Moldovan Medical Journal

11-15

Authors: Vitalie Iacubitchii, Alexandru Betisor, Nicolae Erhan

Background: The constrained knee prosthesis has the basic indication in revision arthroplasty, but the latest literature reveals that it takes place also in primary total knee arthroplasty in cases of knee osteoarthritis associated with major deformities. Material and methods: Present study is based on the surgical treatment, using the constrained knee prosthesis in the primary total knee arthroplasty, during 2019-2021, of 28 patients with knee osteoarthritis associated with severe deformities in varus or valgus, in the Big Joint Replacement Department, Clinical Hospital of Traumatology and Orthopedics, Chisinau. Results: In this study, the following criteria were evaluated: the type of deformity – valgus (10 cases) and varus (18 cases); the degree of deformation – for varus knees was on average 300, and for valgus knee – 250; bone attrition – 11 cases with bone defects where it was necessary to use augmentations; affected side – in 19 cases the right knee was affected and 9 cases the left one; the women/men ratio was 4/1; the mean age of the patients was 67.5 years; average duration of the intervention – 140 minutes; in 5 cases a lateral para-patellar approach was performed, of which 2 cases with tibial tuberosity osteotomy; complications – 1 case with intra-operative periprosthetic fracture and 2 cases with superficial infections of the operated joints. Conclusions: Osteoarthritis of the knee progresses rapidly, leading to severe deformities, significant bone defects and joint instability, which are indications to use the constrained prosthesis in the primary total knee arthroplasty, long-term follow-up is necessary to obtain the last conclusion, but from this study the constrained knee prosthesis like primary implant for special indication had promising results.

21-26

Authors: Mihail Tasnic, Valeriu Revenco, Ilia Catereniuc

Background: Of particular interest are the studies researching the correlations of myocardial bridges with hypertrophic cardiomyopathy and correlations of thick myocardial bridges with the development of coronary atherosclerosis in the proximal to the bridge arterial part. Material and methods: Assessment of the correlation between myocardial bridges, coronary atherosclerosis, and the degree of hypertrophy of the left ventricle was performed by retrospective analysis of 6168 coronary angiography protocols (2012-2019) and echocardiographic data from patients’ clinical records. Results: Moderate systolic compression predominated, and the number of patients detected with severe under the bridge systolic coronary stenosis was double as in patients with nonsignificant coronary atherosclerosis. From the total number, patients with myocardial hypertrophy and myocardial bridges were twice less when compared with the patients with the normal myocardial thickness. The comparative research did not show any interdependence between the degree of vascular compression and the degree of left ventricular myocardial hypertrophy. Proximal to the bridges atherosclerosis was detected in 32% of cases without correlation with the force of the myocardial bridge. Conclusions: The study showed the absence of the correlation between the degree of arterial stenosis caused by the bridge and the degree of hypertrophy of the ventricular myocardium as well as the degree of proximal to the bridge atherosclerosis. Important finding was that the degree of coronary systolic compression is higher in patients with moderate and severe proximal to the bridge atherosclerosis.

33-37

Authors: Ivan Vladanov

Background: Transurethral resection of the bladder is one of the essential methods in the diagnosis, treatment and management of non-muscular- invasive bladder cancer. The purpose of the procedure is to remove completely all visually detected tumors with a following establishment of a very precise histological diagnosis. The aim of the study is to compare the results of conventional transurethral endoscopic treatment and the En-bloc resection method using different types of energy sources in the treatment of bladder tumors. Material and methods: A total number of 88 patients underwent endourological interventions. Regarding the distribution, 23 patients had conventional transurethral resection, 22 – En-bloc monopolar resection, 21 – En-bloc bipolar resection and 22 – En-bloc with Thu:YAG laser. Clinical data, intraoperative and postoperative data and also the histopathological examination results were compared. Results: The compared groups were heterogeneous by age, sex, tumor characteristic (size, number, location). No significant differences were observed during the operations, comparing the intraoperative and postoperative complications of the studied groups. The detrusor musculature was detected in 74% of cases after conventional transurethral resection, in 91% of cases of En-bloc monopolar resection, in 95% of cases of En-bloc bipolar resection and in 96% of cases of En-bloc Thu:YAG laser. Conclusions: The En-bloc resection technique of non-muscular-invasive bladder tumors is a safe and effective method comparing with the conventional transurethral resection; it allows more favorable postoperative results and obtaining better quality tumor samples which allow establishing correct diagnosis of the disease.

42-46

Authors: Constantin Toncoglaz, Serghei Toncoglaz, Alina Toncoglaz

Background: Congenital uterine abnormalities result from abnormal formation, fusion or resorption of the Mullerian ducts during fetal life. These abnormalities have been associated with an increased rate of miscarriage, preterm birth, and other fetal adverse outcomes. Material and methods: Was performed a clinical observational retrospective study of uterine malformations, diagnosed in the Republic of Moldova. Pelvic MRI (1.5-3 tesla) with contrast and without were examined, from 01.01.2016 to 20.11.2016. During this time, 190 MRIs were performed according to the program, 167 MRIs were included in the study, 23 MRIs were excluded, having total or partial hysterectomy performed. The age of the examined persons is between 81 years and 6 months. Results: 15 uterine malformations were detected, which represent 11.13%. Among the uterine abnormalities were detected 6 cases of bicorn uterus, 3 cases of didelph uterus, 2 cases of uterine agenesis and septate uterus and one case of arcuate uterus, and unicorn. Conclusions: In this study it was determined that the prevalence of uterine malformations in an unselected population in the Republic of Moldova is 11.13%, and that of the septate uterus is 1.2%, data that are similar and correspond to the international literature.

51-55

Authors: Dumitru Cheptea

Background: Teaching in schools has been defined as the profession with the most diverse risk factors that affect health. With almost 48000 people currently working in educational institutions, teachers make up the largest occupational group in the Republic of Moldova. Material and methods: The study involved 519 teachers from pre-university educational institutions. For the self-assessment of the health status, a questionnaire was created which was applied online. The subjective assessment was performed by researching the entries in the medical cards. Results: The majority of respondents were women (91.4%), with a mean age of 45.6±7.5 years and a working experience of 22.9±3.2 years. In 75.7% of them health is satisfactory, only 3% have serious health problems and would require hospitalization. In 35.8% of cases, the presence of chronic diseases is registered, their top being led by diseases of the gastrointestinal tract (33.8%), the cardiovascular system (29.2%) and endocrine (27.2%). The most common risk factors mentioned were: high levels of stress (53.5%); increased number of tasks (23.4%); lack of support from family and colleagues (22.9%). Conclusions: The health of teachers is influenced by a variety of risk factors. There were no correlations between the type of institution and the subject taught, which highlights the importance of studying the influence of factors in the occupational environment and the development of prevention measures.

62-69

Authors: Iulia Rodoman, Alexandr Dorif, Ina Palii, Victoria Sacara

Background: Standard pediatric cardiology examinations and echocardiography fail to discover when the cardiomyopathy will occur in patient with Duchenne muscular dystrophy (DMD). Noninvasive markers are needed to fill this gap. Material and methods: This cohort study included a total number of 30 children (21 children (70%) with DMD and 9 (30%) healthy children. Blood samples were used for biochemical (level of creatine kinase, creatine kinase-MB, lactate dehydrogenase) and miRNA (presence of miR133a 3p, miR133b 3p, miR206 3p, miR208a 3p, miR208b 3p) analysis. All patients underwent partial conventional echocardiography ECOCG and Speckle Tracking. Results: The children in the working group presented compared to healthy children: FCC values increased by 15 (71%) vs 2 (22%), high levels of CK, CK-MB, LDH, which is characteristic for the disease and reflects its stage. Also, there is a decrease in systolic function indicators in the working group: mean FE 59 ± 3.8 %, and GLS: -16.2 ± 3.1%. MiRNA analyses confirmed the presence of miR133a 3p, miR133b 3p, miR206 3p, miR208a 3p, miR208b 3p in both working and control group. Conclusions: For the first time in the Republic of Moldova, we developed and adapted protocols for RNA extraction from human blood, performing screening of specific miRNA in the serum of patients with DMD and healthy children. Also, altered LV strain notwithstanding a normal or mildly modified LVEF represents an essential viewpoint for prospective pediatric drug trials in DMD-related cardiomyopathy prevention.

76-80

Authors: Maria-Victoria Racu, Ion Romulus Scorei, Iurie Pinzaru

Background: Boron was classified by the World Health Organization as ‘possible essential elements for human health’. It can be found in different forms in the environment, has beneficial effects on bones and its deprivation can impair calcium and magnesium metabolism and bone development, their health and maintenance. Dietary boron supplementation can help prevent and manage degenerative and inflammatory bones and articular diseases, such as arthritis, osteoarthritis, rheumatoid arthritis and osteoporosis. Relevant articles were identified in PubMed, Google Scholar, ProQuest, and Scopus databases published until June 2021, describing the role of boron in the functioning of the osteoarticular system. Conclusions: From organic and inorganic boron forms that can enter the human body, organic plant based boron compounds are highly bioavailable. In the functioning of the osteoarticular system boron acts by regulation of calcium and magnesium metabolism, enhancing the vitamin D activation process and influencing serum steroid hormone levels. A boron intake equal to or higher than 3 mg per day can help prevent/or correct arthritis, osteoporosis and osteoarthritis. Calcium fructoborate can reduce pain, joint discomfort and increase endogenous vitamin D level in patients with osteoarthritis. Boron may play a role in pathophysiology of rheumatoid arthritis and its severity and a supplementation with boron element may be useful.

10-16

Authors: Livia Uncu, Vladilena Evtodienco, Ecaterina Mazur, Elena Donici, Vladimir Valica

Background: UV-Vis spectrophotometry remains the most accessible spectral method with a high degree of sensitivity and information. The advantage of the method consists in its universality, the ability to combine with other methods, the minimum error, as well as its economic efficiency. The objective of this study was the determination of some validation parameters for the spectrophotometric method of dosing piracetam and nicergoline in combined capsules. Material and methods: Agilent 8453 UV-Vis spectrophotometer, reference standards of piracetam and nicergoline, 0.1 M HCl methanolic solution. Validation of the spectrophotometric method according to the requirements of the ICH guide “Q2R1: For analytical procedures and validation”. Results: Linearity was investigated on concentration ranges 5-40 µg / mL. The regression (R2 ) values were 0.9998 for nicergoline and 0.998 for piracetam, respectively. The limit of detection was 1.737 µg / mL for nicergoline and 0.369 µg / mL for piracetam. Quantification limit values were also calculated as 5.265 and 1.118 µg / mL for nicergoline and piracetam, accordingly. The results obtained showed that the developed spectrophotometric method is accurate, precise and robust, because the value of the relative standard deviation was less than 1.0%. Conclusions: The developed spectrophotometric method showed specificity, linearity, accuracy, precision and robustness, and can be applied on the concentration range between 80-120% of the nominal value of the content of nicergoline and piracetam in the preparation.

23-28

Authors: Lilia Tacu, Valeriu Cobet

Background: The doxorubicin (Dx) cardiotoxicity is manifested by a marked heart failure evolution. The impact of Dx on lusitrop functions of the heart and the inherent diastolic disorders have a theoretical and practical value for the connection cardiology-oncology. Material and methods: Dx cardiotoxicity was reproduced by its administration i/p in white rats in cumulative dose 16 mg/kg (Dx group n=9). Control group (n=9) received only physiological solution. The study was performed in vitro by using models of isolated heart perfusion in either isovolumic or exterior working regimens. The assayed indices of diastole functioning were: left ventricle (LV) end-diastolic pressure (LVEDP), diastolic stiffness, isovolumic relaxation velocity (-dP/dTmax) and protodiastolic pressure of LV (LVPDP). Results: The indices of diastolic disorders induced by Dx were elevation of LVEDP, diastolic stiffness and LVPDP in a range of 97-168% comparing to control as well as diminution of -dP/dTmax in the physiological pattern of hemodynamics. LVEDP increased more in conditions of calcium overloading or endothelin-1 (ET-1) action that are involved in pathogenesis of diastolic rigidity. Dx action led to decrease of myocardium resistance to ischemiareperfusion action resulting in the LVEDP elevation by 53% comparing to control. Conclusions: 1. Diastolic disorders inherent to Dx cardiotoxicity are manifested by the increase of LVEDP and diastolic stiffness. 2. Diastolic disorders compromised the volume-pressure relationship of LV, the adaptation of the heart to effort with volume, being more pronounced during the action of calcium excess and ET-1.

35-38

Authors: Ecaterina Carpenco, Veaceslav Fulga, Valeriu David, Ecaterina Foca, Lilian Saptefrati

Background: Tumor growth and development is determined by the mutual interaction between the cancer cells themselves and the microenvironment. It contains various elements, including immune cells. Of all, mast cells have one of the most controversial roles. The aim of the present study was to evaluate the expression of mast cell tryptase in the luminal and non-luminal subtypes of breast cancer and establish a possible link between infiltration with MCs and expression of hormone receptors. Material and methods: The experimental study included 80 cases of breast carcinomas that were analyzed immunohistochemically in order to establish the molecular profile and the expression of tryptase, a specific marker of mast cells. The data were processed using the SPSS program. Pearson’s coefficient (r) and the other values were considered statistically significant in case of p≤0.05. Results: Both intratumoral mast cells (MCit) and peritumoral mast cells (MCpt) correlated with the expression of hormone receptors for estrogen (ER) and progesterone (PR). Thus, the following relations were established: MCit and ER (r=0.343, p=0.002), MCpt and ER (r=0.394, p=0.000295) and MCpt and PR (r=0.386, p=0.000409). Statistically significant correlations between HER2 expression and mast cells content have not been established. Conclusions: Mast cells invasion, peri- and intratumoral, is strongly influenced by the expression of hormone receptors. The luminal subtypes of breast cancer are characterized by a higher density of mast cells.

45-49

Authors: Serghei Gutu

Background: It is assumed that the incidence of textile foreign bodies (TFB) unintentionally left in abdominal cavity is underreported, mostly due to the legal implications of their detection. Material and methods: One hundred thirty-five responses were received to a specially developed anonymous questionnaire on the TFB problem, including medico-legal aspects. Of the total number of respondents, 81 were surgeons and 54 – gynecologists. Results: Over 80% of respondents consider that if TFB was removed from abdominal cavity during the surgical intervention, it should be indicated in the final diagnosis. At the same time, the fact of detecting and removing TFB retained in abdomen in the real cases known by respondents was reflected in the surgical report and in diagnosis in only 49.1%. False description in case of detection and removal of intra-abdominal TFB admits 29.6% from total number of respondents, but only 24.5% with a shorter length of work (< 15 years), and 40.7% – with a work experience over 15 years. Conclusions: Surprisingly, about 20% of respondents consider it justified not to indicate retained TFB in the final diagnosis. Moreover, the real frequency of TFB diagnosis concealment is 1.6 times higher and sharply contradicts the declared intentions about the need to report the true cause of pathology. Almost half of surgeons with a long lasting work experience allow a false description of intraoperative findings and, as a result, the official diagnosis.

55-61

Authors: Olga Penina

Background: Previous studies have shown long-term unfavourable changes in mortality in the Republic of Moldova accompanied by recent improvements. Little is known about the regional mortality differentiation which is an important tool for evidence-based public health policy. The aim of the study is to assess the current geographical disparities of all-cause and cause-specific mortality in Moldova and to identify evidence-based modalities to reduce them. Material and methods: This cross-sectional study is based on the corrected results of the 2014 census and individual death records for the 2012-2016 period provided by the National Agency for Public Health. Global Moran’s index and local indicators of spatial autocorrelation were computed based on contiguity matrix. Results: All-cause mortality gradient between the northern and central regions was found for males (Moran’s index=0.47, p <0.001) and females (Moran’s index=0.44, p <0.001). Digestive and cardiovascular diseases for both sexes and external causes of death for males had a statistically significant influence on the inter-regional mortality differentiation. Liver cirrhosis contributed the most to the geographical difference between the North and the Centre (Moran’s index=0.59, p <0.001), especially for females. Conclusions: The results of this study point to the existence of different drinking habits of the Moldovan population between the northern and central regions. The central regions that form the cluster of “high-high” mortality from liver cirrhosis should be considered as primarily targets for antialcohol policies.

66-68

Authors: Olga Gavriliuc, Alexandru Andrusca, Lilian Popil, Mihail Gavriliuc

Background: Before L-Dopa’s discovery, anticholinergic drugs were among the first treatments for Parkinson’s disease. Only now trihexyphenidyl (THP) is approved to treat unresponsive L-dopa tremors in young, cognitively unaffected Parkinson’s disease patients. However, there are no specific recommendations for disease duration, medication dose, or cognitive status. In low-income countries, THP is still frequently used in Parkinson’s disease patients with tremor. The objective of the current study was to evaluate cognitive performance in Parkinson’s disease patients receiving a low dose of THP. Material and methods: The study was performed on nineteen PD patients, nine of whom were on THP. All patients completed MoCA cognitive assessment. The patients were matched depending on their age, disease severity based on UPDRS III and duration of the disease. Results: The THP patients were taking an average dose of 3.3 mg of THP daily for an average of 1.8 years. There were no statistical differences between THP patients and non-THP patients in age (64.8± 4.8 vs 67.2±6.9, p=0.4), UPDRS III (32.1±8.9 vs 41.5±20.6, p=0.2) and disease duration (6.2±4.9 vs 7.0 ± 4.0, p=0.7). The THP patients had lower cognitive performance, with a total MoCA of 19.22 ± 3.3 vs. non-THP patients 24.2±3.0, p=0.003. Conclusions: In Parkinson’s disease patients, even a low dose of THP causes significant cognitive loss.

72-85

Authors: Vitalie Chiosa, Dumitru Ciolac, Viorica Chelban, Daniela Gasnas, Anatolie Vataman, Cristina Munteanu, Stanislav Groppa

Background: Drug-resistant epilepsy is the cause of severe disability. Multiple questions remain unanswered both in terms of pathogenesis and therapeutic management. For this narrative review, PubMed database and Infomedica library were searched by using “drug-resistance in epilepsy” and “treatment of drug-resistant epilepsy” as key words. The following filters were applied: “Clinical Trial”, “Meta-analysis”, “Multicenter Study”, and “Randomized Controlled Trial”, covering the period of 01.01.2005–06.01.2021.Several hypotheses have been proposed, i.e., pharmacokinetic, intrinsic severity, gene, target, transporter, and neural network hypotheses. Many controlled trials showed different results in terms of seizure control after combined methods of therapies. Immunotherapy, palliative epilepsy surgery alone or associated with neurostimulation procedures including vagus nerve, trigeminal nerve, or deep brain stimulation may be efficient, however, seizure freedom is not always achieved. Genetic epilepsies might benefit from gene and exosome therapy; however, further studies are needed to verify their safety. Conclusions: Neuroscience of drug-resistant epilepsy faces many challenges. Inflammatory mediators, biomarkers, and genes might allow the identification of new treatment targets, contribute to an earlier diagnosis, and assess the clinical outcomes.

11-15

Authors: Emilia Gheorghian, Mihail Maniuc, Polina Ababii, Lucian Danilov

Background: Chronic hypertrophic rhinitis is a common problem in childhood and adolescence and has a negative impact on both physical, social and psychological well-being. Chronic hypertrophic rhinitis in the prevalence of children is 20-55%, and in the last 5 years this index is increasing. Material and methods: The study included 65 patients, aged 5 to 18 years, being hospitalized in the ENT department of the Emilian Cotaga Clinic of the Institute of Mother and Child, Chisinau, diagnosed with rhinitis complicated chronic hypertrophic over the years January 2018 – December 2020. The study was conducted by retrospective analysis of complicated data from clinical observation sheets and documents accompanying the data. Treatment methods studied: laser coagulation, electrocoagulation, radiofrequency, mucotomy. In most cases, lasercoagulation was chosen. Results: Nasal permeability in children with chronic hypertrophic rhinitis is altered in most cases. The most frequently affected age groups were 10-14 years with a rate of 61.53%, the majority being from urban living environment in 63.08%. The most representative clinical signs and symptoms according to this study are difficult nasal breathing in 96.93% and mouth breathing – 89.24%. From the indicated surgical methods, laser coagulation of the nasal cornets was performed in 47.7% of cases. It proved to be more effective and less invasive compared to electrocoagulation performed in 44.6% of cases and partial mucotomy in 4.62%. Conclusions: From the data obtained in the study, we opted for laser coagulation of the lower nasal horns, which has a faster healing period, shorter postoperative complications, greater acceptability from the doctor and patient.

25-27

Authors: Angela Tomacinschii, Oleg Lozan, Ana Ciobanu

Background: Promoting a healthy lifestyle is one of the basic pieces in the family medicine activity. In order to formulate and / or adjust some approaches in clinical practice of the family doctor in the Republic of Moldova, it was necessary to analyse the knowledge and practices of the family doctor regarding the obese patients counselling. Material and methods: Cross-sectional study was based on primary data collection. The study sample included 316 family doctors. The descriptive analysis was expressed in absolute values, percentages and standard errors, means and standard deviation of the mean. Statistical significance was considered to be p <0.05. Results: Family doctors feel best prepared in counselling patients on stress management (75.9 ± 2.40%), prescribing healthy diets (71.2 ± 2.55%), prescribing physical activity (71.0 ± 2.55%), cerebrovascular accident (CVA) prevention (68.9 ± 2.60%). They feel less prepared in counselling patients with regard to weight control (67.5 ± 2.63%). Conclusions: Managing obesity in primary health care remains indispensably linked with the clinical practices of family doctors. Research has shown that family doctors are less prepared in counselling patients regarding weight control than regarding other important components of obesity management. According to the study, it was found that male family doctors, family doctors over the age of 45, those who work in the primary health care providers located in the rural area, those who have a working experience of over 21 years, and those who serve sectors with a population of up to 1500 people feel more prepared in counselling obese patients.

32-35

Authors: Victoria Rusu

Background: In the intensive care unit, the curative plasmapheresis technique is widely applied among severe patients, who show signs of both endogenous and exogenous intoxication. The impact of isovolemic isooncotic curative plasmapheresis on the status of hemoleukogram and immunological markers has not been studied yet. Material and methods: The study is retrospective, observational. The medical records of 34 COVID-19 patients from the COVID intensive care units of Timofei Mosneaga Republican Clinical Hospital who benefited from isovolemic, curative isooncotic plasmapheresis were analyzed. There were 25 complete, analyzed data sets. General data were recorded: preplasmapheresis, postplasmaphesis hemoleukogram. Results: Isovolemic, isooncotic plasmapheresis, performed in patients with severe COVID-19, SARS-CoV2 showed effects of improving the status of laboratory indices that denote the evolution and favorable prognosis of the disease. The activity of the cytokine storm decreased in both groups of patients, both in those with a mean age of up to 60 years and in those over 60 years of age, with p = 0.001. Patients over 60 years of age had a marked improvement in serum ferritin index, compared to patients in the age group up to 60 years, in the period after plasmapheresis, p = 0.043. Analogously, the level of C-reactive protein was analyzed, which clearly decreases in patients 60 years of age, p = 0.037 Conclusions: Isovolemic, isooncotic plasmapheresis is a procedure performed in severe COVID-19 (SARS-CoV-2) patients to improve the status of the cytokine storm. Moreover, the performance of the procedure in different age groups induced an improvement in the satiety of hemoleukogram and proinflammatory indices.

40-43

Authors: Lilia Rotaru

Background: Cognitive impairment (CI) is frequent in Parkinson’s disease (PD). CI patients have particular features. These are preliminary data of a cohort study of Moldovan patients with incident Parkinson’s disease. Material and methods: 65 out of 111 consecutive PD patients (mean age 64.87 ± 7.69 y.o.; disease duration 50.21 ± 38.61 mo.; 48 women (43.2%), 63 men (56.8%)) underwent Montreal Cognitive Assessment (MoCA) test. Cognitive status graded as: (1) normal and (2) impaired cognition. Results: There were similar: ages (65.79 ± 7.13 vs 62.17 ± 12.21 y.o.), onset ages (61.44 ± 7.61 vs 57.00 ± 12.95 years), disease duration (49.63 ± 36.78 vs 66.00 ± 26.48) months), levodopa (574.58 ± 129 vs 249.55) and agonists doses (5.19 ± 3.02 vs 1.05 ± 0.05) and Beck scores (8.13 ± 6.21 vs 7.4 ± 3.85), in groups. CI was present in 59 (90.8%) patients; more frequent in patients with cardiovascular risk factors (91.7%, p> 0.05), symmetrical Parkinsonism (93.2%, p> 0.05), and in first disease symptom bradykinesia patients (93.8%, p> 0.05). Upper / Lower Asymmetry Index were lower in CI patients, all lower type patients (p> 0.05) having CI. MoCA scores correlated with Unified Parkinson’s Disease Rating Scale in ON fase (UPDRSon), (r = -0.320, p <0.022), and red flags number (r = -0.590, p < 0.006). Conclusions: Cognitive impairment is more expectable in akinetic, symmetric and lower type Parkinsonism, also in patients with cardiovascular risk factors, with probable PD, and a more motor impairment.

50-53

Authors: Dumitru Brinza

Background: Head and neck squamous cell carcinomas (HNSCCs) are particularly aggressive epithelial tumors, that affect more than half a million patients worldwide each year. They represent a multi-factorial group of tumors caused by: alcohol, tobacco, and human papillomavirus (HPV) infections. Over the last ten years the overall 5-year survival rate of HNSCCs remained ~40–50%, inspite of significant improvement in clinical outcome of many tumor types. There are recent data that claim how some of these cells fulfill a suppressive role in the antitumor immune response. It is interesting that new clinical studies demonstrated that HPV (+) HNSCCs were among tumors with the highest immune infiltrates, while HPV (-) presented a reduced number of immune infiltrating cells. Conclusions: Recent researches prove that tumor microenvironment of HNSCC has an important role in tumor progression, aggressivity, metastasis process, in addition to genetic aberrations and molecular alterations of cancer cells. New researches in stromal composition of the HNSCC may be useful in understanding of mechanisms of different responses to therapy, also can be used as a target for therapeutic purposes. Cancer-associated fibroblasts and immune cells, as well as their products found in neck squamous cell carcinoma significantly influence the biological properties of this tumor. Smoking is one of the risk factors of occurrence of most HPV-associated tumors. Promoting smoking cessation should become an essential contributor to the treatment of cancer in all oncologic pathologies. In cases when patients can’t quit smoking completely within the shortest possible period of time, doctors should focus on harm reduction strategies – tobacco harm reduction.

62-67

Authors: Ana Popescu, Gabriela Soric, Victoria Federiuc, Vitalie Ojovan

Background: Aging process involves an increased risk for the development of vulnerability, because senescence is a process characterized by a multitude of changes that influence the living conditions and health of the individuals. In geriatrics, the term “vulnerability” implies a multidimensional aspect, among which, multimorbidity, functional incapacity, socio-economic and cognitive problems in the elderly. The main objective of the article is to systematize data from the literature through the analysis of the concept and prevalence of vulnerability, assessed by the score Vulnerable Elders Survey-13 (VES-13) in the elderly. For this purpose, publications from the database GoogleSearch, PubMed, Hinari, etc. were analyzed. The information was systematized, highlighting the main aspects of the contemporary vision of the last 5 years.A series of studies (USA, Brazil, etc.) revealed a high prevalence of vulnerability in the elderly according to the VES-13 score, it was estimated in respondents aged > 65 years, between 40-50% of cases were vulnerable people, with a score ≥ 3 p. The vulnerability of the elderly results from different conditions, correlated with each other, especially biological, social and genetic factors. There was a functional decline between 13 and 24% of cases, especially in the elderly over 75 years, and an association with health problems, mobility and low autonomy in over 50% of cases, with a poor quality of life and increased risk of institutionalization. Conclusions: Vulnerability assessment measures are important for identifying older people at high risk of deteriorating health, which is an important target for interdisciplinary intervention.

78-84

Authors: Anna Belenciuc, Ana-Maria Bubuioc, Olesea Odainic, Marina Sangheli, Mihail Gavriliuc, Vitalie Lisnic

Background: Multiple sclerosis (MS) is a disease that affects young people of reproductive age (20-40 years old), predominantly women. Therefore, almost every patient has questions about pregnancy and breastfeeding. Family planning is one of the key issues in the choice of treatment tactics. Despite the growing number of therapeutic options for individualized treatment, it is still a question how to manage women with MS who become pregnant while taking disease-modifying drugs or want to become pregnant after starting this treatment. Conclusions: Women with MS should not be discouraged from pregnancy due to their illness. It is necessary to proactively discuss pregnancy planning with all women with MS of childbearing age. Based on available data, interferon beta and glatiramer acetate appear to be most suitable for use up until the time of confirmed pregnancy. A large amount of data (more than 1000 cases) obtained from registries shows that use of interferon beta before conception and during pregnancy suggests no evidence of increase in the rate of congenital anomalies or spontaneous abortions. For women with persistent high disease activity, pulsed immune reconstitution therapy gives additional opportunity for family planning after the last dose. The choice between available options for pulsed immune reconstitution therapy should be based on efficacy balanced against the risks.

12-15

Authors: Cornelia Calcii, Svetlana Hadjiu, Mariana Sprincean, Ludmila Feghiu, Nadejda Lupusor, Ninel Revenco, Stanislav Groppa

Introduction: Status epilepticus (SE) is a life-threatening neurological emergency requiring immediate medical intervention and is associated with high mortality and morbidity. The aim of this research was evaluation of clinical and etiological profile of refractory status epilepticus (RSE) among children aged between 1 month and 18 years. Material and methods: The study was done between January 1, 2017 and December 24, 2019. All children with the age limits mentioned above, who presented convulsive SE, subsequently with development in refractory status epileptic (RSE), were included in the study. Patients were investigated and evaluated according to a standard protocol. Subsequently, the characteristics of children with RSE and those without an evolution in RSE were compared. Results: 55 children, out of whom 32 boys with SE were enrolled in the study, of which 20 children (36%) developed RSE. Central nervous system (CNS) infections were the most common causes of SE and development of RSE (51% in SE and 53% in RSE, p > 0.05). Noncompliance of antiepileptic medication served as the second cause for evolution of RSE. The overall mortality rate was 10.9%, the chances of death in RSE (20%) being higher than in SE (5.7%). The unfavorable prognosis was seven times higher in children with RSE, compared to children who developed SE. Conclusions: In the management of CNS infections, pediatricians should be aware of the high risk of developing RSE. In addition, the possibility of developing RSE should be considered and promptly managed in an intensive care unit in order to reduce the risk of mortality and morbidity of this severe neurological condition.

21-25

Authors: Oleg Arnaut, Ion Grabovschi, Serghei Sandru, Gheorghe Rojnoveanu, Ruslan Baltaga

Background: Trauma remains a medical-social problem, still having high lethality rate. Indirect lung injury (ILI) occurs in trauma due to systemic neutrophils activation and proteases release into primarily intact tissues. There are no data in the literature regarding ILI predictive models in trauma. Material and methods: In the experimental study (19 traumatized male rabbits), the proteases, antiproteases and the pulmonary morphological changes, assessed according to the SAMCRS score (Semiquantitative Reflected Qualitative Changes Assessment Scale) were followed. There were used two statistical instruments – correlational analysis and multivariate linear regression. Results: Initially, a correlational analysis between the values of the SAMCRS score and the proteases/ anti proteases was performed. The null hypothesis was rejected (F = 7.017, p = .002). The correlation coefficient of the predicted results and the real values of SAMCRSlungs was .854, the determination coefficient being .626. The final model included the following parameters: constant (B = 9.427; 95% CI 7.341, 11.513; p <.001); α2-macroglobulin0 (B = -4.053; 95% Cl -6.350, -1.757; p = .002); AEAMP0 (B = .002; 95% CI .000, .004; p = .075); AEAMP24 (B = -. 006; 95% CI -.010, -.002; p = .003); AECG2 (B = .081; 95% CI .040, .122; p = .001); AEE0 (B = -. 026; 95% CI -.040, -.011; p = .002). Conclusions: In this research, a predictive model for indirect lung injury in experimental trauma was developed, the predictors being some elements of the proteases/antiproteases system. This, in turn, allows the hypotheses emission regarding the pathophysiology, prophylaxis and treatment of ILI.

33-36

Authors: Artur Colta

Background: The purpose of the study was to diagnose possible chronic nonbacterial prostatitis (CNP) and chronic pelvic pain syndrome (CPPS) among patients, as well as differentiate between the inflammatory (category IIIA) or non-inflammatory (category IIIB) types in selecting and optimizing differential drug treatment of this category of patients. Material and methods: The study was conducted on 43 patients diagnosed with CNP/CPPS. The control group included 10 healthy men. Both the production of nitric oxides (NO) by phagocytes, as well as prostate secretion and ejaculate were determined according to the procedure described by Metelyskaya B.A., which was modified by Gudumac V, et al. Results: There was a 39.0% (p <0. 05) decrease in NO production by induced NO-synthase (iNOS), determined in the blood of 11 patients (from the main group – 2) with CNP/CPPS and a 115% (p <0.05) increase was determined in 32 patients (from the main group 1) if compared to the same indices in the control group. The prostatic secretion and ejaculate showed a higher macrophage iNOS activity by 80% (p <0.05) and 75% (p <0.05) if compared to the same parameters from the control group. The iNOS activity in prostatic fluid and split-ejaculate fractions from the main group – 2 did not differ from that of the control group. Conclusions: The assessment of NO production, prostate secretion and ejaculate allows to somewhat establish the main diagnosis of CNP and category III types (A – inflammatory and B – non-inflammatory prostatitis), which will significantly contribute to the optimization and selection of an appropriate differential treatment based on the drug action mechanisms.

42-48

Authors: Tatiana Timbalari, Oleg Lozan, Igor Codreanu, Viorel Nacu

Background: Numerous studies focusing on public attitude towards organ donation have been performed at the international level, but very few highlight public attitude towards tissue and cell donation and transplantation. Material and methods: We conducted a survey among a representative sample of the general adult population (N=427). The questionnaire was developed on the basis of previous study and included reuse of some items from the earlier survey to facilitate historical comparison. The analysis of the data was carried out using SPSS, 2011 and focused on descriptive statistics. Results: The vast majority of our respondents (81.0%) agreed with the tissue and cell donation and only every 10th respondent did not accept this. The fewer respondents (68.1%) would agree to have tissues and cells transplanted from other people compared to those who were willing to donate tissues and cells (81.0%). Finally, most of the respondents (85.0%) expressed interest in receiving more information, and were very similar to those in receiving more information on organ donation and transplantation (88.0%) Conclusions: The study revealed the respondents’ positive attitude towards tissue and cell donation and transplantation and demonstrated a remarkable growth in the public positive attitude towards donation. Furthermore, as the vast majority of our respondents wanted to receive more information on these issues, it seems to be a clear opportunity to develop educational and promotional strategies to improve awareness and enhance donation rates in our country.

53-57

Authors: Roman Chornopyshchuk

Background: High mortality and disability of patients with critical and supercritical burns, long-term treatment, unsatisfactory aesthetic and functional results lead to the search for ways to provide assistance aimed at counteracting the formation of a mass of necrotic tissue, which is crucial for life or death of the victim. Material and methods: The experimental study was performed on 60 sexually mature Wistar rats, which were on a regular diet and weighed 150-160 g. The experimental animals were divided into the main and control groups and were used to simulate burns with boiling water of IIb degree. Results: The traumatic effect of hyperthermic exogenous and endogenous damage factors of the animals in the main group were immediately neutralized by a gauze napkin soaked in water at a temperature of 18-20 ° C immediately after the simulation of burns, the duration of which became the criterion for dividing them into subgroups. In animals of subgroup 1 the time of application of a wet wipe to the burn area was 1 min., in the 2nd subgroup it was 5 min., 3rd subgroup – 10 min., 4th subgroup – 15 min., 5th subgroup – 20 min. The application napkin was changed when it was heated to 34 °C. Such applications were not performed to the animals of the control group. Conclusions: The conclusion was made on the necessity of prompt neutralization of traumatic action of hyperthermic exogenous and endogenous damage factors as the main elements of burn wound depth. For a broader understanding of action mechanisms of the suggested technology of self-help and mutual first aid as well as the nature of the impact of neutralization directly on the tissues, it is advisable to supplement the research with morphological methods.

65-69

Authors: Ivan Vladanov, Alexei Plesacov, Vitalii Ghicavii

Background: Transurethral resection of the bladder (TURB) tumor was first described by Stern and McCarthy in 1931, and is still considered the gold standard in diagnosis and treatment of non-muscle-invasive bladder cancer. The quality of TURB affects accuracy of histopathologic evaluation, and subsequently impacts the risk of recurrence and patient outcome. New methods that aim to improve the effectiveness of TURB are reviewed, and recent studies are discussed, including resection methods and image enhancement techniques. Material and methods: Between January 2016 and April 2019, within the Urology Clinic of Nicolae Testemitanu State University of Medicine and Pharmacy 108 patients were surgically treated with bladder tumor pathology. Patients were divided in two groups: En-bloc resection group which includes 51 patients and transurethral resection group with 57 patients, the obtained data were comparatively analyzed. Results: Tumor analysis showed that the majority of the patients’ tumors were localized on lateral urinary bladder walls, single bladder tumors were detected in 64 (59%) cases, tumor sizes up to 3 cm were detected in 74 (69%) patients included in the study. Detrusor muscles were detected in 49 (96%) cases of En-bloc group and 45 (79%) cases of TURB group. Most recurrences occurred in patients with high-grade histological result, recurrence rate in En-bloc group occurred in 18% and in TURB group in 37%. Conclusions: The En-bloc resection technique of non-muscle-invasive bladder tumor proved to be a safe and effective method compared to the conventional transurethral resection technique (TURB). This method provides more favorable results for obtaining better quality tumor samples (present of detrusor muscle) that allow to establish correct diagnosis and staging of the disease and reduces the number of recurrences.

79-86

Authors: Olga Macagonova, Doina Risnic, Adrian Cociug, Viorel Nacu

Background: The extracellular matrix plays an important role in the promoting the tissue regeneration and repair. Decellularization or removal of the cells from the complex mixture of the structural and functional proteins that constitute the extracellular matrix (ECM) can be done by the physical (agitation, sonication, freeze and thaw), chemical (alkaline orchids, ionic detergents, nonionic, tri-n-butyl phosphate (TBP), hypotonic or hypertonic treatments, chelating agents), and enzymatic methods (trypsin or protease inhibitors). However, complications associated with the use of the decellularized skin have been reported, which are widespread and poorly understood. In this synthesis have been included publications, identified by the Google Search engine, National Bibliometric Tool (NBT), Pub Med databases, Web of Science, Springer, Elsevier, Wiley Online Library, Science Direct and Biosience, Biotechnology and Biochemistry. The results of the decellularization were reported in terms of the number of cells remaining in the collagen fibers depending on the duration of exposure to chemical agents. Conclusions: The natural matrix is more widely used than synthetic material, because it has the natural structure and composition of the ECM, it naturally stimulates cell development and allows the incorporation of the growth factors and other proteins increasing cell proliferation.The assessment of the quality of decellularization techniques is done by evaluating the necrosis of the extracellulare matrix, the depletion of the collagen fibers and the remaining amount of genetic material.

10-21

Authors: Jana Bernic, Lilia Baranov, Valentin Bernic, Eva Gudumac

Background: The adhesive disease and its associated complications, caused by adhesive mechanical bowel obstructions, mainly related to genetic causes and disorders of cell homeostasis, is one of the major health problems due to its diverse impact on the growing organism. Material and methods: The clinical study was conducted on a group of 50 children aged 1 month – 18 years old with abdominal adhesion disorders, complicated by bowel obstruction, following a surgical intervention. Apart from the assessment of the anamnesis, clinical, and imaging manifestations, traditional bio-humoral homeostatic imbalance markers, endotoxemia levels, associated complications, and comorbidities, the blood inflammatory and excessive fibrosis biomarkers were assessed at different clinical periods of the pathological process. Results: A non-randomized pro- and retrospective study was carried out to assess the epidemiological, clinical and paraclinical, histopathological, evolutionary, preventive and treatment charcteristics in order to determine the major complication triggers following a surgical intervention on the small intestine, colon, appendix or uterus , as well as to highlight their possible peculiarities in children. Conclusions: This study completed the clinicians’ views on intraperitoneal adhesion pathophysiology, thus confirming the importance of the microbial factor, inflammatory mediators, activation of humoral systems due to organic cellular lesions, the extension of the inflammatory response, as well as the genetic factors depending on the acetylation phenotype in children.

25-28

Authors: Elena Manole, Mihaela Chitoroaga

Background: Recurrent strokes account for about 25% of all strokes that occur annually. Studies show varying recurrence rates, ranging from 7% – 20% at 1 year to 16% – 35% at 5 years. Establishing a clinical pattern of patients with recurrent stroke could optimize the management strategy of this pathology. Material and methods: A retrospective observational study was conducted that included 60 patients with primary stroke (n=30) and recurrent stroke (n=30). The severity of stroke was assessed using the National Institute of Health Stroke Scale scale and the degree of neurological disability – using the mRS scale. Predictive factors, post-stroke infectious complications and compliance with primary and secondary prophylaxis measures were also investigated. For the statistical analysis of the data, the Student’s t test was performed for two independent samples. Results: In the primary stroke group the mean age was 63.7±2.0 years, whereas in the recurrent stroke group it was 68.8±1.42 years. Statistically significant differences between groups were recorded for age (p=0.043), dyslipidemia (p=0.020), post-stroke infectious complications (p=0.032), cerebellar deficit (p=0.029), cognitive deficit (p=0.020) and neurological disability (p=0.003). Also, 93.33% of patients with atrial fibrillation following anticoagulant treatment as a secondary prophylaxis were under coagulated. Conclusions: Elderly patients with poor risk factors control will be prone to experience a stroke of moderate severity, which will involve a moderate-severe degree of post-stroke disability, expressed by motor, sensitivity, verbal, cerebellar and cognitive deficit, as well as post-stroke infectious complications of the respiratory and urinary tract.

35-40

Authors: Liliana Profire, Adriana Niguleanu, Natalia Corolcova, Mihaela Burac, Veronica Cotelea

Background: A healthy vagina is characterized by hydrogen peroxide and acid-producing lactobacilli, which are crucial to maintain the physiological vaginal ecosystem and their depletion speeds up bacterial overgrowth with pH elevation, salidase and amine production, leading to the observed signs and symptoms of vaginal dysbiosis. An effective treatment should be combined of lactobacillary flora and low doses of estrogen to maintain the physiology of the vaginal epithelium. Material and methods: This is a prospective randomized study that included 218 patients, who were divided into 2 groups according to the treatment regimen, performed between October 2018 and December 2019 at the Department of Obstetrics and Gynecology of Nicolae Testemitanu State University of Medicine and Pharmacy. Patients selected were divided into L1 (120 patients assigned to treatment with the combination of two microorganisms Lactobacillus rhamnosus and Lactobacillus reuteri with estriol 0.03 mg vaginal pessaries) and L2 (98 patients who were given Lactobacillus rhamnosus in vaginal capsules). The treatment regimen for both groups was the same – 1 pessary or 1 capsule once in 24 hours, in the evening, for 12 days. Patients were evaluated before treatment (visit 1) and on day 13 of treatment (visit 2) and 1 month after the end of treatment (visit 3). Results: Of the 120 women included in the study in the first group and 98 in the second group, a significant improvement (normocenosis) according to the research physician and patients was found in 93.3% (112) patients of group 1 and 71.4% (70) patients in group 2, satisfactory improvement (consistent with the intermediate type of biocenosis) in 5% (6) patients of group 1 and 15.3% (14) patients from group 2, unsatisfactory result 1.7% (2) patients from group 1 and 13.3% (13) of patients of group 2 (later relapse was noted in these patients). Conclusions: Probiotic treatment with vaginal Lactobacillus rhamnosus, Lactobacillus reuteri and low doses of estriol seems to be useful in hindering bacteria growth especially after antibiotic therapy; therefore this intervention may be considered a new prophylactic treatment for preventing recurrence of bacterial vaginosis, in particular in high-risk patients.

45-49

Authors: Zinovia Zorina, Dan Croitoru, Eugen Cerevan

Background:”Corona mortis” is usually referred to in the majority of the bibliographical sources as an arterial anastomosis, formed after the connection between the pubian branch of the obturator artery and the obturator branch of the inferior epigastric artery. The metaphoric name for this anatomical variant describes the severity of the complications that may manifest after its lesion in case of a herniotomy or in the surgical interventions that are conducted on the acetabulum, with anterior surgical access pathways. The incidence of this anastomosis variates between 12-80%, its individual aspects and morphological characteristics were not mentioned in literature. Material and methods: We have conducted a descriptive, retrospective study, based on which we studied the branches of the external iliac artery and the anterior trunk of the internal iliac artery on 197 angiographies, that were obtained from the database of the Vascular surgery section of Timofei Mosneaga Clinical Republican Hospital, Chisinau, the Republic of Moldova archive in order to determine the incidence of ”corona mortis” and its individual variability based on gender, age and laterality. Results:”Corona mortis” was identified in 39.08% cases, from which 30.96% were in the male gender and 8.12% in the female gender, the majority of patients being in the 61-70-year age group. The classical variant of ”corona mortis” called Lambda, was identified in 70.13% ofcases, the circle type – in 27.27% and the laurel wreath type – in 2.60%. Conclusions: The knowledge of the uncommon anatomical variants of “corona mortis” is vital, because their lesion may lead to severe complications during surgical interventions in the pubic region.

56-62

Authors: Ana Plugaru, Mihaela Ivanov, Victoria Ivanov, Ion Popovici, Lucia Ciobanu, Olga Dicusar, Mihail Popovici

Background: The outcomes of NSTEMI patients are known to be worse than those of STEMI patients and depend on guideline-directed management. The higher the rate of adherence to guideline recommendations the better the prognosis and outcomes of usually high-risk NSTEMI patients. The best efforts should be made to rapidly and correctly diagnose and manage this condition in order to achieve the best results. Material and methods: An observational retrospective study was conducted in 3 PCI centers in Chisinau, Moldova, that included all patients hospitalized with NSTEMI through 2019. Another observational prospective study was conducted in the same 3 PCI centers with the consecutive inclusion of all NSTEMI patients in 2020-2021 and established follow-up dates. Results: Extensive preliminary data from both studies based on 215 patients is presented and compared to that of the FAST-MI registry in France, as an example of care in a developed country. Conclusions: Preliminary data has contoured a picture of NSTEMI patients management in Chisinau and has already detected major drawbacks to be corrected. The follow-up data will provide more insights on patient outcomes and correlations between management, short-term and long-term outcomes, whereas different biomarkers will be tested for diagnostic and prognostic values. Similar studies are needed in regional hospitals in order to assess the situation in these areas and search for improvement solutions.

68-70

Authors: Valerian Cucieru

Backgraund: Breast cancer is one of the three most common cancers along with lung and colon cancer. It is a leading cause of cancer deaths in both developing and developed countries. Within 2 decades, neoadjuvant chemotherapy (NAC) has become a standard treatment option in breast cancer. Relevant articles were identified by means of PubMed, Embase, Web of Science, Cochrane Library and Springer Link databases published during the years 2010-2019, describing the role of molecular biomarkers in the assessment of NAC for breast cancer. Conclusions: The size of the breast primary tumor, the affection of the regional lymph nodes, the degree of tumor differentiation, the expression of hormone receptors, HER2neu, ki67 serve as main criteria for predicting the response to NAC. Preoperative core needle biopsy is the gold standard procedure in cancer diagnostics, in the analysis of predictive biomarkers, particularly utilizing histomorphological characteristics. Carrying out a larger number of cycles of NAC as well as correlating the schemes in relation to the immunohistochemical types have a direct influence on obtaining a good response to treatment. Patients with a pathologic complete response had superior survival outcomes compared with patients who had residual disease.

76-79

Authors: Eleferii Pitel, Serghei Suman, Evghenii Gutu

Background: The advantages of endoscopic retrograde cholangiopancreatography (ERCP) over traditional surgery for correction of various biliary and pancreatic pathologies became apparent immediately after its introduction into large clinical practice and today are also not in doubt. ERCP and endoscopic sphincterotomy (EST) are characterized by efficacy similar to open surgery, but significantly less traumatic, relatively easy, a decrease in the degree of perioperative surgical and anesthetic risk, and a reduction in the time of in-hospital treatment and postoperative recovery. However, therapeutic ERCP with EST can be complicated by gastrointestinal bleeding, the degree of which can range from mild to very severe and even life-threatening. Although the greatest risk for the development of bleeding after EST is caused by preexisting coagulopathy, the anatomical features of the arterial blood supply to the pancreaticoduodenal region and major duodenal papilla should also be taken into account during the endoscopic procedure. Conclusions: The communicating artery, directly vascularizing the area of the major duodenal papilla, usually originates from the posterior superior pancreaticoduodenal artery, and entering in the anterior pancreaticoduodenal arcade. The smallest number of papillary arteries, distributed in potential accessibility to the sphincterotomy incision, are located in the zone between 10 and 11 o’clock of the papilla Vater circumference. Hence, the preferred performance of EST in this area can be accompanied by a significant reduction in the risk of arterial bleeding after ERCP.