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Received: 28 January 2022    Revised: 7 May 2022    Accepted: 18 May 2022

DOI: 10.1111/jocd.15135

ORIGINAL ARTICLE

Sterile abscess due to hyaluronic acid: A new diagnosis and a

proposal for treatment-­A series of eight cases

Gabriela Munhoz MD1 | Fernanda Aquino Cavallieri MD2 |

Laila Klotz de Almeida Balassiano MD3 | Maria Fernanda Tembra MD4 |
José Marcos T. Cunha MD, PhD5  | Alessandro C. O. Silveira MD6 |
Marcos Vinicius Rust Moreira MD7 | Marcia Ramos-­e-­Silva MD, PhD8

1
Clínica Gabriela Munhoz, University
Hospital and School of Medicine, Federal Abstract
University of Rio de Janeiro, Rio de
Background: In recent years, fillers procedures with hyaluronic acid (HA) have grown
Janeiro, Brazil
2
Cavallieri Clinic, Member of Brazilian
significantly. Despite HA relative safety, the number of cases of complications after
College of Radiology and Diagnostic injections has grown, and in many of which, we are not aware of or have little control
Imaging and of the National Commission
of Ultrasound –­Brazilian College of
over.
Radiology and Diagnostic Imaging Rio de Aims: In this article, the authors describe a new adverse reaction after filling with HA
Janeiro, Rio de Janeiro, Brazil
3
injection, the sterile abscess.
HUCFF-­UFRJ and School of Medicine,
Federal University of Rio de Janeiro, Rio Patients/Methods: We present eight patients with similar clinical, laboratory, and
de Janeiro, Brazil ultrasound characteristics for sterile abscess and report a new therapeutic modality
4
Clínica Maria Fernanda Tembra,
for it.
University Hospital and School of
Medicine, Federal University of Rio de Results: All cases were treated with “Munhoz-­Cavallieri Lavage Protocol” procedure
Janeiro, São Paulo, Brazil
5
with complete resolution.
University Hospital and School of
Medicine, Federal University of Rio de Conclusions: “Munhoz-­Cavallieri Lavage Protocol” serves as a guideline in diagnosis
Janeiro, Rio de Janeiro, Brazil and management of sterile abscess.
6
Department of Pharmaceutical Sciences,
Regional University of Blumenau, KEYWORDS
Blumenau, Brazil
complications, fillers, hyaluronic acid, sterile abscess
7
German Society of Infectology, Internal
Medicine, Department of Antibiotic
Stewardship Vivantes Hospitals, Berlin,
Germany
8
Centro Dermatológico Marcia Ramos-­
e-­Silva, University Hospital and School
of Medicine, Federal University of Rio de
Janeiro, Rio de Janeiro, Brazil

Correspondence
Gabriela Munhoz, Clínica Gabriela
Munhoz, University Hospital and School
of Medicine, Federal University of Rio de
Janeiro, Rio de Janeiro, Brazil.
Email: gabimunhozfontoura@gmail.com

J Cosmet Dermatol. 2022;00:1–7. wileyonlinelibrary.com/journal/jocd© 2022 Wiley Periodicals LLC.     1 |

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2      MUNHOZ et al.
1  |  I NTRO D U C TI O N
According to an annual survey by the American Society of Plastic
Surgeons, dermal fillers have become the second most commonly
performed non-­surgical cosmetic procedure among individuals in
the baby-­boomer generation seeking to prevent and treat the signs
of aging.1–­3 For Belezney et al.,4 the number of injectable procedures
grew by 300% from 2000 to 2017. In recent years, fillers procedures
with hyaluronic acid (HA) have shown the most significant growth.
Despite its relative safety, as it is a biologically compatible product
with endogenous HA, there are currently on the market more than
100 HA-­based products for injectable purposes, with particular
physical and chemical properties, being performed by several med-
ical and non-­medical professionals with different techniques and
levels of anatomical knowledge. Consequently, the current cosmetic
dermatology scenario sees an increase in the number of complica-
tions after injections of facial fillers, many of which we are not aware
of or have little control over.
Fillers with HA can be applied on all anatomical levels. The ap-
plication technique is linked to the rheology of the product and its
distribution in tissues.5–­7
In addition, the different technologies used by companies to sta-
bilize and prolong the filling effect of HA should also be questioned,
since the product has been undergoing modifications that could be
responsible for complications. Therefore, companies must support
medical professionals in cases of complications.
In this study, we describe an adverse reaction after filling with
HA presenting clinical, laboratory, and ultrasound similarities in
eight patients. The complication was not initially responsive to the
treatments previously recommended in the literature. However, all
cases evolved with complete resolution after the protocol devel-
oped by the authors named “Munhoz –­Cavallieri Lavage Protocol.”.
2  |  M ATE R I A L S A N D M E TH O DS
We report a series of eight cases of facial abscesses after injections
of HA evaluated and followed up by the authors.
2.1  |  Diagnostic evaluation
2.1.1  |  Face ultrasound
All eight cases had facial ultrasonography for diagnostic evaluation
and intervention guidance (drainage of the material and injection of
the solution created by the authors, called “Munhoz-­Cavallieri Lavage
Protocol”). Ultrasound images were obtained with EPIQ7 equipment
(Philips Medical Systems, Bothell, WA, USA), and two high-­frequency
transducers (7 to 15 and 4 to 18 MHz) were used. Ultrasound examina-
tion included a B-­mode assessment associated with Color Doppler to
evaluate local vascularization. A large volume of gel was used between
the transducer and the region, and the least possible compression with
the transducer, to obtain the best accuracy of superficial structures.
The patients were initially submitted to an ultrasound examination,
always performed or monitored remotely by the same radiologist, one
of the authors of this article, aiming to (1) identify the filler material
used, (2) exclude a filler other than HA, and (3) assess the presence and
characteristics of the collection. Ultrasound diagnosis of the collection
was performed in the presence of an anechoic well-­defined image,
which may have suspended debris and become isoechoic, according
to the high protein content of the collection (the higher the protein
content, the more isoechoic). During dynamic compression and evalu-
ation, it was possible to visualize the fluid in the collection. In the Color
Doppler analysis, peripheral vascularization of the collection stood
out, and never inside the image. In some cases, signs of panniculitis of
the surrounding subcutaneous tissue were observed. The collections
were located at the layer where HA was injected: subcutaneous, intra-
muscular, or periosteal collections were observed (Figure 1).
2.1.2  |  Laboratory examinations
All patients had laboratory blood tests, including white blood cell count
and inflammatory function tests (CRP and ESR). Bloodwork presented
results showing an inflammatory condition, and four patients had mild
leukocytosis; three had increased ESR, three had elevated CRP, and
only one patient had no abnormalities in laboratory tests (Table 1).
F I G U R E 1  Two different patients
presenting unilateral facial edema
associated with few phlogistic signs
and pain in sites previously treated with
injectable HA. (A) Left infrapalpebral
edema. (B) Edema in right zygomatic area
TA B L E 1  Eight cases of sterile abscess

Cleaning
MUNHOZ et al.

Oral protocol
Onset of ATBs corticoid (“Munhoz-­
sypmtons before before Cavallieri
HA injected / Needle x after HA Signs and cleaning cleaning Earlier treatment Microbiology Ultrasound: Others Lavage
Patient volume (ml) Age Facial area cannula injection Trigger symptons Laboratory exams protocol protocol procedures analysis collection episodes Protocol”) Outcome

1 Restylane 50 Left tear cannula 5 days No Few erythema, Leukocytosis, 3 Yes Hyaluronidase once Yes -­Sterile Yes No 2 times Cure
lido/0.5 ml trough edema increased
each tear and pain ESR and
trough normal CRP

2 Juvederm 49 Left cheek cannula 7 days No Intense edema, Leukocytosis, 4 Yes Nothing Yes -­Sterile Yes Right malar 3 times left Cure
Voluma/1 ml few normal ESR after malar and
cheeks erythema and CRP 15 days once right
and pain malar

3 Juvederm 57 Right cheek cannula 10 days No Intense edema, Normal 4 Yes Hyaluronidase 3 times Yes -­Sterile Yes No Once Cure
Voluma/0.5 ml few examinations
each cheek erythema
and pain

4 Juvederm 71 Tear trough cannula + ​ 7 days Dental Edema Normal leukocyte 1 Yes Hyaluronidase once Yes -­Sterile Yes Contralateral Once each Cure
Volux/0.5 ml and right needle procedure and CRP; side side
each cheek chin increased after
Restylane ESR 45 days
Defyne/0.5 ml
each chin

5 Juvederm 33 Right jawline needle 3 months No Edema Leukocytosis, 4 Yes Ultrasound drainage Yes -­Sterile Yes No Once Cure
Voluma/1 ml normal ESR twice
em each and CRP
zygoma
Juvederm
Voluma/1 ml
each chin

6 Hialurox/0.5 ml 26 Right cheek needle 4 months No Intense edema Leukocytosis, 9 Yes Four times of ultrasound Yes -­Sterile Yes No Once Cure
each cheek increased drainage and one
Hialurox/1 ml lips ESR and CRP spontaneous
drainage

7 Juvederm Voluma 40 Bilateral needle 8 days Dental Edema and Leukocytosis, 2 Yes Ultrasound drainage Yes -­Sterile Yes No 3 times Cure, but remained
0.4 ml each temples procedure pain increased twice with negatives with difficulty
temple and (trismus) CRP microbiology in opening the
Juvederm Voluma masseter examinations mouth which
0.6 ml each improved after
zygoma physiotherapy

8 Juvederm Voluma 38 Chin cannula + ​ 7 days Gingivitis Few erythema, Normal leukocyte; 3 Yes One drainage with Yes -­Sterile Yes No Once Cure
4 ml chin needle edema increased negatives
and pain ESR and CRP microbiology
examinations and
two ultrasound
drainage + ​
hyaluronidase
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4      MUNHOZ et al.
F I G U R E 3  Sonographic images in Mode B of abscesses in different layers. (A) Purulent collection in subcutaneous layer. (B) Purulent
collection inside temporal muscle. (C) Purulent collection in periosteal plane, zigomatic arch
2.1.3  |  Analysis of the drained material
Due to the presence of the collection, US-­guided drainage was per-
formed, with the withdrawal of thick liquid material, ranging from
purulent, seropurulent, and serosanguineous (Figure  2). Most pa-
tients were not using antibiotics and/or oral corticosteroids at the
time of the drainage. Considering that the pre-­analytical process is
of great importance for a reliable result, the material was collected
using a strict asepsis and antisepsis protocol recommended by the
microbiologist. The content was then sent immediately for analysis
in a microbiology laboratory. The aspirated material was divided into
three sterile flasks, and the following tests were requested: flask 01:
Cytology, flask 02: search for common germs (Gram and culture),
and flask 03: research for mycobacteria (culture, PCR and Ziehl-­
Neelsen). There was no growth of microorganisms in any case, and
therefore the authors proposed the term “sterile abscess” for this
specific complication.
2.1.4  |  “Munhoz-­Cavallieri Lavage Protocol”
After collection drainage, the patient was submitted to the “Lavage
Protocol,” proposed by the authors.
F I G U R E 2  (A,B) “cold abscesses” –­
intense edema without phlogistic signs.
(A) Edema in right zighomatic arch. (B)
Edema in both malar regions, markedly on
right side
The “Munhoz-­C avallieri Lavage Protocol” consists of the
following:
1. Anesthetic button with lidocaine for the needle entry hole.
2. Aspiration of material for microbiological study—­(including the
two patients that were on antibiotic therapy).
3. Solution for lavage protocol: hyaluronidase Reductonidasa® di-
luted with 3 ml of sterile saline solution (1500 IU) + 3 ml of sterile
saline + 1 ml triamcinolone 20 mg/ml + 3 ml of 2% lidocaine for a
total of 10 ml of solution (Figure 3).
4. Carrying out the washing with a 3  ml syringe and a 22G or
23G needle: injection of 1–­3 ml of the solution, aspirating, and
disposing. The process is repeated two to three times to wash
the collection area. Discard the syringes and needles used in
each step.
5. During the third or fourth injection, with sterile syringe and nee-
dles, it was deposited 0.5–­3 ml of the solution into the cavity, to
occupy the purulent secretion space, that is, to collapse the space
visualized on the US and dilute the remaining HA.
After the “Lavage Protocol,” all patients reached cure criteria,
including clinical, laboratory, and ultrasonographic improvement. It
was not necessary to keep medications or antibiotics during or after
the protocol. (Table 1).
MUNHOZ et al.
F I G U R E 4  Sero-­purulent appearance
of material drained by US-­guided from
differente patients
F I G U R E 5  Patient before (A) and
after 48 h of “Munhoz–­C avallieri Lavage
protocol” (B) with total resolution
3  |   R E S U LT S
The eight cases occurred in women aged between 26 and
71 years. A common feature is the clinical history of unilateral
facial edema associated with few erythema, warm, and pain in
sites previously treated with injectable HA (Figure 4 and Table 1).
Two patients complained of trismus. None had a fever. Two pa-
tients only manifested intense edema without phlogistic signs
(Figure 5). Six of the eight cases had a recent onset within 30 days
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      5
after HA injection, and two were late, with onset after 30 days
of applying the filler. The following products have been identi-
fied: Restylane Defyne® (Galderma/Q-­M ed, Sweden), Hialurox®
(Laboratório Termofrio, SP, Brasil), Juvederm Volux® (Allergan,
Inc., Irvine, CA, USA), and Juvederm Voluma® (Allergan, Inc.). All
cases responded partially to different protocols of oral antibiot-
ics and oral corticosteroids, recurring at variable intervals after
discontinuing the medications. The number of antibiotics used
ranged from 01 to 09 per patient.
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6      MUNHOZ et al.
All patients had soft tissue ultrasonography with a diagnosis of
thick fluid collection corresponding to the swollen area at the site
of the previous HA injection. Ultrasound images of the contralateral
side of the face showed the presence of focal HA deposits.
Four patients were submitted to blind application of hyaluro-
nidase to dilute the HA with little response. Three had ultrasound
guided drainage with a discharge of purulent material, with a recur-
rence of the collection. Most patients underwent more than one
drainage without success. One patient had no other treatment be-
sides the “Lavage Protocol,” at a later moment.
Two patients presented recurrent abscesses on the contralateral
side of the face, 4 weeks after the Lavage Protocol, in sites of previ-
ous injection with hyaluronic acid and not treated before. Both cases
were treated with a single “Munhoz-­C avallieri Lavage Protocol” pro-
cedure with full resolution.
Given the clinical histories that included episodes of relapses,
multiple incomplete regimens of oral antibiotics and previous unsuc-
cessful drainages, the authors established a flowchart for manag-
ing these cases, as described above as “Munhoz-­C avallieri Lavage
Protocol.” All patients remain free of recurrent episodes after
1.5 years of average follow-­up.
4  |  D I S C U S S I O N
The increase in the number of complications after filling with HA can
be observed by the escalation in scientific publications on the sub-
ject, especially in the last 5 years. However, we are still learning to
manage these events as new complications emerge and there is no
standardized treatment consensus. The ultrasound examination has
proven to be an excellent complementary method in complicated
cases as it allows the identification of the cosmetic filler previously
performed,8–­10 in addition to diagnosing possible aesthetic com-
11,12
plications and its evolutionary assessment. Furthermore ultra-
sound can guide the therapeutic intervention.13
In this article, the authors report eight cases of a complication
still very little known: the sterile abscess after HA injection. In litera-
14
ture, we could find only one case described after using HA as filler.
Faced with a patient presenting unilateral or bilateral edema with
few phlogistic signs in a site previously treated with injectable HA,
the procedure proposed by the authors initially consists of perform-
ing an ultrasound exam to assess the presence or absence of a collec-
tion. With the possibility of dynamic visualization of fluid collection
and estimate of its total volume and location, it is possible to aspi-
rate the material for microbiological study and guide the “Munhoz
–­Cavallieri Lavage Protocol.” The imaging method allows the visual-
ization of the best site for puncture, and the assessment of the res-
olution, which is the complete emptying the collection. The drained
material must be sent for analysis to a specific microbiology labora-
tory immediately after drainage, and must not be stored in a refrig-
erator. About 70%–­80% of the materials are discarded due to the
pre-­analytical difficulty, which is why we established a strict protocol
of asepsis, antisepsis, and storage in a sterile flask. Then, the three
samples should be sent to laboratory study, one for cytology, one for
the research of common germs (culture, gram, and bacterial PCR),
and a sample for screening for mycobacteria (culture, PCR and Ziehl-­
Neelsen). In the event of not finding the bacteria and/or mycobacte-
ria in the Gram and not growing in adequate culture media, classifies
the purulent collection as a sterile abscess. Thus, we emphasize that
not every purulent collection is synonymous with infection. Pus may
be just the result of putrefaction of inflammatory cells.15
The pathogenesis of HA-­induced sterile abscesses is not entirely
clear. The immunogenic characteristic of each anatomical layer, the
relation between tissue layer and the technique, in addition to the
rheology and the properties of the product are factors to be con-
sidered in the pathophysiology of complications. HA interacts with
several receptors on endothelial cells and phagocytes, participating
in both inflammatory processes and tissue repair. The trauma related
to the procedure, the concomitant systemic infection, and the partial
degradation of the injected product can contribute to the triggering
of sterile inflammation, from the engagement of cells and receptors
of innate immunity, capable of recognizing harmful signals for cells
and tissues in the absence of infection. The strategy of combining
hyaluronidase with intralesional corticosteroid therapy brought a fa-
vorable outcome in the eight cases analyzed by eliminating the trig-
ger (intact filler and its degradation products) and locally inhibiting
the inflammatory cells.16–­21
Some authors question the role of bacterial biofilms—­communities
of unicellular organisms attached to a surface through a polysaccha-
ride matrix—­in the pathogenesis of late complications of injectable
fillers. Sterile abscess after injectable HA may also occur even long
after the product was injected.21 In both situations, sterile abscess or
presence of a biofilm in the drained material could result in negative
culture, because the bacteria in biofilms grow covered by a polysac-
charide layer, which avoids the detection of the microorganism un-
derneath it. However, in face of biofilms, treatment should include
removal of infected indwelling devices and selection of well pene-
trating and sensitive antibiotics. Nevertheless, for all the patients in
our case series, the cure was reached without the use of antibiotics.
Therefore, we believe that the inflammatory reaction observed in this
case series is an exacerbated foreign body immunogenic reaction to
HA, without the obligatory presence of bacteria. However, this is a
difficult hypothesis to refute, considering the difficulty in its diagno-
sis, and more studies are necessary to reach accurate information.
The “Munhoz–­C avallieri Lavage protocol” (washing the cavity,
with an association of hyaluronidase, sterile saline solution, and in-
jectable corticosteroid) was created after several attempts to treat
sites previously filled with HA using antibiotics and oral corticoste-
roids, hyaluronidase, and even after ultrasound-­guided drainage,
with no success for recurrent abscesses.
5  |  CO N C LU S I O N
Sterile abscesses is a little-­known condition among complica-
tions after filling with HÁ that was previously treated as infectious
MUNHOZ et al.
abscesses without success. Possible etiology includes immunogenic-
ity of HA present in the tissue setting of an inflammatory overre-
action. Munhoz–­C avallieri Lavage protocol serves as a guideline in
diagnosis and management of this condition.
AU T H O R C O N T R I B U T I O N S
G.M., F.A.C., L.K.A.B., and M.F.T. designed the research study and
wrote the paper. J.M., A.C.O.S., M.V.R.M., and M.R.S analyzed the
data.
C O N FL I C T O F I N T E R E S T
The authors have no conflict of interest and there was no financial
support.
DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from
the corresponding author upon reasonable request.
E T H I C S S TAT E M E N T
Authors declare human ethics approval was not needed for this
study.
ORCID
José Marcos T. Cunha  https://orcid.org/0000-0003-3264-0929
Marcia Ramos-­e-­Silva  https://orcid.org/0000-0003-1625-0760
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How to cite this article: Munhoz G, Cavallieri FA, de Almeida
Balassiano LK, et al. Sterile abscess due to hyaluronic acid: A
new diagnosis and a proposal for treatment—­A series of eight
cases. J Cosmet Dermatol. 2022;00:1-7. doi: 10.1111/
jocd.15135