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The aim of the study was to develop a method for assessing the risk of severity of the novel coronavirus infection COVID-19 in patients with chronic hepatitis C depending on the severity of liver fibrosis.Object and methods. The results of laboratory data of patients with COVID-19 and chronic hepatitis C (n = 147) were analyzed. According to the severity of liver fibrosis, patients with COVID-19 with chronic hepati­tis C were divided into 3 subgroups: mild fibrosis (F1), moderate fibrosis (F2), severe fibrosis (F3). In blood serum, the parameters of total and biochemical (C-reactive protein, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, gamma-globulins, ferritin) blood tests, lipid profile (high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B), hemostasis (fibrinogen, activated partial thromboplastin time), cytokines (interleukin-2, tumor necrosis factor-а). All parameters were assessed in the acute period, depending on the severity of COVID-19 and the stage of liver fibrosis.Outcomes. Computer program for predicting the severi­ty of COVID-19 in patients with chronic hepatitis C, depending on the stage of liver fibrosis, can be introduced into clinical practice for managing patients in the certain group.

A series of novel photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline receptor substituent was synthesized. Upon irradiation in acetonitrile or DMSO with light of 436 nm, they underwent Z–E isomerization of the C=C bond, followed by very fast N→O migration of the acyl group and the formation of nonemissive O-acylated isomers. These isomers were isolated preparatively and fully characterized by IR, 1H, and 13C NMR spectroscopy as well as HRMS and XRD methods. The reverse thermal reaction was catalyzed by protonic acids. N-Acylated compounds exclusively with Fe2+ formed nonfluorescent complexes with a contrast naked-eye effect: a color change of the solutions from yellow to dark orange. Subsequent selective interaction with AcO− led to the restoration of the initial absorption and emission properties. Thus, the obtained compounds represent dual-mode “on–off–on” switches of optical and fluorescent properties under sequential exposure to light and H+ or sequential addition of Fe2+ and AcO− ions.

Dysregulated immune response occurring in chronic hepatitis B prevents the virus elimination and contributes to progression of the infectious process. The aim of the study was to evaluate the effectiveness (biochemical, immunological, virological) of combination treatment with tenofovir and Recombinant interleukin-2 in chronic hepatitis B patients. Material and methods. A comparative analysis of the results from laboratory examination of chronic hepatitis B patients in two comparison groups, comparable in sex, age, stage of fibrosis, viral load, was carried out: group I (n = 27) received tenofovir, according to the accepted recommendations, and recombinant interleukin-2 (rIL-2), group II (n = 25) — tenofovir. Results. Before the onset of antiviral therapy all patients with chronic hepatitis B had increased hepatic transaminases, alkaline phosphatase and gammaglutamyl transpeptidase from 1.2 to 5 norms as well as dysregulated cellular immunity factors with significantly decreased absolute count of CD4+, CD8+, CD16+ and increased CD20+ lymphocytes. After 12 months of treatment, patients in observation groups showed normalized cytolysis and cholestasis with insignificant intergroup differences. The level of absolute count of CD4+, CD8+ T-cells and CD16+ lymphocytes in the I group increased (by 24.7%, 24.1%, 34.5%, respectively, all p 0.001 relative to the initial values), not observed in comparison group. The level of CD20+ lymphocytes in group 1 was decreased by 35.9%, and in group 2 — by 7.9% (pI–II 0.001). In group 1, the level of HBsAg after 12 months of treatment became lower by 52% (p 0.001). Conclusion. The conducted pilot study showed that the combination etiopathogenetic therapy of patients with chronic hepatitis B using tenofovir and rIL-2 improves liver functional state, restores the disturbed balance of immunocompetent cells: by increasing level of CD4+, CD8+ T-lymphocytes, CD16+ lymphocytes and reducing the count of CD20+ cells, and also allows to steadily reduce blood serum HBsAg level.

The aim of the study was to assess individual indicators of lipid metabolism in patients with novel coronavirus infection with chronic hepatitis C (CHC) depending on the severity of COVID-19 and liver fibrosis stage.Object and methods. A comparative analysis of the results of laboratory examination of patients of the following groups was carried out: group 1 (n = 147) – patients with COVID-19 and CHC, group 2 (n = 81) – patients with COVID-19, group 3 control (n = 94) patients with CHC without COVID-19. In turn, the patients of the first two groups were divided into subgroups according to the severity of the COVID-19: with moderate (A) and severe course (B). According to the liver fibrosis stage, patients with COVID-19 with CHC were divided into 3 subgroups: F1 (mild fibrosis), F2 (moderate fibrosis), F3 (severe fibrosis). In blood serum, lipid profile parameters (total cholesterol (TC), high-density lipoprotein cholesterol (CHDL), low-density lipoprotein cholesterol (CLDL), triglycerides (TG), apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B)) were evaluated. All parameters were assessed in the acute period, according to the severity of COVID-19 and the liver fibrosis stage.Results. In 100% of patients with COVID-19 and CHC, a decrease in Apo A1 and an increase in Apo B, the ratio of Apo B/Apo A1 were detected, regardless the severity of disease. In patients with severe COVID-19 with CHC, changes in the lipid spectrum were recorded: an increase in TG, Apo AI, Apo B, Apo B/Apo A1 ratio, and a decrease in CHDL, CLDL, Apo A1. In patients with COVID19 and severe liver fibrosis (CHC), a decrease in LDLC, Apo A1 and increase in CLDL, Apo B, ratio Apo B/Apo A1 was observed.

The cooling of a hot free thin viscous film attached to a rectangular colder frame is considered. The film is under the action of capillary and van der Waals forces and is symmetric with respect to a middle plane. The one@dimensional case of the corresponding non‐stationary nonlinear thermo‐dynamic problem is solved numerically by a finite difference scheme. The numerical results for the film shape, longitudinal velocity and temperature are obtained for different Reynolds numbers, dimensionless Hamaker constants and radiation numbers. Apie laisvosios plonosios plėvelės atvėsinimą, atsižvelgiant į Van der Valso jėgų poveikį Santrauka Nagrinejamas karštosios laisvosios plonosios klampiosios pleveles, prikabintos prie stačiakampio šaltesnio remo, atvesinimas. Plevele yra veikiama kapiliariniu ir Van der Valso jegu ir yra simetriška vidurio plokštumos atžvilgiu. Atitinkama nesta‐cionari netiesine termodinamine problema vienmačiu atveju yra skaitiškai išspresta baigtiniu skirtumu schemos pagalba. Yra gauti skaitiniai rezultatai pleveles formai, išilginiam greičiui ir temperatūrai skirtingiems Reinoldso skaičiams, bedimensinems Hamakerio konstantoms ir radiacijos parametrams. First Published Online: 14 Oct 2010

The dynamics of a free thin film attached to a rectangular frame surrounded by an ambient gas is studied theoretically. The mathematical model is described by evolutionary nonlinear system for the longitudinal velocity components and film thickness. The 1D form of the nonstationary problem is solved by a finite difference scheme. The film shape evolution in time is tracked at different Reynolds numbers, Re. The steady state solutions are reached asymptotically in time for a large range of Re. Laisvosios plonosios plėvelės dinamikos skaitinis modeliavimas Santrauka Nagrinėjamas svarbus dujų dinamikai plonosios plėvelės judėjimo matematinio modeliavimo uždavinys. Atlikta diferencialinių lygčių asimptotinė analizė. Pasiūlyta skirtuminė schema skaičiavimams atlikti ir pateikti skaitinių eksperimentų rezultatai. First Published Online: 14 Oct 2010

The new coronavirus infection remains a significant medical and social event in the world, and only active immunization of the population with the achievement of the target level of vaccination coverage of at least 60% is able to stop its spread.Objective: to study the preliminary results of vaccination against a new coronavirus infection caused by the SARS CoV-2 virus in the Samara region.Materials and methods. The material of this study was the results of statistical monitoring of the incidence of a new coronavirus infection caused by the SARS CoV-2 virus in residents of the Samara region and data on the vaccination campaign. Statistical analysis included descriptive, comparative and interval estimation, as well as correlation analysis.Results. As of October 2022, 62.6% of the total population in the Samara region has been vaccinated against a new coronavirus infection caused by the SARS CoV-2 virus. Women predominated among those vaccinated – 60.51%. When analyzing the results of the vaccination campaign, statistically significant negative relationships were revealed between the proportion of vaccinated in a certain month and the incidence in the next three months, as well as between the accumulated percentage of vaccinated and the incidence in the next few months. At the same time, morbidity and vaccination in a normalized form for the population does not depend on the size of the population.Conclusions: Vaccination reduces the risk of a new coronavirus infection caused by the SARS CoV-2 virus in the Samara region by an average of 7.4 times. With the development of a manifest form of a new coronavirus infection caused by the SARS CoV-2 virus, in residents of the Samara region who have undergone a full course of vaccination, the risk of developing severe and extremely severe forms decreases by an average of 1.65 times, and deaths – by 1.71 times.

Aim – to evaluate the effect of direct antiviral drugs (sofosbuvir and velpatasvir) on the formation of the metabolic syndrome in patients with chronic hepatitis C with a high risk of its development 2 years after treatment.Materials and methods. 112 patients with HCV (n=112) were examined, in whom the risk of developing the metabolic syndrome was determined using a specially developed method. In 58 patients, a high risk of developing metabolic syndrome was identified. This cohort of patients was divided into two groups: group 1 (n=26) who took sofosbuvir and velpatasvir and group 2 (n=32) who did not take AVT. Patients were periodically examined and observed for 2 years. At the final stage of observation, a comparative analysis of laboratory and instrumental data was carried out in patients in two comparison groups.Results. At the start of AVT, HCV patients with a high risk of developing metabolic syndrome were found to be over-weight, moderately pronounced stage of liver fibrosis (F2 according to METAVIR), high viral load, increased transaminases, total low-density lipoprotein cholesterol, atherogenic coefficient, insulin, glucose. Two years after the etiotropic therapy in HCV patients with a high risk of developing the metabolic syndrome, normalization of blood lipid metabolism, glucose, insulin levels and a decrease in the concentration of total thyroxine were registered.Conclusion. Etiotropic therapy with direct antiviral drugs in patients with chronic hepatitis C reduces the relative risk of developing the metabolic syndrome by 6,3 times.

Aim to evaluate the individual characteristics of the hemostatic system and lungs CT-scan data in patients with a new coronavirus infection caused by the COVID-19, depending on the severity of the disease. Material and methods.A comparative analysis included the results of clinical, epidemiological and laboratory examination of 209 COVID-19 patients divided in two groups: in-patients of the Samara State Medical University Clinics with moderate (n=106) and severe (n=103) course of the disease. The diagnosis was verified by enzyme immunoassay (ELISA) and polymerase chain reaction (PCR). The following indicators were analyzed: gender, age, body mass index (BMI), epidemiological history, clinical signs of the disease, severity, degree of lung damage according to the results of computed tomography (CT). Results.There were no significant differences between the groups in terms of gender and age characteristics, as well as epidemiological data of COVID-19 patients. In 91% of patients with severe COVID-19, the clinical manifestations of hemorrhagic syndrome were recorded in the form of ecchymoses at injection sites, and in 75% - in the form of bleeding of various localization. The changes in the hemostatic system in patients with severe COVID-19 were characterized by high levels of platelets, INR, APTT, fibrinogen and a decrease in PI. In patients with severe COVID-19, a positive correlation was established between the level of fibrinogen, INR, APTT, PI and consolidation of lung tissue, as well as between the level of INR, APTT, PI and the presence of lung lesions in the form of "ground-glass" opacities on the CT images.

The study objective was to survey the medical students’ attitude to the objectivity and stressfulness of various forms of knowledge assessment, the level and causes of stress at the exams. 70.3% of the students consider the most objective an oral interview followed by a written exam, term paper (project or essay) presentation; structured test on fi ll-in forms and computer testing were found least objective. The students think that main causes of stress at the exams were large amount and complexity of the exam materials, insufficient coverage of the exam materials in the classroom and the changes in the exam timetable. The students consider exams in normal anatomy (38.7%) and pharmacology (35.3%) the most stressful. 70.5% of the students think that the return of the rating system will not increase the objectivity of knowledge assessment, 86.9% of studentsappreciated the exam in the cycle. The survey of the students' attitude to various forms of knowledge assessment gives information for instruction enhancement.

Purpose of the study. An analysis of parameters of the blood coagulation system in breast cancer patients after coronavirus disease.Materials and methods. 50 breast cancer patients were divided into groups: the main group included 30 patients after coronavirus disease, the control group 1–20 patients without confirmed COVID‑19, and control group 2–20 non-cancer women after corona‑ virus disease. All cancer patients received appropriate chemotherapy. The following parameters were studied: activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), prothrombin index (PTI), fibrinogen, soluble fibrin monomer complexes (SFMCs), thrombin time (TT), antithrombin III, D-dimer and plasminogen, fibrin degradation products. Blood tests were performed 4–6 weeks after the infection and two negative PCR test results for COVID‑19.Results. Patients of the main group demonstrated differences in INR values after treatment in the subgroups with asymptomatic disease (Me = 1.24) and with mild symptoms (Me = 0.97) U = 10; Z = 2.766; р = 0.0057, in subgroups with asymptomatic disease (Me = 1.24) and with moderate to severe symptoms (Me = 0.98) U = 26.5; Z = 2.199; р = 0.027, and in TT values in subgroups with asymptomatic disease (Me = 14.5) and with moderate to severe symptoms (Me = 16.5) U = 18.5; Z = –2.725; р = 0.0064. The comparison of the parameters in patients after COVID‑19 before (Me = 0.83) and after treatment (Me = 0.4) showed differences in the D-dimer values in patients with moderate to severe disease U = 6.5; Z = –2.2861; р = 0.022 towards their decrease after the therapy. Differences were found in APTT values between the main group (Me = 30.65) and control group 1 (Me = 27.85) U = 119; Z = 3.574; р = 0.00035, in antithrombin values between the main group (Me = 94) and control group 1 (Me = 106) U = 112; Z = 3.713; р = 0.00021, and in SFMCs values between the main group (Me = 17) and control group 1 (Me = 8) U = 180.5; Z = 2.356; р = 0.018.Conclusions. Determination of plasminogen levels can become an independent factor in detecting thrombotic risk in cancer patients who recovered from COVID‑19. Previous infection with COVID‑19 should be considered an additional risk factor for venous thromboembolic complications for cancer patients.

Introduction. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.The purpose of study. Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.Materials and methods. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.Results. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.Conclusion. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.

The development of a new area of antitumor drug therapy, immunotherapy using immune checkpoint inhibitors targeting PD-1/PD-L1, has significantly changed approaches to the treatment of advanced non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated the clinical benefit as well as the long-term effect of these drugs. Currently, the problem of treatment of patients after disease progression against the background of the use of checkpoint inhibitors is relevant. Equally relevant is the issue of choosing the correct and most effective treatment tactics for NSCLC patients with oligoprogression, as well as with abscopal effect. This paper describes a clinical case of a patient with lung adenocarcinoma without driver mutations with PD-L1-positive status, who was treated with nivolumab after second-line chemotherapy for disease progression, and after oligoprogression of the disease into the brain was given stereotactic radiotherapy of metastatic lesion and continued therapy with nivolumab. Partial regression of metastases was achieved with a prolonged effect on the background of continued treatment with nivolumab for 24 months. Tolerability of therapy was satisfactory: no adverse events were observed. The patient retained the result for 1.5 years.

Aim. To analyze newly diagnosed diseases and features of the post-COVID course in patients after a coronavirus disease 2019 (COVID-19) within 12-month follow-up.Material and methods. A total of 9364 consecutively hospitalized patients were included in the ACTIV registry. Enrollment of patients began on June 29, 2020, and was completed on March 30, 2021, corresponding to the first and second waves of the pandemic. Demographic, clinical, and laboratory data, computed tomography (CT) results, information about inhospital clinical course and complications of COVID-19 during hospitalization were extracted from electronic health records using a standardized data collection form. The design included follow-up telephone interviews with a standard questionnaire at 3, 6, and 12 months to examine the course of post-COVID period.Results. According to the ACTIV registry, 18,1% of patients after COVID-19 had newly diagnosed diseases (NDDs) over the next 12 months. Hypertension (HTN), type 2 diabetes and coronary artery disease (CAD) prevailed in the NDD structure. Comparison of the age-standardized incidence of NDDs (HTN, CAD, diabetes) in the post-COVID period in the ACTIV registry with NDD incidence in 2019 according to Rosstat and the expected incidence of NDDs according to the EPOHA study revealed that HTN, diabetes, CAD in patients after COVID-19 were registered more often as follows: HTN by 7,0 and 4,4 times, diabetes by 7,3 and 8,8 times, CAD by 2,3 and 2,9 times, respectively. NDDs most often developed in patients aged 47 to 70 years. Comparison of the actual and expected number of cases of newly diagnosed HTN, CAD and diabetes depending on age showed that the actual number of cases in the population of patients in the ACTIV register is significantly higher than expected for patients aged 45-69 years and for patients with hypertension or diabetes and aged

Objective: to compare the efficacy and toxicity of aflibercept and bevacizumab in combination with fOLfIRI in secondline therapy for patients with metastatic colon cancer.Materials and methods. we performed a retrospective analysis of data on patients with metastatic colon cancer treated in 9 clinics in the Russian federation. The inclusion criteria were as follows: metastatic or locally advanced colon cancer; treatment with bevacizumab or aflibercept plus fOLfIRI in the second-line therapy. The primary outcome measure was progression-free survival (PfS). Secondary outcome measures included objective response rate and incidence of adverse events.Results. A total of 271 patients with metastatic colon cancer who received second-line therapy with bevacizumab (n = 81) or aflibercept (n = 190) between 2014 and 2018 were selected for this study. Study groups were matched for main prognostic signs. The objective response rate was 18.1 % in the bevacizumab group and 20.5 % in the aflibercept group (p = 0.7). The median PfS was 5 months (95 % confidence interval 3.8–6.1) in the aflibercept group and 7 months (95 % confidence interval 0.81–2.1) in the bevacizumab group (hazard ratio 1.4; 95 % confidence interval 0.99–2.1; p = 0.04). multivariate regression analysis demonstrated that the type of the targeted drug independently had no effect on PfS (hazard ratio 1.3; 95 % confidence interval 0.9–1.9; p = 0.2). we observed no statistically significant differences in the incidence of complications of any grades between the groups (58 % vs 72 %, p = 0.1). Patients receiving aflibercept were more likely to develop grade III–Iv arterial hypertension (2 % vs 9.5 %) and diarrhea (0 % vs 5.4 %), whereas thrombotic complications were more common in the bevacizumab group (10 % vs 1.8 %).Conclusion. we observed no significant differences in objective response rate and PfS between patients with metastatic colon cancer receiving bevacizumab or aflibercept in combination with fOLfIRI as second-line therapy. The toxicity profiles were different. Our findings can be used for choosing an optimal targeted drug for second-line treatment.

Aim. Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. Materials and methods. The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. ClinicalTrials.gov ID NCT04492384. Results. Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. Conclusion. Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

Aim. To investigate on post-COVID period in patients of the Eurasian region.Material and methods. A total of 9364 consecutively hospitalized patients were included in ACTIV registry. Enrollment of patients began on June 29, 2020, and was completed on March 30, 2021, corresponding to the first and second waves of the pandemic. Demographic, clinical, and laboratory data, computed tomography (CT) results, information about inhospital clinical course and complications of COVID-19 during hospitalization were extracted from electronic health records using a standardized data collection form. The design included follow-up telephone interviews with a standard questionnaire at 3, 6, and 12 months to examine the course of post-COVID period.Results. According to ACTIV register, 63% of patients after COVID-19 had new adverse symptoms or exacerbations of the existing symptoms lasting for up to 1 year. After hospital discharge, 79,8% of patients sought unscheduled medical attention in the first 3 months, 79,1% at 4-6 months, and 64,8% at 7-12 months. Readmission rate was 11,8% in the first 3 months, 10,9% at 4-6 months, and 10,1% at 7-12 months. The most common reasons for unscheduled treatment in the first 3 months were uncontrolled hypertension, decompensated type 2 diabetes, destabilization of coronary artery disease, gastrointestinal disease, AF episodes, exacerbation of asthma and chronic obstructive pulmonary disease, decompensated heart failure (HF). The 12-month mortality of COVID-19 survivors after the discharge was 3,08%. Multivariate analysis showed that independent risk factors for fatal outcome were age (direct correlation), the levels of hemoglobin (inverse correlation), oxygen saturation (inverse correlation), and aspartate aminotransferase (direct correlation), as well as class III-IV HF, prior stroke, cancer, inhospital acute kidney injury. Based on these identified risk factors, a nomogram was constructed to determine the 3-month mortality risk after discharge.Conclusion. Analysis of ACTIV register showed that end of the acute phase of COVID-19 does not imply a complete recovery.

Aim. To study the lipid profile in hospitalized patients with coronavirus disease 2019 (COVID-19) depending on the outcome of its acute phase according to the AKTIV international registry.Material and methods. The AKTIV registry included men and women over 18 years of age with a diagnosis of COVID-19, who were treated in a hospital. A total of 9364 patients were included in the registry, of which 623 patients were analyzed for levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides on days 1-2 of hospitalization. The level of high-density lipoprotein cholesterol (HDL-C) was calculated using the Friedewald equation.Results. We found that a decrease in LDL-C level was significantly associated with an unfavorable prognosis for hospitalized patients with COVID-19. This pattern persisted in both univariate and multivariate analyses. LDL-C levels in the final multivariate model had a significant relationship with the prognosis (an increase in the death risk by 1,7 times with a decrease per 1 mmol/l). In addition, we found that the survival of patients with an indicator level of

The methodology basic principles of the neuro-evolutionary synthesis of multi-object multi-criteria systems control models under conflict and uncertainty in real time are discussed. The proposed methodology includes the following main stages: a hierarchical optimization game model under conflict and uncertainty development; a library development of hierarchical coevolutionary algorithms for multi-criteria optimization under conflict and uncertainty; software implementation of hierarchical coevolutionary algorithms library based on distributed computing technology; and game algorithms of control under uncertainty synthesis based on the technology of neural networks ensembles.

The report considers the task of training a multilayer perceptron, formulated as a problem of multiobjective optimization under uncertainty. To solve this problem, the principle of vector minimax was used. A parallel software implementation of a hierarchical evolutionary algorithm for solving a multicriteria optimization problem under uncertainty based on a GPU is presented.

The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria for most clinical trials do not envisage recruiting such patients. The immune-mediated toxicity of immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The first case is of interest due to the presence of brain metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.

Background. Breast cancer is one of the most common malignancies and one of the leading causes of cancer deaths among women in the Russian Federation. The prognosis of the disease is largely determined by thebiological subtype of the tumor. Her2-positive breast cancer is characterized by an aggressive course and unfavorable prognosis. The use of pertuzumab, a recombinant humanized monoclonal antibody to the human epidermal growth factor receptor 2, significantly improved immediate and long-term treatment outcomes. The aim of the study was to evaluate treatment outcomes in patients with Her2-positive molecular subtype of breast cancer receiving chemotherapy combined with a dual anti-Her2 blockade, and to assess the intensityand incidence of side effects. Material and methods. Between 2015 and 2018, 37 patients with Her2-positive breast cancer received chemotherapy combined with a dual anti-HER2 blockade (docetaxel 75 mg/m2 i/v on day 1 + trastuzumab 6 mg/kg (loading dose 8 mg/kg) i/v on day 1 + pertuzumab 420 mg (loading dose 840 mg) i/v on day 1 once every 3 weeks). The mean age of the patients was 45.6 ± 11.6 years. Results. Neoadjuvant pertuzumab in combination with trastuzumab and docetaxel resulted in pathological complete response in 12 % of patients and pathological partial response in 36 % of patients. Among patients who received the above neoadjuvant therapy regimen, disease progression was observed in 4 % of patients. The most common side effects were weakness and fatigue (5.4 % of cases) and grade I–II leukopenia (5.4 %).Conclusion. The study demonstrated the efficacy of antitumor therapy with pertuzumab in combination with trastuzumab and docetaxel as well as the absence of severe side effects associated with this treatment regimen in patients with Her2-positive breast cancer.

Objectives to develop a method of early differential diagnosis of the hemorrhagic fever with renal syndrome (in 3 days after the onset) from other infectious and non-infectious diseases on the basis of mathematical-statistical analysis of clinical, functional and instrumental data. Material and methods. The study presented a complex clinical, functional and ultrasound examinations of 276 patients with various infectious and non-infectious diseases performed within 4 or 5 days from the onset of the disease. Results. Based on the discriminant analysis of the obtained data, a discriminant model for early differential diagnosis of hemorrhagic fever with renal syndrome was developed. Conclusion. The accuracy index of the differential diagnosis of HFRS using the developed discriminant model is 96%.

Objective: to analyze clinical and epidemiological characteristics of patients with COVID-19 treated in a federal hospital of Samara region and their association with disease severity. Materials and methods. We analyzed the results of clinical and epidemiological examination of 361 patients with COVID-19 divided into two groups: patients with moderate disease (n = 285) and patients with severe disease (n = 76). All study participants received inpatient treatment in the federal hospital of Samara State Medical University in 2020. The diagnosis was verified using enzyme-linked immunosorbent assay (ELISA) and/or polymerase chain reaction (PCR).Results. There were no significant differences in the gender and age of COVID-19 patients in the two groups compared. Patients in Group 2 were slightly older than those in Group 1 (62.5 years (range: 53.0–68.8) vs 57.0 years (47.0–65.0) (trend; р = 0.008). The disease severity correlated with the time to hospitalization: the longer patients stayed at home, the more likely they developed severe disease. Such symptoms as sore throat and rhinorrhea were associated with a less severe disease, whereas shortness of breath, any changes in consciousness, nausea, and stool disorders on weeks 2–3 of the disease correlated with a more severe course. The proportion of patients with concomitant diseases (especially, more than one) was significantly higher in patients with severe COVID-19 than in patients with moderate COVID-19 (74% vs 63%).

Aim to develop, using mathematical and statistical analysis of clinical, laboratory and instrumental data, a method for predicting the development of chronic kidney disease (CKD) in patients with hemorrhagic fever with renal syndrome (HFRS). Material and methods. 244 patients at the age from 18 to 50 years with a confirmed diagnosis of HFRS were examined. Patients were observed in the following periods: oliguric, polyuric, early (30th day of illness) and late (90th and 180th day of illness) convalescence. Clinical, laboratory and instrumental data, including computer photoplethysmography, were evaluated. Results. Prediction of CKD in patients with HFRS (polyuria period) based on a linear discriminant model is possible with an accuracy index of 92.2%. In subsequent periods, the accuracy index increases: in early convalescence 98.4%, in late convalescence up to 100%. The following markers were the most informative: RI before ischemia, leukocytes and platelets in the general blood test, total protein and creatinine in the biochemical blood test, GFR calculated using the CKD-EPI and MDRD formulas, daily microalbuminuria, BMI and weight. Conclusion. A complex of discriminant models for predicting the development of CKD in patients with HFRS at various stages of the disease, including convalescence, with an accuracy index from 92 to 100% has been developed. These models are implemented in the software "Calculator for predicting CKD after HFRS".

Introduction. This paper presents the results of a study on the methods for calculating the capacity of level crossings. The purpose of writing this research paper is determine the best methodology for calculating the intervals in the main flows for the prevailing road conditions in the Russian Federation, that a new methodology to calculate capacity adapted to domestic road conditions would be developed in the future.Materials and methods. In recent decades of market relations in the Russian Federation, one can note a rapid increase in motorization in human settlements. The number in 550 vehicles per 1000 people in domestic entities is expected to have been increasde by 2025, which is significantly higher than the current level in European part of the Russian Federation. It is important to note that when the number of vehiclec is increasing, which level is about 80%, it is essential to increase road crossings capacity. Results. At the moment the methodology for calculating capacity and queue length is the same. It should be noted that the current models are not properly described in the domestic studies, but the calculations were made using models developed in the 1960s and 1970s.

Patients with brain metastases of HER2-positive breast cancer (BC) is a special group of patients who are difficult to treat and have a short life expectancy. The possibilities of whole brain radiotherapy, stereotactic radiosurgery and surgery in such patients are rather limited. Trastuzumab emtansine (T-DM1) showed potential activity in this subset of patients. T-DM1 is an antibody-chemical conjugate (ADC) that delivers directly to HER2-positive cancer cells, thereby limiting damage to healthy tissue. At this point, the efficacy of trastuzumab emtansine has been demonstrated in several randomized trials as a second and subsequent lines of therapy for advanced breast cancer with a favorable toxicity profile of the drug. This article describes a clinical case of a patient with luminal B HER-2 positive breast cancer who, underwent stereotactic radiosurgery and was treated with trastuzumab emtansine as a the second line of treatment for disease progression with metastatic brain lesions after trastuzumab/pertuzumab-containing therapy. Partial regression of metastases with long-term duration of the effect was achieved treatment with trastuzumab emtazine has been being continued for 24 months. Tolerability of therapy was good: thrombocytopenia 2 degree was the main among side effects. The effect has been persisted for 2 years and the patient continues the treatment. Discussion of the results of real clinical practice with well-known studies was carried out.

Introduction: Squamous cell carcinoma of the oral cavity is one of the most common head and neck cancers with an aggressive course and high mortality rates. The aim of the study was to determine the EGFR expression levels in tumor tissues in patients with squamous cell carcinoma of the tongue and oral mucosa depending on the efficacy of the therapy. Material and methods: The study included 60 patients with squamous cell carcinoma of the tongue and oral mucosa T3-4N0-1M0. The main group included 30 patients receiving chemotherapy (cisplatin/fluorouracil) in combination with targeted therapy with cetuximab. The control group included 30 patients receiving chemotherapy without cetuximab. Both groups were divided into two subgroups: sensitive and resistant. Results: In treatment-resistant patients of the main group with cetuximab, the average EGFR expression was twice lower than the initial levels (p = 0.0080) and 1.7 times higher than in treatment-resistant patients of the control group (p = 0.0157). In treatment-sensitive patients, the average EGFR expression was 19.8 times lower (p = 0.0020) than initial values and 14.9 times higher (p = 0.0067) than in treatment-sensitive controls. Conclusions: A natural decrease in the EGFR expression in tumor tissues due to the targeted therapy was revealed. However, some patients were resistant to cetuximab, which dictates the need to search for predictors of targeted therapy efficacy in patients with locally advanced squamous cell carcinoma of the tongue and oral mucosa.

Introduction. The randomized MPACT study showed that nab-paclitaxel plus gemcitabine results in statistically significantly longer life expectancy. The objective of this retrospective study is to obtain relevant data on the efficacy of this combination in real clinical practice in Russia. Materials and methods. The study included patients with morphologically proven locally advanced or metastatic pancreatic cancer, with a general condition assessed on the ECOG scale between 0-2, which received gemcitabine and nab-paclitaxel. Immediate and long-term treatment outcomes were evaluated. Results. 142 patients, who received treatment from 2009 to 2019 in 17 centers from 11 regions of Russia, were included in the study. Assessment of the objective effect was made in 134 patients. Objective effects were detected in 34 (25.4%) cases. The median time-to-progression was 6.1 months (95% confidence interval (CI) 4.8-7.4), the median length of life was 14.2 months (95% CI 10.6-17.9). An elevated CA19-9 level is the only independent adverse prognostic factor for progression-free survival (RR = 8.0, 95% CI 1.4 -43.8, p = 0.02) according to Cox multivariate regression analysis. The number of previously conducted chemotherapy lines (p = 0.34), ECOG status (p = 0.70), age over 70 years (p = 0.45), serious comorbidity (p = 0.97) did not have a statistically significant effect on progression-free survival. Findings. The gemcitabine and nab-paclitaxel combination has a relatively higher efficacy in advanced pancreatic cancer. The immediate and long-term results of its use in real clinical practice in Russia are consistent with data obtained in the Western countries.

Background. Metastatic breast cancer is still an incurable disease, and is currently regarded as a chronic process requiring longterm treatment with periodic therapy replacements. Hormonal therapy shows its therapeutic efficacy with less toxicity and a better quality of life for patients compared with chemotherapy and is one of the main treatment for patients with luminal subtypes of breast cancer.The purpose of the study was to assess the efficacy and toxicity of fulvestrant in treatment for metastatic breast cancer.Material and methods. The study included patients with metastatic breast cancer with positive hormonal status developing progression after adjuvant treatment or chemotherapy or hormonal therapy due to metastatic cancer, ECOG≤2, with normal liver, kidney and marrow function. Fulvestrant was administered intramuscularly 500 mg once a month with a loading dose 500 mg on day 14 of the first month. The effect was evaluated every 3 months.Results. We analyzed the efficacy and safety of fulvestrant in second-line and over treatment of 20 patients with metastatic breast cancer. Overall response was 65% (13 patients), including partial remission (PR) in 2 (10%) and stabilization in 11 (55%) patients. Progression was found in 7 (35%) patients. The median of relapse-free survival was 6 month. 1-year overall event-free survival was 45%. The median of overall survival was not reached due to the short observation period. 1-year overall survival was 70%. Adverse events in our group of patients included asthenia (80%), hot flushes (25%), headache and nausea (20%).Conclusions. The efficacy of fulvestrant in patients with metastatic breast cancer was high enough and did not depend on the previous treatment, with a favorable toxicity profile.

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period.

The authors analysed the efficacy and safety of Nab-paclitaxel (Nab-R) monotherapy in patients with metastatic breast cancer with visceral crisis (VC) in the second- and further-line chemotherapy. The objective response rate (ORR) was 35.3% (6 of 17 persons). The most frequent side effects were general weakness, nausea, symptoms of peripheral neuropathy. The degree of toxicity did not exceed 1–2 in 60% of cases. The median time to progression was 7.8 months. (95% CI 6–10.6). The median overall survival for patients with VC was 14.9 months. (95% CI 12.0–16.9). Efficacy and controlled toxicity of Nab-P allows its use in pre-treated patients, including ones with VC.

Objective: to analyze the frequency of metastasectomy in general population of patients with RAS wild-type metastatic colorectal cancer who received chemotherapy and anti-EGFR monoclonal antibodiesMaterials and methods. This prospective, non-randomized, multicenter study was designed to evaluate the frequency of resections of organs affected by metastasis. Our statistical hypothesis was that the addition of anti-EGFR antibodies should increase the frequency of metastasectomy from 5% to 15 %. Sample size calculations showed that to obtain a power of 80 % and an alpha level of 0.05 to detect the difference, we would need to recruit 50 patients. The primary endpoint was the frequency of resections of organs affected by metastasis, whereas the secondary endpoints included objective response rate, progression-free survival, and length of live. Tolerability of the therapy was analyzed separately.Results. Eighteen out of50 (36 %) patients achieved objective response; 32 (64 %) patents achieved stable disease and 18 (36 %) patients had disease progression. Radical resection of organs affected by metastasis was performed in 8 out of 50 patients (16 %): 1 individual had lung resection and 7 individuals had liver resection. Among participants with isolated liver lesions, the frequency of metastasectomy was 24 % (6 out of 25 patients). At a median follow-up of 14 months (between 1 and 34 months), median progression-free survival was 8 months (95 % confidence interval 6.2—9.8) and median length of life was 26 months (95 % confidence interval 19.7—32.2). The estimated 2-year overall survival was 83 % in patients who underwent metastasectomy vs. 51 % in those who had no metastasectomy.Conclusions. The addition of anti-EGFR monoclonal antibodies to standard combination chemotherapy (FOLFOX/FOLFIRI) increases the frequency of metastasectomy in patients with non-resectable metastatic colorectal cancer, which results in an increased length of life.

Objective: to identify factors associated with efficacy of an aflibercept-chemotherapy combination in patients with metastatic colon cancer.Materials and methods. This retrospective multicenter study was conducted in 20 clinics from 15 regions of the Russian Federation. The main efficacy outcome was progression-free survival (PFS). We performed univariate and multivariate analysis to assess the impact of various factors of PFS.Results. Two hundred and fifty-seven patients received aflibercept-containing chemotherapy; of them, 175 participants (68.1 %) received it as a second-line therapy. The objective response rate and median PFS were 18.7% and 5 months (95% confidence interval (CI) 4.2—5.8) respec -tively. The following factors were found to have a positive effect of PFS at multivariate analysis: grade I—II adverse events to aflibercept therapy (hazard ratio (HR) 0.58; 95 % CI 0.38—0.89; p = 0.01), therapy for concomitant diseases (HR 0.47; 95 % CI 0.29—0.76; p = 0.002), and ECOG performance status of 0 (HR 0.53; 95 % CI 0.34—0.81; p = 0.004). Patient with all 3 factors present had median PFS of 9 months, whereas patients without them demonstrated PFS of only 3 months (HR 1.9; 95 % CI 1.5—2.6; p

The international AKTIV register presents a detailed description of out- and inpatients with COVID-19 in the Eurasian region. It was found that hospitalized patients had more comorbidities. In addition, these patients were older and there were more men than among outpatients. Among the traditional risk factors, obesity and hypertension had a significant negative effect on prognosis, which was more significant for patients 60 years of age and older. Among comorbidities, CVDs had the maximum negative effect on prognosis, and this effect was more significant for patients 60 years of age and older. Among other comorbidities, type 2 and 1 diabetes, chronic kidney disease, chronic obstructive pulmonary disease, cancer and anemia had a negative impact on the prognosis. This effect was also more significant (with the exception of type 1 diabetes) for patients 60 years and older. The death risk in patients with COVID-19 depended on the severity and type of multimorbidity. Clusters of diseases typical for deceased patients were identified and their impact on prognosis was determined. The most unfavorable was a cluster of 4 diseases, including hypertension, coronary artery disease, heart failure, and diabetes mellitus. The data obtained should be taken into account when planning measures for prevention (vaccination priority groups), treatment and rehabilitation of COVID-19 survivors.

The organizer of the registers “Dynamics analysis of comorbidities in SARSCoV-2 survivors” (AKTIV) and “Analysis of hospitalizations of comorbid patients infected during the second wave of SARS-CoV-2 outbreak” (AKTIV 2) is the Eurasian Association of Therapists (EAT). Currently, there are no clinical registries in the Eurasian region designed to collect and analyze information on long-term outcomes of COVID-19 survivors with comorbid conditions. The aim of the register is to assess the impact of a novel coronavirus infection on long-term course of chronic non-communicable diseases 3, 6, 12 months after recovery, as well as to obtain information on the effect of comorbidity on the severity of COVID-19. Analysis of hospitalized patients of a possible second wave is planned for register “AKTIV 2”. To achieve this goal, the register will include men and women over 18 years of age diagnosed with COVID-19 who are treated in a hospital or in outpatient basis. The register includes 25 centers in 5 federal districts of the Russian Federation, centers in the Republic of Armenia, the Republic of Kazakhstan, the Republic of Kyrgyzstan, the Republic of Belarus, the Republic of Moldova, and the Republic of Uzbekistan. The estimated capacity of the register is 5400 patients.

Aim - to study clinical and epidemiological characteristics features of hemorrhagic fever with renal syndrome. Materials and methods. A retrospective comparative analysis of the results of clinical and epidemiological examination of HFRS patients was carried out in two groups: with moderate (n=106) and severe (n=22) forms of the disease, who were hospitalized in the clinic of infectious diseases of Samara State Medical University in 2017. Results. A significant predominance of the air-dust pathway of infection in severe forms of the disease was revealed. Most patients were young men in both groups. Clinical features of the current course of HFRS was the presence of subfebrile temperature in the polyuric period; absence of hemorrhagic syndrome in the majority of patients with HFRS, presence of severe asthenovegetative syndrome in the period of convalescence with severe headache, especially in severe form of the disease.

The knowledge society concept which originated from the information society concept is considered. A comparative analysis of two concepts is given. The shift of modern society focus from the problems of information accumulation and transfer to the knowledge production and social innovation that determine the future formation of a new civilizational type is marked.

Aim - to develop the method of non-invasive determination of liver fibrosis in patients with chronic hepatitis С. Materials and methods. 446 patients with chronic HCV infection (aged from 18 to 65 years; male -52.3%; female - 47.7%) were comprehensively surveyed. The linear discriminant analysis with the exception of discriminatory variables used by the all registered laboratory and ultrasound indicators, as well as the age of patients was performed. The results of the survey of 223 patients were used to create the discriminant model and the results of a survey of the remaining 223 patients, were used for the testing of the accuracy of the received discrimination. Conclusion. The discriminant model for noninvasive determination of the degree of liver fibrosis in patients with chronic hepatitis C with high sensitivity - 88.0% and specificity is 96.2% is developed.

Pisciculture of Ukraine, according to the head of the State Agency of Fisheries, is being reformed. At the same time, it is estimated that 60-70% of the fish industry is “in the shade”. Therefore, reliable information is needed, first of all - official statistics on the fish industry development in the country, which would be in line with European approaches. Being recognized as a separate area of economic activity to supply important food products for the population through their extraction from reservoirs, the fish industry should be represented by official statistics in the range of indicators provided for agricultural products. The purpose of the article is to reveal the results of the analysis of existing statistics on the extraction of water bioresources, with an accent on problem aspects, as well as developing proposals for improving the economic bloc of domestic statistics in this economic activity area. On the basis of the analysis of the available official statistic on the extraction of aquatic biological resources, including aquaculture, the problematic aspects of the economic block of indicators in the industry - costs and prices, are defined. It is also emphasized that both general and regional data on the number of business entities and water area are not available. Since 2016 official statistical information on the production of aquaculture is not provided, although earlier it was submitted in the thematic statistical collection; Administrative reports are now provided, but with all possible encumbrances. The proposals for improving the economic statistics on pisciculture are substantiated. A review of available statistics on the development of the pisciculture in Ukraine is provided. The comparative analysis of data by various forms of statistical reports, allowed to identify the problematic aspects of sectoral statistics Based on the results of the analysis, the proposals are maid to improve the economic statistics of the pisciculture in Ukraine. Taking into account the sectoral and statistical proposal will contribute to the formation of reliable data and transparency of this sector; allow to defend the need for its state support as an important part of the national economy

The data of the efficacy and safety regorafenib in the treatment of 7 patients with metastatic colorectal cancer (mCRC) refractory to treatment with cytostatics and monoclonal antibodies - blockers EGFR and VEGF were analyzed. The maximum anti-tumor effect in 1 patient had partial remission, in 6 - stabilization. The duration of progression-free period from start of treatment regorafenib ranged from 1.5 to 6 months. 3 patients continued antitumor therapy after progression, 3 - had the symptomatic therapy after progression, 1 - had stabilization within 4 months and continued therapy of regorafenib. Toxic effects of therapy were nausea, vomiting, diarrhea, complications of the skin, temperature reaction, increased blood pressure, dysphonia. The most clinically significant adverse events were changes in laboratory parameters in 3 patients (increase of ALT, AST and bilirubin), that resulted an interruption in the treatment and correction of the dose. The use of regorafenib in mCRC ensure adequate tumor control, and is characterized by mild toxicity that is relevant for pretreated patients resistant to other forms of anticancer therapy.