ARCHIVES OF THE BALKAN MEDICAL UNION

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.

545-547

Authors: Camelia C. DIACONU

The evolution of medicine is strongly related to technological progresses and to vaccines that increased the life expectancy during the last century. The appearance of vaccines represented a true revolution in medicine. The principle of vaccination has been stated by Louis Pasteur in 1881 and is very simple: the exposure to an attenuated form of the disease to prevent a more severe form. Pasteur has discovered the first attenuated artificial vaccine, represented not by a microorganism similar to that causing the disease, but from the same strain having lost its virulence. The history of vaccination begins in the 18th century, with the monography of Edward Jenner, but there are cases in history that prepared the development of preventive medicine. Mithridates, the king of Pontus, conquered by Romans, wanted to suicide by ingestion of poison. His two daughters died after drinking the poison, but Mithridates survived and asked one of his people to kill him with a sword. His survival after poisoning was linked to the daily usage of certain drugs, which protected him against an otherwise deadly dose of poison. This legend explains the biological phenomenon of habituation by ingestion of progressive doses of poison. Since historical times, it is known that certain infectious diseases (like plague) can not appear twice in humans. The discovery of vaccines led to important changes of public health policies. In 1908, Bacille de Calmette et Guerin (BCG) was discovered, as consequence of accumulated knowledge on tuberculosis. Once the safety of BCG and its protective effects have been demonstrated in animals, human vaccination against tuberculosis was imposed after the First World War, when tuberculosis was responsible for 20-40% of deaths. Nowadays, tuberculosis is still an important public health issue in developing countries, with an increasing number of cases also in developed countries, explained mainly by the multi-resistance to antibiotics. The BCG vaccination remains an effective preventive measure, inexpensive, and with limited side effects. The flu has been known since ancient times and it is caused by an RNA virus. In the 14th century it was called influenza. Influenza can be epidemic or pandemic. Epidemic influenza occurs every year during winter, when more severe pandemic influenza occurs several times a century. The most severe influenza pandemic appeared in Spain, between 1918-1919, and was responsible for 50-100 million deaths worldwide, the most lethal health disaster of all time, comparable to the black plague between 1347-1350. Nowadays, the influenza vaccines can prevent the influenza pandemics. During the last years, because the most severe epidemics have disappeared or are in course of disappearance, it is increasingly difficult to convince the population (especially from developed countries) about the necessity to get vaccinated against a risk that may be considered minor. Moreover, the fear of side effects, stimulated by a part of mass media, led to a decrease of vaccination rate, which explains the recent appearance of cases of measles or diphtheria. Since their apparition, vaccines have been a matter of debate. The risks associated to vaccination are better accepted when the fear of a certain infectious disease is great. In this context, the role of mass media is very important, because when alarmist information regarding a certain vaccine is announced, a certain part of the population understand that it is better to refrain from getting the vaccine. Moreover, the anti-vaccines movement sustains that scientific publications concerning vaccinations are controlled by governments and pharmaceutical companies, who underestimate the side effects of vaccinations. The success of vaccination is based on a double confidence: confidence in the safety of the vaccine (guaranteed by doctors and governments) and confidence in the need for vaccination. To obtain this confidence, it is of utmost importance to intensify the mass education for health, by healthcare professionals who must educate and motivate the population. COVID-19 pandemics put the entire world on pressure and fear. This new viral disease does not have a specific treatment until now, only the current restrictions being able to prevent more people from being infected or dying. A vaccine could be the only solution to fight the pandemics and the best exit strategy, but the population needs to be properly informed and educated.

564-572

Authors: Tsvetelina V. PETKOVA-MARINOVA , Boryana K. RUSEVA, Bozhanka PANEVA-BARZASHKA, Milena A. ATANASOVA, Petya V. DRAGOMIROVA, Pavlina D. LALEVA

Introduction. Iron homeostasis has been extensively studied in the recent years. The factors regulating hepcidin secretion and the significance of hepcidin during pregnancy have not been fully clarified. The objective of the study was to investigate the serum concentrations of hepcidin and interleukin-6 (IL-6) and their relationships to parameters of iron metabolism in women with low-risk and high-risk pregnancies. Material and methods. The study involved 40 pregnant women distributed in two groups: high-risk pregnancies (HRP, n=20) and low-risk pregnancies (LRP, n=20). The HRP were associated with chronic inflammatory disorders and reproductive failures. We evaluated the red blood cell count, hemoglobin (Hb) concentration, hematocrit (Hct), erythrocyte indices, serum concentrations of hepcidin, IL-6, ferritin (Ferr) and iron (Fe), the total iron binding capacity (TIBC) and transferrin saturation (SatTf) twice, at the beginning of the second and third trimester of pregnancy. Results. We found significantly higher serum Ferr and lower TIBC in HRP than in the controls at the beginning of the second trimester (p<0.05). Significant decline in serum Ferr and rise in TIBC were observed during pregnancy in both groups, whereas decrease in SatTf was found only in LRP (p<0.05). In HRP, serum concentrations of IL-6 were negatively related to serum Fe and SatTf, and positively ‒ to Hb concentration, while serum hepcidin was negatively related to Hb concentration and Hct (p<0.05). A significant positive relationship between serum hepcidin and IL-6 was found in LRP (p=0.038). Conclusions. There are significant relationships between IL-6 and hepcidin production and parameters of iron metabolism in pregnancy.

582-591

Authors: Ziyo GASSANOV, Dilyara KAIDAROVA, Zhumagali ISMAILOV, Nurzhan NURGALIEV, Alma ZHYLKAIDAROVA, Kirill NYUSHKO, Zhanna CHINGISOVA, Shynar TANABAYEVA, Ildar FAKHRADIYEV

Introduction. Prostate cancer is the second leading cause of cancer death worldwide, including developed countries. There are epidemiological studies on the prevalence of this disease in Central Asia. However, a study about the prevalence of prostate cancer depending on ethnicity in Kazakhstan was not conducted yet. Objective. To assess the incidence rates of prostate cancer in relation to ethnicity, age and morphological type of tumour (in Kazakhstan). Methods. This is a retrospective study of morphologically verified cases of prostate cancer, performed on 7082 patients during the period 2015-2019. According to ethnicity, the patients were subdivided into the following groups: Central Asians, Slavs, and other nationalities. Four categories were identified by age: <60 yo, 60-69 yo, 70-79 yo and 80+ yo. The information on the age difference, social status, stages of the malignant process, morphological type of cancer was collected and analysed. The age-standardized incidence rate of prostate cancer was calculated depending on ethnicity. All statistical calculations were performed using SPSS software (version 22.0, IBM SPSS Inc., Chicago, Illinois, USA). A p value < 0.05 was considered statistically significant. Results. The mean age of the patients was 69.04±8.5 years. Among 7082 patients, 61.6% were Slavs, 35.01% Central Asians and 3.37% other ethnic groups. Prostate cancer prevailed in the age group 60-69 yo in 41.9% cases, which was higher among Slavs compared to the Central Asians (p≤0.05). The average annual increase in the disease incidence was 2.1%. There was no significant increase in the incidence of prostate cancer in the age groups: <40 yo (r = 0.41), 40–49 y0 (r = 0.31), +80 yo (r = 0.32). Stage II of the tumour process was the most diagnosed in the total number of cases (N = 2856), the highest prevalence being found among Slavs (40.66%) (p ≤ 0.05). Adenocarcinoma was the most frequently detected type of tumour (97.37%) in all ethnic groups. Conclusions. The results of the study showed there was a relatively low increase in the incidence of prostate cancer in the Kazakhstan population between 2015-2019. A high incidence of prostate cancer among men of Slavic nationality than among Central Asians was determined. These findings indicate the importance of the early diagnosis of prostate cancer, especially in ethnic groups with a higher incidence of the disease.

601-607

Authors: Uliana HEVKO, Kateryna KOZAK, Inna KRYNYTSKA, Mariya MARUSHCHAK

Introduction. Diabetes mellitus is associated with overweight and pancreatitis. To date, the results of routine laboratory tests are not being utilized as reliable markers for comorbidities associated with type 2 diabetes mellitus (T2DM). The objective of the study. The aim of this study was to analyze complete blood count parameters in order to determine significant predictors of T2DM comorbid course. Material and methods. The study involved 579 T2DM patients with comorbid overweight/obesity and chronic pancreatitis (CP). Complete blood count (CBC) was performed using a Yumizen H500 CT automatic hematology analyzer. Insulin levels were determined using a standard kit with a Thermo Scientific Multiskan FC enzyme-linked immunoassay analyzer. Glucose levels were determined using a standard kit with a COBAS INTEGRA® Diagnostics automatic biochemical analyzer. The neutrophil-to-lymphocyte ratio (NLR) was calculated based on CBC. Results. In T2DM patients, glucose levels significantly correlated with the fraction of neutrophilic granulocytes, including segmental neutrophils, lymphocytes, and NLR, while glycated hemoglobin (HbA1c) levels were significantly correlated with the lymphocyte and NLR fractions. Notably, no correlations between leukocyte profile and carbohydrate metabolism variables were found in T2DM patients. We found a negative correlation between glucose levels and the rod-shaped neutrophilic granulocyte fraction, as well as between HbA1c and NLR levels in overweight T2DM patients without CP. In overweight T2DM patients with comorbid CP, glucose levels correlated with the lymphocyte and NLR fractions. Conclusion. T2DM in overweight/obese patients with CP is characterized by an abnormal and uncontrolled leukocyte response, therefore a complete blood count is not an adequate marker of the comorbid course of diabetes in such patients.

616-623

Authors: Cezar I. BETIANU, Andrei V. NEAGU, Daniel PANTILE, Ana D. PASCARIU, Alexandru BAJENARU, Andreea I. NEAGU, Giorgiana ION, Andrei BONDARI

Introduction. Percutaneous core biopsy (PCB) is a minimally invasive, widely available and relatively safe procedure enabling pathological diagnosis in oncological patients. The objective of our study was to analyse the complication rates of PCBs between the lungs and other organs, for a better preprocedural evaluation. Material and methods. We performed a retrospective observational study of 558 PCBs, divided into: lung PCBs (n=355) and other PCBs (n=203). Descriptive statistics, the independent sample t-test, and Pearson correlation coefficient were used to analyse the statistical differences and relationships with the rate of complications. Results. The largest number of procedures was performed on the lungs (n=355), followed by breast (n=70) and liver (n=45) biopsies. The complication rate was 7.7% (n=43). The lung had a higher rate of complications (11.3%; n= 40), compared to 1.5% (n=3) from other PCBs. Lung PCBs correlate with complications (r(556) =.18, p < .001). The independent samples t-test was statistically significant, t(501) =5.2, p < 001. The lung PCBs were associated with a statistically significantly larger mean complication occurrence than the other PCBs. Cohen’s d was estimated at .37, which is a medium effect. The most common complication was pneumothorax (n=31), rate of 8.1% (n=29) from lung biopsies. CT-guidance (r(487) =.15, p =.001), repeated biopsies (r(538) =.17, p < .001), and INR (r(524) =-.10, p =.019) are correlated with complications. Conclusions. Lung biopsy is riskier than other biopsies and should be avoided if another biopsy, in the same pathological context, is available, to avoid unnecessary complications.

634-641

Authors: Victoria CHIHAI , Alisa TABIRTA, Anatolie VIZDOAGA, Lucia MAZUR-NICORICI, Oleg PASCAL, Minodora MAZUR

Introduction. Rheumatoid arthritis (RA) is a systemic, chronic condition that belongs to autoimmune diseases, characterized by synovial membrane damage with the involvement of connective tissue, which leads to important functional limitations. The objective of the study was to estimate the functional and psycho-emotional status in people with rheumatic damage in relation to the degree of activity and differentiated programs of medical rehabilitation. Material and methods. The data were collected from 67 patients diagnosed with moderate activity RA, aged 29-73 years, of both sexes, randomized in 2 groups (test group L(T) – 31 patients, and control group L(C) – 36 patients). Patients in the test group were involved in medical rehabilitation programs with active-assisted kinetic techniques, individualized for each patient. All persons included in the study were clinically-functionally examined with the application of a set of identical functional tests at admission and again, more than one month after treatment. The functional capacity of the hand was assessed by testing bi-digital, poly-digital and palm-based forceps (dots). The severity of the pain was assessed by visual analogue scale. The SF-11 (Medical Outcomes Study Short-Form Health Survey) scale was applied to assess the quality of life. The results obtained were analyzed using the Student test (p<0.05 value considered statistically significant). Results. One month after initiation of physiotherapeutic rehabilitation treatment in the L(T) test group, the average pain value decreased from 78.531±1.36 to 51.231±1.38 (р<0.001) points. The testing of the hand function in the L(T) test group showed an increase in scores from 4.27±1.25 to 7.31±1.03 (р<0.01) points. Application of the SF11 scale one month after treatment revealed in the L(T) test group the increase in psycho-emotional parameters: mental state (MS) from 40.12±2.13 to 72.14±7.1 (р<0.01) points; functioning of the emotional role (ER) from 27.24±1.23 to 68.43±3.12 (р<0.01) points, vitality (VT) from 22.37±4.32 to 35.28±3.14 (р<0.01) points. Conclusions. Medical rehabilitation programs with kinetic techniques have considerably improved clinical-functional manifestations, by reducing pain and improving hand function, mental state, emotional role, and general perception of health in people with rheumatic damage.

651-660

Authors: Indira KARIBAYEVA , Botagoz TURDALIYEVA, Nor Zuraida ZAINAL, Fatima BAGIYAROVA

Introduction. Depression in patients with advanced breast cancer is a serious comorbidity that affects the quality of life of these patients, and their survival rates. Objective. This study aims at systematically reviewing the current literature with data on the prevalence of depression symptoms in metastatic and recurrent breast cancer patients, examining the pooled mean prevalence of depression symptoms and potential sources of heterogeneity. Methods. An extensive systematic review of PubMed, Web of Science, Scopus, ScienceDirect, Google Scholar, American Doctoral Dissertations and Open Grey databases, and the following reference list hand-search was performed to retrieve studies from January 2005. Results. We identified 11 eligible studies that assessed 1223 patients on the presence of depression symptoms, and 465 patients met the criteria. According to the random-effects model, the pooled mean prevalence of depression was 38.23% (95% CI [30.92; 45.83]; I2= 87%; Q (df =10)=77.89, p-value < 0.01). Patients with metastatic stage had a slightly higher prevalence of depression symptoms compared to recurrent breast cancer patients. Conclusion. Prevalence of depression symptoms among advanced breast cancer patients is high. It is important to improve psychological prevention methods to decrease the occurrence of depression, as breast cancer patients start receiving care from primary diagnosis and offer continuous support and treatment to meet their psychological needs.

667-675

Authors: Cristina M. TIRZIU

Arterial hypertension (HTN) is one of the most prevalent diseases all over the word. There are many studies and reviews about the coexistence of HTN with coronary, cerebrovascular and renal diseases. However, sometimes clinicians do not search for aortic disease in hypertensive patients. The coexistence of HTN and various aortic diseases raises peculiar issues regarding monitoring and managing of these patients. This review presents data about HTN and aortic aneurism, aortic coarctation and aortic valve disease, emphasizing the particularities of the diagnosis and management of HTN in these patients. Also, a part of the review will focus on the evaluation of arterial stiffness and its clinical implications.

684-690

Authors: Dima K. TSANOVA

Global burden of diseases studies collected and analysed data from more than 195 countries, reflecting premature death and disability related to more than 350 diseases and injuries, by age and sex, since 1990 to the present. The national profile of each country in the studies contains comparative data for 2007 and 2019. The purpose of this paper was to analyse the differences in leading risk factors and causes of global burden of diseases between Balkan countries. The leading causes of years of life lost due to disability are mainly chronic non-communicable diseases, with the leading positions being low back pain, falls, headaches, diabetes, etc. The summary indicator for lost years of life due to premature death and disability-adjusted life years (DALYs) for 2017 again shows the leading role of ischemic heart disease and stroke. Preventable mortality in Bulgaria remains very high. Much of the overall burden of disease in Bulgaria can be attributed to behavioural risk factors, including smoking, alcohol consumption, dietary risks and low physical activity.

696-703

Authors: Raluca T. TATAR , Doina I. NACEA, Dan M. ENESCU

Introduction. Pyogenic granuloma (PG) is a vascular inflammatory hyperplasia involving the skin and oral mucosa, often associated with local irritation or trauma, or with pregnancy. Intraoral location usually affects the gingiva, but tumoral aspect can be misleading, especially in extra-gingival locations. A thorough assessment and diagnosis are therefore important for ensuring the proper treatment. Case presentation. We report the case of a 12-year-old boy who presented for a growing and bleeding tumour of his lower lip mucosa. The tumour was labeled as “hemangioma”. It was growing for several weeks and associated with minor, but repeated mucosal trauma. Although the anatomic location was not common, the patient history suggested a diagnosis of PG. After a dermatologic assessment, which proposed a differential diagnosis with oral papilloma, a soft tissue ultrasound sustained the clinical diagnosis. The tumour was surgically excised and the defect was closed directly with absorbable sutures. Three weeks later the mucosa had a healthy appearance, without signs of impaired healing or tumour recurrence. The histopathological exam confirmed the clinical diagnosis. Conclusions. There are several types of soft tissue solid or vascular tumours that can be mislabeled and the diagnosis of hemangioma is commonly used for various vascular anomalies. In our case, the clinical aspect, together with the tumoral growing pattern and the history of repeated trauma, led us to the correct diagnosis and treatment. Surgical excision completely removes the PG and ensures rapid and esthetically convenient healing, without complication or tumour regrowth.

710-715

Authors: Ninel REVENCO, Lucia MAZUR-NICORICI, Dina BUJOR, Ana-Mihaela BALANUTA, Silvia FOCA, Ion MIHU, Olga GAIDARJI

Introduction. Approaching the pediatric patient with joint pain is often a challenge, even for the most experienced clinicians. The diagnosis of inflammatory bowel disease in children may be difficult because of atypical symptoms and/or extraintestinal manifestations such as arthritis, weight loss, chronic anemia, unexplained fever. Case presentation. We present the case of a 13-year-old girl, presented initially with musculoskeletal complains, feverish, weight loss. After an extensive clinical and paraclinical examination and a proper differential diagnosis, the diagnosis of inflammatory bowel disease was established, confirmed by immunological investigations, colonoscopy with biopsy. The peculiarity of the clinical case translates into the onset of ulcerative colitis through extraintestinal manifestations, the main clinical manifestations being related to articular involvement. Conclusions. Overlap syndromes are a main challenge for clinicians. Inflammatory polyarticular syndrome in a child can often result in a benign self-limiting disease, but sometimes may reveal a serious chronic disease with significant morbidity. Ulcerative colitis diagnosed in children presenting with an amalgam of extraintestinal manifestations requires a multidisciplinary approach.

722-725

Authors: Konstantinos C. CHRISTODOULOU, Dimitrios A. STAKOS, Aliki Th. FISKA

Introduction. In 1706, Raymond de Vieussens described a proximal inter-coronary pathway connecting the conus branch of the right coronary artery (RCA) with an infundibular branch of the left anterior descending artery (LAD) or directly with the proximal LAD. Later, in the 19th century, this anatomical structure would be named in his honour “Vieussens’ arterial ring” (VAR). VAR serves as a collateral pathway in case of coronary artery disease. Case presentation. We present the case of a 58-year-old male with a concurrent ostial chronic total occlusion of the LAD and an acute thrombotic occlusion of the proximal RCA, that survived via a Vieussens’ arterial ring. Conclusions. The existence of collateral circulation holds a crucial role in the manifested symptoms and the prognosis of patients with ischaemic heart disease. The connection between the conus branch and the LAD (VAR) may provide adequate circulation to either the left or right coronary arterial system, preserving the left ventricular ejection fraction and allowing patients to survive even the most severe myocardial infarctions.

728-730

Authors: Christos TSAGKARIS, Konstantinos KALACHANIS, Panagiotis IAKOVIS, George ANDROUTSOS, Marianna KARAMANOU

Aristotle (384-322 BC), the founder of the peripatetic sect of philosophers was a polymath and his work covers almost every major area of human inquiry such as physics, biology, metaphysics, ethics, rhetoric and politics. However, it seems that he had an inclination for the investigation of nature and human being. The heart is considered by Aristotle as the source of life, the part wherein the “psychical fire” is kept burning, the place of passions where all the feelings end and the true seat of the soul. His notions on anatomy were revised by the physicians of the Alexandrian school of medicine, but they prevailed over centuries till the leading discovery of William Harvey (1578-1657) on blood circulation.

373-374

Authors: Camelia C. DIACONU

COVID-19 is an ongoing pandemic infectious disease determined by a new coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV-2). The severity spectrum of the clinical manifestations of the disease is variable, from almost asymptomatic cases to critical, fatal cases. The clinical manifestations usually include fever, dry cough, dyspnea, muscular symptoms, headache, sore throat, diarrhea, nausea/vomiting, abdominal pain, fatigue, loss of smell or taste. The laboratory tests in patients with COVID-19 may reveal lymphopenia, increased aminotransferases, high lactate dehydrogenase, inflammatory syndrome (high C-reactive protein, erythrocyte sedimentation rate, fibrinogen), coagulation tests abnormalities. There are recent reports and small studies that reported an association between COVID-19 and hyponatremia (serum natrium < 135 mEq/L) (1). A few case reports described patients with COVID-19 with only symptoms of hyponatremia(2). The etiology of hyponatremia in patients with COVID-19 is likely to be multifactorial and its early etiologic diagnosis may be extremely important for the evolution of the disease. For a correct diagnosis and treatment, measurement of plasma and urine osmolality is always necessary. An appropriate treatment of hyponatremia may be even more important in hospitalized patients with COVID-19, in whom an inadequate fluid and electrolyte management may increase the risk for respiratory and/or cardiac complications. What could be the causes of hyponatremia in COVID-19 patients? Hyponatremia may be due to the increased release of antidiuretic hormone (ADH) because of gastrointestinal fluid losses (diarrhea, vomiting) or low oral fluid intake, but also to the syndrome of inappropriate ADH secretion (SIADH) induced by pneumonia, respiratory insufficiency or other comorbidities. SIADH is characterized by euvolemic hyponatremia (natrium <135 mEq/L), low serum osmolality (<280 mosmol/Kg H2O), high urine osmolality (>100 mosmol/Kg H2O), increased urine natrium (>40 mmol/L), hypouricemia, in the absence of other causes of hyponatremia. Apart from pneumonia, that is frequent in patients with COVID-19, other causes of SIADH may be psychological and physical distress induced by the disease (with activation of the cortical neurons and increased hypothalamic secretion of ADH), and also the cytokine storm (with lesions of the pulmonary tissue that can induce SIADH and/or the non-osmotic release of ADH stimulated by interleukin-6)(3). The measurement of serum and urine osmolality will help the differential etiological diagnosis and will ensure a proper fluid and electrolyte management, to prevent further deterioration of these patients(4). The association of COVID-19 with hyponatremia needs to be further identified and explored. Until then, a careful approach may be that febrile patients presenting with hyponatremia should be isolated and tested for SARS-CoV-2 infection.

382-387

Authors: Feyzi KURT, Kalbim ARSLAN, Hasan BESIM

Introduction. Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are rare, unusual lesions, that most commonly appear in the right lobe of the liver. Clinical and radiological findings are very similar with liver hydatid cysts. Therefore, the differential diagnosis with liver hydatid cyst (LHC) is usually made by pathological examination, postoperatively. The objective of the study was to detect the prevalence of BCA and BCAC in patients who were treated for hydatid cysts. Material and methods. Data of 720 cases with operated liver hydatid cysts (LHC) at the General Surgery Clinics of Seyhan State Hospital Adana, Turkey, and Near East University Nicosia, Cyprus, were retrospectively reviewed. The study included 10 patients with BCA and two patients with BCAC, who were operated with a preliminary diagnosis of liver hydatid cyst. Results. Of the 12 patients included in the study, 5 were male and 7 were female. The mean age of the patients was 43.58 years. All patients were pre-diagnosed with liver hydatid cyst after preoperative laboratory and radiological evaluations and all underwent partial cystectomy. The results of histopathological examination showed that 10 of these patients had BCA and two had BCAC. The mean follow–up was 28.4 months. During this period, recurrence was seen in 3 out of 10 patients with BCA and total cystectomy was performed in these 3 patients. Two patients with BCAC underwent right hepatectomy. Conclusions. The follow-up and evaluation of the histopathological results are very important in patients operated with the diagnosis of liver hydatid cyst. Cases with biliary cystadenoma and cystadenocarcinoma, which are difficult to detect, especially in the preoperative period, should be re-evaluated and complementary operations should be performed.

398-409

Authors: Sergey LEE, Zarina ROZYBAKIEVA, Marat ASIMOV, Fatima BAGIYAROVA, Aygul TAZHIYEVA, Neilya USSEBAYEVA, Timur SALIEV, Shynar TANABAYEVA, Ildar FAKHRADIYEV

Introduction. Burnout is one of the major unresolved problems of healthcare professionals. Considering the recent situation with COVID-19 and associated psychological stress, this issue becomes high- critical over the world. Objective. The study aimed at validating the effectiveness of Asimov’s coping strategy among a group of primary care physicians in reducing emotional burnout. Material and methods. The study was conducted in Almaty (Kazakhstan). The volunteers (N = 243) were randomly divided into intervention group (IG) and control group (CG). In the IG, short-term psychotherapy based on the coping strategy (Asimov method) was implemented. Methods of measurement of emotional burnout included the use of emotional burnout (‘Maslach’) and Lazarus questionnaires. In addition, factors related to demography, work, and lifestyle were assessed as well. Results. The assessment of the emotional burnout showed a high level of emotional burnout in both groups (p>0.05). After 6 months, emotional exhaustion (EE) (p=0.019) and depersonalization (DP) (p=0.028) indicators in the IG group were reduced, in contrast to the CG group, except for the lack of personal achievement (PA) (p=0.067). However, after 12months, indicators of EE and DP were decreased, at the same time the PA indicator was elevated in the IG group (p <0.05). The data of the study based on the Lazarus questionnaire (12 months) showed the effectiveness of this method (p <0.05). Conclusions. The use of Asimov’s coping strategy showed a positive effect on the emotional status of primary care physicians. Such a strategy possesses the potential for the management of the psychological stability of doctors who underwent emotional burnout.

418-423

Authors: Sanda BURUIANA, Maria ROBU, Lucia MAZUR-NICORICI, Victor TOMACINSCHII, Minodora MAZUR

Introduction. Non-Hodgkin’s lymphoma (NHL) is a malignant cancer of the lymphatic system. Modern treatment of NHL allows patients to extend their lifespan, but at the same time somatic and psychological complications reduce the patients’ quality of life. The objective of the study was to assess the quality of life in patients with NHL. Material and methods. The study included patients with aggressive and indolent NHL. The quality of life was assessed using the standard assessment tools Eastern Cooperative Oncology Group (ECOG), Global Well-Being (GWB) and European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30. Results. The study included 56 NHL patients: 36 women, 20 men, with a mean age of 58.1±1.3 years. The ECOG Scale of Performance Status, the EORTC functional scales, global health status and GWB were according to the primary tumour. Higher values ​​of functional scales were recorded in patients with aggressive NHL (70%). The symptom scales assessment did not clearly vary in both types of lymphomas (70% aggressive, 63% indolent), and the “better” global health status predominated in indolent NHL (36.8%). In 64.3% of cases there is severe suffering, with the predominance in women (72.2%). Conclusions. Patients with indolent NHL had a higher degree of independence. The ECOG scale of NHL patients, regardless of morphological type, does not correspond to the stage of the disease, but to the location of the primary tumour and its size.

431-436

Authors: Martin P. LALEV, Vladislav M. NANKOV, Ludmil S. STOYANOV, Ivelin A. ANGELOV

Introduction. Blastocystis sp. is a common protozoan parasite that colonizes the intestinal tract of humans and animals and in humans nine subtypes have been described so far. Gastrointestinal symptoms and/or allergic reactions are the most common reported symptoms. It is considered that there could be a link between symptoms and the subtype of Blastocystis sp. The objective of the study was to determine the subtype of Blastocystis sp. isolates from a cohort of patients hospitalized in the University Hospital – Pleven, Bulgaria. Material and methods. Blastocystis sp. isolates were collected from hospitalized patients who were clinically referred for parasitological testing and genomic DNA was extracted from cultivated Blastocystis sp. samples. The isolated DNA was then used to perform subtype classification using known sequence-tagged site (STS) primers and RFLP analysis of small subunit (SSU) rRNA gene. Results. Blastocystis sp. was isolated from 42 out of the 261 tested patients – a prevalence of 16.09%. Out of the 42 Blastocystis sp. positive fecal samples, DNA was successfully extracted from 33. The isolated DNA belonged only to two subtypes – ST1 and ST3. No mixed subtypes were detected. Conclusions. We found that ST3 was more prevalent among patients with clinically presenting allergic diseases – 17 of the tested patients (65.38%). ST1 was isolated from patients with allergic and with gastro-intestinal symptoms.

446-452

Authors: Hristiana CAPROS

Introduction. Pulmonary embolism is an important public health problem in both developing and industrially developed countries. Diagnosis and management of pulmonary embolism remain a challenge for the current obstetrics practice, due to pregnancy-associated symptoms, which are sometimes similar to those of venous thromboembolism. The gold standard for diagnosis is computed tomography (CT) pulmonary angiography/ ventilation perfusion scanning, which imply radiation exposure for mother and fetus. Administration of “blind” anticoagulant therapy in pregnant women may increase the risk of hemorrhagic complications. The major challenge in these cases is to decide when angiography is really needed. Several algorithms and scores are proposed to avoid imaging techniques in these patients. The objective of the study was to evaluate local practices regarding the diagnosis of venous thromboembolism in the department of Obstetrics and gynecology of Louis Dommergues Hospital, Trinity, Martinique, and to compare them with the existing international guidelines. Material and methods. Presentation of series of cases with suspicion of venous thromboembolism investigated in the Department of Obstetrics and Gynecology of “Louis Dommergues” Hospital, Trinity, Martinique. Results. Initial diagnostic testing (electrocardiogram, blood gases, D-dimers, troponine, NT-proBNP) was performed for all pregnant patients presenting clinical suspicion of PE. According to the original Geneva score, the majority of patients had a high risk of PE (> 8 points) – 4 (44.44%) and 3 (33.33%) – intermediate (5 – 8 points) and 2 (22.22%) – low-risk of PE (0 – 5 points). PE was confirmed by angio-TC in 2 patients (22.22%). Conclusions. Clinical suspicion of pulmonary thromboembolism should lead to imaging techniques as CT angiography or ventilation/perfusion scanning. Abnormal blood gases, D-dimers, NT-pro BNP or electrocardiogram are not sufficient to confirm nor to invalidate the diagnosis.

462-469

Authors: Ton Nu Hong Hanh HUYEN, Anh Dung HOANG, Trong Khoan LE, Duc Hung NGUYEN, Hung PHUNG, Ha Chau TRINH, Trong Binh LE

Transarterial chemoembolization is a standard locoregional therapy for intermediate stage hepatocellular carcinoma. The tumour is typically supplied by the hepatic arteries, however, extrahepatic collateral arteries may significantly contribute parasitic blood supply to the tumour. Large and exophytic tumour, subcapsular location, direct invasion and adhesion to adjacent organs, hepatic artery dissection, stenosis and occlusion resulting from multiple embolizations are risk factors of extrahepatic collateral arteries. Understanding the prevalence and prediction of these parasitic supplies on pre-procedural imaging is of utmost importance for optimizing technical and clinical outcomes.

483-488

Authors: Veselin IVANOV, Ventsislav DIMOV, Tsonka LUKANOVA, Ivan POPADIIN, Nikola VLADOV

Introduction. Intestinal malrotation and hypertrophic pyloric stenosis (HPS) are both rare diseases, usually diagnosed during infancy. In the medical literature there are only a few reports about infants who suffer from a combination of these diseases. The simultaneous occurrence of both diseases in adult patients is extremely rare. However, in this case, the surgical approach has to be a combination of different techniques, aiming at treating each one of the diseases separately. Case presentation. A 37-years-old female patient who presented for upper gastrointestinal symptoms was diagnosed with adult hypertrophic pyloric stenosis (AHPS), intestinal malrotation and consequent dilated stomach. The diagnosis was based on the history, clinical findings, imaging examinations (X-ray, abdominal computed tomography), and gastroscopy. The surgical approach included division of Ladd’s band and Jaboulay pyloroplasty. Conclusions. The simultaneous occurrence of intestinal malrotation associated with AHPS is an extremely rare condition. Applying a combined surgical approach may have good postoperative results.

495-498

Authors: Rosen B. TSOLOV, Georgi Y. YORDANOV

Introduction. Dirofilariosis is caused by the filarial nematodes Dirofilaria (Nochtiella) repens and Dirofilaria immitis. The vectors are mosquitoes of the Culicidae family of the genus Anopheles, Aedes and Culex. Case presentation. We present the case of a 47-year-old woman, under treatment for suspected atheroma of the facial skin of the eye and nose. The patient presented to medical check-up without symptoms of pain or discomfort. After histological examination of the lesions, the diagnosis of “dirofilariosis repens” was established, a disease extremely rare in Bulgaria. Conclusions. Dirofilariasis repens is a parasitosis, with few cases reported in Bulgaria. It is believed to be a consequence of being bitten by insects from the Mediterranean region. Due to the nature of the disease and the small number of cases in Bulgaria, the diagnosis is difficult. The primary diagnoses are: neoplasms, lymphadenitis of unknown etiology, hydrocele, lipoma, dermoid cyst, fibroadenoma, neurofibroma, allergic conjunctivitis. In this case, the removal of the tumour and histological examination of the removed parasites were made, which guarantees diagnosis and treatment.

504-509

Authors: Volodymyr BUKATA, Andrii CHORNOMYDZ

Introduction. The development of obstructive jaundice caused by hepatobiliary ascariasis is quite rare. The main factors contributing to the occurrence of mechanical obstruction of bile leakage are the death of helminth in the lumen of the duct, the massive invasion of the biliary tract by ascarids, or the accompanying stenotic papillitis. Case presentation. We describe a case of obstructive jaundice in a woman with massive ascariasis of the biliary tract and stenotic papillitis. The treatment strategy consisted in endoscopic retrograde cholangiopancreatography (ERCP) with mechanical removal of helminths from the bile ducts, papillosphincterotomy, antihelmintic drugs and symptomatic therapy. Conclusions. Biliary ascariasis must enter into the differential diagnosis of biliary duct pathologies, especially in endemic regions for this parasitosis. ERCP may be an important therapeutic method for this disease.

518-522

Authors: Leonid I. DVORETSKY, Maria A. KARNAUSHKINA, Georgy O. ZAYRATIANTS, Elend V. SERGEEVA, Svetlana S. BOBKOVA

Introduction. Rhabdomyolysis (RM) is a clinical and laboratory syndrome resulting from skeletal muscle damage, with the release of a big number of intracellular substances of myocytes into the systemic circulation and endotoxemia. The entry of the muscle destruction products into the systemic circulation leads to the development of systemic manifestations, serious disorders in homeostasis, multiple organ failure syndrome, including acute renal failure, often threatening the patient’s life. Case report. A rare case of RM in a patient with staphylococcal sepsis (SS) and development of multiple organ failure is described. The diagnosis of RM was confirmed by the results of pathological and anatomical studies. Possible causes of RM in staphylococcal sepsis are discussed here. Conclusions. Only a few cases of RM upon SS were found in the literature. The development of RM in combination with the systemic inflammatory reaction syndrome in SS exacerbates the course of the disease and worsens its prognosis. Therefore, the timely diagnosis of RM and appropriate treatment are extremely important. The mechanism of RM development upon SS is complex. After staphylococcus was isolated from the affected muscles in a patient with SS, one of the first descriptions of RM upon SS suggested the role of direct invasion of the infectious agent into the muscles, followed by the development of “pyomyositis.” Another mechanism for RM occurrence of PM may be the presence of toxin upon the staphylococcal toxic shock syndrome in patients with SS.

527-531

Authors: Mihail TUSALIU, Iulia TITA, Diana TUAS, Ruxandra RANETE, Cristina GOANTA

Introduction. The aim of this article is to present the advantages of tracheoesophageal puncture using secondary placement of the voice prosthesis, at present the “gold standard” for voice rehabilitation in the laryngectomized patient with advanced cancer following total laryngectomy. Absence of voice and, therefore, inability to verbally communicate, constitutes one of the greatest challenges for laryngeal cancer patients, having a major impact on their quality of life. Case report. The authors illustrate the case of a 61-year-old patient diagnosed with advanced laryngeal cancer, who underwent total laryngectomy. After approximately one year, a voice prosthesis is installed. Phonation was immediate and close to natural laryngeal speech. Conclusions. From a functional, as well as psychological and social point of view, a laryngeal cancer diagnosis can have devastating consequences on all aspects of a patient’s life. Phonation recovery is thus essential for psychological well-being, labour and social reintegration. Correct understanding and management of this pathology and treatment options is of utmost importance in obtaining the best possible medium and long-term outcomes. Secondary placement of the voice prosthesis provides greater oncological safety as well as avoids common post-radiotherapy side effects.

203-205

Authors: Hongyun WANG, Xinyue ZHU, Junjie XIAO

Living forever is a beautiful vision that human being has been pursuing. With the development of science and technology, an increasing number of approaches have been emerging for repairing and regenerating the damaged organs, such as cell therapy, gene therapy and transplant etc. However, the side effects of these methods limit their clinical use. For example, myoblast transplantation leads to an increase in number of early postoperative arrhythmic events(1). Therefore, it has a long way to use these approaches for clinical therapy in a short-term and it is urgent to look for secure effective strategies. Recently, extracellular vesicles (EVs) have attracted extensive interests as a potential therapeutic strategy of diseases such as cancer, cardiovascular diseases etc. A growing number of investigations demonstrate that various engineered EVs can repair the damaged tissue in vivo(2). This editorial highlights 6 selected papers dedicated to the engineered extracellular vesicles as well as nanoparticles, including: 1) classical strategies for modifying EVs; 2) the roles of engineered EVs in treatment. Besides, the outlook for engineered EVs has been briefly discussed. To improve the efficiency of EVs as well as targeted tissue retention, several investigations were performed. Kyle et al firstly used a cardiomyocytes specific peptide (CMP) to make the cardiac-targeted EVs(3). It was then verified that the modified EVS (CMP- EVs) can be specifically taken up by cardio-myocytes both in vitro and in vivo. This approach laid the foundation for cell and cardiac-specific EVs delivery, which gives a reference for studying targeted-EV. Interestingly, Tang et al came up with a novel idea based on the recruitment of platelets by injured endothelial cells(4). These authors decorated platelet-microvesicles (inside of platelet, similar with EVs) on the surface of cardiosphere-derived cardiac stem cells (CSCs), which significantly increased the retention in the heart. This manipulation approach is safe and straightforward, which opens novel insights into targeted-EVs for therapy. Recently, Liming et al used an adhesive hydrogel to enhance the retention of EVs(5). The EVs were immobilized in an adhesive hydrogel (Exo-pGel) and the encapsulated-EVs can stay at the injured area. The Exo-pGel presents a promising strategy for preclinical treatment. It has been well established that the engineered EVs have great potential for disease treatment in animal models. Vandergriff et al systemically investigated the role of CMP- EVs in cardiac dysfunction treatment. The authors found that EVs conjugated with cardiac homing peptide (CHP, similar with CMP) can protect heart from ischemia/reperfusion injury owing to their increased retention(6). This work demonstrates a novel approach for increasing delivery of myocardial infarction treatment. Liu et al reported that EVs loading with novel complex hydrogels can promote wounds healing, which provides another effective hydrogel strategy for engineering EVs(7). Li et al investigated the roles of Exo-pGel in treatment of spinal cord injury. The Exo-pGel significantly promoted nerve recovery via inhibiting oxidative stress and inflammation5. Besides, Chuanjiang He et al give an insight into how EVs engineered as powerful tools in translational medicine(8). In conclusion, there are strategies for engineering EVs/nanoparticles, with potential roles in disease treatment. Notably, more preclinical investigations and clinical trials are still needed to elucidate the possibility of engineered EVs and nanoparticles in human diseases treatment.

215-223

Authors: Krystallenia I. ALEXANDRAKI , Georgios BOUTZIOS, Ioanna ANTONOPOULOU, Theodoros G. PAPAIOANNOU, Lamprini Iro BARTSIOKA, Panagiotis MOSCHOURIS, Angeliki KARAPANAGIOTI, Vasiliki MAVROEIDI, Konstantinos MAKRILAKIS, Leonidas DUNTAS, Gregory A. KALTSAS, Stavros LIATIS

Introduction. The association of autoimmune thyroid disease (AITD) with diabetes mellitus type-1 (DM1) has been previously documented. However, limited data exist regarding the association of AITD and diabetes mellitus type-2 (DM2). The objective of the study was to expose the role of AITD on DM2 and the impact of AITD in euthyroid patients with pre-diabetes. Euthyroid prediabetic patients were defined by impaired fasting glucose and/or glucose intolerance. Material and methods. We assessed static and dynamic insulin resistance (IRI) and insulin secretion indices (ISI), and the disposition index (DI). Results. Out of 166 patients studied, 31.9% had AITD; impaired fasting glucose (IFG) prevalence was the same with non-AITD patients. In contrast, impaired glucose tolerance (IGT) was less prevalent in AITD compared to non-AITD patients (9.4% versus 28.3%, p=0.008). IRI did not differ between the two groups. The dynamic ISI, 1st phase and 2nd phase insulin release, and the DI showed a worse insulin secretion in non-AITD compared to AITD patients (0.54 versus 0.45, p=0.029; 1029.3 versus 864.3, p=0.033; 354.8 versus 286.5, p=0.035; 0.09 versus 0.07, p=0.02, respectively). On the other hand, hsCRP was higher in AITD versus non-AITD individuals (p=0.008). Conclusions. Although individuals with pre-diabetes and AITD presented with higher levels of low-grade inflammation, their dynamic ISI and the DI, were less impaired.

233-242

Authors: Asparuh G. NIKOLOV , Maria L. TZEKOVA, Konstantin M. KOSTOV, Alexander B. BLAZHEV

Introduction. Matrix metalloproteinases (MMPs) are important target genes for angiotensin II (AII), which subsequently alters MMP expression in extracellular matrix (ECM) and lead to remodeling process. Objective. To investigate whether an association between serum levels of MMP-12, AII and left ventricular hypertrophy exists in patients with heart failure with mid-range ejection fraction (HFmrEF) and arterial hypertension (AH). Material and methods. 56 patients with HFmrEF and AH were examined, mean age 65.62±9.69 years, and 22 age and sex-matched healthy subjects, mean age 56.4±5.53 years. 41 patients had hypertension-mediated organ damage and 15 did not. Patients were divided in two subgroups: subjects with left ventricular hypertrophy (n=32), (HFmrEF+LVH), and subjects without left ventricular hypertrophy (n=24), (HFmrEF-LVH). ELISA was used for measuring AII and MMP-12. Results: Serum MMP-12 levels were statistically significant lower in patients, than in controls: 0.0033 ng/mL (0.0022 ÷ 0.0071) vs. 0.0075 ng/mL (0.0068 ÷ 0.016) (KW=7.37; p=0.006). MMP-12 showed correlation with grade of AH (r=0.28; p=0.03). Patients with HFmrEF+LVH showed statistically significant higher levels of AII: 8.533 pg/mL (1.477÷13.009) than HFmrEF-LVH 1.333 pg/mL (0.477÷6.932) and healthy controls 1.539 pg/mL (0.274÷5.218); (KW=3.48; p=0.04). AII correlated with stage of AH (r=0.47; p=0.001). MMP-12/AII ratio was significantly higher in patients with HFmrEF+LVH than in HFmrEF-LVH 3.867 vs. 0.0025 (p<0.001). Conclusions. Our data suggest an association between serum MMP-12 levels, AII and grade and stage of AH. Determination of serum MMP-12/Angiotensin II profile may be a useful method for monitoring of development and progression of left ventricular hypertrophy.

250-256

Authors: Andrei BRADU , Pavel BANOV, Emil CEBAN

Introduction. Urinary lithiasis is an important health issue, with an estimated prevalence of 2-3% in the general population and about 70% of recurrence rate. The objective of the study. To evaluate the efficacy of combined medication (potassium and magnesium tribasic citrate and pyridoxine) versus traditional general recommendations, in removing the remaining stone fragments after extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy. Material and methods. The study enrolled 60 patients after kidney or ureteral stones treatment performed by extracorporeal shock wave lithotripsy (ESWL), with signs of calculus disintegration, ureteroscopy (URS) with contact lithotripsy, and after percutaneous nephrolithotomy (PNL). The patients were randomly divided into 2 groups. Patients from Group I (n=30) were administered potassium citrate tribasic 2.7 gr, magnesium citrate tribasic 376 mg, pyridoxine 25 mg in sachet, twice daily for two months. The control group (Group II), initially consisting of 30 patients, was prescribed only general recommendations. Results. The increase in daily diuresis was statistically significant compared to the control group (2275±257 mL vs 1580 ± 321 mL, p <0.05). The urine pH in the study group was statistically significant higher (7.1±0.3) compared to the control group (6.2±0.9), p <0.01. The renal colic during the expulsion period of disintegrated calculus fragments was present in 1.8±0.3 cases (study group) compared with 6.7±0.8 (control group), p> 0.001. The „stone-free“ rate was the basic index of the study. The rate of spontaneous removal of disintegrated stone fragments was 90.0% in the study group compared with 71.4% in the control group (p <0.05). The visual analogue scale (VAS) score was 4 points in the study group and 7 points in the control group. Conclusions. The addition of combined therapy in the postoperative treatment of urinary calculi reduces the expulsion time of disintegrated calculus fragments, the number of attacks of renal colic and possibly the need for analgesic administration.

264-268

Authors: Andrei BRADU, Emil CEBAN

Introduction. Due to the increase in the incidence of reno-ureteral lithiasis worldwide from 1% to 15%, varying according to age, sex, race, and geographical location, extracorporeal shock wave lithotripsy remains the method of choice in the treatment of reno-ureteral lithiasis. The need for antibacterial prophylaxis is required only in well-defined cases, uroculture with antibacterial sensitivity being crucial in order to reduce the infectious complications. The objective of the study was to evaluate the need for antibiotic administration and to detect risk factors for the development of post-ESWL bacteriuria. Material and methods. Between 05 Nov 2018 – 10 Dec 2019, a group of 120 patients with the diagnosis of reno-ureteral lithiasis was selected, who underwent ESWL treatment in Department of Urology and Surgical Nephrology from Republican Clinical Hospital „Timofei Mosneaga“. In all 120 patients, urine sample was taken before and after ESWL. In all patients included in the study, uroculture with antibiogram was performed. Results. The uroculture results obtained before ESWL were positive in 25 (20.84%) patients without any clinical symptoms and absence of leukocytes in the general urine analysis more than 10 per high power field. At the same time, the number of positive urine culture after ESWL increased significantly in 47 patients. Conclusions. Antibiotic prophylaxis is not justified in the absence of definite risk factors such as positive urine culture before ESWL, JJ stent or nephrostome and a history of infectious reno-ureteral lithiasis or recurrent urinary tract infections.

278-283

Authors: Iryna I. KARPENKO , Elina Yu. FROLOVA-ROMANIUK, Natalia M. ZHELEZNIAKOVA

Introduction. The high medical and social significance of type 2 diabetes mellitus (T2DM) is not only due to its prevalence, but also to serious complications that lead to a decrease in the quality of patients’ life, early disability, and high mortality. The objective of the study was to evaluate the histological and morphometric features of the oesophagus mucous membrane in patients with gastroesophageal reflux disease (GERD) and T2DM compared to patients with GERD without T2DM. Material and methods. 67 patients with GERD and T2DM and 50 patients with GERD without T2DM, matched for age and sex, were examined. Comparative morphometry of histological changes of the oesophageal mucosa was performed. Results. The histological investigation showed that in patients of the main study group (with GERD and T2DM), almost all the studied parameters had a significantly more severe course and exceeded similar indicators of the group with isolated GERD: the thickness of the basal layer (1.86±0.04 points against 0.97±0.02 points), papillae height (1.71±0.06 points versus 0.72±0.07 points), inflammatory epithelial infiltration (1.88±0.03 points against 1.27±0.07 points), width of intercellular spaces (2.04±0.08 against 1.10±0.07 points) (p<0.01 in all cases). Conclusions. The inflammatory process in the oesophageal mucosae in patients with GERD without T2DM has a more superficial character and is limited mainly to the epithelial layer, whereas hyperplastic changes in the mucous membrane of the oesophagus are more pronounced in patients with GERD and T2DM.

290-297

Authors: Leila ALI, Reza ALAGHEHBANDAN, Valentin T. MOLDOVAN, Diana DEREWICZ, Anca M. CORICOVAC, Octav GINGHINA, Maria SAJIN, Mariana COSTACHE

Introduction. The most important histologic prognostic factors for melanoma remain depth of invasion and mitotic rate. In a digital era, precision (in terms of reproducibility and inter laboratories repeatability), as well as image evidence, are new qualitative parameters. The objective of the study was to evaluate in a retrospective analysis any significant difference among the Breslow digital assessments performed using two different immunohistochemical stains and the gold standard, hematoxylin eosin stain. Material and methods. We evaluated 130 primary cutaneous melanomas diagnosed in a two-year period (2016-2017) with known Breslow scale. Immunohistochemistry staining (SOX10 and Melan A) was perform followed by slide scanning. Aperio Imagescope and StataCorp software were used for data acquisition and statics. Results. No significantly statistic differences were recorded between groups in terms of Breslow values (p=0.98, Kruskal-Wallis test). Conclusions. All three stains perform similar in evaluating depth of invasion regardless of the method used to quantify it. The pathologist should consider using an accurate and precise method like a digital measurement technique for daily reports.

304-311

Authors: Mihail BANACU, Bogdan SOCEA, Adrian PELINARU, Ioan LASCAR

Introduction. Ovarian cancer is characterized by a high capacity of relapse, even in cases in whom cytoreductive surgery with curative intent followed by platinum and taxanes-based chemotherapy were performed. In such cases, attention was focused on determining if iterative cytoreduction might improve the long-term outcomes and how far these boundaries can be pushed. While for secondary cytoreduction multiple studies have been conducted, for tertiary and quaternary cytoreduction data are significantly scarcer. The objective of the study. This paper aims to realize a systematic review of the studies published so far on the theme of quaternary cytoreduction. Methodology. We searched medical journals in English language published from January 2010 to December 2019. Results. Six studies involving 110 patients submitted to quaternary cytoreduction met the inclusion criteria. Data reported in the above mentioned studies demonstrate that quaternary cytoreduction can be safely performed both at the level of the lower and the upper abdomen, in order to maximize the debulking effort. However, a significantly lower number of cases will be considered candidates for this type of procedure, when compared to secondary or even tertiary cytoreduction, an adequate selection process being mandatory in order to minimize the postoperative risks. Conclusions. Although it is less frequently feasible when compared to secondary or tertiary cytoreduction, quaternary cytoreduction might be beneficial in selected cases.

320-323

Authors: Nicolae BACALBASA, Irina BALESCU, Mihaela VILCU, Ioana HALMACIU , Camelia C. DIACONU, Simona DIMA, Iulian BREZEAN

Krukenberg tumors are ovarian metastases from different malignancies, most often originating from the gastrointestinal tract. However, in rare cases, other primary tumors, even with extra-abdominal location, might lead to the development of such lesions. Neither the mechanism of development, prognostic significance or therapeutic strategy are not clearly defined so far. It seems that these lesions are more frequently encountered in patients with BRCA1/2 mutations. Most often, Krukenberg tumors are bilateral lesions associated with ascites and with firm areas at the level of the ovarian surface. This paper aims to review existing data regarding Krukenberg tumors from breast cancer.

329-332

Authors: Catalin G. BEJINARIU, Romana MANESCU, Laura M. BOGHIAN, Matei GHEORGHIU – BRANARU, Siramona POPESCU, Silviu A. MARINESCU

Introduction. Scalp tumours raise multiple problems regarding the radical excision of the neoplasm followed by reconstructive surgery. Prolonged sun exposure and administration of immunosuppressive medication are the main risk factors for the onset of this neoplasm. The paper presents the advantages and disadvantages of scalp reconstruction using rhomboid flaps, after surgical excision of the skin cancer. Case presentation. The paper presents the case of a 83-year-old patient admitted for the treatment of squamous cell carcinoma located on the scalp. The pathological history of the patient showed that there were multiple hospitalizations for the treatment of chronic heart failure and hypertension. The therapeutic protocol included excision of a squamous cell carcinoma located in the scalp, followed by immediate reconstruction with three rhomboid flaps advanced towards the midline. The local evolution of the patient was favorable, the flaps integrating without complications, obtaining in this context a very good result from an aesthetic point of view. Conclusions. The use of the reconstructive technique involving the transposition of three rhomboid flaps to cover the soft tissue defects located in the scalp region is a feasible solution that offers very good aesthetic results.

339-344

Authors: Raluca GRIGORE, Anca I. CIRSTEA, Paula BEJENARU, Catrinel B. SIMION-ANTONIE, Gloria S. MUNTEANU, Alexandru NICOLAESCU, Mihnea CONDEESCU-COJOCARITA, Serban V.G. BERTESTEANU

Introduction. Paragangliomas are benign tumours that arise from the paraganglionic system. The most frequently encountered symptoms of tympanojugular paragangliomas are pulsatile tinnitus and conductive hearing loss. High resolution computed tomography, with reconstruction in axial and coronal planes, is mandatory in every suspected case of tympanojugular paraganglioma. The treatment is guided by the classification of Fish. Cases presentation. We present two cases in whom the clinical manifestations and paraclinical investigations established the diagnosis of tympanojugular paraganglioma. Both surgery and postoperative evolution are described for each case. In most of these tumours, surgery remains the mainstay treatment. According to the preoperative plan of the first case, it was decided that the tumour can be resected safely, without compromising the cranial nerves. In the second case, the entire tumour was removed, but with the sacrifice of the inferior cranial nerve, caught in the tumour mass. Conclusions. These tumours have the tendency to involve multiple vital structures of the skull base. A detailed preoperative plan of treatment is required to maximize tumour resection, while minimizing morbidity of the great vessels and lower cranial nerves.

350-357

Authors: Iryna CHORNOMYDZ, Oksana BOYARCHUK, Andrii CHORNOMYDZ , Natalia YAREMA, Uliana MUDRYK

Introduction. Stevens-Johnson syndrome is a rare, severe and life-threatening condition that develops mostly in response to drug use. Case presentation. We present a case of Stevens-Johnson syndrome in a boy of 11 years old, most probably developed in response to a combination of etiologic factors, such as virus infection, use of ibuprofen, and topical use of sulfanilamide agents. The clinical picture of the child was suggestive, involving tunica mucosa of mouth, genitals, conjunctiva, and skin. Parenteral administration of glucocorticoids, detoxification, antibiotic prophylaxis, and topical treatment led to rapid regression of clinical symptoms and prevented the development of complications. Conclusions. The treatment of Stevens-Johnson syndrome involves systemic glucocorticoids in combination with topical therapy. In our patient, the treatment avoided serious complications and led to rapid regression of cutaneous manifestations. The etiology of Stevens-Johnson syndrome is sometimes difficult to establish. Physicians should avoid polypragmasia and unreasonable prescription of drugs and be aware of the risk of Stevens-Johnson syndrome, especially in pediatric patients.

361-362

Authors: Petru E. MUNTEAN, Cristina G. NECULCEA

On 18th of April 2020, a 49-year-old woman developed a fever of 38.40C, with no other symptoms. After taking oral nonsteroidal anti-inflammatory agents for 2 days, the temperature returned to normal. On 20th of April 2020, she complained of persistent dry cough, sore throat, ageusia, anosmia and chest distress. The next day, she presented to the Emergency Department of Arges County Hospital, Pitesti, Romania. She divulged that she had been in close contact with a friend, who had been recently confirmed with the diagnosis of COVID-19. A high-resolution computed tomography (CT) of the chest was performed, that revealed multiple images of patchy ground-glass opacities in bilateral lower lobes (Figure 1). Given the close contact history and imaging findings, she was admitted as a suspected case of SARS-CoV-2 infection. On admission, physical examination unveiled normal vital signs, with oxygen saturation of 96% while breathing ambient air, lung auscultation normal. The antigen test for influenza was negative. Arterial blood gas analysis pointed out a pO2 of 103 mmHg, potassium 3.3 mEq/L, calcium 1.09 mmol/L and glucose 113 mg/dL. The blood routine tests revealed: white blood cell count 3.99 10^9/Liter, red blood cell count 6.41 10^12/Liter, hemoglobin 13.4 g/dL, hematocrit 40.1%, neutrophils 1.99 10^9/Liter, lymphocytes 39.9%, D-dimers 0.526 ug/mL, troponin T 7.22 ng/L, ferritin 192 ng/mL, procalcitonin 15 ug/L, creatine kinase-MB 27 U/L, lactic acid dehydrogenase (LDH) 481 U/L, fibrinogen 455 mg/dL, normal liver and renal function, normal prothrombin time. The electrocardiogram was normal. On 22th of April, the lab confirmed that the oropharyngeal swab test of SARS-CoV-2 by qualitative real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay was positive. After seven days of symptomatic treatment and hydroxychloroquine therapy, the patient’s respiratory symptoms significantly improved. The dynamics of high-resolution CT of the chest revealed systematic absorption of lung lesions (Figure 2). After two consecutive (24 hours apart) oropharyngeal swab tests of SARS-CoV-2 RNA negative, the patient was discharged on 30th of April, with the indication for home quarantine for at least 14 days. SARS-CoV-2 RNA by oropharyngeal swab remained negative in the follow-up visit on 13th of May 2020. Take home messages: The accuracy of chest CT in symptomatic patients with COVID-19 is high, but used as a single diagnostic test, CT can not accurately diagnose or exclude coronavirus infection and should not be relied upon as a screening or diagnostic tool for COVID-19 pneumonia. Chest CT is rather helpful in evaluating the complications of COVID-19 and is indicated in patients with COVID-19 and worsening respiratory symptoms. The most common imaging findings are of an atypical or organising pneumonia, with bilateral involvement, especially of the lower lobes. Point of care lung ultrasound may be useful for the diagnosis and can detect abnormalities even in asymptomatic patients. The definitive diagnostic test for SARS-CoV-2 infection is the RT-PCR test.

11-13

Authors: Camelia C. DIACONU

A novel coronavirus (nCoV) was first identified amid a recent outbreak of respiratory disease cases in China, Wuhan City. This infection was initially reported to the World Health Organization (WHO) on December 31, 2019. One month later, the WHO declared the 2019-nCoV outbreak a global health emergency(1). The WHO named the disease caused by 2019-nCoV as COVID-19, an acronym derived from “coronavirus disease 2019”. According to WHO, “Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). A novel coronavirus (nCoV) is a new strain which has not been previously identified in humans”(2). The recent emergence of COVID-19 in China raised many questions regarding risk factors in the general population, transmission patterns, clinical characteristics, efficient protection methods for health workers or in household and other settings. The medical world is also concerned about the most appropriate means to predict the future evolution of the disease and to limit human-to-human transmission, preventing also further international spread from China. The rapid identification of the new cases and close follow up of their contacts, together with preventive health measures for travelers may be useful methods to prevent a possible pandemia of COVID-19. In mid-February 2020, COVID-19 has been confirmed in more than 64,000 individuals (the majority in China) and has resulted in more than 1300 deaths. The respiratory infection has been reported also in other countries from Middle East, Europe, United States etc. The disease seems to be transmitted by respiratory droplets from sneezing or cough and is usually limited to close contacts with the patients, such as family members and healthcare workers. A more severe evolution was encountered in elderly patients, with comorbidities(3). There are no validated diagnostic tests for COVID-19. In the USA, the Center for Disease Control has developed a diagnostic test and has requested special emergency authorization from the Food and Drug Administration for its use4. This test is a real-time reverse transcription–polymerase chain reaction (rRT-PCR) assay and can diagnose the virus in respiratory and serum samples from clinical specimens. There is no specific treatment until now for infections with COVID-19, the treatment is only supportive. Researchers have started to investigate possible drug treatments for COVID-19. In China there are more than 80 running or pending clinical trials on potential treatments for COVID-19, including old traditional Chinese therapies. Some of these studies were criticized because of their study protocol, lack of specific standards, such as methods of randomization, control groups and measures of clinical outcomes. Until now, there is no specific cure for the disease. The WHO initiated a clinical trial that will compare two or three therapies supported by initial scientific evidence, a HIV-drug combination (lopinavir and ritonavir) and an experimental antiviral (remdesivir). Up to now, the most important measure is the prevention of infection, by limiting the contact with potentially infected patients, travel restrictions for persons originating in the endemic areas of China, use of protection equipment (surgical masks, gloves, protection eyeglasses etc).

22-30

Authors: Andrii V. PANTUS, Mykola M. ROZHKO, Roman V. KUTSYK, Ruslan V. KOZOVYI, Mykola V. MELNICHUK

Introduction. Combinations of fibrous materials with therapeutic agents as a drug delivery system are currently studied. A new direction has appeared in reconstructive surgery – tissue engineering, which aims to restore biological functions, i.e. tissue regeneration, not only to replace it with synthetic material. The objective of the study was to evaluate the antibiotic-sorbing ability of the three-dimensional non-woven matrices we created for reconstructing bone defects, made of polycaprolactone, and the possibility of releasing the impregnated antibiotic from the matrix material. Materials and methods. The study was conducted in the Department of Surgical Dentistry of Ivano-Frankivsk National Medical University, Ukraine, between September 12, 2019 – October 3, 2019. We used samples of three-dimensional micro-fibrous non-woven matrix for the defects’ reconstruction of the bone tissue made of polycaprolactone according to the developed technique. Collagen fragments were used as control. Results. The evaluation of the preservation of antibiotics in samples of matrix materials was performed on the 1st, 3rd, 5th, 7th, 14th, 18th and 21st day of the experiment. The obtained experimental data indicate that both drugs (cefazolin and lincomycin) were stored in significant quantities both in the collagen and the polycaprolactone matrix, throughout the entire observation period. Lincomycin impregnated in the polymer matrix is less stable during storage than cefazolin. Antibiotics impregnated in the collagen matrix are stored slightly better than when impregnated into polycaprolactone, due to a smaller pore diameter in collagen and, accordingly, a better expressed capillary effect. Conclusions. The developed matrix materials are a mean of a one-time local delivery of the drug to tissues in the damaged zone. This is especially relevant in surgical dentistry, since even strict adherence to aseptic rules cannot ensure that individual microbial cells from the surface of the oral mucosa and saliva get into the surgery area.

40-46

Authors: Tetiana KONDRATIUK , Yuriy ODINETS, Tetiana GORBACH, Victoria KOVAL

Introduction. The mortality rate from complications of acute lymphoblastic leukemia (ALL) in children is high and exceeds the mortality rate from relapse of leukaemia. Ultrahigh expression of HSP 70 is associated with treatment resistance and is an adverse clinical outcome in ALL in children. The objective of the study was to evaluate the dynamics of the level of HSP 70 in the blood serum of children with ALL. Material and methods. 46 children with ALL were studied. Before the start of treatment, the level of HSP 70 in the blood serum has been studied (n = 46). In case of appearance of complications during the conduction of the remission induction, the HSP 70 has been restudied in blood serum (n = 29). Results. HSP 70 is significantly increased in children with ALL. A significant decrease in HSP 70 in the blood serum of patients with induction therapy was revealed compared with the initial level of this protein (p <0.05). No correlation between the level of HSP 70 in the blood serum of children with ALL and the manifestations of chemotherapy complications has been found. In contrast to previous studies, we did not find a significant effect of HSP 70 on mortality. Conclusions. Induction therapy leads to a decrease in the level of HSP 70 in the blood serum of children with ALL. We did not find a direct correlation between the occurrence of complications during induction therapy and HSP 70 concentration in the blood serum.

55-63

Authors: Narindra N.M. RAZAFIMANJATO , Guillaume O. TSIAMBANIZAFY, Manjakaniaina RAVOATRARILANDY, Henri J.C. RAZAFIMAHANDRY, Luc H. SAMISON, Andriambelo T. RAJAONERA, Hanitrala J.L. RAKOTOVAO

Introduction. Penetrating wounds of thorax are frequent and require specific cares. The target of this study is to describe the epidemiological, clinical, therapeutic and progressive aspects of penetrating wounds of thorax by stabbing. Material and methods. This is a retrospective study of 73 patients with thoracic wounds by stabbing hospitalized at the Thoracic Surgery Department of University Hospital Center Joseph Ravoahangy Andrianavalona, Madagascar, from January 01, 2015 to January 31, 2018. Results. The mean age was 31.5 years, with a male predominance (89.04%). Most of the patients were in the tertiary sector (56.16%). Most of the cases were criminal assaults (by an unknown person = 91.78%). The thoracic lesions seen were fluid effusion in 58.9%, mixed in 32.88% and air in 6.85%. The association with limb trauma was the most common (16.44%). Chest drainage was performed in 67.12% of cases, thoracotomy in 1.37%. Evolution was favourable for most of the cases (90.41%). We found complications in 9.59% of the patients. Conclusions. Penetrating thoracic wounds by stabbing are frequent and represent an emergency, but patients often arrive late due to remoteness, financial problems, and neglect of chest wounds. Keywords: chest drainage, penetrating wound, stabbing, thoracotomy, video-thoracoscopy.

72-79

Authors: Viktor O. SHIDLOVSKYI, Oleander V. SHIDLOVSKYI, Michael I. SHEREMET , Igor M. PAVLOVSKYI, Gennady S. KUROCHKIN, Viktoria V. KRAVTSIV, Olga V. SKOCHYLO, Hanna P. HAPLYK, Vitaliy V. MAKSYMYUK, Volodimir V. TARABANCHUK, Nina P. TKACHUK, Antonina A. PIDDUBNA

Introduction. The surgical treatment of goiter with severe thyrotoxicosis may lead to an improvement of the general condition of the patient, and amelioration of the clinical manifestations of thyrotoxic cardiomyopathy. The aim of the study was to evaluate the long-term results of surgical treatment in patients with toxic goiter and severe thyrotoxicosis, including the study of changes in cardiac activity and the level of physical activity. Materials and methods. The study was conducted in 123 patients with toxic goiter and severe thyrotoxicosis treated surgically. The duration of thyrotoxicosis ranged from 18 to 74 months. Before the surgical treatment and one year after it, structural and functional changes of the heart were studied by echocardiography and electrocardiogram, and physical activity according to the six-minute walk test. The long-term effects of treatment were considered good, satisfactory, unsatisfactory and ineffective. Results. The results of surgical treatment depend on the severity of the manifestations of thyrotoxic cardiomyopathy. Good and satisfactory results were obtained in 44.7% cases, unsatisfactory results in 32.5% and ineffective treatment was found in 22.8% cases. Conclusions. The surgical treatment of patients with toxic goiter and severe thyrotoxicosis allows eliminating thyrotoxicosis and in some patients the rhythm disorders, reducing the intensity of clinical manifestations of thyrotoxic cardiomyopathy and improving the capacity of physical activity

87-97

Authors: Raluca GRIGORE, Alina L. A. OANCEA , Catrinel SIMION-ANTONIE, Bogdan POPESCU, Liliana NITU, Paula BEJENARU, Gloria MUNTEANU, Anca CIRSTEA, Mihnea CONDEESCU, Luiza SIRETEANU, Amer OTHMAN, Bianca TAHER, Simona RUJAN, Ruxandra NEDELCU, Teodora DIACONU, Denisa MITRAN, Elena ARJOCA, Teodora POPA, Claudiu CURCA, Roxana ANDRONE, Alisa DIMCEA, Alexandru NICOLAESCU, Serban V.G. BERTESTEANU

Introduction. The quality of life of patients after total laryngectomy is influenced by both the disease and the radical therapeutic interventions. After surgical treatment, vocal rehabilitation, along with pulmonary and deglutition rehabilitation, are necessary. The objective of the study was to assess the quality of life in patients with total laryngectomy. Materials and methods. A questionnaire with 14 questions was randomly addressed to 100 patients with total laryngectomy who presented to Coltea Clinical Hospital, Bucharest, Romania, over a period of three months. Results. Fifty patients answered that they had no pain. Regarding everyday activities, 34 patients answered that they were as active as before surgery. Regarding their appearance, 50 patients answered that there is no change, or the change is minor, while 39 answered that their appearance bothers them, but they remain active, and 5 answered that they feel disfigured and limit their activity, while 6 patients answered that they cannot be with other people because of their aspect. 34 patients answered that they could swallow as well as prior to surgery, other 34 patients answered that they cannot swallow certain foods, while 21 answered that they only swallow liquid food or are dependent on a feeding tube. Regarding everyday activity, 67 patients answered there are times when they cannot keep up with their old pace, but they get out of the house and enjoy life. About their mood, 38 patients answered that they were not in a good mood, nor depressed, while 36 said their mood is generally good and only occasionally affected by cancer. Six patients answered that their mood is excellent, while 15 patients were somewhat depressed and 5 were extremely depressed. Conclusions. The quality of life is influenced by the patients’ appearance after total laryngectomy, and their ability to maintain everyday activities. Swallowing, taste and saliva quality have a great impact on the quality of life of patients with total laryngectomy and also influence their nutritional status.

108-112

Authors: Mariam MUKERIA, Besik KIKNADZE, Tengiz VERULAVA

Introduction. Tobacco consumption is one of the global problems that creates serious health risks. The Georgian anti-tobacco law was accepted on 2017. The objective of the study. The research aims to evaluate the effectiveness of tobacco control legislation on tobacco consumption by students in Georgia. Material and methods. A focus group method was used within qualitative research. A nonprobability sampling method and its most convenient type – a snowball sampling was used for the respondent selection. Respondents were the students of Tbilisi State University (Georgia). The group was comprised of Ilia State University undergraduate and postgraduate students (Tbilisi, Georgia). A total of 14 respondents were interviewed: 6 women and 8 men male. The age of the participants ranged from 20 to 24 years. Results. Respondents began smoking between the ages of 14-16 years old. Regarding the reasons to begin smoking, the subjects attributed the decision to a mild curiosity spurned by a positive atmosphere of social encouragement. Respondents are aware of the amendments to the Tobacco Control Law, they being more or less aware of the prohibitions that followed, and what sanctions would be imposed in case of violations. Ten respondents positively evaluate these changes and believe that the positive results are noticeable in the short-term. Conclusions. It is advisable to facilitate the preventing measures of tobacco consumption. In this regard, it is welcome to introduce the Law on Tobacco Control in Georgia that prohibits tobacco consumption and advertising in public places, particularly in educational and other institutions, as well as selling tobacco products near schools.

121-127

Authors: Vanya RANGELOVA , Ani KEVORKYAN, Maya KRASTEVA

Neonates admitted for intensive care are a highly vulnerable population of patients, susceptible to infections. In newborns, the nosocomial infections have characteristics that are not seen in any other group of patients. The incidence rate of nosocomial infections in newborns is one of the highest and there are differences in this rate between developed and developing countries. The etiology of nosocomial infections in intensive care units is diverse and the causative agents might be bacteria, viruses or fungi. There are numerous risk factors associated with the characteristics of the patients, the hospital-stay and the level of care provided, that might increase the risk of nosocomial infections.

134-137

Authors: Spyridon N. MICHALEAS, Gregory TSOUCALAS, Konstantinos LAIOS, Marianna KARAMANOU , George ANDROUTSOS

Biochemistry or biological chemistry is the science that studies all the chemical processes that take place in the living organism of humans, animals, protozoa and plants. In our article we reveal, the contribution of distinguished scientists to this field at the early 20th century tracing also the first steps of the scientific development of biochemistry.

146-153

Authors: Anca EVSEI, Javier F. ANDREU, Carmen M. BLAZQUEZ MAÑA2, Inmaculada M. MENDEZ COCA2, Ruben CARRERA SALA2, Jose A. VAZQUEZ LUQUE, Carmen M. RAMOS GUIJO, Rosa M. RODRIGUEZ MILLAN, Mircea GHEORGHE, Adelina BIRCEANU-COROBEA , Narcis COPCA

Introduction. Myofibroblastomas of the breast are rare mesenchymal lesions thought to be derived from a CD34-positive mammary stromal cell that shows a great capacity for multipotency. Cases presentation. We performed a retrospective analysis of 4 cases with confirmed mammary myofibroblastomas. Hematoxylin and eosin slides and immunohistochemical slides were reviewed. For next-generation sequencing studies we used a TruSight Tumor 15 panel which ran in a MiSeq sequencer and was analyzed with illumina VariantStudio 3.0 and IGV (Integrative Genomic Variation). The case series consisted of 4 patients (3 men, 1 woman). The anatomic location distribution was equal, with a 1:1 ratio between the left and right breast and a gross median size of the lesion of 34 mm. Gross features revealed a well circumscribed lesion with a vaguely lobular cut surface and the microscopical features were that of a classic-type MFB composed of benign, spindle-shaped cells interrupted by thick collagen fibers that show extensive hyalinization. CD34 and desmin immunohistochemical markers were diffusely positive in tumor cells, thus confirming the diagnosis. Next generation sequencing used a TruSight Panel 15 and revealed mutations in TP53, p.P72R gene in two cases and in ERBB2 p.1655V, KIT c.2484C>T, GUSB p.V270M genes in one case. No pathogenic mutations were identified. Conclusions. The diagnosis of these tumors is challenging based on the rareness of these lesions. Molecular analyses are important to confirm the diagnosis based on morphology and immunohistochemistry. Given the fact that these tumors are rare and benign, there is little data about the molecular signature of this tumor.

159-162

Authors: Florin GROSEANU, Roxana MORARU, Cristian BUDICA, Bogdan SOCEA, Gabriela SOARE, Stefan CRISTEA

Open fractures are orthopedic emergencies that require immediate surgical intervention in order to provide fracture stabilization and to prevent development of osteitis. We present the case of a 33-years-old patient presented in our clinic for a type IIIB neglected open fracture of the distal tibia. We used external fixation for fracture stabilization and a distal based fasciocutaneous sural flap for covering the wound. The purpose was to obtain union of the tibia and reducing the risk of infection. The results at 6 months are good, but the patient needs to be closely followed in time.

168-173

Authors: Petru E. MUNTEAN

Introduction. Tuberculosis is a common and treatable human immunodeficiency virus-related (HIV) disease. Intestinal tuberculosis is much more recurrent in immunocompromised patients and presents as a complication of pulmonary tuberculosis due to swallow of infected sputum, hematogenic dissemination or even ingestion of contaminated milk. There is a strong need for close collaboration between HIV programmes and tuberculosis programmes. Case presentation. A 48-year-old male patient presented for a three month history of frequent bowel movements (3-4 stools per day, without blood or mucus), a weight loss of eight kilograms, infrequent dry cough, fatigue, esophageal candidiasis, anorexia, persistent low-grade fever and intermittent pain in the right lower abdominal quadrant. Abdominal X-Ray revealed a marked dilatation of the small intestine. High resolution axial computed tomography described thickening of the terminal ileum and medial caecal wall, with slightly enlarged low density nodes. Histopathological examination of the intestinal mucosa revealed granulomatous design and caseous necrosis. The positive diagnosis was primary extrapulmonary multidrug-resistant tuberculosis with HIV infection. He received an individualized and second line antituberculous treatment combined with antiretroviral therapy. Later on, he developed pneumonia with Pneumocystis jirovecii. The patient had a good clinical response to all therapies. Conclusions. Physicians should be aware that intestinal tuberculosis must be considered in the differential diagnosis of patients with abdominal symptoms, especially in immunocompromised patients.

182-185

Authors: Mirela TIGLIS, Cristina BOLOGA, Tudor HURMUZACHE, Tiberiu P. NEAGU , Camelia C. DIACONU, Ovidiu G. BRATU, Ioana M. GRINTESCU

Introduction. Ischemic colitis develops due to acute reduced blood flow through the colon and appearance of secondary reperfusion injuries. Patients dependent on renal replacement therapies are at highest risk because of frequent periods of hypotension and hypoperfusion, related to haemodialysis. Case presentation. A 66-year-old female patient, with history of stage 4 chronic kidney disease (CKD), presented for haemorrhagic shock following occult gastrointestinal bleeding and secondary acute posthaemorrhagic anaemia. Because of multiple systemic dysfunctions, she was admitted into the intensive care unit (ICU). Continuous renal replacement therapy with cytokine filter was performed, to reduce the level of circulating inflammatory markers. A computed tomography examination was performed, that established the diagnosis of ischemic colitis and she underwent subtotal colectomy with terminal ileostomy. The evolution was favourable, and after 10 days she was transferred from the ICU to the surgical ward. After another 5 days, she returned to the previous functional status and was discharged. Conclusions. Ischemic colitis can lead to lower gastrointestinal bleeding and even to haemorrhagic shock, especially in patients with chronic kidney disease, intermittent hemodialysis, atherosclerotic diseases, heart failure and diabetes mellitus.