REVIEWS AND LECTURES
The widespread introduction of percutaneous coronary intervention (PCI) in the treatment of acute myocardial infarction (AMI) caused a significant reduction in the mortality rate from AMI in developed countries. However, over the past 10 years, there was no significant reduction in in-hospital mortality from AMI. It is clear that there is an urgent need to develop novel drugs that could effectively prevent reperfusion injury of the heart after successful recanalization of the infarct-related coronary artery. Enzyme-resistant peptide agonists of the oxytocin receptor could become a prototype for the creation of such drugs. It was shown oxytocin could selectively prevent cardiac reperfusion injury. The cardioprotective effect of oxytocin in coronary artery occlusion and myocardial reperfusion is distinguished by a decrease in infarct size, an improvement in cardiac contractility, and a decrease in the incidence of ventricular arrhythmias. In addition, oxytocin inhibits apoptosis and pyroptosis of cardiomyocytes in hypoxia/reoxygenation. It has been established that kinases, NO-synthase, and guanylyl cyclase are involved in an oxytocininduced increase in cardiac resistance to ischemia / reperfusion.
Despite timely coronary reperfusion, about 7% of patients with acute myocardial infarction die during hospitalization and around 23% survivors develop heart failure within one year. Reperfusion injury is largely responsible for the final infarct size. Although, there is some progress in myocardial revascularization, prevention and treatment of the reperfusion injury in myocardial infarction patients is not successful enough in clinical practice. Hypothermia can reduce reperfusion injury and improve survival and reduce the number of complications in patients with myocardial infarction.
Background. The high mortality rate among patients with acute myocardial infarction (AMI) is an important problem of modern cardiology. In recent years, there has not been a significant decrease in mortality in AMI. Drugs used to treat AMI are not effective enough, so there is a need to develop fundamentally new drugs that can significantly increase the heart’s tolerance to ischemia/reperfusion (I/R). Angiotensin 1-7 peptide, which can increase cardiac tolerance to I/R by activating Mas receptor in myocardial tissue, could become a prototype of such drugs. The following enzymes are involved in the formation of the cardioprotective effect of angiotensin 1-7: NO-synthase, soluble guanylyl cyclase, phosphoinositide 3-kinase, extracellular signal-regulated kinases-1/2, Akt kinase and, possibly, protein kinase G. Indirect data indicate that the hypothetical end effector in the cardioprotective impact of angiotensin 1-7 could be mitochondrial or sarcolemmal ATP-sensitive K+ channel.
Aim: To review 1-7 role in increasing the heart resistance to ischemia and reperfusion. The literature search was carried out in the PubMed database with queries “angiotensin 1-7 receptors”, “stress”, “angiotensin 1-7”, “mas receptor”, “cardioprotective effects of angiotensin 1-7”.
The article discusses recent research on the effective and safe use of the amino acid L-arginine for medicinal purposes in various pathologies. The practical significance of using L-arginine as a source of nitric oxide is considered. The physiological role of nitric oxide, the main vasodilator, was shown, and its deficiency was found to be a key link in endothelial dysfunction. An analysis of modern studies confirming the effectiveness of L-arginine as a donor of nitric oxide was carried out. Ample evidence suggests that oral administration of L-arginine, within physiological limits, can benefit human health by increasing NO synthesis and hence tissue blood flow.
Arterial hypertension (AH) remains a global problem of modern healthcare, since, despite advances in clinical pharmacology and the use of modern antihypertensive drugs, it continues to be a major risk factor for cardiovascular complications. This necessitates a more in-depth study of the pathogenetic mechanisms of this disease and the development of new pathogenetically based methods of its treatment. Every year more and more studies are published, the results of which indicate the significant role of autonomic imbalance in the pathogenesis of the disease. The article presents the main modern data concerning the study of this problem. A detailed analysis of works devoted to the role of sympathetic hyperactivation in a sustained increase in blood pressure (BP) and the development of pharmacotherapy-resistant forms of hypertension (RAH) was carried out. Particular attention is paid to the influence of modern endovascular methods on changes in the severity of immunoinflammatory processes, through the activation of which the hypertensive effects of increased activity of the sympathetic nervous system are realized. Possible mechanisms of the therapeutic effectiveness of renal denervation and prospects for further clinical application of the method are described.
CLINICAL STUDIES
The article presents preliminary study results of association of direct ultrastructural characteristics of mitochondria (MTC) in cardiomyocytes and indirect signs of mitochondrial dysfunction with clinical course and outcomes of chronic heart failure (CHF). According to electron microscopy of the myocardium a violation of the ultrastructure of MTC of cardiomyocytes is accompanied by a decrease in the rate of oxygen absorption by mitochondria of leukocytes of peripheral blood, separation of oxidation and phosphorylation processes, an increased rate of radiopharmaceuticals leaching from myocardium, indicating mitochondrial membrane damage, low tolerance to physical load and reduced oxygen consumption at peak of load test, which confirms the feasibility of studying associations of indirect signs of mitochondrial dysfunction with ultrastructural changes in the mitochondrial cardiomyocytes and clinical manifestations of heart failure.
Aim: To examine a reaction of young physically active men with early repolarization phenomena (ERP) on an inhalation of a hypoxic gas mixture (IHGM).
Material and Methods.17 men (6 with ERP & 11 without it) participated in our study. ECG, echocardiography, clinical blood test and erythropoietin blood test were carried out to every of them initially and on the 1-st and 10-th days after the IHGM.
Results. It was found that end systolic volume was 13,8% more (р = 0,01) and ejection fraction was 8% less (р = 0,01) in ERP group than in non ERP group. These indicators were not change after IHGM. In ERP group on 1-st day after IHGM erythropoietin concentration was 79% more (р = 0,027) and on a 10-th day was 64% more (р = 0,003) than in non-ERP group. In ERP group high fluorescent reticulocyte count on a 1-st day after IHGM was 69% more (р = 0,03) and middle fluorescent reticulocyte count on a 10-th day after IHGM was 13% more (р = 0,04) than in non-ERP group. On a 10-th day after IHGM hematocrit and hemoglobin concentration were 5% (р = 0,01) and 12% (р = 0,01) less than in non ERP group.
Conclusion. Thus, men with ERP have a pronounced reaction of the erythropoiesis system on normobaric hypoxia.
Introduction. Currently, the study of comorbidity, which is characteristic of the clinical picture of modern patients, is relevant. This also applies to psychiatric disorders in cardiovascular diseases, which are common, affect social functioning and determine the clinical and biological characteristics of patients and prognosis. Bipolar disorder and coronary heart disease are one example of such a comorbidity. Recent evidence suggests that up to 40% of patients with bipolar disorder die from cardiovascular disease.
Aim: To study the frequency of bipolar disorders and their clinical and dynamic features in patients with chronic coronary artery disease with the assessment of seven-year survival rates.
Material and Methods. Patients with confirmed chronic coronary artery disease, aged 35–70 years, living in Tomsk and the Tomsk Region: the main group (with identified mood disorders, diagnosed by a psychiatrist, n = 262) and the comparison group (without mood or other mental disorders, n = 291). The Hamilton Depression Scale for Seasonal Affective Disorders was used to assess depressive symptoms. The survival tables and Kaplan – Meier methods were used to assess survival, survival curves were compared using the Mantel – Cox logrank test.
Results. The frequency of bipolar disorder among hospitalized patients with chronic coronary artery disease was three times higher than that in the population. Depressive symptoms in bipolar disorder did not differ clinically from those in other mood disorders. The prognostic signs indicating the risk of bipolar disorder include: family history with mental disorders, atypical specification of depression, earlier age of onset of depression, high multimorbidity with mental (anxiety disorders, dependence syndrome due to alcohol, nicotine) and physical diseases. According to a retrospective assessment, coronary artery disease in half of the cases developed against the background of bipolar disorder. During the 7-year follow-up period, the number of cases of bipolar disorder doubled compared to the beginning of the study. Patients with bipolar disorder had more frequent acute myocardial infarction and had clinically more significant functional classes of angina pectoris and heart failure.
Conclusion. During the 7-year follow-up period, the number of patients with bipolar disorder doubled. Patients with this comorbidity had an unfavorable prognosis in terms of survival (62.5%) compared with individuals without mood disorders.
Background. The main problem in patient selection for cardiac resynchronization therapy (CRT) is the lack of unified approaches to the definition of mechanical dyssynchrony (MD) and selection criteria, particularly, in patients with left bundle branch block (LBBB).
Aim: To study mechanical dyssynchrony indices and three-dimensional Echo (3DE) criteria of global and local contractility function in patients with chronic heart failure (CHF) and LBBB during different types of isolated left ventricle (LV) pacing.
Methodology and Research Methods. The experimental intraoperative study involved 88 points obtained from 12 patients with CRT class IA indications and LBBB. During isolated LV pacing as part of CRT implantation procedure endocardial and epicardial pacing were obtained. Transesophageal Echo (TEE) cineloops recording and paced QRS complex morphology registrations by means of LabSystem Pro Electrophysiological Recording System (Bard Electrophysiology, USA) were performed during each stimulation episode. Philips Qlab 10 software was used for TEE data analysis.
Results. The global (3D EF, 23.8 [22; 28.4], GLS, –5.33% [10.90%; –15.4%]) and local contractility (ExсAvg 3.5 [2.1; 5.6]) criteria and dyssyncrony indices (SDI-16, 14.9 [8.9; 23.1]) showed severe systolic dysfunction and intraventricular dyssynchrony – typical signs in this patient group, and differed significantly (3D EF, p = 0.003; GLS, p = 0.004; ExcAvg, p < 0.001; Tmsv-6 SD, р = 0.03) depending on the stimulation method and site. A moderate direct correlation between SDI-16 and the QRS duration (common electical dyssynchrony criterium) and inverse correlation with ExcAvg and 3D LVEF also describes LV response.
Knee osteoarthritis (OA) is a disease resulting from the interaction of many local and systemic risk factors, among which an important role is played by genetic (hereditary) factors. This disease affects both men and women, but there are certain differences in the development and progression of the disease in different sexes.
Aim. To study associations of polymorphic loci of candidate genes with the risk of developing knee ОА in the male population of the Central Chernozem region of Russia.
Material and Methods. The study sample included 410 men (208 patients with knee OA and 202 controls). Ten polymorphic loci of candidate genes were genotyped: rs2820436 and rs2820443 LYPLAL1, rs3771501 TGFA, rs11177 GNL3, rs6976 GLT8D1, rs1060105 and rs56116847 SBNO1, rs6499244 NFAT5, rs34195470 WWP2, rs143384 GDF5. The study of associations of polymorphic genetic loci with the development of the disease was carried out by the method of logistic regression, taking into account covariates (age, BMI). The MB-MDR method was used to study intergenic interactions of polymorphisms associated with the disease.
Results and Discussion. It was found that nine out of ten polymorphic loci of candidate genes (with the exception of rs6976 GLT8D1) are associated with the formation of knee OA in men in four models of interlocus interactions (pperm ≤0.024). The rs3771501 TGFA polymorphic locus (included in three of the four most significant models of gene-gene interactions) demon- strates the greatest contribution to the development of the disease in men. Independent effects of the studied polymorphic loci of candidate genes in the development of knee OA in men have not been identified (р > 0,05).
Conclusion. Polymorphic loci rs2820436 and rs2820443 LYPLAL1, rs3771501 TGFA, rs11177 GNL3, rs6976 GLT8D1, rs1060105 and rs56116847 SBNO1, rs6499244 NFAT5, rs34195470 WWP2, rs143384 GDF5 involved in the development of knee osteoarthritis in men in four models of intergenic interactions. Among the studied loci, rs3771501 of the TGFA gene has the greatest contribution to disease susceptibility.
Aim: To study the correlations between Cystatin C (Cys-C) level and values of the markers of immune system and inflammation, and clinical manifestations of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM).
Material and Methods. 3 groups of patients with type 2 diabetes and different stages of diabetic retinopathy were formed (21 people in each). Group I – with nonproliferative diabetic retinopathy (NPDR), Group II – with pre-proliferative diabetic retinopathy (PPDR), Group III – with proliferative diabetic retinopathy (PDR). The comparison group included patients with type 2 diabetes without vascular complications. Clinical study included: visometry, tonometry, assessing critical flicker fusion frequency, biomicroscopy of the anterior segment of the eye, ophthalmoscopy, biomicroscopy and ultrasound of the retina, crystalline lens, vitreous body, photographic recording of the fundus, optical coherence tomography. The content of Cystatin C (Cys-C), soluble forms of molecules B7.2 (CD86), 4-1BB, CTLA-4, Tim-3, LAG-3, PD-1, PD-L1, Galectin-9, proteins sICAM-1, SAA, NGAL and enzymes (MPO, MMP-2, MMP-9) was examined in the blood serum with the use of multiplex analysis.
Results. As DR progresses, the level of Cys-C increases and becomes higher than in individuals with diabetes: with NPDR higher by 94.1% (p < 0.001), with PPDR – higher by 293.6% (p < 0.001). In individuals with PDR, the concentration of Cys-C is maximum. With DR, the amount of PD-1, PD-1L, NGAL, ICAM-1, MMP-9, and MPO increases in the blood serum; as the severity of DR worsens, the levels of ICAM-1, MPO, and MMP-9 increase. Direct correlations were found between the Cys-C values, on the one hand, and the values of some studied indicators, on the other.
Conclusions. In type 2 diabetes and DR, the amount of Cys-C in the blood serum increases relative to individuals with diabetes without microangiopathy; in groups with worsening severity of ophthalmopathy, an increase in Cys-C concentration was recorded with a statistically significant difference between the groups. In groups with DR, the level of ICAM-1, MMP-9, and MPO increases with increasing severity. Moderate direct correlations were found between the amount of Cys-C on the one hand and PD-1, PD-L1, as well as the noticeable ones with the values of ICAM-1, NGAL, MMP-9, MPO on the other. A direct noticeable correlation was revealed between the level of Cys-C and the values of the fundus scale.
Introduction. Thoracic aortic aneurysm (TAA) ranks 17th among all causes of a death. Over the past decade, the incidence rate of TAA increased several times and occurs in about 10 out of 100 thousand people per year. The search for the causes that lead to TAA is an urgent task. Local mechanical stress on the aortic wall leads to significant molecular and cellular changes in its tissue.
Aim: To investigate the relationship between biomechanical properties and histological changes in the TAA tissue.
Material and Methods. Thirty patients with TAA were included in the study. During surgery, fragments of the resected ascending aorta were obtained from each patient and subjected to uniaxial biomechanical testing to failure on an Instron 3343 testing machine (Instron, USA). Ultimate tensile stress at failure (σv, MPa), ultimate strain at failure (ε, mm/mm × %) and area under stress-strain curves (S, cm2) were calculated. In addition, the intraoperative material was fixed in formalin for histological examination of cellular and tissue changes in the aneurysm area. Inflammatory changes, the severity of aortic wall fibrosis and collagen/elastin ratio were assessed.
Results. Atherosclerotic changes of the thoracic aortic wall were found in 43.3% (subgroup 1), aortitis – in 3.3%, connective tissue dysplasia – in 53.3% (subgroup 2) of the patients. Patient with inflammatory changes of the aortic wall was excluded. The biomechanical properties of the aorta were not statistically different between groups. A correlation was found between age with εcirc (r = –0.49) and Scirc (r = –0.54) and Slong (r = –0.5). A correlation was also found between εcirc and the degree of fibrosis in the medial layer of the aortic wall (r = –0.5) and collagen/elastin ratio (r = –0.61).
Conclusions. Atherosclerotic changes in the aortic wall do not change the biomechanical properties of the TAA. However, structural changes in the medial layer of the aortic wall in the aneurysm zone result in reduced of its mechanical strength.
The study presents the possibility of using clinical blood test indicators characterizing the red hematopoietic germ in diagnosing the severity of the clinical condition of patients with COVID-19.
Aim: Dynamic monitoring of changes in the quantitative and qualitative characteristics of erythrocytes and reticulocytes to identify parameters that characterize the severe course of a new coronavirus infection in patients with cardiovascular pathology.
Material and Methods. The study included 94 patients with a confirmed diagnosis of a novel coronavirus infection (NCI), hospitalized in the department for the treatment of patients with CVD and COVID-19 with intensive care unit on the basis of the Academician L.S. Barbarasha between February and March 2022. Clinical blood analysis was performed on the 1st, 3rd and 7th day of hospitalization. Whole blood with K2EDTA was studied on a Sysmex XN-1000 hematological analyzer.
Results. To determine the diagnostically significant indicators of a clinical blood test, patients were divided into 2 comparison groups: group 1 – 71 people with a mild infection, group 2 – 23 people with moderate, severe and extremely severe NCI. On the first day of observation, 70% of patients in the group of unfavorable course were diagnosed with anemia, while in the group of mild course, 38% of patients were diagnosed. In patients with unfavorable development of the disease, normoblastemia was observed, which, according to the results of regression analysis, increased the risk of an unfavorable course by 5 times OR 0.24 (95% CI 0.07–0.884). Also in the severe group, there was a decrease in hemoglobin saturation of reticulocytes, which was expressed in deficient Ret-He and negative Delta-Hb values. Using binary logistic regression, it was found that a negative Delta-Hb 6 times increases the risk of an unfavorable course of NCI, OR 6.18 (95% CI 1.971–19.3).
Conclusion. The parameters of a clinical blood test that characterize the hemoglobinization of reticulocytes reflect the severity of the course of a new coronavirus infection and can be used to assess the clinical condition of patients with this infection.
Introduction. Information about the health status of children with nephrological pathology includes many manifestations of functional system disorders. However, early diagnosis of chronic kidney disease (CKD) is rarely carried out due to the lack of reliable predictors of this process.
The aim: To analyze the association of anamnestic signs, laboratory and genetic research results with chronic kidney disease in children to identify potential predictors of the disease.
Material and Methods. The data were obtained from a single-center retrospective catamnestic cohort study (2011–2022). The main group included 128 children with chronic kidney disease aged 1 to 17 years. The comparison group consisted of 30 children without diagnosed kidney pathology aged from 1 to 17 years. There were no statistically significant differences in sex and age between the two groups. The informative value of more than 150 features, including anamnestic ones, the state of the mother’s health during pregnancy, antenatal and perinatal factors, features of the child’s development and manifestation of the disease, the results of clinical, laboratory, and genetic research methods were evaluated. An integrated approach to the study included methods for hypotheses testing on statistical significance of indicators differences, regression analysis, and ROC analysis.
Results. Hereditary burden of nephrological pathology in the family, unfavorable course of pregnancy (anemia, toxicosis of the first half), obstetric and somatic pathology in the mother, the serial number of childbirth are associated with the subsequent development of CKD. Erythrocytes in the urine and daily protein loss were detected only in the group of children with CKD. In this group, a decrease in the number of red blood cells, increased erythrocyte sedimentation rate (ESR), allergies at an early age, otitis media, persistent viral and bacterial infections, and a number of signs of connective tissue dysplasia were more common. The main group statistically significantly differed from the comparison group by a number of polymorphic genetic markers. It can be assumed that the polymorphisms AGT1 Thr174Thr, AGT2 Thr235Thr, NO3 C786T are associated with a predisposition to CKD, and the products of polymorphisms AGT1 Thr174Met, AGT2 Met235Met, R1 AGT2 C1166C, NO3 T786T may have a protective effect according to development of CKD.
Conclusion. The risk factors for CKD identified in this study can be used to develop software to support medical decision making for early detection of children at high risk of disease progression.
Background: Hyperferritinemia associated with obesity and insulin resistance is a link between the components of the metabolic syndrome and a possible triggering factor in the pathogenesis of carbohydrate metabolism disorders and dyslipidemia.
Aim: To establish possible relationships between ferrokinetic parameters, parameters of lipid and carbohydrate metabolism in overweight and obese patients, and to analyze the possibility of using iron metabolism parameters (ferritin and serum iron) as predictors of carbohydrate metabolism disorders in this cohort of patients.
Material and Methods. The study included 52 overweight or obese patients. In the course of the study, patients were stratified into groups depending on the presence of carbohydrate metabolism disorders (CMD), and depending on the state of iron metabolism. Among all patients included in the study, an assessment of anthropometric data, a study of glycated hemoglobin, a standard glucose tolerance test with 75 g of glucose, a study of hematological parameters, as well as biochemical parameters of iron metabolism – the concentration of serum iron, transferrin and ferritin, was carried out.
Results. Patients with CMD – impaired glucose tolerance or impaired fasting glycaemia – had significantly higher serum ferritin levels than obese patients without CMD (p = 0.019). In persons with a high level of ferritin, CMD developed significantly more often than in patients with a ferritin content in the range below the 75th percentile (χ2 = 5.278, p = 0.022). According to the ROC analysis, ferritin showed a rather high sensitivity – 75%, and specificity – 84.4% at a diagnostic threshold of 126.65 ng/ml (area under the curve = 0.738; p = 0.016) in the diagnosis of prediabetes (IGT/IFG) in overweight and obese individuals.
Conclusion. High concentrations of iron and ferritin are positively associated with CMD, with ferritin being a promising predictor of prediabetes and type 2 diabetes mellitus.
EXPERIMENTAL STUDIES
One of the topical issues of modern circulatory physiology is the study of the peculiarities of the influence of chronic emotional stress on the histostructure of the liver.
Aim: To study changes in the histostructure of the liver in the simulation of chronic predatory stress.
Methodology and Research Methods. The study was conducted on 60 male Wistar rats weighing 220–370 g, divided into control and experimental groups of 30 rats each. Modeling of chronic predatory stress was performed according to the method of V.E. Zeilikman et al. (2021). Histological examination of the liver was performed in animals of the control and experimental groups. The preparations were stained with hematoxylin-eosin.
Results. Under conditions of chronic predatory stress, stress-induced changes develop in the liver of rats. Transformation of hepatocytes occurs with the development of dystrophic changes, expansion and fullness of sinusoidal capillaries with compression of hepatic beams and destruction of hepatic lobules, a decrease in the parenchymal-stromal ratio. Foci of foamy accumulation of macrophages appear without signs of necrosis, single or group apoptotic hepatocytes. Necrotic foci are formed. The number of Kupffer cells and binucleated hepatocytes increases.
Conclusion. With chronic predatory stress, the processes of dystrophy, necrosis and apoptosis of hepatocytes, signs of phagocytosis and regenerative processes, and decreased immune protection develop in the liver of rats.
Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), accompanied by a violation of various parts of the immune system. In this regard, the development of an experimental model of leprosy may be based on the creation of an artificial defect of the macrophage link, in particular, using glucocorticoids.
Aim: To develop and characterize a model of generalized leprosy infection in mice against the background of prolonged administration of hydrocortisone.
Material and methods. To conduct the study, the following groups were formed: the control group – 50 mice infected by the Shepard method; the experimental group – 50 mice similarly infected against the background of hydrocortisone administration. Hydrocortisone was administered intramuscularly in a single daily dose of 25 mg/kg on the first day 2 hours before infection with M. leprae suspension, then in the form of four courses of 2 weeks at two-week intervals.
Results. The administration of hydrocortisone led to an acceleration of the reproduction of mycobacteria in the paw pad compared with the control (without hydrocortisone). The generalization of leprosy infection is confirmed by the presence of lepromatous structures in the form of granulomas from macrophages with a high content of M. leprae in liver, spleen, lungs and kidneys.
Conclusion. This model allows us to study the properties of the pathogen and the mechanisms of pathogenesis of the disease, and to screen pharmacological drugs with potential anti-leprosy activity in the future.
The search for new antifungal drugs is current interest due to the wide spread of fungal infections. To simulate the antifungal effect of new promising compounds with high antifungal activity in planktonic culture in clinical practice, it is necessary to study their effect on the biofilm of micromycetes.
Aim: To study the antifungal activity of new promising representatives of silver salts of pyrazoles and their condensed systems under conditions of biofilm formation.
Material and Methods. To study the antifungal activity of silver salts I and II, the micromethod of two-fold serial dilutions was used. Activity against a typical and 14 clinical highly virulent isolates of C. albicans was studied. The study of the antimycotic activity of substances under biofilm conditions was carried out using resazurin to quantify the degree of biofilm formation. The minimum inhibitory concentrations for biofilms were calculated (sMIC50 - the concentration of the antifungal substance at which a 50% decrease in fluorescence is observed compared to the positive control).
Results and Discussion. It was shown that the antifungal effect of the studied compounds in biofilm culture of clinical strains of Candida spp. is significantly lower than in planktonic culture. High antifungal activity of the silver salt of pyrazole-3- carboxamide in planktonic and biofilm cultures of resistant strains of Candida albicans, exceeding the effect of the reference drug fluconazole by 2.8–11.2 times, was revealed.
Conclusion. A promising pyrazole-3-carboxamide derivative has been identified that effectively inhibits the growth of Candida albicans biofilms, which can be recommended for further study.
Experimental and clinical studies demonstrate the possibility of modulating the development of malignant tumors in thyroid imbalance, in particular hyperthyroidism, which negatively affects the electrophysiology of the heart. In an experimental model of tumor growth during of hyperthyroidism, activation of the tumor was shown.
Aim: To study electrophysiological parameters of the mouse heart at the initial stages of transplantable tumor growth during of hyperthyroidism.
Material and Methods. In female mice of the C57BL/6 line (n = 20) was created a model of melanoma B16/F10 growth during of hyperthyroidism, which was induced by daily intraperitoneal administration of liothyronine sodium (T3) for a long time and confirmed by determining the content of thyroid-stimulating hormone and triiodothyronine in the blood using the radioimmune method. On the 5th day of T3 administration, the melanoma was transplanted. ECG was recorded non-invasively (ecgTUN- NEL, ecgAVG software, emka TECHNOLOGIES, France) on the 1st and 3rd days of T3 administration, in groups with a tumor – on the 6th day after its transplantation.
Results. Pathological changes were revealed: in the group with hyperthyroidism – rhythm irregularity, decrease the amplitude of P and T below the isoline, widening of the QRS, on the 3rd day – the death of 1 mouse was noted due to large-focal myocardial infarction; in the group with melanoma – only sinus arrhythmia and decreased heart rate; in the group with a combination of pathologies – an almost normal ECG, with the exception of an increase in P amplitude and a slight increase in QRS.
Conclusion. Already in the early stages of hyperthyroidism or tumor growth, there was a violation of myocardial depolarization/ repolarization processes, capable of causing even death of the animal. In case of comorbidity, the majority of ECG parameters normalized, indicating the inclusion of compensatory mechanisms in the interaction of pathologies. The results demonstrate the need for a deeper study of the mechanisms of interaction of several simultaneously existing pathologies in the body.
HEALTHCARE AND PUBLIC HEALTH
Relevance. In a very short period of time, surgical treatment methods have become widespread due to the expansion of indicators for performing heart surgery in patients with severe complicated forms of coronary heart disease and the use of combined surgical operations.
Aim: To study changes in the clinical and functional status of patients depending on the type of surgical intervention for coronary artery disease in different time periods in the gender aspect.
Material and Methods. The study was conducted retrospectively. For comparative analysis, patients with an established diagnosis of coronary heart disease who underwent surgical treatment at the Federal Center for Cardiovascular Surgery of the of the Ministry of Healthcare of the Russian Federation (Chelyabinsk) in 2015 (n = 1017) and 2020 (n = 967) were included. Of the total number of patients in 2015, there were 771 (75.8%) men and 246 (24.2%) women, in 2020 718 (74.3%) and 249
(25.7%), respectively.
Results. In the structure of interventions performed, there is a decrease in the number of almost all types of surgical interventions for complications of myocardial infarction, most pronounced in relation to resection of the left ventricular aneurysm, reconstruction of the left ventricle and operations in combination with mitral valve replacement. In a large percentage of cases, patients with a history of risk factors for cardiovascular diseases are referred for coronary artery bypass surgery, regardless of gender. The majority of patients had angina pectoris of the 3rd–4th functional class. However, there is a trend towards a decrease in the proportion of people with post-infarction cardiosclerosis when referred for surgery.
Conclusion. Despite the significant volume and availability of practical information, the number of patients with major cardiovascular risk factors is not decreasing.
More than a third of the total population of the planet needs medical rehabilitation and the need will increase in the future. The prospective increase in life expectancy by the middle of the 21st century will be accompanied by an increase in the share of malignant neoplasms and diseases of the circulatory system in the morbidity structure, and the level of injuries will remain unchanged. These factors will negatively affect a person’s functional capabilities and will contribute to an increase in disability, increasing the relevance of medical rehabilitation. In Russia, according to the current procedure, there is a three-stage organization of medical rehabilitation. The implementation of these stages is carried out within the regional territorial programs of state guarantees (TPSG) of free medical care to citizens, which limits the financial accessibility of the completed cycle of medical rehabilitation for patients, due to budgetary allocations and the compulsory health insurance program, negatively affecting the quality of care provided. The article assesses the volume of medical rehabilitation provided in inpatient settings in the TPSG of the Tomsk oblast for the period of 2019–2022. Currently, three medical organizations in the region of different forms of ownership provide medical rehabilitation. In total, over a four-year-period, 8,804 cases in the specialty of medical rehabilitation were completed in the amount of 378.9 million rubles. An underfulfillment of the volume and costs of medical care during medical rehabilitation approved by the TPSG was recognized, as well as an outflow of patients for treatment to other regions (1,864 people during the study period). The most popular clinical and statistical groups (CSG) for which residents of the Tomsk oblast need rehabilitation measures have been identified, and organizational ways to improve the profile of this medical care have been substantiated.
DIGITAL TECHNOLOGIES FOR DECISION SUPPORT IN MEDICINE
Aim: To perform a quantitative analysis of the effectiveness of three concepts of heart valve prosthesis support frames from the perspective of their safety under the most critical loads, conducted through numerical modeling.
Materials and Methods. The study utilized three computer-generated concepts of stent-like support frames, created based on the analysis of similar balloon-expandable prostheses. The modeling was conducted using Abaqus/CAE software and included the analysis of two key loads characteristic for this element: compression and implantation phases. A linear description of cobalt-chromium was used as the material model. The feasibility of the concepts was quantitatively assessed using von Mises stress and its qualitative distribution on the surface of the models as stress contours.
Results. The analysis revealed that two of the three proposed models experienced stresses exceeding the strength limit (933 MPa) – 999.6 and 954.0 MPa during the compression phase and reaching 1022.4 and 1044.7 MPa, respectively, during the implantation phase. Concept 3 had significantly lower stresses during loading; however, in the working state, the indicators approached the threshold, reaching 924.2 MPa.
Conclusion. Numerical modeling identified the inefficacy of concepts 1 and 2 and directions for optimizing concept 3 – reducing amplitudes to form a “strength reserve” for stress. The analysis emphasized the importance of numerical modeling in the early assessment and optimization of medical devices.
Introduction. Determining the minimum sample size for solving various tasks is an extremely important and at the same time unexplored problem. There are many methods, but most of them are not applicable for AI-based software validation.
Aim: To consider a methodology for determining a balance of classes “norm”/ “abnormality” and propose a statistical approach to determine the data amount necessary for testing AI-based software (validation).
Material and Methods. The results of AI-based software were analyzed using dataset of mammograms. Mammograms were classified by the presence of breast cancer (“abnormality”) and the absence of breast cancer (“norm”). The general set contains 123,301 unique studies. The original balance of classes in the study was “norm” 89.3%/“abnormality” 10.7%. As the results of AI-based software (ML-algorithm), a probability of the presence of pathology in the entire study was taken. The following values were used as empirical data (GT): 0 – in case of Bi-RADS classes 1 or 2 diagnosed by a doctor, and 1 – in case of Bi-RADS classes 3, 4, 5. Each data sample is transferred to AI-based software for processing. Quality metrics are calculated based on its results: AUC ROC. All the described actions were repeated 10,000 times for all the studied balances of “norm”/”abnormality”. Based on the results of AUC ROC calculations, mean values were calculated for different random data series with the same balances. Mean AUC ROC values were subjected to analysis.
Results. A maximum value of the coefficient of variation of AUC ROC values for 10% “abnormality” share is achieved at the number of studies equal to 190; for the 20% share, it is 80 studies; for the 30% share – 120 studies, for the 40% share – 110 studies, and for the 50% share – 70 studies.
Conclusion. Summarizing the conducted study results, it can be concluded that when testing AI-based software, it is necessary to consider that the number of studies reflecting the greatest heterogeneity of AUC ROC values (the largest deviation from the mean value) is different for various class balances. If the purpose of validation is to establish the worst-case behavior of AUC ROC values, then for the studied AI-based software, the “abnormality” share should be 10%, and the number of studies 190. If the validation is carried out under conditions of a limited amount of data, then the “abnormality” share should be 50% and the number of studies equal to 70.
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