The Journal of V. N. Karazin Kharkiv National University, series "Medicine"

Fuzzy logic approach for heart rate variability

Alexander Martynenko — 2021-06-30

Intrioution. The heart rate variability (HRV) is based on measuring (time) intervals between R-peaks (of RR-intervals) of an electrocardiogram (ECG) and plotting a rhythmogram on their basis with its subsequent analysis by various mathematical methods that are classified as Time Domain (TD), Frequency Domain (FD) and Nonlinear (NM) [1, 2]. Diversity of methods and approaches to analysis of HRV is stemming from complexity and nonlinearity of the phenomenon itself, as well as from greater diversity of physiological reactions of an organism, both in normal and pathological states. Therefore, it appears relevant and important to incorporate currently existing HRV indicators and norms into a unified Fuzzy Logic (FL) methodology, which in turn will allow to integrally assess each metric and HRV results as a whole. Objective. We propose a Fuzzy Logic algorithm for incorporating into a single view of each metric, – Time Domain, Frequency Domain, Nonlinear Methods and HRV as a whole. Materials and methods. We define by FL the extent of belonging to normal state both for each distinct HRV metric – TD, FD and NM, and for a patient's HRV in general. Membership functions of any HRV index and defuzzification rules for FL scores was defined. In order to implement the proposed algorithm, specified parameters of mean values of HRV (М) indicators and their standard deviation (σ) have been found in scientific publications on HRV [1, 3, 7, 8, 9, 10]. We use for FL algorithm demonstration a long-term HRV records by Massachusetts Institute of Technology - Boston’s Beth Israel Hospital (MIT-BIH) from [11], a free-access, on-line archive of physiological signals for Normal Sinus Rhythm (NSR) RR Interval, Congestive Heart Failure (CHF) RR Interval and Atrial Fibrillation (AF) Databases [12]. Conclusion. In this article, we have presented a comprehensive view of HRV by Fuzzy Logic technology and thoroughly examined the peculiarities of its application and interpretation. Of all considered examples of FL analysis, the worst result is demonstrated by a patient from the AF group, while the best one belongs to a patient from the NSR group. Difference in FL Scores between these patients from NSR and CHF groups is almost 4 times, while between patients from NSR and АF groups it is almost 6 times. It appears especially important to implement such a design in portable medical devices for quick and easy interpretation of numerous parameters measured by them.

Dynamics of blood lipid spectrum indicators in children with juvenile idiopathic arthritis taking into account basic therapy

Ludmila Bogmat — 2021-06-30

Summary. In patients with rheumatoid arthritis, the risk of cardiovascular disease associated with atherosclerosis, is significantly increased compared to the general population. Studies of a cohort of children and young adults indicated that the atherosclerotic process usually begins long before its clinical manifestation, and the degree of vascular changes is associated with both the number of risk factors and their severity. The use of basic drugs in rheumatic patients contributed to a decrease in cardiovascular mortality, mainly due to the elimination of the activity of the process, which itself is an inducer of the onset and progression of atherosclerosis. The aim of the study was to establish the nature of changes in the blood lipid spectrum in children with juvenile idiopathic arthritis under the influence of basic therapy. Object and methods. We examined 85 children (8–18 years old) with juvenile idiopathic arthritis and oligo- (61.5 %) and polyarticular (38.5 %) variants of the disease, twice, with an interval of one year. The parameters of the blood lipid spectrum were determined by the level of: total cholesterol, triglycerides, high density lipoproteins, atherogenic coefficient by the enzymatic method on an automatic biochemical analyzer-photometer A25, low lipoproteins and very low density cholesterol by calculation method. Research results. Analysis of the lipid profile in the group as a whole showed that patients with juvenile idiopathic arthritis had significantly higher total cholesterol values (p < 0.05), a tendency to an increase in the level of triglycerides, low lipoproteins and very low density cholesterol, which led to an increase in the atherogenic coefficient level. When analyzing the lipid spectrum of blood after a year, a tendency towards a decrease in the level of atherogenic and an increase in antiatherogenic fractions of the lipid spectrum with normalization of atherogenic coefficient was noted. In the group of patients receiving monotherapy with methotrexate, no significant changes in the lipid spectrum of blood were observed after one year. Against the background of combined basic therapy, the blood lipid spectrum normalizes, namely, a decrease in total cholesterol, an increase in high density lipoproteins of cholesterol, a decrease in the level of low density cholesterol (p < 0.05), triglycerides and very low density cholesterol and, as a consequence, significant decrease in atherogenic coefficient (p < 0.01). Conclusions. The dynamics of changes in blood lipid spectrum indicators in children with juvenile idiopathic arthritis confirms the need to use combined basic therapy not only to control the activity of main pathological process, but also to prevent the development of atherogenic dyslipoproteinemias.

The role of the muscular system in the pathogenesis of thrombotic complications of the lower extremities in cancer patients

Petro Bodnar — 2021-06-30

Introduction. Thrombosis occurs in 15 % of cancer patients, most of these thrombosis is localized in the venous system of the lower extremities. In addition to biological and chemical factors that increase thrombosis, changes in the muscles of the lower extremities play an important role. Disorders of hemodynamic and metabolic processes in the muscles of the lower extremities lead to morphological changes and increase the risk of thrombosis in cancer patients. The aim of the study. Investigate morphological changes in the muscles of the lower extremities and evaluate their role in the formation of thrombosis in cancer patients. Materials and methods. Histological examination of 90 patients, which were divided into four groups depending on the location of the cancer process and the cause of death. The first group A – 34 patients with colon cancer, the second group B – 20 patients with pancreatic cancer, patients from these groups died as a result of thromboembolism. Group B – 19 patients, and group G – 17 patients - people whose cause of death was not thromboembolism. The analysis of biomaterial by means of histological and polarization methods of research is carried out. Additionally, electron microscopy of the obtained biopsy materials was performed. The number of citrate blood endothelial cells was determined in all subjects according to the method of J. Hladovez. Research results and their discussion. The study revealed a large number of morphological changes in blood vessels and muscle fibers. The data obtained indicate that patients with cancer of the pancreas and colon have significant changes in the endothelial lining of the venules and areterioles. All cells have signs of interstitial edema, changes in organelles and signs of hemodynamic disturbances. In some areas, there were complete atrophy of some muscle fibers and compensatory hypertrophy of others. Studies have shown areas of sarcoplasmic homogenization and myocytolysis. Conclusions. In the case of cancer of the pancreas or/and colon, there is significant damage to the endothelium of the vessels of the lower extremities, there are dystrophic-atrophic changes in the muscles with impaired function. Cells suffer from interstitial and perivascular edema, there are contractures of change, myocytolysis. Morphological changes lead to disruption of their function of damage, myocytolysis and remodeling of muscle fibers. The result is an increased risk of thrombosis with subsequent thrombus consideration and a possible risk of pulmonary embolism.

Interleukin-31 new biomarker of infectious skin diseases

Diana Dorosh — 2021-06-30

Introduction. The introduction of antiretroviral therapy has significantly improved the long-term prognosis of AIDS patients, but opportunistic infections can still be life-threatening for this population. Among them, a large group constitutes of herpesvirus infections, which are frequent manifest forms of dermatological manifestations of HIV. The researching of IL-31, as a prospective diagnostic predictor of dermatological diseases, has been actively conducted in recent years. This is due to the interest in its biological action, which extends primarily to the skin. Тhe identification of molecular targets underlying inflammatory and infectious dermatoses is promisingly for the development of new, targeted treatments. Objective: to study the role of IL-31 in the immunopathogenesis of herpesvirus infections associated with HIV infection. Research objectives: 1) to compare the levels of IL-31 in the blood serum in patients with herpesvirus skin diseases associated with HIV infection and in healthy subjects; 2) to determine the presence of a relationship between the levels of IL-31 in the blood serum and the clinical stage of the disease. Materials and methods. The study included patients with herpesvirus infection caused by HSV-1, HSV-2, VZV-3, EBV and HHV-8 associated with HIV infection and healthy individuals. Serum IL-31 levels were measured by ELISA using commercial kits (Human IL-31 ELISA Kit, Abcam, Cambridge, MA, USA). Were collected the baseline clinical characteristics, assessment of the activity of the infectious process and the degree of immunosuppression. Results. Our study involved 39 patients with herpesvirus infection associated HIV and 31 patients of the control group. In patients with herpesvirus infection against the background of HIV infection, the average level of IL-31 in the blood serum was significantly higher than that of healthy subjects. Serum IL-31 levels in patients with herpesvirus infection did not differ significantly depending on the severity of the process and the degree of immunosuppression. Conclusion. The levels of IL-31 in the blood serum of patients with herpesvirus infection were differed by statistically significant validity in comparison with similar indicators of healthy individuals, which confirms its role in the pathogenesis of infectious skin diseases.

Structure of abdominal injury and its consequences

Madona Gogiya — 2021-06-30

Introduction. Mechanical injuries are a leading cause of disability and premature death among the working-age population in most countries worldwide. Injuries to the abdominal and retroperitoneal organs (abdominal trauma) significantly aggravate the course of trauma and are a frequent cause of death. The aim of the study was to analyse the structure and outcome of the treatment of abdominal trauma victims. Materials and methods. On the basis of the polytrauma department of the municipal non-profit enterprise «Municipal clinical hospital of emergency and urgent medical care named after A. I. Meshchaninov» of Kharkiv City Council councilаnalysis damage structure and the results of treatment of 240 patients with abdominal trauma were carried out, the main causes of lethal outcomes were determined. Results. Most of the patients with abdominal trauma were male (78,7%), and they were young (18 to 44 years old) (72,5 %). The cause of injury in 95 (39.6 %) victims was road traffic accident, in 58 (24.2 %) – catatrauma; in 65 (27.1 %) – domestic injury. In the abdominal cavity, parenchymatous organs (spleen and/or liver) were injured most frequently, identified in 66.7 % of victims. In 26.3 % of patients revealed damage to the small or large intestine, in some cases, trauma to the stomach and gallbladder was detected. In 37 (15.4 %), mesenteric injury was detected, and in 32 (13.3 %), omental injury was detected. Among retroperitoneal organs the renal trauma was frequent – 46 (19.2 %), pancreatic and urinary bladder injuries were revealed in 27 (11.2%) and in 13 (5.4%) cases, retroperitoneal haematoma was revealed in 63 (26.7 % ) victims. In 178 (74.2 %) victims a combined trauma was diagnosed: thoracic in 129 (53.8%) cases, skeletal in 96 (40 %), craniocerebral in 84 (35 %). Combined injuries of one anatomofunctional region were diagnosed in 80 (33.3 %), two in 67 (27.9 %), and three in 31 (12.9 %) victims. During in-hospital treatment, 34 (14.2 %) victims died, of which 12 (35 %) during the first week after injury. The duration of inpatient treatment for the victims who were discharged was 15.0 [12.0; 25.0] beds/day. The causes of mortality and prolonged hospitalization (more than 14 days) in most cases were cardiovascular, respiratory, purulent-septic and renal complications. Conclusion. Abdominal parenchymal injuries predominate in the structure of abdominal trauma, occurring in 66.7 % of victims. Combined (thoracic, skeletal and/or craniocerebral) trauma occurs in 74.2 % of victims. The fatality rate for isolated abdominal trauma was 4.8 %, with a significant increase in cases of combined trauma, up to 41.9 % for combined thoracic, skeletal and craniocerebral trauma.

Increasing efficiency of preterm birth prediction

Serhiy Korovai — 2021-06-30

Abstract. The disturbed placentation in a certain way plays an important role in the pathogenesis of great obstetric syndromes. Therefore, the possibility of using biochemical indicators of the level of placental growth factor (PlGF) and fms-like tyrosine kinase (sFlt-1) for predicting preterm labor is of great interest. The aim of the study was developing criteria for predicting preterm labor based on the combined use of ultrasound cervicometry and the concentration of PlGF and sFlt-1. Materials and methods. A total of 227 pregnant women were examined, 190 of whom had preterm birth. Group I included 48 women whose pregnancy completed at 23 to 27 weeks. In group II, 142 women with prematurity in terms of 28 to 36 weeks were observed. Group III included 37 women with a healthy pregnancy, which completed at 38–41 weeks. All patients involved in the study underwent ultrasound cervicometry on a Voluson 730 (GE Healthcare, USA) at 16 weeks, and also the concentration of PlGF and sFlt-1 in blood serum by electrochemiluminescence immunoassay using a Cobas e411 analyzer was studied (Roche diagnostics, Switzerland). Results. The study revealed a significant (p < 0.001) decrease in the average concentration of PlGF in the blood serum by 65 % associated with an increased level of sFlt-1 by 93% in women with early termination of pregnancy – 23–27 weeks (group I) in relation to women with a healthy pregnancy. In women with preterm birth at 28–36 weeks of gestation (group II), a similar trend of changes was observed: the PlGF level significantly (p = 0.014) decreased on average by 68 % in relation to women with a healthy pregnancy. In women of group I, the value of the sFlt-1 / PlGF ratio exceeded (p < 0.001) the values of patients in group III by 14 times. But an even more pronounced imbalance of angiogenic factors was observed in women of group II – on average 16 times. Two main markers were used to predict premature birth: shortening of the cervix according to ultrasound cervicometry data of less than 30 mm, as well as the sFlt-1/PlGF ratio of more than 50 conv. units. The odds ratio (OR) of preterm birth in the case of using only the length of the cervix was 34,133 (95 % confidence interval – 12.308–94.660). OR in the case of combined use of cervicometry data and angiogenesis variables was 148.750 (95 % confidence interval – 33.243–665.593). Conclusion. Thus, the use of an additional biochemical marker significantly improved the accuracy of preterm labor prediction.

Prediction of changes in central hemodynamics in overweight men with further development of obesity

Marianna Nemesh — 2021-06-30

Introduction. There is a wide range of anthropometric methods for determination overweight and obesity. The most popular are body mass index, waist and hip circumference or waist-hip ratio and the measurement of body composition using bioimpendance method. Each of these methods has a lot of pros and cons, but none of them is the «gold standard». Therefore, it is not enough to rely only on the results of indirect methods to assess the state of the human body. They should be taken into account with laboratory or diagnostic methods, to better assess the morpho-functional features of the human body. The aim. To determine the relationship between central hemodynamic parameters and indices obtained by bioimpedance and anthropometric methods in order to predict changes in central hemodynamics in overweight men with the further development of obesity. Materials and methods of the research. 49 men aged 18–25 were examined. Body component composition was measured using Tanita BC-601 analyzer scales. Also body mass index and waist, hip circumference were measured. The indices of the cardiovascular system were determined using the rheographic complex «REOKOM», the method of tetrapolar rheography according to Kubicek. The results of the study were statistically processed using correlation and multifactor regression analysis. Results. According to the results of multifactor regression analysis, it was found that waist circumference and the index of visceral fat were associated with indices of cardiac index and the index of workload of left ventricular and the index of the peripheral vascular resistance (p < 0.05). Waist circumference and index of visceral fat had negative correlations with total peripheral resistance (r = -0,351 and r = -0,34, p < 0,01). Moreover, waist circumference and the index of visceral fat have positive correlation with cardiac output and the workload of left ventricle (r = 0,543, p < 0,001; r = 0,378, p < 0,001). Conclusions. Waist circumference and indices of visceral fat and subcutaneous fat in the trunk are the most accurate methods for predicting in future not only abdominal obesity but also an increase in workload of the left ventricle, cardiac output, and decreased vascular resistance.

BRCA1 and BRCA2 genes mutations among women with clinical signs of hereditary breast cancer in western Belarus

Alena Savanevich — 2021-06-30

Background: Breast cancer is the most common malignancy in women. In the countries of Central and Eastern Europe founder mutations in the BRCA1 and BRCA2 genes are responsible for a significant proportion of breast cancer cases; however, regional differences in the frequencies of various mutations may occur. The spectrum and frequency of BRCA1 and BRCA2 mutations among breast cancer patients have not yet been fully explored in Belarus. Aim: In this study, we aimed to estimate the incidence of BRCA1 and BRCA2 causative founder variants in breast cancer female patients with clinical signs of hereditary disease in western Belarus. Materials and Methods: Blood samples from 71 breast cancer female patients with clinical signs of hereditary disease from the western region of Belarus were examined. We studied 13 causative founder variants in BRCA1 (c.5266dupC, c.4035delA, c.5251C>T, c.181T>G, c.676delT, c.68_69delAG, c.3770_3771delAG, c.1687C>T, c.3756_3759delGTCT) and BRCA2 (c.658_659delGT, c.7910_7914delCCTTT, c.3847_3848delGT, c.5946delT) genes characteristic for the population of Central Europe. The study included 22 female patients with early-onset form, 8 individuals with bilateral and 41 women with multiple primary breast cancer. Results: 32 out of 71 patients (45 %) had one of the causative founder variants in the BRCA1 and BRCA2 genes. The most common mutation defined in these genes was BRCA1 c.5266dupC; it was detected in 19 women with breast cancer (27 %). The carrier of the pathogenic BRCA1 allele c.4035delA was confirmed in 8 cases (11 %). BRCA1 gene mutations were found to be significantly more common in presence of two or more signs of genetic predisposition to breast cancer. However, among 50 patients with a family medical history of breast and/or ovarian cancer and clinical signs of hereditary cancer, mutations in the BRCA1 and BRCA2 genes were found only in 24 (48 %) cases. Conclusion: The study showed high incidence of germinal BRCA1 mutations (45 %) among breast cancer patients in the western region of Belarus. Only two BRCA1 mutations (c.5266dupC, c.4035delA) are detectable in approximately 84 % of carriers. It is necessary to continue studying the mutations in the genes associated with development of breast cancer that are typical for Belarusian population, especially in the group of young female patients, since this study has confirmed the genetic predisposition only in every third patient under the age of 50.

Peculiarities of structural-functional indicators of the heart in the combined of hypertension and gastroesophageal reflux disease in liquidators of consequences of Chornobyl accidents

Nataliia Tkachenko — 2021-06-30

The Chornobyl accident in Ukraine affected more than 3 million people. The impact of the disaster on human health is multifaceted and is associated with both the direct effects of ionizing radiation and other negative factors of the accident. Diseases of the circulatory system are one of the leading causes of death in this population. The combination of hypertension disease and gastroesophageal reflux disease reveals forms of structural and functional indicators of the heart, characterized by a higher level of left ventricular myocardial hypertrophy, regardless of the stage of HD and the degree of blood pressure. The aim was to determine the features of structural and functional indicators of the heart in the combined course of HD and GERD in the liquidators of the Chornobyl accident, as well as to establish differences from the indicators of patients with isolated HD. Materials and methods of research. A comprehensive survey of 105 liquidators of the Chornobyl accident aged 52 to 69 years (mean age 58.5 ± 0.8 years), 85.7 % of men and 14.3 % of women was conducted. All of them were hospitalized in therapeutic and / or observed on an outpatient basis in the outpatient departments of the «Regional Clinical Specialized Dispensary for Radiation Protection of the Population» of Kharkiv. Patients were divided into 2 groups. The first group – 52 patients with a combined course of HD and GERD, 44 (84.6 %) men and 8 (15.4 %) women. The second – 53 patients with isolated HD, 46 (86.8 %) men and 7 (13.2 %) women. All patients in outpatient settings underwent a comprehensive medical examination, including Doppler echocardiography. Results and conclusions. When comparing the structural and functional parameters of the heart in the combined course of HD and GERD in the liquidators of the Chornobyl accident with an isolated course of HD, it was found that almost all indicators of systolic, diastolic and pumping heart function are statistically significantly increased, p ≤ 0.05, except for aortic pressure size gradient and diameter of right ventricule. Thus, patients with a combined course of pathology have more pronounced changes in the structural and functional parameters of the heart, thereby increasing the risk of cardiovascular complications. Prospects for the study are relevant and necessary for further prediction of the risk of complications and individual therapeutic approach in comorbid pathology in the liquidators of the Chernobyl accident.

Viscose and Thrombocytic-Aggrega-Tion Disorders On Patients With Myocardial Infarction With Stable Elementation of ST Segment

Dmitriy Uzun — 2021-06-30

Abstract. Clinical studies indicate a significant role in the pathogenesis of acute myocardial infarction, the functional state of platelet aggregation and blood viscosity, which determine the nature of blood flow in the vessels at the level of macro- and microcirculation. The aim of the study was to analyze changes in viscosity and platelet-aggregation disorders under the influence of different tactical, diagnostic and interventional approaches in patients with myocardial infarction and stable elevation of the ST segment in the presence of multivascular coronary artery disease. Materials and methods. The study used 4 tactical and treatment-diagnostic approaches during the year of observation. Results. Patients with myocardial infarction with persistent ST-segment elevation were found to have hyperviscosity and hypercoagulability syndromes, manifested in the first weeks by a compensatory increase in platelet count, blood viscosity, fibrinogen levels, and an increase in platelet aggregation. Conclusions. Carrying out additional in-depth examination of coronary circulation (coherent tomography and intravascular sonography) as the main methods of detailed assessment of atheromatous process and further application of delayed stenting of infarct-independent arteries in group 1, contributed to lower amplitude of fluctuations, due to the systemic step-by-step improvement of arterial blood supply, to optimize the state of viscosity and processes of adhesion / aggregation of platelets. Traditional tactical and medical-diagnostic principles of this category of patients do not allow to fundamentally improve the state of viscosity and coagulation-aggregation parameters, even with the use of dual antiplatelet therapy.

Modern concept of the etiology and pathogenesis of androgenetic alopecia

Yuliya Ovcharenko — 2021-06-30

Introduction. The understanding of the etiology and pathogenesis of androgenetic alopecia (AGA) has formed modern therapeutic strategies for the treatment of this trichopathy. However, the significant prevalence of this pathology, limited therapeutic success, and differences in the response to standard therapy in male and female patients determine the interest in a more in-depth study and search for new links in the etiopathogenesis of AGA. Goal. Using a review of scientific publications in recent years on AGA in male and female patients, analyze and formulate the modern concept of the etiology and pathogenesis of this disease in order to further search for new treatment methods. Materials and methods. We searched and analyzed publications for the query «androgenetic alopecia, etiology, pathogenesis», the search was carried out using Google Scholar, considered articles that have been published since 2016. Results. The effect of androgens on hair follicles in androgen-dependent areas of the scalp under conditions of genetic predisposition is considered as the most studied and proven concept of AGA etiopathogenesis. However, recent studies have also revealed nonandrogenic cofactors, among which the pathological cascade of events «oxidative stress-microinflammation-fibrosis», which are determined at different stages of disease progression, is potentially interesting for further study. Knowledge of the phenomenon of apoptosis as an important factor in the disturbance of the dynamics of the hair cycle has been expanded. The management of perifollicular microinflammation and apoptosis can allow the control of the processes of sequential hair miniaturization and give a pronounced clinical result during the treatment of AGA. Thus, the nonandrogenic mechanisms of AGA pathobiology require further study. Conclusions. New data on the causes and mechanism of development of androgenetic alopecia in women and men have expanded our understanding of these processes. The need to supplement knowledge on this topic causes significant scientific interest and is very relevant, since they can be used to improve treatment for use in practical medicine.