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Contents EDITORIAL 7 Triple Antithrombotic Therapy – Is It History or Should We Still Do It? Diana Opincariu REVIEW 11 Coronary Shear Stress after Implantation of Bioresorbable Scaffolds – a Modern Interdisciplinary Concept at the Border between Interventional Cardiology and Cardiac Imaging Dan Păsăroiu, Zsolt Parajkó, Ionuț Ferenț, Diana Opincariu, Annabell Benedek ORIGINAL RESEARCH 19 Evaluation of Three Esthetic Restorative Materials Used for Carious or Non-carious Cervical Lesion Restoration Gabriela Beresescu, Emanuela Tegla, Despina Temistocle, Alina Ormenisan, Alina Baldean 25 Low Level of Physical Activity in Two Roma Subgroups Compared to Non-Roma Population in Niraj Valley, Transylvania Monica I. Szabó, Anita Balázs, Beáta Máté, Piroska Kelemen CLINICAL UPDATE 29 The Role of Pedobarography and Therapeutic Padding in the Management of Hyperkeratosis due to Mechanical Stress Anca Chiriac, Cristian Podoleanu, Adrian Năznean, Simona Stolnicu CASE REPORT 33 Uncommon Differential Diagnosis of Acute Right-sided Abdominal Pain – Case Report Cédric Kwizera, Benedikt Wagner, Johannes B. Wagner, Călin Molnar 37 Skin Lesions in a Daclizumab-treated Patient with Multiple Sclerosis Anca Chiriac, Adrian Năznean, Cristian Podoleanu, Claudiu Molnar, Simona Stolnicu IMAGE FOCUS 41 Congenital Malalignment of the Nails Anca Chiriac, Adrian Năznean, Cristian Podoleanu, Claudiu Molnar, Simona Stolnicu Volume 4 / / Issue 1 / / March 2019
Transcript
Page 1: Contents - Journal of Interdisciplinary Medicine · Padding in the Management of Hyperkeratosis due to Mechanical Stress Anca Chiriac, Cristian Podoleanu, Adrian Năznean, Simona

Contents

Editorial

7 Triple Antithrombotic Therapy – Is It History or Should We Still Do It?

Diana Opincariu

rEViEW

11 Coronary Shear Stress after Implantation of Bioresorbable Scaffolds – a Modern Interdisciplinary Concept at the Border between Interventional Cardiology and Cardiac Imaging

Dan Păsăroiu, Zsolt Parajkó, Ionuț Ferenț,

Diana Opincariu, Annabell Benedek

original rEsEarch

19 Evaluation of Three Esthetic Restorative Materials Used for Carious or Non-carious Cervical Lesion Restoration

Gabriela Beresescu, Emanuela Tegla, Despina Temistocle,

Alina Ormenisan, Alina Baldean

25 Low Level of Physical Activity in Two Roma Subgroups Compared to Non-Roma Population in Niraj Valley, Transylvania

Monica I. Szabó, Anita Balázs, Beáta Máté,

Piroska Kelemen

clinical UPdatE

29 The Role of Pedobarography and Therapeutic Padding in the Management of Hyperkeratosis due to Mechanical Stress

Anca Chiriac, Cristian Podoleanu, Adrian Năznean,

Simona Stolnicu

casE rEPort

33 Uncommon Differential Diagnosis of Acute Right-sided Abdominal Pain – Case Report

Cédric Kwizera, Benedikt Wagner, Johannes B. Wagner,

Călin Molnar

37 Skin Lesions in a Daclizumab-treated Patient with Multiple Sclerosis

Anca Chiriac, Adrian Năznean, Cristian Podoleanu,

Claudiu Molnar, Simona Stolnicu

iMagE FocUs

41 Congenital Malalignment of the Nails

Anca Chiriac, Adrian Năznean, Cristian Podoleanu,

Claudiu Molnar, Simona Stolnicu

Volume 4 // Issue 1 // March 2019

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Editorial Board

Editor-in-chiEF

Theodora Benedek Clinic of Cardiology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Center for Advanced Research in Multimodality Cardiac Imaging, Cardio Med Medical Center, Tîrgu Mureș, Romania

dEPUty Editors

Charalambos AntoniadesDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK

Imre BenedekClinic of Cardiology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Christos ChantziantoniouUniversité Pierre-et-Marie-Curie, Sorbonne Uni-versités, Paris, France

Dietmar GlogarMedical University of Vienna, Austria

Ota HlinomazClinic of Cardiology, University of Brno, Czech Republic

Monica Marton PopoviciDepartment of Critical Care, Swedish Hospitals, Seattle, USA

Managing Editors

Diana OpincariuUniversity of Medicine and Pharmacy, Tîrgu Mureș, Romania

Nóra RatUniversity of Medicine and Pharmacy, Tîrgu Mureș, Romania

Editorial board

Charalambos AntoniadesDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK

Vladimir BacâreaDepartment of Research Methodology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Simona BățagăClinic of Gastroenterology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Imre BenedekClinic of Cardiology, University of Medicine and Pharmacy Tîrgu Mureș, Romania

Carmen BirișDepartment of Dental Health, University of Medi-cine and Pharmacy Tîrgu Mureș, Romania

Elena BobescuClinic of Cardiology, "Transilvania" University, Brașov, Romania

Florin BuicuDepartment of Public Health, University of Medi-cine and Pharmacy, Tîrgu Mureș, Romania

Simona CerneaDepartment of Internal Medicine, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Christos ChantziantoniouUniversité Pierre-et-Marie-Curie, Sorbonne Uni-versités, Paris, France

Călin ChibeleanClinic of Urology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Monica ChițuClinic of Cardiology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Radu Ciudin"Carol Davila" University of Medicine and Phar-macy, București, Romania

István ÉdesUniversity of Debrecen, Hungary

Dan GeorgescuClinic of Gastroenterology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Dietmar GlogarMedical University of Vienna, Austria

Mariann GyöngyösiMedical University of Vienna, Austria

Ota HlinomazClinic of Cardiology, University of Brno, Czech Republic

Adrian IancuClinic of Cardiology, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj Napoca, Romania

Radu IliescuDepartment of Physiology, University of Medicine and Pharmacy, Iași, Romania

Piroska KelemenClinic of Internal Medicine, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

István KovácsClinic of Cardiology, University of Medicine and Pharmacy Tîrgu Mureș, Romania

Erzsébet LázárClinic of Haematology and Stem Cell Transplanta-tion, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Marius George LinguraruSheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, Washington DC, USA

Monica Marton PopoviciDepartment of Critical Care, Swedish Hospitals, Seattle, USA

Pál Maurovich HorváthSemmelweis University, Budapest, Hungary

Călin MolnarClinic of Surgery, University of Medicine and Phar-macy, Tîrgu Mureș, Romania

Anca NegovanClinic of Internal Medicine, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Dan OlinicClinic of Cardiology, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj Napoca, Romania

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indExing

The Journal of Interdisciplinary Medicine is indexed via De Gruyter Open in the following international databases:

•Baidu Scholar•Celdes•CNKI Scholar (China National Knowledge

Infrastructure)•CNPIEC•EBSCO Discovery Service•Google Scholar

• J-Gate•Naviga (Softweco)•Primo Central (ExLibris)•ReadCube•Summon (Serials Solutions/ProQuest)•TDOne (TDNet)•WorldCat (OCLC)

Mihaela OprișClinic of Cardiology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Zoltán PávaiDepartment of Pathology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Maria PeleFaculty of Biotechnology, University of Agronomic Sciences and Veterinary Medicine, București, Romania

Alexandru Rafila"Carol Davila" University of Medicine and Phar-macy, București, Romania

Alexandru Rogobete"Victor Babeș" University of Medicine and Phar-macy, Timișoara, Romania

Simona StolnicuDepartment of Pathology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Mónika SzabóClinic of Diabetology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Sándor SzilágyiDepartment of Medical Informatics, "Petru Maior" University, Tîrgu Mureș, Romania

Tamás Szili-TörökErasmus Medical Center, Rotterdam, The Neth-erlands

Mariana TilincaDepartment of Cell and Molecular Biology, Uni-versity of Medicine and Pharmacy, Tîrgu Mureș, Romania

Rodica TogănelClinic of Pediatric Cardiology, University of Medi-cine and Pharmacy, Tîrgu Mureș, Romania

Ioan ȚileaClinic of Cardiovascular Rehabilitation, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Lia Yero EremieDepartment of Dental Health, University of Medi-cine and Pharmacy, Tîrgu Mureș, Romania

Endre ZimaSemmelweis University, Budapest, Hungary

tEchnical Editor

Zoltán Sárkány

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The Journal of Interdisciplinary Medicine aims to publish top quality papers related to any fields of medicine that present an interdisciplinary dimension.

The journal will mainly focus on recent advances in the field of diagnosis and treatment of the most common situations encountered in the clinical or research prac-tice. Interdisciplinary approaches will be extremely wel-comed, presenting new advances in the approach of dif-ferent pathologies from the perspective of various clinical fields.

The Journal of Interdisciplinary Medicine will publish high-quality basic and clinical research related to interdis-

ciplinary medical fields, in a common approach that will integrate the clinical studies with the pre-clinical work dedicated to the discovery of new mechanisms involved in the development and progression of a large spectrum of diseases.

The journal will try to provide the entire medical com-munity with the perspective of the regional specifics of Central and Eastern European countries. The journal will primarily focus on publishing original research papers, but also other types of materials (such as review articles, case reports, state-of-the-art papers, comments to editor, etc) will be extremely welcomed.

Aims and scope

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Journal of Interdisciplinary Medicine 2019;4(1):7-10

Triple Antithrombotic Therapy – Is It History or Should We Still Do It?Diana Opincariu

University of Medicine, Pharmacy, Sciences and Technology, Târgu Mureș, Romania

Editorial

DOI: 10.2478/jim-2019-0006

Patients with atrial fibrillation (AF) typically require oral anticoagulants for the prevention of cardioembolic events, as the left atrium is an environment characterized by low shear stress. This low shear stress leads to the formation of thrombi that are not as platelet-dependent such as, for example, thrombi that form during an acute coronary syndrome, an event associated with high shear stress and platelet-rich thrombi. This explains the need for oral anticoagulants in AF patients and the need for dual antiplatelet therapy in coronary thrombosis. However, when a combination of the two is met (AF in patients undergoing PCI, or acute coronary events in AF patients), the so-called triple antithrom-botic therapy emerges as a therapeutic indication, which also comes with its associated high bleeding risk.1,2

The latest therapeutic guidelines propose that individuals with atrial fibrilla-tion, with a CHA2DS2-VASc score of minimum 2 for males and 3 for females, should be treated with oral anticoagulants, and that non-vitamin K antagonists (NOACs) are preferred over warfarin if there are no contraindications which include valvular AF, defined in the presence of moderate-to-severe mitral steno-sis, or a mechanical cardiac valve.3

There is a continuously growing elderly population and the coexistence of AF with coronary artery disease (CAD), which will also increase the incidence of patients that require long-term oral anticoagulation. Furthermore, there is a high number of AF patients, up to 20–30%, that will require percutaneous coro-nary revascularization, either during an elective procedure, or for an acute coro-nary syndrome (ACS).4 The implantation of a coronary stent brings about the clear indication for dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel, cangrelor), for a variable duration of time, for the prevention of secondary ischemic events and major adverse cardiac events (MACE).5

On the other hand, around 7% of patients undergoing PCI with stent angio-plasty present AF with indication of oral anticoagulation. The management of such patients is clinically challenging, as they present indication for both dual antiplatelet regimens as well as oral anticoagulation and are at high risk for

CORRESPONDENCE

Diana Opincariu Str. Gheorghe Marinescu nr. 38540139 Tîrgu Mureș, RomaniaTel: +40 265 215 551E-mail: [email protected]

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8 Journal of Interdisciplinary Medicine 2019;4(1):7-10

both ischemic events (including stroke, stent thrombosis, coronary thrombosis) and hemorrhagic ones.6 Previous guideline recommendations in such cases were to pre-scribe triple antithrombotic therapy for a period of time, with aspirin, a P2Y12 inhibitor (clopidogrel; prasugrel or ticagrelor is to be avoided as part of the triple therapy due to greater risk of bleeding), and an oral anticoagulant (usu-ally vitamin K antagonists), followed by a dual antithrom-botic regimen (oral anticoagulant and a single antiplate-let). If NOACs were considered in this clinical scenario, the recommendation was to use the lowermost effective dose for the prevention of cerebrovascular cardioembolic events in AF patients.7

Several studies have been conducted in order to adjust current guideline recommendations in subjects who need both antiplatelet and anticoagulant therapies. Initial stud-ies have investigated vitamin K antagonists (VKAs) to-gether with single – or dual – antiplatelet therapies in AF subjects undergoing PCI.

The WOEST trial (What is the Optimal antiplatelet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing) investigated dual versus triple antithrombotic therapies in individuals with indication of oral anticoagulants (70% with AF), who experienced coronary revascularization. The dual-therapy arm re-ceived clopidogrel and warfarin, while the triple-therapy arm added aspirin to the combination. Although the trial did not include a sufficient number of patients in order to evaluate the ischemic outcomes, the results showed that the dual-therapy group presented a lower incidence of ma-jor and non-major hemorrhagic episodes, lower one-year all-cause death, but no significantly different rates of myo-cardial infarction, ischemic stroke, or stent thrombosis compared to patients that had been assigned to the triple antithrombotic regimen.8

The ISAR-TRIPLE study (Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Im-plantation) aimed to study the time length of triple anti-thrombotic treatment in subjects who receive oral anti-coagulants and undergo percutaneous implantation of a coronary drug-eluting stent, as in such cases, there is a high risk of stent thrombosis and concomitant high bleed-ing risk. The study blindly assigned a total of 614 patients to group 1 (6 weeks of clopidogrel in association with aspi-rin and warfarin) and group 2 (6 months of triple therapy). Most included patients required oral anticoagulation for AF (82.7% of group 1, 85% of group 2), followed by the presence of a mechanical heart valve or venous thrombo-embolic events. The results showed no difference between groups regarding the cumulative incidence of death, myo-

cardial infarction, in-stent thrombosis, stroke, or major hemorrhagic episodes (HR 1.14, p = 0.63), but the BARC bleeding frequency was higher in the 6-months group (27.9% vs. 20.5%, HR 0.68, p = 0.04). However, the main study finding was that the reduction of triple therapy to 6 weeks was not superior to the 6-month regimen, regarding clinical net outcomes.9

Numerous large clinical studies have already established the safety and efficacy of NOACs for preventing ischemic cerebrovascular events in subjects with non-valvular AF, including the RELY trial (dabigatran 110 mg and 150 mg twice/day), the ROCKET-AF study (rivaroxaban 20 mg daily), ARISTOTLE (apixaban 5 mg twice/day), and the newest ENGAGE AF-TIMI 48 study (edoxaban 30 mg and 60 mg daily), all showing the superiority of NOAC to warfarin in terms of ischemic stroke, systemic embolism, or transient ischemic attacks compared to VKAs.10 In ad-dition, three randomized open-label clinical studies have aimed to evaluate the use of NOACs in AF subjects who experience percutaneous coronary revascularization or ACS, in order to establish their use in this particular clini-cal setting, without increasing the bleeding risk.

The PIONEER AF-PCI trial aimed to investigate the safety and efficacy of rivaroxaban in combination with ei-ther one or two antiplatelet agents in AF patients under-going PCI, by including 2,124 subjects with non-valvular AF and PCI stent placement, who were divided into 3 study arms: group 1 – Rivaroxaban 15 mg/day + one P2Y12 inhibitor for 12 months; group 2 – Rivaroxaban 2.5 mg twice/day + dual antiplatelet therapy for 1, 6, and 12 months respectively; group 3 – VKA + dual antiplatelet therapy for 1, 6, and 12 months. A fact worth mention-ing is that most patients received clopidogrel as a P2Y12 inhibitor (93.1% of group 1; 93.7% of group 2; 96.3% of group 3). The bleeding rates were significantly lower for patients assigned to group 1 and group 2 respectively, compared to patients who received triple antithrombotic therapy (16.8% for group 1 vs. 18.0% for group 2 vs. 26.7% for group 3, p <0.001), while the rates of cardiovascular deaths, myocardial infarction, and stroke did not differ sig-nificantly among the three study arms (6.5% for group 1 vs. 5.6% for group 2 vs. 6.0% for group 3, p >0.05).11

REDUAL-PCI was a randomized study that had inves-tigated dual therapy with dabigatran compared to triple therapy with warfarin in AF subjects undergoing PCI. The study included 2,725 patients that were blindly assigned to dual therapy: dabigatran 110 mg twice/day (n = 981) or 150 mg twice/day (n = 763) with a P2Y12 inhibitor, or to triple therapy: warfarin + a P2Y12 inhibitor + aspirin (n = 981). In the dual-therapy group, study subjects were

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9Journal of Interdisciplinary Medicine 2019;4(1):7-10

administered clopidogrel or ticagrelor in association with two doses of dabigatran, while in the triple-therapy group, participants were administered warfarin adjusted for an INR of 2.0–3.0, clopidogrel or ticagrelor, and aspirin (for one month if bare metal stents were implanted, 3 months if drug-eluting stents were used). The results revealed that the rate of major and clinically relevant bleeding events were significantly lower for subjects assigned to the dual-therapy regimen (15.4% vs. 26.9%, p for non-inferiority <0.001), while even the higher dose regimen for dabiga-tran was less likely to cause significant bleeding compared to the triple-therapy regimen (20.2% vs. 25.7%, p for non-inferiority <0.001). And while being associated with a sig-nificantly lower bleeding risk, dabigatran dual therapy was comparable to the triple warfarin therapy regarding the rate of composite end-point of ischemic events (coronary, cerebrovascular, or systemic ischemia).12,13

AUGUSTUS is the latest trial with published results in March 2019, its primary aim being to shed some light on the still unclear matter of choosing the right antithrom-botic regimen for patients who require oral anticoagulants for various clinical reasons, but who also undergo coronary percutaneous revascularization, thus needing antiplatelet therapies as well. This phase IV randomized study included 4,614 non-valvular AF subjects from 33 countries that had suffered an ACS or had undergone elective PCI for signifi-cant CAD. The primary outcome measure included the rate of major or clinically relevant non-major bleeding during the treatment period with either apixaban or a VKA, or with aspirin versus no-aspirin regimen. The study population had been divided into two major groups: group 1 – apixa-ban 5 mg/2.5 mg twice/day versus group 2 – a VKA once daily for INR 2.0–3.0. The subjects were further assigned to receive either placebo once daily, or aspirin 81 mg once daily.14 A majority of 92.6% of patients included in the study received clopidogrel as the main antiplatelet treatment fol-lowing PCI, while a total of 37.3% had suffered an ACS who underwent PCI, 23.9% had ACS and were managed pharmacologically, and 38.8% had undergone elective PCI. The results showed that during the 6-month follow-up, the apixaban group presented significantly lower rates of major bleeding events than the VKA group (10.5% vs. 14.7%, p for non-inferiority <0.001, p for superiority <0.001; HR: 0.69, 95% CI: 0.58–0.81). Concomitantly, patients receiving aspi-rin presented significantly higher rates of major or clinically relevant non-major bleeding compared to patients that had been assigned to placebo (16.1% vs. 9.0%, HR: 1.89%, 95% CI: 1.59–2.24, p <0.001). The highest rate of hemorrhages was recorded among subjects who had received a VKA and aspirin (18.7%), while the lowest was recorded in the apix-

aban-placebo group (7.3%). The rates of hospitalization or death were higher in the VKA group (57.2% vs. 69.2%, HR 0.83, p = 0.002) compared to apixaban, while the rates of death or ischemic events were not different between the two anticoagulant groups (14.3% for apixaban vs. 15.3% for VKA, p >0.05). The antiplatelet group showed no sig-nificant difference between aspirin vs. placebo regarding the death and hospitalization outcome measure (65.7% for aspirin vs. 60.6% for placebo, p >0.05), while the rates of death and ischemic events were not assessed for this par-ticular study population.15

Current clinical trial data suggest that less is more in the context of the antithrombotic regimens of subjects with non-valvular atrial fibrillation who undergo coronary PCI, either electively or during an acute coronary event. The risk of bleeding decreases significantly with simpler anti-thrombotic therapeutic schemes, with apparently no con-comitant elevation of the ischemic risk. However, not all trials have studied the subsequent risk for coronary isch-emic events or in-stent thrombosis, which strongly indi-cates the need for further trials on larger patient cohorts in order to establish this hazard. All in all, there is a trend to-wards choosing non-vitamin K antagonists for the preven-tion of cardioembolic risk in AF subjects with coronary stenting procedures, but still there is scarce data on their association with newer-generation P2Y12 inhibitors such as ticagrelor, which is currently prescribed at a large scale in acute coronary syndromes, as well as a lack of long-term follow-up of over a year in these patients, thus indicating the need for further research on the matter.

conFlict oF intErEst

Nothing to declare.

rEFErEncEs

1. Capodanno D, Angiolillo DJ. Triple Antithrombotic Therapy at the Intercept Between Threats and Opportunities: Don't Throw Out the Baby With the Bath Water. JACC Cardiovasc Interv. 2017;10:1086-1088.

2. Lamberts M, Olesen JB, Ruwald MH, et al. Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation. 2012;126:1185-1193.

3. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019. pii: S0735-1097(19)30209-8.

4. Mantis C, Alexopoulos D. Antithrombotic treatment in atrial fibrillation patients undergoing PCI: Is dual therapy the winner? Thrombosis Research. 2019;176:133-139.

5. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J. 2018;39:213-254.

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10 Journal of Interdisciplinary Medicine 2019;4(1):7-10

6. Senoo K, Lane D, Lip GY. Stroke and Bleeding Risk in Atrial Fibrillation.

Korean Circ J. 2014;44:281.

7. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the

management of atrial fibrillation developed in collaboration with EACTS.

Eur J Cardiothorac Surg. 2015;50:e1-e88.

8. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with

or without aspirin in patients taking oral anticoagulant therapy and

undergoing percutaneous coronary intervention: an open-label,

randomised, controlled trial. Lancet. 2013;381:1107-1115.

9. Fiedler KA, Maeng M, Mehilli J, et al. Duration of Triple Therapy in Patients

Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: The

ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015;65:1619-1629.

10. Hammersley D, Signy M. Navigating the choice of oral anticoagulation

therapy for atrial fibrillation in the NOAC era. Ther Adv Chronic Dis.

2017;8:165-176.

11. Gibson CM, Mehran R, Bode C, et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016;375:2423-2434.

12. Oldgren J, Steg PG, Hohnloser SH, et al. Dabigatran dual therapy with ticagrelor or clopidogrel after percutaneous coronary intervention in atrial fibrillation patients with or without acute coronary syndrome: a subgroup analysis from the RE-DUAL PCI trial. Eur Heart J. 2019. pii: ehz059.

13. Cannon CP, Bhatt DL, Oldgren J, et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017;377:1513-1524.

14. Lopes RD, Vora AN, Liaw D, et al. An open-label, 2 × 2 factorial, randomized controlled trial to evaluate the safety of apixaban vs. vitamin K antagonist and as¬pirin vs. placebo in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention: rationale and design of the AUGUSTUS trial. Am Heart J. 2018;200:17-23.

15. Lopes RD, Heizer G, Aronson R, et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med. 2019;380:1509-1524.

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Journal of Interdisciplinary Medicine 2019;4(1):11-18

CORRESPONDENCE

Zsolt ParajkóStr. 22 Decembrie 1989 nr. 76540124 Târgu Mureș, RomaniaTel: +40 265 217 333E-mail: [email protected]

ARTICLE HISTORY

Received: January 15, 2019 Accepted: February 20, 2019

Coronary Shear Stress after Implantation of Bioresorbable Scaffolds – a Modern Interdisciplinary Concept at the Border between Interventional Cardiology and Cardiac ImagingDan Păsăroiu1, Zsolt Parajkó1, Ionuț Ferenț1, Diana Opincariu2, Annabell Benedek2

1 Center of Advanced Research in Multimodality Cardiac Imaging, Cardio Med Medical Center, Târgu Mureș, Romania2 University of Medicine, Pharmacy, Sciences and Technology, Târgu Mureș, Romania

rEViEW CARDIOLOGY // IMAGING

DOI: 10.2478/jim-2019-0007

ABSTRACT

Bioresorbable scaffolds/stents offer new and exciting perspectives in the treatment of patients with acute coronary syndromes, especially after the recent development of invasive imaging techniques, such as optical coherence tomography, which allow complete assessment of vas-cu-lar segments. A particular advantage of bioresorbable scaffolds is that once the biosorption of the scaffold is complete, the vascular segment regains its normal physiological functions, thus eliminating the risk of late complications. New studies show the importance of shear stress in the progression of vascular atherosclerosis or in accelerating endothelial turnover. Based on the current knowledge in this field, a future standardized determination of shear stress may help in the long-term follow-up of patients that have suffered or are at risk of developing an acute coronary syndrome.

Keywords: acute coronary syndrome, bioresorbable scaffolds, shear stress, atherosclerosis

Dan Păsăroiu • Str. 22 Decembrie 1989 nr. 76, 540124 Târgu Mureș, Romania. Tel: +40 265 217 333, E-mail: [email protected]

Ionuț Ferenț • Str. 22 Decembrie 1989 nr. 76, 540124 Târgu Mureș, Romania. Tel: +40 265 217 333, E-mail: [email protected]

Diana Opincariu • Str. Gheorghe Marinescu nr. 50, 540136 Târgu Mureș, Romania. Tel: +40 265 212 111, E-mail: [email protected]

Annabell Benedek • Str. Gheorghe Marinescu nr. 50, 540136 Târgu Mureș, Romania. Tel: +40 265 212 111, E-mail: [email protected]

introdUction

Atherosclerosis is a chronic, inflammatory, systemic disease, which affects par-ticularly the arteries with large and middle caliber.1,2 Even though the systemic risk factors for atherosclerosis—dyslipidemia, smoking, high blood pressure, diabetes, chronic inflammatory disorders, genetic predisposition—affect the en-tire coronary tree, the atherosclerotic lesions are formed in specific segments of the coronary arteries such as the origin of a coronary branch, the external part of a bifurcation, or the inner wall of a vascular curvature, leading to a hemodynamic impairment characterized by a turbulent flow at this level.3 Local factors, espe-cially hemodynamic forces, play an important role in the regional disposition of

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atherosclerosis.4–7 These local hemodynamic disturbances include endothelial shear stress (ESS), which is generated by the blood flow and the tangential wall tension, the first of which has a fundamental role in development and pro-gression of atherosclerosis.

EndothElial shEar strEss

The earliest data regarding the influence of ESS on the location of atherosclerotic lesions was described by Caro et al. four decades ago.8 Later on, computational simu-lations of fluid dynamics in autopsy-based models of the coronary vasculature,9 the carotid bifurcations,10 and of the distal part of the abdominal aorta11 indicated that ar-eas with decreased shear stress develop atherosclerotic lesions.

Several in vivo animal experiments also supported the atherogenic role of decreased ESS.12–14 In vivo investiga-tions on human subjects, using combined intravascular ultrasound (IVUS) or magnetic resonance imaging (MRI) and computational fluid dynamics have established the role of decreased ESS in the evolution of atherosclerotic lesions in various vascular sites.15,16 Current molecular and cellular research has clarified in detail the pathophysiologi-cal mechanism involved in the development of atheroscle-rosis on the basis of increased ESS, leading to the forma-tion of fibroatheromas with a thin fibrotic layer, presumed to be “vulnerable plaques”, responsible for triggering acute coronary syndromes (ACS).17–21

A central determinant in the development and evolu-tion of the atheromatous process is the local remodeling of the arterial wall that occurs as a response to plaque progression and growth, influencing both the natural his-tory as well as the clinical evolution of individuals affected by atherosclerotic disease. The vascular remodeling pro-cess is indisputably affected by local hemodynamic fac-tors.15,21,22–24 ESS represents the tangential force resulting from the friction of blood flow on the endothelial layer of the arterial wall, being expressed in unit of force/unit of surface (N/m2 or Pascal [Pa] or dyne/cm2; 1 N/m2 = 1 Pa = 10 dyne/cm2).25,26 ESS is correlated with the product of blood viscosity (μ) and the spatial gradient of blood veloc-ity in the wall (μ × dv/dy).

The particularities of a fluid streaming through a tube depend on flow velocity and on the presence of geomet-ric irregularities or obstructions. Fluid flow can be either laminar or turbulent.25,27 Laminar flow is characterized by a linear flow, which subsequently can be divided into lami-nar flow with undisturbed debit, described by a linear flow line, and turbulent laminar flow, which is characterized by

areas with reversed flow or a circumferential vortex.25,28 In case of turbulent flow, velocity at any point continuously varies in time, even if the flow is stable.

For a certain geometry, both turbulent and laminar flow are determined by the Reynolds number (Re): for low values the flux is laminar, while for high values (typically above 2,000), the flow is turbulent.7,10,29

Certain vascular segments, such as the branching site of arteries, vascular curvatures, bifurcations, as well as downstream from an obstruction, are more prone to de-velop atheromatous lesions. Even with the systemic effect of cardiovascular risk factors, only a small percentage of coronary lesions lead to an acute clinical event. Therefore, local factors such as ESS are required in the process of de-velopment and progression of atherosclerosis.

Arterial geometry determines the shear stress model on the respective arterial segment. The presence of bifurca-tions, curves, or obstructions modifies flow and the pattern of shear stress. Therefore, intricate interactions between blood flow, viscosity, and arterial geometry generate dif-ferent patterns of ESS, characterized by direction (unidi-rectional, bidirectional) and variable degrees of magnitude (low, moderate, high).30

Moderate shear stress varies between 1.5–3.0 Pa during a cardiac cycle, being identified in almost linear arterial seg-ments, where unidirectional flow is present, with protec-tive effects regarding atherosclerosis. Increased values of shear stress are considered above 3 Pa and are usually mea-sured at the level of a stenotic lesion caused by an athero-sclerotic plaque, while a decreased ESS (below 1–1.5 Pa), with a non-turbulent unidirectional flow, generally ap-pears in the inner region of a vascular curve, as well as the upstream region of a stenotic plaque.31,32 A low oscillating ESS is characterized by a bidirectional (retrograde) flow, being observed at the level of a collateral branch ostium, downstream of a stenotic lesion, or at the lateral walls of bifurcations. Low and/or oscillated shear stress promotes atherogenesis, being a crucial factor in the development of focal atheromatous plaques.5,32

Biomechanical factors contribute substantially to the process of vulnerabilization of atheromatous plaques, with subsequent development of an acute cardiovascular or cerebrovascular event via plaque erosion, rupture, and subsequent thrombosis. Atherosclerotic plaques are char-acterized by a lipid-rich necrotic core and a thin fibrous cap which delineates the core from the vascular lumen, preventing contact between its thrombogenic content and the blood flow. Plaque rupture is caused by thinning of the fibrous layer, which makes it susceptible to the effect of he-modynamic mechanical forces. The concentration of col-

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lagen in the plaque cap is crucial for the resistance of the fiber layer against these forces.33,34

Excessive and expansive plaque remodeling with low shear stress and intense matrix metalloproteinase (MMP) activity has been linked to a high vulnerability degree of atheromatous plaques.35–37 The underlying mechanisms that are accountable for plaque erosion have not been as profoundly studied as the processes that may lead to plaque rupture. However, most plaque erosions occur in the downstream region of the atherosclerotic lesion, which is exposed and characterized by a low local ESS. Areas with decreased shear stress are characterized by in-creased endothelial cell turnover, endothelial cell apopto-sis, and endothelial glycocalyx, which leads to endothelial denudation. Consequently, a reduced ESS is involved in the pathogenesis of plaque erosion. An increased proteo-lytic function of MMP and a reduced collagen synthesis in places with reduced ESS may influence the thinning of the fiber layer, which increases the risk of plaque rupture.38–40

The detrimental role of ESS in the initiation and pro-gression of atherosclerosis shown in animal studies under-lies the importance and need of a validated study on hu-man subjects. The pattern of shear stress depends on the arterial geometry and the type of blood flow, and a pre-cise 3D reconstruction of vascular geometry and coronary blood flow is the premise for the estimation of ESS. These data are obtained using intravascular imaging methods such as IVUS and optical coherence tomography (OCT), as well as noninvasive imaging methods such as computed tomography angiography.

Early studies on human subjects have been published a decade ago, demonstrating that ESS is a significant fac-tor in the progression of atherosclerotic plaques, as well as in the process of vascular remodeling.15,22 Stone et al. stated that the progression of atheromatous plaques was observed almost exclusively in areas with decreased ESS and may be associated with an expansive or constrictive remodeling process of the underlying vasculature. Further studies conducted by Samady et al. supported the role of shear stress in coronary disease as well, linking the progres-sion of plaques with low values of ESS. These researches have contributed considerably to investigating and clarify-ing the role of ESS in the initiation and development of atherosclerosis; however, these studies were limited by a low number of included subjects. Other studies have fo-cused on the evaluation of shear stress in interventional cardiology and its dynamics following stent implantation procedures. Neointimal hyperplasia, neoatherosclerosis, and in-stent restenosis are the interventional cardiologist’s enemies.41–43

Shear stress has recently been studied as an influencing factor on the prognosis and clinical evolution of patients following stent angioplasty. Stent implantation leads to endothelial and arterial wall damage, which will alter the local geometry and blood flow (flow separation, recircu-lation).44 After the introduction of drug-eluting stents, there has been a considerable decrease in the frequency of in-stent restenosis and neointimal hyperplasia, which had been relatively high in the era of bare-metal stents. Several studies sustain the theory according to which ESS leads to in-stent neointimal hyperplasia and neointimal neo-atherosclerosis, which requires the search for optimal positioning strategies and stent structure.45–47 Shear stress apparently does not influence the arterial wall under the stent struts, perhaps due to the altered, compressed arte-rial structure.45,48

thE bEnEFits oF biorEsorbablE stEnts

Bioresorbable stents have several potential advantages over drug-eluting stents, including:

1. Reduction of adverse events such as stent thrombo-sis: the stent itself is temporary, the release of acti-ve substance is secured by the stent until the vessel is healed, and there is no foreign material such as non-endothelialized stent struts or polymers of the active substance (which are triggers for intrastent thrombosis) that may persist for a prolonged pe-riod.

2. Removal of the rigid vascular binding by bioresor-ption can facilitate the recovery of vasomotricity, shear stress adaptability, and late vascular expansi-on. Furthermore, it can reduce the collateral ostial obstruction problems observed in metallic stents.

3. Reduction of bleeding complications: once the bioresorption of the temporary stent has been completed, the dual antiplatelet therapy may be suspended. This is a particularly relevant feature, as the elderly, with the highest risk of hemorrhagic complications, benefit from an increasing propor-tion of invasive interventions for the treatment of ischemic coronary artery disease.49 Furthermore, the premature discontinuation of dual antiplate-let therapy after the implantation of drug-eluting stents for any indication has been shown to be an independent predictor of intrastent thrombosis.50

4. Improvement of future therapeutic options: in-terventional therapy of complex multivascular co-ronary disease involves the use of multiple, long,

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drug-eluting stents. For example, in the SYNTAX trial, an average number of 4 stents were used, and in 1 out of 3 patients the implanted stents were lon-ger than 100 mm. In such cases, repetitive revascu-larization, either interventional or surgical, may be potentially challenging due to the metallic embos-sing formed by previously implanted drug-eluting stents. The use of bioresorbable stents would not restrain a future percutaneous revascularization procedure or any surgical interventions.

5. The possibility to use imaging techniques such as angiography, computed tomography (CT), or MRI for follow-up of stents. Right now, metallic stents make it difficult to interpret such images because they leave a metallic artefact. Poly-L-lactic acid/amorphous calcium phosphate bioabsorbable stents are not metallic, thus they should not hinder the usage of CT or MRI; once bioresorption has been finalized, bioresorbable stents do not impair the use of CT or MRI for the evaluation of stent and vessel permeability. This could mean that such noninvasive imaging techniques could become an alternative to invasive imaging in the long-term follow-up of patients.50

6. The local release of active substances: the duration of bioresorption is influenced by the type of utili-zed polymer. A controlled release of multiple sub-stances could be obtained through the early release of antiproliferative agents from the outer polymer layer of the stent, in conjunction with the late re-lease of anti-inflammatory agents from polymers that are located in the stent structure.

7. Aid in decreasing patient concern regarding stent implantation, aiming to conquer the fears of pati-ents who will live with this implant for the rest of their life.51

One of the biggest hopes concerning bioresorbable stents is that after bioresorption is complete, the stented vascular segment will regain its normal function and will be completely free of foreign bodies; this in fact mini-mizes the possibility of thrombotic events later on and eliminates the need for double antiplatelet treatment regi-ments on long term. Bioresorbable scaffolds could have the potential to eliminate certain factors that contribute to late stent thrombosis such as delayed epithelialization, chronic inflammatory response, and hypersensitivity local reaction.52 A lower incidence of stent thrombosis has been observed in patients treated with a biodegradable poly-mer stent versus a durable polymer stent (0.4% vs. 1.8%,

p = 0.004).53 Notably, a recently published study has found that patients undergoing simple coronary angioplasty are at risk of developing late stent thrombosis, which could in-dicate that bioresorbable stents cannot eliminate this com-plication entirely.54

Metallic stents seem to not protect the blood vessel against neoatherosclerosis or progression of plaques. It is postulated that the implantation of bioresorbable scaffolds could offer a coating that is symmetric and uniform, which, alongside the delayed expansion of the interior lumen and the absence of a permanent prosthesis, could help in the stabilization of vulnerable plaques and thus prevent future cardiovascular events.55 This is a very tempting idea, and it is supported by studies based on the concept of stabiliz-ing plaques by stenting and by the fact that bioresorbable stents offer a coating that is fibrous, symmetric, circumfer-ential, with a normally functioning endothelium, a delayed extension of the lumen and normal distribution of shear stress.55

The IVUS analysis of ABSORB bioresorbable scaffolds between 6 months and 2 years has uncovered a significant reduction of plaques without modifying the structure of the vascular wall.56,57

thE adVantagEs oF biorEsorbablE

stEnts in rEstoring thE norMal blood

FloW in thE coronary artEriEs

Bioresorbable scaffolds are considered a very important leap in the field of percutaneous transluminal coronary angioplasty.58 They have been conceived for the purpose of bypassing certain disadvantages of metallic drug-eluting stents such as, for example, the chronic local inflammatory reaction, the absence of physiological vascular mobility, late stent thrombosis, and, last but not least, the possibility of cardiovascular bypass further on.18,19,59,60

Bioresorbable scaffolds function in a three-phase sys-tem: revascularization, restoration, and resorption. In the first phase, bioresorbable stents are meant to mimic the characteristic of drug-eluting metal stents, this meaning the expansion of stents with minimum rebound and high radial force, and the controlled release of antiproliferative substances. Thus, in the restoration stage, vascular motric-ity is reestablished and the transitioning from an active support to a more passive one begins. The last stage, re-sorption, is characterized by degradation and metaboliza-tion of the stent.61

Stents have been developed to prevent and to manage the complications of percutaneous transluminal coronary angioplasty, mainly acute vascular obstruction determined

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by arterial dissection, elastic recoil, late constrictive re-modeling, and neointimal proliferation. Ideally, the cov-erage provided by bioresorbable stents in the first months should be as good as the one provided by metallic stents.62

Poly-L-lactic acid is a biodegradable, thermoplastic, aliphatic polyester, which suffers autocatalytic hydrolytic degradation to normal lactic acid, which is then metabo-lized into carbon dioxide and water. Bioresorbable stents based on this kind of substance are made from a com-bination of semi-crystalline polymers (which provide mechanical strength) and amorphous polymers (which provide the ability to release the active substance at the desired time). The degradation process is influenced by the crystallization level of the polymers and can vary from 2 to 4 years.63

Metallic stents can alter the geometry and biomechan-ics of the blood vessel; furthermore, chronic irritation and turbulent blood flow favor neointimal proliferation and ad-verse effects.64,65 Bioresorbable scaffolds offer the potential of preserving vascular geometry. The ABSORB bioresorb-able stent is more compliant than a metallic one, this in fact determines less lesions at the site of vascular angulations.56 It has been observed in 6- to 12-month follow-ups that bio-resorbable stents tend to restore the normal configuration of the coronary vessel, as opposed to metallic stents which alter coronary geometry forever.66

A series of studies using drug-eluting stents have re-ported abnormal vasomotricity in the distal segment of the blood vessel after stenting, this limiting the blood flow and thus predisposing the patient to late in-stent thrombosis. Bioresorbable scaffold technology has been described as a reconstructive vascular therapy. After bioresorption, these stents promise the restoration of dynamic vasomotric-ity, pulsatility, distensibility and mechano-transduction, demonstrating the ability to transform mechanical forces into chemical signals (mediated by nitric oxide and pros-tacyclin).56 Cohort A from the ABSORB trial showed that the stented segment had vasomotricity after administering acetylcholine at 2 years after stent implantation.14

shEar strEss in athErosclErotic

PlaqUEs trEatEd With

biorEsorbablE stEnts

A recent study has indicated the importance of hemody-namic factors in neointimal response after the implanta-tion of ABSORB bioresorbable stents. This led to an im-provement of stent design in order to make them more ergonomic.48 The same study suggested that the evalu-ation of the stented artery from the perspective of shear

stress should be carried out by fusing images from OCT with invasive angiography, which are superior to the im-ages resulted from fusing images provided by IVUS with angiography.67

Bioresorbable medical tools have been gaining ground in recent years; however, a lot of questions remain unan-swered, mainly because it is not known how these devices will fade in the long run. These questions are especially important in bioresorbable coronary stents, in which late stent thrombosis may occur.68–71 The mechanism pro-posed for these kinds of complications imply dismantling of the polymer and late stent inflammation.72,73 However, there are other factors that collide when this kind of com-plication occurs, one being the local dynamic blood flow. Other factors that can be incriminated in stent thrombosis are neointimal abnormal regeneration, uncovered struts, and wrong placement of the stent.17,74 In some cases, local suboptimal hemodynamic characteristics, right after the implantation of a bioresorbable scaffold, could contribute to a bad neointimal proliferation, uncovered struts, and poor stent positioning.75

With the permanent presence of struts in the lumen, the stent is exposed to extreme shear stress, which activates the platelets.76 The distal regions are predisposed to lower shear stress and higher viscosity, in which case the activat-ed thrombocytes can aggregate.

The dynamic attribute of the blood flow directly regu-lates vascular biology and influences the development of atherosclerosis.77,78 Abnormally high or low ESS has been correlated with the progression, vulnerability, and maybe even with the rupture of atherosclerotic plaques and sub-sequent thrombosis.21,79–81

Remarkably, due to the resorption of scaffold material in time, the coronary arteries that were treated with such devices develop a partial return of vasomotricity, which completes the latent lumen expansion, this way stabilizing the plaque.47,76,82,83 It is believed that some of these obser-vations may be correlated with the normalization of blood flow after the implantation of bioresorbable scaffolds.

We must keep in mind the therapeutic objectives of this technique. The final goal can sound abstract and theo-retical, but it has a name: endothelial shear stress. Normal shear stress has to be the main criteria for an optimal im-plantation; this means optimal stent apposition, no pro-trusion of struts in the vascular lumen that can disturb the blood flow, no significant difference between the diameter of the proximal and distal end of a stented segment (in oth-er words the perfect incorporation of stents in the vascular wall), no asymmetry of the blood vessel, and a bioresorb-able scaffold/artery ratio between 1 and 1.1.84 In fact, only

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intravascular imaging techniques can accurately evaluate the criteria mentioned above for optimal implantation. Only OCT with a resolution of 20 microns can examine the blood vessel and the interaction with the bioresorbable stent for the required precision.84,85

The possibility of identifying a pathologic alteration of shear stress using computational simulations based on flu-id dynamics in the coronary regions, after the implantation of a stent, as well as achieving dynamic simulations, could open up new horizons for percutaneous transluminal coro-nary revascularization.

conclUsions

Current knowledge suggests that low or oscillating shear stress has an important role in the development of athero-sclerosis. Furthermore, the affected vascular segment has a higher endo-thelial turnover. Even though risk factors affect the entire vascular system, atherosclerotic le-sions develop only in certain areas such as arterial branching sites, curvatures, bifurcations, or distal from a stenotic le-sion. This observation emphasizes the role of local hemo-dynamic fac-tors in the development and progression of atherosclerotic plaques.

The most important advantage of using bioresorbable scaffolds is that after bioresorption is completed, the af-fected segment regains its normal physiological functions. Other important advantages include a lower risk of major cardiac events or bleeding complications, associated with the possibility to use modern imaging techniques for stent follow-up.

conFlict oF intErEst

Nothing to declare.

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50. Van Werkum JW, Heestermans AA, Zomer AC, et al. Predictors of coronary stent thrombosis: The Dutch stent thrombosis registry. J Am Coll Cardiol. 2009;53:1399-1409.

51. Spuentrup E, Ruebben A, Mahnken A, et al. Artifact-free coronary magnetic resonance angiography an coronary vessel wall imaging in the presence of a new, metallic coronary magnetic resonance imaging stent. Circulation. 2005;111:1019-1026.

52. Di Mario C, Borgia F. Assimilating the current clinical data of fully bioabsorbable stents. EuroIntervention. 2009;5:F103-F108.

53. Stefanini GG, Kalesan B, Serruys PW, et al. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. Lancet. 2011;378:1940-1948.

54. Yamaji K, Kimura T, Morimoto T, et al. Very long-term (15 to 23 years) outcomes of successful balloon angioplasty com- pared with bare metal coronary stenting. J Am Heart Assoc. 2012;1:e004085.

55. Brugaletta S, Gogas BD, Garcia-Garcia HM, et al. Vascular compliance changes of the coronary vessel wall after bioresorbable vascular scaffold implantation in the treated and adjacent segments. Circ J. 2012;76:1616-1623.

56. Gomez-Lara J, Garcia-Garcia HM, Onuma Y, et al. A comparison of the conformability of everolimus-eluting bioresorbable vascular scaffolds to metal platform coronary stents. JACC Cardiovasc Interv. 2010;3:1190-1198.

57. Ormiston JA, Serruys PW, Onuma Y, et al. First serial assessment at 6 months and 2 years of the second generation of absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study. Circ Cardiovasc Interv. 2012;5:620-632.

58. Bourantas CV, Zhang Y, Farooq V, Garcia-Garcia HM, Onuma Y, Serruys PW. Bioresorbable scaffolds: current evidence and ongoing clinical trials. Curr Cardiol Rep. 2012;14:626-634.

59. Nakazawa G, Ladich E, Finn AV, Virmani R. Pathophysiology of vascular healing and stent mediated arterial injury. EuroIntervention. 2008;4:C7-C10.

60. Nakazawa G, Otsuka F, Nakano M, et al. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol. 2011;57:1314-1322.

61. Oberhauser JP, Hossainy S, Rapoza RJ. Design principles and performance of bioresorbable polymeric vascular scaffolds. EuroIntervention. 2009;5: F15-F22.

62. Iqbal J, Sumaya W, Tatman V, et al. Incidence and predictors of stent thrombosis: a single-centre study of 5,833 consecutive patients undergoing coronary artery stenting. EuroIntervention. 2013;9:62-69.

63. Onuma Y, Serruys PW. Bioresorbable scaffold: the advent of a new era in percutaneous coronary and peripheral revascularization? Circulation. 2011;123:779-797.

64. Bourantas CV, Raber L, Zaugg S, et al. Impact of local endothelial shear stress on neointima and plaque following stent implantation in patients with ST-elevation myocardial infarction: A subgroup-analysis of the COMFORTABLE AMI-IBIS 4 trial. Int J Cardiol. 2015;186:178-85.

65. Gyongyosi M, Yang P, Khorsand A, Glogar D. Longitudinal straightening effect of stents is an additional predictor for major adverse cardiac events. Austrian Wiktor Stent Study Group and European Paragon Stent Investigators. J Am Coll Cardiol. 2000;35:1580-1589.

66. Gomez-Lara J, Brugaletta S, Farooq V, et al. Angiographic geometric changes of the lumen arterial wall after bioresorbable vascular scaffolds and metallic platform stents at 1-year follow-up. JACC Cardiovasc Interv. 2011;4:789-799.

67. Bourantas CV, Papafaklis MI, Lakkas L, et al. Fusion of optical coherence tomographic and angiographic data for more accurate evaluation of the endothelial shear stress patterns and neointimal distribution after bioresorbable scaffold implantation: comparison with intravascular ultrasound-derived reconstructions. Int J Cardiovasc Imaging. 2014;30:485-494.

68. Kimura T, Kozuma K, Tanabe K, et al. A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus- eluting metallic stents in patients with coronary artery disease: ABSORB Japan. Eur Heart J. 2015;36:3332-3342.

69. Ellis SG, Kereiakes DJ, Metzger DC, et al. Investigators AI. Everolimus-eluting bioresorbable scaffolds for coronary artery disease. N Engl J Med. 2015;373:1905-1915.

70. Wykrzykowska JJ, Kraak RP, Hofma SH, et al. Investigators A. Bioresorbable Scaffolds versus Metallic Stents in Routine PCI. N Engl J Med. 2017;376:2319-2328.

71. Collet C, Asano T, Miyazaki Y, et al. Late thrombotic events after bioresorbable scaffold implantation: a systematic review and meta-analysis of randomized clinical trials. Eur Heart J. 2017;38:2559-2566.

72. Otsuka F, Pacheco E, Perkins LE, et al. Long-term safety of an everolimus-eluting bioresorbable vascular scaffold and the cobalt-chromium XIENCE V stent in a porcine coronary artery model. Circ Cardiovasc Interv. 2014;7:330-342.

73. Raber L, Brugaletta S, Yamaji K, et al. Very late scaffold thrombosis: intracoronary imaging and histopathological and spectroscopic findings. J Am Coll Cardiol. 2015;66:1901-1914.

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74. Finn AV, Nakazawa G, Joner M, et al. Vascular responses to drug eluting

stents: Importance of delayed healing. Arterioscler Thromb Vasc Biol.

2007;27:1500-1510.

75. Foin N, Gutierrez-Chico JL, Nakatani S, et al. Incomplete stent apposition

causes high shear flow disturbances and delay in neointimal coverage

as a function of strut to wall detachment distance: implications for the

management of incomplete stent apposition. Circ Cardiovasc Interv.

2014;7:180-189.

76. Holme PA, Orvim U, Hamers MJAG, et al. Shear-induced platelet activation

and platelet microparticle formation at blood flow conditions as in arteries

with a severe stenosis. Arterioscler Thromb Vasc Biol. 1997;17:646-653.

77. Martorell J, Santoma P, Kolandaivelu K, et al. Extent of flow recirculation

governs expression of atherosclerotic and thrombotic biomarkers in

arterial bifurcations. Cardiovasc Res. 2014;103:37-46.

78. Nam D, Ni CW, Rezvan A, et al. Partial carotid ligation is a model

of acutely induced disturbed flow, leading to rapid endothelial

dysfunction and atherosclerosis. Am J Physiol Heart Circ Physiol.

2009;297:H1535-H1543.

79. Bark DLJr, Ku DN. Wall shear over high degree stenoses pertinent to

atherothrombosis. J Biomechanics. 2010;43:2970-2977.

80. Bark DL, Para AN, Ku DN. Correlation of thrombosis growth rate to pathological wall shear rate during platelet accumulation. Biotechnol Bioeng. 2012;109:2642-2650.

81. Fukumoto Y, Hiro T, Fujii T, et al. Localized elevation of shear stress is related to coronary plaque rupture: a 3-dimensional intravascular ultrasound study with in-vivo color mapping of shear stress distribution. J Am Coll Cardiol. 2008;51:645-650.

82. Brugaletta S, Radu MD, Garcia-Garcia HM, et al. Circumferential evaluation of the neointima by optical coherence tomography after ABSORB bioresorbable vascular scaffold implantation: can the scaffold cap the plaque? Atherosclerosis. 2012;221:106-112.

83. Lane JP, Perkins LE, Sheehy AJ, et al. Lumen gain and restoration of pulsatility after implantation of a bioresorbable vascular scaffold in porcine coronary arteries. JACC Cardiovasc Interv. 2014;7:688-695.

84. Tateishi H, Suwannasom P, Sotomi Y, et al. investigators of the ABSORB Cohort B study. Edge Vascular Response After Resorption of the Everolimus-Eluting Bioresorbable Vascular Scaffold – A 5-Year Serial Optical Coherence Tomography Study. Circ J. 2016;80:1131-41.

85. Tamburino C, Latib A, van Geuns RJ, et al. Contemporary practice and technical aspects in coronary intervention with bioresorbable scaffolds: a European perspective. EuroIntervention. 2015;11:45-52.

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Journal of Interdisciplinary Medicine 2019;4(1):19-24

CORRESPONDENCE

Emanuela TeglaStr. Gheorghe Marinescu nr. 38540139 Tîrgu Mureş, RomaniaTel: +40 756 488 817E-mail: [email protected]

ARTICLE HISTORY

Received: January 3, 2019 Accepted: January 21, 2019

Evaluation of Three Esthetic Restorative Materials Used for Carious or Non-carious Cervical Lesion RestorationGabriela Beresescu1, Emanuela Tegla1, Despina Temistocle2, Alina Ormenisan1, Alina Baldean2

1 University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureş, Romania2 County Emergency Hospital, Tîrgu Mureş, Romania

original rEsEarch DENTAL MEDICINE // CHEMISTRY

DOI: 10.2478/jim-2019-0001

ABSTRACT

Background: Cervical lesions appear on the cervical surface of the lingual or buccal side of the tooth and are classified into carious and non-carious lesions. Aim: The present study evaluates the performance of three different types of aesthetic restorative materials, used for the restora-tion of carious or non-carious cervical lesions. Materials and methods: The study comprised 195 cervical lesions in 45 patients. The restorations were carried out for non-carious cervical le-sions in 34.62% of the cases, for primary carious lesions in 40.00% of the cases, and to replace a previous restoration in 25.38% of the cases. The restorations were evaluated at 2 weeks (the reference line), and then at 1 and 2 years after placement. The following have been assessed: restoration retention, color harmonization, surface texture, margin discoloration, anatomical contour, margin integrity, and the presence of secondary caries. The characteristics were reg-istered in conformity with the modified USPHS criteria. Results: At the one-year evaluation, we noticed the loss of 12 restorations, and after 2 years, the loss of 19 restorations. The results showed significant differences between restorative materials regarding color, margin adapta-tion, margin coloration, surface texture, as well as criteria regarding the anatomical contour (p <0.05). Conclusions: The evaluation of the success of restorative material retention must consider the location of the cervical lesion. A successful treatment depends particularly on a full understanding of the factors that caused the lesions and on the method of their treatment.

Keywords: carious, non-carious, cervical lesions, restoration materials, retention rates

Gabriela Beresescu • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureş, Romania. Tel: +40 265 215 551, E-mail: [email protected]

Despina Temistocle • Str. Gheorghe Marinescu nr. 50, 540136 Tîrgu Mureș, Romania. Tel: +40 265 212 111, E-mail: [email protected]

Alina Ormenisan • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureş, Romania. Tel: +40 265 215 551, E-mail: [email protected]

Alina Baldean • Str. Gheorghe Marinescu nr. 50, 540136 Tîrgu Mureș, Romania. Tel: +40 265 212 111, E-mail: [email protected]

introdUction

Cervical lesions appear on the cervical surface of the lingual or buccal side of the tooth. Conventionally, from an etiological point of view, they are classified into carious and non-carious lesions.1,2

Nowadays, non-carious cervical lesions represent a serious problem for oral healthcare. It is well known that they can be caused by abrasion through brush-ing. In the last twenty years, it has been hypothesized that the etiological factor of these lesions with angular shape could be found in the dental flexion, which appears as a result of tensile stress. Non-carious cervical lesions are classified into

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abrasions, erosions, and abfractions.3,4 Grippo et al. used the term abfraction to refer to the pathological loss of tooth substance at the cervical level.5 He reported several cases with predisposition to the formation of abfraction-type le-sions. Shafer, Hine, and Levy maintain that abrasion and erosion are two distinct, separate processes, each leading to the loss of tooth substance.6 A study carried out by Bader et al. showed that the development of cervical lesions has a multifactorial etiology, which includes diet, brushing style, as well as occlusal mechanisms, and that it can have inde-pendent effects on various points on the same tooth.7 In a longitudinal study that lasted fourteen years, Pintado et al. showed that there is a correlation between occlusal wear and the development of non-carious cervical lesions.8 In most cervical lesions, the cavity presents mixed margins, positioned in the enamel and in the dentine, and/or in the cement. As a consequence, the restoration of this type of cavities is more difficult due to the lack of a material which adheres equally to both the enamel and the dentine.

The most challenging problems are posed by the reliabil-ity of restorations set with the margin in the dentine. For several years, glass ionomer cements have been thought to be the best materials for the reparation of cervical lesions, because they can form a chemical reaction with both the enamel and the dentine, and can release fluoride for long periods of time, thus having a protective effect against car-ies. Various clinical researchers have highlighted the possi-bility to restore cervical caries with the use of conventional glass, with great results.2,9,10

Recently, much attention has been paid to the new generation of hybrid, photopolymerizable restoration materials, to resin-modified glass ionomer cements, and to polyacid-modified resin-based composites, all having been increasingly used in the treatment of cervical lesions. In the case of resin-modified ionomer cements, the fun-damental reaction of acid-base-polymerization is supple-mented by a process of photopolymerization. These mate-rials allow an almost instantaneous hardening, thus trying to solve, at the same time, the problem of sensitivity to hu-midity. Moreover, the positive properties of glass ionomer cements, such as fluoride release, have been preserved or even improved in the hybrid ionomers.11,12

In the oral cavity, the performance of restorative materi-als can be affected by multiple and clinically interactive vari-ables. Although several earlier studies have evaluated the util-ity of novel esthetic materials in cervical lesion restorations, there are still certain controversies with regard to the mate-rial that can ensure the best results when used clinically.11,13,14

As a consequence, we conducted a clinical study for a pe-riod of two years, at the end of which we analyzed the per-

formance of four different materials, namely: conventional glass ionomer cement, two resin-modified glass ionomer ce-ments, and a polyacid-modified resin-based composite. The present study evaluates the performance of three different types of esthetic restorative materials, used for the restora-tion of carious or non-carious cervical lesions.

MatErials and MEthods

Study subjects

The study included 220 cervical lesions in 53 patients, aged between 25 and 63 years. Inclusion criteria were the ab-sence of the following:

– serious medical condition; – extended carious lesions; – severe chronic periodontitis; – xerostomy; – apical periodontitis or pulpitis.

Before beginning the conservative treatment, the study subjects were informed about the purpose of the study and the necessity of regular dental checkups. Each patient par-ticipated voluntarily and signed a written informed con-sent.

The patients were also informed about eating habits and received instructions on oral hygiene, particularly through practical demonstrations of correct brushing. Each patient was checked twice a year, using an oral health progress re-cord (OHPR).

According to the OHPR:

– 0/1 indicates good oral hygiene; – 2 indicates slight problems by a narrow margin; – >2 indicates certain problems which require additio-nal interventions or scaling.

Patients with poor oral hygiene, strong occlusion and/or tooth wear were excluded from the study.

There were 45 patients left in the study (28 women and 17 men), who underwent a total of 195 restorations, the rest of the patients being excluded for various reasons (tooth extraction, emergence of periodontal complica-tions, the patient’s absence from the checkup session).

The restorations were carried out for non-carious cervi-cal lesions in 34.62% of the cases, for primary carious le-sions in 40% of the cases, and to replace a previous restora-tion in 25.38% of the cases. All cavities presented mixed margins, both in the enamel and in the dentine (Table 1).

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Each patient presented at least two cervical lesions, which were restored with minimum 2 and maximum 4 different materials. The teeth were divided into 4 groups, based on the restoration material used:

a) Group 1: restorations with conventional glass iono-mer cement – G1 (n = 30);

b) Group 2: restorations with resin-modified glass iono-mer cement – G2 (n = 68);

c) Group 3: restorations with resin-modified glass iono-mer cement – G3 (n = 54);

d) Group 4: restorations with polyacid-modified resin-based composites – G4 (n = 43).

We applied the restoration materials randomly, on in-cisors, canines, or premolars, either on the mandibular or maxillary arches.

Preparation and pre-treatment of cavities

All cavities were prepared in advance, and the restorations were applied by a single dentist. Each patient received at least two restorations.

For the present study, none of the restorations were performed under local anesthesia or using a rubber dam. Humidity control was ensured using cotton rolls and saliva suction pumps. In some situations, a gingival retraction cord was also applied, in order to prevent contamination with saliva or blood.

After the preparation of the operation field and the dry-ing of the cavities, the restoration materials were placed in conformity with the producer’s instructions. Restoration materials which had a polymerization indicator were photo-polymerized with a high-energy light source (550 W/cm2).

Evaluation of restorations

The restorations were evaluated using a blind evaluation technique, all restorations being evaluated during the pa-tient’s three visits: at 2 weeks (the reference line), and then

at 1 and 2 years after the placement. The following param-eters were assessed: restoration retention, color harmoni-zation, surface texture, margin discoloration, anatomical contour, margin integrity, and the presence of secondary caries. In order to determine the stability of the material color, intraoral color photographs were taken right after the placement of the material and at each of the patient’s visit for a check-up.

During patient follow-up, the restorations were not modified (for example, refined and polished).

The characteristics were registered in conformity with the modified United States Public Health Service (USPHS) criteria (Table 3).3,6 The USPHS evaluation3,6 is based on several performance criteria, which are applied to all the parameters concerned:

1. Alpha score (A) – ideal from a clinical point of view – clinical situation with a maximum of clinical performance;

2. Bravo score (B) – acceptable from a clinical point of view – all the parameters are satisfactory, and the restoration is acceptable;

3. Charlie score (C) – unacceptable from a clinical point of view – when one or several characteristics require replacement of the restoration;

4. Delta score (D) – loss of restoration or maximal modification of certain characteristics.

Restoration retention rates were assessed in accordance with the guidelines of the American Dental Association (ADA):

Cumulative failure % = [(PF + NF)/(PF + RR)] × 100%

PF – number of previous failures, before the present procedure

NF – number of new failures, at the present procedureRR – number of restorations at the present procedure

TABLE 1. The distribution of restorations based on the clinical

situation

Clinical situation Number of restorations

Cervical non-carious lesions 67

Primary carious lesions 78

Preexisting restorations 50

Total 195

TABLE 2. The distribution of restorations based on the affected

tooth and arch

Distribution of restorations Number of restorations

Upper incisors 58

Upper canines 25

Upper premolars 32

Lower incisors 25

Lower canines 29

Lower premolars 26

Total 195

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Statistical analysis

All results were obtained in the form of Alpha, Bravo, Charlie, and Delta scores, and the statistical analysis of the data was conducted using the SPSS 10.0 for Windows software (SPSS Inc., Chicago, IL, USA). The data were analyzed using the Chi-square test and the Fisher test, with a level of significance of 5%. Because a substantial rate of patients presented more than one restoration, the analysis was performed with a non-independent observa-tion criterion.

rEsUlts

A number of 45 patients were left in the study, therefore we were able to examine 195 restorations. The reasons for not including the rest of the restorations in the evaluation were either a crown replacement, or the patient’s decision to stop participating in the study, for personal reasons. Dur-ing the testing period, we did not notice any loss of vitality or any progression of periodontal pathology in the teeth under investigation.

At the one-year evaluation, of the total number of res-torations, we noticed the loss of 12 restorations, and after 2 years, the loss of 19 restorations (Figure 1). The total number of placed and lost restorations according to the anatomical placement of the restoration is listed in Table 3. Retention failure at the level of the mandibular arch was higher than in the maxillary one. The mandibular incisors presented a higher rate of retention failure (Table 3).

The retention rate of the restorative materials for a pe-riod of two years was 70% in G1, 100% in G2, 67% in G3, and 68% in G4. During the entire period of our study, four secondary caries emerged. Nevertheless, we discovered significant differences between the restorative materials regarding color, margin adaptation, margin coloration,

surface texture, as well as the criteria regarding the ana-tomical contour (p <0.05) (Table 4).

On the other hand, from the point of view of the reten-tion, G1 presented excellent characteristics compared to the other materials (p <0.05). Only 2 restorations with conventional glass ionomer cement (G1) received a score of 4 for margin adaptation after 2 years. Despite its higher retention, resin-modified glass ionomer cement (G2) dis-played the lowest Alpha scores for margin discoloration, margin adaptation, and anatomical contour, followed by conventional glass ionomer cement (G1) and polyacid-modified resin-based composites (G4) (Table 4).

discUssions

The ADA guide imposes the acceptance of the evaluation of a two-year clinical study and a failure rate of 5%. In the present study, the retention rates of the utilized materi-als did not exceed this loss percentage. Consequently, we can say that our results demonstrated the efficacy of resin-modified glass ionomer cement (G2) for cervical lesion restorations. Its ionic binding to the structure of the tooth seemed to be more efficient than the binding of other ma-terials tested during our study.15

In the present study, we used the modified USPHS cri-teria for the clinical evaluation of restorations of class V cavities. Altogether, for the clinical evaluation of tooth restorations, several different protocols have been devel-oped and described, including USPHS, Ryge, or CDA. In order to perform a high-quality evaluation, most evalua-tion algorithms are based on the classification of quality: retention, anatomical contour, margin integrity, nuance harmonization, and margin discoloration, which can be categorized as acceptable or unacceptable. An objective and reproducible clinical evaluation of tooth restorations can be carried out with the use of any of these classifica-tion tools.

TABLE 3. Placed and lost restorations

Restorations (n)

Lost restorations

(n)

Lost restorations

(%)

Upper incisors 58 5 5.17

Upper canines 25 3 12

Upper premolars 32 1 3.12

Lower incisors 25 12 48

Lower canines 29 8 27.58

Lower premolars 26 3 11.53

Total 195 31 15.89

195 195183

012 19

0

50

100

150

200

250

2 weeks 1 year 2 years

Total restorations Lost restorations

FIGURE 1. The distribution of lost restorations

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23Journal of Interdisciplinary Medicine 2019;4(1):19-24

Restoration loss can be caused by the alteration of den-tine binding, by the continuous flexion of the tooth, and by occlusal stress. These factors affect teeth at the level of the maxillary and mandibular arch in a different manner. Re-searchers have noticed a decrease in retention of cervical lesions due to high flexion in mandibular teeth.16

We registered this phenomenon as well, especially in the case of retention in the front mandibular teeth, which reached a level of 47%; despite this, none of the restora-tions located on the maxillary premolars was lost. Our study also sought to evaluate the success rate of the materi-als according to different groups of teeth, from the point of view of the occlusion. Therefore, the selection and distri-bution were random.

Another factor that has been described to affect the re-tention percentage is the elastic module of materials used for restoration. Heymann et al. showed that the retention frequency in case of restorations with low-level elastic-ity materials was significantly higher compared to those

with a highly elastic module.17 In our study, we observed that Group 1 had the highest retention rates, conventional glass ionomer cement having the lowest elastic module of the tested materials. In areas where the occlusal forces are more intensely concentrated, especially at the level of the mandibular incisors, it would be more useful to use restor-ative materials with a low elastic module, thus increasing the retention rates over time.11,13,18

The improvements we noticed regarding the retention of glass ionomer cements were not as significant as we anticipated. The retention rates of various esthetic restor-ative materials used for the reparation of cervical lesions has been described to be between 69% and 100%. Reten-tion success depends on the patient’s choice, the place and shape of the lesion, but also on the properties of the used materials. Regardless of the material tested, we can expect a high retention rate if the material is set in an area with low concentration of stress. The main reason for the different results of studies might be found in the different

TABLE 4. Clinical evaluation of the materials used in the study – USPHS-corresponding

scores

G1 G2 G3 G4

1 2 1 2 1 2 1 2

Retention

A 29 21 68 68 49 36 35 29

B 1 9 0 0 5 18 9 14

Color match

A 30 30 53 24 24 4 39 20

B 0 0 15 44 30 50 4 23

Marginal discoloration

A 28 26 45 11 41 27 37 23

B 2 4 23 57 13 27 6 20

C 0 0 0 0 0 0 0 0

D 0 0 0 0 0 0 0 0

Marginal adaptation

A 30 26 60 27 44 27 35 17

B 0 4 8 26 11 26 9 26

C 0 0 0 0 0 0 0 0

Surface texture

A 30 30 49 31 39 24 38 29

B 0 0 19 37 15 30 6 14

C 0 0 0 0 0 0 0 0

Anatomic form

A 29 28 51 29 38 27 30 26

B 1 2 17 39 16 27 13 17

C 0 0 0 0 0 0 0 0

D 0 0 0 0 0 0 0 0

Secondary caries

A 30 28 68 67 54 54 43 42

B 0 2 0 1 0 0 0 1

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24 Journal of Interdisciplinary Medicine 2019;4(1):19-24

location of restorations. The differences in retention rates may be due, for example, to the lack of preparation of re-tentions in the enamel. Moreover, these different results might also be explained by the random distribution of the materials according the groups of teeth and the maxillary or mandibular arch.19,20

Regarding the reference line, the high percentage of Al-pha scores (100%) obtained by resin-modified glass iono-mer cement, in the characteristics of the surface may have been due to the protective layer applied over the surface of the material.21 This smooth and shiny layer turned into a rough layer by the end of the study. The roughness of the surface may be the result of the very erosive wear of the ma-terial, which led to external discoloration, thus tending to have more spots or discoloration than a smooth surface.4,14

The anatomical and physiological contour is difficult to reproduce with glass ionomer cements because of their low viscosity and relatively sticky properties. Secondly, the modification in the anatomical contours of the obtura-tion with resin-modified glass ionomer cement might be due to physical-mechanical properties.22

According to Levitch et al., occlusal stress, which leads to the distortion of cervical lesions, is the main factor in-volved in the pathogenesis of cervical lesions.22

In our research, strict standards were applied in the eval-uation of restorations. An Alpha score was conferred to an excellent restoration. Therefore, most Bravo scores repre-sent the result of this strict rule of observation, while the differences between Alpha and Bravo were only marginal.

Since both Alpha and Bravo show clinical satisfactori-ness, all restorative materials that had been used in this study were within adequate limits. Our study is concurrent with the results of previous studies in the fact that the restorative materials used for cervical lesions had different results, in all the aspects of clinical evaluation. According to our results, resin-modified glass ionomer cement (G2), which present-ed the highest rate of retention, seems to be the most suit-able material for the restoration of cervical lesions, although it requires clinical improvements. Nevertheless, the repair of cervical lesions appears to be an ongoing challenge.

conclUsions

The evaluation of the success of restorative material reten-tion must consider the location of the cervical lesion. The retention is influenced by several factors, including den-tal flexion, occlusal stress, dentine surface, and the elastic module of the materials used for restoration. The applica-tion of a photopolymerizable cover material can be con-sidered an efficient procedure, especially when the polish-

ing procedures are performed right after the restoration. Successful treatment depends particularly on a full under-standing of the factors that caused the lesions and on the method of their treatment.

conFlict oF intErEst

Nothing to declare.

rEFErEncEs

1. Gladys S, Van Meerbeek B, Lambrechts P, Vanherle G. Marginal adaptation and retention of glass-ionomer, resin-modified glass ionomers and a polyacid-modified resin composite in cervical class V lesions. Dent Mater. 1998;14:294-306.

2. Bereşescu G, Bocskay St. Glass ionomer cements used in atraumatic restorative treatment technique. Revista de Medicină şi Farmacie, Universitatea de Medicină şi Farmacie Tg.Mureş. 2009;55:509-510.

3. Ngo H, Mount GJ, Peters MC. A study of glass-ionomer cement and its interface with enamel and dentin using a low-temperature, high-resolution scanning electron microscope technique. Quintessence. 1997;28:63-69.

4. Mount GJ. An atlas of glass-ionomer cements. A clinician’s guide. 3rd ed. London: Martin Dunitz Ltd, 2002.

5. Grippo JO. Noncarious cervical lesion the decision to ignore or restore. J Esthet Dent. 1992;4:55-64.

6. Neo J, Chew CL, Yap A, Sidhu S. Clinical evaluation of tooth-colored materials in cervical lesions. Am J Dent. 1996;9:15-18.

7. Bader JD, Levitch LC, Shugars DA, Heymann HO, McClure F. How dentists classified and treated non-carious cervical lesions. J Am Dent Assoc. 1993;124:46-54.

8. Pintado MR, Delong R, Ko CC, Sakaguchi RL, Douglas WH. Correlation of noncarious cervical lesion size and occlusal wear in a single adult over a 14-year time span. J Prosthet Dent. 2000;84:436-443.

9. Van Dijken JWV. Durability of three simplified adhesive systems in class V non-carious cervical dentin lesions. Am J Dent. 2004;17:27-32.

10. Beresescu G, Ormenisan A, Comaneanu RM, Carp Veliscu AM, Manea MM, Ion R. FEM Analysis of stress in non-carious cervical lesion restoration with four different restorative materials. Rev Mat Plast. 2018;55:42-45.

11. Yaman SD, Sahin M, Aydin C. Finite element analysis of strength of various resin-based restorative materials in class V cavities. J Oral Rehabil. 2003;30:630-641.

12. Brackett WW, Dib A, Blackett MG, Reyes AA, Estrada BE. Two-year clinical performance of class V resin-modified glass-ionomer and resin composite restorations. Oper Dent. 2003;28:477-481.

13. Kubo S, Kawasaki K, Yokota H, Hayashi Y. Five-year clinical evaluation of two adhesive systems in non-carious cervical lesions. J Dent. 2006;34:97-105.

14. Rees JS, Jacobsen PH. The effect of interfacial failure around a class V composite restoration analysed by the finite element method. J Oral Rehabil. 2000;27:111-116.

15. Xie D, Wu W, Puckett A, Farmer B, Mays J. Novel resin modified glass ionomer cements with improved flexural strength and ease of handling. Eur Polym J. 2004;40:343-351.

16. Feigal RJ, Musherure P, Gillespie B, Levy-Polack M, Quelhas I, Hebling J. Improved sealant retention with bonding agents: A clinical study of two-bottle and single-bottle systems. J Dent Res. 2000;79:1850-1856.

17. Heymann HO, Sturdevant JR, Bayne S, Wilder AD, Sluder TB, Brunson WD. Examining tooth flexure effects on cervical restorations: a two-year clinical study. J Am Dent Assoc. 1991;122:41-47.

18. Pintado MR, Delong R, Ko CC, Sakaguchi RL, Douglas WH. Correlation of non-carious cervical lesion size and occlusal wear in a single adult over a 14-year time span. J Prosthet Dent. 2000;84:436-443.

19. Aranda M, Garcia-Godoy F. Clinical evaluation of the retention and wear of light-cured pit and fissure glass ionomer sealant. J Clin Pediatr Dent. 2015;19:273-277.

20. Croll TP, Nicholson JW. Glass ionomer cements in pediatric dentistry: a review of the literature. Pediatric Dentistry. 2002;24:423-429.

21. Beresescu FG, Hancu V, Mucenis S, Cosarca AS, Comaneanu R, Ormenisan A. In vitro study regarding the wearing of glass ionomer cements. Rev Mat Plast. 2015;52:272-274.

22. Levitch LC, Bader JD, Shugars DA, Heymann HO. Non-carious cervical lesions. J Dent. 1994;22:195-207.

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Journal of Interdisciplinary Medicine 2019;4(1):25-28

CORRESPONDENCE

Mónika I. Mária Szabó Str. Gheorghe Marinescu nr. 38540139 Târgu Mureș, RomaniaTel: +40 722 338 141, +40 265 268 595E-mail: [email protected], [email protected]

ARTICLE HISTORY

Received: October 4, 2018 Accepted: January 18, 2019

Low Level of Physical Activity in Two Roma Subgroups Compared to Non-Roma Population in Niraj Valley, TransylvaniaMonica I. Szabó1,2, Anita Balázs2, Beáta Máté2, Piroska Kelemen1,3

1 Department of Internal Medicine, University of Medicine, Pharmacy, Sciences and Technology, Târgu Mureș, Romania 2 Clinic of Diabetology, Emergency County Clinic, Târgu Mureș, Romania3 Clinic of Internal Medicine, Emergency County Clinic, Târgu Mureș, Romania

original rEsEarch PUBLIC HEALTH // EPIDEMIOLOGY

DOI: 10.2478/jim-2019-0002

ABSTRACT

Objective: A low level of physical activity is a cardiovascular risk factor. Physical activity pat-terns may differ among different ethnic groups. Aim of the study: Our aim was to evaluate the physical activity patterns of two different Roma populations compared to non-Roma. Material and Methods: The study population included 231 Gabor Roma, 111 Băieși Roma, and 183 non-Roma. A 70-item questionnaire was administered, including also the short form of the Interna-tional Physical Activity Questionnaire, evaluating daily physical activity in minutes and physical activity categories such as walking, gardening, household activity, and sports. Anthropometric parameters (weight, height, waist and hip circumference) were measured. Results: The level of physical activity was the lowest among Gabor Roma and was lower in both Roma groups than in non-Roma (Gabor Roma 118.6 ± 91.1 min/day, Băieși Roma 207.55 ± 172.1 min/day, and non-Roma 234.12 ± 167.3 min/day). Both Roma groups had significantly lower percentages of gardening and sport activities compared to non-Roma. Women had a higher level of daily physical activ-ity than men in the Gabor Roma population (144.22 ± 109.4 min/day vs. 79.71 ± 58.2 min/day, p = 0.001). In the two other groups the differences were not statistically significant. Conclu-sions: Both Roma groups had significantly lower levels of daily physical activity, with differences between genders. Both Roma groups were lesser engaged in sports and gardening than non-Roma subjects.

Keywords: Gabor Roma, Băieși Roma, physical activity level

Anita Balázs • Str. Gheorghe Marinescu nr. 50, 540136 Târgu Mureș, Romania. Tel: +40 746 959 886, E-mail: [email protected]

Beáta Máté • Str. Gheorghe Marinescu nr. 50, 540136 Târgu Mureș, Romania. Tel: +40 743 045 282, E-mail: [email protected]

Piroska Kelemen • Str. Gheorghe Marinescu nr. 50, 540136 Târgu Mureș, Romania. Tel: +40 740 148 589, E-mail: [email protected]

introdUction

Roma ethnicity represents 3.29% of Romania's population, but it is assumed that the real percentage is higher.1 The Roma population experienced a fundamental change in their way of life in the last few years. On the other hand, originating from the northern part of India, they are still a group with distinct genetic and socio-cultural features, which has on impact on their phenotype.2 Traditionally, they do not own land, and, even in rural settings, their income is mainly from trading, not farming. The evaluation of the metabolic status and lifestyle habits

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26 Journal of Interdisciplinary Medicine 2019;4(1):25-28

of the Roma started a decade ago, showing higher degrees of obesity, metabolic syndrome, and cardiovascular risk profile; however, data were conflicting.3–7 Studies existing so far did not take into account the heterogeneity of this ethnic group, with subgroups having different languages, traditions, income, and beliefs; consequently, the evalua-tion of these groups needs to be done distinctly. It is well established that the level of physical activity is one of the key risk factors in cardiovascular disease.8,9 Physical activity patterns may differ among different ethnic groups, as it was demonstrated in several studies.10 There were no specific epidemiological studies conducted among the Roma re-garding their lifestyle and level of physical activity. Our aim was to evaluate the levels and patterns of physical activity of two different Roma populations compared to non-Roma.

MatErial and MEthods

We present preliminary data on physical activity-related findings of an ongoing larger non-interventional, popula-tion-based, cross-sectional survey, evaluating lifestyle, so-cio-cultural status, metabolic syndrome, and genetic traits among two Roma subgroups.

The study population consisted of Gabor Roma, Băieși Roma, and non-Roma subjects living in a rural environ-ment in Mureș County, Romania. The community was ap-proached through the general practitioner and community leaders. Screening took place at the general practitioner’s office and facilities at the local church. Previously trained medical staff was involved in assisting participants to answer the questionnaires and helped to complete measurements.

In total, 231 Gabor Roma, 111 Băieși Roma, and 183 non-Roma were included. The Gabor Roma is a gipsy sub-group living mainly in Transylvania, having an archaic and strong community structure. They are relatively prosper-ous, affiliated to a neo-protestant church. The Băieși Roma are on average poor, less well organized, not keeping tradi-tions. We involved non-Roma participants from the same area. The groups were age and sex matched. We included all subjects older than 18 years who were residing in the area and were willing to sign the informed consent.

A lifestyle and social life-related questionnaire was ad-ministered, which also included the short form of the In-ternational Physical Activity Questionnaire.11 We evalu-ated daily physical activity in the last 7 days (min/day), considering minutes of moderate-intensity activity and physical activity categories in which they mainly took part such as walking, gardening, household activity, and sports.

Anthropometric parameters: weight, height, waist and hip circumferences (WC and HC) were measured with a

standard clinical scale and a centimeter according to stan-dard procedures. Body mass index (BMI) and waist-hip ratio (WHR) were calculated (weight/height2 and waist circumference/hip circumference, respectively). The pres-ence of obesity was defined as a BMI ≥30 kg/m2.

The study was approved by the Ethics Committee of the University of Medicine, Pharmacy, Sciences and Technol-ogy of Târgu Mureș, Romania.

Statistical analysis

The results of the three groups were compared using one-way ANOVA test for scale variables and the Chi square test for categorical variables. Student’s t-test was used to compare gender differences. Correlations within groups were tested with linear logistic regression, and distribution was tested with the Kolmogorov Smirnov test. Statistical analysis was performed using SPSS version 18 (SPSS Inc., Chicago, USA), and a p value of <0.05 was considered to be statistically significant.

rEsUlts

The study population consisted of Gabor Roma (n = 231, mean age 41.74 ± 14.03 years, 45.8% men), Băieși Roma (n = 111, mean age 40.30 ± 14.0 years, 40.5% men), and non-Roma (n = 183, mean age = 44.62 ± 14.6 years; 41.5% men) participants. Demographic and health-related char-acteristics of the study population are presented in Table 1.

In our study population, Gabor Roma had a significant-ly higher BMI, WC, and prevalence of obesity compared to Băieși Roma or non-Roma, with Băieși Roma having the lowest values. Gabor Roma had a significantly higher percentage of obesity compared to Băieși Roma and non-Roma, and there was no difference between the other two groups (Table 1).

The lowest level of daily activity was registered in the Gabor Roma group (118.6 ± 91.1 min/day), followed by the Băieși Roma (207.55 ± 170.3 min/day) and the non-Roma subjects (243.12 ± 167.3 min/day), the difference being statistically significant (p = 0.00). Using a linear re-gression model, BMI and WC being the dependent vari-ables, we found a strong correlation between daily activity and BMI (F = 4.25, p = 0.04) in the Gabor Roma group.

Both Roma groups had significantly lower percentages of gardening and sport activities compared to non-Roma, but there was no difference between them (Figure 1).

Men had a higher level of daily physical activity than women in the Gabor Roma population (144.22 ± 109.4 min/day vs. 79.71 ± 58.2 min/day, p <0.001). In the other

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27Journal of Interdisciplinary Medicine 2019;4(1):25-28

groups the differences between genders were not statisti-cally significant: in the Băieși Roma 211.52 ± 171.1 min/day for women vs. 195.3 ± 186.0 min/day for men (p = 0.79), and in the non-Roma 229.4 ± 121.3 min/day for women vs. 253.6 ± 117.6 min/day for men (Figure 2).

discUssions

This study evaluated physical activity patterns in two Roma subgroups and a non-Roma group. The entire cohort had a relatively high average daily level of moderate physical activity (Gabor Roma 118.6 ± 91.1 min/day, Băieși Roma 207.55 ± 172.1 min/day, and non-Roma 234.12 ± 167.3 min/day), probably due to their lifestyle in the rural environment where they all came from. However, both Roma subgroups

had a lower level of physical activity compared to non-Ro-ma, with no significant differences between the two Roma groups, despite their different socioeconomic status and lifestyle. The results are consistent with other findings,12,13 and might be explained by the fact that Roma are not tied to land and generally do not own agricultural areas larger than their garden. Gabor Roma men are involved mostly in trade, and Băieși Roma frequently are unemployed, thus less en-gaged in work-related physical activities.

Gabor Roma were significantly more obese than Băieși Roma and non-Roma. The level of physical activity was strongly correlated with the BMI, mainly in the Gabor Roma group. The relationship between obesity and physi-cal activity is well documented in many different age, gen-der, and ethnic groups.14

TABLE 1. Demographic and health-related characteristics of the three ethnic groups

Gabor Roma Băieși Roma Non-Roma p value * #

N 231 111 183

Age (years) 41.74 ± 14.0 40.30 ± 14.0 44.62 ± 14.6 0.861*, 0.122#

Gender (n/% men) 106 / 45.8 45 / 40.5 76 / 41.5 0.127*, 0.451#

BMI (kg/m2) 31.1 ± 4.6 27.4 ± 5.2 28.66 ± 5.7 0.004*, 0.021#

Obesity (n/%) 157 / 68 47 / 42.3 79 / 43.1 0.013*, 0.028#

WC (cm) 102.73 ± 13.35 89.54 ± 13.83 98.21 ± 13.8 0.003*, 0.041#

WHR 0.91 ± 0.1 0.83 ± 0.0 0.91 ± 0.0 0.035*, 0.896#

Daily moderate physical activity (min/day) 118.6 ± 91.1 207.55 ± 172.1 234.12 ± 167.3 0.001*, 0.000#

Practicing sports (N / %) 6 / 2.6 0 23 / 12.5 0.041*, 0.004#

Walking (N / %) 93 / 40.2 40 / 36.0 53 / 28.9 0.392*, 0.044#

Gardening (N / %) 54 / 23.3 30 / 27.0 130 / 71.0 0.284*, 0.000#

Household activity (N / %) 143 / 61.9 60 / 54.0 126 / 68.8 0.186*, 0.532#

* between Gabor Roma and Băieși Roma; # between Gabor Roma and non-Roma. Continual values mean ± SD

40.2

23.3

61.9

2.6

36.0

27.0

54.0

0.0

28.9

71.068.8

12.5

0

10

20

30

40

50

60

70

80

Walking Gardening Household Sports

Perc

enta

ge o

f par

ticip

ants

cho

osin

g th

e gi

ven

phys

ical

act

ivity

Gabor RomaBăieși RomaNon-roma

FIGURE 1. Percentage of the three ethnic groups choosing specific types of physical activity

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28 Journal of Interdisciplinary Medicine 2019;4(1):25-28

As it was presented in the Roma Health Report of the European Union,15 the gipsy population has an unhealthy lifestyle overall. They are less engaged in physical activi-ties with higher intensity such as sports or gardening, their main exercise being walking and everyday work in and around the house.

Women had a very distinct physical activity pattern in both Roma subgroups compared to the non-Roma.16 Ga-bor Roma women had a higher level of physical activity, albeit they were walking less than men, explained by the fact that they are mostly at home, almost none of them be-ing engaged in any sport. Gender differences were widely observed in Roma studies. In our study, differences in BMI and physical activity patterns were more obvious in the Gabor Roma population, which has a very archaic family model.

Our investigation included a relatively small number of participants so far, but the local Roma population is very hostile towards any screening action, considering it an ag-gression upon their community and not wanting to have diseases diagnosed, disease being a shame in their culture. The strength of our investigation is the fact that it com-pares the physical activity patterns of two different Roma subgroups.

conclUsions

Both Roma groups had significantly lower levels of daily physical activity, differences between genders being more obvious in the Gabor Roma group, where men were less

active. Both Roma groups were lesser engaged in sports and gardening than non-Roma.

acknoWlEdgEMEnt

Funding: This work was supported by SC Cosamext through the University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Romania [grant number 13429, 2016].

conFlict oF intErEst

We have no conflict of interests to declare.

rEFErEncEs1. Institutul Național de Statistică. Recensământul populației și a locuințelor

2011. http://www.recensamantromania.ro/noutati/volumul-ii-populatia-stabila-rezidenta-structura-etnica-si-confesionala (7 January 2019)

2. Mendizabal I, Lao O, Marigorta U, et al. Reconstructing the Population History of European Romani from Genome-wide Data. Curr Biol. 2012;22:2342-2349.

3. Weiss E, Japie C, Balahura A, Bartos D, Badila E. Cardiovascular risk factors in a Roma sample population from Romania. Rom J of Intern Med. 2018;56:193-202.

4. Kosa Zs, Moravtsik Kornitzky A, Dioszegi J, et al. Prevalence of metabolic syndrome among Roma: a comparative health examination survey in Hungary. Eur J of Public Health. 2015;25:299-304.

5. de Courten B, de Courten M, Hanson R, et al. Higher prevalence of type 2 diabetes, metabolic syndrome and cardiovascular diseases in gypsies than in non-gypsies in Slovakia. Diabetes Res and Clin Pract. 2003;62:95-103.

6. Enache G, Rusu E, Ilinca A, Rusu F, Costache A, Radulian G. Prevalance of obesity and newly diagnosed diabetes in the roma population from a county in the south part of Romania (Călărași county) – preliminary results. Rom J Diabetes Nutr Metab Dis. 2016;23:027-036.

7. Enache G, Rusu E, Ilinca A, et al. Prevalence of overweight and obesity in a Roma population from Southern Romania – Calarasi County. Acta Endo. 2008;14:122-130.

8. Agarwal SK. Cardiovascular benefits of exercise. Int J Gen Med. 2012;5:541-545.

9. Warburton DER, Nicol CW, Bredin SSD. Health benefits of physical activity: the evidence. CMAJ. 2006;174:801-9.

10. He XZ, Baker DW. Differences in leisure-time, household, and work-related physical activity by race, ethnicity, and education. J Gen Intern Med. 2005;20:259-66.

11. Ainsworth BE, Bassett DR Jr, Strath SJ, et al. Comparison of three methods for measuring the time spent in physical activity. Med Sci Sports Exerc. 2000;32:457-64.

12. Babinská I, Gecková AM, Jarcuska P, et al. Does the population living in Roma settlements differ in physical activity, smoking and alcohol consumption from the majority population in Slovakia. Cent Eur J Public Health. 2014;22:22-27.

13. Beenackers MA, Kamphuis CBM, Giskes K, et al. Socioeconomic inequalities in occupational, leisure-time, and transport related physical activity among European adults: a systematic review. Int J Behav Nutr Phys Act. 2012;19:116-119.

14. Nelson CC, Wagner GR, Caban-Martinez AJ, et al. Physical Activity and Body Mass Index: The Contribution of Age and Workplace Characteristics. Am J Prev Med. 2014;46:42-51.

15. Roma Health Report. Health status of the Roma population Data collection in the Member States of the European Union, 2014. https://ec.europa.eu/health//sites/health/files/social_determinants/docs/2014_roma_health_report_es_en.pdf (7 January 2019)

16. Coe K, Čvorović J. The health of Romanian Gypsy women in Serbia. Health Care Women Int. 2017;38:409-422.

Gabor Roma Băieși Roma Non-Roma

Ethnic groups

Daily a

cti

vit

y (

min

)

200

0

400

600

200

144.2

79.7

195.3 211.5

p <0.001

262

253.6 229.4

MaleFemale

FIGURE 2. Daily activity among men and women in the three

ethnic groups

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Journal of Interdisciplinary Medicine 2019;4(1):29-32

CORRESPONDENCE

Adrian NăzneanStr. Gheorghe Marinescu nr. 38540139 Târgu Mureș, RomaniaTel: +40 265 215 551E-mail: [email protected]

ARTICLE HISTORY

Received: February 3, 2019 Accepted: April 24, 2019

The Role of Pedobarography and Therapeutic Padding in the Management of Hyperkeratosis due to Mechanical StressAnca Chiriac1,2,3, Cristian Podoleanu4, Adrian Năznean5, Simona Stolnicu6

1 Department of Dermato-Physiology, Apollonia University, Iași, Romania2 Department of Dermatology, Nicolina Medical Center, Iași, Romania 3 “P. Poni’’ Institute of Macromolecular Chemistry, Apollonia University, Iași, Romania4 Department of Cardiology, University of Medicine, Pharmacy, Sciences and Technology, Târgu Mureș, Romania5 Department of Foreign Languages, University of Medicine, Pharmacy, Sciences and Technology, Târgu Mureș, Romania6 Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, Târgu Mureș, Romania

clinical UPdatE DERMATOLOGY // PODIATRY

DOI: 10.2478/jim-2019-0003

ABSTRACT

Hyperkeratotic lesions result from continuous mechanical action on the skin forming a callus or a corn. The accumulation of horny layers will increase pressure, creating a vicious cycle. We present a new approach based on relieving pressure or friction, strictly based on the results of pedography (pedobarography).

Keywords: skin, mechanical hyperkeratosis, therapy, pedography

Anca Chiriac • Str. Hatman Șendrea nr. 2, 700613 Iași, Romania. Tel: +40 332 808 703

Cristian Podoleanu • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureș, Romania. Tel: +40 0265 215 551

Simona Stolnicu • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureș, Romania. Tel: +40 0265 215 551

backgroUnd

Various mechanical factors may induce distinctive skin changes. Hyperkeratotic lesions do not correspond to a skin disease; they are the result of a continuous mechanical action on the skin. The body reacts by hyperkeratosis, trying to pro-tect the skin by forming a callus or a corn. However, the accumulation of horny layers will increase the pressure, creating a vicious cycle.

It is estimated that approximately 20% of the general population suffers from hyperkeratotic lesions induced by mechanical trauma, which are distributed mostly on the foot and toes, especially in women and the elderly.1

A callus is a non-penetrating circumscribed hyperkeratosis induced by pres-sure, most frequently on the palms and soles, over the bony prominences of the joints. It is a painful local thickening of the skin as a result of a mechanical injury, with acute evolution, caused by intermittent pressure. Some sportsmen may de-velop callosities, as well as people with specific occupations, as stigmata of their profession (violin players for example).2,3

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30 Journal of Interdisciplinary Medicine 2019;4(1):29-32

Ill-fitting shoes, rheumatic diseases, orthopedic anoma-lies (exostoses) of the foot are the main causes of callosi-ties. Plantar keratosis and metatarsal head callus are often associated with metatarsophalangeal dislocation in rheu-matoid arthritis.

A callus must be differentiated from a clavus (corn) for being more diffuse and without a penetrating central core. A clavus, in contrast, is a circumscribed conical thicken-ing of the skin, penetrating the subjacent structure. Three types of clavuses have been described: hard corn (heloma durum) on the dorsa of the toes or soles; soft corn (heloma mole) between the toes; and seed corn (heloma millare). Extreme pain caused by a clavus is explained by its pen-etrating effect, by irritating the sensory nerves from the papillary dermis, and by mechanical trauma (Figure 1 A, B, C, D).

The soft interdigital clavus occurs especially in the fourth interdigital space of the foot.

Plantar callosities are a common cause of pain in the forefoot and the main cause of alterations in plantar pres-sure.

FIGURE 1. Bilateral plantar clavus of the left (A) and right (B) foot; hard corn on the dorsal aspect of

toe I, II (C); Corn on the plantar face of toe III (D).

FIGURE 2. Personalized pedography showing the pressure

points and orthopedic anomalies in the left (A) and right (B) foot

A

A B

C

B

D

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31Journal of Interdisciplinary Medicine 2019;4(1):29-32

thEraPEUtic MEasUrEs For

hyPErkEratotic dErMatosEs

The treatment of hyperkeratotic dermatoses is difficult and relies on various methods. Emollients, warm saline water, and pumice stone are used to remove the thickened skin in minor forms, in the absence of diabetes mellitus or foot infection.

Due to its mechanism of producing the lesions, plantar callosities may disappear when the offending mechani-cal pressure is removed. The most practiced methods of treatment of callosities and clavus are based nowadays on mechanical debridement with a scalpel or curette, and/or removing the thickened skin using various kera-tolytics (salicylic acid-containing products associated with the risk of irritant effects on the normal surround-ing skin).4–6

Surgery is the most invasive method and must be used when all other attempts have failed in providing relief.

thE rolE oF PEdobarograPhy

Pedobarography (pedography) can quantify static and dy-namic foot pressure, abnormal pressure across the plantar surface; any detected pedobarographic modifications must be corrected in order to relieve the pain that accompanies foot callosities, especially in the elderly.

Pedography shows the distribution of plantar pressure in the foot, it is easy to perform and specific to each in-dividual and to each foot.7,8 Clinical examination of the patient, inspection of the footwear and plantography provide very useful information about the state of the foot and the type of load in certain phases of walking and orthostatism (Figure 2). Pedographic results enable the manufacturing of orthopedic devices to reduce symptoms and load on the feet, highly improving the quality of life of the patients.

This new approach is based on the relief of pressure or friction, removing the cause of the disease, strictly based

FIGURE 3. Different orthopedic corrections correlated to underlying foot deformity (A, B); silicone

toe separators (spreaders) (C); silicon toe-protector and corrective pads (D)

A

C

B

D

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32 Journal of Interdisciplinary Medicine 2019;4(1):29-32

on the results of pedography. Orthotic devices should be prescribed to the patient in order to redistribute mechan-ical pressure in the foot, allowing the lesion to heal. Clear explanations must be provided to the patients regarding the mechanisms through which the lesions are induced and the corrections that are required, because many of them search for a surgical intervention to alleviate the pain.

Silicon padding redistributes and corrects mechanical pressure, relieves the pain and represents the best conser-vatory measure, especially in the elderly. Specialized pad-ding cushions protect the callus or corn and put the foot and affected toes in a position that does not permit kera-totic lesions to develop (Figure 3 A, B). Currently, a great variety of pads exists on the market, for example pads for hard corns, pads for soft corns, metatarsal pads, and even so-called “internal pads” (injection of liquid silicone).9 In daily dermatological practice, pads are used based on the type of keratotic disorder and the results of pedography. Toe separators prevent and reduce friction, preserve the metatarsal phalangeal joint alignment in deformations and deviations, and reduce irritation and mechanical trauma (Figure 3 C). They keep toes from rubbing each other and prevent the occurrence of soft corns. Interdigital pads are also used to correct digital deformity, to reduce local trau-ma to the skin overlying the prominent interphalangeal joints and to reduce the risk of development of interdigital heloma molle.

Custom-made padded shoe inserts (orthotics) are rec-ommended to prevent and to treat corns or calluses in the presence of underlying foot deformity. There are different personalized types of plantar covers made accordingly to the results of pedography and with an interdisciplinary approach: dermatology, rheumatology, podiatry, surgery, and even psychology.

Dorsal bars or corrective pads correct digital deformi-ties, reduce trauma and pain, and eliminate skin injuries (Figure 3 D).

conclUsions

In conclusion, protective padding of different types, rec-ommended based on clinical examination and pedogra-phy, could be of value, particularly in the elderly, in terms of reducing plantar pressure, relieving pain and functional impairment, and avoiding surgery and hospitalization.

Prevention is also very important and can be done by wearing shoes with a large toe box and that fit well to each person. Thicker soles and all kind of protective padding re-lieve pressure while walking.

conFlict oF intErEst

Nothing to declare.

rEFErEncEs1. Höglund HC, Jeannot E, Delmi M, Chastonay P. Non traumatic lesions of

the foot, calluses and nails: socioeconomic impact of an unexplored issue. Rev Med Suisse. 2011;7:2148-2152.

2. Freeman DB. Corns and Calluses Resulting from Mechanical Hyperkeratosis. Am Fam Physician. 2002;65:2277-2280.

3. Richards RN. Calluses, corns, and shoes. Semin Dermatol. 1991;10:112-114.4. Silfverskiold JP. Common foot problems. Relieving the pain of bunions,

keratoses, corns, and calluses. Postgrad Med. 1991;89:183-188.5. Singh D, Bentley G, Trevino SG. Callosities, corns, and calluses. BMJ.

1996;312:1403–1406.6. Gijon-Nogueron G, Garcia-Paya I, Ortega-Avila AB, Paez-Moguer J,

Cervera-Marin JA. Changes in the parameters of gait after a mechanical debridement of a plantar callosities. J Tissue Viability. 2015;24:12-16.

7. Skopljak A, Muftic M, Sukalo A, Masic I, Zunic L. Pedobarography in diagnosis and clinical application. Acta Inform Med. 2014;22:374-378.

8. Panesar K. Corns and Calluses: Overview of Common Keratotic Lesions. US Pharm. 2014;39:4750.

9. Bowling FL, Metcalfe SA, Wu S, Boulton AJ, Armstrong DG. Liquid Silicone to Mitigate Plantar Pedal Pressure: A Literature Review. J Diabetes Sci Technol. 2010;4:846-852.

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Journal of Interdisciplinary Medicine 2019;4(1):33-36

CORRESPONDENCE

Cédric KwizeraStr. Gheorghe Marinescu nr. 50540136 Târgu Mureș, RomaniaTel: +40 729 937 393E-mail: [email protected]

ARTICLE HISTORY

Received: February 22, 2019 Accepted: March 27, 2019

Uncommon Differential Diagnosis of Acute Right-sided Abdominal Pain – Case ReportCédric Kwizera1, Benedikt Wagner2, Johannes B. Wagner3, Călin Molnar1

1 Department of Surgery, Emergency County Hospital, Târgu Mureș, Romania2 Student, Faculty of General Medicine, University of Medicine, Pharmacy, Sciences and Technology, Târgu Mureș, Romania3 Department of General, Abdominal and Endovascular Surgery, District Hospital Landsberg am Lech, Germany

casE rEPort SURGERY // RADIOLOGY

DOI: 10.2478/jim-2019-0004

ABSTRACT

The appendix is a worm-like, blind-ending tube, with its base on the caecum and its tip in multiple locations. Against all odds, it plays a key role in the digestive immune system and appendectomy should therefore be cautiously considered and indicated. We report the case of a 45-year-old male with a known history of Fragile-X syndrome who presented to the emer-gency department with intense abdominal pain and was suspected of acute appendicitis, after a positive Dieulafoy’s triad was confirmed. The laparoscopic exploration showed no signs of inflammation of the appendix; nonetheless, its removal was carried out. Rising inflammatory laboratory parameters led to a focused identification of a pleural empyema due to a tooth inlay aspiration. Our objective is to emphasize the importance of a thorough anamnesis, even in cases of mentally impaired patients, as well as to highlight a rare differential diagnosis for ap-pendicitis. Acute appendicitis is an emergency condition that requires a thorough assessment and appropriate therapy. Clinical examinations are important, but in this particular case, imaging methods had a much more important role in establishing the right treatment approach. Further-more, the signs of acute appendicitis are mimicked by several medical conditions including respiratory tract infections.

Keywords: appendicitis, pleural empyema, differential diagnosis, tooth inlay aspiration

Benedikt Wagner • Str. Gheorghe Marinescu nr. 38, 540139 Târgu Mureș, Romania. Tel: +40 265 215 551

Johannes B. Wagner • Bürgermeister-Dr.-Hartmann-Straße nr. 50, 86899 Landsberg am Lech, Germany. Tel: +49 8191 3330

Călin Molnar • Str. Gheorghe Marinescu nr. 38, 540139 Târgu Mureș, Romania. Tel: +40 265 215 551

introdUction

The appendix or vermiform process is a worm-like, blind-ending tube connect-ed to the caecum, about 2 cm beneath the Bauhin valve. Its average dimensions are 7–8 mm wide and 9 cm long, but its length can range from 2 to 20 cm, the longest ever recorded appendix being 26 cm long, discovered postmortem in a 72-year-old Croatian patient (Guinness World Record 2006). Its base is attached to the cecum, but the position of its tip can vary, as it can be retrocecal, subcecal, pre-ileal, retroileal, pelvic, or ectopic.1 The appendix has long been considered worthless due to the absence of noticeable reactions post appendectomy, hence the assumption of its vestigial characteristics.2 Nevertheless, William Parker et al. suggested that it may act as a storage unit of beneficial microbiome, activated especially after the reduction of normal intestinal bacteria following infectious

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34 Journal of Interdisciplinary Medicine 2019;4(1):33-36

diseases,3 because the immune system participates in the formation of the benefi cial microbiome due to the location of the appendix and its histological structure with immune tissues.4 Research has shown that patients were four times more prone to a recurrent Clostridium diffi cile colitis fol-lowing an appendectomy.5 Its structure contains B cells, extra-thymic T cells along with lymphatic vessels, partici-pates in the elimination of gastrointestinal waste, stopping pathogens and assuring an early immunological defense.6 In most of the cases, pain located in the right iliac fossa is usually a sign of acute appendicitis. Th e present case re-port is about a mentally impaired patient admitted and in-advertently operated for acute appendicitis. Subsequently, he was diagnosed and treated for pleural empyema due to a foreign body aspiration.

casE PrEsEntation

A 45-year-old male presented to the emergency depart-ment with severe abdominal pain. Due to his mental im-pairment with a known diagnosis of Fragile X-syndrome, collecting his past medical record was heavily impeded, and nothing else – besides a positive Dieulafoy’s triad – was determined. Th erefore, an acute appendicitis was suspect-ed. An ultrasonography examination was impossible, due to the lack of compliance. Following the informed consent

of his caregiver and a laboratory evaluation which revealed a CRP of 3.41 mg/dL and leucocytes of 15.3 × 10^3/L, a laparoscopic exploration was performed on the same day of admission. Although the appendix presented no major signs of infl ammation or other pathological characteristic upon laparoscopic inspection, it was removed in order to exclude neurogenic appendicopathy. Th e histologic exam-ination showed no signs of malignancy and no signifi cant infl ammatory infi ltrates. Th e initial postoperative course proved to be without any complications and without signs of wound infection. Postoperative oral feeding also took place without complications. Nevertheless, on the fi rst day following surgery, the laboratory revealed raising in-fl ammatory parameters such as CRP of 34.09 mg/dL and leucocytes of 18.2 × 10^3/L, which led to further investi-gation of the patient. Th oracic X-ray (Figure 1) raised the suspicion of a foreign body in the area of the inferior lobe of the right lung and of an incipient pleural empyema.

To complete the records of medical fi ndings, a comput-ed tomography (CT) scan of the thorax was performed, which confi rmed the suspicion (Figure 2).

Th us, bronchoscopy and video-assisted thoracoscopic surgery (VATS) was indicated. Under general anesthesia and intubated with a double-lumen tube, a golden tooth inlay was retrieved from the segmental bronchus of the right inferior lobe with the aid of the bronchoscope. Dur-

FIGURE 1. Thoracic X-ray, coronal view: aspect of encapsulated,

presumably interlobular eff usion, component of the right lung with

basal ventilatory dysfunction. Unidentifi able, radiopaque, foreign

body of approximately 1.3 cm in diameter, in the right cardiophrenic

angle.

FIGURE 2. Thoracic CT, coronal view: expanding serous pleural

eff usion on the right side (no distinct empyema criteria), with

adjacent partial ventilatory dysfunction, particularly in the lower

right lobe. Presumably intrabronchial aspirate lying in a proximal

segmental bronchus.

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35Journal of Interdisciplinary Medicine 2019;4(1):33-36

ing the first access into the thoracic cavity, putrid liquid was emptied. On investigation of the pleural cavity, a mo-bile fibrous block covering the right lung was observed, and consecutively a progressive decortication of the lung took place (Figure 3).

The patient was monitored postoperatively in the inten-sive care unit. The postoperative course henceforward was without any complications, the drainages were removed in time. Under antibiotic therapy with Meropenem, the in-flammatory laboratory parameters regressed, in the end the serum level of CRP was 3.90 mg/L and leucocytes were 10.8 × 10^9/L. Also, the right lung showed no signs of pneumothorax or ventilatory dysfunctions on the con-trol X-ray. The patient was discharged after 12 days of hos-pitalization with good general status, both clinically and biologically. Three months later, he is free of symptoms concerning his pulmonary situation.

discUssion

McBurney’s sign, characterized by a deep tenderness in the right iliac fossa, contributes significantly to the diagnosis of

acute appendicitis.7 The pain felt in the epigastrium upon continuous pressure over McBurney’s point is called Aar-on’s sign.8 In practice, there are a number of clinical signs that indicate acute appendicitis: obturator sign, psoas sign, Rovsing’s sign, Blumberg’s sign, Markle’s sign.9–11 Howev-er, these clinical signs are encountered in a minority of pa-tients. The typical signs of acute appendicitis are: general-ized abdominal pain, more intense in the umbilical region, inappetence, nausea, vomiting, leukocytosis and fever. Afterwards, the pain installs in the lower right quadrant/fossa (same situation in patients with situs inversus with a left lengthy appendix). Georges Paul Dieulafoy described his famous triad in acute appendicitis: hypersensitivity of the skin, tenderness, and muscular contraction at McBur-ney’s point.12 However, there are several atypical signs for acute appendicitis, with only pain as described above and peritonitis, which requires further investigations such as imaging techniques.13 Our patient presented with gener-alized abdominal pain and elevated inflammatory blood tests, but due to his mental impairment, we could neither gather enough details for an appropriate history nor per-form imaging investigations, thus the case was labeled as

FIGURE 3. VATS. A – empyema before decortication; B, C – empyema during decortica-

tion; D – finalized decortication

A

C

B

D

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36 Journal of Interdisciplinary Medicine 2019;4(1):33-36

an atypical acute appendicitis. A C-reactive protein level higher than 1 mg/dL is often encountered in acute appen-dicitis, and if leukocytosis with neutrophilia is present, it could indicate a gangrenous appendicitis at onset. A nega-tive predictive outcome of 97–100% for acute appendicitis is encountered in adult patients with clinical symptoms but with a normal level of C-reactive protein.14,15 CT scan with oral contrast is the most used diagnostic tool in atypical ap-pendicitis. However, another primary tool for diagnosis is ultrasound imaging. The American College of Emergency Physicians recommends the use of ultrasound for the con-firmation of acute appendicitis and CT scan for its exclu-sion.16 The emergency assessment of acute appendicitis is the following: nil per os for patients with acute appendicitis suspicion, intravenous access for fluids and preoperative antibiotic prophylaxis using broad spectrum antibiotics for gram-negative and anaerobic germs, category A or B antibi-otics in pregnant women and carbapenems in patients who are allergic to penicillin. In our case, a single shot of cefu-roxime/metronidazole was administered. Overall, the sur-gical approach is the gold standard method of care in acute appendicitis. A number of clinical conditions can mimic the signs and/or symptoms of acute appendicitis such as: pelvic inflammatory disease (PID) or tubo-ovarian abscess, endometriosis, ovarian cyst or torsion, ureterolithiasis and renal colic, degenerating uterine leiomyoma, diverticulitis, Crohn’s disease, colon carcinoma, rectus sheath hematoma, cholecystitis, bacterial enteritis, mesenteric adenitis and ischemia, omental torsion, biliary colic, renal colic, urinary tract infection (UTI), gastroenteritis and enterocolitis.17 Other clinical conditions that should be taken into account are stump appendicitis after an incomplete appendectomy, typhlitis, epiploic appendagitis, and, last but not least, an extra-abdominopelvic cause in which pain is projected into the abdomen.18,19 Acute appendicitis is often misdiagnosed as gastroenteritis and upper or lower respiratory infection in children; the rate of misdiagnosis decreases with age, ranging from almost 100% in children aged 3 and below to 15% in teenagers.20 Although our case is about an adult patient, it was later on that a respiratory infection was di-agnosed, leading to the correct treatment of his condition.

conclUsion

Acute appendicitis is an emergency condition that requires a thorough assessment and an appropriate therapy consist-ing in a medico-surgical approach, with classic or laparo-scopic surgery being the gold standard method of care. In some cases, certain conditions can mimic the signs and/or symptoms of acute appendicitis, leading to a non-negligi-

ble number of misdiagnoses, which can be life-threaten-ing. In mentally healthy patients, a series of elements are required for a correct diagnosis and treatment: a thorough clinical history, which must include information regarding the onset and the evolution of symptoms until admission to the hospital, as well as information regarding the intake of drugs; physical examination, the most important part being palpation; and last but not least, paraclinical investi-gations such as laboratory tests (complete blood count, C-reactive protein) and imaging investigations (ultrasound and CT scan, especially in cases of atypical acute appen-dicitis). In some cases, several rare conditions should be taken into account for abdominal pain, especially if inflam-mation signs persist postoperatively.

conFlict oF intErEst

Nothing to declare.

rEFErEncEs

1. Collins DC. 71,000 human appendix specimens. A final report summarizing forty years study. Am J Proctol. 1963;14:365-381.

2. Sarkar A. Congenital absence of the vermiform appendix. Singapore Med J. 2012;53:e189-191.

3. Bollinger RR, Barbas A, Bush E, Lin S, Parker W. Biofilms in the large bowel suggests an apparent function of the human vermiform appendix. J Theor Biol. 2007;249:826-831.

4. Sonnenburg JL, Angenent LT, Gordon JI. Getting a grip on things: how do communities of bacterial symbionts become established in our intestine? Nat Immunol. 2004;5:569-573.

5. Dunn R. Your Appendix Could Save Your Life. Sci Am. 2012;306:22-22. 6. Zahid A. The vermiform appendix: not a useless organ. Journal of the

College of Physicians and Surgeons Pakistan. 2004;14:256-258.7. Bevan P. Diagnosis Of Acute Appendicitis: Three Physical Signs. The

Lancet. 1961;277:404.8. Wyer P. Review: symptoms, signs, and lab tests have moderate accuracy

for detecting appendicitis in children. Evid Based Med. 2008;13:23-23.9. Dave WW. Rovsing's sign. Br Med J. 1956;2:28-30.10. Alvarado A. How to improve the clinical diagnosis of acute appendicitis in

resource limited settings. World J Emerg Surg. 2016;11:16. 11. Markle GB. Heel-drop jarring test for appendicitis. Arch Surg. 1985;120:243. 12. Karamanou M, Fiska A, Demetriou T, Androutsos G. Georges-Paul

Dieulafoy (1839-1911) and the first description of “exulceratio simplex”. Ann Gastroenterol. 2011;24:188-191.

13. Debnath J, George RA, Ravikumar R. Imaging in acute appendicitis: What, when, and why?. Med J Armed Forces India. 2016;73:74-79.

14. de Carvalho BR, Diogo-Filho A, Fernandes C, Barra CB. Leukocyte count, C reactive protein, alpha-1 acid glycoprotein and erythrocyte sedimentation rate in acute appendicitis. Arq Gastroenterol. 2003;40:25-30.

15. Albu E, Miller BM, Choi Y, et al. Diagnostic value of C-reactive protein in acute appendicitis. Dis Colon Rectum. 1994;37:49-51.

16. Howell JM, Eddy OL, Lukens TW, Thiessen ME, Weingart SD, Decker WW. Clinical policy: Critical issues in the evaluation and management of emergency department patients with suspected appendicitis. Ann Emerg Med. 2010;55:71-116.

17. Karamanakos SN, Sdralis E, Panagiotopoulos S, Kehagias I. Laparoscopy in the emergency setting: a retrospective review of 540 patients with acute abdominal pain. Surg Laparosc Endosc Percutan Tech. 2010;20:119-124.

18. Roberts KE, Starker LF, Duffy AJ, Bell RL, Bokhari J. Stump Appendicitis: A Surgeon’s Dilemma. JSLS. 2011;15:373-378.

19. Singh AK, Gervais DA, Hahn PF, Sagar P, Mueller PR, Novelline RA. Acute Epiploic Appendagitis and Its Mimics. RadioGraphics. 2005;25:1521-1534.

20. Almaramhy HH. Acute appendicitis in young children less than 5 years: review article. Ital J Pediatr. 2017;43:15.

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Journal of Interdisciplinary Medicine 2019;4(1):37-40

CORRESPONDENCE

Cristian PodoleanuStr. Gheorghe Marinescu nr. 38540139 Tîrgu Mureș, RomaniaTel: +40 265 215 551E-mail: [email protected]

ARTICLE HISTORY

Received: September 1, 2018 Accepted: December 12, 2018

Skin Lesions in a Daclizumab-treated Patient with Multiple SclerosisAnca Chiriac1,2,3, Adrian Năznean4, Cristian Podoleanu5, Claudiu Molnar6, Simona Stolnicu7,8

1 Department of Dermatology, Nicolina Medical Center, Iași, Romania2 Apollonia University, Iași, Romania3 “P. Poni” Research Institute, Romanian Academy, Iași, Romania4 Department of Foreign Languages, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania5 Department of Internal Medicine, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania6 Department of Gynecology, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania7 Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania8 Histopat Invest Laboratory, Tîrgu Mureș, Romania

casE rEPort DERMATOLOGY // INTERNAL MEDICINE

DOI: 10.2478/jim-2018-0038

ABSTRACT

Background: Daclizumab is a humanized monoclonal antibody against the α-subunit (CD25)

of the high-affinity interleukin (IL)–2 receptor, used for the treatment of relapsing-remitting

multiple sclerosis with a large spectrum of cutaneous adverse reactions. Case presentation:

We present the case of a middle-aged man treated with daclizumab for multiple sclerosis,

who developed skin reactions difficult to evaluate. A 4 mm punch-biopsy was taken from the

plantar area. Histological examination of the biopsy revealed hyperkeratosis and acanthosis

but no parakeratosis, while a discrete inflammatory infiltrate was noticed around vessels in

the dermis. Treatment with fluconazole 50 mg/day for 10 days, moisturizers, and grade I topi-

cal steroids was followed by slight improvement of the clinical picture. Treatment with dacli-

zumab was not discontinued. Conclusion: The clinical efficacy and side effects of daclizumab

have to be reported and confirmed in clinical practice in the following years. Any clinical

report can contribute to validate the efficacy and risk of the drug’s administration. Any type of

adverse skin reaction must be reported for clarifying the diagnosis.

Keywords: daclizumab, skin lesions, multiple sclerosis

Anca Chiriac • Str. Hatman Șendrea nr. 2, 700613 Iași, Romania. Tel: +40 332 808 703

Adrian Năznean • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureș, Romania. Tel: +40 0265 215 551

Claudiu Molnar • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureș, Romania. Tel: +40 0265 215 551

Simona Stolnicu • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureș, Romania. Tel: +40 0265 215 551

backgroUnd

Daclizumab is a humanized monoclonal antibody against the α-subunit (CD25) of the high-affinity interleukin (IL)–2 receptor, used for the treatment of relaps-ing-remitting multiple sclerosis, with a large spectrum of cutaneous adverse re-actions.1,2 Physicians should be aware of potential side effects induced by dacli-zumab in the treatment of patients with relapsing multiple sclerosis. We present the case of a middle-aged man treated with daclizumab for multiple sclerosis, who developed skin reactions difficult to evaluate.

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38 Journal of Interdisciplinary Medicine 2019;4(1):37-40

casE PrEsEntation

A 56-year-old man, treated with daclizumab for multiple sclerosis, was referred to Dermatology. The dermatologi-cal examination revealed an intensely pruritic desqua-mating rash localized on the central facial area (mostly on the chin and nasal wings) associated with inferior blepha-ritis (Figure 1); androgenic alopecia and discrete silver scales over the parieto-temporal area (Figure 2); nail pit-ting, discrete distal onycholysis and chronic perionixis on all digits (Figure 3); bilateral plantar hyperkeratosis (Fig-ure 4); no other skin lesions were observed or described by the patient. He admitted having the alopecia from the second decade of life, as well as a long history of cutane-

ous problems, and a recent facial rash forced him to seek treatment.

Before referral to the hospital, emollients were used regularly as self-medication for the last 2 months, with no improvement. No personal or familial medical history of psoriasis was declared or recorded in medical files.

A clinical suspicion of seborrheic dermatitis or psoria-sis motivated a skin biopsy. A 4 mm punch-biopsy was taken from the plantar area. Histological examination of the biopsy revealed hyperkeratosis and acanthosis but no parakeratosis, while a discrete inflammatory infiltrate was noticed around vessels in the dermis. Treatment with flu-conazole 50 mg/day for 10 days, moisturizers, and grade I topical steroids was followed by slight improvement of the clinical manifestations. Treatment with daclizumab was not discontinued.

A month later, the patient was seen again; typical small patches of seborrheic-like dermatitis were observed on the sternal area (Figure 5) and on the scapular area (Fig-ure 6), while the old cutaneous lesions were still pres-

FIGURE 1. Large erythematous plaques covered by scales over

the chin and on the middle area of the face; inferior blepharitis

FIGURE 3. Nail pitting, discrete distal onycholysis and chronic

perionixis on all digits

FIGURE 2. Androgenic alopecia and discrete silver scales over

the parieto-temporal area

FIGURE 4. Hyperkeratosis covering the entire plantar surface

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39Journal of Interdisciplinary Medicine 2019;4(1):37-40

ent. Potent topical steroids were recommended for two weeks for the scalp and trunk lesions, associated with 10% urea cream for the plantar area, ketoconazole gel as cleaning agent for the face, followed by emollients. No restriction for daclizumab treatment was recommended from a dermatological point of view, taking into consid-eration the lack of severity of skin lesions and the ben-eficial effect of daclizumab on his neurological disease. The patient will be closely followed-up with an interdis-ciplinary approach.

discUssions

Daclizumab is a humanized monoclonal antibody against the α-subunit (CD25) of the high-affinity interleukin (IL)–2 receptor used for the treatment of relapsing-remitting multiple sclerosis.1 Recently, several reports have commu-nicated a large spectrum of cutaneous adverse reactions observed in patients treated with daclizumab for multiple sclerosis.2

Cutaneous adverse reactions induced by daclizumab high-yield process (DAC-HYP), recommended for mul-tiple sclerosis, have been previously reported in 37% of pa-tients, mainly represented by “rash and eczema”.2 Another open-label phase I study of DAC-HYP reported that 77% of the enrolled patients presented skin adverse reactions, described clinically as “severe rash of psoriasiform pheno-type” but with no characteristic histological features.3 The severity of skin reactions was mild to moderate, with good response to topical steroids, and rare cases of severe reac-tions, such as angioedema or Stevens-Johnson syndrome, were reported.4,5 In a recent study performed on 2,236 pa-tients with 5,214 patient-years of exposure to daclizumab

for relapsing-remitting multiple sclerosis, the cumulative incidence of skin adverse reactions was found in 33% of patients, represented by rash, eczema, and allergic der-matitis, with rare (only 2%) cases of severe adverse events (toxic skin eruption treated with systemic steroids and plasma exchange).5

Daclizumab treatment in multiple sclerosis expands CD56bright NK cells; this same lymphocyte subset is in-volved in the pathogenesis of psoriasis and may lead to psoriasis in genetically predisposed patients.6,7

Our patient had developed inflammatory skin lesions during treatment with daclizumab, but the exact diagno-sis was not ascertained. Although clinical features argued in favor of psoriasis, histology did not certify the diagno-sis. Moreover, in some cases, a clear distinction between psoriasis and seborrheic dermatitis cannot be made, or both diseases can coexist in the same patient. Daclizumab was approved for use outside of clinical studies in May 2016; its clinical efficacy and side effects have to be re-ported and confirmed in clinical practice in the following years.7

conclUsions

Psoriasis-like skin lesions may present as adverse effects of treatment with Daclizumab in patients with relapsing-remitting multiple sclerosis. Any clinical report can con-tribute to validate the efficacy and risk of the drug’s ad-ministration. Any type of adverse skin reaction must be reported for clarifying the diagnosis.

FIGURE 5. Seborrheic-like lesions on the sternal area

FIGURE 6. Seborrheic-like lesions on the scapular area

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40 Journal of Interdisciplinary Medicine 2019;4(1):37-40

consEnt to ParticiPatE

Informed consent to publish the case was obtained from the patient.

conFlict oF intErEst

None for all authors.

rEFErEncEs

1. Bielekova B. Daclizumab therapy for multiple sclerosis. Neurotherapeutics. 2013;10:55-67.

2. Krueger JG, Kircik L, Hougeir F, et al. Cutaneous Adverse Events in the Randomized, Double-Blind, Active-Comparator DECIDE Study of Daclizumab High-Yield Process Versus Intramuscular Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis. Adv Ther. 2016;33:1231-1245.

3. Cortese I, Ohayon J, Fenton K, et al. Cutaneous adverse events in multiple sclerosis patients treated with daclizumab. Neurology. 2016;86:847-855.

4. Kircik L, Krueger J, Lebwohl M, et al. Incidence, severity, duration, and treatment of cutaneous adverse events in the DECIDE study of daclizumab HYP versus intramuscular interferon beta-1a in patients with relapsing-remitting multiple sclerosis. Mult Scler. 2015;21:251-252.

5. Gold R, Giovannoni G, Selmaj K, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet. 2013;381:2167-2175.

6. Diao L, Hang Y, Othman AA, et al. Population PK-PD analyses of CD25 occupancy, CD56bright NK cell expansion, and regulatory T cell reduction by daclizumab HYP in subjects with multiple sclerosis. Br J Clin Pharmacol. 2016;82:1333-1342.

7. Michel T, Poli A, Cuapio A et al. Human CD56bright NK Cells: An Update. J Immunol. 2016; 196:2923-2931.

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Journal of Interdisciplinary Medicine 2019;4(1):41-43

CORRESPONDENCE

Cristian PodoleanuStr. Gheorghe Marinescu nr. 38540139 Tîrgu Mureș, RomaniaTel: +40 265 215 551E-mail: [email protected]

ARTICLE HISTORY

Received: September 2, 2018 Accepted: December 11, 2018

Congenital Malalignment of the NailsAnca Chiriac1,2,3, Adrian Năznean4, Cristian Podoleanu5, Claudiu Molnar6, Simona Stolnicu7,8

1 Department of Dermatology, Nicolina Medical Center, Iași, Romania2 Apollonia University, Iași, Romania3 “P. Poni” Research Institute, Romanian Academy, Iași, Romania4 Department of Foreign Languages, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania5 Department of Internal Medicine, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania6 Department of Gynecology, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania7 Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania8 Histopat Invest Laboratory, Tîrgu Mureș, Romania

iMagE FocUs DERMATOLOGY // PEDIATRICS

DOI: 10.2478/jim-2018-0037

ABSTRACT

Congenital malalignment of the toenail is characterized by the lateral (rarely medial) devia-

tion of nail plates that affects mostly the great toes from one foot or both, but has also been

described on other toes, even on the hands. This nail disease is still considered a rare en-

tity, although it is not a rare clinical observation in daily practice. We present a few cases in

children and adults, highlighting the diagnosis made by clinical observation, regardless of

the different grades of severity of the nail disease. Conclusion: It is of great importance to

clinically recognize this entity in young children and to make the correct recommendations.

Keywords: nail, disorders, development, defects

Anca Chiriac • Str. Hatman Șendrea nr. 2, 700613 Iași, Romania. Tel: +40 332 808 703

Adrian Năznean • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureș, Romania. Tel: +40 0265 215 551

Claudiu Molnar • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureș, Romania. Tel: +40 0265 215 551

Simona Stolnicu • Str. Gheorghe Marinescu nr. 38, 540139 Tîrgu Mureș, Romania. Tel: +40 0265 215 551

introdUction

The first description of the nail disorder was done in 1978 by Samman, who named it ”great toenail dystrophy”.1 In 1979, Baran gave the disorder its actual name: ”congenital malalignment of the big toenail”.2

Although initially considered a rare congenital disease, affecting only the great toenails of both genders, during the last decades, more and more reports have been published, describing cases affecting other nails of the feet or hands, and not only congenital but also acquired forms.3

Diagnosis is made by clinical observation, regardless of the different grades of severity of the nail disease. The mild form cannot be observed until puberty or adulthood, although the nail changes are present at birth. This form is char-acterized by minor displacement of the nail, without characteristic changes in the nail plate, and remains undiagnosed during childhood; it is more common in both great toenails as external deviation of the nail plate with hyperkeratosis and shorter aspect; medial deviation is extremely rare. Unilateral cases can oc-cur, more often affecting the right great toenail (Figure 1A, 1B, 1C).4,5 Esthetic

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42 Journal of Interdisciplinary Medicine 2019;4(1):41-43

concerns and/or previous extended antifungal treatments with no efficacy represent the main causes of seeking med-ical advice.

The classic form of malalignment of the great toenail is diagnosed based on the following criteria:2–5

• it is noticed at birth or in early infancy (Figure 1D);• it is bilateral in the majority of cases (Figure 1E);• the nail plate has a triangular or trapezoid shape and

is shorter than normal or than the other nails (Figure 1F);

•nail plate hyperkeratosis aggravates with age and chronic trauma, and it can have an “oyster shell-like appearance” (Figure 1G); onychogryphosis can be a severe complication;

•onycholysis and onychomadesis can be associated in complicated cases (Figure 1H);

•nail discoloration is a distinctive feature, varying from brown, gray, green due to thickened nail plate, and fungal or Pseudomonas infection;

• transversal grooves or ridges can cross the nail plate (Figure 1I).

Apart from the congenital malalignment of the great toenail, the condition can be extremely rarely diagnosed on other toenails, uni- or bilateral (Figure 1J, 1K).

The etiology and pathogenesis of the disorder are still unknown; clinical appearance is explained by deviation of the growth axis of the nail plate related to the longitudinal axis of the distal phalanx.3

An autosomal dominant inheritance with variable pen-etrance has been postulated in some cases,6 and further ge-netic clinical examination is recommended.

Therapeutic approach, especially in small children, should be done carefully in order to avoid unnecessary diagnostic tests (mycological examination, nail biopsy) and aggressive curative methods. In cases with minimal deviation, in the absence of any sign of complication and bearing in mind that spontaneous improvement is reported in many cases before puberty, surveillance is recommended.7 Surgical correction is the mainstay of therapy in severe cases, preventing com-plications such as acute paronychia (Figure 1L).

conclUsion

It is of great importance to clinically recognize this entity in young children and to make the correct recommendations.

consEnt to ParticiPatE

Informed consent to publish the case was obtained from the parents.

FIGURE 1. Congenital malalignment of the great toenail at puberty. A – Bilateral congenital malalignment of the great toenail with

hyperkeratosis and nail discoloration; B – Unilateral congenital malalignment of the great toenail; C – Short and hyperkeratotic deviated

nail; D – Malalignment of the great toenail in early infancy; E – Bilateral congenital malalignment of the great toenail in a 2-year-old boy;

F – Triangular or trapezoid shape of the nail plate and deviated nail plate in a child; G – “Oyster shell-like appearance” in a child; H – On-

ychomadesis associated with congenital malalignment of the great toenail in a child; I – Transversal grooves or ridges on the nail plate in

a child; J – Congenital malalignment of the second toenail in a child; K – Congenital malalignment of the fifth toenail in a child; L – Acute

bilateral paronychia in a teenager (17-year-old male) diagnosed since birth with congenital malalignment of the great toenail

A

G

B

H

C

I

D

J

E

K

F

L

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43Journal of Interdisciplinary Medicine 2019;4(1):41-43

conFlict oF intErEst

None for all authors.

rEFErEncEs1. Samman PD. Great toe nail dystrophy. Clinical and Experimental

Dermatology. 1978;3:81-82.2. Baran R, Bureau H, Sayag J. Congenital malalignment of the big toe nail.

Clinical and Experimental Dermatology. 1979;4:359-360.3. Chieco P. Congenital malalignment of the great toenail. Eur J Pediat

Dermatol. 2013;23:5-8.4. Wagner G, Sachse MM. Congenital malalignment of the big toe nail. J

Dtsch Dermatol Ges. 2012;10:326-30.5. Batalla A, Curto JR. Congenital malalignment of the great toenail. Report

of two cases. Dermatol Online J. 2014;20:21251.6. Kus S, Tahmaz E, Gurunluoglu R, Candan İ, Uygur T. Congenital

Malalignment of the Great Toenails in Dizygotic Twins. Pediatric Dermatology. 2005;22:434-435.

7. Senayli A, Sezer E, Sezer T, Senayli Y, Yuksek J. Coexistence of congenital malalignment of the great toenails with ocular melanocytosis. Eur J Dermatol. 2008;18:208-209.

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About JIM

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All manuscripts submitted to the Journal of Interdisciplin-ary Medicine ( JIM) will be first subject to a technical re-view, including quality check of all the files submitted, in-cluding tables, figures and references. Plagiarism check will be performed prior to referring the manuscript for review, in order to identify any possible fraud or scientific misconduct.

After technical review and anti-plagiarism assessment, the articles will be referred for review following a double-blinded review procedure. Reviewers can be suggested by the authors, however selection of the reviewers will be made by the editors, according to their expertise in the field of the article. The identity of the reviewers will not be disclosed to the authors, as well as the identity of the authors will not be disclosed to the reviewers.

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The editorial decision will be communicated to the au-thors as soon as the review process has been finalized. In case of revisions, the revised article will be sent to the reviewers, who will decide on a new recommendation for revision, ac-ceptance or rejection. The estimated time from the submis-sion to first decision is approximately 4 weeks, and from the final revision to acceptance approximately 2 weeks.

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In cases where the Managing Editor has any conflict of interest in connection with a manuscript, the entire work related to the review process of that manuscript will be undertaken by the Editor-in-Chief. In cases where the

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Editor-in-Chief has any conflict of interest in relation to a manuscript, the entire work related to the review process of that manuscript will be undertaken by the Managing Editor. In cases where both the Managing Editor and the Editor-in-Chief have any conflict of interest in relation to a manuscript, the entire work related to the review process of that manuscript will be undertaken by another member of the editorial board.

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The authors should make sure that all the experiments on humans or animals are in accordance with the guiding principles described in the Declaration of Helsinki. Ani-mal experiments should comply with the institutional and national guidelines or regulations for laboratory animals. Informed consent should be obtained from all the subjects participating in any experiment or clinical study and all the clinical studies should obtain the approval from the eth-ics committee of the institutions where the study is carried out, prior to initiation of experiments or studies.

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Clinical trials

Authors of manuscripts related to clinical trials should reg-ister the clinical trial in the official clinical trial related pub-lic registries prior to submission to JIM, following the rules stated by the International Committee of Medical Journal

Editors. Information related to registration of clinical trials can be found at ClinicalTrials.gov. In case of clinical trials, the trial registration number should be mentioned at the end of the abstract. Whenever a trial registration number is available, the authors should list this number the first time they use the trial acronym.

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ManUscriPt sUbMission

All manuscripts should be submitted via email to [email protected].

The journal does not have article processing charges nor article submission charges.

The submission should include the following attachments:1. Cover letter: all manuscripts submitted to JIM should be accompanied by a cover letter, signed by the corre-sponding author on behalf of all co-authors, stating that the reported study and manuscript are original and have not been published elsewhere, and the manuscript has not been submitted “in extenso” to any other journal. All disclosures relating to the preparation of the manuscript should be mentioned in the cover letter. The correspond-ing author should state clearly whether or not there are any conflicts of interest.2. License to publish: The Journal of Interdisciplin-ary Medicine requires authors of original papers to as-sign copyright of their published contributions to the journal. A model of the License to Publish is available at www.interdisciplinary.ro.

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as authors should meet all four criteria for authorship, and all who meet the four criteria should be identified as authors. Those who do not meet all four criteria should be acknowledged.

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ManUscriPt tyPEs

The Journal of Interdisciplinary Medicine accepts the fol-lowing categories of articles:

Original research

Manuscripts should be word processed. The manuscript must contain the title of the article, the authors' names, qualifications and address/es.

Peer Review: all articles undergo initial screening for suitability for the Journal of Interdisciplinary Medicine.

The length of contributions: ideally contributions should be no more than 4,000 words, including tables and figures. Suitable papers are then peer reviewed by two or more referees. Additional specialist advice may be sought if necessary, for example, from a statistician, before a final decision is made by the Editor-in-Chief.

Instructions for authors

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An original research article should include a short Abstract of no more than 300 words, using the follow-ing headings: Background, Aim of the study, Material and Methods, Results and Conclusions.

The manuscript should be structured as follows:1. Introduction/Background: This introduces the aim

of the study and the corresponding research hypothesis/es.2. Material and methods: This section should describe

all experimental details, research methodology, and study groups. The methodology should be detailed enough to al-low reproducibility of the experiments. Give full descrip-tions of all equipment used (type, manufacturer, town, country). Details of statistical analysis should be reported here together with a level of significance [α value]. Authors should provide details of the statistical software package used (name, version, producer, town, country). Abbrevia-tions of standard SI units of measurement should be em-ployed. Declaration of Helsinki: The authors should state that their study complied with the Declaration of Helsinki, that the locally appointed ethics committee approved the research protocol and that written informed consent was obtained from the subjects (or their guardians) before the commencement of the study. Where animals are involved, the authors should state that their study complies with their institutional guidelines for the care and use of labora-tory animals.

3. Results: This section should present the data arising from the experiments and their statistical significance. Do not discuss these findings in the Result Section.

4. Discussions: This section should contain a detailed analysis and interpretation of the results. Results should not be repeated in the Discussion section.

5. Conclusions: This presents the conclusions deriving from the outcome of the study and their clinical signifi-cance if appropriate.

Case reports

Case reports are intended for the presentation of interesting cases of interdisciplinary medicine encountered in clinical practice and should refer to actual and uncommon cases.

The report should have an abstract limited to 200 words, structured in the following manner: Introduction, Case presentation, and Conclusions.

The manuscript should be no more than a maximum of 2000 words, excluding references, figures, and figure leg-ends. It should be structured as Introduction, Case presen-tation, Discussions, and Conclusions.

A case presentation should have a maximum of four au-thors, twenty references, and five figures.

Case series

Case series should include an abstract limited to 200 words, structured into Introduction, Case series presentation, and Conclusions.

The manuscript should be no more than 2000 words ex-cluding references, tables, figures and figure legends. Case series should have a maximum of four authors, twenty ref-erences, and five figures.

Case report / Image focus

This category is intended to facilitate the publishing of representative images related to any clinical pathology. Ac-cepted images may be published on the cover of the Jour-nal. Images should be submitted as a figure accompanied by a clinical message that contains a description of the case and a detailed explanation of the figure, using a maximum of 300 words. For Case report / Image focus, the number of authors should be limited to four and the number of refer-ences to 10.

Reviews

The Journal of Interdisciplinary Medicine publishes review papers in any medical field of interest at an international level. Review articles should include a non-structured ab-stract of no more than 200 words with a maximum of 6000 words excluding references, tables, and figures.

Clinical update

The Journal of Interdisciplinary Medicine publishes up-date articles that describe current advances in any clinical field related to interdisciplinary medicine. Articles should include a non-structured abstract of no more than 200 words with a maximum of 4500 words excluding referenc-es, tables, and figures.

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Letters to the editor should address either a recently published article in the Journal of Interdisciplinary Med-icine, or a new topic in the field of cardiovascular emer-gencies.

Concerning a letter, discussing a recently published article, the comments contained in the letter will be for-warded to the authors of the original paper who will be invited to respond. Any response will be published in the same journal issue as the letter to the editor. A letter to the

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editor should be no longer than 500 words, 5 references, and three authors. No abstract is required.

Editorial

Editorials should address either a particular topic that is currently of interest in the field of interdisciplinary medi-cine or to an article which is published in the same issue of the journal. The number of references should not exceed twenty-five in total.

ManUscriPt contEnt

Style and spelling: Authors, whose first language is not English, are requested to have their manuscripts checked carefully, preferably by an English native-speaker, before submission, to expedite the review process.

Manuscript format: The manuscript must be submitted as a Word document and should be presented in the follow-ing order:

•Title page.•Abstract, or a summary of case reports (references

should not be included in abstracts or summaries).•Main text separated under appropriate headings and

subheadings using the following hierarchy: BOLD CAPS, bold lower case, Plain text, italics.

•Tables should be in Word format and placed in the main text where the table is first cited. Tables must be cited in the main text in numerical order.

•Acknowledgements, Competing Interests, Funding, and all other required statements.

•Reference list. • Images must be uploaded as separate files (view

further details under the Figures/illustrations sec-tion). All images must be cited within the main text in numerical order, and legends should be provided at the end of the manuscript. Appendices should be uploaded using the File Designation “Supplementary File” and cited in the main text.

The contents of your manuscript should be arranged in the following order:

1. Title page – should include: (1) the title of the arti-cle; (2) the name(s) of authors; (3) the institutional affiliations of the authors; (4) the position, institu-tion, and location of all authors; (5) the telephone number, fax number and e-mail address of the cor-responding author; (6) disclosure of grants, contracts

and any other form of financial support received for the study.

2. Abstract – an abstract prepared in accordance to the type of the manuscript.

3. Keywords – between 3 and 6 keywords.4. Full text – All manuscripts should be typed double-

spaced, in Times New Roman 12 fonts, using Word format. References, tables and figures should be ci-ted in numerical order, as they appear in the text. The abbreviations should be explained the first time they appear in the text, followed by the abbreviation in brackets.

5. Acknowledgements – should indicate clearly any source of funding received for the study, including grants, research contracts or any form of financial support.

6. References. References should be cited in numerical order, as they appear in the text, and should be indi-cated in superscript following the end of the sentence or the end of the part of the phrase they refer to.

7. Tables should be typed on separate pages at the end of the manuscript and should be numbered in Ara-bic numerals in the order of mention in the text. The abbreviations used in the table should be explained in a footnote below the table. Tables should not repeat the text and should be clear enough to be self-expla-natory.

8. Figures should be prepared in TIF or JPG format, at a resolution of minimum 300 dpi. For figures repro-duced or adapted from another source, this should be labeled as "Reproduced with permission from…" or "Adapted with permission from…" and should be accompanied by written permission from both the author and publisher of the original material. Figures should be combined with a legend which clearly de-scribes the illustration.

rEFErEncE stylE

The journal will publish the reference list according to the style of Index Medicus (or spelled out if not listed in Index Medicus). List all the authors in each reference following the format and punctuation indicated below as examples:

Reference to an article 1. Benedek I, Gyongyosi M, Benedek T. A prospective regional registry of ST-elevation myocardial infarction in Central Romania: impact of the Stent for Life Initia-tive recommendations on patient outcomes. Am Heart J. 2013;166:457-465.

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Reference to a book2. Nichols WW, Rourke MF. Aging, High Blood Pressure and Disease in Human. 3rd ed. London/Melbourne: Lea and Febiger; 1990.

Reference to a chapter in a book3. Nichols WW, O'Rourke MF. Aging, high blood pres-sure and disease in humans. In: Arnold E, ed. McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. 3rd ed. London/Melbourne/Auck-land: Lea and Febiger, 1990; p. 398-420.

Reference to a webpage 4. Panteghini M. Recommendations on use of bio-chemical markers in acute coronary syndrome: IFCC proposals. eJIFCC 14. http://www.ifcc.org/ejifcc/vol14no2/1402062003014n.htm (28 May 2004)

coMPlaints

In cases where the authors wish to file a complaint, please contact the editorial office:

Journal of Interdisciplinary MedicineStr. 22 Decembrie 1989 nr. 76–78, Tîrgu Mureș, Romania E-mail: [email protected]

Please describe the reason for complaining and specify the address for correspondence. Where the complaint is related to the editorial process, related to a manuscript, please include the name of the manuscript and the date the manuscript was submitted. The Editor-in-Chief, together with the editorial office will analyze the complaint and will answer in maximum three working days.


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