021-0001
Online ISSN 2285-7079

CONSIDERATIONS REGARDING THE PROFESSIONAL

PRACTICING CHOICE OF THE STUDENTS FROM THE
MEDICAL FACULTIES IN ROMANIA

SIMONA PÂRVU (BEU)1

1
“Carol Davila” University of Medicine and Pharmacy, Bucharest

Keywords: students, Abstract: Analysing students’ options regarding the specialty and the country in which they want to
medical, migration, practice, provides useful information in judicious planning of human resources in the health system,
disparity, health services the factors that motivate the choice, being both personal, difficult to change, but also economic or
social that can be influenced by legislation, so that the number of deficient specialties decreases, and
the disparity of the ensuring the medical services in urban to rural areas is reduced. This paper is a
qualitative study, with voluntary response, applied to students of public and private medical schools in
Romania, that investigates the intention to the professional practicing choice after graduation and the
reasons of their decisions. The results show the orientation towards the urban environment in a
percentage of 100% or for migration - between 2.2% and 50%. Regarding the chosen specialties, the
results show that the most frequently chosen specialties were as follows: cardiology, surgery, internal
medicine, specialties considered deficient in 2020.(1)

INTRODUCTION MATERIALS AND METHODS

The insufficient human resources in the public
health system is a challenge for all health systems in the 21st
century, the estimated deficit for 2030 being 18 million
workers.(2)
The migration of the health workforce is a natural
consequence of this reality. The phenomenon of migration of
health professionals is not fully understood, being
encountered in the case of developed countries.
In order to cover the needs of health services for
the entire population of a country, the migration of the health
workforce from rural to urban areas and to areas with greater
economic development must also be taken into account.
The effect of this phenomenon is exacerbating the
crisis of health professionals in poor or developing countries
from which they are leaving. Although tools have been
created at globally level to reduce the negative effects of
migration in countries of origin and at the same time respect
the freedom of movement of health workers, the Code of
Practice adopted in 2010 by the World Health Organization
did not have the expected effects, nor globally,(3) either in
Romania, but progress has been steady in reducing the
negative effects of migration.(4)
AIM
The aim of the paper is to investigate the
professional practicing options for medical students, as well
as the factors that contribute to the migration of doctors from
the Romanian health system, by analysing the options for
insertion on the labour market of students after graduation.
The study also aims to analyse the correlations
between legislative changes in 2006-2018 and the migration
of the workforce from the health system.
The students of the medical universities in Romania
represented the target population, and the research stages were:
- development and validation of an opinion questionnaire
with 23 items, in order to survey students’ perception of the
impact of legislative changes on the quality of health
services, as well as their options for the medical specialty
and the place where they want to carry out their activity, at
the end of their studies;
- establishing of the sample characterized by the age, sex,
specialties, seniority, level of training; with the help of
OpenEpi applications, Version 3, open source computer-
SSPropor,
- collecting of the data through the Google-Form platform
using the questionnaire and creating a database with the
answers;
- statistical processing of the collected data, by introduced in
an analysis software (Excel and EpiInfo);
- data analysis and presentation of the study results.
The calculated sample based on the total number of
14029 students enrolled at budget and fee places, from the
educational offer of 5 public and private university centres, is
374. However, the number of respondents exceeded the
estimated sample, being 920.
RESULTS
By statistically analysing the students’ answers,
relevant conclusions were drawn regarding the options for the
professional practice. Figure no. 1 represents the preferences of
the students, the surgical specialties being in the first place while
the deficient specializations are family medicine, oncology or
specialities of preventive medicine that are not among the
declared intentions.

1
Corresponding author: Simona Pârvu, Str. Dr. A. Leonte, Nr. 1-3, Sector 5, Cod 050463, Bucureşti, România, E-mail: simona.parvu@insp.gov.ro,
Phone: +40724 943392
Article received on 20.12.2020 and accepted for publication on 26.02.2020
AMT, vol. 26, no. 1, 2021, p. 1
 PUBLIC HEALTH AND MANAGEMENT
Figure no. 1. Structure of respondents by targeted specialties Figure no. 3. Reasons for emigration by specialty

Emergency Medicine 50,0% 33,3% 16,7%

Dentistry 50,0% 50,0%
Radiology & Imagistics 28,6% 28,6% 14,3% 28,6%
Pediatrics 50,0% 25,0% 25,0%
Obstetrics & Gynecology 44,4% 55,6%
Internal Medicine 26,7% 40,0% 13,3%20,0%
Surgery 40,7% 32,5% 16,3%
10,6%
Cardiology 53,9% 30,8% 15,4%

0% 20% 40% 60% 80% 100%

Limited access Lack of jobs
Low chances promotion Small income

The predominant reason for each specialty is limited

access to high performance technology. The second reason
invoked is the lack of jobs, for certain specialties, respectively
for internal medicine or obstetrics-gynecology.

Figure no. 4. Participation in legislation courses, in total and

by student segments

Figure no. 2. The intention to carry out the activity

depending on the specialty concerned

In general, a higher share of courses is found among

older students (20%) and more among female students (15.0%)
than among male students (9.3%).

Figure no. 5 Participation in legislation courses in the 5

university centres
The greatest intention to leave the country is found
among students aiming at the specialty of Radiology and/or
Imagistics. The slightest intention to leave Romania is found
among students who want specialize in internal medicine.
Applying the chi-square test, it results that accepting a risk p
<0.01, there is a statistically significant difference regarding the
intention to carry out the activity depending on the targeted
specialty. Another observation that emerges from the analysis of
students’ responses is the intention to practice in the city where
they study, respectively in the university centres, reaching a
percentage of 62.5% in the case of those who choose internal DISCUSSIONS
medicine or in another city in a percentage of 25%. Thus, we Graduates of medical schools enrol in the annual
observe the majority choice to practice in urban areas, residency exam, joining those who want another specialty or
accentuating the deficit in terms of providing medical services in those who did not pass the previous exams. In 2020, 6396
rural areas, even if 10.2% of students come from these areas. candidates registered for the residency exam (5) for the 4645

AMT, vol. 26, no. 1, 2021, p. 2

 PUBLIC HEALTH AND MANAGEMENT
places and positions,(6) but 298 places and positions remained
vacant, including surgical specialties, emergency medicine or
family medicine.(7)
Stimulating the reputation(8) the publication of
information on doctors' incomes, but also the free movement of
professionals with the recognition of diplomas in the European
Union have intensified migration to developed countries.
The intention of Romanian students to migrate after
graduation was recorded in national(9) and international
studies,(10) but the phenomenon of migration of the health
workforce is a global one, and discussions on the effectiveness
of this migration must be discussed both from the perspective of
the country of destination and from the perspective of the source
country.(11)
For the countries where the health professionals
migrate, analysing at European level the effects of migration, it
was found that the problem of human resources is not solved:
the health workforce migration is random, based mainly on the
personal projection of the professional career, without a real
coverage of deficiencies in the country of destination, the
mobility does not take into account the design of human
resources made by the system in which the migrant is inserted,
and the tendency to change jobs is significantly higher among
migrants. Some countries condition access to the labour market
by filling jobs in poor areas, such as Germany, but this policy is
not the rule. Thus, we can speak of a moderate impact of
migration on the real coverage of labour needs in the health
services sector in the destination country.(12,13)
For the source country, migration has the effect of
exacerbating the deficit for certain areas or for certain specialties
that overloads the remaining professionals.(14) The beneficial
effects on the source health system in the case of temporary
mobility, in the case of those working for short periods abroad
or of those returning to the system should also be noted. This
transfers good practices through professionals and creates links
between health units in different systems.
The causes of migration are multiple and not only
related to economic aspects. The respondents in the present
study indicated as main reasons: limited access to technology,
reduced chances of promotion or lack of jobs. These motivations
are also found in other national and international studies. It
should be noted that personal migration is also common in
developed countries, with most European countries being both
source and migrating countries. In developed countries, a
negative correlation was observed between job satisfaction and
the desire to migrate.(15)
The same negative correlation was found between the
perceived quality of medical services provided by a health
system indirectly influences the decision to leave the system by
medical staff.(16)
It was recently found that they returned to the country
from which they migrated, possibly due to the improvement of
the conditions in the country of origin, but also due to the lack
of integration on the labour market. The phenomenon of reverse
migration was found both in Romania and in Spain or Finland.
Another result of this research is the intention of
students to practice in university centres or in urban areas. The
disparity of service provision in urban areas compared to rural
areas is a finding in many health systems.(17) Primary health
care is among the poorest services in more and more rural areas.
A recent study showed that in 2020, 328 rural localities that do
not have a family doctor were reported, but also 271 urban
localities with a surplus of family doctors.(18) Possible solutions
to reduce the gap, can be specially created programmes to attract
family doctors in rural areas,(19) creating connections between
rural communities and educational units(20) or conducting
internships in rural areas during training.(21) Directed and
AMT, vol. 26, no. 1, 2021, p. 3
sustained efforts can lead to a good integration of young doctors
in rural areas.(22)
The legislative framework from 2006-2018 led in
certain periods to the acceleration of the migration of medical
staff. Thus, with Romania’s entry into the European Union,
most of the medical specializations were recognized, and new
geographical horizons were opened for practitioners to practice.
In 2010, after 67 hospitals were closed by reorganizing beds and
reducing the number of beds nationwide, some doctors were
again encouraged to practice abroad in the absence of coherent
retention policies. Another major legislative factor that has
contributed to the migration of doctors is the chronic
underfunding of the system, with the blocking of employment in
the health system (23) initially for 2010, then with employment
in the system for 7 vacancies position - one put up for
competition in 2011(24) or for 3 vacancies, one put up for
competition between 2011-2019. This policy on securing human
resources in the budget system, including the health system, has
had the effect of migrating labour force abroad or in the private
health system and exacerbating the human resource crisis in the
public system by increasing the burden on remaining doctors.
The negative impact on the health of the population came as a
natural consequence.
Another observed phenomenon is the reversal of the
pyramid of health services provided, with the decrease of
primary health care services and the increase of the number of
specialized consultations. The choice by students of the
specialties of obstetrics-gynecology, internal medicine, surgery
in which to practice comes as an adaptation to the demand for
services on the health services market. In urban areas,
specialized health care services are accessed directly by patients
who have financial resources. In addition, employees of
multinational companies benefit from medical service packages
that include free specialist consultations.
In order to counteract all these effects, to diminish the
migration phenomenon and to fight the urban/rural disparity in
the provision of medical services, so that the access to services
ensures to the citizens the right guaranteed by the Constitution
to take care of their health, energetic measures are required.
from socio-economic realities,(25) and the implementation of
these measures must be monitored to correct any deficiencies in
effect. Addressing the limitation of migration only in financial
terms has proved ineffective.(26)
At the global level as well as in the countries of the
European Union, there is a real crisis every year, in terms of the
number of doctors, of various specialties, which will ensure
healthcare at an optimal level according to demographic, socio-
economic characteristics and in particular, of specific
morbidity.(27) There are many explanations for this shortfall,
and government structures must be concerned to permanently
identify these real causes and to take measures to urgently
correct factors that may adversely affect the efficiency of health
systems in each country, but and as a whole, at European level.
In Romania, repeated legislative changes have been based on
somewhat different views on reform, without a coherent global
vision.(28)
A specific problem of the reforms in the system is the
image created by the media and politicians. An IRES survey
from 2010 highlights dissatisfaction with the quality and variety
of food, comfort and hygiene in the hospital, but most of the
interviewees (77%) said they were satisfied and very satisfied
with the care given. The migration of medical staff, of all
professional categories, is a reality of the transition period,(29)
and the phenomenon has been the subject of numerous studies,
in an attempt to identify not only causes but also solutions for
ensuring the human resources necessary for the functioning of
the health system.(30) The opinion of the medical staff
 PUBLIC HEALTH AND MANAGEMENT
regarding the changes in the system and the impact on the
quality of the medical act has been the subject of extensive
studies, some even targeting the sphere of national security.(31)
Another study,(32) conducted in 2016 by the deans of
medical schools in Romania and Chișinău, analysed broad
aspects of the medical system, such as human resources, patient
satisfaction, physician satisfaction, resident physicians and
knowledge of medical students, on the legislation in domain.
The general conclusion of the study shows how necessary is the
involvement of universities in collaboration with decision
makers, but also with local authorities, to solve pressing
problems in the field. The inclusion of health legislation courses
in the curricula of some of the medical faculties and the
participation of students in these courses is beneficial for the
correct information, but the percentage of students who
participated in these courses is reduced.(33)
CONCLUSIONS
The intention to study abroad is an option for most
students from medical schools in Romania, even when they
choose specialties considered deficient such as cardiology,
internal medicine or anesthesia-intensive care. The reasons
invoked are related to the limited access to state-of-the-art
technology, but also to the lack of jobs.
The students’ knowledge regarding the health
legislation, as well as the way of informing on this subject is
reflected in the choice of the specialty they will embrace and,
last but not least, in the choice of the state in which after
graduating they choose to practice.
From the analysis of the professional practice option,
one can observe the choice for the urban areas, especially in
university centres, with the accentuation of the disparity
between rural and urban.
Through curricula that include health legislation
courses, medical schools have created the prerequisites for
taking social responsibility, but the student participation is low.
It is necessary to include these courses in the curricula of all
medical schools and to train students to participate in these
courses.
In order to counteract the negative effects of these
findings in ensuring human resources and implicitly in the
health of the population, it is necessary to ensure sufficient
funds and the involvement of local authorities to attract doctors
to rural areas by collaborating with faculties and students during
training.
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AMT, vol. 26, no. 1, 2021, p. 5

 PUBLIC HEALTH AND MANAGEMENT
ACTA MEDICA TRANSILVANICA March 26(1):6-8
DOI: 10.2478/amtsb-2021-0002
Online ISSN 2285-7079

THE IMPACT OF LEGISLATIVE CHANGES ON THE NUMBER

OF CALLS TO THE ROMANIAN COVID 19 TELVERDE
HELPLINE

MIHAI BUZATU1, GEORGETA DINCULESCU2, FLORENTINA LIGIA FURTUNESCU3,

DANA GALIETA MINCĂ4
1,2,3,4
“Carol Davila” University of Medicine and Pharmacy, Bucharest

Keywords: Covid 19, Abstract: On 24th of February 2020, the Ministry of Health in Romania announced the
telverde, green line, operationalization of the Green Line, known as Telverde, within the National Institute of Public
emergency, military Health, in order to provide citizens with information related to the prevention of Sars-Cov-2 infection.
ordinances The number of registered calls increased considerably at the time of the declaration of the pandemic,
the beginning and the cessation of the state of emergency and during the issuance of military
ordinances. Different key periods were studied and compared so that we could determine if the major
administrative and legislative events have influenced the number of registered calls. Our findings
sustained the supposition that the major events that took place during this period have indeed
influenced the number of telephone calls made to TelVerde helpline.

INTRODUCTION MATERIALS AND METHODS

After the first confirmed case of coronavirus in
Romania, the authorities put into operation a free telephone line,
telverde, aimed to inform citizens about the infection with the
Sars-cov-2 virus.(1,2)
The program began to operate within the National
Institute of Public Health (NIPH) with employees of the
institution as phone operators. In a short time, due to the high
demand, the Green Line (TelVerde) project increased the
number of telephone stations, thus needing more operators,
including resident doctors and personnel from the Ministry of
Defense.(1)
In addition to the fact that TelVerde has proven to be
the most effective platform for informing citizens about the new
coronavirus, it has also become an environment conducive to the
development of the professional skills of the medical staff
involved.(1,2)
Both the number of calls made to the TelVerde
helpline and the type of questions asked varied from one day to
another.
The citizens, calling either from Romania of from
abroad, often wanted to find out new information on the status
of countries at epidemiological risk for travel purposes, isolation
or quarantine measures that were to be taken for people who
were to enter the country, as well as basic information about the
new virus, symptoms infection prevention methods.(1,2)
AIM
The aim of this six-month analysis is to identify
whether the number of registered TelVerde calls was influenced
by major administrative events dating from the 26th of February
2020 (first reported case) to the end of the State of Emergency,
the beginning of the State of Alert and until the 29th of August
2020.
To comprehend the impact, we studied the main
sources of information such as the official daily newsletters
issued by the Ministry of Health (MH), the public data reports
from the Ministry of Internal Affairs (MIA) as well as the press
release statements of the Strategic Communication Group from
within MIA and other national databases in order to acquire the
essential data.
First, we identified and then we analysed several
parameters as followed:
a. The number of Covid-19 Green Line calls that were made
before, during the enforcement and after the cessation of the
State of Emergency.(3,4)
b. The number of calls that were made after the World Health
Organization (WHO) declared the Covid-19 pandemic.(3,4)
c. The number of calls made on the day of the announcement of
each military ordinance and after the provisions came into force.
d. The comparison between a two-month period consisting of
the State of Emergency between the 16th of March till the 15th of
May and another two-months period from the State of Alert
from the 16th of May till the 15th of July.(3,4)
e. The number of calls made after the cessation of the State of
Emergency and the beginning of the State of Alert followed by
Government decision issues.(3,4)
For the analysis of the number of calls that were made
before, during and after the State of Emergency, we summed up
all the calls from each period and calculated the respective
percentages. Then we compared the three obtained values,
pointing out the effect of the enforcement of the state of
emergency over the number of calls.
After that we studied the period between the
implementation of TelVerde up until the enforcement of the
State of Emergency, underlining the effect of WHO declaring
the Covid-19 pandemic had on the number of calls that were

1
Corresponding author Mihai Buzatu, Str. Leonte Anastasievici Nr. 1-3, București, România, E-mail: mihai.buzatu@drd.umfcd.ro, Phone: +40731
458438
Article received on 15.02.2020 and accepted for publication on 02.03.2021
AMT, vol. 26, no. 1, 2021, p. 6
 PUBLIC HEALTH AND MANAGEMENT
registered in that brief period of time.(5) 9359 calls on the 25th and 10024 calls on the 26th.(3,4,6,8,9)
The overall evolution was taken into consideration in
order to point out the trend line of the TelVerde calls during the Figure no. 2. The spiking of TelVerde calls on the days of
whole studied period, from the 28th of February till the 29th of MO announcements and following the enforcement of their
August. provisions
The next parameter analysis consisted in evaluating
the effects of the military ordinances on the number of calls
from the days of issuance and the days following their entry into
force, during the whole period of the State of Emergency
between the 16th of March and the 15th of May 2020.(2)
The last parameter was chosen to show the effect of
the Government Decisions over the number of calls made in that
period, between the 16th of May till the 29th of August, during
the State of Alert.(4,9)

RESULTS
Our analysis over this six-month period, from the 26th
of February to the 29th of August, has revealed that the
enforcement of the State of Emergency increased the number of
phone calls to the TelVerde line by 44%, thus reaching a value The rest of the military ordinances continued to
of 56% (191.081 calls) in comparison with the number of calls influence the number of TelVerde calls as followed in table no.
from the Pre-State of Emergency period which represented 12% 1.(3,4)
(41.129 calls). Its cessation also influenced the number of
TelVerde calls, reducing the number of calls by 24% and Table no. 1. Number of TelVerde calls made on the days of
reaching a value of 32% (111.776 calls).(3,4) Announcement of Military Ordinances no. 4 to 12 and of
Furthermore, before the World Health Organization Empowerment of their provisions
declared the pandemic, the mean number of calls was around Military No. of calls on No. of calls on
1450 calls per day, whereas after the pandemic was declared, the
mean number of calls per day spiked at 6268 (figure no.
Ordinance No. Announcement Empoverement day
2).(3,4,5) 4 4118 3912
5 3912 6393
Figure no. 1. The mean number of TelVerde calls before and 6 3912 6393
after the World Health Organization declared the Covid-19
pandemic 7 4164 3300
8 2109 2183
9 1917 1982
10 1197 2282
11 815 1905
12 1794 1932
By comparing the two periods, one from the State of
Emergency and one from the State of alert, both consisting of a
two-month interval we discovered that the number of calls that
were registered during the 16th of March and the 15th of May
interval was considerably higher than the number registered to
the second period between the 16th of May and the 15th of June
(figure no. 3).(3,4)
Each military ordinance (MO) came with a set of strict
provisions and restrictions and the most impactful were the first Figure no. 3. Comparison between the number of registered
MO, that announced the lockdown, restrictions regarding public calls in State of Emergency and State of Alert two-month
and private events, hospitality industry activity, public and cargo intervals
transports and flights (green) and the third MO (purple) that
brought changes regarding the restrictions of circulation of
citizens in public space that required an affidavit which was
previously stated in the second MO (yellow).(6,7,8,9)
The number of calls registered on the days of
announcement was always higher than the previous days, except
for the case of MO 1 (5517 calls) that came right after the
pandemic declaration period (5616 calls on the 15th of
March).(2,3,6)
An increase of phone calls was also observed in the
following days right after the provisions of each ordinance came
into force (figure no. 3). The number of calls registered after the
enforcement MO 1, were 6187 calls on the 17th and 7885 on the
18th of March. After the MO 3 enforcement on the 24th of March
(8171 TelVerde calls), there were two days of spiking values of

AMT, vol. 26, no. 1, 2021, p. 7

 PUBLIC HEALTH AND MANAGEMENT
As previously discovered, during the State of Alert, REFERENCES
the number of registered TelVerde calls followed a downward 1. National Institute of Public Health
trajectory, with two exceptions that generated spikes in the https://insp.gov.ro/dj/comunicate/Informare%20cu%20priv
registered phone calls. ire%20la%20activitatea%20TELVERDE.pdf Accessed at
The first one was right at the beginning, on the 15th 20.05.2020.
th
and 16 of May, when the Government Decisions no. 24 and 2. Ministry of Internal Affairs
394 (GD 24 and GD394) were announced and later enforced. https://www.mai.gov.ro/buletin-informativ-27-februarie-
These decisions brought various changes such as modifications ora-10-00/ Accessed at 10.03.2020.
to the affidavit and education access, citizen circulation outside 3. Ministry of Health. Newsletter. Press releases.
the residential area or the reopening of dental offices and http://www.ms.ro/comunicate/ 65-154 Accessed at
outpatient clinics for non-urgent cases.(9) 30.08.2020
The second spike, and the most impressive, was 4. Ministry of Internal Affairs, Strategic Communication
caused by the Government Decision 476/2020 on the 16th and Group. Press releases
17th of June. This was the one that announced the reopening of https://www.mai.gov.ro/category/comunicate-de-presa/
certain hospitality industry sectors and fitness and spa treatment Accessed at 30.08.2020.
centres, kindergartens and afterschool programmes, changes to 5. World Health Organization. Director General’s opening
private event planning restrictions and the organization of exams remarks at media briefing. https://www.who.int/director-
in the educational sector.(9) general/speeches/detail/who-director-general-s-opening-
remarks-at-the-media-briefing-on-covid-19---11-march-
Figure no. 4. Registered TelVerde calls during the State of 2020 Accessed at 13.03.2020.
alert, descending trend and Government Decision related 6. Ministry of Internal Affairs. Military Ordinance 1.
peaks 16.03.2020 https://www.mai.gov.ro/wp-
content/uploads/2020/03/Ordonan%C8%9Ba-
militar%C4%83-nr.-1-2020-m%C4%83suri-de-prima-
urgen%C8%9B%C4%83-Decret.pdf Accessed at
19.03.2020.
7. Ministry of Internal Affairs. Military Ordinance 2.
21.03.2020 https://www.mai.gov.ro/wp-
content/uploads/2020/03/Ordonanta-militar%C4%83-nr.-2-
2020-m%C4%83suri-prevenire-COVID-19-1-1.pdf
Accessed at 22.03.2020.
8. Ministry of Internal Affairs. Military Ordinance 3.
27.03.2020 https://www.mai.gov.ro/ordonanta-militara-nr-
3-din-24-03-2020-privind-masuri-de-prevenire-a-
raspandirii-covid-19/ Accessed at 29.05.2020.
9. Government of Romania. Measures. GD24, GD24 Annex,
Accessed at 29.05.2020.
10. Government Decision 394/18.05.2020
http://legislatie.just.ro/Public/DetaliiDocument/225876
Accessed at 22.05.2020.
11. Government Decision 476/2020 16.06.2020-17.06.2020
http://legislatie.just.ro/Public/DetaliiDocument/226824
Accessed at 25.06.2020.

DISCUSSIONS
Our analysis revealed that the major legislative and
administrative events that occurred during this period had
indeed influenced the number of calls that the citizens of
Romania have made to TelVerde helpline. Even though the
State of Alert came with its own set of changes, those were
relaxation measures that led to less incoming calls.
Moreover, the study indicates that 68% of the calls
(232.210) were received from the beginning of the pandemic
until the end of the State of Emergency and only 32% (111.776)
for the rest of the study period.(3,4)

CONCLUSIONS
The provisions and restrictions that came with the
Military Ordinances have generated a series of questions
spanning from the medical aspects of the pandemic, to the
legislation alterations that were changing frequently.
It was most obvious that people felt the need to access
this source of information at a greater level during the State of
Emergency period since that was the time when the legislative
and administrative modifications had the most impacting
consequences on their everyday lives.
AMT, vol. 26, no. 1, 2021, p. 8
 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):9-12
DOI: 10.2478/amtsb-2021-0003
Online ISSN 2285-7079

CARDIOVASCULAR RISK FACTORS - ASSOCIATION WITH

LOWER EXTREMITY VERSUS CORONARY ARTERY DISEASE

CORNEL IOAN BITEA1, IOAN MANIŢIU2, GEORGIANA BĂLŢAT3, OANA STOIA4

1,3,4
Emergency County Clinical Hospital, Sibiu, 1,2,3,4”Lucian Blaga” University of Sibiu,
1,3
Invasive and non-invasive research centre in the field of cardiac and vascular pathology in adults - CVASIC, Sibiu

Keywords: cardiovascular
risk factors, C-reactive
protein, chronic kidney
disease, lower extremity
artery disease, coronary
artery disease
Abstract: Atherosclerosis is the main cause of lower extremity artery disease (LEAD) and coronary
artery disease (CAD). These two arterial territories share the major cardiovascular risk factors:
smoking, hypertension, dyslipidaemia and diabetes. Current guidelines draw attention to other
possible risk factors: homocysteine level, inflammation markers (e.g. high-sensitive C reactive-protein
(CRP), interleukin 6) and chronic kidney disease (CKD.) The objective of this study was to evaluate
the cardiovascular risk factors strength association with LEAD and CAD on a study population of 203
patients. Our study concluded that smoking seems to be the most powerful risk factor for LEAD,
especially for significant lesion in femoral arteries, while diabetes mellitus, hypertension and CKD
were significantly associated with CAD. The highest chance of association with multivessel-CAD is
for diabetes mellitus compared to hypertension and CKD respectively. Moreover, in diabetic patients
the percent of multivessel-CAD was significantly higher than the percent of single-CAD and non-
significant CAD.

INTRODUCTION with symptomatic LEAD were evaluated. The patients

Lower extremity artery disease (LEAD) and coronary
artery disease (CAD) are associated with considerable
morbidity, diminished quality of life and mortality.(1) These
two pathologies refer to different degrees of arterial stenosis
subsequent to several causes: embolism, thrombosis, vasculitis
disease and atherosclerotic disease.(2) Atherosclerosis is the
most common cause of LEAD and CAD; thus, this two arterial
territories share the major cardiovascular risk factors: smoking,
hypertension, dyslipidaemia and diabetes (3). However, current
guidelines also draw attention to other possible risk factors for
atherosclerotic disease: homocysteine level, markers of
inflammation (e.g. high-sensitive C reactive-protein (CRP),
fibrinogen, interleukin 6) (4) and chronic kidney disease (CKD).
Each risk factor is associated with variable strength
with each vascular territory; thus, screening of all major risk
factors should be considered.(3)
Each vascular region affected by atherosclerotic
disease can be considered a marker of cardiovascular risk.(3)
Atherosclerosis is a slow process, which leads to a
disease slow progression. In this context, early identification and
control of risk factors may contribute to a late symptomatology
onset, less severe disease, better outcome and life quality
improvement.
AIM
The aim of the current study is to evaluate the strength
of association between cardiovascular risk factors and LEAD
versus CAD.
MATERIALS AND METHODS
From January 2017 to December 2019, 203 patients
underwent digital subtraction angiography for LEAD evaluation
and coronary angiography for CAD evaluation in Sibiu County
Clinical Emergency Hospital, CVASIC research centre.
Significant LEAD and CAD were defined as at least
one lesion with ≥ 50% lumen diameter stenosis. Lower
extremity arteries were divided into three segments: iliac
(common iliac artery, external iliac artery, internal iliac artery),
femoral (common femoral artery, superficial femoral artery) and
infrapopliteal (popliteal artery, tibioperonier trunk, anterior
tibial artery, posterior tibial artery, fibular artery). CAD was
classified as significant-CAD (any coronary artery stenosis ≥
50% lumen diameter in left main (LM) artery or left anterior
descending (LAD) artery or circumflex artery (CA) or right
coronary artery (RCA)) or non-significant-CAD (without
coronary artery stenosis ≥ 50% lumen) and as single-CAD (only
one of LAD or CA or RCA with lesion above 50%) or
multivessel-CAD (LM stenosis ≥ 50%, or any of two arteries
from LAD, CA, RCA with arterial stenosis ≥ 50%).
Hypertension, dyslipidaemia and diabetes were
defined according to current guidelines: hypertension as a
history of antihypertensive drug use or newly diagnosed
hypertension by repeated arterial blood pressure measurements
(at least two) ≥ 140/90 mmHg during hospitalization, diabetes
was considered present when patients were taking an
hypoglycemic treatment - oral agents or insulin, and/or had a
fasting glucose level ≥ 126 mg/dL or glycosylated hemoglobin ≥
6.5%. Dyslipidemia diagnosis was considered if a patient had a
history of lipid-lowering therapy (statin) use, or had a total
cholesterol level ≥ 200 mg/dL or triglyceride (TG) level ≥ 150
mg/dL. The patients were considered positive for smoking if
they were active smokers or former smokers - but not more than

1
Corresponding author: Cornel Ioan Bitea, Str. Corneliu Coposu, Nr. 2-4, Sibiu, România, E-mail: cornelioanbitea@yahoo.com, Phone: +40766
210522
Article received on 17.02.2021 and accepted for publication on 02.03.2021
AMT, vol. 26, no. 1, 2021, p. 9
 CLINICAL ASPECTS
1 year abstinence. claudication in less than 200
m walk
Normal values for C reactive-protein in our laboratory III: limb rest pain 40 (19.7%)
were 0-5 mg/dl. Chronic kidney disease was classified form IV: ischemic lesions – 28 (13.8%)
grade I to V according to KDOQI classification, and creatinine necrosis, gangrene
clearance was calculated with Cockcroft-Gault formula. Claudication index, m 144±24 Min: 0 Max: 1000
Ankle-Brachial index 0.62±0.24 Min: 0 Max: 1
Statistical analysis was performed using IBM SPSS
Statistic software. The Shapiro-Willk test was used to analyse
data normality. Normally distributed continuous variables were Table no. 2. Patients’ biological characteristics
expressed as the mean±SD, and non-normally distributed Parameter Mean±SD Minimun Maximum
continuous variables were expressed as the median value. Total cholesterol, 207.60±55.86 107 357
Pearson Chi-Square tests, for discontinuous variables, and mg/dl
Kruskal Wallis test, for continuous variables, were used to LDL-cholesterol, 117.57±43.76 31 290
evaluate the risk factors association with LEAD and CAD. mg/dl
Statistical significance was considered at a P value <0.05 (two- HDL – cholesterol, 44.91±10.93 27 86
tailed). mg/dl
Triglycerides, mg/dl 185.78±148.4 44 1356
RESULTS Creatinine, mg/dl 1.02±0.59 0.55 6.88
Patients’ characteristics Clearance 85.75±25.59 8.32 166.99
Creatinine,
Of the 203 patients with symptomatic LEAD, 166 ml/min/1.73m2
(81.8%) were males, 37 (18.2%) were females; the mean age C reactive-protein , 8.07±12.79 0.57 127.62
was 65.31±8.616 (range 39-85years). 135 (64.5%) patients were mg/dl
in stage II Leriche-Fontaine, 40 (19.7%) in stage III Leriche- Risk factors association with LEAD
Fontaine, 28 (13.8%) in stage IV Leriche Fontaine. In our study population smoking was highly
Hypertension had the higher prevalence in our study group associated with significant arterial stenosis in iliac and femoral
(79.8%) followed by smoking (76.84%), CKD (58,1%), segments (table no. 3). 92 (59%) smoking patients had
hypercholesterolemia (54.7%), hypertriglyceridemia (48.3%) significant iliac lesions, versus 19 (40%) non-smokers patients
and diabetes mellitus (34.5%). The majority of patients were with significant iliac lesions. The association was statistically
with stage II Leriche-Fontaine LEAD with a mean claudication significant (p=0.021). In femoral segment a statistically
index of 144±24 m and a mean ankle-brachial index of significant association is also registered (p 0.0001). The highest
0.62±0.24. chance of smoking association is with significant lesions in
Patient’s demographic, clinical and biological femoral segment (likelihood ratio 20.85) compared with iliac
characteristics are summarised in table no. 1 and table no. 2. segment (likelihood ratio 8.3) For infrapopliteal segment the
association was not statistically significant (p 0.356).
Table no. 1. Patients’ demographic and clinical
characteristics Table no. 3. Smoking association with LEAD
Variable Value Arterial Smoking Chi Square test
Age, years 65.31±8.6 Min: 39 Max: 85 stenosis>50
BMI, kg/m2 27.44±4.48 Min: 17.72 Max: 43.21 %
Underweight 2 (1%) Yes No χ² df p Like-
Normal weight 67 (33%) lihood
Overweight 82 (40.4%) ratio
Grade I obesity 40 (19.7%) Iliac segment 92 (59%) 19(40%) 7.7 2 0.021 8.30
Grade II obesity 10 (4.9%) Femoral 132 47 17. 2 0.000 20.85
Grade III obesity 2 (1%) segment (84.7%) (100%) 4 1
Gender Male 166(81.8%) Infrapopliteal 130 43 2.0 2 0.356 2.26
Female 37 (18.2%) segment (83.3%) (91.5%) 6
Smoking Yes 156 (76.84%)
No 47 (23.16%)
The others risk factors evaluated, diabetes mellitus,
Diabetes mellitus (DM) Yes 70 (34.5%) hypertension, CKD, hypercholesterolemia,
No 133 (65.5%) hypertriglyceridemia, C reactive protein were not associated
Hypertension Yes 162 (79.8%) with significant arterial stenosis in any of the iliac, femoral and
Grade I 0 (0%)
Grade II 76 (37.4%)
infrapopliteal arterial segments (p>0.05) as shown in table no.4.
Grade III 85 (41.9%)
No 41 (20.2%) Table no. 4. Diabetes mellitus, hypertension, CKD,
hypercholesterolemia, hypertriglyceridemia, C reactive
Hypercholesterolemia Yes 111 (54.7%) protein association with LEAD.
No 92 (45.3%) Arterial DM Hyper- CKD Hyper- Hyper- CRP
Hypertriglyceridemia Yes 98 (48.3%) stenosis>50 tension choleste triglycer
No 105 (51.7%) % rolemia idemia
CKD Yes (Creatinine clearance 118 (58.1%) p two-tailed Chi – Square Test
<90ml/min/1.73m2) Iliac 0.241 0.891 0.986 0.890 0.349 0.058
Grade II 85 (41.9%) segment
Grade IIIa 28 (13.8%)
Femoral 0.116 0.096 0.445 0.144 0.349 0.337
IIIb 3 (1.5%)
segment
Grade IV 0 (0%)
Infrapoplitea 0.158 0.708 0.249 0.819 0.174 0.058
Grade V 1 (1%)
l segment
No (Creatinine Clearence > 85 (41.9%) Similar with the value of total cholesterol, LDL-
90 ml/min/1.73m2) cholesterol value was not significantly associated with
Leriche-Fontaine I : Asymptomatic 0 (0%) significant LEAD, in none of the three arterial segments: iliac
classification IIa: intermittent 17 (8.4%)
claudication at more than (p=0.786), femoral (p=0.461), infrapopliteal (p=0.342).
200 m walk Risk factors association with CAD
IIb: intermittent 118 (58.1%) In our study population smoking,
AMT, vol. 26, no. 1, 2021, p. 10
 CLINICAL ASPECTS
hypercholesterolemia, hypertriglyceridemia was not factor for lower extremity artery disease. In a paper published in
significantly associated with significant CAD or multivessel- 2012 by Joosten et al it was pointed out that smoking has a
CAD as shown in table no. 5. population attributable fraction for LEAD of approximately
44%.(9) In our study group smoking was highly associated with
Table no. 5. Smoking, hypercholesterolemia, significant arterial stenosis in iliac and femoral segments, but
hypertriglyceridemia association with CAD the association was not statistically significant for infrapopliteal
Smoking Chi Square test segments.
Yes No χ² df p Like- Regarding smoking and CAD, there is a strong
CAD
lihood
ratio association with ischemic heart disease.(5) Heavy smokers -
Significant 111(71.2 38(80.9% 1.74 1 0.187 1.82 more than 20 cigarettes per day - have a 2- to 3-fold increase in
CAD %) ) total heart disease. Moreover, continued smoking is a very
Multivessel 73(46.8 28(56.9% 2.74 2 0.254 2.81 important risk factor for recurrent myocardial infarction.(5,10)
CAD %) )
Hypercholesterolemia Chi Square test In our study population smoking was not significantly
Yes No χ² df p Like- associated with CAD.
lihood In the Framingham Heart Study, even high-normal
ratio blood pressure (defined as a systolic blood pressure of 130-139
Multivessel 56(50.5%) 45(48.9% 0.19 2 0.908 0.193
CAD ) mm Hg, diastolic blood pressure of 85-89 mm Hg, or both)
hypertriglyceridemia Chi Square test increased the risk of cardiovascular disease 2-fold, as compared
Yes No χ² df p Like- with healthy individuals.(7) Studies have also shown that a 20
lihood mmHg increase of systolic blood pressure was associated with a
ratio
Multivessel 50(51%) 51(48.6% 2.07 2 0.354 2.09 63% higher risk for LEAD.(8) In our study group hypertension
CAD ) was significantly associated with CAD, but there was no
The other risk factors – diabetes mellitus, significant association with LEAD.
hypertension and CKD were significantly associated with Dyslipidemia is a major cardiovascular risk factor.
significant CAD and multivessel-CAD (p<0.05). The highest The risk of CAD increases proportional with the cholesterol
chance of association with multivessel-CAD is for diabetes level, as shown in Framingham Heart Study.(5,7)
mellitus (likelihood ratio 28.73), compared to hypertension Hypercholesterolemia is a significant contributor to peripheral
(likelihood ratio 12.14) and CKD (likelihood ratio 6.23), artery disease, being independently associated with incident
respectively (table no. 6). clinical LEAD.(9) Several studies have shown that high LDL-
cholesterol and low HDL-cholesterol are associated with an
Table no. 6. Diabetes mellitus, hypertension and CKD increased risk for atherosclerotic disease.(4) Moreover, in large
association with CAD epidemiological studies, high levels of HDL-cholesterol ware
Diabetes mellitus Chi Square test found to be protective for CAD and LEAD.(4,11) In univariate
Yes No χ² df p Like-
CAD
lihood
analysis hypertriglyceridemia is associated with LEAD, but in
ratio multivariate analysis it usually drops out as an independent risk
Significant 61(87.1%) 88(66.2% 10.3 1 0.001 11.24 factor.(4,12,13) In our study group hypercholesterolemia and
CAD ) hypertriglyceridemia were not associated with significant
Multivessel 52(74.3%) 49(36.8% 27.1 2 0.0001 28.73
CAD )
arterial stenosis in any of the iliac, femoral and infrapopliteal
Hypertension Chi Square test arterial segments and with significant CAD. The small number
Yes No χ² df p Like- of patients enrolled in this study among with lipid-lowering
lihood therapy can explain this discordant result compared to literature
ratio
Significant 126(77.8 23(56.1% 7.87 1 0.005 7.32
data.
CAD %) ) Diabetes mellitus is an important risk factor for CAD
Multivessel 90(55.6%) 11(26.8% 12.08 2 0.002 12.14 and LEAD. Diabetic patients are more likely to experience
CAD ) future cardiovascular events compared with healthy
CKD Chi Square test
Yes No χ² df p Like-
population.(5,14) Strong diabetes – LEAD association was
lihood proved in populations studies, with ORs ranging from 1.9 to
ratio 4.(4,12) For our study group diabetes mellitus was significantly
Significant 94(79.7%) 55(64.7% 5.66 1 0.017 5.60 associated with significant CAD and multivessel-CAD.
CAD )
Multivessel 66(55.9%) 35(41.2% 6.26 2 0.044 6.23
Moreover, the percent of diabetic patients with multivessel-
CAD ) CAD was significantly higher than the percent of diabetic
Also, in diabetic patients the percent of multivessel- patients with single-CAD and non-significant CAD. On the
CAD was significantly higher (74.3%) than the percent of other hand, diabetes was not associated with LEAD in our study
single-CAD (17.1%) and non-significant CAD (8.6%). group, probably due to the small cohort and small percent of
diabetic patients evaluated.
DISCUSSIONS Classic cardiovascular risk factors are common
The predominance of male gender in our study group findings in CKD patients, but CKD brings additional specific
is concordant with literature data, both LEAD and CAD risk factors that promote atherosclerotic process (e.g. pro-
affecting more frequently males than females.(5,6) The mean calcific state, chronic inflammation and hypoalbuminemia.(16)
age in the studied group correspond to literature information; it CKD is also an independent risk factor for CAD, being
is well known that the risk of developing CAD and LEAD associated with both development and severity of CAD.(15) In
increases with age, and includes age greater than 45 years in this study, CKD was significantly associated with significant
men and greater than 55 years in women.(5,6) CAD and multivessel CAD, but there was no association with
The increased incidence of smoking, hypertension and LEAD.
hypercholesterolemia among studied patients coincides with A large number of studies have shown that
literature data.(4,5) inflammation plays an important role in atherosclerosis
Smoking was found to be a particularly strong risk pathophysiology (4). High-sensitivity C-reactive protein is an
AMT, vol. 26, no. 1, 2021, p. 11
 CLINICAL ASPECTS
inflammation marker and is associated with an increased risk of protein, fibrinogen, homocysteine, lipoprotein(a), and
LEAD presence, progression and complication.(17) In our study standard cholesterol screening as predictors of peripheral
group, the C-reactive protein was determined and not the High- arterial disease. JAMA. 2001;285:2481–2485.
sensitivity C-reactive protein and no significant association with 12. Criqui MH, Aboyans V. Epidemiology of peripheral artery
LEAD was detected. disease. Circ Res. 2015;116:1509–152.
The main limitation of this study is the small numbers 13. Murabito JM, Evans JC, Nieto K, Larson MG, Levy D,
of patients enrolled. This is a possible explanation for discordant Wilson PW. Prevalence and clinical correlates of peripheral
study result with literature data. arterial disease in the Framingham Offspring Study. Am
Heart J. 2002;143:961–965.
CONCLUSIONS 14. Howard BV, Rodriguez BL, Bennett PH et al. Prevention
LEAD and CAD share the same cardiovascular risk Conference VI: Diabetes and Cardiovascular Disease:
factors. The strength of associations between each conventional Writing Group I: epidemiology. Circulation. 2002;
or non-conventional cardiovascular risk factor with LEAD and 105(18):e132-7
CAD was an important topic in large epidemiological studies. 15. Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney
Among risk factors evaluated in this study, smoking disease as a risk factor for development of cardiovascular
and hypertension had the higher prevalence followed by CKD disease: a statement from the American Heart Association
and hypercholesterolemia. Councils on Kidney in Cardiovascular Disease, High Blood
In our study group, only smoking was strongly Pressure Research, Clinical Cardiology, and Epidemiology
associated with LEAD. The other risks factors – diabetes and Prevention. Circulation. 2003;108(17):2154.
mellitus, hypertension, dyslipidaemia, CKD and C-reactive 16. Garimella PS, Hirsch AT, Peripheral Artery Disease and
protein – did not have statistically significant association with Chronic Kidney Disease: Clinical Synergy to Improve
LEAD, probably due to the small number of patients evaluated. Outcomes. Adv Chronic Kidney Dis. 2014 Nov;
In contrast, for CAD, diabetes mellitus, hypertension, 21(6):460–471. doi: 10.1053/j.ackd.2014.07.005.
dyslipidaemia and CKD were associated with the presence and 17. Chuang YW, Yu MC, Lin CL, Yu TM, Shu KH, Huang
severity of coronary lesions; instead smoking was not ST, Kao CH. Risk of peripheral arterial occlusive disease in
significantly associated with coronary stenosis ≥ 50% of lumen patients with rheumatoid arthritis. A nationwide
diameter. population-based cohort study. Thromb Haemost
2016;115:439–445.
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riskfor recurrent coronary events after myocardial
infaction. Ann Intern Med. Sep 17 2002;137(6):494-500.
11. Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for
systemic atherosclerosis: a comparison of C-reactive
AMT, vol. 26, no. 1, 2021, p. 12
 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):13-16
DOI: 10.2478/amtsb-2021-0004
Online ISSN 2285-7079

DISTAL TRANS-RADIAL APPROACH FOR CORONARY

ANGIOGRAPHY AND PERCUTANEOUS CORONARY
INTERVENTIONS - SINGLE-CENTRE EXPERIENCE

MAGED MOKBEL1, NICOLAE FLORESCU2, CRINA JULIETA SINESCU3

1,3
“Carol Davila” University of Medicine and Pharmacy Bucharest, 1“Sfântul Ioan” Clinical Emergency Hospital, București, 2Polisano Clinic, Sibiu,
3
“Bagdasar Arseni” Clinical Emergency Hospital, București

Keywords: snuff-box, Abstract: Right distal transracial approach in the anatomical snuff box could reduce the probability
transradial, of radial artery occlusion. Also, that approach allows a more comfortable hand position, especially in
coronarography obese patients. We prospectively evaluated right distal transracial approach (DTRA) in patients
treated trans-radially. Materials and methods: Prospective, observational, single centre study.
Various relevant objectives were assessed, for example radial artery occlusion in the evaluated
patients at discharge by ultrasonography, procedural success, time of scopy and time required for
haemostasis. 57 eligible patients were included in the study. The mean age was 63 years, 63% men,
and PCI was performed in 37% of patients. In all patients we used 6Fr radial sheaths, standard
catheters and TR-band with verification after one hour, then within 30-minute intervals. Results:
Procedural success was 89.5%, no patients had radial artery occlusion, two patients had a local
hematoma remitted later, the medium time required for hemostasis was 83.5 minutes, no patients
suffered ischaemia or any effect in right hand’s functions. Conclusion: Distal radial puncture seems
feasible, safe and can be considered routinely.

INTRODUCTION MATERIALS AND METHODS

Atherosclerotic coronary heart disease is the most
common cause of death in adults. Coronary atherosclerosis
causes stenosis or coronary occlusion, leading to myocardial
ischemia or necrosis. Coronary angiography and percutaneous
coronary intervention (PCI) are important tools for the diagnosis
and treatment of ischaemic heart disease. The pathways for
coronary angiography and PCI include the femoral artery, radial
artery, brachial artery, and ulnar artery.
With the improvement of technology and equipment,
transradial coronary intervention has become the preferred
approach for interventional cardiology procedures in the
world.(1)
The anatomical snuff-box is an empty space located
on the back of the hand and can be clearly seen after the thumb
is fully extended. The ulnar margin of anatomical snuff-box is
formed by the tendon of the extensor pollicis longus. The radial
boundary includes the tendons of the abductor pollicis longus
and extensor pollicis brevis. The basis is the scaphoid and
trapezius bones. The distal part of the radial artery passes
through the anatomical snuff-box.(2) In 2017, Kiemeneij
reported the trans-radial arterial approach in the anatomical
snuff box of his left arm and the result suggested that the
procedure was safe and feasible.(3) This new approach may
overcome some disadvantages of the conventional trans-radial
approach in several respects.
AIM
The purpose of this study is to evaluate the safety and
feasibility of trans-radial access in the anatomical snout of the
right forearm.
This is a prospective, single-centre observational
study. Ethical approval was obtained from the hospital
committee. Patients were selected from those scheduled for
coronary angiography or PCI at the Polisano Clinic in Sibiu,
Romania, between January and February 2018. Informed
consent was obtained both verbal and written for each patient.
Patient’s selection
Our study included 57 patients. The most important
inclusion criterion was the presence of a pulse in the anatomical
snuff-box. All patients underwent Barbeau’s test before the
procedure to assess the permeability of the distal vascular bed.
Exclusion criteria
1. Absence of pulse.
2. Known malformation of forearm’s arteries.
3. Severe hepatic / renal impairment or known coagulopathy
4. Cardiogenic shock.
5. History of coronary bypass with a radial arterial graft.
Technique (figure no. 1)
1. The patient is placed in supine position on the angiography
table.
2. The right arm is comfortably positioned next to a side
extension.
3. The operator who had extensive experience (over 100
radial procedures performed) stands on the patient’s right
side and reconfirms the puncture site.
4. After the subcutaneous injection of 1 ml lidocaine through
a 5 ml needle, the Seldinger’s technique was performed in
the anatomical snuff-box.
5. 21G needle, a metallic guide-wire and 6Fr radial sheath
were used in all patients.

Corresponding author: Sinescu Crina Julieta, Șos. Berceni, Nr. 12, Bucureşti, România, E-mail: crinasinescu@gmail.com, Phone: +40722 300301
3

Article received on 20.01.2021 and accepted for publication on 02.03.2021

AMT, vol. 26, no. 1, 2021, p. 13
 CLINICAL ASPECTS
6. Unfractioned heparin is administered intra-arterially after RESULTS
sheath insertion, dose of 50 u.i / kg, subsequently increased From January to February 2018, a total of 57 patients
to 80-100 u.i / kg in case of PCI. were included in this study. The mean age of the patients was
62.93 ± 9.71 years, 63% were men (table no. 1).
Figure no. 1. Technique of distal transradial access
Table no. 1. Mean age of patients
Age
N Valid 57
Missing 0
Mean 62.93
Std Dev 9.71
Minimum 45.00
Maximum 82.00
Hypertension, dyslipidemia, diabetes and smoking
were present in 68.4%, 56.1%, 35.1% and 29.8%, respectively.
A degree of renal impairment greater than or equal to 2 was
present in 24.6% of patients (figure no. 3).

Haemostasis Figure no. 3. Patient’s characteristics and relevant history

Gradual deflation technique was used as follows
(figure no. 2):
 TR-Band inflation with 20 ml of air at a time, then remove
the sheath.
 Slow deflation till the slightest sign of bleeding at the site
of access.
 2 ml of air are inflated and the total amount of air used is
noted.
 The same technique of slow deflation is repeated after an
hour, then at an interval of 30 minutes.
 TR-Band is removed as soon as there’s no sign of local
bleeding.
 Total haemostasis time is noted.
There were 6 failures, requiring the conventional
Figure no. 2. Removing distal trans-radial sheath approach of the right radial artery or right femoral artery. In 3
patients, the puncture failed due to severe distal vasospasm that
did not allow the introduction of 0.02” guide-wire even in the
presence of a good arterial flow through the needle, while in the
other 3 patients there were more than 3 attempts to cannulate the
artery without any success. The total number of successful cases
was 51, with a success rate of 89.5%, in all patients 6Fr
catheters were used, both diagnostic and guiding. Of the
successful cases, 37.2% had coronary angioplasty (n = 19), with
an average of 1.52 stents / patient (n = 29).

Figure no. 4. Post procedural local hematoma

Data collection
1. Initial characteristics of patients (age, sex, coronary risk
factors).
2. Number of trials.
3. Access time in seconds.
4. Total fluoroscopy time in seconds.
5. Haemostasis time in minutes.
6. Hospitalisation time in days.
7. Postoperative complications (major and minor bleeding, On average, the number of puncture attempts was 1.33
hematoma, vasospasm, arteriovenous fistula, radial artery ± 0.59 with a maximum number of 3 attempts used, otherwise it
occlusion (RAO), loss of arm functions). is considered a failed case. The mean overall artery access time
Statistical analysis (calculated after local anaesthesia) was 65.22 ± 36.37 seconds,
Statistical analysis was performed using the statistical ranging from 32 to 176 seconds.
software PSPP 1.0.1 MacOS. The measurement data were all The mean time of post-procedural haemostasis was
expressed as means ± standard deviation. 83.53 ± 25.68 minutes. The mean length of hospital stay was
AMT, vol. 26, no. 1, 2021, p. 14
 CLINICAL ASPECTS
1.98 ± 1.14 days. The mean X-ray exposure time was 252.12 ±
169.23 seconds. No patients complained of significant
discomfort during the procedure.
Two patients (3.9%) had local hematoma after the
procedure, probably due to multiple punctures. After the
dressing under pressure, the hematoma improved without
ultrasonographic signs of radial artery occlusion and the activity
of the hands was not affected (figure no. 4).
Three patients (5.9%) had intra-procedural vasospasm,
treated medically and with the help of more hydrophilic
catheterisation materials. No major bleeding, arteriovenous
fistulas, radial artery occlusion or other significant
complications were observed. No patient complained of hand or
arm dysfunction.
DISCUSSIONS
Radial artery and femoral artery are commonly used
as arterial approaches for coronary angiography and PCI. In
recent years, trans-radial access has become more rapidly
widespread. A large number of studies have confirmed that
trans-radial access can eliminate some of the shortcomings of
femoral access. Patients with trans-radial access feel more
comfortable, have less local pain and complications; radial
access reduces mortality and major adverse cardiac events in
patients with STEMI.(4) Anatomically, the radial artery is more
superficial than the femoral artery and can be easily compressed.
The end of the radial artery is anastomosed with the deep palmar
branch of the ulnar artery to form deep palmar arch with an
effective collateral circulation. The incidence of hand ischaemia,
necrosis or dysfunction after trans-radial artery puncture is
low.(5) However, the standard radial artery approach has its
disadvantages. The most common complication is radial artery
occlusion (RAO).(6)
After Kiemeneij (3) first reported left distal trans-
radial access in the anatomical snuff-box for interventional
therapy, several studies (7) found that interventional therapy
through this approach is feasible.
The new access has become a new hot spot. Left distal
radial artery access offers a new approach to coronary
intervention, especially in patients with right RAO or if the right
radial artery used for coronary bypass grafting. This new
approach can improve both patient’s and operator’s comfort,
allowing a more comfortable position during the procedure and,
apparently a shorter postoperative haemostasis time is required.
In addition, there may be a reduced risk of RAO.
Our study found that coronary intervention through
the distal right trans-radial approach seems safe and feasible, the
haemostasis time is short, using minimal resources.
No major complications were reported, and patients
tolerated it well. The main advantages of access to the distal
radial artery appear to be:
1. Less haemostasis time.
2. More patient’s comfort.
3. More operator’s comfort.
4. For patients requiring coronary artery bypass grafting,
distal access may reduce the likelihood of vascular injury,
especially to the radial artery’s trunk.
From an anatomical point of view, the radial artery in
the anatomical snout is located at the distal end of the radial
artery. Its diameter at the puncture site is obviously smaller,
access is more difficult and the learning curve is longer. In this
study, the success rate of distal radial artery access was up to
89%, the number of punctures was 1-3 times, minimising the
risk of peripheral nerve damage, arteriovenous fistula and
thrombosis. With the continuous accumulation of the puncture
experience, the number and timing of the punctures will be
improved.
AMT, vol. 26, no. 1, 2021, p. 15
Whether the approach is left or right, placing the arm
during the procedure is more comfortable than conventional
access to the radial artery. For obese patients and patients with
shoulder or elbow disorders, the placement requirements of the
arms during the procedure can be better achieved and patient
comfort can be improved. Although the sample size of this study
was small, it was consistent with other studies on patient
comfort.
The radial artery, the cephalic vein and the superficial
branch of the radial nerve pass through the anatomical snuff-
box.(8) Radial nerve injury is a common injury to the peripheral
nerve that can cause abnormal sensations in the back of the
hand. A close relationship was found between the radial nerve
and the radial artery.(9) Although there were no neurological
problems in this study, we still argue more studies to further
clarify the relationship between radial artery and nerve
distribution in anatomical snuff-box. In some previous studies,
in more than 85% of patients, the diameter of the radial artery
was larger than that of the 6Fr (2.52 mm) sheath.(10) Currently,
most cardiac centers choose 6F sheaths for PCI through the
radial artery, and most procedures can be performed with this
sheath size. In this study, we used only 6Fr sheaths in all
patients and managed to successfully complete all the
procedures. Because the size of the distal radial artery is smaller
(usually less than 2 mm), femoral artery access and standard
radial artery access are still recommended for interventions
requiring 7F sheath.
If patients need coronary artery bypass grafting
(CABG), the radial artery has a higher permeability rate than the
great saphenous vein, when used in addition to the internal
mammary artery graft. Studies have found that catheterised
radial arteries have a modified morphology and function and it
is not recommended anymore to be used for coronary artery
bypass grafting, however, even then it remains an important
option compared to venous grafts.
The distance between artery and puncture site can
reduce the likelihood of injury to the radial artery trunk, which
can bring some benefits, an assumption that requires further
studies as to be confirmed.
Limitations
This observational study represents a single centre's
experience, with a relatively small number of patients. Multiple
multi-centre studies are needed to compare distal access with
conventional one, in terms of procedural success, complications,
postoperative haemostasis time, amount of contrast agent, time
of X-ray exposure, etc.
CONCLUSION
Coronary angiography and percutaneous coronary
interventions appear to be safe and feasible through the distal
puncture of the right radial artery. In our experience, this
approach can routinely be considered by interventional
cardiologists.
Acknowledgement:
“I undersign, certificate that I don’t have any
financial or personal relationships that might bias the content of
this work”, Maged Mokbel
REFERENCES
1. Bertrand OF, Rao SV, Pancholy S, et al. Transradial
approach for coronary angiography and interventions:
results of the first international transradial practice survey.
JACC Cardiovasc Interv. 2010;3:1022–31.
2. Cerda A, del Sol M. Anatomical snuffbox and it clinical
significance. A Literature Review. Int J Morphol.
2015;33:1355–60.
3. Kiemeneij F. Left distal transradial access in the anatomical
 CLINICAL ASPECTS
snuffbox for coronary angiography (ldTRA) and
interventions (ldTRI). Euro Intervention. 2017;13:851–7.
4. Sinha SK, Mishra V, Afdaali N, et al. Coronary
angiography safety between transradial and transfemoral
access. Cardiol Res Pract. 2016;2016:4013843.
5. Mattea V, Salomon C, Menck N, et al. Low rate of access
site complications after transradial coronary
catheterization: a prospective ultrasound study. Int J
Cardiol Heart Vasc. 2017;14:46–52.
6. Avdikos G, Karatasakis A, Tsoumeleas A, et al. Radial
artery occlusion after transradial coronary catheterization.
Cardiovasc Diagn Ther. 2017;7:305–16.
7. Valsecchi O, Vassileva A, Cereda AF, et al. Early clinical
experience with right and left distal transradial access in
the anatomical snuffbox in 52 consecutive patients. J
Invasive Cardiol. 2018;30:218–23.
8. Hallett S, Ashurst JV. Anatomy, Upper Limb, Hand,
Anatomical Snuff Box. StatPearls. Treasure Island
(FL)2018.
9. Robson AJ, See MS, Ellis H. Applied anatomy of the
superficial branch of the radial nerve. Clin Anat.
2008;21:38–45.
10. Tanaka Y, Moriyama N, Ochiai T, et al. Transradial
coronary interventions for complex chronic total
occlusions. JACC Cardiovasc Interv. 2017;10:235–43.

AMT, vol. 26, no. 1, 2021, p. 16

 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):17-20
DOI: 10.2478/amtsb-2020-0005
Online ISSN 2285-7079

BIOMARKERS – A NEW PERSPECTIVE IN URINARY TRACT

INFECTION

IOANA MĂTĂCUŢĂ-BOGDAN1
1
“Lucian Blaga” University of Sibiu, Pediatric Clinical Hospital of Sibiu

Keywords: urinary tract Abstract: Urinary tract infection continues to be an important cause of morbidity and mortality for
infection, biomarker adults and children. The early and correct diagnosis is very important considering that upper urinary
tract infection can lead to renal scarring, secondary hypertension and, end-stage renal disease.
Recent years brought into attention a whole new perspective for the diagnosis, making the biomarkers
a very promising field.

INTRODUCTION Biomarkers used for the urinary tract infection can

Urinary tract infection – UTI- has a long history,
being first documented over 3500 years ago in Egypt and
continues to be one of the most frequent infections wide world.
The concept refers to any infection that affects any part of the
urinary tract. These infections have either bacterial, viral or,
fungal etiology but the generally accepted etiology is bacterial
when referring to UTI.
It is being estimated that 150 million people
experience at least one episode of urinary tract infection, with an
incidence four times higher for women compared to men. UTI is
responsible for 5% of all episodes of fever in infants.(1,2,3)
Fifty percent of the women will have at least a bacterial UTI
during their life span.(2) It is a common infection in childhood,
occurring in 1.1% of the girls and 1.4% of the boys in the first
year of life.(3) Two percent of the boys and four times more
girls have at least one episode of UTI by the age of 7.(4)
The early and correct diagnosis is very important
considering that upper urinary tract infection can lead to renal
scarring, secondary hypertension and end-stage renal disease.
60% of the febrile UTI will result in renal scarring.(5)
Urinary tract infection was a study subject for long,
but recent years brought into attention a whole new perspective,
the biomarkers’ perspective. This field is very promising
considering that the „gold standard” for the diagnosis of UTI is
urine culture which is a time-consuming investigation. „Urine
culture is an imperfect gold standard” having some
shortcomings.(6)
The utility of these biomarkers for the diagnosis at the
onset of the symptoms is obvious. Finding the right biomarker
or the right combination to make an early diagnosis is desirable
and would bring many advantages, such as unnecessary
antibiotic use or investigations and lower costs in terms of
patient health and resources.
Biomarkers in urinary tract infection
To be useful as a biomarker, a molecule has to be
organ-specific, secreted promptly by the injured cells, an
objective measure of this injury, measurable, reproducible, and
sensitive.(7)
have two major sources, urine and serum.
Urinary biomarkers
Urine sediment is considered a “good urinary
biomarker for early detection of kidney diseases, like acute
urinary tract infection”.(5) Besides its obvious advantages like
accessibility, availability and, low costs, the urine microscopy
can offer information about the site of renal injury,
inflammation or infection.(5)
Interleukins
IL-6 and IL -8 play an important part in the
inflammation of the urinary tract.(3) Studies show that urinary
Escherichia coli activates a cytokine response in the monocytes
and uroepithelial cells. After E. Coli stimulation the peak
concentration was 2 hours for IL-8 and 6 hours for IL-6.(7)
IL-6 is only found in small quantities in the urine of
healthy children, but the levels are higher in acute
pyelonephritis. The uroepithelial cells secrete cytokines that
chemoattract inflammatory cells to the infection site.(8)
IL-6 appears to be correlated with infections with P
fimbriae bacterial strains and IL-8 with pyuria.(3,7) IL-8 has
higher urinary levels in patients with bacteriuria and it is
associated with higher neutrophilia, suggesting its role in
attracting neutrophils in the infected urinary tract.(5) Children
less than 12 months of age have higher urinary IL-8 levels.(1,5)
IL-6 and IL-8 correlate positively in patients with UTI and also
correlate with fever, WBC, leucocyturia and CRP.(3,5) Urinary
level cannot differentiate pyelonephritis from low UTI in
children younger than 2 years of age.(8)
The urinary level was significantly higher in
pyelonephritis compared to cystitis or asymptomatic bacteriuria
and IL-6 became undetectable when the symptoms disappear
and after completion of the antibiotic treatment.(3,7,9) The
cytokine level is higher in febrile vs. non-febrile UTI.(3)
Neutrophil gelatinase-associated lipocalin – NGAL-
known as lipocalin 2, belongs to the lipocalin protein family
which gathers small proteins with very diverse functions and
structural roles. Considered initially as transport proteins, their
roles are expending: synthesis of prostaglandins and regulation

1
Corresponding author: Ioana Mătăcuță-Bogdan, Str. Pompeiu Onofreiu, Nr. 2-4, Sibiu, România, E-mail: ioanaoctavia_bogdan@yahoo.com, Phone:
+40269 217927
Article received on 07.10.2020 and accepted for publication on 26.02.2021
AMT, vol. 26, no. 1, 2020, p. 17
 CLINICAL ASPECTS
of the immune response.(10,11,12)
NGAL, a small positive acute-phase protein, with
levels changing during the acute-phase response. NGAL is
expressed in many tissues, human neutrophils, monocytes and,
macrophages and also in the kidney.(10,13) It is implicated in
immune defence against bacterial infection, (13) its levels are
upregulated when infection or inflammation is present. The
level in the serum can be useful for detecting bacterial infections
from viral infections.(5,10,11) It is also an iron-carrier
protein.(5)
NGAL is secreted by the injured epithelium of the
kidney, is considered one of the earliest and valuable markers of
acute kidney injury, one of the most promising immunological
biomarkers, a useful marker for the detection of UTI and “has
been postulated as a marker”.(4,6,12,13,14)
Urine NGAL has high levels in both upper and lower
UTI and has significantly lower levels in patients with recurrent
UTI. An increase of NGAL has been reported in the early stages
of UTI, especially if they are produced by Gram-negative
bacterias. This statement is true for both adults and children,
mentioning that for children a previous acute kidney injury or
chronic kidney disease has to be excluded.(1,5,11,12,13,14)
Beta-2 microglobulin was first discovered in 1964 in
the urine of Wilson disease patients or cadmium poisoning.(15)
It is a low molecular protein, encoded by a gene in chromosome
15 which can be found on the surface of all nucleated cells. This
protein is a component of the cellular immune response. During
the inflammatory response that activates lymphocytes, this
protein is released into the bloodstream and then passes through
glomerular filtration, reabsorption and, excretion. The urinary
level is higher if any injury occurs in the proximal
tubules.(13,15,16)
The immunological roles are complex and due to
interaction with classical and non-classical MHC-1 molecules:
mucosal immunity, maternofetal immune tolerance, or tumour
surveillance.(15)
In UTI, its levels increase three folds by the third day,
making it a valuable but not an early biomarker.(13) The
urinary levels are significantly higher in upper tract urinary
infection and have normal levels in cystitis, which can make it a
valuable biomarker for pyelonephritis. (15,16)
N-acetyl-beta-glucosaminidase –NAG - is a
lysosomal enzyme with a molecular weight of 140 kDa. Its
hydrolytic function is necessary for the degradation of various
parts of the cell. It is found in many tissues but high
concentration is present in proximal renal tubular cells. (5,17)
Besides acute kidney injury, high levels of NAG can be found in
other pathological states, such as UTI, glomerulonephritis,
nephrotic syndrome, nephrocalcinosis, urolithiasis,
vesicoureteral reflux.(5,18,19,20)
Urinary NAG in children has a circadian variation,
with highest levels at the age of 3 and the lowest between six
and eight years of age.(5)
In UTI, there is increased urinary excretion of NAG.
The levels are higher in pyelonephritis when compared to
cystitis, and can be a predictor for UTI for febrile patients.(5,21)
Urinary YKL-40 – cartilage glycoprotein-39 or
chitinase -3-like-1 belongs to the mammalian chitinase-like
protein family. It is expressed in a variety of cells including
primary immune cells. It is involved in inflammation,
remodeling of the extracellular matrix, angiogenesis, or fibrosis.
This biomarker is produced by the injured tissue and is a
measure of local inflammation.(22)
The urinary concentration is inversely proportional to
the urinary flow rate. The level is significantly higher for
patients with UTI than in the control group and in febrile UTI in
children. The levels are positively associated with other
AMT, vol. 26, no. 1, 2020, p. 18
biomarkers, such as white blood cells, CRP, nitrite, or the
pyuria, and negatively with the duration of fever. It appears that
the diagnostic value is higher than pyuria or nitrite.(22)
Significant higher values of YKL-40 were found in the UTI
group compared to febrile children with other infections.(23)
The specificity and sensitivity for the diagnosis of febrile UTI
are higher than of urinary NGAL. (23)
Serum biomarkers
Immunoglobulins – Ig M, Ig A, IgG are significantly
higher in patients with UTI than in healthy controls, especially
in the reccurent infections. (1)
Procalcitonin – is a peptide with 116 amino acids and
a precursor of the hormone calcitonin. It is an indicator of
bacterial infection and is considered as a reliable biomarker for
the diagnostic of bacterial infections. It expresses the
characteristics of a good biomarker, such as specificity, a long
half-life, short time of induction and can be detected in serum in
2 hours after the infection.(16)
Procalcitonin is a reliable biomarker that permits to
differentiate the pyelonephritis form a lower UTI, in
pyelonephritis the levels being significantly higher. This
conclusion refers to both adult and children.(7,9,16) It is also a
„sensitive indicator for early diagnosis of febrile UTIs in
children”.(16)
High procalcitonin was proven to be an independent
predictor for vesicoureteral reflux, especially in children with a
first febrile UTI and also an early predictor of kidney injury in
children with UTI. (7,16) It was demonstrated that a high
concentration of serum procalcitonin is related to kidney
scarring in UTI patients and it is considered an independent risk
factor for renal involvement in UTI.(16)
Cytokines
UTI stimulates the release of both local and systemic
cytokines and the response is very variable with the severity of
the infection.(7)
Interleukins as IL-5, Il-6, IL-8 were extensively
studied in relation to UTI and the results show that they are
promising and reliable biomarkers for early diagnosis.(24)
As recent studies show, IL-6 and IL-8 were related
with age, gender, symptoms, risk factors such as vesico-ureteral
reflux, and other biomarkers. They had higher levels in children
with febrile UTI compared to the asymptomatic children.(7,9)
Children with pyelonephritis have higher levels of IL-6
compared to those who have lower UTI or those in the control
group.(9,24)
The sensitivity and the specificity are good, but IL-6
appears to have better sensitivity and specificity than IL-8. (7)
IL-5 has higher levels at the onset of recurrent cystitis
and also predicts the development of chronic cystitis in
experimental models.(1,25)
Vitamin D
Vitamin D exerts its function on many levels in the
organisms, related to the distribution of vitamin D receptor
(VDR). The major role is in mineral and bone metabolism but
has important immunological functions due to the presence of
VDR on immune cells such as monocytes and
macrophages.(1,26,27,28)
The immunological roles of vitamin D can be
summarized:
- stimulation of macrophage maturation, antimicrobial
function and antibacterial peptide expression in both
macrophages and monocytes
- induction of autophagy as a macrophage response to
Mycobacterium tuberculosis infection
- neutrophilic phagocytic function and motility
- antiviral effects
- immunomodulator by preventing macrophages to release
 CLINICAL ASPECTS
cytokines too excessively
- suppress inflammation.(1,26,27,28)
Vitamin D deficiency is a risk factor for bacterial
infections: respiratory, digestive, and urinary tract infection.
Recent studies show that both adults and children with vitamin
D deficiency are more prone to infections.(26,27)
In urinary tract infection, in particular, vitamin D
induces expression of cathelicidin and β-defensin with
bactericide efect on intracellular bacteria. (24,26) Cathelicidin is
strongly stimulated by vitamin D. Cathelicidin produced by
epithelial cells in the urinary tract exerts a protective role against
bacterial adherence. Studies show that low levels of vitamin D
are related to low levels of cathelicidin and associated with UTI,
while patients with sufficient levels of vitamin D have higher
levels of cathelicidin.(27,29)
Urinary tract infection is dependent of vitamin D
status.(27,29) Vitamin D and UTI is a subject of recent studies
that conclude as follows: vitamin D is a risk factor for infections
in general and UTI, in particular, children with pyelonephritis
have lower levels of vitamin D in serum.(28)
Vitamin D deficiency in children is independently
associated with UTI (29) associated with recurrent UTI (1) and
for patients with kidney transplant vitamin D deficiency is an
independent risk factor for UTI.(26)
CONCLUSIONS
Urinary biomarkers are very diverse and promising. It
is a challenge to find the perfect combination with good
specificity and sensitivity to achieve prompt and accurate
diagnosis.
Acknowledgements
A part of this preliminary paper review has been
conducted by dr. Bogdan Neamtu in the Pediatric Clinic
Hospital Sibiu, within Research and Telemedicine Center in
Neurological Diseases in Children - CEFORATEN project
(ID928 SMIS-CSNR 13605) financed by ANCSI with the grant
number 432 / 21. 12. 2012 thru the Sectoral Operational
Programme „Increase of Economic Competitiveness.”
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AMT, vol. 26, no. 1, 2020, p. 20

 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):21-24
DOI: 10.2478/amtsb-2021-0006
Online ISSN 2285-7079

LOWER EXTREMITY ARTERY DISEASE AS A PREDICTOR OF

CORONARY ARTERY DISEASE

CORNEL IOAN BITEA1, IOAN MANIȚIU2, GEORGIANA BĂLȚAT3

1,3
Emergency County Clinical Hospital, Sibiu, 1, 2,3“Lucian Blaga” University of Sibiu,
1,3
Invasive and non-invasive research centre in the field of cardiac and vascular pathology in adults - CVASIC, Sibiu

Keywords: lower Abstract: Coronary artery disease (CAD) is an important determinant of long-term outcome in
extremity artery disease, patients with lower extremity artery disease (LEAD). In this study we evaluated the CAD prevalence
coronary artery disease, among LEAD patients and the association of LEAD lesions location with the CAD presence and
predictor severity. 203 patients with LEAD, referred for peripheral and simultaneous coronary angiography,
were evaluated. LEAD and CAD were considered angiographically significant for stenosis higher
than 50% of arterial lumen. More than two-thirds of LEAD patients had significant CAD, half of them
having multi-vessel CAD and a quarter single CAD. Infrapoplitheal arterial lesions seemed to be the
strongest predictor of CAD being associated with significant and multi-vessel CAD and also with the
presence of left main (LM) lesions. Femoral artery lesions were highly associated with multi-vessel
CAD, but there was no association with significant CAD and LM lesions. No association was found
between iliac artery lesions and CAD.

INTRODUCTION
Atherosclerosis is the main cause of lower extremity
artery disease (LEAD) and coronary artery disease (CAD).
Previous studies have shown that peripheral artery disease,
which includes LEAD, is a CAD risk equivalent.(1,2)
High prevalence of CAD in peripheral artery disease
patients was noted, ranging from 46 to 71%.(3,4,5) LEAD is
highly associated with CAD, one-third of patients having a
history and/or electrocardiographic signs of CAD, two-thirds
presents changes in stress tests and up to 70% have at least
single-CAD.(6,7,8) Studies have shown that patients with stable
atherosclerotic disease, but without previous ischemic events,
have more cardiovascular events in context of multi-arterial
disease.(9) Moreover, mortality and long term prognosis in
LEAD patients is directly correlated with CAD
coexistence.(5,10,11,12) Not only the presence, but also the
LEAD severity is correlated with CAD association: a high
percentage of patients (up to 90%) that present in medical units
with chronic limb-threatening ischemia also have CAD.(6)
The predictive value of LEAD lesion location for
CAD was evaluated in several studies. Sung Woo et al
demonstrated that the prevalence of proximal disease, defined as
aortic-iliac and femoral-popliteal arteries stenosis, was higher in
the normal or single CAD group, whereas that of involvement of
both levels (proximal and distal, the last one being defined as
below knee arteries) was higher in the multivessel CAD
group.(5)
Multisystemic involvement of vascular disease is
demonstrated in day by day practice. Association of CAD with
peripheral artery disease, including LEAD, is clinically
important, being well known that outcome of LEAD patients is
influenced by the presence and severity of CAD. In this context,
Current European guideline for peripheral artery disease (2017)
recommends CAD screening in LEAD patients for risk
stratification.(6)
AIM
The aim of this study was to see if there is any
association between significant LEAD and CAD, if higher than
50% arterial stenosis in different segments of lower extremity
arterial bed correlates with significant vs non-significant CAD,
with single- vs multivessel-CAD and with left main lesions.
MATERIALS AND METHODS
We retrospectively reviewed 203 patients with
symptomatic LEAD (intermittent claudication or critical limb
ischemia) which underwent simultaneously digital subtraction
angiography for LEAD evaluation and coronary angiography for
CAD evaluation in Sibiu Emergency County Clinical Hospital,
CVASIC research centre. There were excluded patients with
embolic or non-atherosclerotic lower extremity artery lesions,
being included only patients with chronic atherosclerotic
lesions.
Significant LEAD and CAD were defined as at least
one lesion with ≥ 50% lumen diameter stenosis. Lower
extremity arteries were divided into three segments: iliac
(common iliac artery, external iliac artery, internal iliac artery),
femoral (common and superficial femoral artery and popliteal
artery) and infrapopliteal (tibioperonier trunk, anterior tibial
artery, posterior tibial artery, fibular artery). CAD was classified
as significant-CAD (any coronary artery stenosis ≥ 50% lumen
diameter in left main (LM) artery or left anterior descending
(LAD) artery or circumflex artery (CxA) or right coronary artery
(RCA)) or non-significant-CAD (without coronary artery
stenosis ≥ 50% lumen) and as single-CAD (only one of LAD or
CxA or RCA with lesion above 50%) or multivessel-CAD (LM
stenosis ≥ 50%, or any of two arteries from LAD, CxA, RCA
with arterial stenosis ≥ 50%).

1
Corresponding author: Cornel Ioan Bitea, B-dul. Corneliu Coposu, Nr. 2-4, Sibiu, România, E-mail: cornelioanbitea@yahoo.com, Phone: +40766
210522
Article received on 18.02.2021 and accepted for publication on 02.03.2021
AMT, vol. 26, no. 1, 2021, p. 21
 CLINICAL ASPECTS
Cardiovascular risk factors – hypertension, Leriche-Fontaine I : Asymptomatic 0 (0%)
classification IIa: intermittent claudication at 17 (8.4%)
dyslipidaemia and diabetes mellitus – were defined according to more than 200 m walk
current guidelines. The patients were considered positive for IIb: intermittent claudication
smoking if they were active smokers or former smokers - but not in less than 200 m walk 118 (58.1%)
more than 1 year abstinence. Normal values for C reactive- III: limb rest pain
IV: ischemic lesions –
protein in our laboratory were 0-5 mg/dl. Chronic kidney necrosis, gangrene 40 (19.7%)
disease was classified form grade I to V according to KDOQI 28 (13.8%)
classification, and creatinine clearance was calculated with Claudication index, m 144±24 Min: 0 Max: 1000
Cockcroft-Gault formula. Ankle-Brachial index 0.62±0.24 Min: 0 Max: 1
Statistical analysis was performed using IBM SPSS
Table no. 2. Patients’ biological characteristics
Statistic software. Categorical variables are expressed as the Parameter (N=203) Mean±SD Minimum Maximum
number (percentages) and continuous variables were first
Total cholesterol, mg/dl 207.60±55.86 107 357
analysed for data normality. The Shapiro-Willk test was used to
LDL-cholesterol, mg/dl 117.57±43.76 31 290
analyse data normality. Normally distributed continuous
variables were expressed as the mean±SD, and non-normally HDL – cholesterol, mg/dl 44.91±10.93 27 86
distributed continuous variables were expressed as the median Triglycerides, mg/dl 185.78±148.4 44 1356
value. Pearson Chi-Square tests was used to evaluate LEAD Creatinine, mg/dl 1.02±0.59 0.55 6.88
association with CAD. As a measure of association, we used the Clearance Creatinine, 85.75±25.59 8.32 166.99
gamma- γ coefficient (Kendall’s tau-c). Statistical significance ml/min/1.73m2
was considered at a P value <0.05 (two-tailed). C reactive-protein, mg/dl 8.07±12.79 0.57 127.62
Coronary angiography characteristics of patients
RESULTS In our study group 175 (86.2%) patients had right
Patient’s characteristics coronary dominance. The prevalence of CAD in LEAD patients
Of the 203 patients with symptomatic LEAD, 166 was 75.4 % (153/203). Among these patients, 49.8% (101/203)
(81.8%) were male, 37 (18.2%) were female; the mean age was had multivessel-CAD and 25.6% (52/203) had had single-CAD.
65.31±8.616 (range 39-85years). Hypertension had the higher LM lesions were found in 34% (69/203) of patients, including
prevalence in our study group (79.8%) followed by smoking 32% (65/203) of patients with <50% stenosis, 0.5% (1/203) of
(76.84%), CKD (581%), hypercholesterolemia (54.7%), patients with 50-75% stenosis and 1.5% (3/203) of patients with
hypertriglyceridemia (48.3%) and diabetes mellitus (34.5%). >75% stenosis. 57.6% (117/203) patients had significant LAD
The majority of patients were with stage II Leriche-Fontaine stenosis, 39.5% (80/203) patients had significant CxA stenosis
LEAD - 135 (64.5%) patients in stage II Leriche-Fontaine, 40 and 44.82% (91/203) patients had significant RCA stenosis
(19.7%) in stage III Leriche-Fontaine, 28 (13.8%) in stage IV (table no. 3).
Leriche Fontaine - with a mean claudication index of 144±24 m
and a mean ankle-brachial index of 0.62±0.24. Table no. 3. Coronary angiography characteristics of
Patient’s demographic, clinical and biological patients
characteristics are summarised in table no. 1 and table no. 2. Characteristic Frequency Percent
N = 203 patients (%)
Dominance Right 175 86.2
Table no. 1. Patients’ demographic and clinical Left 22 10.8
characteristics Co-dominance 6 3
Variable (N=203) Value Significant/non- Non-significant CAD 50 24.6
Age, years 65.31±8.6 Min: 39 Max: 85 significant CAD Significant CAD 153 75.4
BMI, kg/m2 27.44±4.48 Min: 17.72 Max: 43.21 Non- Non-significant CAD 50 24.6
Underweight 2 (1%) significant/single/mul Single-CAD 52 25.6
Normal weight 67 (33%) tivessel- CAD Multivessel-CAD 101 49.8
Overweight 82 (40.4%) Lesion severity 0-50% 50-75% 75-100%
Grade I obesity 40 (19.7%) LM 199 (98%) 1 (0.5%) 3 (1.5%)
Grade II obesity 10 (4.9%) LM - no (no stenosis): 134 (66%)
Grade III obesity 2 (1%) LM - yes (stenosis of any severity): 69 (34%)
Gender Male 166(81.8%) LAD 86 77 40
Female 37 (18.2%) (42.4%) (37.9%) (19.7%)
Smoking Yes 156 (76.84%) CxA 123 33 47
No 47 (23.16%) (60.6%) (16.3%) (23.2%)
Diabetes mellitus (DM) Yes 70 (34.5%) RCA 112 21 (10.34%) 70
No 133 (65.5%) (55,17%) (34.48%)
Hypertension Yes 162 (79.8%) Association of LEAD with non-significant/single -
Grade I 0 (0%)
Grade II 76 (37.4%) /multivessel-CAD
Grade III 85 (41.9%) In our study group, significant lesions >50% in iliac
No 41 (20.2%) segment were not associated with multivessel-CAD (p 0.271)
(table no. 5).
Hypercholesterolemia Yes 111 (54.7%) Instead, in patients with significant arterial stenosis
No 92 (45.3%)
Hypertriglyceridemia Yes 98 (48.3%)
(>50%) in femoral segment, the percentage of multivessel-CAD
No 105 (51.7%) was higher than the percentage of single-CAD and non-
CKD Yes (Creatinine clearance 118 (58.1%) significant CAD, respectively (94% versus 78.8% versus 86%,
<90ml/min/1.73m2) respectively). The difference was statistically significant
Grade II 85 (41.9%)
Grade IIIa 28 (13.8%) (χ²=11.8, df 4 p=0.019) (table no. 5). As a measure of
IIIb 3 (1.5%) association, it was used the gamma- γ coefficient, indicating a
Grade IV 2 (0%) proportion of 30.2% of the association of multivessel-CAD with
Grade V 3 (1%)
significant femoral lesions, but without statistical significance (p
No (Creatinine Clearence > 90 85 (41.9%) 0.157).
ml/min/1.73m2) Similar result was found for infrapopliteal segment: in
AMT, vol. 26, no. 1, 2021, p. 22
 CLINICAL ASPECTS
patients with significant arterial stenosis (>50%) in (>50%) is associated with LM lesion in proportion of 84.1%
infrapopliteal segment, the percentage of multivessel-CAD was versus 15.9% in the case of nonsignificant lesions (χ²=6.2, df=2,
higher than the percentage of single-CAD and non-significant p=0.043), the chance that the association is verified being 4.7
CAD, respectively (90.1% versus 88.5% versus 72%, times higher (p 0.05).
respectively). The difference was statistically significant
(χ²=9.9, df=4 p=0.041) (table no. 5). As a measure of DISCUSSIONS
association, it was used the gamma- γ coefficient, indicating a LEAD and CAD affect more frequently males than
proportion of 27.8% of the association of multivessel-CAD with females. Age greater than 45 years for men and greater than 55
significant infrapopliteal lesions, but without statistical for women is associated with risk of CAD and LEAD
significance (p 0.59). developing.(14,15) In our study group, male gender
predominance was observed and the mean age correspond to
Table no. 5. Association of LEAD with non-significant/single literature information.
-/multivessel-CAD The increased incidence of smoking, hypertension and
Iliac segment – lesion severity (%) Chi-Square test
CAD hypercholesterolemia among studied patients coincides with
0-50 50-75 75-100 χ² p
Non- 26 4 20 (40%) literature data.(4,5)
significant (52%) (8%) Multisite artery disease is common for patients with
CAD atherosclerotic lesions ranging from 60 to 70% in patients with
Single-CAD 22 11 19 5.165 0.271 severe LEAD (6) - with CAD ranging from 46-71%.(3,4,5)
(42.3%) (21.2%) (36.5%)
Multivessel- 44 23 34 Significant CAD was found in more than two-thirds of patients
CAD (43.6%) (22.8%) (33.7%) evaluated in this study, half of patients having multivessel-CAD
Femoral segment – lesion severity Chi-Square test and one quarter having single-CAD. The interest for CAD
CAD (%) association with LEAD is explained by the fact that the main
0-50 50-75 75-100 χ² p
Non- 7 1 42 cause of late death in patients with peripheral artery disease is
significant (14%) (2%) (84%) ischemic heart disease (up to 50% of deaths in patients with
CAD peripheral artery disease).(16) CONFIRM registry showed that
Single-CAD 11 1 40 11.803 0.019 in LEAD patients, obstructive CAD was associated with annual
(21.2%) (1.9%) (76.9%)
Multivessel- 6 9 86 mortality rate of 1.6% versus 0.7% in the absence of severe
CAD (5.9%) (8.9%) (85.1%) CAD.(6,17)
Infrapopliteal segment – lesion Chi-Square test Proximal lesions defined as iliac, femoral, popliteal
CAD severity (%) artery stenosis are more likely associated with normal or single
0-50 50-75 75-100 χ² p
Non- 14 1 35 CAD. Involvement of lower extremities proximal and distal
significant (28%) (2%) (70%) arteries has a high chance of association with multi-vessel
CAD CAD.(5) Our study results were concordant with data mentioned
Single-CAD 6 3 43 9.950 0.041 above: infrapopliteal lesions were associated with both the
(11.5%) (5.8%) (82.7%)
Multivessel- 10 (9.9%) 6 85 presence and severity of CAD (defined as multi-vessel CAD and
CAD (5.9%) (84.2%) LM lesions), femoral lesions were associated with multi-vessel
Association of LEAD with significant/non-significant CAD, while iliac lesions were not significantly associated with
CAD the presence of CAD.
The association of significant arterial lesions >50% in Prognosis of peripheral artery disease patients is
iliac and femoral segments with significant CAD (>50%) was different according to lesion location.(5) Chan, et al
not statistically significant with a p value of 0.134 for iliac demonstrated that the presence of lower extremity distal arterial
segment and 0.394 for femoral segment. disease is associated with a poorer prognosis compared with
On the other hand, in the present study, 133 (89.2%) patients without distal disease. In contrast for patients with
patients with significant infrapopliteal lesions (>50%) had proximal disease there were no prognosis differences.(13)
significant-CAD (>50%), compared with 16 (10.7%) cases with Multilevel LEAD disease determined a poorer prognosis in
infrapopliteal lesions below 50% that had significant-CAD. The LEAD patients.(18) This prognosis differences may be
association was statistically significant (χ²=8.1, df=2, p=0.017). explained by the higher association of distal and multilevel
Association of LEAD with LM lesions LEAD with multivessel-CAD, compared with proximal LEAD.
The association of significant arterial lesions >50% in
iliac and femoral segments with the presence of LM lesion was CONCLUSIONS
not statistically significant with a p value of 0.278 for iliac Significant CAD has a high prevalence among
segment and 0.091 for femoral segment. symptomatic LEAD patients.
Significant infrapopliteal lesions (>50%) were Significant lesions in different segments of lower
significantly associated with LM lesions (p 0.043), as shown in extremity arterial bed are differently associated with significant
table no. 7. CAD.
Infrapopliteal significant lesions seems to be the
Table no. 7. Association of significant infrapoplileal lesions strongest predictor of CAD, being associated with significant
(>50%) with LM lesions CAD, multivessel-CAD and with the presence of LM lesions of
Infrapopliteal segment – lesion Chi-Square test any severity. Thus, infrapopliteal significant lesions correlates
LM lesion severity (%) with the presence of significant CAD and also with CAD
0-50 50-75 75-100 χ² p severity quantified by the number of vessels affected
No (no 19 2 112
stenosis) (14.3%) (1.5%) (84.2%) (multivessel-CAD) and by LM involvement.
Yes 11 8 (11.6%) 50 Significant lesions in femoral segments were highly
6.294 0.043
(stenosis of (15.9%) (72.5%) associated with multivessel CAD, but there was no association
any with significant CAD and with LM lesions.
severity)
Finally, there was no significant association between
The presence of significant infrapopliteal lesions
iliac segment lesions and significant, multivessel-CAD and LM
AMT, vol. 26, no. 1, 2021, p. 23
 CLINICAL ASPECTS
lesions. artery disease in 2000 and 2010: a systemic review and
The study results suggest that CAD evaluation should analysis. Lancet. 2013;382:1329-1340.
be performed in symptomatic LEAD patients, with increased 16. Norgren L, Hiatt W, Dormandy J, Nehler M, Harris K,
attention for patients with significant lesions in femoral and Fowkes F.Inter-Society Consensus for the Management of
infrapopliteal segments. In addition, reduced daily activity in Peripheral Arterial Disease (TASC II). Eur J Vasc
symptomatic LEAD patients can reduce angina symptoms in Endovasc Surg. 2007;33:S1-S75.
CAD patients; therefore, screening for “asymptomatic” CAD 17. Cho I, Chang H, Sung JM, et al. CONFIRM Investigators.
might be an option for LEAD patients. Coronary computed tomographic angiography and risk of
all cause mortality and nonfatal myocardial infarction in
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Perioperativeand long-term mortality rates after major
vascular surgery: the relationship to preoperative testing in
the medicare population. Anesth Analg. 1999;89:849-55.
12. Welten GM, Schouten O, Hoeks SE, et al. Long-term
prognosis of patients with peripheral arterial disease: a
comparison in patients with coronary artery disease. J Am
Coll Cardiol. 2008;51:1588-96.
13. Chen Q, Smith CY, Bailey KR, Wennberg PW, Kullo IJ.
Disease location is associated with survival in patients with
peripheral arterial disease. J Am Heart Assoc.
2013;2:e000304.
14. Boudi FB, Yasmine S. Risk Factors for Coronary Artery
Disease: https://emedicine.medscape.com/article/164163-
overview#a3 Mar 30; 2020.
15. Fowker FG, RudanD, Rudan I, et al. Comparison of global
estimates of prevalence and risk factors for peripheral
AMT, vol. 26, no. 1, 2021, p. 24
 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):25-27
DOI: 10.2478/amtsb-2021-0007
Online ISSN 2285-7079

DRIL PROCEDURE: TREATMENT FOR VASCULAR ACCESS

INDUCED HAND ISCHEMIA. CASE REPORT

CLAUDIU HELGIU1
1
“Lucian Blaga” University of Sibiu

Keywords: vascular Abstract: Native vascular access (AVF arteriovenous fistula) for chronic hemodialysis (CH)
access, arteriovenous performed proximally to the diabetic patient, between the brachial artery and the basilic vein or
fistula, hemodialysis, cephalic vein, determines the risk of distal (hand) ischemia. The correction of the ischemia can be
hand, ischemia done differently depending on its severity, starting from the vasodilator medication, reaching the
cancellation of the vascular access with the accomplishment of the chronic hemodialysis on the
central venous catheter. DRIL procedure (Distal Revascularization and Interval Ligation) corrects
distal ischemia while maintaining functional vascular access, an important aspect in diabetic patients
in whom vascular capital is deficient. We further describe a case of a diabetic patient with right L-T
brachiocephalic arteriovenous fistula, with important ischemic phenomena in which the DRIL
procedure resolved the ischemia, the patient using vascular access as usual, the second postoperative
day.

INTRODUCTION Triplex examination, to which is added the examination of the

Native vascular access for chronic hemodialysis is the
best way to achieve chronic hemodialysis, with a much lower
rate of complications (sepsis, thrombosis) than using a central
venous catheter or synthetic graft.(1) Ideally, vascular access is
performed distally (at the level of the forearm vessels) to the
non-dominant limb. The diabetic patient candidate for chronic
hemodialysis has a very poor distal vascularity (calcified
arteries, phlebitic veins), so that vascular access will have to be
achieved proximally (at the level of the arm).(2) The brachial
artery is anastomosed with the cephalic vein or the basilic vein
at the level of the arm (3), this type of vascular access having an
important risk of developing distal ischemia of the hand through
vascular steal at the level of arteriovenous anastomosis in
systole and diastole.
Depending on the severity of the ischemic symptoms,
vascular access induced hand ischemia (VAIHI) is classified
in:(4)
 Grade 0 - no symptoms, no treatment.
 Grade 1 - cold skin on the extremity with AVF with mild
symptoms that do not require treatment.
 Grade 2 - intermittent ischemic phenomena that occur
during hemodialysis, intermittent claudication that requires
treatment depending on severity.
 Grade 3 - ischemic rest pain, necrotic lesions, requiring
rapid intervention.
DRIL procedure consists of distal revascularization of
the hand through an anastomosed venous graft, proximally to at
least 10 cm cranially to the initial arteriovenous anastomosis,
and distally to the brachial artery under the primary anastomosis
or to the radial or ulnar artery if they do not present extensive
calcifications.
The ligation of the brachial artery is accomplished
between the primary and distal anastomosis (interval
ligation).(5) Preoperatively, the examination of the vascular
network at the level of the upper limb is done by Duplex,
bilateral internal saphenous vein from the level of the arch vein
to the distal 1/3 of the calf. Pulseoximetry is done on both hands
symmetrically.
The case we present consist of using DRIL procedure
like a solution for correcting ischemic phenomena while
maintaining functional vascular access and its usual use for
chronic hemodialysis.
CASE REPORT
Patient aged 60 years old, male, with chronic
hemodialysis on right proximal vascular access (right L-T
brachiocephalic arteriovenous fistula). His past medical history
consists of: diabetes with diabetic retinopathy, hypertension,
obesity.
The patient has been performing chronic hemodialysis
on the right brachio-cephalic fistula for 2 years. For about 3
months he has been progressively showing ischemic phenomena
in the right hand with cold skin and paresthesias in the fingers II
- V with pains during hemodialysis (grade 2 of VAIHI). The
pulse is not perceptible in the radial and ulnar arteries, but
becomes perceptible after compression of the arteriovenous
anastomosis.
Sa O2 at the right hand is 70 - 75% in the fingers II -
V and after compression of the arteriovenous anastomosis Sa O2
> is higher than 90%.
The ultrasound examination at the level of the right
arm highlighted:
Afferent branchial artery with a diameter of 6 mm
with compressible calcified walls, efferent artery with a
diameter of 4 mm with the same appearance. The ulnar artery in
the lower 1/3 of the forearm with a diameter of 4 mm, with
relatively soft, compressible walls. Radial artery at the same
level with a diameter of 2 mm, with calcified walls that cannot
be compressed. Brachial artery 10 cm cranial to AVF have a 6
mm diameter compressible.

1
Corresponding author: Claudiu Helgiu, Str. Lupeni, Nr. 21, Sibiu, România, E-mail: claudiuhelgiu@yahoo.com, Phone: +40745 317854
Article received on 24.01.2020 and accepted for publication on 02.03.2020
AMT, vol. 26, no. 1, 2021, p. 25
 CLINICAL ASPECTS
Right internal saphenous vein with a diameter of 4 - 6
mm, supple in the thigh, with a rectilinear trajectory, without
varicose dilatations, without ostial reflux. The ultrasound was
performed from the groin to the level of the calf. It is completed
with the examination of the arterial circulation at the level of the
lower limb in order to diagnose a severe arteriopathic process
that may contraindicate the harvest of the saphenous vein (long
incision).
In the evening before the surgery, the patient is
disinfected with betadine in the right upper and lower limb and
then he is sterile covered on these surfaces.
The surgery was performed under general anesthesia
on the day without hemodialysis and lasted about 3 hours (figure
no. 1).
Figure no. 1. Dril procedure
(A) preoperative aspect, 1 brachial artery, 2 arteriovenous anastomosis, 3 cephalic vein, 4 cubital
artery, 5 radial artery (B) DRIL, 1 first arteriovenous fistula, 2 second arteriovenous fistula, 3
third arteriovenous fistula, 4 venous graft, 5 brachial ligatures
The surgical field comprises the entire right upper
limb, in the abduction position at 90 degrees and the right lower
limb along its entire length.
Initially, the right L - T brachiocephalic primary
anastomosis was detected (primary anastomosis) and the
afferent and efferent brachial artery was put on elastic ribbon.
Then, the brachial artery is dissected at 10 cm cranial to the
primary anastomosis. After confirming that the proximal
brachial artery is suitable, right internal saphenous vein was
harvested on a length of 25-26 cm through a continuous incision
in the right thigh, after which the incision is closed by a second
surgical team.
The saphenous vein is washed with heparinized serum
(12.500 UI Unfractionated heparin per 500 ml physiological
saline), dilated and inverted. Cranial anastomosis is performed
between the brachial artery and the inverted saphenous graft
(secondary anastomosis) in a latero-terminal manner on a
diameter of 6 mm with Premilene suture 7 - 0. The tunneling of
the vein on the inner face of the arm is performed, so that the
graft does not intersect the basilic vein (for a future fistula
between the brachial artery and the basilic vein). The distal
anastomosis (tertiary anastomosis) is performed at 3 cm distally
from the primary anastomosis, between the venous graft
(terminal) and the brachial artery (lateral) on a diameter of 6 mm
with Premilene suture 7 - 0.
After filling the venous graft with heparined serum,
we performed the purge, completed the distal anastomosis (third
anastomosi ) and the vein graft was under pressure.
After brachial artery is ligated between the primary
and the tertiary anastomosis with Silk no. 3, intraoperative Sa
AMT, vol. 26, no. 1, 2021, p. 26
O2 after the assembly is finished is over 90% and fistula was
functional with thrill. In the evening of the surgery, the patient
has Sa O2 over 94%, without ischemic complaints (figure no 2).
The patient performs the first hemodialysis session 24
hours postoperatively, without ischemic phenomena. He is
discharged 72 hours postoperatively. At 6 months
postoperatively the assembly was permeable, vascular access
was used for chronic hemodialysis and the patient had no
ischemic symptoms.
Figure no. 2. Postoperative appearance
DISCUSSIONS
Achieving vascular access for proximal chronic
hemodialysis through anastomosis between the brachial artery
and the cephalic or basilic vein leads to steal phenomenon
where, in the systole, part of the blood flow to the hand is
diverted in the area with minimal resistance (anastomosed
veins).(6) During diastole, blood from the distal territory
(forearm, hand) is aspirated at the level of arteriovenous
anastomosis, in this way the steal phenomenon was present in
both systole and diastole, leading to insufficient arterial flow in
the hand and ischemia or necrosis. Ischemic pain is continuous
when resting and was accentuated during the hemodialysis
session, requiring cessation of hemodialysis.(7)
The surgery indication is given by the presence of rest
pain, gangrene of the fingers and the hand. The arteriovenous
fistula is usually closed by ligating the vein immediately in the
postanastomotic segment. The surgery can be performed under
local anesthesia and it restores the distal flow. The disadvantage
is that the native vascular access is compromised, and the patient
will need to perform HD on CVC, with the decrease of the
patient's lifetime. Banding of the vein can be useful, maintaining
the vascular access.(8)
After clinical and ultrasound vascular evaluation of
arterial and venous capital at the right upper limb and of the
saphenous vein we decided to perform a DRIL procedure. Why?
Because we can correct the hand ischemia and preserve the
vascular access in the same time. The patient despite his
diabetes did not have a severe arteriopathy of inferior limb, so
we considered that the long tigh incision will heal.
The DRIL procedure was performed for first time in
1988 and reported by Schanzer et al. and it has the advantage of
allowing the correction of ischemic manifestations and the
functional preservation of vascular access at the same
time.(9,10)
CONCLUSIONS
The use of the DRIL procedure to correct distal and
secondary arterial flow of ischemic phenomena in the hand in
diabetic patients with HD on proximal AVF is a noteworthy
solution that improves the arterial flow in the hand and
preserves native vascular access for chronic hemodialysis.
However, the cases must be carefully selected in terms of
arterial pathology in the upper limb (extensive diffuse
mediocalcosis that does not allow clamping of the arteries) and
 CLINICAL ASPECTS
in the lower limb (severe arteriopathy with distal lesions). The
duration of the surgery can be shortened if there are two surgical
teams simultaneously.

REFERENCES
1. Ballard JL, Blunt TJ, Malone JM. Major complications of
angioaccess Surgery. Am J Surg. 1992;164:229-232.
2. Sidawy AN, Spergel LM, Besarab A, et al. The Society for
Vascular Surgery: Clinical practice guidelines for the
surgical placement and maintenance on arteriovenous fistula
hemodialysis access. J Vasc Surg. 2008;48(suppl 5):25-255.
3. Nazzal MM. The brachiocephalic fistula: a succesfull
secondary vascular access procedure. Vasa. 1990;19:326-
329.
4. Al Hassanein and Samuel E Wilson. Dialysis Access -
Associated Ischemic Steal Syndrome. Samuel Eric Wilson
Vascular Access Principles and Practice fifth edition.
Wolters Kluwer and Lippincott Wiliams and Wilkins
Phyladelphia; 2010. p. 178-181.
5. Schanzer H. Overview of complications and management
after vascular access creation. In: Gray RJ, ed. Dialysis
Access. Philadelphia: Lippincot Williams and Wilkins;
2002. p. 93-97.
6. Holman E, Taylor G. Problems in the Dynamics of blood
flow. II. Pressure relations at the site of an arteriovenous
fistula. Angiology. 1952;3:415-430.
7. Ingebrigtsen R, Wehn PS. Local blood pressure and
direction of flow in experimental arteriovenous fistulae.
Acta Chir Scan. 1960;120:142-150.
8. Frank van Hoek, Marc Scheltinga, Martin Luirink, Huub
Pasmans, Charles Beerenhouts. Banding of Hemodialysis
Access to Treat Hand Ischemia or Cardiac Overload.
Seminars in Dialyse. 2009;22(2):204-208.
9. Huber TS, Brown MP, Seeger JM, Lee WA. Midterm
outcome after the Distal revascularization and interval
ligation (DRIL) procedure. J Vasc Surg. 2008;48(4):926-
232.
10. Knox RC, Berman SS, Hughes JD, Gentile AT, Mills JL.
Distal revascularization - interval ligation: a durable and
effective treatment for ischemic steal syndrome after
hemodialysis access. J Vasc Surg. 2002;36(2):250-255.

AMT, vol. 26, no. 1, 2021, p. 27

 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):28-30
DOI: 10.2478/amtsb-2021-0008
Online ISSN 2285-7079

THE DAMAGE OF OCULAR SURFACE DUE TO

UNCONTROLLED INTRAOCULAR PRESSURE IN
NEOVASCULAR GLAUCOMA

ALINA-ADRIANA PANGA1, DAN MIRCEA STĂNILĂ2, ADRIANA STĂNILĂ3,

ALEXANDRA JURCĂ4
1,2,3
OFTA TOTAL Clinic, Sibiu,1,2 Sibiu County Clinical Emergency Hospital Sibiu, 1,2,3,4“Lucian Blaga” University of Sibiu, 1,2,3 Ocular Surface
Research Center, Sibiu

Keywords: neovascular
glaucoma, ocular surface,
intraocular pressure
Abstract: Neovascular Glaucoma (NVG) is a severe form of glaucoma characterized by
neovascularization and the proliferation of fibrovascular tissue in the anterior chamber angle.
Patients with NVG generally present with elevated intraocular pressure (IOP) and may experience
severe pain. Ocular surface is affected by high IOP and can lead from moderated to marked
conjunctival congestion that is frequently associated with edematous cornea. The aim of the study is to
show how the high IOP can affect the ocular surface of the NVG patients and how we can treat and
prevent the suffering. Materials and methods: We took in the study a number of 38 eyes from 35
patients with NVG in stage 3 with angle closure glaucoma, that presented high IOP and impaired
ocular surface. Results and discussions: The ocular surface was damaged in patients that presented
IOP between a minimum of 38 mmHg and maximum of 89 mmHg. The symptoms that patients
presented were: conjunctival congestion in particular perikeratic, epithelial and stromal corneal
edema, epithelial bubble, corneal ulcerations. Treatment followed rapid drop in IOP and the
restoration and protection of ocular surface. The management of neovascular eye with high IOP was
medical, laser and surgical. The restoration of ocular surface was made with lubricating
hyperosmotic ophthalmic solutions, regenerative and protective agents. In all cases after the
treatment was performed the ocular surface was restored. Conclusions: NVG is a very difficult
pathology and is very hard to manage. The uncontrolled IOP in NVG patients affect the ocular
surface and leads to complications. Long-term maintenance of normal intraocular pressure is
important in NVG management but also in protecting the ocular surface.

INTRODUCTION
Neovascular Glaucoma (NVG) is characterised by a
severe tipe of glaucoma, described in the special literature like a
malignant glaucoma. It is described by neovascularization and
the proliferation of fibrovascular tissue in the anterior chamber
angle.(1)

Figures no. 1, 2. Rubeosis iridis

Ocular surface (OS) is deeply affected by high IOP in

NVG and can lead to marked mixt conjunctival congestion
associated with edematous cornea (figure no. 1).(2.3)
Acute angle closure in GNV is an ophthalmic
emergency that is the result of a sudden increase in IOP along

1
Corresponding author: Alina Panga, Str. Semaforului Nr 4, Sibiu, România, E-mail: pangaalina@gmail.com, Phone: +40740 407918
Article received on 20.09.2020 and accepted for publication on 26.02.2021
AMT, vol. 26, no. 1, 2021, p. 28
 CLINICAL ASPECTS
with the next symptoms and clinical signs, such as corneal
edema, shallow anterior chamber, blurred vision, severe ocular
pain or headache, nausea and vomiting sometimes.(3)
According to a large number of studies and
publications, angle closure leads to a significant decrease in
endothelial cell density.(2,4) Corneal endothelium can adapt to a
gradual and modest increase in IOP, but this happens and it
persists for an extended period of time, without developing
major changes.(2,4) In contrast, corneal edema can be can
induced by a rapid and transient increase of IOP.
An acute, sudden, and large increase in IOP has been
suggested to modify the ultra-structural appearance of corneal
endothelium by disrupting the cytoplasm and causing pycnosis,
excrescences and even loss of cells but the mechanism is not
well understood.(2) Increased IOP can affect endothelial cells
through direct mechanical damage, impaired endothelial pump,
and ischemic, oxidative stress.(2) Long-term high IOP induce
deformation and affect endothelial function, reduce blood flow,
induce hypoxia.(2,5)
Figure no. 3. (A,B) Mechanism of corneal edema
AIM
The aim of the study is to show how we can prevent
and treat the suffering of the ocular surface in the NVG patients
MATERIALS AND METHODS
We took in the study a number of 38 eyes from 35
patients with NVG in stage 3, with angle closure glaucoma,
presenting high IOP and impaired ocular surface (figures no.
4,5) We conducted ocular examination, IOP measurement, and
imagistic investigations.
The etiology of NVG in the group was classified in
diabetic retinopathy, central or branch vein occlusion and ocular
ischemic syndrome.
RESULTS AND DISCUSSIONS
The ocular surface was damaged in patients that
presented IOP between a minimum of 38 mmHg and maximum
of 89 mmHg (figure no. 4). Corneal edema is one of the obvious
clinical signs of this disease.
The main factor in the ocular surface damage in NVG
is elevated IOP (figure no. 3).
The symptoms that patients presented were:
conjunctival congestion in particular perikeratic, epithelial and
stromal corneal edema, epithelial bubble, corneal ulcerations
(figure no. 2).
Treatment algorithm followed aimed at dropping the
high IOP with medical treatment applied locally, generally and
the restoration and protection of ocular surface.
AMT, vol. 26, no. 1, 2021, p. 29
Figure no. 4. Cases of high IOP with corneal edema (A,
B,C)and ulcer (D)
Figure no. 5. The values of the IOP before the surgery, after
surgery and at 3 months
Local ocular hypotensive therapy has been the foirts
step and it was consisted by fixed combinations of Carbonic
anhydrase inhibitors and Beta blockers, Alpha-adrenergic
agonist, and for putting at rest ciliary body and reduce the pain
we administrated. Atropine, Cyclopentolate and anti-
inflammatory topical agents (Steroids, Nonsteroids).
Acetazolamide was used in systemic therapy with the purpose to
drop the aqueous humor production and osmotic agents to
reduce the vitreous volume. To reduce the inflammation and
pain were used antalgic agents and anti -inflammatory agents.
Protection and restoration of ocular surface with artificial tears,
autologous serum, matriceal therapy, liposome therapy, ocular
surface bioprotection, antibiotic drops, corticosteroids,
nonsteroidal anti-inflammatory drops. Protective treatment, with
therapeutic contact lenses.
After we succeed to drop the IOP we made intravitreal
injections with anti-VEGF agents and panphotocoagulation
when clear media was obtained. Intravitreal injection of anti-
VEGF agents in patients with NVG reportedly causes reduced
vascular permeability, decreased inflammatory reaction, loss of
vascular function, and endothelial cell degeneration.(6,7,8)
Surgical therapy by trabeculectomy with application
of antimetabolite local (Mitomycin C, 5-Fluorouracil) and
Interferon alfa-2b was performed in all cases.(9,10,11,12)
Figure no. 6. (A,B) Filtration bleb at 3 months after
glaucoma surgery and normal IOP
If the algorithm treatment plan was in made in 3
directions, medical, laser and surgery. We noticed that the
average IOP before surgery was very high, with values over 50
mmHG, and decreased by 40.57 mmHg after surgery at 3 days
and was maintained with values under 40 mmHg 1 months later.
We observed an average increase of IOP (10-15
mmHg) at 3-month evaluation after this algorithm treatment and
we repeated the anti-VEGF injections and measured IOP 2
weeks later We repeated the injections after 4 weeks depending
of the value of IOP measured. In cases where visual function
was preserved and we observed cataract progression, cataract
surgery was performed with intraocular lens implantation.
 CLINICAL ASPECTS
Figure no. 7. Percentage of decrease in IOP reported in the
type of substance used in trabeculectomy
Figure no. 8. Ocular surface at 3 months
Evaluations of patients with NVG was made at 3
months or prior in cases where IOP was increased and ocular
symptoms like decreased vision, corneal edema and pain were
present. A part of the patients was lost from the study due to
noncompliance or they passed away. In the cases with
persistence of high IOP after performing algorithm treatment we
succeed to maintain low values of IOP by completing the
treatment process with injections of anti-VEGF followed by
cyclophotocoagulation with IRIDEX Cyclo G6.
Ocular surface was restored in all cases that remained
in the study because of the controlled IOP by this algorithm
treatment.
Figure no. 9. Treatment algorithm of NVG and ocular
surface protection
CONCLUSIONS
NVG is a very difficult pathology and is very hard to
manage. The uncontrolled IOP in NVG patients affect the ocular
surface and leads to complications. Uncontrolled IOP is the
main risk factor implicated in the suffering of ocular surface.
Long-term maintenance of normal intraocular pressure is
important in NVG management but also in protecting the ocular
surface.
REFERENCES
1. Melamed S, Ben-Sira, Ben-Shaul. Corneal endothealial
changes under induced intraocular pressure elevation: a
scanning and transmission electron microscopic study in
AMT, vol. 26, no. 1, 2021, p. 30
rabbits. British Journal of Ophthalmology. 1980;64:164-
169.
2. Li X, Zhang Z, Ye L, Meng J, Zhao Z, Liu Z, Hu Z. Acute
ocular hypertension disrupts barrier integrity and pump
function in rat corneal endothelial cells. Scientific Reports,
Nature; 2017.
3. Olmos LC, Lee RK. Medical and Surgical Treatment of
Neovascular Glaucoma. Bascom Palmer Eye Institute,
University of Miami Miller School of Medicine Miami, FL,
Int Ophthalmol Clin. 2011;51(3):27-36.
4. Borgman CJ. Neovascular Glaucoma: A Serious Secondary
Condition. Review of Optometry; 2014.
5. Satoko Nakano, Takako Nakamuro, Katsuhiko Yokoyama,
Kunihiro Kiyosaki, Toshiaki Kubota, Prognostic Factor
Analysis of Intraocular Pressure with Neovascular
Glaucoma. Journal of Of Ophtalmology. 2016 Volume
2016 |Article ID 1205895
https://doi.org/10.1155/2016/1205895
6. Rodrigues AI, Sheng L. Reversing the rubeotic rampage –
Current approaches in the management of neovascular
glaucoma, European Ophthalmic Review. 2016;10(1):19–
21.
7. Nakano S, Nakamuro T, Yokoyama K, Kiyosaki K, Kubota
T. Prognostic Factor Analysis of Intraocular Pressure with
Neovascular Glaucoma. J Ophtalmol; 2016.
8. Park J, Lee M. Short-term effects and safety of an acute
increase of intraocular pressure after intravitreal
bevacizumab injection on corneal endothelial cells, BMC
Ophthalmology. 2018;18:17.
9. Sun Y, Liang Y, Zhou P, Wu H, Hou X, Ren Z, Li X, Zhao
M. Anti- VEGF treatment is the key strategy for
neovascular glaucoma management in the short term. BMC
Ophthalmology. 2016;16:150.
10. Gillies MC, Morlet N, Sarossy MG. Treating ophthalmic
fibrosis using interferon-.alpha”, Sydney, Australia, Jan.;
1999.
11. Gillies M, Su T, Sarossy M, Hollows F. Interferon-alpha
2b inhibits proliferation of human Tenon's capsule
fibroblasts”, Department of Ophthalmology P rince of
Wales Hospital Ranwick, Auastralia; 1993
12. Gillies MC, Goldberg I, Stephanie H, Su, Tao. Glaucoma
filtering surgery with interferon alpha-2b, Journal of
Glaucoma. 1993;2(24).
 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):31-33
DOI: 10.2478/amtsb-2020-0009
Online ISSN 2285-7079

SMOKING – TRIGGER AND AGRAVATING FACTOR IN DRY

EYE DISEASE

ALEXANDRA-MARIA JURCĂ1, ADRIANA STANILĂ2, AURORA GAJTA3,

DAN MIRCEA STĂNILĂ4
1,2,4
“Lucian Blaga” University of Sibiu, Sibiu, 3West University of Timisoara, General Hospital Dept. of Ophthalmology Vrsac, Abraseviceva
bb.,Vrsac Serbia, Vrsac, Serbia

Keywords: smokers, risk
factor, dry eye syndrome
Abstract: The purpose of the study is to analyse the relationship between smoking and dry eye
syndrome. The instrumentation consists of the Ocular Surface Disease Index (OSDI) questionnaire,
based on 12 questions related to subjective ocular signs and symptoms that appeared during the
different activities of daily life, qualitative tests like Schirmer I (without anesthesia) and for assessing
the quality of tears the T-BUT and the tears pH was performed. In the study 75 subjects were included
with ages between 20-45 years old, smokers and non-smokers, healthy persons with no medication,
with no ophthalmic surgery in the last 6 months and not contact lens wearers. Results show the
presence of dry eye symptoms more advanced in smokers compared to non-smokers.

INTRODUCTION MATERIALS AND METHODS

Dry eye disease is one of the most common ocular
comorbidities and may overlap with other causes of ocular
surface disease, such as ocular allergy and meibomian gland
dysfunction.(1,2) Dry eye syndrome is a multifactorial disease
whose outcome is malfunctioning of the tear film due to
insufficient tear production or increased tear film evaporation,
with potential damage to the ocular surface.
Prevalence of dry eye syndrome increases with age;
studies show a prevalence between 5-30% of the adult
population.(3) Dry eye is associated with many risk factors
such as environment, lifestyle, age, sex, drug history, and
systemic diseases, among which the lifestyle factors may play
an important role. Smoking is already known as an important
risk factor for many chronic diseases and however is still an
unclear risk factor of dry eye.
Smoking represents a major health problem in
worldwide and it is the cause of many disease like
cardiovascular, respiratory, tobacco-alcoholic amblyopia, dry
eye syndrome.(4)
The definition of dry eye was suggested according to
tear break-up time (T-BUT) and Schirmer score. Smoking was
found to decrease T-BUT in some of the studies.(5) Sayin et al
found the decreasing of Schirmer score in smokers.(6)
Ocular surface is exposed to chronic oxidative stress:
UV radiation, oxygen action in the air, exchange of oxygen
pressure during blinking, the action of various environmental
factors.
Furthermore, smoking affects the ocular surface
homeostasis and is a risk factor that intervenes in the tear film
stability by damaging lipid layer.(7,8)
AIM
The purpose of the study was to determine the quality of
the tear film and the possible risk of dry eye syndrome in
smokers compared to non-smokers.
In the study, 150 eyes, 75 subjects were included, aged
ages between 20-45 years old, smokers and non-smokers,
healthy persons with no medication, no ophthalmic surgery in
the last 6 months, not contact lens wearers.
Subjective symptoms were evaluated with OSDI
questionnaires, qualitative tests like Schirmer I (without
anesthesia) and for assessing the quality of tears the T-BUT and
the tears pH was performed.
For the Schirmer I test we used the standard test paper
strip, inserted in the bottom of the conjunctival sac, without
anesthesia; after 5 minutes it was removed and the wet length of
the strips was read, the results being noted in millimeters.
Normal values of Schirmer I measurements are > 15 mm/5
minutes.
Tear break time (T-BUT) - a drop of fluorescein 0,5%
it's applied in of the lower conjunctival fornix. The patient is
asked to blink several times and the interval between the last
blink and the appearance of the first black spots on the cornea is
measured. A normal T-BUT >10 seconds, values <10 sec are
considered abnormal and indicate tear film instability.
For the tear pH, we used pH strips of paper inserted into
the conjunctival sac and left to soak with tears, then the colour
obtained was compared with the colour of the test scale. We
noted two groups for tear pH, one with a pH between <7.2-8>
and one with PH > 8, associated with eye film instability and the
possible occurrence of dry eye syndrome.
RESULTS
Of the 75 patients, the greatest percent, almost 55%, is
represented by persons aged between 20 and 30 years old,
followed by the age between 31-40 years old with 32 % (figure
no. 1).
From all the patients, we found a higher percentage of
dry eyes in women, respectively 48 women representing 64% of
the total patients and 27 of patients were man (figure no. 2).

1
Corresponding author: Alexandra-Maria Jurca, Splaiul Nistrului, Nr. 6, Timișoara, România, E-mail: dr.alexandra.jurca@gmail.com, Phone: +40726
657839
Article received on 20.11.2020 and accepted for publication on 26.02.2021
AMT, vol. 26, no. 1, 2021, p. 31
 CLINICAL ASPECTS
Figure no. 1. Distribution of patients by age Figure no. 3. OSDI scores in smokers/non-smokers

Schirmer I test is more affected in smokers than non-

smokers. The most affected are smokers aged 41-50 years, in
which the Schirmer I test is ≤ 5 mm/5 min. We did not find a big
difference between right eye and left eye (figure no. 4, figure no.
Figure no. 2. Distribution of patients by age/gender 5).

Figure no. 4. Right eye - Schirmer I test in smokers/ non-

smokers

36 of the patients were smokers and 39 were non-smokers (table

no. 1).

Table no. 1. Distribution of patients by age/ gender/

smokers/ non-smokers
AGE MAN MAN- WOMA WOMA TOT
- NON- N N-NON- AL Figure no. 5. Left eye - Schirmer I test in smokers/ non-
SMO SMOK SMOK SMOKE smokers
KER ER ERS RS
20-30 7 6 11 17 41
31-40 4 5 8 7 24
41-50 4 1 2 3 10
TOTAL 15 12 21 27 75
OSDI scores were: OSDI A 5,77 ± 3,11, OSDI B 5,57
± 2,49, OSDI C 3,6 ± 2,37, OSDI D 14,96 ±7,53, OSDI score
was 31,13 with a standard deviation of 15,67 (table no. 2). This
score corresponds to a mild to moderate dry eye syndrome.

Table no. 2. OSDI scores

OSDIA OSDI OSDI OSDI score
B C D OSDI
Mean 5.77 5.57 3.6 14.96 31.13
Standard 0.35 0.28 0.27 0.86 1.81
Error
Standard 3.11 2.49 2.37 7.53 15.67 Regarding the tear break up time (T-BUT), we can
Deviation observe that smokers from age group 41-50 years are the most
Minimum 0 1 1 2 4.16 affected (table no. 3), where the T-BUT is less than 5 seconds.
Maximum 17 15 10 42 87.5 The next age group affected is the one between 31-40 years, also
Sum 433 418 270 1122 2335.41 smokers being more affected than non-smokers (table no. 4).
Count 75 75 75 75 75
Confidence 0.716251 0.575102 0.545517 1.733117671 3.607610709 Table no. 3. T-BUT in smokers
Level T-BUT 5 % 10 % 15 % Total
(95.0%) (sec)
We can see in the graph below (figure no. 3) a higher 20-30 0 3 3.75 15 18.75 18
percentage of the total OSDI score in smokers compared to non- 31-40 0 9 11.25 3 3.75 12
smokers and the highest percentage of the OSDI score is 41-50 4 3.75 3 3.75 0 6
represented by persons in the age group of 41-50 years, Total 4 3.75 14 18.75 18 22.5 36
respectively 59.72%.

AMT, vol. 26, no. 1, 2021, p. 32

 CLINICAL ASPECTS
Table no. 4. T-BUT in non-smokers cause ocular discomfort and affect the quality of life of patients.
T-BUT 5 % 10 % 15 % Total The current study brings more evidence for the negative
(sec) effects of smoking.
20-30 0 2 2.5 21 26.25 23 In order to control this global health issue, there is a dire
31-40 0 3 3.75 9 11.25 12 need to increase knowledge and provide support and motivation
41-50 1 1.25 1 1.25 2 2.5 4 towards cessation of tobacco use.
Total 1 1.25 6 7.5 32 40 39
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 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):34-35
DOI: 10.2478/amtsb-2021-0010
Online ISSN 2285-7079

CERVICAL FRACTURE WITH PIRIFORM SINUS LACERATION

MIHAELA CHIALDA1
1
Sibiu County Clinical Emergency Hospital

Keywords: fracture, Abstract: Particular case of complex cervical trauma by associating a cervical fracture with piriform
laceration, piriform sinus sinus laceration. The trauma is located in the anatomo-topographic zone II. Delayed onset at 24
hours of digestive symptoms, swallowing disorders, sialorrhea, dysphagia, subcutaneous cervical
emphysema. CT with Optiray contrast agent is performed, an investigation that reveals a gap in the
left piriform sinus of 5-6 mm. The evolution is favourable under conservative treatment, nasogastric
tube, broad spectrum antibiotic treatment.

INTRODUCTION headache, dizziness that started suddenly following a spinal

As the incidence of violent trauma is increasing
nowadays, the rate of trauma to the neck and head is also
increasing. At present, penetrating neck injury comprises 5% to
10% of all trauma cases.
All penetrating neck wounds are potentially dangerous
and require emergency treatment. In the neck region there are
many sensitive and vital structures, all merged in a small area
that is not protected by bone tissue.(1,2) These can be divided
into 4 groups: airways (trachea, larynx, fringe and lungs), blood
vessels (carotid, jugular, subclavian artery, aortic arch),
gastrointestinal tract (pharynx and esophagus) and nerve
structures (brachial pleura, peripheral nerves, spinal cord,
cranial nerves).
The signs and symptoms specific to the structures in
all 4 groups should alert the otolaryngologist that trauma has
occurred at this level. The neck can be divided into 3
anatomotopographic areas.(1,3,4)
Zone I is located under the cricoid cartilage, being an
area where important vacuole structures are protected by the rib
cage and collarbones.
Zone II is the area above the cricoid cartilage to the
level of the mandible. Zone II does not have bone protection,
thus being more exposed to trauma with a rate of 65-70%.
The least common traumas in zone II are venous and
pharyngoesophageal because they are not diagnosed in the
initial assessments.
A substantial number of patients can be selectively
managed, depending on sings, symptoms and direction of the
trajectory. When patients are stable and lack physical signs of
obvious major neck injury, they are evaluated by diagnostic
radiologic and endoscopic techniques. All patients are admitted
for observation, in the next 24 h after trauma, clinical and
physical examinations being repeated.(1,2,3)
CASE REPORT
A 63-year-old patient presented to the Emergency
Room within the Sibiu County Clinical Emergency Hospital,
presenting the following symptoms: pain in the cervical region,
trauma by falling objects in the cervical region.
At the general emergency consultation, the patient
presents: relatively good general condition, preserved state of
consciousness, cervical area immobilized in Minerva type collar,
hyperstenic constitution, respiratory rate 19, afebrile, heart rate
103, tachycardia, rhythmic noises, well beaten, blood pressure
within normal limits, clean, normally coloured skin with
contusion present at the cervical level. Integral and mobile
osteoarticular system, no eye disorders, no open trauma. The
patient is admitted to the neurosurgery department for
specialized treatment.
Neurological examination at hospitalization:
conscious patient, temporo-spatially oriented, Glasgow Coma
Scale 15 points, no meningeal signs or pathological reflexes,
reflexivity and motility preserved, no sphincter disorders,
cortical functions preserved.
At 24 hours after admission, the patient complains of
dysphagia with inability to swallow fluids, solids, sialorrhea,
sore throat, voice change, crackling in the neck, subcutaneous
emphysema, subfebrile.
After examination by a general surgery specialist, a
traumatic esophageal injury is suspected. CT is performed with
the ingestion of the Optiray contrast substance, which reveals
the rupture of the piriform sinus, blood collection at this level
and retropharyngeal, aerial collection in the soft parts, cervical
prevertebral and upper mediastinum. Upper digestive endoscopy
reveals left hypopharyngeal hematoma and an ulceration of
approximately 5-6mm. Thus, the immobilized patient with a soft
cervical collar is transferred to the Otorhinolaryngology
department, where the nasogastric tube is urgently mounted and
antibiotic therapy is initiated with Cefuroxim, Metronidazole,
Fluconazole for 10 days. Following the treatment performed, the
evolution is favourable.
A CT scan is performed that reveals a cervical region
within normal limits. C1-C6 cervical spine radiograph (AP, LL)
in conjunction with previous CT examinations, reveals:
Small bone fragment projected antero-inferiorly by the
spinous process C5 of about 1 cm, parcel fracture with

1
Corresponding author: Mihaela Chialda, B-dul. C. Coposu, Nr. 2-4, Sibiu, România, E-mail: mihaela_chialda@yahoo.com, Phone: +40744 551390
Article received on 20.09.2020 and accepted for publication on 08.01.2021
AMT, vol. 26, no. 1, 2021, p. 34
 CLINICAL ASPECTS
displacement. It does not show spondylolisthesis or vertebral
body subsidence. Spondylarthrosis degenerative changes with
anterior osteophytosis.
Narrowing of the distal space and reversal of the
physiological curve at C5-C6. No pathological changes in the
soft prevertebral parts.
Figure no. 1. Cervical native CT scan
Figure no. 2. Cervical native CT scan
DISCUSSIONS
We presented a case of complex cervical trauma, with
fracture of spinous processes c5-c6, fracture by compaction of
vertebral body c7 with small bone fragment projected antero-
inferiorly by spinous apophysis c5, a parcel fracture with
displacement, which secondarily affects the sinus piriform. It
should be noted that the gap in the piriform sinus was 5-6 mm, a
fact highlighted by endoscopy.(4) This trauma is located in
topographic area 2, and the vital signs were good, the patient
being hemodynamically stable, without hypovolemic shock or
hemomediastinum.
This justified us for a conservative treatment, without
performing an exploratory cervicotomy.(1,3,5,6,7,8) The case
was initially labelled as a neurosurgical case by
symptomatology and paraclinical examination in the emergency
department.(1) At 24 hours after hospitalization, the patient
presents with subcutaneous cervical emphysema and swallowing
disorders, which raises the suspicion of damage to the digestive
tract, which is why cervical CT is repeated with Optiray contrast
ingestion and endoscopy, which reveals the piriform sinus
lesion.(9,10)
AMT, vol. 26, no. 1, 2021, p. 35
In the assessment of pharyngo-esophageal trauma,
radiological examination with the ingestion of the contrast
substance Gaastrografin or Optiray is necessary to highlight the
lesions, because the administration of barium can
radiographically distort the soft tissues and is even more toxic. If
at the radiological evaluation, no changes are observed, but we
still suspect a pharyngo-esophageal lesion, barium can also be
administered. Pharyngeal-esophageal endoscopic evaluation is
important in cervical trauma.(1)
In cervical spine fractures, rigid esophagoscopy
should be avoided. Omission of cracks or tears in the
cricopharyngeal and hypopharyngeal can lead to serious
complications such as mediastinitis, increasing morbidity and
mortality considerably.
Thus, if there is the slightest suspicion of perforation
at this pharyngeal level, it is very important to suppress food by
mounting a nasogastric tube and initiating broad-spectrum
antibiotic therapy, to avoid major complications.(1)
CONCLUSIONS
Cervical injuries are constantly increasing and can
affect several anatomical elements in the region, which involves
a complex examination of the case and proper monitoring.
Severe life-threatening cases due to massive
hemorrhage, expansive hematoma, hemodynamic instability,
hemomediastinum or hypovolemic shock require exploratory
cervicotomy with ligation or suturing of large vessels,
tracheostomy, pharyngorrhagia.
For stable patients with cervical trauma in topographic
area 2, the evolution of symptoms is monitored and massive
broad-spectrum antibiotic therapy is administered, covering
gram-positive and gram-negative aerobic and anaerobic germs.
Complex cases of cervical trauma require a
cooperative, multidisciplinary approach, thus, in any
traumatology team, the otorhinolaryngologist must be included,
in order to evaluate and treat the pharyngolaryngeal and vascular
traumas.
REFERENCES
1. Cummings CW, Haughey BH, Thomas JR, Lee A. Harker
LA, Flint PW. Otolaryngology Head&Neck Surgery
Cumings, Ed. Elsevier Mosby Fourth Edition.
2004;3:2525-2538.
2. Anniko M, Bernal-Sprekelsen M, Bonkowsky MV, Bradley
P, Iurato S. Otorhinolaryngology Head& Neck Surgery, Ed.
Springer; 2010. p. 503-505.
3. Anghelina F, Beuran M, Borangiu A, Popescu I, Constantin
Ciuce C, Sarafoleanu C. Otorinolaringologie Si Chirurgie
Cervico-Faciala Sub Redactia Irinel Popescu, Ed.
Academiei Romane; 2012. p. 691-695.
4. Greenberg MS. Hand Book Of Neurosurgery, Ed.Thieme,
Eighth Edition - Traumatisme Cervicale; 2019.
5. Anghel I. Otorinolaringologia Ed. Universitara Carol
Davila; 2013. p. 190-193.
6. Popescu CR, Zainea V. Otorinolaringologie, Ed.
Universitara Carol Davila; 2010. p. 256-257.
7. Zenner HP. Otorinolaringology, Ed. Mirton; 2004. p. 284-
285.
8. Goldenberg D, Golstein B I. Neck Trauma Hand Book of
Otolaryngologye, Ed. Thieme; 2011.
9. Becker W, Naumann HH, Pfaltz CR. Ear, Nose, Throat
Disease, Ed. Thieme; 1994. p. 409-413.
10. Sarafoleanu D. Explorarea Paraclinica Si Functionala In
Otorinolaringologie Vol. II Ed. Albatros, Explorare
Laringe; 2000.
 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March;26(1):36-40
DOI: 10.2478/amtsb-2021-0011
Online ISSN 2285-7079

MODERN ASPECTS IN THE DIAGNOSIS AND SURGICAL

TREATMENT OF BREAST CANCER IN EARLY STAGES

ANDREI MOISIN1, CIPRIAN TĂNĂSESCU2

Sibiu County Emergency Clinical Hospital, 2 “Lucian Blaga” University of Sibiu
1,2

Keywords: surgery, breast Abstract: Breast cancer is the most common cancer in women and a major public health problem,
cancer, early stages, affecting 2.1 million women each year globally and causing the highest number of cancer-related
modern surgical deaths among women. In 2018, an estimated 627,000 women died from breast cancer (about 15% of
treatment all cancer deaths among women). To improve survival, early detection is essential. There are two
strategies for early detection of breast cancer: early diagnosis and screening.(1) In Romania, the
latest statistics show a higher incidence of breast cancer compared to the European average of 7929
new cases / year with a mortality of 3101 deaths / year.(2)

INTRODUCTION surgical treatment are significantly reduced through the use of

Surgical resection was the first effective treatment for
breast cancer and remains the most important treatment for
curative purposes. Over time, significant improvements have
been made to surgical techniques which, together with the use of
adjuvant radiotherapy and advanced chemotherapeutic agents,
have allowed the orientation towards more modern surgical
techniques. Surgical management of breast cancer has
undergone significant changes, starting from extensive
procedures with increased morbidity, to the modern concept,
thus obtaining the best possible cosmetic result, in tandem with
the appropriate oncological resection. A growing understanding
of breast cancer biology has led to significant advances in
molecular diagnosis and targeted therapies. All these
improvements have contributed to the development of more
modern, more targeted therapeutic interventions that have also
led to a decrease in morbidity and mortality. The current
standard of care for breast cancer patients consists of a
multidisciplinary approach that involves a coordinated effort
between the surgeon, oncologist and radiologist to achieve the
best possible outcome for each patient.(3)
Surgical management of breast cancer has undergone
continuous changes over the past three decades. For patients
with early-stage breast cancer, conservative breast surgery
followed by radiation therapy has been definitively validated as
a safe alternative to radical mastectomy, with similar survival
rates and better cosmetic results. Due to improvements in the
diagnostic process, as well as the expansion of screening
programmes and efforts in patient education, breast tumours are
detected more frequently at an early stage, facilitating the
increasing use of breast preservation techniques.(4)
Gradual reduction of tumour size can be achieved by
using neoadjuvant chemotherapy and/or endocrine therapy,
allowing most patients to perform breast preservation surgery. In
this context, the decision to continue conservative surgical
treatment is guided by the clinical and radiological response to
neoadjuvant therapy. Local recurrence rates after conservative
adjuvant radiotherapy and, therefore, should be considered as a
standard of care, unless distant metastases are detected.(5)
Conservative therapy is considered an important step
in the treatment of early breast cancer, representing a modern
method of primary treatment for women with stage I and II
breast cancer, being preferred due to the survival rate equivalent
to those with total mastectomy and axillary dissection, while
preserving the breast.
Conservative therapy involves extensive local excision
of the tumour formation, along with 1-2 cm of healthy
peritumoral tissue, in order to locally control the disease and
evaluate the ipsilateral axillary lymph nodes by axillary
lymphadenectomy or sentinel node biopsy. The selection criteria
for patients who can benefit from conservative therapy are based
on the correct evaluation of the clinical, imaging and
pathological elements. Age is not a selection criterion. The
clinical examination allows the assessment of the tumour size
and the tumour-breast ratio, as well as the existence of several
tumours. The mammographic examination provides us with
information on the diameter of the tumour, the presence or the
absence of multicenter lesions and microcalcifications.
Histopathological examination is particularly important in
establishing conservative behaviour, especially in the case of
invasive intraductal carcinoma, positive margins or lobular
carcinoma. Verification of intraoperative resection margins
reduces the risk of postoperative recurrence.(6)
AIM
This paper is a comprehensive analysis of modern
methods currently used in the detection and surgical treatment of
early-stage breast cancer, increasing quality of life and
decreasing the incidence among patients diagnosed with this
disease.
The aim of this paper is to evaluate and describe the
main modern methods of diagnosis and surgical treatment of
breast cancer currently used in the Surgery I Clinic of the Sibiu

1
Corresponding author: Andrei Moisin, B-dul. Corneliu Coposu, Nr. 2-4, Sibiu, România, E-mail: moisin_andrei93@yahoo.com, Phone: +40741
664654
Article received on 23.06.2020 and accepted for publication on 26.02.2021
AMT, vol. 26, no. 1, 2021, p. 36
 CLINICAL ASPECTS
County Emergency Clinical Hospital. One of the major
objectives of this study is to evaluate the efficacy, safety and
applicability of conservative surgical treatment by using
different surgical techniques in patients with early-stage breast
cancer.
MATERIALS AND METHODS
This study is a descriptive one regarding the patients
hospitalized in the Surgery I ward of Sibiu County Emergency
Clinical Hospital, diagnosed with breast cancer. The study
includes a batch of 83 cases diagnosed with breast cancer over a
period of 3 years, from 01.01.2016 to 31.12.2018. We included
in the study all patients for the last 3 years, hospitalized in a
chronic regimen. Patients with benign tumours were excluded.
Statistical data processing was performed using Microsoft
Office Excel 2016.
The data collection and integration was performed
from the sources that were extracted from the database of the
Sibiu County Emergency Clinical Hospital. Based on the
collected data, the analysis and comparison of the cases that
were represented with the help of tables and figures was
prepared. These results were correlated with current data on
breast cancer from the literature. Patients were analyzed
according to the following parameters: age and environment of
origin; topography of the primary tumour; presence of
comorbidities (diabetes, hypertension, ischemic heart disease);
TNM staging; patients who have received neoadjuvant therapy
or with direct surgical indication; type of biopsy; surgical
technique used and postoperative complications.
RESULTS AND DISCUSSIONS
Regarding the distribution of the cases by age groups,
a predominance of the number of cases was observed in the age
group 61-70 years representing a percentage of 33% for 27
cases, followed by the age group 51-60 years with 19 patients
(23 %) and the age group 71-80 years with 16 cases (19%). The
age distribution of the patients is illustrated in table no. 1.
Table no. 1. Distribution of patients according to age
Age group Number of cases Percentage (%)
31-40 2 2%
41-50 15 18%
51-60 19 23%
61-70 27 33%
71-80 16 19%
>80 4 5%
Total 83 100%
Out of a total of 83 cases, 19 patients belonged to the
rural environment, i.e. a percentage of 23%, and the remaining
64 patients belonged to the urban environment, that is a
percentage of 77%. This criterion emphasizes the fact that breast
neoplasm is a pathology especially in women in urban areas, in
rural areas being considerably less common. The environment of
origin of patients is presented in table no. 2.
Table no. 2. Distribution of patients according to the
environment of origin
Origin environment Number of cases Percentage (%)
Rural 19 23%
Urban 64 77%
Total 83 100%
The patients in the study group were assigned
according to the location of the primary tumour in the quadrants
of the breast. Out of the total of 83 patients included in the study
group, 56 presented a tumour formation at the level of the
external quadrants representing 68% of the total. Also, a
predominance of tumour localization was observed in the
AMT, vol. 26, no. 1, 2021, p. 37
superoexternal quadrant with 42 cases (51%) followed by the
inferoexternal quadrant with 14 cases and a percentage of 17%.
The least frequent locations were at the level of the internal
superointernal and inferointernal quadrants with 7 cases for
each. Instead, 13 cases were reported that showed a tumour
formation in the central quadrant (16%).
Several studies have attempted to establish the
prognostic significance of breast cancer depending on the
location of the primary tumour. Following a study conducted in
the USA on a group of 980 patients who had tumours in
different quadrants of the breasts, it was found that tumours
located in the external quadrants, which are also the most
common, are usually associated with a favourable prognosis
unlike those located in the internal quadrants which are
associated with a mortality twice as high due to the difficulty of
detecting positive lymph nodes in the internal mammary lymph
nodes. Tumours located in the central quadrant are associated
with an unfavourable prognosis and increased mortality.(7) The
distribution of patients according to the location of the primary
tumour is illustrated in figure no. 1.
Figure no. 1. Distribution of patients according to the
location of the primary tumour
Regarding the presence of comorbidities in patients
diagnosed with breast cancer, 42 cases out of the total group had
hypertension (51%), followed by 27 patients with ischemic heart
disease and 14 cases with diabetes. Following the analysis of the
data, there is an increased prevalence of hypertension and
ischemic heart disease in patients diagnosed with breast cancer.
Between January and December 2012, Indian researchers
conducted a study that included 156 patients diagnosed with
breast cancer. The most common comorbidities associated with
breast cancer were high blood pressure, diabetes, chronic
obstructive pulmonary disease and rheumatic disease. All four
pathologies were reported in more than 75% of the cases
included in the study. The data correlate with the values
obtained in the personal study.(8) The distribution of cases
according to the presence of comorbidities is presented in figure
no. 2.
Figure no. 2. Distribution of cases according to the presence
of comorbidities
For the analysis of the distribution of cases according
to the stage of the disease, we used the clinical staging c-TNM,
which is established following the clinical and imaging
examination. Of the 83 patients included in the study group, 2
patients were in stage 0 of the disease (Tis, No, Mo),
 CLINICAL ASPECTS
representing 2% of all cases. Stage I comprises 20 cases (24%),
while stage II comprises 28 cases, accounting for 34% of the
total group. 25 patients were diagnosed with stage III breast
cancer (30%), and 8 patients with stage IV breast cancer, i.e.
10% of cases. These data confirm that the number of cases
detected in stage I is still small compared to stages II and III,
when the therapeutic conduct already becomes more complex
and the prognosis more unfavourable. The distribution of cases
according to c-TNM staging is illustrated in table no. 3.
Table no. 3. Distribution of cases according to c-TNM
staging
c-TNM staging Number of cases Percentage (%)
Stage 0 2 2%
Stage I 20 24%
Stage II 28 34%
Stage III 25 30%
Stage IV 8 10%
Total 83 100%
Regarding the first-line therapeutic indication,
following the analysis of the collected data, 63% of the patients
included in the study group received neoadjuvant treatment. The
rest of the patients (37%) had a first-line surgical indication.
These data emphasize the importance of using neoadjuvant
chemotherapy in the selected cases in order to reduce tumour
size to allow limited resection. Although many studies have not
shown significant differences between the same systemic
treatment administered pre- and postoperatively, in terms of
overall survival of breast cancer patients, neoadjuvant therapy
still has a number of advantages. By reducing the size of the
tumour, mastectomy can be avoided, and the patients can opt for
conservative surgical treatment. Moreover, it can reduce the
volume of excision in patients with an indication for
conservative treatment by improving the cosmetic result. It also
improves locoregional control of the disease and reduces the risk
of long-term spread.(9) Since its introduction, neoadjuvant
chemotherapy has led to an increase in the rate of conservative
treatment and a reduction in morbidity.(10) The distribution of
cases according to the therapeutic strategy is presented in table
no. 4.
Table no. 4. Distribution of cases according to the
therapeutic strategy
Primary treatment Number of cases Percentage (%)
Neoadjudvant 52 63%
Surgical 31 37%
Total 83 100%
Biopsy of tumour formations in the mammary gland is
essential in the diagnosis of breast cancer. Although it is a more
or less invasive method (depending on the type of biopsy), it
allows the diagnosis of certainty. In addition, it provides
information on the type of cancer and the degree of tumour
differentiation. The biopsy completes the information obtained
from the clinical and imaging examination so that the patient
can benefit from a correct and targeted treatment depending on
the result of the histopathological examination. Following the
analysis of statistical data obtained from the database of the
Sibiu County Emergency Clinical Hospital, we found that in the
Surgery I department, three types of biopsy were used to
diagnose breast cancer, namely incisional, excisional and
percutaneous surgical biopsy (with needle). Of the 35 cases
hospitalized for a breast biopsy, the majority had an incisional
biopsy (15 cases). Percutaneous biopsy was performed in 11
patients and excision biopsy in 9 patients. Although in most
cases the surgical biopsy was performed, the percutaneous
biopsy (with fine needle/cutting needle) is gaining more and
more ground due to the fact that it is less invasive and better
AMT, vol. 26, no. 1, 2021, p. 38
supported by the patient. Unlike surgical biopsies, the risk of
bleeding through the use of needle biopsy is much reduced.(11)
The graphical representation of cases according to the type of
biopsy is illustrated in figure no. 3.
In 2009, the U.S. Agency for Research and Quality in
Health (AHRQ) conducted a comparative study that evaluated
the effectiveness of percutaneous needle biopsy compared to
surgical biopsy. The performance and frequency of
postoperative complications for the two types of biopsy were
also studied. The results showed that surgical biopsy remains the
gold standard in terms of breast cancer diagnosis, with a
sensitivity and specificity of over 98%. The rate of postoperative
complications is between 2 and 10%, the most common being
hematoma and local infection. Regarding the needle biopsy
performed under palpation control, the studies show a sensitivity
of 91% and a specificity of 98%.
It was also found that adding imaging methods
(ultrasound, MRI) to guide the biopsy, led to an increase in the
sensitivity of the method up to 99%. The rate of postoperative
complications for percutaneous biopsy was 1%, the most
common being local bleeding and infection at the puncture site.
The authors of the study concluded that percutaneous biopsies
have a high accuracy in detecting breast cancer and
postoperative complications are minimal, but it is up to the
clinician to choose the optimal diagnostic method for each
patient.(12)
Figure no. 3. Graphical representation of cases according to
the type of biopsy
Breast cancer surgery has been and will remain the
most important treatment modality for curative purpose. Over
time, significant improvements have been made to surgical
techniques which, together with the use of neoadjuvant
chemotherapy and adjuvant radiotherapy, have allowed the
orientation towards more modern and less invasive surgical
techniques, while improving the final cosmetic appearance.(3)
Following the analysis of statistical data obtained from
the database of the Sibiu County Emergency Clinical Hospital,
we found that out of the total of 48 patients who benefited from
surgical treatment of breast cancer, most of them underwent
Madden modified radical mastectomy with axillary lymph node
dissection, i.e. 28 cases representing a percentage of 34%. In 9
of the patients, sectorectomy with axillary lymph node
dissection was performed.
The “cleaning” mastectomy was performed in 8 cases
and only one patient benefited from Patey’s operation. There
were also registered 2 patients hospitalized on the Surgery I
ward with a history of breast surgery, in which a complementary
axillary lymphadenectomy was performed. The most commonly
used type of surgery was the Madden modified radical
mastectomy. This aspect confirms the superiority of Madden
surgery over other types of surgery such as radical mastectomy
or Patey’s operation, surgeries that are more mutilating and with
 CLINICAL ASPECTS
an oncological outcome similar to Madden mastectomy.
However, conservative breast surgery is the treatment
of choice for stage I and II breast cancer and includes surgical
excision of the tumour/sector/quadrant followed by axillary
lymphadenectomy and adjunctive breast radiotherapy. The
distribution of patients according to the type of surgery is
presented in table no. 5.
Following a comparative study between conservative
surgery and Madden surgery, the superiority of conservative
surgery in early-stage breast cancer patients was demonstrated.
In the case of conservative treatment, the duration of the
operation was shorter, the intraoperative hemorrhage was
minimal and the hospitalization days were few compared to the
group that benefited from the Madden operation. In addition, the
cosmetic result was in favour of conservative surgery.(13)
However, a recent study by the European Organization for
Research and Treatment of Cancer found no significant
differences in the overall 20-year survival rate between patients
receiving conservative surgical treatment followed by adjuvant
radiotherapy and those receiving modified radical mastectomy
for stage I and II. Overall survival at 20 years was 44% in those
with conservative surgery and 39% in those with Madden
mastectomy.
An important aspect to mention is that in the same
study it was found that the locoregional recurrence of breast
cancer at 10 years was higher in the group that received
conservative surgery (20%) than those with Madden
mastectomy (12%). However, modified radical mastectomy
remains a topical method in early breast cancer, in situations
where conservative treatment cannot be performed.(14)
Table no. 5. Distribution of patients according to surgery
Type of surgery Number of cases Percentage (%)
Madden mastectomy 28 34%
Sectorectomy 9 11%
Cleaning mastectomy 8 10%
Patey mastectomy 1 1%
Complementary axillary 2 2%
lymphadenectomy
Total 48 58%
Breast cancer surgery is generally considered a
surgery with a low risk of morbidity. However, a number of
postoperative complications can occur with more or less serious
consequences.
For example, local wound infection, skin necrosis,
seromas, hematomas or postoperative haemorrhage can lead to
both increased morbidity and costs through prolonged
hospitalization and delay in the application of adjuvant
treatments. After analyzing the statistical data, we found that out
of the total of 83 patients included in the study group, only 10
cases had immediate postoperative complications, representing
12% of all cases. Graphical representation of cases according to
postoperative complications is illustrated in figure no. 4.
Although the literature indicates serum as the most
common postoperative complication of breast surgery, no
patient in the study group presented this complication. This can
be explained by the use of drainage tubes at the end of surgery.
However, the most common complication was prolonged
lymphorrhagia, which occurred in 6 patients and accounted for
7% of cases.
A study conducted at the University of Naples, on a
group of 449 patients, found that 18.2% of them developed one
or more immediate postoperative complications. Among the
most common are seruma, wound infection, hematoma,
postoperative bleeding, cardiovascular complications, anemia
AMT, vol. 26, no. 1, 2021, p. 39
and pulmonary thromboembolism. On Surgery I ward, during
the three years included in the study, only 2 cases with
postoperative hematoma and two other patients with infected
wound and axillary lymphocele were reported. An important
aspect identified in the study of the University of Naples, was
the increase in the incidence of postoperative complications with
age and the number of associated pathologies. We can conclude
that old age and comorbidities influence the appearance of
complications in patients treated surgically for breast
cancer.(15)
Figure no. 4. Graphical representation of cases according to
postoperative complications
Another article recently published in the International
Journal of Surgery Science, aimed at a comparative study of
postoperative complications after modified radical mastectomy
and conservative surgery in early breast cancer. This study
included two groups of patients of 15 people each. The first
batch benefited from Madden surgery and the second from
conservative surgery. Of the 15 cases that benefited from
Madden mastectomy, 2 developed seromas and one patient had
marginal skin necrosis. From the group that benefited from
conservative surgery, only one patient developed seroma.
Therefore, conservative surgery has been shown to be superior
to modified radical mastectomy in terms of the incidence of
immediate postoperative complications.(16)
CONCLUSIONS
Breast cancer is a major public health problem and a
major cause of morbidity and mortality globally. It is the most
common neoplasm among women and the second leading cause
of cancer, after lung cancer.
The current study suggests an increased incidence of
breast cancer, especially in patients aged 50 to 70 years who
also have numerous comorbidities. Among the most common
associated pathologies are high blood pressure, ischemic heart
disease and diabetes.
Most cases of breast cancer were identified in 2018,
their number being continuously rising in those 3 years studied,
and regarding the origin environment, the majority of cases were
registered in the urban environment. The increased incidence of
patients in urban areas can be explained by their better
addressability and accessibility to specialized medical services.
The development and application of screening
programmes is essential for the diagnosis and treatment of breast
cancer. The detection of breast neoplasia at an early stage,
allows the orientation of the therapeutic conduct to modern
surgical methods such as conservative surgery that allows a
good control of the disease and aesthetic outcomes superior to
classical radical surgery.
Tumour biopsy allows the establishment of the
certainty diagnosis, the degree of tumour differentiation and the
type of breast cancer. Most cases benefited from incisional
 CLINICAL ASPECTS
biopsy, followed by percutaneous and excisional biopsy. Biopsy
is mentioned in the literature as the gold standard for the
diagnosis of breast cancer.
The use of neoadjuvant chemotherapy in the treatment
of breast cancer, allows both the reduction of tumour size in
view of limited resection and locoregional control of the disease,
being applied to most cases in the study group. The application
of preoperative oncological treatment can allow the conversion
of selected cases to conservative surgery.
The most used surgical technique was Madden
modified radical mastectomy, being the technique of choice in
locally advanced breast cancer, with a high success rate and low
risk of recurrence.
Conservative surgery is the treatment of choice in
early breast cancer, being considered a safe alternative to radical
mastectomy, with similar survival rates and good aesthetic
outcomes. The selection of patients for this type of intervention
is based on the evaluation of clinical, imaging,
anatomopathological elements but also on the surgeon’s
experience.
Postoperative complications were recorded in a small
number of cases, the most common being prolonged
lymphorrhagia. Much rarer were local wound infection,
hematoma and axillary lymphocele.
Madden mastectomy is more commonly associated
with immediate postoperative complications as opposed to
conservative surgery where their incidence is low.
11. http://chirurgiagenerala.ro/02.003_Biopsia.htm. Accessed
on 28.12.2018.
12. Dahabreh IJ, Wieland LS, Adam GP, et al. Core Needle
and Open Surgical Biopsy for Diagnosis of Breast Lesions:
An Update to the 2009 Report. Comparative Effectiveness
Reviews, No. 139. [PubMed].
13. Chen Z, Xu Y, Shu J, Xu N. Breast-conserving surgery
versus modified radical mastectomy in treatment of early
stage breast cancer: A retrospective study of 107 cases.
Date of Web Publication 31-Aug-2015. DOI:
10.4103/0973-1482.163835.
14. Kuwajerwala NK, Washburn BJ, Widders KL, Badwe RA.
Modified Radical Mastectomy. [Medscape].
15. Rocco N, Rispoli C, Pagano G, Rengo G, Compagna R,
Danzi M, Accurso A, Amato B. Breast cancer surgery in
elderly patients: postoperative complications and survival.
Published online 2013 Oct 8. doi: 10.1186/1471-2482-13-
S2-S25. [PubMed].
16. Vishwakarma M, Sahani IS. Comparative study of
complications of modified radical mastectomy and breast
conservation therapy in early invasive breast cancer.
International Journal of Surgery Science. 2019; 3(1): 01-03.
DOI: 10.33545/surgery.2019.v3.i1a.01.

REFERENCES
1. http://www.who.int/cancer/prevention/diagnosis-
screening/breast-cancer/en/. Accessed on 15.12.2019.
2. Blidaru A, Bordea CI, Pleșca M, Radu M. Compendiu de
specialități medico-chirurgicale/ Stoica V, Scripcariu V.
Editura Medicală, ISBN 978-973-39-0804-3, București.
2016;2:273,
3. Rostas JW, Dyess DL. Current Operative Management of
Breast Cancer: An Age of Smaller Resections and Bigger
Cures. Published online 2011 Dec 18. doi:
10.1155/2012/516417. [PubMed].
4. Franceschini G, Sanchez AM, Leone AD, Magno S,
Moschella F, Accetta C, Natale M, Giorgio DD,
Scaldaferri A, D'Archi S, Scardina L, Masetti R. Update on
the Surgical Management of Breast Cancer. Ann Ital Chir.
Mar-Apr 2015;86(2):89-99. [PubMed]
5. White J, Achuthan R, Turton P, Lansdown M. Breast
Conservation Surgery: State of the Art. Volume 2011,
Article ID 107981. [International journal of breast cancer]
6. Popescu I, Petelcu G, Ionescu M, Lesaru M, Anghel R,
Minea N, Oprea L, Median D, Tratat de Chirurgie, Vol. 8,
Partea 1: Chirurgie generală, ISBN-978-973-27-1679-3,
Editura Academiei Române; 2008. p. 792-793.
7. Rummel S, Hueman MT, Costantino N, Shriver CD,
Ellsworth RE. Tumour location within the breast: Does
tumour site have prognostic ability? Published online 2015
Jul 13. doi: 10.3332/ecancer.2015.552. [PubMed]
8. Sharma N, Narayan S, Sharma R, Kapoor A, Kumar N,
Nirban R. Association of comorbidities with breast cancer:
An observational study. Date of Web Publication 5-Jul-
2016. DOI: 10.4103/1119-0388.185449.
9. Franceschini G, Leone AD, Natale M, Sanchez MA, Masett
R. Conservative Surgery After Neoadjuvant Chemotherapy
in Patients With Operable Breast Cancer. Ann Ital Chir.
2018;89:290. [PubMed]
10. Masood S. Neoadjuvant chemotherapy in breast cancers.
Published online 2015 Sep 1. doi:
10.1177/1745505716677139. [PubMed

AMT, vol. 26, no. 1, 2021, p. 40

 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):41-43
DOI: 10.2478/amtsb-2021-0012
Online ISSN 2285-7079

INTRAMUSCULAR ABDOMINAL WALL ENDOMETRIOSIS, AN

UNUSUAL FINDING FOR GENERAL SURGEON

ALIN MIHEŢIU1, DAN BRATU2, OANA POPESCU3

1,2,3
“Lucian Blaga” University of Sibiu,1,2 Sibiu County Emergency Clinical Hospital

Keywords: endometriosis,
abdominal wall, cesarean
section, recurrence
Abstract: Defined as the ectopic development of uterine tissue outside the uterine cavity,
endometriosis is an increasingly common condition that can lead to various complications from
chronic pain syndrome, infertility, obstruction due extrinsic compression to malignancy of
endometriosis foci. Extrapelvic positioning of endometriosis is rare, diagnosis can be difficult both
clinically and imaging, and treatment does not always ensure the absence of recurrences.

INTRODUCTION Abdominal ultrasound shows in the thickness of the

Endometriosis was first described by Karl Freiherr left side of rectus abdominal muscle a hypoechoic formation,
von Rokitansky in 1860. inhomogeneous with microcalcifications, well vascularized, well
It is most common in the pelvis, ovaries, Douglas delimited with dimensions of 3/1.1/ 2.2 cm, without exceeding
pouch, uterine ligaments, or posterior cul-de-sac, but it may also the muscle fascia.
have extrapelvic locations in the abdominal wall, umbilical cord, Anamnestic and clinical examination raises the
ileum, colon, vulvar, or sacs of inguinal or femoral hernia. suspicion of parietal endometriosis.
The incidence of this condition in childbearing age
women is between 5-15%, localizations in the abdominal wall Figure no. 1. Ultrasound appearance - tumour in the
being rare. thickness of the rectus abdominal muscle
The appearance of endometriosis implants in the
abdominal wall is related to surgery, most commonly with
cesarean section, the tumours usually appear in the postoperative
scars.
The appearance of a tumour in the abdominal wall, in
the proximity of a scar, in the lower abdomen and especially the
painful manifestations in relation to the menstrual cycle,
indicates the suspicion an outbreak of endometriosis.
The treatment is a multimodal one, but surgical
excision remains the main choice as therapy, especially since
there is also the risk of malignant transformation.(1,2,3,4)

CASE REPORT
A 34-year-old patient presents a left paramedian
tumour in the lower abdomen, first discovered two years ago.
The patient is known to have epilepsy, cesarean section
(Pfannenstiel incision) 8 years ago.
For about a year and a half, the patient complains of
pain related to the menstrual cycle in the newly formed nodule,
pain that for about 3 months is no longer cyclical but
continuous.
On clinical examination, in left paramedian lower
abdomen, in the lower third of the left rectus abdominal muscle
and at about 8 cm from the post-cesarean scar, a tumour located
deep in the thickness of the muscular structures was highlighted.
The formation was sensitive to palpation with relatively regular
edges, hard consistency with the size around of 4/3 cm. No other
changes were found at clinical examination of the abdomen.
Lab tests were without pathological values, in normal
limits.
Surgery was performed under spinal anesthesia,
posterior to the anterior sheath of the left rectus abdominal
muscle, medial to the epigastric vessels (that are intercepted and
preserved) in muscle thickness, adherent to muscle fibers a
tumour of about 4/3/3cm, was highlighted.
The tumour was completely removed with safety
limits included.
Myoraphy, rectus abdominal aponeurosis closure and
skin suture were performed.
On the section, yellow-grey looking piece
The evolution was favourable, the patient being
discharged the next day.

1
Corresponding author: Alin Miheţiu, B-dul Corneliu Coposu, Nr. 2-4, Sibiu, România, E-mail: alin_mihetiu@yahoo.com, Phone: +40751 619292
Article received on 22.10.2020 and accepted for publication on 26.02.2021
AMT, vol. 26, no. 1, 2021, p. 41
 CLINICAL ASPECTS
Figures no. 2, 3. Resection piece and sectioned specimen
Figures no. 4, 5. Postoperative aspect in evolution (the dotted
line coincides with the post-cesarean scar)
The anatomopathological result showed fragments of
connective tissue and striated muscle with chronic inflammatory
changes (gigantocellular reaction, macrophage and histiocytic
reaction) around some endometriotic foci (glands and
endometrial stroma), hematological infiltrates with the presence
of hemosiderin pigment. The histological diagnosis was parietal
endometriosis.
Subsequent surgical checks showed no signs of local
recurrence.
DISCUSSIONS
Endometriosis is defined as the ectopic spread of
functional endometrial glans and stroma.(5)
In 1860, von Rokitansky described the first case of
endometriosis as “sarcoma”. In 1899, Russel first identified and
described the existence of endometrial tissue in the ovary.(5)
It affects between 5-15% of women of reproductive
age. The distribution of endometriosis can be pelvic or
extrapelvic. At the pelvic level, foci of endometriosis are found
in the bottom of the Douglas pouch, ovaries, in the reflection of
the peritoneum on the pelvic organs and in the uterine ligaments.
Extrapelvic localizations are rare and may involve the
abdominal wall, umbilicus, small intestine, appendix, large
intestine, kidneys, pleura, lungs, or central nervous system. (5)
Endometriosis of the abdominal wall with functional
endometrial tissue was first described in 1950.
Frequently this localization associates surgical
interventions in the background with an incidence between 0.03-
1.08%.(6,7)
The vast majority of cases of parietal endometriosis
have a history of gynecological surgery, usually after
hysterectomy, cesarean section or hysteroscopy.
Thus, it is considered that the risk of endometriosis in
the scar abdominal wall is 2.7% after obstetric interventions,
1.5% after gynecological interventions and 0.6% after
laparoscopic interventions.
The location of endometrial tumours in the abdominal
wall is common in the postoperative scar (especially in their
extremities) or in their vicinity.
Parietal locations distant from postoperative scars are
a rare finding. Also, parietal endometriosis has as favourite
place of development the subcutaneous cellular tissue, the
placement strictly intramuscularly or without the involvement of
the peritoneum is not frequently encountered.(1,2,8,9,10)
As a preventive measure, before abdominal closure it
is recommended to isolate the incision with sterile fields and
AMT, vol. 26, no. 1, 2021, p. 42
abundant lavage with saline solutions to limit the risk of
intraoperative contamination.(8)
Surgery is not the only way to develop parietal
endometriosis, the literature also describes cases of de novo
abdominal wall damage. Also, not only gynecological surgeries
have the potential for parietal endometriosis, cases being
described after laparoscopic treatment of inguinal hernia,
appendicitis or colorectal surgery.(11,12,13)
The etiopathogenesis of this condition is still unclear
and controversial, there are several theories that try to explain
how the outbreaks of endometriosis appear, spread and
proliferate.
The implantation theory - considered basically a
secondary implantation either by retrograde menstruation or
iatrogenic, surgical. However, menstrual reflux or gynecological
surgery does not always progress to endometriosis, the
explanation being that the immune system recognizes and
destroys endometrial cells outside the uterus. A dysfunction of
the immune system (with the genetic component) explains why
yet ectopic endometrial tissue implants develop.(9)
The theory of metaplasia (Meyer) describes the spread
of endometrial cells in the embryonic stage and their migration
along the coelomic cavity.(6)
Lymphatic (metastatic) theory explains the appearance
of endometrial structures in atypical places: brain, lung, lymph
nodes, myocardial tissue, etc.(14)
Alcohol consumption, heavy menstrual cycle,
obstructions in the evacuation of the menstrual cycle (Müllerian
abnormalities), prolonged exposure to estrogen and dioxin are
incriminating factors in the occurrence of endometriosis.
Clinically, parietal endometriosis may have
nonspecific symptoms, with suspicion of endometriosis rising
when the triad described by Esquivel is present: tumor,
catamenial pain, and history of cesarean section.(15)
If they are associated with dysmenorrhea or heavy
menstrual or intermenstrual bleeding, then the diagnosis can be
oriented from the clinical-anamnestic examination phase.
Superimposed pain on the menstrual cycle is the main
symptom that guides the clinician, but it is not always cyclical,
sometimes having a permanent character and making the
diagnosis more difficult.
The differential diagnosis is made with desmoid
tumors, granulomas, fetal necrosis, lipomas, hernias, metastatic
secondary determinations.
Imaging diagnosis is usually performed by ultrasound,
CT or MRI.
In ultrasound, the vast majority of nodules appear as
decrete solid masses, with a lower echogenicity than adipose
tissue or compared to the neighboring musculoskeletal planes.
The proximity to a postoperative scar or history of
endometriosis guides the diagnosis.(16,17,18)
MRI provides superior data to CT examination,
detecting smaller formations, periendometrial vascularization
and the boundary between the muscular, aponeurotic planes or
the degree of infiltration of deep structures.
Fine needle aspiration cytology (FNAC) increases the
risk of implantation of endometrial tissue on the puncture site.
The post-excision or post-FNAC histopathological
diagnosis is positive for endometriosis if two of the following
three elements are detected: endometrial glands, endometrial
stroma and hemosiderin laden macrophages.(1,18)
The treatment is a multidisciplinary one, the most used
being the hormonal treatment as an association with the surgical
or analgesic treatment. For abdominal wall endometriosis,
surgery is the only curative treatment.
Preoperatively, intra-femoral injection of
radioisotopes can be used to guide the excision of small foci of
 CLINICAL ASPECTS
endometriosis.
Sclerotherapy with ultrasound guided injection into
the lesion and high intensity focused ultrasound ablation used
preoperatively appear to reduce bleeding and limit the size of
the resection and decrease the risk of recurrence.(19)
Endometriosis has a 1% risk of malignancy.
80% of malignancies occur in the ovary and 20% in
other locations (including the abdominal wall). The most
common types of malignancies are endometrial carcinoma
(70%), sarcoma (25%) and clear cell carcinoma (5%). Clear cell
carcinoma and endometrial carcinoma have the lowest survival
rate (44% mortality in the months immediately following
diagnosis).(20,21)
General surgeons often misdiagnose parietal
enometriosis due to its rarity interpreting it as a tumour of
another nature. Thus in a study that considered cases of
endometriosis of the abdominal wall, treated by a general
surgeon 55.55% of them they didn’t suspected endometriosis
preoperatively.(22,23)
Although it is a rare entity, general surgeons must also
consider this type of tumour, so that the surgical strategy to be
such as to avoid the implantation of endometrial cells, thus
avoiding local recurrence.
CONCLUSIONS
Endometriosis of the abdominal wall is an
increasingly common condition in the context of the
proliferation of gynecological and obstetric procedures.
The diagnosis can be guided by clinical and imaging
examination but is established by histologic exam.
Surgical removal of the endometrial implant remains
the best therapeutic option, reducing the risk of recurrence or
progression to malignancy.
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9. Paşalega M, Mirea C, Vîlcea ID, et al. Parietal abdominal
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Embryol. 2011;52(1 Suppl):503-508.
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doi:10.1016/j.jss.2010.07.043.
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Mattei, A. Abdominal Wall Endometriosis on the Right
Port Site After Laparoscopy: Case Report and Literature
Review. The Ochsner Journal. 2015;15:251-5.
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T. A case of abdominal wall endometriosis after
appendectomy. Journal of Japan Surgical Association.
2012;73(4):993-996.
13. Ducarme G, Uzan M, Poncelet C. Endometriosis
mimicking hernia recurrence. Hernia. 2007;11(2):175-177.
doi:10.1007/s10029-006-0159-2.
14. Blumenthal R, Samoszuk M, Taylor A, Brown G,
Alisauskas R, Goldenberg D. Degranulating Eosinophils in
Human Endometriosis. The American journal of pathology.
156. 1581-8.(2000) 10.1016/S0002-9440(10)65030-4.
15. Esquivel-Estrada V, Briones-Garduño JC, Mondragón-
Ballesteros R. Implante de endometriosis en cicatriz de
operación cesárea [Endometriosis implant in cesarean
section surgical scar]. Cir Cir. 2004;72(2):113-115.
16. Savelli L, Manuzzi L, Di Donato N, et al. Endometriosis of
the abdominal wall: ultrasonographic and Doppler
characteristics. Ultrasound Obstet Gynecol.
2012;39(3):336-340. doi:10.1002/uog.10052.
17. Vagholkar K, Vagholkar S. Abdominal Wall
Endometrioma: A Diagnostic Enigma-A Case Report and
Review of the Literature. Case Rep Obstet Gynecol.
2019;2019:6831545. Published 2019 Mar 26.
doi:10.1155/2019/6831545.
18. Gupta RK. Fine-needle aspiration cytodiagnosis of
endometriosis in cesarean section scar and rectus sheath
mass lesions - a study of seven cases. Diagn
Cytopathol.2008;36(4):224-226.doi:10.1002/dc.20797.
19. Vitral GSF, Salgado HC, Rangel JMC. Use of radioguided
surgery in abdominal wall endometriosis: An innovative
approach. World J Nucl Med. 2018;17(3):204-
206.doi:10.4103/wjnm.WJNM_47_17.
20. Kajiyama H, Suzuki S, Yoshihara M, et al. Endometriosis
and cancer. Free Radic Biol Med. 2019;133:186-192.
doi:10.1016/j.freeradbiomed. 2018.12.015.
21. Carsote M, Terzea DC, Valea A, Gheorghisan-Galateanu
AA. Abdominal wall endometriosis (a narrative review).
Int J Med Sci. 2020;17(4):536-542. Published 2020 Feb 10.
doi:10.7150/ijms.38679.
22. Oh EM, Lee WS, Kang JM, Choi ST, Kim KK, Lee WK. A
Surgeon's Perspective of Abdominal Wall Endometriosis at
a Caesarean Section Incision: Nine Cases in a Single
Institution. Surg Res Pract. 2014;2014:765372.
doi:10.1155/2014/765372.
23. Horton JD, Dezee KJ, Ahnfeldt EP, Wagner M. Abdominal
wall endometriosis:a surgeon's perspective and review of
445 cases. Am J Surg. 2008;196(2):207-212.
doi:10.1016/j.amjsurg.2007.07.035.
 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):44-46
DOI: 10.2478/amtsb-2021-0013
Online ISSN 2285-7079

LAPAROSCOPIC APPENDECTOMY VERSUS OPEN

APPENDECTOMY IN CHILDREN: EVOLUTION OVER TIME

LAURA DUMITRICĂ1, LUMINIŢA DOBROTĂ2, BOGDAN NEAMŢU3

1,3
Pediatric Clinic Hospital Sibiu, 2 “Lucian Blaga” University of Sibiu,
3
Pediatric Clinic-Research and Telemedicine Center in Neurological Diseases in Children, Sibiu

Keywords: appendicitis, Abstract: Laparoscopic appendicitis surgery is accepted in more and more centers around the world.
laparoscopic Studies and meta-analyses of studies have shown that laparoscopic appendicitis is a feasible and safe
appendectomy, open procedure with numerous clinical benefits, such as shorter postoperative ileus, lower incidence of
appendectomy, wound infection, lower postoperative pain and duration, recurrence faster to activities. Because
laparoscopy, comparative laparoscopic appendectomy has been associated with a reduced risk of surgical complications, it may
evaluation provide a better alternative versus open surgery. A review of data relevant to the evaluation of
laparoscopic appendectomy versus open appendectomy as reflected in the literature of the last 2
decades would be relevant for the growing progressive interest of laparoscopic surgery for acute
appendicitis and for its comparative evaluation with classical open appendicitis intervention.

INTRODUCTION laparoscopic appendectomy should remain an option in both

Laparoscopic appendicitis (LAP) surgery is accepted in
more and more centres around the world. Studies and meta-
analyses of studies have shown that LA is a feasible and safe
procedure with numerous clinical benefits, such as shorter
postoperative ileus, lower incidence of wound infection, lower
postoperative pain and duration, recurrence faster to activities.
A review of data relevant to the evaluation of
laparoscopic appendectomy (LA) vs. Open appendectomy (OA)
as reflected in the literature of the last 2 decades would be relevant
for the increasing progressive interest of laparoscopic surgery for
acute appendicitis and for its comparative evaluation with
classical open OA intervention.
AIM
The main aim consists in a brief review of the relevant
data for the stated topic as they are reflected in the literature of the
last 2 decades as well as highlighting the progress of LA and how
this surgical technique has been evaluated compared to OA,
evolving in the last 2 decades.
MATERIALS AND METHODS
Consulting the specialized medical literature regarding
the stated topic using as search keywords: laparoscopic
appendectomy, open appendectomy, comparative evaluation.
Selecting the significant studies for the last 20 years, a
selection based on the relevance of the study for the comparative
evaluation of LA vs OA and the evolution over time of this
concept of the comparative evaluation of the two surgical
techniques.
RESULTS AND DISCUSSIONS
In 2004, the question of the opportunity of laparoscopic
appendectomy was still raised when it was discussed in
comparison with the classic intervention, respectively with the
open appendectomy.
In this context, Hitoshi Ykeda concluded that
children with uncomplicated appendicitis and those with
complicated appendicitis. The author pleads for this option which,
although it was more expensive than the classic intervention and
requires a longer operating time, was distinguished from it by the
shorter duration of hospitalization (for those with uncomplicated
appendicitis).(1)
In both types of appendicitis, uncomplicated and
complicated too, there were no significant differences between
laparoscopic and open appendectomies in terms of complications
or their incidence.
Finally, the author concludes that LA may remain an
option provided that the advantages and disadvantages of the
procedure are considered.(1)
In the same context, 7 years later (2011), Ching-Chung
Tsai et al. conducted a study in which they aim to answer the
question of whether laparoscopic appendectomy is an alternative
therapeutic tool to classical open appendectomy for all types of
appendicitis, respectively simple, perforated and with abscess.(2)
The authors conclude that laparoscopic appendectomy
can be considered a safe alternative for both perforated
appendicitis and abscessed appendicitis. The laparoscopic
intervention results in statistically significant postoperative with
fewer minor complications for perforated appendicitis and with
fewer major complications for abscessed appendicitis compared to
open (classic) appendectomy, (9/32 compared to 0/20, p = 0.009)
and respectively (9/26 compared to 1/24, p = 0.011).(2)
In the same year, Steven L. Lee published a
retrospective cohort study that included 7.650 children, 3.551 with
LA and 4.099 with OA.(3) Assuming that the results of LA will
be similar to OA in children of all ages, however, finds that LA is
the preferred operation for children with appendicitis, because LA
compared to OA was associated with a low risk of wound
infection, abscess drainage and length of hospital stay.(3)
In the study signed by Hossein Masoomi et al. in 2012
(USA) the authors aim to explore the benefits of laparoscopic
appendectomy on a case series of 212.958 children with

Corresponding author: Luminiţa Dobrotă, Str. Lucian Blaga, Nr. 2A, Sibiu, Romania, E-mail: luminitadobrota@yahoo.com, Phone: +40722 501145
2

Article received on 01.09.2020 and accepted for publication on 26.02.2021

AMT, vol. 26, no. 1, 2021, p. 44
 CLINICAL ASPECTS
emergency operated appendicitis over a period of 2 years,
according to 2006-2008 Data from The Nationwide Inpatient
Sample (NIS).(4) In cases of non-perforated appendicitis, LA was
associated with a percentage of comparable overall complications
(LA, 2,56% vs OA, 2.66%; p 0,26), shorter length of hospital stay
(LA, 1,6 days vs OA, 2,0 days; p < 0,01), comparable mortality
(LA, 0,01% vs OA, 0,02%; p 0,25) and higher hospital fees (LA,
20,328 USD vs. OA, 16,830 USD; p < 0,01). In cases of
perforated appendicitis, LA was associated with a lower
percentage of general complications (LA, 16,03% vs OA, 18,07%;
p < 0,01), shorter length of hospital stay (LA, 5,1 days vs OA, 5,8
days; p < 0,01), lower mortality (LA, 0,0% vs OA, 0,06%; p <
0.01) and similar hospital expenses (LA, 33,361 USD compared
to OA, 33, 662 USD, p = 0,71).(4)
The authors conclude that LA (performed in 56,9% of
cases) is:
- safe in the case of children with acute perforated or non-
perforated appendicitis;
- associated with a shorter hospital stay than OA;
- associated with lower complications and mortality than OA
in both non-perforated and perforated appendages.(4)
It is mentioned, however, that in cases of non-perforated
appendicitis, the benefits are modest and associated with higher
hospitalization costs.(4)
Assuming that LA or open OA are associated with hospital
procedural preferences, Jun Tashiro et al. in 2016, consulted the
database for children hospitalized in the USA during 1997-2009
for simple appendicitis and complicated.(5) The authors evaluated
LA vs. OA comparatively according to a series of parameters and
complications (symptoms, duration of hospitalization, infusion
treatment, surgical wound infections, perforations/lacerations,
total hospitalization costs) in two different hypostases of simple
and complicated appendicitis.(5)
Selective analysis of simple appendicitis (91.118 cases with
LA vs 97.496 with OA), LA vs OA generated the following data:
- an increased percentage of infusions (1,7%),
- fewer wound infections (0,6%),
- a lower percentage of perforations/lacerations (0,3%),
- a shorter length of hospital stay (1,7 versus 2,1 days) but
higher total hospitalization costs (19.501 USD vs. 13.089
USD).
For complicated appendicitis (28.793 cases with LA vs.
30.782 with OA), LA vs. OA presented:
- higher percentage of nausea/vomiting (1,9%),
- lower percentage of surgical wound infections (0,5%) and
cases that required infusions (0,6%).
- shorter length of hospital stay (5,1 vs. 5,9 days) but higher
total costs (32.251 vs. 28.209 USD).
The discussions, results and conclusions outline the
following aspects: complications and the use of appendicitis
resources are associated with surgical technique and hospital
procedure preferences.
Hospitals that prefer laparoscopic interventions had:
- higher percentages of complications with the OA technique
for complicated appendicitis, and
- higher expenses, regardless of the technique of
appendectomy or the type of appendicitis.
Comparing “Laparoscopic vs. Open Appendectomy in
children with complicated appendicitis, 2017” authors of the
mentioned study, Mohammad G. Kirallah et al., concludes that
LA vs. OP was an appropriate, efficient and safe procedure in
complicated cases, in addition to being associated with an
operating time and a lower percentage of complications.(6)
Also, in 2017, Liping Dai et al published in the United
European Gastroenterology Journal a meta-analysis of controlled
and randomized studies.(7) The authors aim to evaluate LA vs OA
in adults and children in terms of the following criteria: type of
AMT, vol. 26, no. 1, 2021, p. 45
appendicitis, postoperative complications, percentage of operative
re-interventions, operative time, duration of postoperative
hospitalization, return to normal activity. The analysis of the
subgroups of children did not show significant differences
between the two techniques in terms of wound infection,
postoperative complications, duration of postoperative
hospitalization and return to normal activity.(7)
At the end of the study, it is concluded that high-
performance LA in adults can be recommended as an effective
and safe procedure for acute appendicitis, but for children
additional high-quality randomized studies comparing the two
techniques would be needed.(7)
Roshan Ali et al., in 2017, addresses the comparative
assessment of LA vs OA in a controlled and randomized study in
developing countries.(8) The study proposes this evaluation
according to the following parameters: length of hospital stay,
operative time and postoperative wound infection. The results did
show that the operative time was 56 ± 24 minutes in the LA group
and 39 ± 8 minutes in the OA group (p <0,0001 in favor of OA);
the mean length of hospital stay was 34 ± 13 hours for the LA
group and 40 ± 11 hours for the OA group (p = 0,01 in favor of
LA). The results did not show a significant association of wound
infection between the two groups (p = 0,31). In conclusion, it is
specified that no statistically significant differences were found
between the 2 groups in terms of length of hospital stay and
postoperative wound infection. However, the authors mention, the
laparoscopic procedure is more technically difficult.(8)
Ping Li et al., in 2017, publishes an article presenting a
retrospective review of patients operated on by the two techniques
for abscessed appendicitis between 2005 and 2016, therewith
proposing a comparative assessment of recovery and
postoperative complications in LA versus OA.(9) Patients with
LA received a rapid postoperative recovery of gastrointestinal
function, such as the first bowel movement (RR = 0,52 [95% CI
0,44-0,69] p < 0,001, respectively RR = 0,53 [95% CI, 0,41-0,76]
p 0,001) compared to patients with OA. In addition, the number of
leukocytes (RR = 0,56 [95% CI, 0,46-0,73] p < 0,001) and C-
reactive protein, CRP (RR = 0,58 [95% CI 0,86] p 0,11) as
postoperative inflammatory tests recorded lower values in patients
with LA vs. patients with OA. A general percentage of
postoperative complications, including surgical wound infection
(OR = 0,38; 95% CI; 0,18-0,81; p 0,008) and incision dehiscence
(OR = 0,06; 95 % CI; p < 0.001) was observed in patients with
LA compared to OA. LA has been feasible and effective for
abscessed appendicitis and associated with beneficial clinical
effects, such as recovery of postoperative gastrointestinal function
and reduced postoperative complications. LA should be seriously
considered to be the first line of choice.(9)
Kengo Inagaki et al., in 2019, publishes in the Journal
of Surgical Research a study that aims to evaluate the associated
factors, complications and re-admissions related to the 2 types of
LA and OA interventions, stating that the particularities of the
patient with OA are weak characterized.(10)
Factors associated with OA were the percentage of
readmission after 30 days and the length of hospital stay.
Of the 46.147 children operated for appendicitis, 85,2% benefited
from LA. Laparoscopic appendectomy was associated with a
shorter length of hospital stay (incidence ratio: 0,77 [95% CI:
0,69-0,87]), fewer re-admissions with wound infection, without
being motivated by readmission after 30 days or readmission for
intra-abdominal abscess.
Open appendectomy has been associated with smaller
hospitals (OR: 3,01 [95% CI: 1,81-5,01]), rural hospitals (OR:
2,36 [95% CI: 1,63-3,40]), public insurance (OR: 1,19 [95% CI:
1,03-1,36]), lower income neighbourhood residence (OR: 1,40
[95% CI: 1,06-1,86]), younger than 5 years old of age (OR: 5,00
[95% CI: 3,64-6,86], complicated - abscessed appendicitis (OR:
 CLINICAL ASPECTS
1,91 [IC 95%: 1,58-2,31]). The conclusions of the study show on
the one hand how clinical factors and the rural/didactic status of
treatment hospitals play a role in choosing the surgical approach,
and in the other hand how awareness of patient and hospital-
related factors associated with OA may influence resource
allocation or improve access to in-care.
Zhi Xuan Low et al., in 2019, start from the premise
that LA is preferred vs. OA in patients with uncomplicated
appendicitis. However, for patients with complicated appendicitis
(suppurative, gangrenous or perforated or with periappendicular
abscess formation), the decision to perform OA or LA remains
unclear.(11) Following the PRISMA guidelines, the search in
databases from 1997 to 2017 (Cochrane, Medline, PubMed,
Scopus, Ovidiu, Embase and Web of Knowledge) and the analysis
of the study subgroups of randomized control, was performed
using RevMan 5.3. The assessment of methodological and
statistical heterogeneity was performed, and 7 randomized control
studies (296 LA versus 373 OA) and 33 control case studies
(3.106 LA versus 4.149 OA) were analysed. LA vs OA has a
shorter hospital stay (weighted mean difference - WMD = - 0,96
[95% CI 1,47-0,45]) and a lower rate of operative wound infection
(OR 0,37 [95%CI 0,25-0,54]), although the percentages of intra-
abdominal abscess formation were similar (OR 1,01 [95% CI
0,71-1,43]). LA had lower readmission rates, lower incidence of
postoperative ileus or intestinal obstruction, lower incidence of
need for reoperation, and a shorter time to resume oral intake. The
operative time for OA was shorter than LA (WMD = 12,44 [95%
CI 2,00-22,87]). The conclusion of the study LA should be the
procedure of choice for pediatric patients with complicated
appendicitis because the percentages of postoperative intra-
abdominal abscess are similar for both techniques.(11)
Ritvik Resutra and Rajive Gupta, in 2020, publish in the
International Journal of Minimal Access Surgery a study
evaluating the technical feasibility and safety of LA in acute
appendicitis versus the results obtained with OA.(12) A total of
400 pediatric patients with acute appendicitis, 200 by LA and 200
by OA were operated on by a single surgeon at various private
hospitals in Jammu and Kashmir, India, between June 2017 and
May 2020. The following were evaluated: operating time,
duration of hospitalization, postoperative pain, percentage of
complications, time required to resume activity and patient
satisfaction correlated with the cosmetics of the intervention.
Better results with LA (vs. OA) were: significantly lower
postoperative pain, faster recovery, resumption of activities
earlier, reduction of postoperative complications and better
cosmetic patient satisfaction. The conclusion of the study was that
the LA is a safe and feasible technique for experts, results
comparable to OA, without an increase in complications being the
procedure of choice for the treatment of acute appendicitis.
CONCLUSIONS
Laparoscopic appendicitis surgery is accepted in more
and more centres around the world. Studies and meta-analyses of
studies have shown that LA is a feasible and safe procedure with
many clinical benefits, such as: shorter postoperative ileus, lower
incidence of wound infection, lower postoperative pain, and faster
return to normal work activities.
Because LA has been associated with a reduced risk of
surgical complications, it may provide a better alternative vs. OP
is currently a first choice option.
In the age group specific to younger children, there are
not yet enough studies to evaluate LA vs OP. In this regard,
additional high-quality randomized studies are needed to compare
the two techniques in children.
Acknowlegdement:
Part of the analysis has been conducted in the Pediatric
Clinic Hospital Sibiu, within Research and Telemedicine Center
AMT, vol. 26, no. 1, 2021, p. 46
in Neurological Diseases in Children - CEFORATEN project
(ID928 SMIS-CSNR 13605) financed by ANCSI with the grant
number 432 / 21. 12. 2012 thru the Sectoral Operational
Programme „Increase of Economic Competitiveness”.
REFERENCES
1. Ikeda H, Ishimaru Y, Takayasu H, Okamura K, Kisaki Y,
Kosighaya JF. Laparoscopic versus open appendectomy in
children with uncomplicated and complicated appendicitis;
Journal of Pediatric Surgery. 2004;39(11):1680-1685,
https://doi.org/10.1016/j.jpedsurg.2004.07.018.
2. Tsai CC, Lee SY, Huang FC. Laparoscopic versus Open
Appendectomy in the Management of all stages of acute
appendicitis in children: a retrospective study; Pediatrics and
Neonatology. 2012;53:289e294.
http://dx.doi.org/10.1016/j.pedneo.2012.07.002.
3. Lee SL, Yaghoubian A, Kaji A. Laparoscopic vs Open
Appendectomy in Children, Outcomes Comparison Based on
Age, Sex, and Perforation Status; Arch Surg.
2011;146(10):1118-1121. Published online June 20, 2011.
doi:10.1001/archsurg.2011.144.
4. Masoomi H, Mills S, Dolich MO, Ketana N, Carmichael JC,
Nguyen NT, Stamos MJ. Comparison of Outcomes of
Laparoscopic Versus Open Appendectomy in Children: Data
from The Nationwide Inpatient Sample (NIS), 2006–2008;
World Journal of Surgery March 2012;36(3):573-578.
5. Tashiro J, Einstein SA, Perez EA, Bronson SN, Lasko DS,
Sola JE. Hospital preference of laparoscopic versus open
appendectomy: Effects on outcomes in simple and
complicated appendicitis; jpedsurg. 2016.02.028,
https://doi.org/10.1016/j.
6. Kirallah MG, Eldesouki NI, Elzanaty AA, Ismail KA.
Laparoscopic versus open appendectomy in children with
complicated appendicitis; Annals of Pediatric Surgery.
2017;13(1):17-20. January 2017, DOI:
10.1097/01.XPS.0000496987.42542.dd.
7. Dai L, Shuai J. Laparoscopic versus open appendectomy in
adults and children: A meta-analysis of randomized
controlled trials; Gastroenterology Journal 2017;5(4):542–
553, DOI: 10.1177/2050640616661931.
8. Roshan A, et al. Laparoscopic versus open appendectomy in
children: a randomized controlled trial from a developing
country; J Pediatr Surg. 2018 Feb;53(2):247-249.
doi:10.1016/j.jpedsurg.2017.11.022. Epub 2017 Nov 14.
9. Li P, Han Y, Yang Y, Guo H, Hao F, Tang Y, Guo C.
Retrospective review of laparoscopic versus open surgery in
the treatment of appendiceal abscess in pediatric patients;
Medicine (Baltimore). 2017 Jul;96(30):e7514. doi:
10.1097/MD.0000000000007514.
10. Inagaki K, Blackshear C, Morris MW, Hobbs CV. Pediatric
Appendicitis–Factors Associated With Surgical Approach,
Complications, and Readmission; Journal of Surgical
Research; October 16, 2019,
https://doi.org/10.1016/j.jss.2019.09.031
11. Low ZX, Bonney GK, So JBY, Loh DL, Ng JJ.
Laparoscopic versus open appendectomy in pediatric patients
with complicated appendicitis: a meta-analysis; Surg Endosc.
2019 Dec;33(12):4066-4077. doi: 10.1007/s00464-019-
06709-x. Epub 2019 Feb 25.
12. Resutra R, Gupta R. Comparative Study of Laparoscopic
Appendectomy versus Open Appendectomy for the
Treatment of Acute Appendicitis. International Journal of
Minimal Access Surgery, 2020, Volume 1 | Article 1005.
 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):47-50
DOI: 10.2478/amtsb-2021-0014
Online ISSN 2285-7079

PREDICTIVE BIOLOGICAL MARKERS FOR ANASTOMOTIC

LEAKAGE AFTER CURATIVE SURGERY FOR COLORECTAL
CANCER

ERIKA BIMBÓ-SZUHAI1, ADRIAN MAGHIAR2, ANCA HUNIADI3, MIRCEA ȘANDOR4, MIHAI

BOTEA5, CODRUȚA MACOVEI6, CORINA BEIUȘAN7, CLAUDIA TEODORA JUDEA PUSTA8
1,2,3,4,5,6,7,8
University of Oradea

Keywords: colorectal Abstract: anastomotic leakage is one of the most important postoperative complications for colorectal
cancer, anastomotic cancer patients undergoing curative surgery. Early recognition of patients in risk would be essential
leakage, CRP level, for preventing the high mortality rates associated with these complications. C reactive protein (PCR),
granulocyte/lymphocyte tumour necrosis factor (TNF-alpha), cortisol levels and granulocyte/lymphocyte ratio (G/L) were
ratio compared in this period in patients who developed leakage vs patients without this complication.
Material and methods: 52 colorectal cancer patients who underwent elective surgery in a private
clinical hospital were evaluated preoperatively and postoperatively for the patients. Results: 14
patients (26,9%) developed clinically significant anastomotic leakage. The best cut-off value for
preoperative G/L ratio of 5,8 had sensitivity of 71,43% and specificity of 73,68%. Conclusions:
Preoperative G/L ratio can be used as a largely available tool for identifying the colorectal cancer
patients at high risk for anastomotic leakage.

INTRODUCTION procedure it is well known that increasing PCR levels in 2 – 3

Anastomotic leakage is a severe complication after
colorectal surgery associated with a high perioperative mortality
and morbidity, prolonged hospital admittance and higher care
expenses. This complication is also an independent risk factor
for a reserved prognosis in patients undergoing curative
colorectal surgery procedure, resulting in a higher chance of
local recurrence and general survival. There are multiple
associated risk factors for anastomotic leakage, and as a
consequence it is complicated to predict this complication for a
certain patient.
Despite evolution in understanding risk factors for
anastomotic leakage and surgical technique development,
anastomotic leakage remains an important complication that
occurs in some patients without an evident cause and without
any known risk factors. Early diagnosis of anastomotic leakage
should be possible as a way to reduce morbidity and associated
mortality.
The role of cytokine and Alpha-TNF, interleukin 1
and interleukin 6 in stimulation of production of acute phase
protein is well-known and its release in the postoperative phase
could be correlated with surgical stress extension and increased
rate of complications.
Reactive C protein (PCR), is an acute phase protein -
synthesized in the liver- which was intensively studied as a
predictive marker for postoperative complication in abdominal
surgery(1).
Due to relatively short half-life (19 h), PCR is a
trustful marker for predicting systemic inflammatory response
secondary to surgical procedures and even for complications,
with a sharp drop in his rates as the patient recovers.(2) As for
anastomotic leakage secondary to curative colorectal surgical
days in postoperative period is associated with higher risk of
developing this complication.(3)
Another marker for systemic inflammatory response
could be leukocyte formula.(4) It is known that leukocytes
express cholinergic and adrenergic receptors.(5) As a
consequence, changes in the vegetative nervous system, as in
stress inflammation may affect leukocytes that carry cholinergic
and adrenergic receptors.(6) It is believed that during operation,
neutrophils and lymphocytes are differently affected so they
intermediate different actions.
An inborn immune answer against different stimuli
has granulocytosis as response, and lymphopenia also observed
in patients with cancer in advanced phases.(7) Granulocytes and
lymphocytes show changes as a response to biochemical
mediators and stress hormones equally in quantity and quality.
Improving clinical status after surgical procedures also concur
increasing lymphocyte level and decreasing granulocyte levels
at the same time.(8)
Based on these observations it is reasonable to
presume its clinical value for granulocytes / lymphocytes rates.
AIM
Under the circumstances we proposed that biomarkers
identification which permit rapid patient check up for high risk
of developing anastomotic leakage after a curative surgical
procedure for colorectal cancer.
Analysing the current literature and the current routine
available biological markers in our surgery department we
proposed the next following markers in pre- and post-operative
day 1: alpha TNF ,serum cortisol levels, PCR levels and the
granulocytes/lymphocytes rates (G/L).

1
Corresponding author: Bimbó-Szuhai Erika, Str. Delavrancea, Nr. 13, Ap. 2. 410058, Oradea, România, E-mail: bszera@gmail.com, Phone: +40740
154365
Article received on 25.11.2020 and accepted for publication on 26.02.2021
AMT, vol. 26, no. 1, 2021, p. 47
 CLINICAL ASPECTS
MATERIALS AND METHODS several days in the post-operative period would increase the
Our clinical study, a prospective observational cohort precision of predictors for anastomotic leakage but also the
study, has been conducted in the Surgery Department of Oradea correlation in between pre-and postoperative biological markers.
Pelican Clinical Hospital between January 2015-August 2019. It is possible that some patients may have a subclinical
The research has been analysed and approved by the hospital’s anastomotic leakage undiagnosed which may imply inevitable
ethics committee and in case of identifying an eligible patient, statistical error. But this subclinical anastomotic leakage usually
we proceeded to present and sign an informed consent protocol. has favourable evolution without treatment and the purpose of
Patients’ inclusion criteria for colorectal cancer confirmed after our study is to identify the patients with complications which in
colonoscopy and histological confirmed results. turn implies increased morbidity and mortality.
Exclusion criteria: Age under 18, pregnant patient,
evident distant metastasis, any pre-existing inflammatory bowel RESULTS
disease, or rheumatoid arthritis, clinical evident preoperative 14 patients (26,9%) from 52 patients enrolled in the
infection, postoperative infection from another proved source study, presented anastomotic leakage in the postoperative
different form anastomotic leakage. The blood samples were period. The main characteristic for the two groups are presented
taken a-jèun, by puncturing a peripheral vein. The blood in the table no. 1.
sampling was made by blood prelevation from a vein in a
vacutainer with anticoagulant for blood samples for whole blood Table no. 1. Main characteristic for two groups
count-leukocytes formula (for G/L ratio), and in vacutainer Lot A Lot B
p
Basic features (statistical
without anticoagulant in case of biochemical determinations n=14 n=38
significance)
such as alpha-TNF, serum cortisol levels and CPR levels. The Sex (M/F) 10/4 26/12 0,8964
following analysing methods were applied are automated Age (year) – average 62,42 70,26
0,0342
analyser on fluorescent principle in cytometric flux using (±DS) (±12,04) (±11,31)
semiconductor LASER, and hydrodynamic focusing for Resident (U/R) 4/10 16/22 0,5697
Tumor stage (%)
complete blood count for leukocytes formula, chemiluminescent Dukes A 2 (14,4%) 11 (28,9%)
immunochemical detection method for alpha-TNF, latex 0,4070
Dukes B 6 (42,8%) 17 (44,8%)
immunoturbidimetric method for CRP, and immunochemical Dukes C 6 (42,8%) 10 (26,3%)
detection method by electrochemiluminescence for serum Type of surgery
Laparotomy 10 (71,4%) 14 (36,9%) 0,0567
cortisol levels. Besides these lab findings, the study file has been Laparoscopy 4 (28,6%) 24 (63,1%)
completed with the following date for each patient enrolled: age, Tumor location
6 (42,9%) 8 (21,1%)
sex, environment, tumoral stage (Duke’s classification), type of Ascending colon
0 (0,0%) 8 (21,1%)
Transverse colon
surgical procedure- classic or laparoscopic approach- and Colon descending
0 (0,0%) 10 (26,3%) 0,0346
tumoral site. Anastomotic leakage was diagnosed by clinical 6 (42,9%) 8 (21,1%)
Sigmoid colon
2 (14,2%) 4 (10,5%)
findings of a peritonitis and/or evident free fecaloide liquid in Recto-sigmoid colon
abdominal cavity or on the drain tube confirmed through M = male, F = female, DS = standard deviation, U = urban, R = rural
abdominal and pelvic CT with IV contrast substance or The data presented indicates that neither the sex of a
anorectal. The two groups were built based on this factor. Group patient nor the environment does not influence the risk of
A with anastomotic leakage and Group B without anastomotic developing anastomotic leakage, in post-operative period it is
leakage diagnosed. maintained the prevalence of male patients and patients from
Statistical analyses: Continuous variables will be rural areas. Elderly patients seem to benefit from their age, this
presented under an arithmetic average, respectively geometrical complication being more frequent in the young patients in our
one with a standard deviation - in brackets - having normal groups. The stage of developed cancer among the groups did not
distribution some of them after a logarithmic transformation. influence the postoperative complications. complication. In
Categorical variables will be described by number of contrast, the tumour site has presented significant differences
observations and percentages in brackets-significant differences between patients who developed anastomotic leakage compared
from statistical point of view where considered at lower values two those who did not have it: surgical procedures performed
then 0.05 off zeros hypothesis(p). Statistical tests were done for tumours located on transverse and descending colon have not
with the help of MedCalc° version 12.5.0.0 (MedCalc° developed postoperative complications at all in this group
Software, Mariakerke, Belgium). Comparison of the two groups (figure no. 1).
for categorical variables has been done with chi square cast and
chi square cast with Yates correction when used in table 2×2; Figure no. 1. Incidence of anastomotic leakage for different
and for continuous variables with the help of student test for locations of tumour
independent groups (with or without logarithmic transformation
as needed after case). For correlation check-up in between
biological markers it has been used.
Pearson correlation factor. ROC curves (receiver
operator characteristic) and the area under the curves (AUC)
were used to compare diagnostic tests and for determination of
limit values that indicates the risk of anastomotic leakage. ROC
curves are points terminated by real positive values (sensitive)
and false positive one (1-specificity) for each value detected
(level of PCR or G/L rate).
Limitations of the study: The power of the study
statistically depends on the number of cases for each group and
the number of patients with postoperative complication.
Fortunately, this number was not high, but this aspect of the
study limits the importance of the conclusion referring to risk Determination of biological markers have been giving
factors. Monitoring the evolution of biological markers during us the results in the two groups of patients (table no. 2). We can
AMT, vol. 26, no. 1, 2021, p. 48
 CLINICAL ASPECTS
easily observe, from a statistical point of view, that significant accurate identification of the patients with an increased risk for
differences have been registered in determination of the postoperative complication, we have tried to identify some
postoperative period for PCR and the G/L rate in the preoperator limiting values for these two markers. Analysing ROC curves
period. All the other markers have not been valuable in for both determinations, we found the following limits with best
identifying the patients with risk of developing postoperative values for sensibility and specificity: for PCR the limit of 71
anastomotic leakage. mg/dl with an sensibility of 71,43% ( IC 95%: 41,9-91,6) and
Knowing the role of PCR in identifying patients at risk specificity of 68,42% ( IC95%: 51,3-82,5); for G/L rate the 5,8
for anastomotic leakage after surgical procedures and seeing the units with sensibility of 71,43% ( IC 95%:41,9-91,6) and
values of the results, we proceeded in analysing the correlation specificity of 73,68% (IC 95%: 56,9-82,5).
between the modification found in the WBC formula and the Moreover, we made the observation that all patients
perioperative PCR value evolution considering all 104 with GL rate above 10 units in the postoperative period
prelevated biological blood samples. In these conditions we developed anastomotic leakage. Combining the two criteria
succeeded to demonstrate a strong linear correlation between (G/L rate above 5,8 and postoperative day 1 PCR above 71
these two values with an important statistical significance mg/dl) does not come with benefits in the sense of increased
(r=0,3083, p=0,0015) (figure no. 2). sensibility, but it becomes an excellent excluding test with a
96,97% of specificity (IC 95%: 84,24-99,92%) and negative
Table no. 2. Values of biological markers predictive value of 80% (IC 95%:64,3590,95).
p
Lot A Lot B DISCUSSIONS
Biological markers (statistical
n=14 n=38 The incidence of anastomotic leakage after colorectal
significance)
cancer surgery varies between 1% and 40% depending on the
TNF-α – average (±DS)
pg/ml 14,41 13,89 definition of leakage and the type of resection.(8,9) The
preoperatively (±3,2) (±11,4) 0,2046 incidence observed in our study is 26.9% which is in the average
postoperatively 8,87 9,75 0,5714 range. This complication is frequently associated with a high
day 1 (±1,6) (±8,9) mortality rate between 4% and 15% and under these
Cortisol – average (±DS) circumstances the early diagnosis is very important. But an early
nmol/l 153,99 143,63 diagnosis of an anastomotic leakage is not always easy in
preoperatively (±86,3) (±137,2) 0,7942 immediate postoperative period due to reduced clinical evidence
postoperatively 119,40 133,24 0,7440
in this period, a fact that may contribute to an increased
day 1 (±70,0) (±150,8)
PCR – average (±DS)
mortality. The presence of respiratory, neurological and
mg/dl 21,66 17,80 abdominal symptoms will not allow the early diagnosis of
preoperatively (±11,5) (±21,2) 0,5232 anastomotic leakage, because these symptoms usually appear
postoperatively 87,67 54,69 0,0165 with the beginning of the 4th day after surgery (11) and fever
day 1 (±53,8) (±37,7) and abdominal sensibility are not specific signs for anastomotic
leakage being frequently present due to other causes in the
G/L ratio – average (±DS)
10,09 4,68 immediate postoperative period.(8) According to Alves & Amp
preoperatively
(±7,3) (±2,1) 0,0031 (12) a late diagnosis of anastomotic leakage (after the 5th day of
postoperatively
10,94 9,34 0,1945 surgery) is associated with a mortality of 18%, but diagnosed
day 1
(±6,6) (±7,8) and treated earlier, mortality could decrease under 1%. As a
TNF-α = tumour necrosis factor alpha, DS = standard deviation, PCR consequence, early detection and treatment of anastomotic
= C-reactive protein, G/L = granulocytes/lymphocytes leakage is essential and makes the early biological markers
become very useful. Tissue ischemia of the suture line at the
Figure no. 2. Correlation between pcr and g/l rate in level of the anastomosis appears to be responsible for early
perioperative period inflammatory response with a release of acute phase proteins
(such as PCR).(13,14) Decrease of pH at the level of mucosa in
the anastomotic suture line in the first 24-hours after the surgery
increases the risk of dehiscence (15) and sustains the theory that
inadequate perfusion in the anastomosis appears in the early
phase and increases the risk of complications.
Exponential increase of PCR level in 2-3 days after
surgery indicates an increased risk of complications at the level
of the suture in patients with other excluded infectious causes
(respiratory, urinary or suture cause) (3), but we wanted an
earlier marker detection even in the preoperative period which
could predict an unwanted evolution of the anastomosis. We
have found that G/L rate increases in the preoperative period can
serve as an indicator for anastomotic leakage with a comparable
power as the levels of PCR in post-operative period: a
sensitivity of 70 to 80% and a specificity of 80 to 86% for PCR
above of 140 mg/dl in the postoperative 3rd day(3,13) versus
Comparison of the two diagnostic tests for sensibility of 71,43% and specificity of 73.68% for G/L rate
postoperative anastomosis leakage has been accomplished by above 5,8 unites postoperative.
comparing the two ROC curves (receiver operating Considering observations tied to modified WBC
characteristic) and AUC (area under curve), meaning the curve formula in different types of stress and inflammation correlated
for post operative G/L rate and postoperative day 1 PCR level. with results of our study we can presume that an increased
The results indicated that these two tests are almost identical for preoperative G/L rate could exist in the presence of a local
G/L rate =0,692, as for PCR= 0, 691 (p=0,9999). For a more subclinical inflammation that marks the evolution of
AMT, vol. 26, no. 1, 2021, p. 49
 CLINICAL ASPECTS
anastomosis in the postoperative period. 2005;48:1460-70.
15. Millan M, Garcia-Granero E, Flor B, Garcia-Botello S,
CONCLUSIONS Lledo S. Early prediction of anastomotic leak in colorectal
Early identification of patients with colorectal cancer cancer surgery by intramucosal pH. Dis Colon Rectum
exposed to anastomotic leakage risk may be careful check-up of 2016;49:595-601.
biological markers in the immediate postoperative period and
early treatment considerably decreasing the mortality due to this
complication. Our study brings attention to the importance of
GL rate as a marker of inflammation immediately available and
accessible. Reprogramming patients seems reasonable if a G/L
rate is greater than 10 before surgery.

Conflict of interest: No conflict of interests.

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7. Zahorec R. Ratio of neutrophil to lymphocyte counts-rapid
and simple parameter of systemic inflammation and stress
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Early predictors of anastomotic leaks after colectomy. Tech
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9. Kingham TP, Pachter HL. Colonic anastomosis leak: risk
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10. Soeters PB, de Zoete JPJGM, Dejong CHC, Williams NS,
Baeten CGMI. Colorectal Surgery and Anastomotic
Leakage. Digestive Surgery. 2002:150-5.
11. Ortega-Deballon P, Radais F, Facy O, d'Athis P, Masson D,
Charles PE, et al. C-reactive protein is an early predictor of
septic complications after elective colorectal surgery.
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12. Alves A, Panis Y, Trancart D, Regimbeau JM, Pocard M,
Valleur P. Factors associated with clinically significant
anastomotic leakage after large bowel resection:
multivariate analysis of 707 patients. World J Sur.
2012;26:499-502.
13. Welsch T, Müller SA, Ulrich A, Kischlat A, Hinz U,
Kienle P, et al. C-Reactive protein as early predictor for
infectious postoperative complications in rectal surgery. Int
J Colorectal Dis. 2007;22:1499-507.
14. Attard JA, Raval MJ, Martin GR, Kolb J, Afrouzian M,
Buie WD, et al. The effects of systemic hypoxia on colon
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 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March;26(1):51-58
DOI: 10.2478/amtsb-2020-0015
Online ISSN 2285-7079

EPIDEMIOLOGY OF PREGNANCY INDUCED HYPERTENSION

– A MULTIFACTORIAL INFLUENCE.
A RETROSPECTIVE STUDY

RADU CHICEA1, PAULA NIȚĂ2, IOANA CODRUŢA LEBADA3

1,2,3
“Lucian Blaga” University of Sibiu, 1,2² Sibiu County Emergency Clinical Hospital

Keywords: preeclampsia, Abstract: Pregnancy-related hypertension is a major cause of maternal and fetal mortality worldwide.
gestational diabetes, About 10% of maternal mortality in Asia and Africa is due to high blood pressure in pregnancy. In
intrauterine growth Latin America, hypertensive disorders in pregnancy are responsible for 25% of maternal mortality.(1)
restriction, cardiac The paper aims to evaluate the incidence of hypertensive disorders associated with the pregnancy
pathology between January 2019 and December 2019 at the Obstetrics and Gynaecology Clinic of the County
Emergency Clinical Hospital in Sibiu, Romania. Between January 2019 and December 2019, in the
Obstetrics and Gynecology clinic of the Sibiu County Emergency Clinical Hospital, 69 pregnant
women with pregnancy-related hypertensive pathology were hospitalized. Of these, 95,65% of
pregnant women had a single fetal pregnancy and 4,34% had a twin pregnancy. The patients were
between 16 and 44 years old. In the first age category, there was only one pregnant woman who
developed hypertensive pathology in pregnancy. The second age category included 50 pregnant
women, while the third age category included 18 pregnant women. The average age parameter at the
time of admission was 30.79 years old.

INTRODUCTION The increased maternal mortality due to hypertensive

Prevalence
Pregnancy-related hypertension is a major cause of
maternal and fetal mortality worldwide. About 10% of maternal
mortality in Asia and Africa is due to high blood pressure in
pregnancy. In Latin America, hypertensive disorders in
pregnancy are responsible for 25% of maternal mortality.(1)
Also, fetal growth restriction (FGR) defined as an estimated
fetal weight below the 10th percentile often associated with
preeclampsia (PE) is an important cause of perinatal morbidity
and mortality. Intrauterine growth restriction is frequently
associated with acute fetal distress antepartum and intrapartum.
Approximately 25% of antepartum stillbirths are associated with
intrauterine growth restriction, without fetal hypotrophy being
detected antepartum. One of the great challenges of modern
obstetrics is to identify as early as possible patients who are at
risk of developing preeclampsia. An important step is the
evaluation of maternal risk factors, including: nulliparity,
preeclampsia at a previous pregnancy, age> 40 years / <18
years, hereditary history of cardiac pathology in pregnancy,
chronic hypertension, chronic kidney disease, antiphospholipid
syndrome, collagen diseases (systemic lupus erythematosus),
type 1 or 2 diabetes, multiple pregnancy, obesity, thrombophilia,
previous unexplained intrauterine growth restriction, fetal death
in utero, pregnancy obtained by in vitro fertilization.(2)
Pregnant women at high risk of preeclampsia can be closely
monitored for signs such as intrauterine growth restriction or
altered blood flow to the uterine arteries with the appearance of
notch. Randomized studies in the literature and meta-analyzes
have shown that the administration of aspirin initiated in the first
trimester of pregnancy is associated with decreased risk of
preeclampsia.(2)
disorders associated with pregnancy, aroused the interest of the
World Health Organization, which launched a study in 2014 in
order to assess the incidence of hypertensive disorders
associated with pregnancy. Another goal of the World Health
Organization was to identify other pathologies associated with
hypertension and their impact on maternal mortality. The study
included 29 countries from Africa, Asia, Latin America and the
Middle East. In Africa, the highest incidence of chronic
hypertension, preeclampsia and eclampsia was recorded in
Nigeria, respectively 0.56%; 2.33% and 1.35%. In Latin
America, the highest number of cases of chronic hypertension
associated with pregnancy was registered in Mexico (0.83%),
preeclampsia in Peru (3.5%) and eclampsia in Ecuador (0.32%).
The Middle East had the highest rates of chronic hypertension in
Pakistan 0.53%, preeclampsia in Afghanistan 0.97% and
eclampsia also in Pakistan 0.36%. In Southeast Asia, the highest
number of cases of chronic hypertension 0,21%, preeclampsia
1,97% and eclampsia 0,43% was recorded in India. In the
Western Pacific Region, chronic hypertension associated with
pregnancy was most common in China 0.6%, preeclampsia in
Mongolia 6.7% and eclampsia in the Philippines 0.28%.(1)
The incidence of eclampsia in Europe is similar to that
of developed countries in North America and is estimated at
around 5-7 cases per 10,000 births.(3) The incidence of
preeclampsia worldwide varies between 2-10% of
pregnancies.(4) The prevalence of pregnancy-associated
hypertensive pathology decreased in Northern Europe and
Australia between 1997 and 2007. This condition has decreased
over time in most populations, although risk factors such as
obesity and advanced maternal age are generally increasing.
However, this may be due to the fact that there has been a

Corresponding author: Paula Niţă, B-dul. Corneliu Coposu, Nr. 2-4, Sibiu, România, E-mail: nitapaula.90@gmail.com, Phone: +40744 695310
1

Article received on 11.08.2020 and accepted for publication on 26.02.2021

AMT, vol. 26, no. 1, 2021, p. 51
 CLINICAL ASPECTS
decrease in the number of pregnancies that reach up to 40 weeks
of gestation.(5) In Romania, the exact prevalence of
hypertension associated with pregnancy is not known.
Etiopathogenesis of pregnancy-associated
hypertension.
Over time, several theories involved in the
etiopathogenesis of pregnancy-associated hypertension have
been stated. Until now, the occurrence of pregnancy-associated
hypertension and the factors that lead to its occurrence have not
been fully elucidated. However, studies over the past decade
have highlighted the potential mechanisms involved in the
pathogenesis of pregnancy-associated hypertension. The state of
gestation determines the activation of adaptive mechanisms and
the mobilization of the functional reserves of the maternal
organism. These adaptive changes affect all body systems, but in
different proportions. Pregnancy causes an increased demand on
the cardiovascular system to meet progressively increased needs
as the pregnancy progresses. In order to meet maternal and fetal
metabolic needs during pregnancy, significant changes in
maternal cardiovascular and renal function occur.(6)
In pregnancy the heart is moved upwards and suffers a
slight hypertrophy with increasing transverse diameter due to
increased diastolic volume. Heart rate increases on average by
15% - the increase starts from 8-10 weeks of gestation and
reaches a maximum between 32-34 weeks of gestation. Heart
rate increases due to increased heart rate and heart rate by up to
about 45%. There is also an increase in cardiac labor and blood
flow during pregnancy. Blood pressure drops slightly due to
decreased peripheral resistance and pregnancy-specific
hormonal impregnation. Due to the compression exerted by the
pregnant uterus on the inferior vena cava, the venous pressure
increases.(7)
Over time, several theories have been proposed in an
attempt to explain the etiology of hypertension in pregnancy.
Currently there are 4 important theories that are
widely accepted:
1. Placental implantation with abnormal trophoblastic
invasion of uterine vessels,
2. Altered immune tolerance between maternal and fetal
tissues,
3. Inadequate maternal adaptation to cardiovascular or
inflammatory changes in normal pregnancy,
4. Genetic factors including inherited predisposing genes and
epigenetic influences.
Over the past two decades, the central piece in the
contemporary understanding of the pathogenesis of
preeclampsia has been the injury of endothelial cells. Abnormal
trophoblastic invasion reduces the lumen of the spiral arterioles
with reduced placental flow. Reduced placental blood flow
creates a local hypoxic environment. In response to placental
factors released due to ischemic changes, a cascade of events
occurs. It is considered that both antiangiogenic and metabolic
factors as well as a number of mediators of the inflammatory
response cause injury to endothelial cells.(8) Decreased
concentrations of angiogenic factors such as the vascular
endothelial growth factor (VEGF) and placental growth factor
(PlGF) and increased concentration of their antagonist, the
placental soluble fms-like tyrosine kinase 1 (sFlt-1) are
angiogenic imbalances associated with the development of
preeclampsia.(9,10)
Nitric oxide synthesis, a crucial factor in vascular
remodeling and vasodilation, which may be able to ameliorate
placental ischemia, is inhibited by the binding of VEGF and
PlGF to their receptors.
Preeclampsia with early onset that occurs before 34
weeks of gestation is thought to be caused by
syncytiotrophoblast stress leading to poor placentation.
AMT, vol. 26, no. 1, 2021, p. 52
Preeclampsia that occurs after 34 weeks of gestation is more
commonly associated with intrauterine growth restriction due to
prolonged placental dysfunction.(10,11)
AIM
The aim of the paper is to evaluate the incidence of
hypertensive disorders associated with pregnancy between
January 2019 and December 2019 at the Obstetrics and
Gynecology Clinic of the County Emergency Clinical Hospital
in Sibiu, Romania. We also aim to evaluate the presence of other
pathologies associated with this condition as well as the
identification of associated risk factors and their impact on fetal
weight at birth.
MATERIALS AND METHODS
The study included all pregnant women who presented
to the OG Clinic of the Sibiu County Emergency Clinical
Hospital during January 2019-December 2019 and who suffered
from hypertensive disorder associated with pregnancy,
intrapartum or postpartum immediately.
The data were extracted from the clinic database as
well as from the patient observation sheets. From the
observation sheets of the patients there were extracted data
related to the mother’s age, height, weight, rural or urban
background, personal physiological history, toxic consumption
(smoking), degree of gestation and parity, gestational age at the
time of hospitalization, gestational age at the time of diagnosis
of hypertensive pathology associated with pregnancy,
gestational age at birth, single or twin pregnancy, other
associated diseases, birth pathway, indication for birth by
cesarean section where he was born by cesarean section, fetal
ultrasound parameters and Doppler values on the umbilical
artery, cerebral artery middle and uterine arteries. The collected
data were centralized in an Excel table. For the analysis of the
obtained data, data sorting and filtering functions were used, as
well as various calculation formulas.
The values 0 and 1 were assigned to certain studied
parameters. The value 0 was assigned to vaginal birth, while the
birth by cesarean section was marked with the value 1. The
urban environment was marked with the value 0, and the rural
one with 1. The smoking pregnant women were assigned the
value 1, while the non-smoking pregnant women were marked
with 0. Pregnancy-induced hypertension was assigned a value of
0, and pregnancy-associated chronic hypertension was assigned
a value of 1. The mild clinical form of hypertension was marked
with 0, and the severe with 1.
For the evaluated parameters we calculated the
average of the parameter, as well as the standard deviation. To
obtain these values we used the standard calculation formulas.
The data related to the age of the pregnant women at the
hospitalization were processed by dividing them into 3
categories. The first category included pregnant women aged
between 16 and 18 years. The second category included
pregnant women aged between 19 and 35 years, and the third
category included pregnant women aged between 36 and 44
years.
The data corresponding to the gestational age
parameter were processed by dividing them into 3 categories. In
the first category, there were included pregnant women with
gestational age between 24 and 33 weeks of gestation, in the
second category, pregnant women with gestational ages between
34 and 36 weeks of gestation, and the third category included
pregnant women with gestational ages between 37 and 42 weeks
of gestation.
Gestational age at admission, at the time of diagnosis
of hypertension pathology and at birth was established and noted
in the completed weeks of pregnancy.
 CLINICAL ASPECTS
RESULTS The gestational age at the time of hospitalization was
Between January 2019 and December 2019, in the between 28 weeks of gestation and 42 weeks of gestation. The
Obstetrics and Gynecology clinic of the Sibiu County average gestational age at the time of hospitalization was 37.18
Emergency Clinical Hospital, a number of 69 pregnant women weeks of gestation, and the standard deviation was 2.39.
with pregnancy-related hypertensive pathology were
hospitalized. Of these, 95,65% pregnant women had a single Figure no. 2. Incidence of twin pregnancy in the evaluated
fetal pregnancy and 4,34% had a twin pregnancy. The average group
number of single-fetal or twin pregnancies was 1.04, and the
standard deviation 0.203.
4.34% of the pregnancies in the studied group were
obtained by in vitro fertilization.
The patients were between 16 and 44 years old. In the
first age category there was only one pregnant woman who
developed hypertensive pathology in pregnancy. The second age
category included 50 pregnant women, while the third age
category included 18 pregnant women. The average age
parameter at the time of admission was 30.79 years old, and the
standard deviation 6.58. 18.84% of pregnant women with
hypertension were multiparous and only 1.44% of patients were
juvenile primiparous.

Table no. 1. Results for average of the parameter and 89,85% of the 69 patients developed high blood
standard deviation for each parameter pressure during pregnancy, while 10,14% of the patients were
Average of the Standard known to have cardiac pathology prior to pregnancy.
Parameter
parameter deviation The average of the pre-existing or pregnancy-induced
Patients age 30,79 6,58
hypertension parameter is 0.10 and the standard deviation is
Gestational age at admission 37,184 weeks of 2,393
gestation
0.30.
Gestational age at diagnosis 34 weeks of gestation 0 71.01% of patients had a mild form of hypertension,
Gestational age at birth 37 weeks of gestation 2 and 28.98% had severe preeclampsia.
Single fetal-1/ twin 1,043 0,20
pregnancy-2 Figure no. 3. Comparative representation of cases with high
Vaginal birth-0/ Caesarian 0,666 0,4714 blood pressure values acquired in pregnancy and those
section-1 birth present before pregnancy
Rural-1 / urban -0 0,3623 0,480
environment
Non-smoker-0 / smoker- 1 0,144 0,352
Maternal weight 95,375kg 8,23
Maternal height 154,62 cm 5,998
Mild preeclampsia -0 / 0,2898 0,45
severe-1
Pre-existing hypertension -1 0,101 0,301
/ pregnancy-induced 0
Fetal weight at birth 2443,3 g 625,15

Figure no. 1. Age distribution of the patients

Figure no. 4. Graphical representation of cases with severe

preeclampsia

Table no. 2. Age distribution of the patients

Age Number of cases
years old %
16-28 1.44%
19-35 72,46% Between 24 and 33 weeks of gestation, 5,79% of the
36-44 26,08% patients presented with pregnancy-associated hypertensive
AMT, vol. 26, no. 1, 2021, p. 53
 CLINICAL ASPECTS
pathology, 20,28% developed hypertension between 34 and 36
weeks of gestation, and 73,91% were diagnosed with
hypertension between 37 and 42 weeks of gestation.
Figure no. 5. Gestational age distribution at admission
Table no. 3. Gestational age distribution at admission
Gestational age at admission Number of cases
(weeks of gestation) %
24-33 weeks of gestation 5.79%
34-36 weeks of gestation 20.28%
37-42 weeks of gestation 73.91%
Figure no. 6. Age of gestation at the time of diagnosis
The average gestational age at the time of diagnosis
was 34 weeks, and the standard deviation was 0.
The average gestational age at birth was 37 weeks of
gestation the standard deviation is 2.
36,23% patients came from rural areas and 63,76%
from urban areas.
Figure no. 7. Graphic representation of patients according to
the environment of origin
AMT, vol. 26, no. 1, 2021, p. 54
14.49% of patients are smokers and 85.5% non-
smokers. The average value of smoking and non-smoking
patients is 0.144, and the standard deviation 0.35. The mean
weight of the patients was 95.37 kg and the standard deviation
8.23.
The average height of the pregnant women was 154.62
cm, and the standard deviation was 5.99.
66,66% of the patients gave birth by cesarean section,
and 33,33% gave birth vaginally. The average of the parameter
is 0.66, and the standard deviation is 0.47. 62.5% of births by
Caesarean section was a surgical emergency. The average
weight of girls at birth was 2443.3 grams, and the standard
deviation was 625.15
At the time of hospitalization, Doppler ultrasound was
performed on the umbilical artery in 44 patients. Of these, only
one pregnant woman showed reverse flow on the umbilical
artery. The resistance index on the umbilical artery had values
between 0.43 and 0.82.
Figure no. 8 Incidence of birth by caesarean section in the
studied group.
Figure no. 9. Incidence of toxic consumption (smoking) in
the studied group
Figure no. 10. Graphic representation of cases with
intrauterine growth restriction at birth
 CLINICAL ASPECTS
Figure no. 11 Graphical representation of the incidence of
premature birth in the studied group
Figure no. 12 Graphical representation of the incidence of
intrauterine growth restriction on established gestational
age groups.
Table no. 5 Birth weight of newborns with intrauterine
growth restriction depending on gestational age at birth
Gestational age at birth Weight at birth
(weeks of gestation) (grams)
24-33 weeks of gestation 710 g - 1310 g
34-36 weeks of gestation 1130 g - 2370 g
37-42 weeks of gestation 1410 g - 2920 g
33.33% of patients did not present other pathologies
associated with pregnancy except for hypertensive pathology.
66.66% of patients had other pregnancy-related
conditions. Of these, 50% had fetuses with intrauterine growth
restriction associated with severe oligoamnios in 4.34% of
cases. Also, 21.73% of them had scarred uterus after cesarean
section and 2.17% double scarred uterus after cesarean section.
7.39% of patients with pregnancy-associated
pathology had minor or major thrombophilia. Of the 46 pregnant
women with other pathologies associated with pregnancy, 4 had
gestational diabetes. There were 4 cases of patients with
hypothyroidism. Other pathologies associated with pregnancy
were lumbar discopathy (3 cases), single congenital maternal
kidney, asthma, myopia of both eyes and genital herpes. 33.33%
of pregnant women with hypertension also had associated
obesity. 13.4% of pregnant women were over 35 years old at the
first pregnancy. The main indications for which it was decided
to end the birth by cesarean section were: acute chronic fetal
distress in labor in 47.91% of cases, severe preeclampsia in
20.83% of cases. Other indications for birth by cesarean section
were scar or double scar, uterine primiparous, acute genital
herpes, major thrombophilia in treatment with anticoagulant and
lack of progression of labor by pelvic cephalopod disproportion.
AMT, vol. 26, no. 1, 2021, p. 55
Of course, there have been many cases in which indications for
cesarean delivery have overlapped.
Table no. 6. Incidence of pregnancy-related pathologies in
the studied group
Pregnancy-related pathologies except cardiac pathology Number of cases %
Intrauterine growth restriction 33%
Urinary tract infection 1.45%
Scar uterus 14.49%
Double scarred uterus 1.45%
Thrombophilia 11.59%
Gestational diabetes 5.80%
Oligoamnios 2.90%
Hypothyroidism 5.79%
Lumbar discopathy 4.35%
Unique congenital maternal kidneys 1.45%
Pulmonary asthma 1.45%
Acute genital herpes 1.45%
Strong myopia 1.45%
DISCUSSIONS
Preeclampsia and intrauterine growth restriction are
thought to be the result of abnormal changes in the placenta.
Clinical manifestations are dependent on gestational age at the
onset of cardiac pathology and are dependent on the phenotypic
characteristics of each individual.(22) The etiopathogenesis of
preeclampsia is complex and frequently associated with other
pathologies.
Recent data from the literature suggest that the risk of
preeclampsia may be reduced by prophylactic administration of
aspirin. Thus, identifying patients who are at risk for developing
preeclampsia is essential to establish prophylactic treatment.
Individual assessment of risk factors is essential to determine
patients at high risk of developing preeclampsia.
Risk factors for preeclampsia include nulliparity,
multiple pregnancy, preeclampsia in a previous pregnancy, a
hereditary history of chronic hypertension or pregnancy-induced
hypertension, age over 40 years or under 18 years. Among the
conditions that are involved in the occurrence of pregnancy-
induced hypertension are: diabetes of 1 or 2, thrombophilia,
chronic kidney disease, antiphospholipid syndrome and some
collagen diseases such as systemic lupus erythematosus.
Also, other risk factors for preeclampsia that are
recommended to be evaluated are obesity (BMI> 35 Kg / m2),
fetal death in utero, unexplained intrauterine growth restriction
in a previous pregnancy and pregnancies obtained by in vitro
fertilization and embryo transfer.
The results of our study show that 53.62% of pregnant
women who had pregnancy-associated high blood pressure are
nulliparous. Null parity is assessed as a risk factor in numerous
studies in the literature. Several studies published in the
literature have included exclusively nulliparous pregnant
women. The aim was to assess the risk factors associated with
nulliparity.
It is noteworthy that 60.86% of pregnant women
enrolled in our study with fetuses with intrauterine growth
restriction are nulliparous.
Another important factor in assessing the risk of
preeclampsia is preeclampsia in a previous pregnancy. Data
from the literature show that the incidence of developing
preeclampsia in a future pregnancy after a first pregnancy with
preeclampsia is between 7-20%. The risk of developing
preeclampsia increases in direct proportion to the number of
previous pregnancies with preeclampsia. Following data from
patients enrolled in our study, no patient had preeclampsia in a
previous pregnancy.
Regarding maternal age in assessing the risk of
developing preeclampsia, the results obtained from our study
show that one pregnant woman was 16 years old and 8 were
over 40 years old. This shows that only 13.04% of pregnant
 CLINICAL ASPECTS
women who developed preeclampsia were of extreme age.
Extreme maternal age is thought to be associated with
adverse pregnancy outcomes. Obtaining a pregnancy in
adolescence is often associated with premature birth and low
birth weight. On the other hand, obtaining a pregnancy at an
advanced maternal age has an increased risk of complications
and is associated with premature birth, low birth weight etc.
It is well known that preeclampsia is frequently
associated with intrauterine growth restriction. However, there
are other diseases associated with preeclampsia in pregnancy
that may contribute to the onset and progression of intrauterine
growth restriction.
Evaluation of the data obtained from the study group
showed that 33.33% of patients had fetuses with intrauterine
growth restriction. However, in addition to preeclampsia and
intrauterine growth restriction, patients also had other associated
diseases. The most common conditions associated with
pregnancies with preeclampsia and intrauterine growth
restriction were hereditary thrombophilia, gestational diabetes,
diabetes type 2, pregnancy obtained by in vitro fertilization, twin
pregnancy and obesity.
However, 5.80% of pregnant women with
preeclampsia also had associated gestational diabetes.
Data from the literature highlight several similarities
between preeclampsia and gestational diabetes. Both
preeclampsia and gestational diabetes are diseases that begin
during pregnancy and are characterized by placental
insufficiency and maternal pancreatic dysfunction.(23)
The American College of Obstetrics and Gynecology
claims that preeclampsia is associated with the development of
cardiovascular disease later in life.(24)
Gestational diabetes is also a risk factor for the
development of type 2 diabetes later in life.(25)
The data in the literature are, however, contradictory.
There are studies that argue that gestational diabetes is a risk
factor for preeclampsia, and others that claim that preeclampsia
is a risk factor for the development of gestational diabetes. This
draws attention to the possibility of common pathophysiological
mechanisms for the two diseases.
One of the hypotheses stated in the literature is that
insulin resistance may contribute to the pathophysiology of
preeclampsia. It is considered that women who develop
preeclampsia have increased insulin resistance before
pregnancy, in pregnancy and late in life after birth compared to
women who have normal blood pressure in pregnancy. This can
be explained by the fact that some of the risk factors for
preeclampsia are associated with insulin resistance. However,
after eliminating the common risk factors for preeclampsia and
gestational diabetes (obesity, advanced maternal age, black race,
etc.), increased insulin resistance remains a significant predictor
of preeclampsia.(26,27,28,29,30,31,32)
To assess whether gestational diabetes and
preeclampsia have a common etiology, studies have been
conducted to see if early treatment for diabetes reduces the risk
of preeclampsia. The data from the studies were contradictory.
Some studies show that early treatment for gestational diabetes
reduces the risk of preeclampsia, while other studies show that
there is no significant decrease in the risk of
preeclampsia.(33,34,35,36)
In the group we studied preeclampsia and gestational
diabetes were associated, gestational diabetes was diagnosed
before preeclampsia. It is difficult to say whether these data
support the fact that gestational diabetes is a risk factor for
preeclampsia, especially given that most cases did not have
gestational diabetes associated with preeclampsia.
However, it is noteworthy that pregnant women with
gestational diabetes and preeclampsia had fetuses with
AMT, vol. 26, no. 1, 2021, p. 56
intrauterine growth restriction.
Another pathology associated with preeclampsia and
progresses with intrauterine growth restriction is hereditary
thrombophilia. Most likely this is due to altered placental
perfusion followed by insufficient maternal-fetal intake,
resulting in intrauterine growth restriction.(37,38)
Several studies show that protein S deficiency,
MTHFR gene mutation, prothrombin gene mutation, and Leiden
factor V mutation are more commonly associated with
intrauterine growth restriction.(39,40,41)
In our study, 17.39% (8 patients) of pregnant women
had thrombophilia. Of these, only one patient had major
thrombophilia. 6 of the pregnant women diagnosed with
thrombophilia had pregnancies with fetuses with intrauterine
growth restriction. Given the fact that both preeclampsia and
hereditary thrombophilia are characterized by intrauterine
growth restriction, it is difficult to attribute the low weight of the
fetus to one of them. Most likely both pathologies through a
combination of factors determined this evolution of pregnancy.
However, in the study group, fetuses from mothers
with thrombophilia and preeclampsia associated with
intrauterine growth restriction had higher birth weights than
girls from mothers with preeclampsia associated with
intrauterine growth restriction. The average weight of fetuses
from mothers with thrombophilia was approximately 2,267 g,
and of fetuses from mothers with preeclampsia with intrauterine
growth restriction was 1,910 g. This can be justified by the fact
that all pregnant women who have been known to have
thrombophilia have received anticoagulant treatment, which
reduces placental pathology such as thrombosis and placental
infarction.
There are numerous studies in the literature that
highlight the evolution of hypothyroidism in pregnancy with
intrauterine growth restriction.(42,43)
Hypothyroidism is thought to cause intrauterine
growth restriction by inducing pathological changes in the
placenta.(44)
It is well known that twin / multiple pregnancy is
associated with intrauterine growth restriction. The mechanism
of fetal hypotrophy in twin pregnancy is complex and involves
the distribution of placental territory and the insertion of the
umbilical cord. Most of the risk factors for intrauterine growth
restriction in twin pregnancies are common to those of
preeclampsia and gestational diabetes and overlap with other
pregnancy-related pathologies in the study group.(45)
Obesity is a global health problem. Data published by
the National Institute of Public Health in 2014 show that
Romania has a high percentage of overweight people, but
obesity is a lower percentage compared to other European
countries. Globally, obesity is the fifth leading cause of death.
Romania presents the epidemiological profile of all developed
countries characterized by increasing the incidence of
cardiovascular diseases and lifestyle diseases. In Romania, the
incidence of obesity has had an upward trend since 1995 when
this condition began to be reported until today. In the states of
the European Union in 2011 between 8% and 23.9% of women
were obese.
In addition to gestational diabetes, infertility,
thrombotic complications, premature birth, miscarriage, obesity
is associated with an increased risk of preeclampsia. The risk of
developing preeclampsia increases in direct proportion to the
body mass index. The higher the body mass index, the higher
the risk of developing preeclampsia. Of the 69 pregnant women
enrolled in the study, 23 were obese both during pregnancy and
at birth. Of the 69 pregnant women enrolled in the study, 23
were obese both during pregnancy and at birth. Given that
obesity is characterized by increased insulin resistance, only 4
 CLINICAL ASPECTS
patients developed gestational diabetes out of 23 with obesity.
All newborns from mothers with gestational diabetes were
normal weight at birth.
CONCLUSIONS
In conclusion, the epidemiology of preeclampsia is
multifactorial and in our study we did not find all the epidemic
factors usually mentioned in the literature. Intrauterine growth
restriction found in the foetuses delivered from mothers with
preeclampsia is a usually complex, multifactorial mechanism,
dependent on a number of pregnancy-associated pathologies that
are based on common risk factors.
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 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):59-62
DOI: 10.2478/amtsb-2020-0016
Online ISSN 2285-7079

THE EFFECTIVENESS OF PROGESTINS FOR PITUITARY

SUPPRESSION DURING OVARIAN STIMULATION IN IVF
PROCEDURES

ALEXANDRU POLEXA1, SULE YILDIZ2, BARIS ATA3

1
“George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș,
1,2,3
Koc University Hospital, Istanbul, Turkey

Keywords: progestins, Abstract: Progestins are capable of suppressing endogenous luteinizing hormone (LH) secretion from the
Ovarian stimulation, IVF pituitary; are less expensive than GnRH analogues. This systematic review summarizes the effectiveness of
progestins as compared with GnRH analogues and identifies some of the future research perspectives.
Several public resources were screened with a combination of keywords related to assisted reproductive
technology, progesterone, GnRH analogue and ovarian stimulation. Overall, duration of stimulation,
gonadotropin consumption and oocyte yield were similar with progestins and GnRH analogues. The live
birth, ongoing and clinical pregnancy rates per embryo transfer were similar with progestins and GnRH
analogues. There is still a low quality of evidence. Available information is reassuring regarding obstetric
and neonatal outcomes with the use of progestins. As a wider implication, progestins can present an
effective option for women who do not contemplate a fresh embryo transfer, anticipated hyper responders,
preimplantation genetic testing, oocyte donors, double stimulation cycles.

INTRODUCTION woman starting a stimulation cycle. Secondary outcomes were i)

Pituitary suppression is commonly achieved by
gonadotropin releasing hormone (GnRH) analogues. GnRH
antagonists have become the most commonly used agents for
over a decade, since they require less injections, provide similar
pregnancy rates and lower risk of ovarian hyperstimulation
syndrome than the former standard of care, i.e. GnRH
agonists.(1) Progestins are also capable of suppressing
endogenous luteinizing hormone (LH) secretion from the
pituitary.(2) Unlike GnRH analogues, progestins can be used
orally and cost significantly less than GnRH antagonists.
However, early endometrial exposure to progestin precludes a
fresh embryo transfer.(3) Yet, with the advent of high-survival
embryo vitrification and increasing number of oocyte
cryopreservation cycles progestins are being more frequently
used in ART. However, there is limited information about the
effectiveness of progestins as compared with GnRH analogues.
live birth or ongoing pregnancy beyond 12 weeks per woman
starting a stimulation cycle, ii) live birth rate per embryo
transfer procedure, iii) live birth or ongoing pregnancy per
embryo transfer procedure, iv) clinical pregnancy (defined as
evidence of a gestational sac at six weeks or later, confirmed
with ultrasound) rate per embryo transfer procedure, v) number
of oocytes retrieved per OR, vi) number of metaphase two
oocytes per OR, vii) the duration of a stimulation cycle, viii)
total gonadotropin consumption per stimulation cycle.
Adverse events included; i) ectopic pregnancy per
embryo transfer, ii) miscarriage per pregnancy: defined as the
number of spontaneous abortions (pregnancy loss before 20
completed weeks of gestation) and the number of stillbirths
(pregnancy loss after 20 completed weeks of gestation), iii)
multiple pregnancy rate per embryo transfer and iv) ovarian
hyperstimulation syndrome (OHSS) per stimulation cycle.

AIM
This systematic review summarizes the effectiveness
of progestins as compared with GnRH analogues and identifies
some of the future research perspectives.
MATERIALS AND METHODS
Briefly, we searched Cochrane Central Register of
Controlled Trials (CENTRAL); Medline via PubMed; Web of
Science; Scopus and manually screened the reference lists of
selected articles. Search period was from the date of inception of
each database until 1 April 2020. There were included all studies
that compared the effectiveness of a progestin with GnRH
analogue for pituitary suppression in ART, which were
published as full text in English. The primary outcome was live
birth of a fetus after 20 completed weeks of gestational age per
RESULTS
We included 10 studies comparing progestins with
GnRH antagonists, six with GnRH agonists (one of which was
treated as two separate studies since there were two distinct
study populations involved, Shen et al. 2020) (4), and six with
other progestins or different dosages of the same progestin
(figure no. 1).
There are several important limitations of the available
studies; i) majority of them were conducted in the same center
by the two groups of investigators from China, ii) in most
studies patients were allocated to different protocols in a non-
randomized manner, iii) pregnancy outcomes were reported per
transfer rather than per woman starting stimulation. Moreover,
cumulative live birth rates per stimulation, which is the most
relevant outcome measure was not reported at all.

1
Corresponding author: Alexandru Polexa, Str. Ştefan cel Mare, Nr. 2, Bl. 10, Sc. B, Ap. 11, Braşov, România, E-mail: polexa_a@yahoo.com, Phone:
+40744 125195
Article received on 02.11.2020 and accepted for publication on 26.02.2021
AMT, vol. 26, no. 1, 2021, p. 59
 CLINICAL ASPECTS
Figure no. 1. Study flowchart vs 18.2%, respectively, p=0.42) However, in addition to the lack
of allocation concealment, it is unclear whether women
underwent multiple embryo transfers, i.e. fresh followed by
frozen transfers if the fresh transfer did not result in live birth.
Moreover, the trial was underpowered for comparison of live
birth rates (figure no. 2).

Figure no. 2. Progestins versus GnRH Antagonists – Embryo

transfer outcomes

Possible implications of these limitations vary

depending on the outcome of interest. In order to address these
shortcomings, it can be useful to separate outcomes in two
categories; the first category includes outcomes related to the
response to ovarian stimulation (ROS), i.e. duration of
stimulation, total gonadotropin consumption, number of oocytes
and mature oocytes collected, risk of OHSS, while the second
category includes outcomes after embryo transfer (ET), i.e.
pregnancy, multiple pregnancy, miscarriage and live birth rates.
We are presenting as numeric data the ET outcomes for the both
GnRH antagonists and agonists. The outcomes in ROS category
were reported per woman starting stimulation cycle and the
major risk is selection bias in the non-randomized studies.
Despite similar baseline characteristics regarding age and
ovarian reserve parameters being reported for study groups in all
papers, it is impossible to completely rule out systematic
differences in other parameters that can probably effect ovarian
response between the groups, e.g. the selection of starting
gonadotropin dosage, which would have an impact on total
gonadotropin consumption and could have been effected by the
knowledge of pituitary suppression protocol planned for a
patient, or monitoring could have been done differently. Yet, we
think outcomes in this category are more reliable than outcomes
in the ET category. The latter is crippled by the failure to report
pregnancy/live birth rates per woman starting stimulation and
cannot account for women not reaching an embryo transfer or
women undergoing multiple embryo transfers. The proportion of
women undergoing ET over women starting stimulation ranged
between 25 – 91% in PPOS arms and 50 – 88% in comparators
and were significantly different between PPOS and GnRH
analogue groups in some studies (data not shown). Moreover,
observations in ROS category can have higher generalizability
than the observations in ET category. The data is dominated by
studies on Chinese women, while ethnic differences may
arguably have an effect on pregnancy and live birth rates,
ovarian response does not seem to be effected by ethnic
background based on limited data.(5,6,7)
Progestins versus GnRH Antagonists
Progestins were compared with GnRH antagonists in
ten studies. Three were RCTs (8,9,10) two were prospective
(11,12) and five were retrospective cohort
studies.(13,14,15,16,17) Regarding ET outcomes, only one
study reported live birth rate per woman starting stimulation.(9)
There were 170 women in each group and women in the PPOS Progestins vs GnRH agonists
and GnRH antagonist groups had similar live birth rates (21.8% Progestins were compared with GnRH agonists in six

AMT, vol. 26, no. 1, 2021, p. 60

 CLINICAL ASPECTS
studies. Two were RCTs, one prospective and three were
retrospective cohort studies.(4,18,19,20,21,22) One of the RCTs
was indeed a quasi-randomized trial and assignment was by
patient numbers, which clearly breaches the principle of
allocation concealment.(19) All studies were from the Dept. of
Assisted Reproduction of Shangai Ninth People’s Hospital and
included women with an anticipated normal ROS or PCOS.
Figure no. 3. Progestins versus GnRH Agonists – Embryo
transfer outcomes
Regarding ET outcomes (figure no. 3), none of the
AMT, vol. 26, no. 1, 2021, p. 61
studies reported live birth rate or ongoing pregnancy rate per
woman starting stimulation.
Live birth rate (RR = 0.83, 95% CI = 0.39 to 1.78, two
studies, 445 transfers) (18,21) and live birth or ongoing
pregnancy rate per embryo transfer (RR =1.06 95%CI = 0.87 to
1.28, 6 studies, 1490 transfers) (4,18,19,20,21,22) were similar
with progestins and GnRH agonists. Sensitivity analyses for trial
design, short or long GnRH agonist protocol, MPA or MIP,
ovarian reserve status suggested similar results.
DISCUSSIONS
This study suggests that progestins are capable of
effectively preventing premature ovulation in ART cycles.
Progestins seem to provide higher pregnancy rates than the short
GnRH agonist protocol following frozen embryo transfers.
Safety profile of progestins seems similar with GnRH
analogues. However, the quality of evidence concerning their
effectiveness with regard to oocyte yield and live birth rate in
comparison to GnRH analogues is yet low and there is a strong
need for more research.
The underlying assumptions of these analyses
regarding the cost effectiveness were i) similar live birth rates
with PPOS, the short GnRH agonist and GnRH antagonist
protocols, and ii) 462 IU higher gonadotropin consumption with
PPOS than the protocols using GnRH analogues. The increased
cost of PPOS cycles were due to i) increased gonadotropin
consumption and ii) the cost of additional monitoring and
embryo thawing for the first transfer (even when the cost of
freezing supernumerary embryos after the first fresh transfer in
GnRH analogue protocols was assumed to balance out the cost
of total embryo freezing in PPOS cycles).
The presence of a limited number of trials/studies,
most of which are not randomized nor accounts for every
woman starting stimulation are drawbacks, preventing definitive
conclusions on the subject. However, we present an unbiased
overview of the current literature and identify gaps in
knowledge for future research. A reliable comparison between
progestins and GnRH antagonists, the current standard of care
for pituitary suppression is urgently needed, such as a
comparison between flexible and the common PPOS.
Future Perspectives
An increasing number of studies suggest similar ROS
and pregnancy outcomes per transfer with PPOS and GnRH
analogues. MPA, DYG and MIP seem to be effective inhibitors
of premature ovulation and provide similar quality oocytes as
evidenced with pregnancy outcomes. Embryo euploidy rates as
well as obstetric outcomes seem to be similar with PPOS and
GnRH analogues. However, more high quality RCTs,
comparing PPOS with both GnRH agonists and antagonists,
which report live birth rates per woman starting stimulation,
ideally in a cumulative manner, are needed from different
centers and countries. Gonadotropin starting dosages and the
requirements for dose adjustments must be pre-specified in these
trials. Different progestins and PPOS protocols, e.g. fPPOS,
require further assessment.
Avoiding GnRH analogue injections and taking
progestin pills are assumed to be more convenient for the
patients, however, none of the studies reported on side effects,
or compared them with those in conventional OS cycles. Patient
satisfaction should be properly assessed and compared in future
studies. Different routes of administration or progestins, e.g.
vaginal, transdermal, can be investigated.
Cost-effectiveness analyses based on local costs
would be informative to assess the cost effectiveness of PPOS
outside the U.S. with updated reliable information especially
regarding gonadotropin consumption from good quality studies.
Finally, more information on the course of pregnancy, obstetric
 CLINICAL ASPECTS
complications, neonatal and long-term infant outcomes,
including health and development of children is needed.
CONCLUSIONS
In conclusion, if future high-quality trials confirm the
assumptions of this review, progestins can become the agent of
choice for pituitary suppression in ovarian stimulation cycles
when a fresh embryo transfer is not intended, such as
preimplantation genetic testing or fertility preservation cycles
with oocyte or embryo cryopreservation. This would be a real
benefit by eliminating the need for relatively costly GnRH
analogues.
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1. Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam
WS, Broekmans FJ. Gonadotrophin-releasing hormone
antagonists for assisted reproductive technology. Cochrane
Database Syst Rev. 2016;4:CD001750.
2. La Marca A, Capuzzo M. Use of progestins to inhibit
spontaneous ovulation during ovarian stimulation: the
beginning of a new era? Reprod Biomed Online; 2019.
3. Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC.
Progesterone elevation and probability of pregnancy after
IVF: a systematic review and meta-analysis of over 60 000
cycles. Hum Reprod Update. 2013;19:433-457.
4. Shen X, Gao H, Chen Q, Cai R, Lyu Q, Wang Y, Wang L,
Kuang Y. Effect of Switching from a Progestin-Primed
Ovarian Stimulation Protocol to a Modified Ultra-Long
Protocol Among Women Who Had 1 Progestin-Primed
Ovarian Stimulation (PPOS) Failure Verses Those Who
Had 2 PPOS Failures. Med Sci Monit; 2020;26: e918705.
5. Franasiak JM, Olcha M, Shastri S, Molinaro TA, Congdon
H, Treff NR, Scott RT, Jr. Embryonic aneuploidy does not
differ among genetic ancestry according to continental
origin as determined by ancestry informative markers.
Hum Reprod. 2016;31:2391-2395.
6. Humphries LA, Chang O, Humm K, Sakkas D, Hacker
MR. Influence of race and ethnicity on in vitro fertilization
outcomes: systematic review. Am J Obstet Gynecol.
2016;214:212 e211- 212 e217.
7. Olcha M, Franasiak JM, Shastri S, Molinaro TA, Congdon
H, Treff NR, Scott RT, Jr. Genotypically determined
ancestry across an infertile population: ovarian reserve and
response parameters are not influenced by continental
origin. Fertil Steril. 2016;106:475-480.
8. Begueria R, Garcia D, Vassena R, Rodriguez A.
Medroxyprogesterone acetate versus ganirelix in oocyte
donation: a randomized controlled trial. Hum Reprod.
2019;34:872-880.
9. Chen Q, Chai W, Wang Y, Cai R, Zhang S, Lu X, Zeng X,
Sun L, Kuang Y. Progestin vs. Gonadotropin-Releasing
Hormone Antagonist for the Prevention of Premature
Luteinizing Hormone Surges in Poor Responders
Undergoing in vitro Fertilization Treatment: A
Randomized Controlled Trial. Front Endocrinol
(Lausanne). 2019;10:796.
10. Eftekhar M, Hoseini M, Saeed L. Progesterone-primed
ovarian stimulation in polycystic ovarian syndrome: An
RCT. Int J Reprod Biomed (Yazd). 2019;17:671-676.
11. Iwami N, Kawamata M, Ozawa N, Yamamoto T,
Watanabe E, Moriwaka O, Kamiya H. New trial of
progestin-primed ovarian stimulation using dydrogesterone
versus a typical GnRH antagonist regimen in assisted
reproductive technology. Arch Gynecol Obstet.
2018;298:663-671.
12. Mathieu d’Argent E, Ferrier C, Zacharopoulou C.
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Outcomes of fertility preservation in women with
endometriosis: comparison of progestin-primed ovarian
stimulation versus antagonist protocols. J Ovarian Res.
2020;13:18.
13. Huang P, Tang M, Qin A. Progestin-primed ovarian
stimulation is a feasible method for poor ovarian
responders undergoing in IVF/ICSI compared to a GnRH
antagonist protocol: A retrospective study. J Gynecol
Obstet Hum Reprod. 2019;48:99-102.
14. Martinez F, Rodriguez-Purata J, Clua E, Garcia S, Coroleu
B, Polyzos N. Ovarian response in oocyte donation cycles
under LH suppression with GnRH antagonist or
desogestrel progestin: retrospective and comparative study.
Gynecol Endocrinol. 2019;35:884-889.
15. Turkgeldi E, Yildiz S, Cekic SG, Shakerian B, Keles I, Ata
B. Effectiveness of a flexible progestin primed ovarian
stimulation protocol compared to the flexible GnRH
antagonist protocol in women with decreased ovarian
reserve. Human Fertility; 2020.
16. Xiao ZN, Peng JL, Yang J, Xu WM. Flexible GnRH
Antagonist Protocol versus Progestin-primed Ovarian
Stimulation (PPOS) Protocol in Patients with Polycystic
Ovary Syndrome: Comparison of Clinical Outcomes and
Ovarian Response. Curr Med Sci. 2019;39:431-436.
17. Yildiz S, Turkgeldi E, Angun B, Eraslan A, Urman B, Ata
B. Comparison of a novel flexible progestin primed
ovarian stimulation protocol and the flexible gonadotropin-
releasing hormone antagonist protocol for assisted
reproductive technology. Fertil Steril. 2019;112:677-683.
18. Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A,
Shoham Z. Medroxyprogesterone acetate is an effective
oral alternative for preventing premature luteinizing
hormone surges in women undergoing controlled ovarian
hyperstimulation for in vitro fertilization. Fertil Steril.
2015;104:62-70.e63.
19. Wang Y, Chen QJ, Wang NL, Chen H, Lyu QF, Kuang
YP. Controlled Ovarian Stimulation Using
Medroxyprogesterone Acetate and hMG in Patients With
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Blind Randomized Crossover Clinical Trial. Medicine.
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20. Xi Q, Tao Y, Qiu M, Wang Y, Kuang Y. Comparison
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Outcome with the First IVF/ICSI Cycle: A Randomized
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21. Zhu X, Ye H, Fu Y. The Utrogestan and hMG protocol in
patients with polycystic ovarian syndrome undergoing
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22. Zhu X, Zhang X, Fu Y. Utrogestan as an effective oral
alternative for preventing premature luteinizing hormone
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 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):63-66
DOI: 10.2478/amtsb-2021-0017
Online ISSN 2285-7079

RECOMMENDATIONS FOR SPORT AND PHYSICAL ACTIVITY

AFTER TOTAL HIP AND KNEE ARTHROPLASTY: A
SYSTEMATIC REVIEW

LORAND VITALIS1, OCTAV RUSSU2, SANDOR ZUH3, TUDOR SORIN POP4

1,2,3,4
Mureș Clinical County Hospital, 2,3,4 “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș

Keywords: sports and
joint replacement, total
hip arthroplasty, total
knee arthroplasty
Abstract: Due to the high success of arthroplasty, patients suffering from osteoarthritis have higher
expectations regarding the relief of pain, functional recovery and capacity to perform physical and
sports activity. The purpose of our article is to present a literature review based on papers published
during the last decades, with emphasis on the current recommendations regarding sports after total
joint replacement. We conducted a search using PubMed/Medline databases, selecting the scientific
articles published between 2005-2020 which discuss the association between physical activity and
total hip or knee arthroplasty. The benefits of physical activity in all kinds of joint prostheses
outweigh the negative effects; therefore, the recommendation for low-impact sports (hiking,
swimming, cycling or golf) at a moderate intensity is considered valid and patients with total hip or
knee arthroplasty who preoperatively had a high level of physical activity can return to low-impact
sports performed at moderate intensity after 3-6 months.

INTRODUCTION
The joint replacement surgery has received
recognition as a very successful intervention and is indicated in
advanced stages of hip and knee osteoarthritis, in order to offer
pain relief, to correct deformities, to re-establish the function
and finally to improve the quality of life of these patients.(1,2)
Usually, these are older sedentary adults, with comorbidities
such as overweight or obesity, high blood pressure or diabetes.
In these cases, regular physical activity could have a beneficial
effect on the general health and therefore total joint arthroplasty
(TJA) could contribute to this outcome, as it facilitates not only
the relief of pain, but also an increased sport activity.(3,4)
During the last decade, a lower tolerance to joint
discomfort in cases with less advanced osteoarthritis and an
increased demand for arthroplasties in younger patients have
been recorded, factors considered responsible for the increased
number of joint replacements worldwide, with around 500 000
such interventions yearly. Beside pain, considered as a primary
indication, more patients are preoccupied by being able to
maintain a high level of physical activity and a healthy
lifestyle.(5-7) As a consequence, specialists were forced to
quantify the amount of sport activity allowed to be performed
after TJA and also to establish the acceptable kinds of activities.
Postoperatively, patients are advised to regain an active lifestyle
which not only promotes their general health but also favours an
adequate bone quality at the interface with the implant and
reduces the risk of early loosening.(8,9) However, defining the
beneficial level of physical activity and predicting its outcomes
proved to be a difficult task. For example, jogging was shown to
increase the load on the hip joint to more than 500% of the body
weight and high joint loads might lead to implant wear, debris,
periprosthetic osteolysis and finally implant failure.(10)
Scientific data suggests that during the last decades there was an
increasing number of allowed physical activities, although not
all surgeons shared the same opinion and therefore changed the
indications over the years.(11,12) The intensity of physical
activity continues to be a matter of intense debate in the
scientific literature, in an effort to distinguish between
favourable and dangerous levels of sport activity that might
jeopardize the long-term success of TJA.(13)
AIM
The aim of our review is to summarize the current
recommendations for sports and physical activity in patients
with TJA, in order to provide surgeons up-to-date guidelines
regarding a rapid return to an active lifestyle, based on the
existing scientific evidence.
MATERIALS AND METHODS
We conducted a search of scientific articles published
in the time span 2005-2020, discussing the association between
physical activity and TJA, using PubMed/Medline databases. As
key words we used: physical activity, hip and knee arthroplasty,
sports after joint replacement. From a total of 114 articles, we
selected 33 original and review articles. The inclusion criteria
for studies were: assessment of physical activity pre- and
postoperatively, longitudinal design, recommendation for
physical activity or sports in patients with TJA. The exclusion
criteria for studies were: evaluation of the range of motion,
intensity of pain, quality of life TJA, but with no reference to
physical activity.
TOTAL JOINT ARTHROPLASTY AND SPORTS
Current interventions for TJA have a mean longevity
of over 90% at 10-20 years, therefore the minimum follow-up
period for the assessment of clinical and radiological success of
this procedure is 10 years, a time period after which most
complications start to appear.(5,13) Based on an analysis

Corresponding author: Octav Russu, Str. Mihai Viteazu, Nr. 31, Târgu Mureș, România, E-mail: octav.russu@umfst.ro, Phone: +40744 266735
2

Article received on 01.02.2021 and accepted for publication on 02.03.2021

AMT, vol. 26, no. 1, 2021, p. 63
 CLINICAL ASPECTS
conducted in Sweden on 92 675 hip arthroplasties and 30 003
knee arthroplasties, the rates of revision after 10 years for
patients aged less than 55 and 65 years respectively were
significantly higher (20% and 18%, respectively) than in older
patients (5% and 6%, respectively). This could have been
correlated to the higher level of physical activity of the younger
patients.(1)
During physical activity, the increased force exerted
through the prosthesis can represent an important risk factor for
early failure, as it determines a high stress and wear between
prosthetic components and also at the interface with the bone,
inducing early loosening and implant instability. Beside material
properties of the prosthetic components, the load force exerted
on the implant is very important, as it can increase exponentially
the amount of wear. Therefore, only activities such as
swimming, power walking or cycling, characterized by low joint
loads should be recommended.(14)
Scientific data suggested that physical inactivity might
increase the risk of early loosening (<10 years) as a result of
insufficient osseointegration of non-cemented implants and
osteopenia. On the other hand, an increased physical activity is
associated with polyethylene wear and delayed loosening (>10
years), due to reactive particle release and osteolysis.(15)
However, regarding the longevity of a new joint, there
is no scientific evidence for the type and level of physical
activity to be recommended or avoided after TJA.(5,10) For
each patient with TJA, the recommendations for a specific sport
or physical activity must take into consideration the type of
implant, but also the joint load and wear, as the reduction of
these factors are the most important in the successful long-term
results of the surgical intervention. Therefore, the goal is to find
a balance that guarantees the benefits of physical activity and at
the same time does not reduce the longevity of the
prosthesis.(16)
TOTAL HIP ARTHROPLASTY
During the last decade, the number of total hip
arthroplasties increased dramatically and it is estimated that the
number of these interventions will exceed 575 000 every year.
Another observation was related to patient’s demographic
characteristics, with an increase of 50% of patients aged 50-59
years old, who expect to return to high levels of physical activity
after surgery. Most available data on the type of sports
recommended after total hip arthroplasty (THA) comes from
surveys based on clinical experience and preferences of
surgeons and not from retrospective or prospective
analyses.(17,18) Data collected in 2007 from 614 surgeons
showed that low-impact activities were mostly recommended
(swimming, stationary biking, dancing, bowling, walking).(10)
Other activities such as pilates, downhill skiing, ice-skating or
weightlifting were allowed with experience. The general
consensus was that jogging, squash, contact sports, high impact
aerobic, snowboarding and baseball/softball were not allowed.
(table no. 1).(13)
Table no. 1. Physical activity and sports recommended after
total hip arthroplasty
NOT Recommended with Recommended
recommended experience
Singles tennis Cross-country skiing Doubles tennis
Jogging/running Downhill skiing Swimming
Contact sports Weight lifting Low-impact aerobics
(football, hockey) Weight machines
High impact aerobic Ice skating Cycling, Elliptical
Martial arts Pilates Speed walking, Golf
Handball Dancing
Waterskiing Hiking
(Adapted from Vogel et al) (13)
AMT, vol. 26, no. 1, 2021, p. 64
The time interval after which patients could return to
allowed physical activity was estimated at 3 to 6 months after
surgery, but about 30% of the specialists considered that 1-3
months after THA is an acceptable time interval.(19,20) In a
study from 2009, Swanson et al (15) analysed the answers from
139 surgeons regarding the allowance of these physical
activities, grouped as unlimited, occasional (1-2 times/month)
and discouraged. The results showed that the low impact sports
were indicated unlimited (swimming, golf, walking, cycling,
doubles tennis), while activities such as sprinting, jogging, and
skiing difficult terrain were discouraged by most of the
respondents. In 2012, Delasotta et al (21) reported their results
regarding the participation of patients with THA to physical
activities based on the recommendations stated by Klein et al in
their survey from 2007.(10) The included patients declared that
high impact sports were avoided not as a result of pain, lack of
interest or fatigue but due to fear (28.6%) or surgeon indications
(25.7%).
Abe et al (22) confirmed that fear was an important
factor that prevented 61% of patients with hip resurfacing,
which is a more conservative surgical procedure, from returning
to jogging, while only 15% avoided it due to pain. This data was
confirmed by Huch et al (23) who reported that 56% of patients
with THA gave up participating to sports “as a precaution, to go
easy on the artificial joint.” The authors considered that the fear
of movement was an important issue, influenced by the post-
operative education of the patient in adopting a healthy lifestyle.
However, in a questionnaire retrospective study, Jassim et al
(24) considered that the avoidance of intense physical activity
after THA has a multi-factorial etiology. There are few
prospective studies on the correlation between high levels of
physical activities (considered a risk factor for dislocation,
loosening, periprosthetic fracture, polyethylene wear) and poor
clinical outcomes after THA. There is some evidence suggesting
that wear may be related to activity level, but the impact on
clinical outcomes was conflicting.(25,26)
TOTAL KNEE ARTHROPLASTY
Knee osteoarthritis restricts the usual activity of a
person, reducing the sports capacity and working but this
condition can be treated by arthroplasty, a reliable and well
accepted intervention; however, little information is available
regarding the extent to which the patients can return to normal
physical activity and sports.(27,28) As a consequence of
overwhelming data indicating that the lack of physical activity
favours the onset of serious health problems, people became
aware of the importance of staying physically active. In Europe,
the number of osteoarthritis patients is expected to rise
exponentially until 2040, with an increase in knee arthroplasties
of 297%, up to 57 900 new cases annually in 2030.(29)
The indications for surgical intervention in knee
osteoarthritis became broader due to better techniques and
implants. A survey based on a questionnaire conducted by Vu-
Han et al (14) aimed to find the current recommendations, type
of implant and surgical technique selected by the specialists
when treating younger patients who have high expectations after
surgery in terms of sports level. The results showed that within
3-6 months after surgery most surgeons indicated low-impact
sports, while fewer considered that also high-impact sport is
recommended. However, the answers regarding the choice of
the surgical method or implant design were considered
controversial and the authors presented no clear conclusions
(table no. 2). In a systematic review, Witjes el al (30) considered
that physical activity was possible after unicondylar and total
knee arthroplasty (TKA) in 36-100% of patients, who returned
to physical activity in about 12-13 weeks and chose in 90% of
the cases lower-impact sports. The authors concluded that
 CLINICAL ASPECTS
higher-impact physical activity is more appropriate after
unicondylar arthroplasty.
Table no. 2. Physical activity and sports recommended after
total knee arthroplasty
NOT recommended Recommended Recommended
with experience
Contact sports Cycling Low impact
(football, hockey) aerobics
Rock climbing Hiking Dancing
Singles tennis Doubles tennis Walking
Running/ Jogging Speed walking Swimming
Handball Ice skating Bowling
Martial arts Skiing Golf
(Adapted from Vogel et al) (13)
The evaluation was based on studies that gave little
attention to parameters such as preoperative level of sports
(considered important in quantifying the return to physical
activity), comorbidities or restrictions from the surgeon. In order
to make proper recommendation after TKA, it is important to
evaluate the load and the knee flexion angle of the peak load;
during jogging or hiking, high joint loads are present during
knee flexion of 40-600, angles at which in many implants
designs polyethylene stress occurs. If performed regular, these
physical activities rise the risk of delamination and polyethylene
destruction for most current total knee implants. Therefore, it is
advisable to be more conservative after TKA for sports that
induce high joint loads in knee flexion.(31-33)
CONCLUSIONS
There is a significant discrepancy between previous
expert recommendations and the actual activity levels that may
be achieved after the implantation of a joint prosthesis. Future
studies have to define the sports level, the type of sports and the
type of prosthesis that provide a positive benefit-risk ratio using
state-of-the-art low-abrasion bearing surfaces and prosthesis
designs. It is important to recommend appropriate activities after
TJA, being unwise to indicate technically demanding sports,
which might represent a risk factor for injuries, especially in
untrained individuals. Patients should be motivated to return to
physically activity for their overall health and also for
maintaining an adequate quality of bone, which facilitates
prosthesis fixation and prevents early loosening. When
recommending a certain activity after TJA one should take into
consideration multiple factors such as wear, joint load, intensity
and the type of implant in each particular case. However, the
reduction of wear remains of utmost importance in the long-term
success of TJA.
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6. Learmonth ID, Young C, Rorabeck C. The operation of the
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7. Walker T, Streit J, Gotterbarm T, Bruckner T, Merle C,
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8. Levine B, Kaplanek B, Jaffe WL. Pilates training for use in
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preliminary report. Clin Orthop Relat Res.
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9. Liebs TR, Herzberg W, Ruther W, Haasters J, Russlies M,
Hassenpflug J. Ergometer cycling after hip or knee
replacement surgery: a randomized controlled trial. J Bone
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10. Klein GR, Levine BR, Hozack WJ, Strauss EJ, D'Antonio
JA, Macaulay W, Di Cesare PE. Return to athletic activity
after total hip arthroplasty. Consensus guidelines based on
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11. Hoorntje A, Janssen KY, Bolder SBT, Koenraadt KLM,
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12. Naal FD, Impellizzeri FM. How active are patients
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14. Vu-Han TL, Gwinner C, Perka C, Hardt S.
Recommendations for Patients with High Return to Sports
Expectations after TKA Remain Controversial. J Clin Med.
2020 Dec 26;10(1):54.
15. Swanson EA, Schmalzried TP, Dorey FJ. Activity
recommendations after total hip and knee arthroplasty: a
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Surgeons. J Arthroplasty. 2009;24(6 Suppl):120-6.
16. Fawaz WS, Masri BA. Allowed Activities After Primary
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Orthop Clin North Am. 2020;51(4):441-52.
17. Arbuthnot JE, McNicholas MJ, Dashti H, Hadden WA.
Total hip arthroplasty and the golfer: a study of
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osteoarthritis. J Arthroplasty. 2007;22(4):549-52.
18. Sechriest VF 2nd, Kyle RF, Marek DJ, Spates JD, Saleh
KJ, Kuskowski M. Activity level in young patients with
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up. J Arthroplasty. 2007;22(1):39-47.
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Haddad FS. Sport after total hip arthroplasty: undoubted
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G, Plachel F, et al. Return to Sport After Short-Stem Total
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4.

AMT, vol. 26, no. 1, 2021, p. 66

 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):67-69
DOI: 10.2478/amtsb-2021-0018
Online ISSN 2285-7079

THE TECHNOLOGY OF OBTAINING FLEXIBLE DENTURES IN

DENTAL PRACTICE, THEORETICAL AND PRACTICAL
ASPECTS

MĂDĂLINA ADRIANA MALIȚA1, CAMELIA IONESCU2, VIOREL ȘTEFAN PERIEANU3,

MIHAI BURLIBAȘA4, MAGDALENA NATALIA DINA5, RADU COSTEA6, MĂDĂLINA
VIOLETA PERIEANU7, RALUCA COSTEA8, IULIANA BABIUC9, IRINA ADRIANA BEURAN10,
GABRIELA TĂNASE11, MIHAELA CHIRILĂ12, MIHAI DAVID13, IOANA VOINESCU14, LILIANA
MORARU15
1,2,3,4,5,6,7,8,9,10,11,12,13,14
“Carol Davila” University of Medicine and Pharmacy Bucharest, 15“Titu Maiorescu” University of Medicine and Pharmacy,
Bucharest

Keywords: flexible Abstract: Flexible dentures are an increasingly interesting prosthetic alternative both for dental
dentures, edentulous practitioners (dentists and dental technicians), but also for patients. This type of prosthetic restoration
spaces, acrylic partial can rehabilitate a wide range of edentulous, but the financial effort that patients have to make is more
dentures, skeletal partial consistent than in the case of a partial acrylic dentures. In this study, we will try to present some
dentures essential aspects in the technology of creating flexible partial dentures.

INTRODUCTION Specifically, the purpose of this study is to familiarize the

Elastic or flexible dentures are a modern alternative to medical dental team (dentist, dental technician) with the
classic dentures made of acrylic resins and they are a solution manufacture process of such prosthetic restorations.
for patients who want to enjoy the benefits of a denture for a Next, we will briefly present the technological
long time. workflow of making flexible dentures, both clinical and
Thus, the material from which these dentures are made technical stages:(1,2,3)
is an elastic, thin, resistant and biocompatible with the tissues of - Clinical examination of the patient.
the oral cavity. The base of this denture is pink and promotes - Preliminary impression.
successful integration into the oral cavity.(1-3) - Pouring the preliminary model.
- Making custom trays.
GENERAL DATA - Functional impression.
There are several types of flexible dentures, depending - Pouring the master cast.
on the number and distribution of the remaining teeth on the - Making wax occlusion rims.
dental arches or depending on their total absence and are named - Recording intermaxillary relationships.
after the materials from which they are made of: Biodentaplast, - Mounting the master casts in the simulator (occluder,
TCS, Polyon etc.(1,2,3) Among the advantages of flexible articulator).
dentures that the production companies bring into question, the - Duplication of the master cast.
following must be mentioned:(1,2,3) - Wax-up Biodentaplast type framework.
 Does not retain plaque and tartar. - Flasking the model.
 Does not affect the support teeth. - Obtaining the pattern
 They are biocompatible and the material does not contain - Resin injection.
toxic residues. - Deflasking.
 They are durable over time. - Processing the Biodentaplast type resin framework.
 It has a low stretch on the palate, the taste and - Making the wax setup of partial denture.
pronunciation are not affected, due to the shape and - Wax try-in.
flexibility of the denture. - Flasking the model with a silicone index.
 They are very stable, offer great comfort, do not cause - Packing the acrylate.
injury, allow a fairly effective chewing of food. - Acrylate polymerization.
 It offers a superior aesthetic etc. - Deflasking, processing and polishing the partial denture
In general, the dental team (dentist, dental technician) - Deliver the partial denture to patient.
avoids approaching a treatment plan that includes these flexible
dentures and especially recommends acrylic and / or skeletal CLINICAL EXAMPLE
partial denture, usually due to either convenience, either the Next, we will exemplify how to obtain a flexible
absolute refusal to inform or to invest in a different technology. partial denture through a clinical case, focusing mainly on

2
Corresponding author: Camelia Ionescu, Str. Plevnei, Nr. 19 Sector 1, Bucureşti, România, E-mail: mburlibasa@gmail.com, Phone: +40723 472632
Article received on 22.11.2020 and accepted for publication on 02.03.2021
AMT, vol. 26, no. 1, 2021, p. 67
 CLINICAL ASPECTS
laboratory steps. Figure no. 5. Functional casts mounted in occluder
A male patient named Y.S. aged 46 years, presented in
the dental office following the loss of masticatory units in the
lateral area, masticatory efficiency decreased significantly. To
fix this problem, the dentist in collaboration with the patient and
the dental technician, decided as a treatment plan to make two
Biodentaplast type flexible dentures.
In a first stage, preliminary impressions were made,
and preliminary casts were poured. On the preliminary casts two
individual impression trays were made. With the help of the
individual impression trays (figures no. 1-3), the maxillary and
mandibular functional impressions were taken with silicone
materials, in which functional casts were poured. On the
functional casts, the occlusion rims were made, necessary to
record maxillomandibular relationship. The functional casts The master casts were duplicated and, on the obtained
were then mounted in a simulator in centric relation, with the casts the wax framework of the two flexible dentures were
help of the intermaxillary relationship recorded in the dental made. The cast were packed in special flasks, specific to elastic
office with occlusion rims (figures no. 4, 5). resin injection system. The injection of the elastic resin was
followed by the deflasking and processing trimming of the
Figure no. 1. Preliminary impressions taken in stock trays denture.
with alginate The frameworks obtained were adapted to the master
casts (figure no. 6) and then the wax setup of the dentures was
made. Subsequently, wax dentures were flasked and the wax
was removed. In the pattern obtained the acrylic resin was
introduced. After polymerization of the acrylic resin, the final
product was deflasked, trimmed and polished. The clasps were
made of the same flexible material, from which the base of the
prosthesis was made.
This was followed by try-in of the dentures in the oral
cavity (figure no. 7-9).
Figure no. 2 a, b. The two preliminary casts, maxillary and Figure no. 6 a, b. Framework of flexible dentures,
mandibular, made of class III plaster, with the limits of the mandibular (a) and maxillary (b)
custom trays drawn on them

a b a b
Figure no. 3. a, b. Custom trays made of light-curing resin
plates. Figure no. 7 a, b. Flexible dentures mandibular (a) and
maxillary (b) after defalsking

a b
a b
Figure no. 8. Mandibular(a) and maxillary(b) flexible
Figure no. 4. The master casts mounted in centric relation dentures after processing
with occlusion rims

a b

AMT, vol. 26, no. 1, 2021, p. 68

 CLINICAL ASPECTS
Figure no. 9. The flexible dentures in occlusion on master
casts
Flexible dentures can be a viable alternative,
especially for replacing partial acrylic dentures. Unfortunately,
the technology of making such dentures involves some
additional financial efforts from the technical department, the
dental laboratory, efforts that consist in the purchase of
equipment, materials and instruments necessary for the
manufacture of such prosthetic restorations. But, all these
investments from the dental laboratory will definitely pay off
over time, due to higher costs, compared to classic acrylic
partial dentures.
Other disadvantages of flexible dentures, apart from
the high price, can be systematized as follows:
- They need a rigorous hygiene.
- They can stain over time (especially for smokers and people
who drink coffee regularly).(4-6,13)
DISCUSSIONS
Polyzois in a study conducted in 2015, showed that,
although flexible dentures are prosthetic works that are not
learned during faculty, the interest of doctors and technicians in
their realization is growing. Long-term success is based on
investing in oneself by taking specialized courses in the field,
but also in the materials and equipment needed to make flexible
partial dentures.(7)
Singh 2013, following a rigorous analysis, concluded
that the success of a treatment in which a flexible partial denture
is used is based on establishing a correct diagnosis accompanied
by establishing a rigorous treatment plan followed strictly.(8)
In an attempt to evaluate how flexible dentures,
influence the oral health related to quality of life (OHRQoL)
compared to acrylic dentures, Akinyamoju in 2019 found an
improvement in OHRQoL for patients wearing flexible partial
dentures, which may change future therapeutic behaviour for
such patients.(9)
In 2011, Singh conducted an assessment of the
satisfaction of using flexible dentures compared to conventional
rigid acrylates in a group of 18 patients, with clear results in
favour of flexible dentures.(10-12)
CONCLUSIONS
Flexible partial denture is a widespread prosthetic
work, as it can restore any form of partial edentulous spaces.
From a topographical point of view, it was discovered
that there are approximately 60,000 clinical possible
combinations of teeth and edentulous spaces, these being most
often restored with flexible dentures, due to their flexibility and
elasticity.
Flexible partial denture is a prosthetic work made of
an elastic material that does not contain monomer and is
obtained through an injection process and has the ability to
restore aesthetically, morphologically and functionally the
dental arches.
This type of prosthetic restorations, with clasps made
of the same material from which the base of the denture is made,
AMT, vol. 26, no. 1, 2021, p. 69
offers patients more comfort and a substantial aesthetic,
compared to the partial acrylic denture.
Acknowledgement:
In this article, all the authors have equal
contributions.
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1. dentalexcellence. Proteze elastice. [Online] [Cited: 11 23,
2020.] https://www.dentalexcellence.ro/proteze-elastice-
alternativa-avantajoasa/.
2. dentfix. Proteze dentare elastice. [Online] [Cited: 11 23,
2020.] http://www.dentfix.ro/2013/12/protezele-dentare-
elastice/.
3. Negrescu EC, Malița M. Particularități de realizare a
protezelor flexibile de tip Biodentaplast. În: Tendințe
moderne în științele biomedicale, Vol. IX, p. 251-297,
coordonatori: Malița MA, Dina MN, Ionescu C, David M,
Burlibașa M. Editura Matrix Rom, București; 2020.
4. Yunus N, Rashid AA, Azmi LL, Abu Hassan MI. Some
Flexural Properties of a Nylon Denture Base Polymer. J
Oral Rehabil. 2005;32:65-71.
5. Dhiman RK Col, Roy Chowdhury SK. Midline Fracture in
Single Complete Acrylic vs Flexible Dentures. MJAFI.
2009;65:141–5.
6. Anusavice KJ. 10th ed. Philadelphia: WB Saunders; 1996.
Phillips’ Science Of Dental Materials; 1996; p. 238.
7. Polyzois G, Lagouvardos P, Kranjcic J, Vojvodic D.
Flexible Removable Partial Denture Prosthesis: A Survey
of Dentists' Attitudes and Knowledge in Greece and
Croatia. Acta Stomatol Croat. 2015;49(4):316-324.
doi:10.15644/asc49/4/7.
8. Singh K, Aeran H, Kumar N, Gupta N. Flexible
thermoplastic denture base materials for aesthetical
removable partial denture framework. J Clin Diagn Res.
2013;7(10):2372-2373.
doi:10.7860/JCDR/2013/5020.3527.
9. Akinyamoju CA, Dosumu OO, Taiwo JO, Ogunrinde TJ,
Akinyamoju AO. Oral health-related quality of life: acrylic
versus flexible partial dentures. Ghana Med J.
2019;53(2):163-169. doi:10.4314/gmj.v53i2.12.
10. Singh JP, Dhiman RK, Bedi RP, Girish SH. Flexible
denture base material: A viable alternative to conventional
acrylic denture base material. Contemp Clin Dent.
2011;2(4):313-317. doi:10.4103/0976-237X.91795.
11. Mocuța D, Popovici IA, Cristache G, Sfeatcu R, Bodnar T.
Impact of the living conditions on population health.
Metalurgia International. 2009;14:17-19.
12. Burlibasa L, Chifiriuc MC, Lungu MV, Lungulescu EM,
Mitrea S, Sbarcea G, Popa M, Marutescu L, Constantin N,
Bleotu C, Hermenean A. Sythesis, physico-chemical
characterization, antimicrobial activity and toxicological
featurs of Ag-ZnO nanoparticles, Arabian Journal of
Chemistry. 2020;13(1):4180-4197.
13. Burlibașa M, Cernușcă-Mițariu M, Cernușcă-Mițariu S,
Mițariu M, Malița M. Theoretical and practical aspects
related to biomaterials decontamination in dental medicine
(with reference to dental prosthetics). Metalurgia
International. 2013;(XVIII):4:261-267.
 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):70-74
DOI: 10.2478/amtsb-2021-0019
Online ISSN 2285-7079

BEHAVIOURAL ETIOLOGICAL FACTORS THAT CONTRIBUTE

TO THE OCCURRENCE OF SEVERE EARLY CHILDHOOD
CARIES

DANIELA EŞIAN1, CRISTINA BICA2, ANAMARIA BUD3, OANA STOICA4,

EUGEN BUD5
1,2,3,4,5
“George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Tîrgu-Mures

Keywords: severe early Abstract: Severe early childhood caries (S-ECC) is one of the most common pathologies affecting
childhood caries, primary dentition. The complex etiology is the result of the interaction of microbial factors and also of
breastfed, behavioural dietary factors. For this study a group of 40 children diagnosed with S-ECC was compared with a
factors control group of 35 children without caries. The study data was obtained through clinical
examination of both children and mothers, and on the basis of a questionnaire completed by the
mothers of the subjects. The odontal status of the mothers was evaluated by determining the DMFT
index. The results of the study showed that the mothers of the subjects with S-ECC had a significantly
higher DMF-T caries index than the ones in the control group and that there is a close link between
the birth of the child, newborn feeding method, mother’s habits, cariogenic diet and the occurrence of
severe early childhood caries.

INTRODUCTION tissue.(4) According to some authors the first lesions occur at

Severe-Early Childhood Caries (S-ECC) is currently a
challenge for specialists and practitioners who frequently
interact with small patients due to the early and aggressive onset
immediately after the eruption of temporary teeth, but also to the
rapid evolution of this type of caries that leads to a disturbance
in the functional and aesthetic balance and thus an impairment
of the little patient’s quality of life. The complex and still
incompletely elucidated etiology, is the result of the interaction
of microbial factors represented in particular by S. mutans,
which is the main microorganism responsible for the onset of
the carious process which is transmitted during early childhood
from mother to child, but also of dietary factors that are
particularly related to the type of food intake, duration and
method of administration (consumption habits). The following
factors are involved in the development of severe early caries:
pathogenic bacteria, fermentable carbohydrates and the quality
of hard dental tissues. In addition to these three factors, incorrect
eating behaviours associated with the absence of hygiene
measures are also involved, leading to the rapid onset and
evolution of S-ECC compared to other types of caries found in
temporary dentition.(1,2) Apart from S. mutans, S. sobrinus and
Bifidobacteria also play an important role.(3)
In the absence of an early diagnosis and a complex
treatment plan or even in the case of adopting late specific
therapeutic measures, the difficulty of the treatment and also the
costs involving a complex treatment can increase, and this is
often a major obstacle for both doctors and parents. The first
signs of caries appear at very young ages, shortly after dental
eruption. When the pathogenic factors persist, the carious
process can extend to all the erupted teeth at any given time, and
it will have a tendency to rapidly evolve in surface and depth,
with rapid crown destruction and early interest of the pulp
the age of 20-22 months (5), while other authors report the
occurrence of carious lesions at the age of 12-16 months (6) or
even from the age of 10 months or earlier.(7) The localization of
carious lesions depends on 3 factors: the chronology of the
eruption of temporary teeth, the duration of bad habits and the
muscle pattern of sucking. Thus, the first carious lesions occur
in temporary superior incisors, but the carious process can
extend to all erupted teeth at that time.(5) Expansion is done in
the order of the eruption thus, the first affected group is of the
upper central incisors, then the first molars, canines and finally,
temporary second molars. If the lower incisors are not affected,
the caries are called “bottle caries”, but when they are affected,
the caries are called “ramping caries”.
In the evolution of S-ECC, 4 stages are described: the
first stage, when incipient caries occur on the smooth surfaces of
the temporary upper incisors in the 10-20 months old child.
They occur in the form of white demineralization spots or an
opaque or brown strip in the cervical third of the buccal and
palatal surfaces of the upper incisors, parallel to the gingival
margin.(2) In the second stage, which begins at the age of 16-24
months, cavitation lesions occur that destroy the enamel and
reach the dentin, which becomes soft and changes in colour.(8)
Stage three (at the age of 20-36 months) is characterized by the
presence of deep carious lesions, extended in surface and with
damage to the pulp tissue, in the upper incisors. Cavitation
lesions occur in the upper molars and incipient caries occur on
the first mandibular molars and the maxillary canines. The
fourth stage, between 30-48 months, is characterized by massive
destruction of the upper incisors, complicated caries occur on
the superior molars, and deep simple caries occur in the inferior
molars and superior canines.
Prevention of severe early childhood caries in

4
Corresponding author: Oana Stoica, Str. Gheorghe Marinescu, Nr. 38, Târgu Mureș, România, E-mail: oana.stoica@umfst.ro, Phone: +40747
127603
Article received on 26.11.2020 and accepted for publication on 26.02.2021
AMT, vol. 26, no. 1, 2021, p. 70
 CLINICAL ASPECTS
temporary teeth should begin in the prenatal and perinatal
period, with recommendations for mothers on the care of the
infant and young child.(9) Pregnancy is an ideal period to
promote ECC prevention given the profound influence of
maternal oral health and behaviours on children’s oral
health.(10)
Secondary prophylaxis refers to the diagnosis and
treatment of the caries process in the early stages (11)
Complications resulting from severe early caries can have
serious loco-regional and general consequences in the short or
long term.(8) Thus, it was observed that within one year,
children with carious lesions on their upper frontals had a mean
dmfs index of the posterior teeth 2.5 times higher than those
who did not initially have this type of caries.(12)
The consequences on the permanent teeth refer to the
appearance of carious lesions, structure anomalies of local
cause, the deviation of the eruption axis of the upper incisors
and the reversal of the eruption order of the central incisors.8
The actual treatment of severe early childhood caries depends on
the stage at which the carious process is detected but also on the
degree of cooperation of the child. When the carious process is
detected in the initial stages, the treatment involves stopping it’s
evolution by topical fluoride applications and restoring the
existing carious lesions. If carious lesions are more extensive
and pulp complications have occurred, an endodontic treatment
is performed, specific to the stage of dental development,
associated with a complex crown restoration with zirconium
pedodontic crowns.
AIM
The purpose of our clinico-statistical study was to
determine the role played by the prenatal and postnatal
etiological factors in the occurrence of the severe early
childhood caries S-ECC in a group of preschool children and
their mothers.
MATERIALS AND METHODS
This study was carried out with the approval of the
Local Ethics Committee of the Mureș Emergency Clinical
County Hospital, in accordance with Decision No. 7843 of
28.05.2019.
For this study, a total of 75 children were examined,
aged 1 to 3 years, with a mean age of 2.12 years. A main group
consisting of 40 children diagnosed with S-ECC was selected
and a control group consisting of 35 children without carious
processes. In the study group 15 children were under 2 years of
age and 25 children over 2 years of age. In the control group 21
children were under 2 years of age and 14 children over 2 years
of age. The study data was obtained through clinical
examination of both children and mothers, as well as on the
basis of a questionnaire completed by the mothers of the
children. All 75 children were examined in the presence of a
parent, who was asked to sign an informed consent form before
the consultation.
In the first stage, the subjects from the study group
were clinically examined to confirm the diagnosis of S-ECC.
The criteria for diagnosis of S-ECC according to American
Academy of Pediatric Dentistry (AAPD) (13), are: in children
younger than 3 years age any sign of smooth surface caries and
over 3 years age one or more cavitated, missing or filled smooth
surfaces in primary upper anterior teeth or filled score of ≥ 4
(age 3), or ≥ 5 (age 4), or ≥ 6 (age 5).
In the second stage, a questionnaire was developed
containing data on: age of the child, age of the mother at the
time of birth, whether or not they consulted a dentist before
birth, the type of diet and other aspects (table no. 1).
In the last stage of the study, the mother’s clinical
AMT, vol. 26, no. 1, 2021, p. 71
examination was performed and the DMF-T caries index was
determined. During the determination of the DMF-T index, the
following criteria were used:
- each tooth was registered only once;
- temporary restorations were considered carious lesions;
- a tooth was considered present, even though the crown part
was completely destroyed and there was only a remaining
root fragment.
The processing of the obtained data was done using
the Microsoft Excel software – entering measured parameters,
obtaining graphs, schematic representations through diagrams.
Table no. 1. Questionnaire addressed to the mothers of the
subjects
QUESTIONNAIRE
Name, First name: Age:
1. At what age did you give birth?
2. Was the birth natural or caesarean section?
3. Was the birth at term?
4. Have you consulted your dentist for pre-birth treatments?
5. How was the child fed: natural or artificial?
6. To what age has he been breastfed?
7. Did you usually feed your child at night (milk or tea)?
8. Did the child use to sleep with a bottle in his mouth?
9. Did you usually taste your child's food before feeding him?
10. Do you give your child natural juices or carbonated beverages?
11. At what age did the first carious lesions begin to appear in the child?
Affected teeth of the child:
Carious lesions of the mother:
RESULTS
Following the statistical processing of the data
obtained from the questionnaire and from the clinical
examination, the following results were obtained:
From the first questions it was observed that, 67.5% of
mothers gave birth before the age of 30, the rest after 30 years
and within the control group 60% of mothers gave birth before
30 years and the rest after the age of 30.
To the question “Was the birth natural or caesarean
section?”, 75% of the mothers in the study group and 71.4% in
the control group gave birth naturally, the rest being by
caesarean section.
Regarding the question “Have you consulted your
dentist for pre-birth treatment” it was observed that only 37.5%
of the women in the study group attended a dental practice,
while 60 % of the women in the control group carried out a
specialist appointment (figure no. 1).
Figure no. 1. Distribution of mothers of the subjects
according to the pre-birth treatments
According to how the children were fed after birth the
results show that 77.5% of the subjects in the study group and
60% of subjects in the control group were naturally fed (figure
no. 2)
Regarding the eating habits, respectively “Did you
 CLINICAL ASPECTS
usually feed your child at night?”, the results show that 97.5% of
the subjects in the study group and 71.4% in the control group
were fed at night.
Another question relates to the child's habit of
sleeping with a bottle in his mouth, and the results obtained are
presented in figure no. 3.
Figure no. 2. Graphic representation of the subject’s feeding
behaviour after birth
In terms of the bad habit of the child sleeping with the
bottle in his mouth, only 65% of the subjects in the study group
had this habit while in the control group the percentage is
significant (91.4%).
Figure no. 3. Graphic representation of the subjects
according to eating habits
Regarding the answers to the question “Do you give
your child natural juices or carbonated beverages?”, it was
observed that in the study group these drinks were administered
at a percentage of 47.5% and within the control group only 20 %
of the subjects received this type of drinks (figure no. 4).
In terms of age of occurrence of the first carious
lesions it was observed that in a high percentage of subjects
(77.5%) from the study group the first carious lesions started
after the age of 1 year.
Figure no. 4. Graphic representation of the consumption of
carbonated beverages in subject groups
AMT, vol. 26, no. 1, 2021, p. 72
Another important factor involved in the occurrence of
S-ECC is the age up to which the baby was breastfed, so the
data obtained from the questionnaire showed that 67.5% of the
subjects in the study group were also breastfed after the age of 1
year while in the control group 28.5% exceeded the age of 1
year.
In the statistical data obtained from calculating the
DMF-T caries of the mothers of the subjects in the study group,
a mean index value of 4,575 was determined, while the mothers
of the children in the control group had a mean value of 2.5
(figure no. 5).
Figure no. 5. The mean value of the DMF-T index of the
mothers in both study and control groups
DISCUSSIONS
The correlation between the occurrence of severe early
childhood caries and childbirth, the eating behaviour and the
habits of the mother, is a widely debated topic in the literature.
Various clinical studies conducted in other countries, focused on
the consumption of cariogenic foods and the presence of
bacteria have indicated a statistically significant correlation
between these elements. Thus, a study conducted in the USA on
110 children, of which 72 children had severe carious lesions,
out of all subjects it was observed that the ones affected by
recurrent caries had higher scores in the consumption of
carbonated drinks between meals and also the meals were more
common than in children who did not have carious lesions.
Among the bacteria, those associated with the occurrence of
recurrent lesions are S. mutans and S. sobrinus. Children with S.
mutans had higher food cariogenicity scores. The conclusion of
this study was that frequent meals, presumed cariogenicity and
S. mutans are associated with the presence of severe early
childhood caries.(14)
Our study revealed an increased percentage of S-ECC
occurrence in children who used to consume carbonated
beverages.
Regarding the importance of breast-feeding, additional
sugary food or pre-chewed mother food, a study carried out in
Southeast Asia among mothers with children aged 25 to 30
months, in a community where prolonged breastfeeding is a
common practice, it was observed that all children who
consumed additional sugary food or rice pre-chewed by the
mother or children who fell asleep with the breast in their
mouth, had lesions specific to severe early caries. The infants
without these habits, who were breastfed up to 12 months had
no carious lesions. The conclusion of this study was that in this
population, in addition to the sugar and pre-chewed rice
consumption, nocturnal breastfeeding after the age of 12 months
is a risk factor in the development of severe early childhood
caries.(12)
In the present study, it was observed that the age to
which the child was breastfed is an important factor in the
occurrence of S-ECC. The obtained data showed that 67.5% of
 CLINICAL ASPECTS
the children in the study group and 28.5% of the children in the
control group were breastfed for more than one year.
In 2017, in Moradabad, India, the association between
maternal risk factors and early severe caries was studied among
children aged 3 to 5 years. The study involved 150 child-mother
pairs. The maternal risk factors were assessed using a
questionnaire. After obtaining consent, the mothers and children
were clinically examined for caries using the Radike criteria
(1968). Saliva was collected from all participating mothers in
order to assess the level of Streptococcus mutans. The obtained
data showed significant differences between the carious activity
of the mothers, the high level of Streptococcus mutans, the
educational level, the socio-economic status, the frequency of
maternal sugar consumption and caries incidence in children. 15
In our study, the results show that the mothers of the children in
the study group had a significantly higher DMF-T caries index
(4,575) than the mothers of the children in the control
group(2.5).
Another study conducted in the city of Xiamen in
China, made the correlation between social and behavioural
factors in the occurrence of S-ECC. The study was carried out
on 1523 children with a prevalence of severe early childhood
caries of 56.8%-78.31%. The factors associated with this pattern
of caries were: age, consumption of sweets, carbonated drinks,
eating before bedtime, late start of oral hygiene, low parental
education, flawed care of children, increased number of siblings,
rural residence and lack of knowledge of oral health. The study
concluded that tooth brushing and topical application of fluoride
are two effective methods of preventing caries. The results
showed that the brushing frequency and type of toothpaste are
not significant, but the earlier start time of brushing and topical
application of fluoride is significantly associated with decreased
incidence of caries.(16)
In Salvador, Bahia the association between S-ECC
and low birth weight was studied. The examined independent
variables were socio-demographic, perinatal and behavioural,
such as the type of breastfeeding. The survival analysis was used
to estimate the development period of the caries using the
Kaplan-Meier method. Rural or urban environment, daily self-
care habits, age, skin colour, maternal education, family income,
biofilm presence and subsequent experience with caries were the
determining factors until the occurrence of caries. A positive
association was found between low birth weight and the period
for the development of caries. In conclusion, low birth weight is
associated with the appearance of carious lesions.(17)
The relationship between severe early childhood
caries and salivary alpha amylase, carbonic anhydrase VI and
the presence of biofilm was shown in a study conducted by
Brazil. The purpose of the study was to determine whether these
factors can predict the risk for caries. 100 children were
examined, who were divided into two groups: 45 children with
carious lesions and 55 children without carious lesions. The
presence of biofilm on the maxillary incisors was recorded,
followed by the diagnosis of caries at the initial time and later.
Saliva samples were collected and the activities of carbonic
anhydrase VI and alpha amylase were determined. The
normality of the data was assessed using the Shapiro-Wilk test.
The results showed that the activity of carbonic anhydrase VI
was higher in children with caries, and the activity of alpha
amylase was significantly higher in the saliva of children
without cavities. Children with alpha amylase activity in saliva
less than 122.8 U/mL and visible presence of biofilm on the
superior incisors are more prone to developing of severe early
childhood caries. In conclusion, the visible presence of biofilm
and the decreased activity of alpha amylase can be considered
risk factors in the development of severe early childhood
caries.(18)
AMT, vol. 26, no. 1, 2021, p. 73
In our study, another important factor related to the
occurrence of S-ECC is night-time feeding. Thus, it was
concluded that in the study group, there were 26% more
breastfed children during night-time than in the control group.
CONCLUSIONS
The results of the studies show that there is a close
link between the birth of the child, the newborn feeding method
(natural or artificial), mother’s habits (pre-chewing the food of
the child), the cariogenic diet (sweetened drinks, sweet foods)
and the occurrence of severe early childhood caries. Significant
differences were found between the mother’s caries index, high
level of Streptococcus mutans, educational level, socio-
economical status, frequency of maternal sugar consumption
and the onset of severe early childhood caries.
There was also a positive association between the
consumption of carbonated beverages and the development of
this type of caries. The child’s night-time feeding, the
breastfeeding that extends beyond the age of one year and the
mother’s DMF-T caries index, also play an important role in the
occurrence of S-ECC, and they all indicate high values in the
study group.
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1. Luca R, Ivan A, Stanciu I, V A. Severe early childhood
caries in a sample of preschool children attending a
Pediatric Dentistry Clinic from Bucharest. Oral Health
Dent Manag. 2002;1: 29-35.
2. Attari N, Roberts JF. Restauration of primary teeth affected
by Early Childhood Caries. Eur J Paed Dent.2004;2: 92-7.
3. O'Sullivan DM, Tinanoff N. Social and biological factors
contributing to caries of the maxillary anterior teeth.
Pediatr Dent. 1993;15(1):41-4.
4. Tinanoff N, Kanellis MJ, Vargas CM. Current
Understanding of the epidemiology, mechanism and
prevention of dental caries in preschool children. Pediatr
Dent. 2002;24(6): 543-51.
5. Luca R. Pedodonție, Vol. 2, Ed. Cerma, București; 2003. p.
49-70.
6. Ramos FJ, Weintraub JA, Gansky, H CI, F JDB. Bacterial,
behavioral and environmental factors associated with early
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7. Anil S, Anand PS. Early Childhood Caries: Prevalence,
Risk Factors, and Prevention. Front Pediatr. 2017;5:157.
8. Aneta M, Luca R. Caria severă precoce la dinții temporari,
Ed. Eurobit, Timișoara; 2014.
9. Ismail AI, Sohn W. A sistematic review of clinical
diagnostic criteria of early childhood caries. J Public Health
Dent. 1999;59(3):171-91.
10. Xiao J, Alkhers N, Kopycko-Kedzierawski DT, Billings RJ
er al. Prenatal Oral Health Care and Early Childhood
Caries Prevention: A systematic review and Meta-Analysis.
Caries Res. 2019;53(4):411-421.
11. Oltean D, Pătroi G, Cuculescu M. Stomatologie preventivă,
Ed. Anotimp; 1996.p. 7-12,47-50, 61-140.
12. WH van Palenstein Helderman, Soe W, van 't Hof MA.
Risk factors of early childhood caries in a Southeast Asian
population. J Dent Res. 2006;85(1):85-88.
13. American Association of Paediatric Dentistry, Policy on
Early Childhood caries: Classification, Consequences,
Preventive Strategies.Oral Health Policies. 2011;33(6):47-
49.
14. Palmer CA, Kent R Jr, Loo CY, Hughes CV, Stutius E,
Pradhan N, Dahlan M, Kanasi E, Arevalo Vasquez SS,
Tanner AC. Diet and caries-associated bacteria in severe
early childhood caries. J Dent Res. 2010;89(11):1224-9.
15. Agarwal V, Nagarajappa R, Keshavappa SB, Lingesha RT.
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Association of maternal risk factors with early childhood
caries in schoolchildren of Moradabad, India. Int J Paediatr
Dent. 2011;21(5):382-8.
16. Li Y, Zhang Y, Yang R, Zhang Q, Zou J, Kang D.
Associations of social and behavioural factors with early
childhood caries in Xiamen city in China. Int J Paediatr
Dent. 2011;21(2):103-11.
17. da Silva Castro CR, de Sousa Cabral MBB, Mota ELA,
Cangussu MCT, Vianna MIP. Analysis of the influence of
low birth weight on the time of eruption of dental caries in
children in early childhood. J Public Health Dent.
2019;79(4):292-297.
18. Gabriela N, Livia P, Lenita L. Relationship among alfa
amylase and carbonic anhydrase VI in saliva, visible
biofilm and early childhood caries: a longitudinal study. Int
J Paedr Dent. 2016;27(3):174-182.

AMT, vol. 26, no. 1, 2021, p. 74

 CLINICAL ASPECTS
ACTA MEDICA TRANSILVANICA March 26(1):75-78
DOI: 10.2478/amtsb-2021-0020
Online ISSN 2285-7079

TREATMENTS’ COMPLEXITY IN DENTAL CARE ASSISTANCE,

URBAN VERSUS RURAL ENVIRONMENT - PRELIMINARY
STUDY
CAMELIA IONESCU1, MĂDĂLINA ADRIANA MALIȚA2, VIOREL ȘTEFAN PERIEANU3, MIHAI
BURLIBAȘA4, MAGDALENA NATALIA DINA5, RADU COSTEA6, MĂDĂLINA VIOLETA
PERIEANU7, RALUCA COSTEA8, IULIANA BABIUC9, IRINA ADRIANA BEURAN10, GABRIELA
TĂNASE11, MIHAELA CHIRILĂ12, IOANA VOINESCU13, MIHAI DAVID14,
LILIANA MORARU15
1,2,3,4,5,6,7,8,9,10,11,12,13,14
“Carol Davila” University of Medicine and Pharmacy Bucharest, 15
”Titu Maiorescu” University of Medicine and Pharmacy,
Bucharest

Keywords: dental care, Abstract: When talking about dental assistance we actually refer to the prevention, detection and
dental treatments, urban treatment of diseases of the oral and maxillo-facial region which, in most cases, have as a starting
environment, rural point or interest the dento-maxillary system. In this material, we tried to present a comparative study
environment on the typology and complexity of different stages of dental treatments that can be performed in urban
areas, compared to various stages of dental treatments that are performed and / or could be made in
rural dental offices from in Romania.

INTRODUCTION compared to the urban population in Romania. Of course, a

Dental care in urban areas is a very complex activity,
usually of good quality, compared to rural areas. By the end of the
last century (1998-1999), this was mainly due to a population in
the rural area who were extremely uneducated and uninformed
about the prevention and treatment of oral and dental diseases, due
to the lack of financial possibilities corresponding to the same
population in the rural area, as well as a poor training of dental
specialists working in rural areas. This poor training of rural
dentists was due in part to an extremely poor material endowment
at the time (for example, there were areas without running water,
where the installation of a dental unit was done in extremely
difficult conditions at an inadequate water source, source provided
by a submersible pump, sterilization equipment was obsolete; a
dental x-ray usually meant a trip to a larger town where there were
X-ray devices, town that could be even at extremely long
distances from the residence), and on the other hand due to a
rather difficult access to modern sources of information: internet,
specialized literature, courses, congresses, conferences etc.
Currently, we consider that the access to information
has been solved almost entirely by extending the coverage of the
Internet to the entire territory of Romania (basically, today only if
you don't want to, you don't inform yourself), and clinical-material
endowments in dentistry in rural areas it has improved
substantially, due to the transfer of dental services to the private
sector (including dental laboratories and dental x-ray offices),
which means in fact substantial investments of dental
entrepreneurs in rural areas of Romania.
However, the discrepancy between the quality of dental
treatments in urban areas compared to the same type of treatments
in rural areas remains and is mainly due both to the lower training
of dental professionals working in rural areas, aspect with which
we, the authors, agree only to a rather small extent, as well as on
account of very low financial possibilities of the rural population,
certain lack of education of the rural population in our country
regarding the prevention and treatment of diseases from oral and
dental areas should not be excluded.
AIM
A characteristic of urban dentistry is a high patient
demand (an average of 12-20 patients daily in the peak months),
presented unevenly over time (large variations from day to day,
but also within the same day).(1) Thus, the urban population,
especially the adult population, shows a pronounced sense
regarding the preservation of teeth on dental arches but, whose
therapy requires it in most cases late, but insistently opting on
rehabilitation prosthetics of existing edentations, including
implant-supported rehabilitations.(1-5) Usually, fixed prosthetic
restorations are required, because wearing of mobile prostheses is
related to some people to the idea of aging. Practically, all types of
prosthetic restorations, both mobile and especially fix, including
implant-supported ones involve not only a very good professional
training of the dentist, an excellent clinical-material endowment of
the office where it takes place the activity of dentistry, but also the
quick and easy access to high-performance dental laboratories,
able to approach and carry out any kind of prosthetic
restorations.(1-5)
Another type of demands that we find mainly in the
urban population, refers to orthodontic appliances for teeth
straightening, fixed and removable, especially in children,
adolescents and young people. Specifically, specialists in
orthodontics and dento-facial orthopedics are found concentrated
in urban areas, knowing that this category of dentists performs
treatments with a special complexity, especially since most of
their patients are in the age range 5-18 years, which makes the
collaboration between medical staff and patient more difficult,
compared to the case of adult patients.(1-5)

14
Corresponding author: Mihai David, Str. Plevnei, Nr. 19 Sector 1, Bucureşti, România, E-mail: mburlibasa@gmail.com, Phone: +40723 472632
Article received on 21.01.2021 and accepted for publication on 02.03.2021
AMT, vol. 26, no. 1, 2021, p. 75
 CLINICAL ASPECTS
Regarding coronary fillings, even when discussing
extensive coronary damage, patients in urban areas frequently opt
for such conservative therapies, avoiding tooth extraction, a more
radical therapeutic method frequently practiced in rural areas.
(especially until the end of the twentieth century).(1-5)
Thus, these types of dental treatment requests that we
frequently find in the urban population, is a common phenomenon
for this category of patients, compared to patients from rural areas
of Romania where, as mentioned in the introductory part, we
discuss, at least in theory, about a population with fairly limited
financial resources and training, in terms of prevention and
treatment of diseases with oral and dental areas.(1-8)
AIM
Starting from the ideas presented so far, we tried to
make a material regarding the complexity of different stages of
dental treatments that can be performed in urban areas, compared
to various stages of dental treatments that are and / or could be
performed in dental offices from rural areas in Romania. In fact,
the issues presented so far are both the purpose and arguments for
conducting this study, even if it is a preliminary one. Specifically,
in this material, we will discuss general and particular aspects of
the way of carrying out the medical activity with dental profile,
from the urban areas of our country.
MATERIALS AND METHODS
In the urban environment not only in Romania, there is
a very large and unequal demand of the population for all types of
medical services, but especially for dentistry, which results in a
fluctuating activity, which does not allow a careful use of time and
it is not very effective for performing complete and complex
therapeutic acts, specific to dentistry.(1-5,9-13)
Thus, if the dentist lets himself involved in this activity,
it ends up performing an insufficient examination of the patient
and correct therapeutic acts, thanking himself with performing
palliative treatments (sedative filling, temporary filling, halves or
even fragments of therapeutic acts), things that lead both to a low
quality, inefficient and sometimes harmful dental care, but also to
the maintenance of overload.(1-5)
The examination, which requires at least some
anamnestic data and a careful examination of the entire dento-
maxillary system, requires a variable time, which can last between
15 and 30 minutes. But, the examination in dentistry can take even
longer and for the fact that, most of the time, we are dealing with
several conditions that require, each one, a careful investigation
for a correct diagnosis. Thus, the examination in dentistry must be
done in a single session and cannot be limited to an inventory of
the various conditions found. In order to make a decision, they
must be corroborated, in a synthesis that can be called “the state of
the dento-maxillary system”. This operation constrains us to
record what was found in an examination form, which at this time
has become mandatory, once with the informed consent of the
patient. Based on the established diagnoses, the dental practitioner
draws up the therapeutic indications, which he records in a
therapeutic plan staggered in time, in phases. Only after such a
complete examination, it is possible to proceed to a complete and
complex dental treatment of a dento-maxillary system.(1-5)
Another problem that must be the basis for organizing
the practical activity of dental care is represented by the practice
of complete documents, completed correctly in the consulting
session. Thus, in the complex dental care, which characterizes the
activity of the dentist in the 21st century, there are a multitude of
various therapeutic acts. These therapeutic acts are not identical to
each other and the same therapeutic act is not identical for all
teeth. This results in a varied time of performing these therapeutic
maneuvers, a duration that also depends on the quality of
materials and instruments used, but also on the skill and
AMT, vol. 26, no. 1, 2021, p. 76
conscientiousness of the dental practitioner. Thus, dental
extractions, coronary and root fillings, as well as various
therapeutic acts characteristic of different types of prosthesis (fix,
mobile, etc.) cannot be considered to have the same value of
time.(1-5) For an efficient dental care, with complete and complex
therapeutic acts in the session, it is necessary to practice the
planned sessions, reserving the time necessary to perform these
acts, corresponding to the experience of the practitioner.(1-5)
But, planning patients for an effective dental treatment
can encounter 2 quite serious difficulties, as follows:(1-5)
- It is complicated for a dentist working alone to precisely
delimit the time of his planned therapeutic sessions, in
relation to the cases that require at least an examination and,
possibly, an emergency treatment;
- Scheduling requires strict compliance both by the dental
team (dentist and nurse) and by patients. Failure to comply
with the schedule can cause either congestion or gaps in the
medical team's program, aspects that thus compromise the
principle, based on which the model of planning therapeutic
acts in the medical system of dentistry was introduced.
Depending on the type of dental condition for which the
patient requests specialized treatment, most often there is an acute
condition that caused him to request examination, and which
requires immediate intervention. Basically, the dentist must be
prepared to perform this therapeutic act or the dental service must
be organized in such a way that the therapeutic act can be
performed immediately. And this is usually a feature of dental
services located in urban areas of Romania.(1-5)
Another criterion that must be taken into account in a
dentistry service in urban areas of Romania, is the importance of
the oral and dental pathological condition for the health of the
individual. In this category, attention should be paid to the
following issues:(1-5)
- firstly, chronic infections, which may be the cause of a
systemic disease (outbreak), diagnosed or at least suspected;
- secondly, to pregnant women, whose state of dentition may
influence the health of the mother and fetus; it is known that
the more advanced the pregnancy is, the harder to bear the
treatment;
- thirdly, to patients with ailments or disabilities can hardly
stand dental treatment.
Starting from the previously mentioned aspects,
important in order to carry out dental therapeutic maneuvers in
urban areas, we compiled a 7-point questionnaire, which we
applied to a number of 47 dentists, who work in the private sector
from various urban regions in Romania, more precisely in large
cities, such as Bucharest, Constanța, Pitești, Brașov and Râmnicu
Vâcea. The study, with a preliminary character, took place
between October 15 and November 15, 2019.
All subjects involved in the study were aged between 30
and 65 years, being distributed as follows: 25 of the subjects were
females (53.19%), while the remaining 22 subjects were males
(46.81%) (figure no. 1).
Next, we will present the 7 questions addressed to the
study participants:
1. What is the most important moment of a dental treatment?
a. Follow-up care; b. Examination; c. Performing dental
treatment; d. Establishing the dental treatment steps?
Correct answer: b.
2. In how many treatment sessions should an appropriate
dental examination should be carried out? a. 1 session; b. 2
sessions; c. 3 or more sessions? Correct answer: a.
3. In order to establish a diagnosis and to be able to develop a
feasible treatment plan, the dentist performs the following
steps: a. Performs an examination that lasts at least 15-30
minutes; b. Performs only a review of the general ailments
from which the patient suffers; c. Performs the so-called
 CLINICAL ASPECTS
„state of the dento-maxillary system”, and records what he the study considered that any dental treatment should start with
found in the observation sheet; d. Record the patient's a thorough examination to establish the correct starting point.
informed consent; e. Based on the established diagnoses, he
draws up the therapeutic indications, which he records in a Figure no. 2. Assessment of importance of the stages of
therapeutic plan staggered in time, in phases? Correct dental treatment
answers: a, c, d, e.
4. One of the organizing problems of the practical activity of
dental care is represented by: a. Performing complete and
correct therapeutic acts in treatment session; b. Performing
dento-alveolar surgery maneuvers, such as dental
extraction, apical resection, etc., in time intervals between
20-45 minutes; c. Performing specific dental prosthetics
maneuvers only in dental laboratories? Correct answer: a.
5. For an efficient dental assistance, with complete and
complex therapeutic maneuvers in treatment session, it is
necessary for: a. The practice of the planned treatment
sessions, with the reservation of the time necessary to
perform these acts, corresponding to the experience of the
practitioner; b. Picking up patients as they arrive at the Regarding the steps that the dentist must follow in
dentist's office, without prior appointment; c. As the dentist order to establish an accurate diagnosis that will lead to an
completes a therapeutic act, the next patient is asked by appropriate treatment plan, 35 of the practitioners (representing
telephone to go to the office for specialized treatment? 74.47%) answered correctly (variants a, c, d and e) and only 12
Correct answer: a. practitioners (representing 25.53%) included, in addition to the
6. Patient planning for efficient dental treatment may correct answers, a smmary analysis of the general ailments the
encounter the following difficulties: a. It is difficult for a patient suffers from (figure no. 3).
dentist working alone to precisely establish the time of his
planned therapeutic sessions, in relation to the demands Figure no. 3. The necessary steps to establish a correct
that require at least an examination and, possibly, an diagnosis and the appropriate treatment plan
emergency treatment; b. The programming requires a
rigorous observance both by the dental team (dentist and
nurse) and by the patients, in order to avoid both
overcrowding and time gaps in the program; c.
Collaboration with the dental laboratory is an
insurmountable problem, in case of poor patient planning?
Correct answers: a, b.
7. A criterion that must be taken into account in a dental
service in urban areas of Romania, is the importance of the
oral and dental pathological condition for the health of the
individual. In this category, attention should be paid to the
following issues: a. Chronic infections, which may be the Concerning the main problem of organizing the dental
cause of a systemic disease (outbreak), diagnosed or at least activity, most of the subjects participating in the study (40
suspected; b. Pregnant women, in whom the state of dental representing 85.11%) answered correctly, namely maneuvers
health can influence the health of the mother and fetus; c. performed completely during a treatment session. Only 7
Patients with ailments or disabilities who are undergoing subjects (representing 14.89%) answered incorrectly referring to
heavy dental treatment? Correct answers: a, b, c. the duration of surgery (figure no. 4).

Figure no. 1. Gender distribution of study group Figure no. 4. Analysis of the problems in organizing the
dental activity

RESULTS
The analysis of the answers led to the following
results:
The most important stage of dental treatment was
correctly considered by most respondents: examination (25
representing 53.19%), while 14 respondents considered follow-
up care and 8 respondents (representing 17.02%) the treatment
itself (figure no. 2).
It is not surprising that all the specialists included in
All respondents to the study considered that the
activity of efficient dental care is based on a thorough planning
of treatment sessions, for the proper performance of therapeutic
maneuvers.
Regarding the difficulties that may arise in patient
planning, most specialists (37 representing 78.72%) took into
account the complex process of planning and treatment for

AMT, vol. 26, no. 1, 2021, p. 77

 CLINICAL ASPECTS
doctors working alone in the office but also the problems that
arise from non-compliance with appointments (figure no. 5). A
small number of specialists also wrongly considered the
communication with the dental laboratory (10 representing
21.28%).
Figure no. 5. Assessing issues that may arise in patient
planning
The last question related to the criteria to be taken into
account in dental care, most practitioners correctly included
chronic infections, pregnant women as well as patients with
diseases or disablements (39 representing 82.98%). A small
number of practitioners (8 representing 17.02%) omitted chronic
infections from the correct answers (figure no. 6).
Figure no. 6. Criteria to be taken into account in dental care
CONCLUSIONS
The conclusions arising from the analysis of the
answers obtained by applying the questionnaire are as follows:
The examination in dentistry is the most important
maneuver not only for diagnosing a dental condition, but to
establish the condition diagnosis of the dento-maxillary system,
in order to establish the therapeutic attitude.
The complete examination of a patient must be done
in a treatment session planned for it.
Regardless the reason for which the patient presents in
a dental office, the examination act acquires an overwhelming
importance for it.
Planning patients at precise times, with the reservation
of the time necessary to perform the indicated therapeutic acts,
is the only way of working able to ensure qualitative and
quantitative efficiency of dental care in urban areas.
The dentists included in the study work in several
large cities in Romania, and the majority provided correct
answers to the questionnaire applied (over 50%), which proves a
good professional training both theoretically and practically for
this category of dental specialists working in urban areas.
It is necessary to develop a methodology or a practice
guide, which should include, from our point of view, the
following ideas:
a) the scheduling of the examination must be done in
AMT, vol. 26, no. 1, 2021, p. 78
relation to the volume of requests;
b)immediate insurance of the dental emergency;
c)planning patients for complex and comprehensive dental
care, in relation to the capacity of the dental office and
based on priority criteria;
d) planning patients to perform complete therapeutic acts in
the rigorous scheduling system;
e) follow-up of rebalanced patients, in order to maintain the
balance obtained (follow-up care).
Acknowledgement:
In this article, all the authors have equal
contributions.
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