ARCHIVES OF THE BALKAN MEDICAL UNION

3

Authors: Camelia C. DIACONU

Atrial fibrillation is one of the most common arrhythmias encountered in clinical practice, associated with a higher risk of cardioembolic stroke and systemic embolism. Oral anticoagulant therapy is needed to prevent stroke, based on a structured risk assessment of each patient, to decide whether this therapy should be prescribed. The selection of the optimal therapy for patients with atrial fibrillation is sometimes difficult, because of the lack of a proper prediction of benefits and risks. To facilitate this decision, the 2020 European Society of Cardiology Guidelines for the diagnosis and management of atrial fibrillation recommend the use of CHA2DS2-VASc (Congestive heart failure, Hypertension, Age  75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65-74 years, Sex category – female) and HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly > 65 years, Drugs/Alcohol concomitantly) scores1. These scores take into consideration only clinical variables, that can limit their power of prediction and calibration. Due to the heterogeneity of the population of patients with atrial fibrillation, recent research has focused on identifying new biomarkers for a better prediction of an individualized risk of stroke.

3

Authors: Adrian COTIRLET, Laura GAVRIL, Eduard POPA, Marius NEDELCU

L’Académie Nationale de Chirurgie de France est la plus ancienne institution chirurgicale française. Elle développe des relations avec un grand nombre de sociétés spécialisées et a pour ancêtre l’Académie Royale de Chirurgie créée en 1731 par Georges Mareschal, premier chirurgien de Louis XV et par François La Peyronie, successeur de Mareschal. Le rôle de l’Académie Nationale de Chirurgie est représenté par la grande responsabilité morale en tout ce qui concerne la chirurgie, étant un gardien de son histoire, le témoin de son évolution et le garant de son éthique. L’évaluation prudente et rigoureuse du développement des aspects techniques de l’art chirurgical et de leurs changements, la définition des bonnes pratiques chirurgicales : références, recommandations, stratégies, le contrôle des conditions de l’exercice spécifique de la chirurgie et l’appréciation de la formation et du recrutement des

5

Authors: Cuong TRAN CHI, Phung NGUYEN KIM, Tuan NGO MINH, Duy Toan PHAM

Introduction. Pseudoaneurysms of superior mesenteric artery and its branches are extremely rare but life threatening when complications occur. However, the diagnosis is often missed or delayed because of its non-specific signs and symptoms. Treatments depend on patient’s characteristics. In contrast to conventional open surgery, endovascular therapy has been reported as an effective option with minimally invasion, low complication, short recovery time and good outcome, especially in high-risk patients. Case presentation. We describe a case of ruptured pseudoaneurysm of ileal artery, a branch of superior mesenteric artery, presenting with gastrointestinal bleeding signs while on anticoagulant therapy. Both upper and lower gastrointestinal endoscopy were inconclusive. The diagnosis was confirmed by angiography and the patient was successfully treated by coil embolization. Conclusions. Ruptured pseudoaneurysm of superior mesenteric artery and its branches should be suspected in patients with unexplained gastrointestinal hemorrhage. Endovascular intervention is a feasible approach, especially in patients with multiple comorbidities and high bleeding risk.

6

Authors: Vasile MUSTEATA

Introduction. A growing number of studies indicates the increased susceptibility of patients with hematologic malignancies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as compared to the apparently healthy population. The objective of our study was to identify and evaluate the contemporary epidemiological and diagnosis patterns of chronic myeloid leukemia (CML) in the context of coronavirus disease 2019 (COVID-19) pandemic, to optimize the management of this hematologic malignancy. Material and methods. This analytical, descriptive and prospective study included 15 patients with CML and COVID-19, who were treated and followed up in the Institute of Oncology Chisinau, Republic of Moldova, between 2005–2021. SARS-CoV-2 infection was diagnosed in these patients between April 2020– September 2021. Results. These 15 cases represented 10.6% out of 142 patients diagnosed with CML and followed up under the treatment with tyrosine kinase inhibitors. There were 9 (60.0%) males and 6 (40.0%) females, with the male/female ratio 1.5/1. The patients’ age at diagnosis of COVID-19 ranged between 38-74 years (average age 54.2 years). According to the World Health Organization classification of COVID-19 severity, mild forms were registered in 4 (26.7%) cases, moderate in 6 (40.0%) and severe in 5 (33.3%) cases. Eight (53.3%) patients were hospitalized for treatment of COVID-19: 5 patients with severe forms and 3 patients with moderate forms. Viral pneumonia was diagnosed in 6 patients: 5 with severe and one with moderate form of COVID-19. Non-infectious comorbidities were registered in 4 of 5 patients with severe COVID-19 forms. Conclusions. COVID-19 commonly affects CML patients of male gender and older than the average age of patients with CML. Patients without hematologic response presented an unfavorable evolution of both diseases, CML and COVID-19.

6

Authors: Ilir GJERMENI, Ergita NELAJ, Irida KECAJ, Eliona GJERMENI, Mihal TASE

Introduction. Acetaminophen (paracetamol) is a widely used drug and known as a safe analgesic and antipyretic. Hepatotoxicity is usually the first complication of acetaminophen overdose. Nephrotoxicity usually appears after liver toxicity. Most studies on this topic focused on cases of acute over dosage of acetaminophen, with fewer studies on the effects of chronic overdose. Case presentation. We present the case of 74-year-old woman with acute kidney failure because of chronic overdose of acetaminophen and a minireview of the literature. The patient presented to the emergency unit for confusion, with altered vital parameters. She had regularly used 5-6 g/ day of paracetamol over the previous 4 weeks because of articular pain. Acute kidney and hepatic failure were diagnosed. After specific treatment, the patient was discharged in a good condition. Conclusions. An appropriate history of administered drugs (including those without prescription by the physician) allows the accurate diagnosis and enables a faster therapeutic management. In the case presented, hyperkalemia accompanied by syncope from bradycardia raised the suspicion of the diagnosis of acute kidney injury.

7

Authors: Victor TIMERCAN, Tatiana TIMERCAN

Introduction. Metabolism is the key factor underlying the cardiomyocyte function. The inadequate coronary perfusion results in tissue acidosis due to elevated lactate production, which is considered a sensitive marker of myocardial ischemia. Isoproterenol is a synthetic catecholamine that produces diffuse myocardial necrosis at high doses. The aim of the study was to assess the changes of serum and tissue lactate content in isoproterenol-induced acute myocardial infarction to evaluate the lactate potential as an early diagnosis marker of cardiac ischemia. Materials and methods. Forty adult male rats were divided into 5 groups: sham (L1=11), control 0.9% NaCl (L2=11), and with experimental myocardial infarction (L3=6, L4=6; L5=6), induced by the subcutaneous injection of Isoproterenol Hydrochloride solution 100 mg/kg, and sacrificed over 6 hours, 24 hours and 7 days post infarction. The results were presented by median and interquartile range. The groups were compared using Kruskal-Wallis and Mann-Whitney nonparametric tests, and the Spearman correlation coefficient was calculated (SPSS 23.0). A p≤0.05 was considered statistically significant.Results. Both glucose and lactate serum levels presented a slight decrease in L3, followed by a significant increase in L4, with a repeated fall in L5 group. In homogenate glucose content initially expressed an elevation in L3, with relevant decrease in L4, and inconsistent increase in L5, while lactate values significantly decreased in L3, returned to baseline levels in L4 and slightly declined in L5 compared to sham and control groups. Conclusion. The collected data suggest the utility of lactate assessment in early diagnosis and risk stratification in acute myocardial infarction.

8

Authors: Veska T. GERGOVA, Asena H. SERBEZOVA, Dobriana A. SIDJIMOVA

Introduction. Sponsors of clinical trials propose variations of home visits and virtual contact points with the patients instead of visits at the clinical sites, as well as other digital and remote solutions. The objective of the study was to search and analyse the experience and practice of European countries on applying decentralized elements and a hybrid approach of conducting clinical trials’ activities and procedures, as well as to establish the applicable rules and regulation. Material and methods. A questionnaire survey was conducted among European countries in the period December 2020 – February 2021, by email communication. Results. In most of the countries, it was not forbidden, and respondents indicated the opportunity of medical specialists to help patients at their home. 37.50% of the countries indicated that the applicable legislation cannot be related to the medical or clinical trials legislation or national commercial law but “Other”. Based on the practice, all or some of the activities can be done as a home care. 68.75% responded negatively to the application of the “site-less” model, but 81.25% considered that the combination of on-site and home visits can be better than only visits at sites. Conclusion. Based on this research, the implementation of decentralized elements in the clinical trials in Europe is often based on a case-by-case evaluation only. Notwithstanding the application of various national requirements and acts, they are either fragmentary, or not specifically applicable for such cases.

9

Authors: Raluca A. CORB ARON, Delia M. TIT, Radu MOLERIU, Cosmin M. VESA, Sergiu BUNGAU, Alexandra G. TARCE, Tapan BEHL, Simona G. BUNGAU

Introduction. The composition of gut microbiota can be affected by type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), its improvement is frequently ignored in metabolic disorders. The objective of the study was a comparative evaluation of the faecal microbiota of healthy controls and of T2DM and MS patients (n = 150). Materials and methods. A retrospective crosssectional study was performed, between July 2019- December 2020 in the Bio-standard laboratory Oradea, Romania. A group of 75 patients with non-insulin dependent T2DM and MS (study group = SG) and 75 healthy subjects (control group = CG) has been included in the study. The composition of the microbiome and the influence of oral antidiabetic treatment on the microbiome in SG patients were compared. Results. 8 out of 19 species of the analysed bacteria had a different relative abundance in the SG, compared to CG; Enterococcus spp. were significantly higher (3.18x106 vs 1.94x106, p=0.004), while Akkermansia muciniphila (2.55x109 vs. 4.66x109, p<0.001) and Eubacterium spp. (3.51x108 vs 4.16x108, p=0.047) had significantly lower values in the SG vs. CG. Conclusions. The results indicated differences in the relative abundance of microbial species between the two groups, with significant changes in gut microbiome in the SG.

9

Authors: Galyna Ya. STELMAKH, Tatiana V. KHMARA, Inna V. LUKASHEVYCH, Volodymyr V. VIZNIUK, Iryna D. KIIUN, Ruslan P. KNUT

Introduction. The development of angiosurgery requires the morphologists to clarify in more details the topographic anatomical peculiarities of arterial vessels, considering their morphogenesis, peculiarities of innervation, age and individual anatomical variability in different periods of human ontogenesis. The objective of the study was to clarify the sources and peculiarities of innervation of the aortic arch and thoracic aorta in human fetuses. Materials and methods. The study was performed on 36 preparations of human fetuses of 81.0-375.0 mm of parietal-coccygeal length using a combination of methods, such as macro-microscopic preparation, vascular injection, application staining, making of 3D reconstruction models, morphometry. Results. The sources of innervation of the aortic arch in human fetuses are the cervical cardiac branches of the vagus nerve, the cervical cardiac nerve and the single branches of the upper three or four thoracic ganglia of the sympathetic trunks. The innervation of the thoracic aorta is performed by the branches of the thoracic aortic plexus, collateral trunk and also the branches of the paraaortic plexus, which is located between the sympathetic trunk and the thoracic aorta on both sides. From each thoracic ganglion and internodal branch of the sympathetic trunks depart 2-6 branches, some of which go to the thoracic aorta along the posterior intercostal arteries, and the other branches are connected by connecting branches forming the collateral trunk. The vagus nerve throughout the thoracic region gives branches to the thoracic aorta with the formation of the thoracic aortic plexus. Conclusions. In human fetuses, the paraaortic plexus is found between the right and left sympathetic trunks and the thoracic aorta, in addition to the intermediate plexus or collateral trunk. In the dynamics of the fetal period of ontogenesis, a bilateral asymmetry in the structure and formation of plexuses of the thoracic aorta is observed. At the end of the human fetal period, the number of connecting branches between the nerve branches of the paraaortic plexus increases.

281-283

Authors: Camelia C. DIACONU

The clinical data obtained during the pandemic of coronavirus disease 2019 (COVID-19) indicated that this is a disease associated with an increased risk of thrombosis. Thromboembolic events in patients with COVID-19 lead to a worse clinical evolution and a poor prognosis. Some studies analyzed the prevalence and risk factors for thrombotic complications in patients with COVID-19. An observational study on 3,334 patients admitted for COVID-19 has found that 16% of patients had a thrombotic complication during hospitalization(1). 11.1% of these cases had an arterial thrombosis, 8.9% had myocardial infarction, 1.6% ischemic stroke and 1% systemic arterial thrombosis(1). Venous thromboembolism was encountered in 6.2% of patients(1). Older age, man sex, personal history of ischemic heart disease, and increased D-dimers were all risk factors for thrombosis in this study1. Almost one third of patients admitted in the intensive care unit presented thrombotic events and these were associated with a higher risk for in-hospital mortality(1). Interestingly, another study on non-hospitalized patients with COVID-19 did not find a significant difference regarding the incidence of venous thromboembolism between these patients and those without COVID-19(2). The authors analyzed data of 220,588 patients tested for COVID-19 and reported the incidence of thrombosis in out-patients and in-patients, at 30 days. From these patients, 11.8% tested positive for infection with SARS-CoV-2; within 30 days after the positive test, 0.8% of patients developped venous thromboembolism, compared to 0.5% of patients with negative tests(2). However, this study had some limitations regarding the diagnosis of venous thromboembolism and the empirical use of anticoagulants and/or anti-inflammatory drugs. The authors of this study suggested that anticoagulants need to be studied in prospective clinical trials, to evaluate the impact of anticoagulant treatment on outpatients’ outcomes. Regarding the pathophysiology of thrombosis in COVID-19, new data highlight that patients with severe forms of disease have sustained platelet activation, that contribute to the increased risk of thrombosis. Endhotelial injury is another pathophysiological factor that may intervene, by altering hemostasis. Cytokine storm, that appears in patients with severe forms of the disease, will also increase the risk of coagulopathy and thrombosis. The overproduction of inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-6, interleukin-8 and interleukin-1 is considered the cause of cytokine storm, that may cause multiorgan failure and possibly death(3). Laboratory tests usually reveal increased D-dimers, thrombocytopenia, elevated fibrin degradation products, and fibrinogen(4). D-dimer levels are especially increased in patients with critical forms of disease, admitted in intensive care units(4) and may be a surrogate marker for the disease severity(5). Because of the clinical consequences of hypercoagulability in patients with COVID-19, hemogram with platelet count, peripheral blood smear, prothrombin time, aPTT, fibrinogen and D-dimers should be monitored in all hospitalized patients with COVID-19. Furthermore, these patients must be investigated and screened for deep venous thrombosis, preferably by duplex scan. Pulmonary thromboembolism, in some studies, has been more frequent than deep venous thrombosis in patients with COVID-19. A study of 1,765 patients diagnosed with COVID-19 reported an incidence of pulmonary embolism of 22%, and even higher in patients admitted in intensive care units(6). Patients with COVID-19 may also present coagulation abnormalities similar to thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, or hemolytic uremic syndrome. Thrombotic complications in COVID-19 have some unique characteristics that must be deeper investigated, for a better management of this disease.

291-297

Authors: Ecaterina PAVLOVSCHI, Valeriana PANTEA, Djina BOROVIC, Olga TAGADIUC

Introduction. Arterial hypertension (HTN) is one of the leading public health problems, causing a challenging and complex visual impairment known as hypertensive retinopathy (HR). Its pathogenesis is caused not only by changes in retinal homeostasis because of high blood pressure (BP) but, undoubtedly, other pathological mechanisms are involved, including oxidative stress (OS). The aim of the study was to evaluate the serum and tears total antioxidant capacity (TAC), as a single parameter of oxidative stress associated with the development of HR and to establish whether there is a correlation between its level and the grade of HR. Materials and methods. 90 hypertensive patients divided according to the Keith-Wagner-Barker grading system of HR into three groups: GI – 36 patients; GII – 35 patients; GIII – 19 patients. TAC in tears and serum was measured and the obtained results were analysed by Kruskal-Wallis and Mann-Whitney tests in SPSS Statistics. The Spearman correlation coefficient was determined. A p≤0.05 was considered statistically significant. Results. TAC values in the tears samples of hypertensive patients increased statistically significant as HR advanced in grade (p=0.003). Serum level of TAC showed only a tendency of decrease (p=0.182). Only tears TAC levels correlate significantly with low power with HR degree (r=0.357**, p=0.001). Serum and tears levels of TAC have a statistically significant negative low power correlated with each other (r= – 0.226*, p=0.032). Conclusions. The continuous rise in TAC levels in tears along with HR progression is a possible mechanism by which the eye copes with the damaging reactive oxygen species produced by OS. The increase in TAC may partially explain the gradual and delayed development of retinopathy stages in HTN.

309-316

Authors: Tatiana ROTARU, Natalia LOGHIN-OPREA, Lucia MAZUR-NICORICI, Virginia SALARU, Maria GARABAJIU, Victoria SADOVICI-BOBEICA, Minodora MAZUR

Introduction. Psoriatic arthritis (PsA) is chronic disease associated with considerable psychological burden and impaired quality of life (QoL). The objective of the study was to determine the medical and social status of patients with PsA, to optimize the management of these patients and increase their QoL. Material and Methods. We performed a cross-sectional study in which were included patients with PsA. Demographic and clinical data were collected using a special questionnaire, including employment and profesional status, information related to disease onset and duration, clinical overview related to the disease. In order to apreciate the burden of PsA, we applied the Rankin’s scale, Health Assessment Questionnaire (HAQ), Short Form 8 (SF-8), Work Productivity and Activity Impairment (WPAI) and Disease Activity score in Psoriatic Arthritis (DAPSA), Patient Global Assessment (PGA) to assess the disease activity. Results. 92 PsA patients were enrolled in the study. Male to female ratio was 1.09:1, the patient’s mean age was 48.53±11.42 years. According to DAPSA, patients had moderate to high disease activity. 34.78% of patients from the group of study were full-time employees. The assessment of work productivity by WPAI determined a level of absenteeism of 9.39±11.79% and presenteeism of 37.57±27.31%. The QoL in PsA patients was diminished in both mental and physical domains; the average HAQ score value was 0.61, which indicates a moderate functional status. According to Rankin’s scale, the most frequent degree was the 2nd, found in 32 (34.78 %) patients. Conclusions. Patients with PsA have medium/low medical and social status, caused by low physical functionality and psychological problems. To optimize the management of patients with PsA, it is necessary to integrate rheumatological, dermatological, psychological and social services.

329-335

Authors: Vanya RANGELOVA, Ani KEVORKYAN, Ralitsa RAYCHEVA, Diruchi AMUDZHIYAN, Mariana ALEKSANDROVA, Sara SARIYAN

Introduction. Vaccination is the most effective and safest means of preventing influenza infection. The coverage with influenza vaccine is not satisfactory across Europe and one of the main obstacles is vaccine hesitancy. The objective of the study was to assess the knowledge, attitudes, and practices of the population towards the seasonal influenza vaccine. Materials and methods. Between November 2016 – February 2017 a cross-sectional study using a semi-structured questionnaire was conducted in Plovdiv (Bulgaria), covering 545 people over 18 years old. Standard descriptive statistics was used to summarize demographic characteristics. Differences between observed and theoretical distributions were tested using chi-square test for independence. A 2-sided p-value of <0.05 was considered statistically significant. Results. The vaccine uptake was 11%. An association was found between the age of the respondents and administration of the vaccine (χ2=16.687 p=0.005), vaccination status and educational level (χ2=27.002, p=0.00002). 27.6% of the unvaccinated respondents were uncertain about the effectiveness of the vaccine and 26.8% had the perception this is not a serious disease. More than half of the respondents (51.1%) were willing to change their attitude towards the influenza vaccination, the recommendation from a doctor being the most important (40.8%). Conclusions. Seasonal influenza vaccine uptake was low in our study and the main drivers for vaccine hesitancy were concerns regarding its safety and effectivenes. Recommendation of the vaccine from a general physician was the most important source for influencing the attitudes towards the vaccine. This highlights the importance of general physicians’ involvement and the need to spread public awareness regarding the efficacy and benefits of seasonal influenza vaccination.

342-348

Authors: Calin POPOVICI, Petru ARMEAN, Andrei KOZMA

Introduction. In Romania, the number of cases of maternal death has decreased significantly in recent years. Material and methods. The objective of this review is to assess maternal mortality in Romania in the last decade (2010-2019) in terms of the evolution of the number of cases and socio-demographic characteristics, by death groups and the identification of predictors of severe obstetric morbidity. Results. The number of maternal deaths decreased during the analyzed period by almost 60% (from 51 deaths in 2010 to 20 in 2019). We observed the decrease of maternal death index from 24.0/100,000 live births in 2010 to 10.6/100,000 live births in 2019. Considering maternal death groups, the result is mainly due to the decrease of abortion and indirect obstetrical risk, maintaining the trend of a higher mortality through direct obstetrical risk. Maternal deaths and mortality as a whole also decreased in terms of distribution by area for this period, generally maintaining the gap in favor of the rural environment. A number of factors have been identified as playing a predictive role for severe obstetric morbidity. Conclusions. The decrease in maternal mortality has been influenced by several factors, including the increase in the number and quality of prenatal care, reducing the risk of maternal death from indirect causes. Another factors are the quality and promptness of hospital care, more relevant in the case of deaths from direct obstetric causes; nevertheless, the risk of death in this group is still almost double. The analysis of severe obstetric morbidity can be performed considering the following groups of predictors: demographics (over 34 years old, etc.), general medical (hypertension, etc.) and obstetric factors (multiple pregnancies, antenatal hospitalizations, emergency cesarean section, etc). Their identification can determine a focus on women who require higher attention during pregnancy.

358-362

Authors: Vanya BOZHIDAROVA GEORGIEVA

The coronavirus disease 2019 (COVID-19) is the latest life-threatening disease affecting health and economic sectors worldwide. The ethical principles during the COVID-19 pandemic can be shaken because of distributive and social injustice, healthcare collapse, distress among healthcare workers, lack of confidentiality of personal data, development of strategies for exiting pandemics, isolation, mass vaccination and last, but not least, ethical principles of scientific studies during COVID-19. This overview article discusses the ethical issues raised during the COVID-19 global pandemic.

376-382

Authors: Iulia SIMA, Eliza M. POPA, Lavinia RAICU, Rosana MANEA

Introduction. Sinusitis is caused by allergens, viruses, fungi or bacteria. The main signs of the disease are those of a common cold. Untreated sinusitis can lead to severe orbital or intracranial complications, such as brain abscess. Case presentation. We present the case of a 52-year-old man who presented to the emergency department with aphasic speech disorders and headache persisting for two days. After computed tomography (CT) evaluation, the suspicion was raised of a brain abscess and subdural empyema, with the starting point in the paranasal sinus infection. The treatment included neurosurgery and broad-spectrum antibiotics continuously for 4 weeks. The aim of this case study is to underline the importance of properly administered treatment in chronic sinusitis and the severity of the complications that may occur. Conclusions. Untreated sinusitis can lead to life-threatening complications, such as brain abscess and subdural empyema, even though the symptoms are often ignored. For the complete diagnosis and further treatment, the use of CT and magnetic resonance imaging (MRI) is necessary.

139-141

Authors: Camelia C. DIACONU

Coronavirus disease 2019 (COVID-19) is mainly a respiratory disease, that can lead also to cardiovascular complications such as myocarditis, acute coronary syndromes, arrhythmias, heart failure, stroke, venous and arterial thromboembolism etc. Furthermore, cardiovascular patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have worse outcomes and higher risk of death1.

150-156

Authors: Anca EVSEI, Adelina BIRCEANU-COROBEA, Mihai GHITA, Maria SAJIN, Narcis COPCA

Introduction. Recent research has demonstrated that the immunohistochemical nuclear -catenin expression is a valid surrogate for CTNNB1 exon 3 mutation in endometrial carcinomas (ECs). This mutation is an independent prognostic factor which identifies a subgroup of low-grade endometrial carcinomas that have a tendency for recurrence and worse prognosis. The objective of the study was to evaluate nuclear -catenin expression in different molecular subgroups of E Cs. Material and methods. We tested immunohistochemical nuclear -catenin expression in 50 cases of endometrial carcinomas diagnosed in two clinical institutions. Statistical analysis was performed between -catenin expression and various clinical, demographic, pathological and immunohistochemical parameters (age, myometrial invasion, FIGO grade, histopathological subtype, hormone receptors – ER, PR etc). Additionally, we analysed what molecular subgroup of ECs (MSS, MSI, p53wt, p53abn) revealed the most frequent cases with -catenin expression. Results. Our study indicated that ECs with nuclear -catenin positivity were observed in cases with higher FIGO grade (p=0.02), in endometrioid carcinomas (p=0.04) and in cases with lympho-vascular invasion (p=0.05). ER and PR were frequently expressed in the positive -catenin subgroup (p=0.03, p=0 .02). Our results show that ECs which express nuclear -catenin correlate with parameters that are already considered unfavourable. Conclusions. mmunohistochemical -catenin nuclear expression is an excellent replacement for the CTNNB1 exon 3 mutation in ECs and helps to stratify and predict prognosis in certain cases of ECs. We believe that future research will include this marker as part of the routine immunohistochemical panel for ECs.

165-171

Authors: Tho Kieu Anh PHAM, Van De TRAN , Kien Trung NGUYEN, Phuong Van PHAM, Tam Thai Thanh TRAN, Rebecca S. DEWEY, Binh Thanh NGUYEN, Tung Dinh LE

Introduction. Nerve stimulation tests are crucial in the early diagnosis and monitoring of neuromuscular disease. The objective of the study was to clinically characterize and validate repetitive nerve stimulation (RNS) testing in patients with the chronic autoimmune neuromuscular disease, myasthenia gravis (MG). Material and methods. Clinical assessment and RNS testing were performed in 30 myasthenic patients. Clinical assessments were classified using the Myasthenia Gravis Foundation of America (MGFA) clinical classification. Results. 30 myasthenic patients were recruited, with a mean age of 48.57 2.4 years and a female/male ratio of 2/1. MGFA classification placed 7 patients in group I (23.3%), 7 in group IIa (23.3%), 7 in group IIb (23.3%), 6 in group IIIa (20%), 2 in group IIIb (6.7%), and 1 in group IVa (3.3%). Additionally, 73.3% of patients had positive acetylcholine receptor (AChR) antibodies, and 20% had been diagnosed with thymoma. The RNS test was positive in 21 patients (70%). Patients with involvement limited to the orbicularis oculi muscles (group I) had a positive RNS test rate of 42.9%, whereas this rate increased to 64.2% in patients where the limbs and truncal muscles were affected (“a” groups: IIa, IIIa, IVa). Where respiratory and pharyngeal muscles were affected (“b” groups: IIb, IIIb), patients had a 100% positive RNS test rate. A statistically significant association was found between RNS test results and AChR antibody levels (p = 0.0041). Conclusions. These findings are of interest for physicians treating MG patients and administering RNS testing and suggest an alternative method for the diagnosis and monitoring of MG, in cases where AChR antibody quantitation is not appropriate.

179-184

Authors: Dumitru CHEPTEA, Raisa DELEU, Victor MESINA, Grigore FRIPTULEAC, Serghei CEBANU

Introduction. The closure of schools and the transition to online teaching, results of the restrictions imposed by COVID-19 pandemic, have led to major changes in the work environment, as well as the emergence of various negative manifestations on teacher’s health, such as burnout. The objective of the study was the assessment of burnout among teachers during the COVID-19 pandemic in the Republic of Moldova. Material and methods. A two-stage research questionnaire was applied on a sample of 375 teachers. As a result of the influence of pandemic restrictions, the occurrence of burnout was investigated using Maslach Burnout Inventory. Results. We found significant relationships between some demographic variables and the burnout. It has also been shown that women are more susceptible to burnout than men. Occupational stress and poor working conditions, as well as the absence of physical contact with students, are strong predictors of burnout, work experience being the only protective factor. Conclusions. The sudden change in physical working conditions, as well as the need to quickly change the teaching methods because of the COVID-19 pandemic,have a negative impact, increasing the incidence of burnout in teachers.

193-200

Authors: Liliia D. TODORIKO, Olena V. PIDVERBETSKA, Olga S. SHEVCHENKO, Ihor O. SEMIANIV, Rostyslav S. SHEVCHENKO, Inga V. YEREMENCHUK, Stanislav I. SHEVCHENKO, Victor I. SLYVKA, Petro I. POTEIKO, Oleg Ya. PIDVERBETSKYI

Introduction. To date, there are virtually no data on pathomorphological changes in the mucous membrane of the small intestine in coinfection HIV/ Mycobacterium tuberculosis (HIV/TB), which could be the basis for the development of malabsorption. The objective of the study was to investigate the pathomorphological characteristics of the small intestine mucosa in patients with coinfection HIV/TB. Materials and methods. The prospective pathomorphological study included 24 patients with HIV/TB coinfection (main group), and 20 patients without HIV infection, gastrointestinal pathology or morphological signs of TB (control group). Results. The thickness of the small intestine mucosa, the average height and width of villi were significantly lower in the HIV/TB group compared with the control group (p<0.05). The relative area of connective tissue in the small intestine mucosa was increased in the main group (p<0.05). The coefficient of variation of the optical density of nuclear chromatin in the main group noticeably exceeded the coefficient in the control group: 42.7 6.47% vs. 6.7 0.34% (p<0.05). The red/blue (R/B) ratio in the main group almost doubled that of the control group, while the quantitative index of the optical density of the specific colour for free amino groups was 1.7 times higher than in the control group (p<0.05). Conclusions. Coinfection HIV/TB is accompanied by the development of atrophic and sclerotic changes in the small intestine, a decrease in the functional activity of enterocytes and increased intensity of free radical processes.

213-220

Authors: Nelea MATRAGUNA, Svetlana COJOCARI, Lilia BICHIR-THOREAC, Ninel REVENCO, Lucia MAZUR-NICORICI

Introduction. The worldwide alarming rise in the incidence of metabolic syndrome (MS) in children has made the prevention and early treatment of obesity an important medical goal. The objective of the study was to assess the role of proinflammatory markers, such as tumour necrosis factor-alpha (TNF-) and high-sensitivity C-reactive protein (hs-CRP), and adipokines (leptin, adiponectin) in the development of MS in children and the impact of treatment with gastrointestinal lipase inhibitors on the degree of obesity and blood pressure values. Material and methods. The study included 24 children with metabolic syndrome. The serum values of lepine, adiponectin, TNF- and hs-CRP were determined in children with MS compared to a control group of 50 children of similar age. Results. The serum level of leptin, hs-CRP, and TNF- was higher in children with MS as compared with the control group. The adiponectin level was lower in children with MS, compared to the control group. After eight weeks of drug treatment with gastrointestinal lipase inhibitors in all children, a decrease in body mass index, abdominal circumference and blood pressure values was found, but the most important decreases were found in children who received non-pharmacological treatment in combination with gastrointestinal lipase inhibitors and angiotensin-converting enzyme inhibitors. Conclusions. Hypoadiponectinemia, hyperleptinemia, increased serum hs-CRP and TNF- suggest that these adipokines/cytokines contribute to subclinical inflammation in children with MS and may also serve as biomarkers of MS. In combination with a low-calorie diet, regular exercise and lifestyle changes, treatment with gastrointestinal lipase inhibitors may help to reduce the prevalence of obesity and hypertension in children.

229-233

Authors: Gregory TSOUCALAS, Spyros N. MICHALEAS, Georges ANDROUTSOS, Nikolaos VLAHOS, Marianna KARAMANOU

In ancient Greece, many textbooks were written in order to provide comprehensive, pioneering, and ingenious guides on the philosophy and medical aspects of sexual behaviour. Unfortunately, only fragments of these texts have survived among the treatises from Greek and Roman antiquity. The aim of this study is to examine these texts and understand the triad of the female prostitution-hygiene-medicine in ancient Greek populations. We conduct a thorough study of ancient texts, using PubMed, Google Scholar, and medical libraries of Athens, Greece. Prostitution in ancient Greece symbolized both lust and sexual freedom of women, while at the same time it could signal the relationship of female potency to control men. Most prostitutes served men in need of medical and psychological services. They also addressed issues like physical violence, sexually transmitted infections, post-traumatic stress, and unplanned pregnancies. The contribution of female prostitution in ancient Greece, demonstrates the polysemous development of terms such as  sexual pleasure ,  lust , and  eroticism  in the medico-philosophical texts of that era.

242-247

Authors: Gabriela ANGELESCU, Victor FLORESCU, Mihai T. ANGELESCU

Introduction. Primary neuroendocrine tumours of the gallbladder represent 0.2% of all neuroendocrine tumours. The diagnosis is incidental in most cases. Case report. We present the case of a male patient, with no significant personal pathological history, who presented for pain in the right hypochondrium with posterior irradiation. The abdominal ultrasound examination performed at presentation in the emergency room described an acute lithiasis cholecystitis. Laparoscopic surgery proved difficult due to adhesions and difficulties in grasping the gallbladder. The results of the histopathological examination established the diagnosis of a small cell neuroendocrine carcinoma, confirmed by the immunohistochemical tests. Conclusions. In most cases of primary neuroendocrine tumours of the gallbladder the paraclinical examinations suggest a benign disease. The positive diagnosis is done after surgery, by histopathological examination, which can change the postoperative therapeutic management.

253-256

Authors: Hasan BESIM

In troduction. Postoperative foreign body retention is a well-known and rare complication of all types of surgical interventions. The clinical presentation of a patient with an abdominal retained foreign body is generally as an infectious syndrome, such as intraabdominal sepsis, peritonitis, abscess formation, intestinal perforation or obstruction. However, these foreign bodies may remain dormant for years or may generate vague symptoms. Contained rupture and spontaneous passage through a hollow organ and subsequent rectal expulsion are very rare outcomes. Case presentation. We present the case of a 23 years-old female patient previously operated who had a spontaneous rectal expulsion about two months after the operation, with no need for any further operative intervention. Conclusions. The spontaneous expulsion of a postoperative foreign body is a very rare but possible situation. This is a very serious medicolegal problem and many safe operating room practices are implemented to minimize the occurrence of this complication, defined as gossypiboma or textiloma, as the most common foreign body retained is a surgical sponge.

263-267

Authors: Gregory TSOUCALAS, Eleni PANAGOULI, Anastasios VASILOPOULOS, Anastasios KARAYIANNAKIS, Vasilios THOMAIDIS, Aliki FISKA

Introduction. Common hepatic artery is one of the three branches of Haller tripod and gives rise to the left and right hepatic arteries. We describe the case of a 62-year-old woman with the right hepatic artery rising from abdominal aorta, diagnosed incidentally during an abdominal computed tomography angiography. Case report. The common hepatic artery was absent. In its place, the left hepatic artery originated from the celiac trunk, while the right replaced hepatic artery was observed arising directly from the abdominal aorta. Conclusions. The uncommon abnormal vascular pattern presented has not been yet classified as an anatomic variation. Such arterial aberrations should be considered by surgeons during cholecystectomy, liver transplantation and pancreatectomy, to avoid complications.

5-7

Authors: CAMELIA C. DIACONU

COVID-19 is one of the most severe crises of the last decades, with unprecedented and unpredictable losses. COVID-19 is mainly a disease with respiratory symptoms, but cardiovascular and neurological complications are more and more reported and should not be ignored. Some patients with COVID-19 experience delirium during hospitalization, with confusion, agitation and disorientation. The neurological complications are insufficiently known and they may alter the prognosis of these patients. The researchers struggle to understand why these neurological signs appear, who is at higher risk and how they should be managed. Two hypotheses have been advanced: the first one is related to the direct viral invasion and infection of the brain and the second one to an overstimulation of the immune system. The appropriate treatment of the neurological signs depends on the correct knowledge and understanding of the pathophysiological mechanisms.

16-23

Authors: Nina D. TSVETKOVA, Rumen N. HARIZANOV, Iskra G. RAINOVA, Iskren T. KAFTANDJIEV, Raina B. ENIKOVA, Nina S. YANCHEVA, Kalina S. PAVLOVA

Introduction. Cryptosporidiosis is a protozoan infection, and in humans is most often caused by two species, Cryptosporidium parvum and C. hominis. The disease most often presents with diarrhea, and it has been defined by the World Health Organization (WHO) as a human immunodeficiency virus (HIV)-related infection. Although in Bulgaria the tests for cryptosporidiosis have been performed for almost thirty years, the disease is still insufficiently known to healthcare professionals. The objective of the study was to determine the incidence and demographic characteristics of human cryptosporidiosis in Bulgaria for a 10-year period, from 2009 to 2018. Material and methods. During the study period, a total of 2706 patients were examined for cryptosporidiosis by microscopic and immunochromatographic methods, of whom 2618 were immunocompetent and 88 were HIV-infected. Results. 22 patients were diagnosed with oocysts of Cryptosporidium sp., of whom 15 were immunocompetent and 7 immunocompromised. The average annual incidence of the disease for the studied period was 0.03 per 100 000 population, and the level of this indicator is similar in some European Union countries such as Poland, Czech Republic, Latvia, Norway. The data from our study showed that the most affected were the age groups from 0 to 4 years and the female patients, and that the disease prevails in the summer months of the year. Conclusions. In Bulgaria, human cryptosporidiosis has a low incidence rate, but in our opinion, this is mostly due to the fact that, currently, only а small number of laboratories perform tests, that hinder the determination of the actual prevalence among the population.

33-42

Authors: Tatiana ROTARU, Maria GARABAJIU, Lucia MAZUR-NICORICI, Natalia LOGHIN-OPREA, Victoria SADOVICI-BOBEICA, Virginia SALARU, Minodora MAZUR

Introduction. Psoriatic arthritis (PsA) is an inflammatory joint disease associated in up to one-third of patients with psoriasis. Studies performed on PsA showed the high burden of the disease, but it still has not been totally quantified due to variable course of the disease. The applicability of the existing clinical tools in the disease activity appreciation still needs to be approved. The objective of the study was the assessment of the disease activity level and the evaluation of reliability and applicability of disease activity measures in PsA. Materials and methods. A descriptive study of 46 PsA patients was performed. The disease activity indices for PsA were evaluated and compared. The level of the disease activity according to each index was assessed and applicability of these indices was appreciated. Results. The disease activity by Disease Activity Index for Psoriatic Arthritis (DAPSA) was appreciated as moderate in nearly half of the patients (47.8%), and according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) moderate disease activity was assessed in 56.5% cases. Minimal disease activity was encountered in only 8.69% of patients. Psoriasis Area and Severity Index (PASI) was estimated as moderate (mean 20.21 points). The data analysis of clinical tools showed that the most affected were pain and general condition, objectified by Visual Analogue Scale (VAS) and Patient Global Assessment (PGA). Conclusions. The DAPSA demonstrated the highest objectiveness and was best able to designate between different levels of disease activity. DAPSA together with Minimal Disease Activity index (MDA), were best related to patient’s quality of life. Therefore, assessing the activity of the disease by MDA and DAPSA can be recommended for use in clinical practice.

51-57

Authors: Zlatina V. PETEVA, Stanislava K. GEORGIEVA, Ginka N. KALINOVA, Snezha Z. ZLATEVA, Mona D. STANCHEVA

Introduction. Shellfish poisoning could be caused by ingestion of shellfish contaminated by bacteria, viruses, heavy metals, pesticides, marine biotoxins etc. The objective of the study was to determine the theoretical human exposure to shellfish toxins of Bulgarian consumers. The incidence of registered cases of intoxications due to marine biotoxins ingestion – “Toxic effect: Other fish and shellfish poisoning (T61.2)” in regional hospitals was investigated. Materials and methods. Acute exposure (AE), chronic exposure (CE) and hazard quotient (HQ) are calculated based on experimentally-determined levels of shellfish toxins in mussels harvested from North Bulgarian coast in the period 2012 – 2018. We performed a retrospective analysis of the frequency of the diagnosis T61.2, based on medical documentation for the period 1.05.2012 – 7.12.2018 in hospitals in Varna and Dobrich, Bulgaria. Results. Shellfish toxins that most often occur in mussels are domoic acid (DA), yessotoxin (YTX) and pectenotoxin-2 (PTX2). The calculated maximum AE was 1.00 mg/kg bw for DA, 0.02 mg/kg bw for YTX and 0.0045 mg/kg bw for PTX2, respectively. Maximum CE for DA was 0.01 mg/kg bw/day. All estimated values were much lower than those legislated by European Food Safety Authority thresholds. The exposure to marine biotoxins was estimated based on contamination data of mussels harvested from the same region. The analysis for the whole period showed that its frequency is lower than 1%. Clinicians report that this diagnosis is presumptive, based on recent ingestion of shellfish and presence of symptoms consistent with shellfish poisoning. Conclusions. Estimated theoretical acute and chronic exposures agree upon the incidence of clinical cases with the studied diagnosis. A parallel investigation on a prolonged period is required, to increase the accuracy of these results.

66-71

Authors: Ivan VLADANOV, Pavel BANOV, Vitalii GHICAVII

Introduction. The treatment requirements for non-muscle invasive bladder cancer (NMIBC) (Ta, T1) and muscular invasive bladder disease (T2) differ considerably, therefore a correct staging of the disease is most important. The staging of the disease is frequently underestimated during the primary tumour resection. The objective of the study. To evaluate the results of repeated transurethral resections of the bladder tumours, to assess the treatment outcomes. Material and methods. 160 patients diagnosed with NMIBC underwent transurethral resection of the bladder tumours (TUR) and repeated TUR (reTUR). A data analysis was carried out following the interventions, with histopathological examination, disease staging, and dynamic assessment after 1-year follow up. Results. The average age of the patients was 65.7 years (range 28–86 years) and most of the patients were male, 139 (87%). In most of the cases, the tumours were single, less than 3 cm, and of low-grade in 52%. At reTUR, the residual disease was found in 33% (25/76) of cases. Of these patients, 12 were Ta and 7 were T1, while 2 were carcinoma in situ (Tis) with residual T1 and 4 were upstaged to T2 disease. 62% of residual tumours were detected within the initial resection area. The recurrence rate after 1-year follow-up in the group of reTUR vs. TUR group was lower (29% vs. 56%), as well as disease progression (5% vs. 13%), respectively, after the 1-year follow up. Conclusions. Residual tumours commonly occur following a transurethral resection of high-risk non-muscle invasive bladder cancers. The repeated resection procedure helps in diagnosing residual tumours which have been initially assessed as the T1 stage and may improve the treatment outcomes.

80-87

Authors: Alexandr GOLUBEV

Introduction. The COVID-19 pandemic has revealed number of problems in the global medical system. This article is targeted to show solutions based on the technical information technologies to help patients, medical professionals and institutions for using DICOM Network application in the context of special requirements during pandemic. The objective of the study was to show how to minimize contacts with the patients by using telemedicine and online consultations based on the information technologies solutions. Material and methods. The data used in this study are based on the DICOM Network informational system, that is targeted to collect medical images based on DICOM format. This system collects all type of DICOM investigations, including tomography investigations, X-Ray images, ultrasonography and others. The average flow of the data is about 10 TB per year. In this study, we used input data collected by this system from 4 medical institutions. Results. There were defined the gaps in the existing software solutions for telemedicine. Based on the existing workflow analysis and urgent requirements of the medical institutions with COVID-19 patients, it was implemented a set of new modules and functionalities for existing DICOM Network system to limit direct contacts with the patients and to reduce the costs of the imaging investigations. Conclusions. All the DICOM Network changes were done in parallel with the spreading of the pandemic “on the fly”, but all the functionalities were implemented in time and have helped, on one hand, to reduce the direct contact of physicians with the infected patients and, on the other hand, to reduce the costs for an investigation for about 2 EUR per investigations and 3000 EUR per month only for X-Ray investigations for COVID-19 patients.

94-100

Authors: Marcel STOITA, Areha Abid, Cosmin VESA1, Raluca A. CORB ARON, Timea C. GHITEA, Gabriela ANGELESCU, Amorin POPA

Chronic kidney disease of diabetic cause is a highly prevalent complication in diabetes mellitus patients. Complex phenotypes of the disease start to be recognized, such as albuminuria (micro- or macroalbuminuria) and non-albuminuric phenotype reduced glomerular filtration rate <60 mL/min/1.73m2. Numerous pathogenic pathways contribute to the development of this disorder, as follows: the alterations of glucose metabolism with excess degradation of glucose on alternative pathways, hemodynamic changes, glomerulosclerosis, inflammation. As this review demonstrates once more, all these pathophysiological modifications can be linked to hyperglycaemia. Both glomerular and tubular interstitial lesions occur and contribute to disease progression. Adequate glycaemic control and an early diagnosis of diabetes mellitus are key measures in preventing this complication.

106-109

Authors: Igor V. LAKHNO, Kemine UZEL

Introduction. Adenomyosis increases obstetrical and perinatal complications. Case presentation. We present a rare case of spontaneous pregnancy, large fetus, and cephalopelvic disproportion in a woman with diffuse adenomyosis. No biophysical or biochemical markers of failed placentation were detected during pregnancy. However, delivery was complicated by cephalopelvic disproportion. A male baby of 4350 g in weight, 59 cm in length, with a head circumference of 38 cm and Apgar score of 8 to 9 was delivered via Caesarean. The spontaneous conception and the absence of chronic placental insufficiency were unusual presentations in this case. Conclusions. The fact of complete cervical dilation and cephalopelvic disproportion in diffuse adenomyosis is of great interest. The presented clinical case is a ground for the continuation of the studies in the field of fetal outcome and uterine contractile activity in adenomyosis.

114-120

Authors: Rosen TSOLOV, Georgi YORDANOV, Nikolay PAVLOV

Introduction. Rhinophyma is a disfiguring nasal deformity due to the proliferation of sebaceous glands and underlying connective tissue. It affects mainly men, aged between 50 and 70 years old. The disease is associated with negative stigma, low self-esteem, reduction in quality of life. The main reasons patients seek medical help are cosmetic problems and functional impairments. Surgery is indisputably the treatment of choice for rhinophyma. Cases report. We present the cases of two patients diagnosed with rhinophyma, who underwent surgical treatment in the University Hospital “St. George”, Plovdiv, Bulgaria. The subtlety and innovation of the surgery was that the hypertrophied skin of the nose was dissected in layers, the sebaceous glands that produced pus were extirpated. The normal glands sought to be preserved, to nourish the newly formed dermis postoperatively. Both patients responded well to the procedure, without postoperative complications or wound infections. Conclusions. These cases highlight the importance of an accurate treatment of rhinophyma and the post-operative period, and the need for an appropriate follow up of patients until the complete recovery of the surgical wound and the formation of new skin.