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COVID‑19 continues demonstrating possible complications after recovery. One of these complications is avascular osteonecrosis, which can lead to bone destruction and patient disability. Cases of the development of osteonecrosis associated with coronavirus infection were widely reported during and after the SARS epidemic in 2003. They also appear to be common in COVID‑19 infection. All patients who have recovered from COVID‑19 infection, especially who received glucocorticoids, are threaten of osteonecrosis development.We describe a case of bone necrosis in a healthy young woman without additional risk factors with a mild course of COVID, who received a short course of glucocorticoids.This is the first described case of COVID‑induced osteonecrosis in our country, although due to the large‑scale use of glucocorticoids, there are probably more such cases. Early diagnosis is important to prevent disease progression. Therefore, clinical alertness is necessary in all patients with COVID‑19.

The subject of the study incorporates the problems and prospects of remote sensing of the Earth, an analysis of the effectiveness of the international legal framework in this area is given in the article.General and special methods of legal analysis were used.The main results of the research include the proof that from a technical point of view, the definition and concept of remote sensing do not cause disagreement among professionals, but it was not possible to achieve consensus on the international legal status of remote sensing. It is not in the main sources of international space law. The Principles of Remote Sensing of 1986 are imperfect and outdated in many respects, although they remain the only universal international document regulating remote sensing, and have not been challenged for more than 30 years. A balance has been established between the interests of states on the main controversial issues, such as the relationship between freedom of space monitoring, state sovereignty and access to remote sensing data.The results are practically significant, as they can serve as the basis for new normative legal acts at the international level, in the long term it is important to further expand cooperation in the field of remote sensing within the UN and other international organizations, conclude regional and bilateral agreements and develop national legislation.The conclusion of the study is that the formation of the legal framework for remote sensing occurs by integrating the norms of "soft laws" into national laws, fixing them in international treaties and, as a consequence, the emergence of norms of customary law and norms of international law.

Introduction. The new coronavirus infection, COVID-19, caused by SARS-CoV-2 has reached the scale of a pandemic. Detection of antibodies to SARS-CoV-2 is an aid in the diagnosis of COVID-19, and is also used to assess the immune response to the infection. Since COVID-19 is a new disease, seroconversions and kinetics of antibody to SARS-CoV-2 are not well understood. The aim of the study is to evaluate seroconversions and kinetics of antibodies to SARS-CoV-2 (IgA, IgM, IgG and total) in real clinical practice using test systems of national production. Materials and methods. 327 blood samples obtained from patients with a confirmed diagnosis of COVID-19 with active infection, convalescents and healthy donors were analyzed. Detection of antibodies to SARS-CoV-2 was carried out by enzyme immunoassay method using registered test systems Antigma-A, Antigma-G, Antigma-Screen and an unregistered test system for the detection of class M immunoglobulins. Results. When testing for total antibodies, 50.0% of samples were positive on days 1-7; 89.4% on days 8-14; 96.2% on days 15-45; and 93.3% after the 46th day after disease onset. The earliest seroconversions occurred on the 3rd day; antibodies were detected up to 81 days after the disease onset. Conclusions. The frequency of detecting seroconversions when using test systems of the Antigma series in real clinical practice is comparable to the data published in the world scientific literature and is high enough to use these test systems in the COVID-19 diagnostics.

BACKGROUND: Patients with Type 2 Diabetes (T2DM) and patients on maintenance hemodialysis (MHD) are at a high risk of adverse clinical course of COVID-19. To date, the causes of high mortality in these groups are not fully understood. Data about peculiarity of clinical course and Tocilizumab (TCZ) administration in patients with T2DM receiving MHD due to outcome of diabetic kidney disease (DKD) are not yet highlighted in current publications.AIMS: Identification of risk factors (RF) of adverse COVID-19 outcome and evaluation of TCZ administration in patients with T2DM receiving MHD due to DKD.MATERIALS AND METHODS: The patients treated in Moscow City Hospital No52 were included in retrospective observational study. The observation period was from 04.15 to 07.30 2020. The study endpoints were the outcomes of hospitalization — discharge or lethal outcome. Data were collected from electronic medical database. The following independent variables were analysed: gender, age, body mass index, time from the onset of symptoms to hospital admission, cardiovascular and general comorbidity (Charlson Index, CCI), cardiovascular event (CVE) during hospitalization, treatment in ICU, mechanical ventilation (MV), degree of lung damage according to CT data, level of prandial glycemia at admission, MHDassociated parameters (vintage, type of vascular access, frequency of complications). The autopsy reports were evaluated for the purpose of lethal structure investigation. In a subgroup treated TCZ the time from symptoms onset to TCZ administration and number of laboratory indicators were evaluated.RESULTS: 53 patients were included, mean age 68 ±9 y, males — 49%. General mortality in observation cohort was 45%, mortality in ICU — 81%, mortality on MV — 95%. High cardiovascular and general comorbidity was revealed (mean CCI — 8,3 ±1,5 points). The causes of outcomes according to autopsy reports data: CVE 37,5% (among them — acute myocardial infarction during hospitalization), severe respiratory failure — 62,5%. The independent predictors of lethal outcome were: MV (OR 106; 95% CI 11,5–984; р CONCLUSIONS: The number of RF of adverse COVID-19 outcome in patients with T2DM receiving MHD due to DKD are identified. CVE is one of the leading causes of mortality in study cohort. According to our experience the preventive (instead of rescue) strategy of TCZ administration should be used.

Materials and methods: a prospective non-randomized pilot multicenter study of the informativeness and clinical significance of hemostasis laboratory tests in 1210 patients with COVID-19 in disease course, including favorable and unfavorable outcomes, was performed Hemostasis was assessed using clotting tests and D-dimer concentration, thromboelastography (TEG) and thrombodynamics (TD) Results: comparison of COVID-19 laboratory parameters and clinical picture showed that 75% of patients have pronounced activation of the plasma coagulation system upon admission to the hospital Hypercoagulation is recorded in all tests, reaching a maximum in patients with subtotal (CT-3) and total (CT-4) lung lesion and/or resuscitation patients with a clinical picture of pulmonary embolism and unfavorable outcome Low molecular weight heparins (LMWH) in a standard dosage leads to suppression of the initial hypercoagulable syndrome in more than half of the patients (from 75 to 31%) All patients without LMWH laboratory effect developed thrombotic complications For clotting tests, insufficient sensitivity to changes in hemostasis against the background of LMWH was revealed The D-dimer test effectively correlates with the severity and outcomes of COVID-19, but is not suitable for the control of heparin therapy, which is associated with the effect of lysis of existing blood clots and the lack of response to a decrease in the coagulation activity of patients Methods of thromboelastography and thrombodynamics effectively record a decrease in the activity of the coagulation system and can be used to control heparin therapy The correlation coefficient between the methods was 0,77 The dynamic indices of D-dimers, TEG and TD in severe patients and, especially, in patients with fatal outcomes revealed the greatest sensitivity to the control of heparin therapy in the Thrombodynamics test, which allows, along with thrombosis, to record hypercoagulable states and the risk of bleeding, which are the outcome of thrombohemorrhagic syndrome in patients with COVID-19 Материалы и методы исследования: проведено проспективное открытое нерандомизированное пилотное многоцентровое исследование информативности и клинической значимости лабораторных тестов гемостаза у 1210 пациентов с COVID-19 в динамике заболевания, включая благоприятные и неблагоприятные исходы Оценку гемостаза проводили с использованием клоттинговых тестов и концентрации D-димера, тромбоэластографии (ТЭГ) и тромбодинамики (ТД) Результаты: при сопоставлении лабораторных показателей и клинической картины COVID-19 показано, что у 75% больных при поступлении в стационар наблюдается выраженная активация плазменной системы свертывания Гиперкоагуляция фиксируется по всем тестам, достигая максимума у больных с субтотальным (КТ-3) и тотальным (КТ-4) поражением легких и/или реанимационных больных с клинической картиной тромбоэмболии легочной артерии и неблагоприятным исходом Назначение низкомолекулярных гепаринов (НМГ) в стандартной дозировке приводит к подавлению исходного гиперкоагуляционного синдрома более чем у половины больных (с 75 до 31%) Все пациенты без лабораторного эффекта НМГ развили тромботические осложнения Для клоттинговых тестов выявлена недостаточная чувствительность к изменениям гемостаза на фоне НМГ Тест на D-димер эффективно коррелирует с тяжестью и исходами COVID-19, но непригоден для контроля гепаринотерапии, что связано с эффектом лизиса существующих тромбов и отсутствием ответа на снижение коагуляционной активности больных Методы ТЭГ и ТД эффективно регистрируют снижение активности свертывающей системы и могут использоваться для контроля гепаринотерапии Коэффициент корреляции между методами составил 0,77 Заключение: динамические индексы D-димеров, ТЭГ и ТД у тяжелых больных и особенно у пациентов с летальными исходами выявили наибольшую чувствительность к контролю гепаринотерапии у теста ТД, что позволяет наряду с тромбозами фиксировать гиперкоагуляционные состояния и риск кровотечений - исходы тромбогеморрагического синдрома у больных с COVID-19

We herein present our initial report from «ROKKOR-recipient», a national multicenter observational study. The prevalence, risk factors, clinical manifestations and outcomes of the novel coronavirus disease 2019 (COVID-19) in solid organ transplant recipients receiving immunosuppressive therapy were investigated. The study enrolled 251 COVID-19 patients (220 kidney recipients, 7 liver recipients, 1 liver-kidney recipient, and 23 heart recipients). The subjects came from 20 regions in Russia. The symptoms, clinical presentation, imaging and lab test results, therapy and outcomes of COVID-19 were described. It was established that solid organ transplant recipients with COVID-19 have a higher risk of developing adverse events. Predictors of adverse events include associated cardiovascular diseases, pulmonary diseases, diabetes, and kidney failure. Symptoms of the disease include dyspnea, rash and catarrhal signs, as well as initial low blood oxygen saturation (SpO2 10 × 109/L), elevated creatinine levels (>130 μmol/L) and a marked decrease in glomerular filtration rate, requiring hemodialysis. Performing organ transplant surgery in COVID-19 does not increase the risk of adverse events but could save the lives of waitlisted terminally ill patients.

Background: Pandemic COVID-19 pneumonia due to SARS-2 is an important cause of morbidity and mortality. Emerging evidence links poor outcomes to an inflammatory cytokine storm.Methods: We treated 89 hospitalized patients with COVID-19 pneumonia and heightened systemic inflammation (elevated serum C reactive protein and interleukin-6 levels) with an infusion of tocilizumab (TCZ), a human monoclonal IgG1 antibody to the interleukin-6 receptor.Results: Clinical and laboratory evidence of improvement was evident when baseline and 1-2-day post-infusion indices were compared. Among the 72 patients receiving supplemental oxygen without mechanical ventilation, severity of condition on the NEWS2 scale scores fell from 5 to 2 (P30 mg/L) and low lymphocyte counts (

The objective: to predict lethal outcomes in patients with COVID-19 based on the result of chest computed tomography (chest CT) using a semi-quantitative visual scale of the pulmonary parenchyma lesion.Subjects and methods. Inclusion criteria: patients who underwent chest CT from March 2 to May 1, 2020, inclusively, upon referral of a general practitioner due to suspected community-acquired pneumonia caused by COVID-19. Chest CT was performed in 48 medical organizations providing primary medical care to the adult population in Moscow. Exclusion criteria: patients whose chest CT was not assessed by CT 0-4 score; patients who were not confirmed as COVID-19 positive.In the Russian Federation, CT 0-4 score is recommended to be used for assessment of the extent of lung parenchyma lesion in cases with suspected COVID-19.Data on fatal outcomes were received on May 4, 2020 inclusive.Results: data of 13,003 patients from the Unified Radiological Information Service were retrospectively included in the study according to inclusion and exclusion criteria. The test aimed to detect a trend of directional changes in the proportion of deceased patients among various categories using CT 0-4 score demonstrated a statistically significant result (p < 0.0001). The chance of a lethal outcome increases directionally from CT-0 to CT-4. The test for deviations from the linear trend also provided p < 0.0001, i.e. when moving to higher scores (CT-3 and CT-4), there was an accelerated increase in the risk of death. Analysis of overall survival using the Cox regression model showed that the assessed factors (age and CT 0-4 score) were statistically significantly associated with the time to death from COVID-19 (p < 0.05). The risk of death increased with age, on average, 8.6% for every 5 years (95% CI 0.8-17.0%). When transferring from one category of CT to the next one, the risk increased by 38% on the average (95% CI 17.1-62.6%). There was no statistically significant association of gender factor with overall survival (p = 0.408).The visual score of CT 0-4 recommended for use in the Russian Federation to assess lung parenchyma lesions according to chest CT data, is a predictor of a lethal outcome in patients with COVID-19. CT 0-4 score is convenient for practical use.

The article describes a clinical case of a new covid-19 coronavirus infection in a patient receiving immunosuppressive therapy after allotransplantation of a cadaveric kidney in the present observation, the course of covid-19 was manifested by bilateral pneumonia with respiratory failure, which required the use of active therapy with antiviral drugs, complicated by a nephrotoxic effect with the correction of immunosuppressive therapy В статье описан клинический случай новой коронавирусной инфекции COVID-19 у пациентки, получающей иммуносупрессивную терапию, после аллотрансплантации трупной почки В настоящем наблюдении течение COVID-19 проявлялось двусторонней пневмонией с дыхательной недостаточностью, потребовавшей применения активной терапии противовирусными препаратами, осложнившейся нефротоксическим эффектом с коррекцией иммуносупрессивной терапией

The article reviews studies that confirm the relationship of a negative prognosis with the presence of risk factors for cardiovascular complications during respiratory infections, including novel coronavirus infection COVID-19. The article presents the relevant research results that provide evidence on the myocardial damage in coronavirus infection. We present a clinical case of a patient with confirmed diagnosis of COVID-19 and severe viral myocarditis, verified by histological and immunohistochemical studies.

According to accumulated clinical data, one of the causes of severe damage to lung epithelial cells associated with SARS-CoV-2 (2019-nCoV) is an acute, timely underestimated "cytokine storm" (cytokine cascade, hypercytokinaemia) with characteristic signs of an expressed hyper-inflammatory syndrome with subsequent polyorganic failure. The study presents the results of the analysis of the effectiveness of tocilizumab therapy (TCZ) in patients (n = 181) of different age groups with developed pneumonia caused by SARS-CoV-2. The aim of the study was to evaluate the effectiveness of TCZ therapy in patients of different age groups with developed pneumonia in the frame of COVID-19. Methods. Patients (n = 181) with community-acquired pneumonia caused by coronavirus SARS-CoV-2 are included in a one-center, non-randomized, prospective study to evaluate the effectiveness of TCZ therapy conducted at the State Public Health Institution "City Clinical Hospital No.52" of the Moscow City Health Department. Patients were divided into 3 age subgroups – up to 50 years, 50–70 years and over 70 years. Patients with community-acquired SARS-CoV-2-induced pneumonia receiving non-invasive oxygen support and patients who had artificial lung ventilation (ALV) were given a single dose of 400 mg of TCZ in addition to basic therapy. Results. There are no significant differences between age groups in the severity of pneumonia according to the data of the computed tomography (CT), however, a more severe condition and a higher mortality rate (p < 0.001) were reliably observed in patients over 70 age compared to the other age groups. After TCZ treatment in patients of each age group, the severity of the condition assessed on the National Early Warning Score (NEWS2) has been significantly reduced compared to the baseline. Conclusion. According to the data of the pilot study the efficacy and safety of TCZ in patients of all presented age groups with COVID-associated pulmonary tissue lesion and signs of "cytokine storm" was demonstrated. At the same time, patients up to 50 years after the therapy of TCZ managed to achieve greater clinical efficiency compared to patients in other groups. According to the severity of the state and laboratory criteria, the lowest clinical efficacy of TCZ therapy was observed in patients over 70 years of age; as a consequence, the highest mortality rate was observed in the same group. At the same time, the TCZ therapy has not had a positive impact on the change of laboratory values and the severity of the disease in case of unfavorable outcome.

Background: patients on maintenance hemodialysis (MHD) are at high risk of adverse clinical course of COVID-19 Study objective: analysis and evaluation of heart condition and risk factors of adverse clinical course of COVID-19 in patients on MHD Materials and methods: 85 patients were included in retrospective observational hospital-based study in Moscow City Hospital 52 from 04 15 to 06 02 2020 The endpoints were results of hospitalization: discharge or lethal outcome Several demographic, anamnestic, clinical and instrumental indicators were analyzed Among them: gender, age, general and cardiovascular comorbidity (Charlson index, CCI), the type of vascular dialysis access, the etiology of ESKD, dialysis vintage, body mass index (BMI), cardiovascular events (CVE) in the course of hospital stay (myocardial infarction, MI, pulmonary embolism, PE, and others), ICU admission, mechanical ventilation (MV), the results of echocardiography and lung computed tomography (CT) Odds ratio (OR) was calculated and logistic regression with step-by-step algorithm was applied to assess risk factors of adverse outcomes of COVID-19 in cohort under study Results: The mean age was 65±13 years (59%, males) Mortality in whole cohort was 43 5% (75%, in ICU patients, and 89% in patient on MV) The concomitant diseases were hypertension (92%), ischemic heart disease (54%), recent MI (19%), chronic heart failure (55%), permanent atrial fibrillation (20%) and diabetes (45%) Mean CCI was 6 6±2 4 Obesity was observed in 33% of cases No statistical confidence was found in CCI (6 3±2 4 points (survivors) vs 7 0±2 3 points, p>0 05), BMI (26 8±5 3 kg/m2 vs 27 1±5 8 kg/m2, p>0 05) The total number of CVE - 20 (4 vs 16, p=0 019), MI - 10%, PE - 6% No statistically significant difference was found in LV myocardial mass index - average index 140±33 g/m2 (138±36 g/m2 vs 143±30 g/m2, p>0 05), LA volume index - median 35 (33;40) ml/m2 - 35 (33;40) ml/m2 vs 36 (35;38) ml/m2, p>0 05 In 35% systolic disfunction of right ventricle was observed with no difference between groups The average index of left ventricle ejection fraction (LVEF) was 53±9% (54±6% vs 50±10%, p=0 019) The median of pulmonary artery systolic pressure - 40 mm Hg (30;53) (38 (30;52) mm Hg vs 42 mm (34;53) Hg, p>0 05) The highest OR was calculated for following parameters: MV (OR=31 95% CI 18-121, p=0 0001), CVE (OR=8 3, 95% CI=2 5-2 8, p=0 0001), CCI ≥6 (OR=4 8, CI=1 6-11 2, p=0 002) and LVEF ≤45% (OR=3-8, 95%, CI=1 3-11,3, p=0 018) Regression logistic analysis demonstrated a strong relationship of lethal outcome with MV (OR=18 0) and CVE (OR=8 5), the moderate relationship with male gender (OR=2 1) and CCI (OR=1 25) Conclusion: the predictors of adverse outcome of COVID-19 in patients on MHD are the need for MV, CVE, CCI ≥6, decline of LVEF ≤45%, male gender Введение: пациенты на программном гемодиализе (ПГД) формируют группу высокого риска неблагоприятного течения COVID-19 Цель исследования: анализ структурно-функциональных особенностей сердца и факторов риска (ФР) неблагоприятного исхода COVID-19 у пациентов на ПГД Материалы и методы: в ретроспективное наблюдательное исследование с 15 04 по 02 06 20 г включено 85 пациентов Конечные точки исследования - исходы госпитализации (выписка/летальный исход) Сбор данных осуществлялся путем анализа электронных историй болезни Независимые переменные: пол, возраст, сердечно-сосудистая, общая коморбидность (индекс Charlson, ССI), тип сосудистого доступа, причина тПН, винтаж диализа, индекс массы тела (ИМТ), кардиоваскулярное событие (КВС) в ходе госпитализации (острый инфаркт миокарда (ИМ), тромбоэмболия легочной артерии (ТЭЛА) и др ), лечение пациента в ОРИТ, проведение ИВЛ, данные МСКТ ОГК и эхокардиографического исследования Для оценки ФР неблагоприятного исхода рассчитывалось отношение шансов (ОШ), построена модель логистической регрессии с пошаговым алгоритмом включения и исключения предикторов Результаты: средний возраст 65±13 лет, мужчины - 59% Общая летальность - 43,5%, среди пациентов ОРИТ - 75%, на ИВЛ - 89% Сопутствующие заболевания: артериальная гипертензия (92%), ишемическая болезнь сердца (54%), постинфарктный кардиосклероз (19%), хроническая сердечная недостаточность (55%), постоянная форма фибрилляции предсердий (20%), сахарный диабет (45%) Средний CCI - 6,6±2,4 баллов, ИМТ >30 кг/м2 - у 33% Не выявлено статистически значимой разницы в группах исхода по ССI (6,3±2,4 балла (выжившие) vs 7,0±2,3 балла, p>0,05), ИМТ (26,8±5,3 кг/м2 vs 27,1 ±5,8 кг/м2, p>0,05) Общее количество КВС - 20 (4 vs 16, p=0,019), ОИМ - в 10% случаев, ТЭЛА - в 6% Не выявлено статистически значимой разницы в группах исхода по индексу массы миокарда ЛЖ (средний показатель 140±33 г/м2 (138±36 г/м2 vs 143±30 г/м2, p>0,05), индексу объема левого предсердия - медиана 35 (33;40) мл/м2 (35 (33;40) мл/м2 vs 36 (35;38) мл/м2, p>0,05) У 35% выявлена систолическая дисфункция правого желудочка Средние показатели % фракции выброса ЛЖ (ФВЛЖ) - 53±9%, (54±6% vs 50±10%, p=0,019) Медиана систолического давления в легочной артерии - 40 mm Hg (30;53), с тенденцией к более высоким показателям в группе летальных исходов - 38 (30;52) mm Hg vs 42 (34;53) mm Hg, p>0,05 Получены следующие отношения шансов (ОШ): ИВЛ (ОШ 31;95% ДИ 8-121;p=0,0001), КВС (ОШ 8,3;95% ДИ 2,5-2,8;p=0,0001), CCI ≥6 баллов (ОШ 4,8;95% ДИ 1,6-11,2;p=0,002), ФВЛЖ ≤45% (ОШ 3,8;95% ДИ 1,3-11,3;p=0,018) Регрессионный логистический анализ выявил сильную связь летального исхода с пребыванием на ИВЛ (ОШ 18,0) и с КВС (ОШ 8,5), умеренную - с мужским полом (ОШ 2,1) и CCI (ОШ 1,25) Выводы: предикторами неблагоприятного течения COVID-19 у пациентов на ПГД являются: потребность в ИВЛ, КВС в ходе госпитализации, CCI ≥6 баллов, ФВЛЖ ≤45%, мужской пол

Vasculitis associated with the antineutrophilic cytoplasmic antibodies (ANCA) is an autoimmune systemic severe, often life-threatening, disease characterized by necrotizing inflammation of small vessels In 75-90% of cases of ANCA-associated vasculitis (AAV), a rapidly progressive pauci-immune necrotizing crescentic glomerulonephritis develops Despite current treatment with high-dose glucocorticoids and either cyclophosphamide or rituximab, patients have a nine-fold increased mortality risk during the first year of disease compared with healthy subjects This high mortality is attributed mainly to infections and vasculitis activity Recent data suggest that the activation of the complement system, and in particular the alternative complement pathway, plays a significant role in the pathogenesis of AAV It has been suggested that neutrophils primed by infection or pro-inflammatory cytokines release properdin, which activates an alternative complement cascade with cleavage of C5 into C5a and C5b Anaphylatoxin C5a binds to receptors on the surface of neutrophils, enhancing their priming and activation and thus contributing to the inflammation The randomized clinical trial showed that the selective C5a-receptor inhibitor avakopan was effective in the treatment of AAV However, avacopan is currently not available in the everyday clinical practice On the other hand, reports showing successful usage of monoclonal antibody against C5 eculizumab in severe AAV had been published Here we present four cases of AAV complicated by COVID-19, for which conventional therapy with cyсlophosphamide could not be applied due to the particularly high risk of serious infectious complications, and eculizumab was used off-label by decision of the medical council and special commission Taking this decision, we took into account data demonstrating the role of complement activation and, in particular, C5a in the pathogenesis of acute lung disease, induced by pathogenic viruses Moreover, the successful usage of eculizumab in severe COVID-19 was reported recently Thus, we sought to apply an approach aimed simultaneously at the pathogenetic mechanisms of both AAV and viral lung damage Васкулит, ассоциированный с действием антинейтрофильных цитоплазматических антител (АНЦА) представляет собой аутоиммунное системное тяжелое, часто угрожающее жизни заболевание, которое характеризуется некротизирующим воспалением сосудов малого калибра В 75-90% случаев при АНЦА-ассоциированном васкулите (ААВ) развивается быстропрогрессирующий пауци-иммунный некротизирующий полулунный гломерулонефрит Несмотря на современную терапию высокими дозами глюкокортикоидов и циклофосфамидом или ритуксимабом риск смерти больных на первом году болезни повышен в 9 раз по сравнению со здоровыми лицами, что связано с инфекциями и активностью васкулита В последние годы появились новые данные, которые позволяют полагать, что активация системы комплемента, и в частности, альтернативного пути комплемента, играет важную роль в патогенезе ААВ Полагают, что нейтрофилы, праймированные инфекцией или провоспалительными цитокинами, высвобождают пропердин, который активирует альтернативный каскад комплемента с расщеплением С5 на С5а и С5b Анафилатоксин C5a связывается с рецепторами на поверхности нейтрофилов, усиливая их праймирование и активацию и таким образом содействуя воспалению В рандомизированном клиническом исследовании продемонстрирована эффективность селективного ингибитора С5а-рецептора авакопана при лечении ААВ Однако в настоящее время авакопан недоступен в повседневной клинической практике С другой стороны, в литературе имеются сообщения об успешном применении при тяжелом течении ААВ препарата моноклональных антител к С5 - экулизумаба В настоящем сообщении мы представляем 4 клинических случая ААВ, осложнившегося COVID-19, когда общепринятая терапия циклофосфамидом не могла быть применена в связи особенно высоким риском тяжелых инфекционных осложнений, и по решению консилиума и специальной врачебной комиссии было предпринято введение экулизумаба вне существующего стандарта (off-label) Принимая такое решение, мы исходили из данных, согласно которым активация комплемента и специально С5а участвуют в развитии острого заболевания легких, индуцированного патогенными вирусами Более того, в литературе имеются сообщения об успешном применении экулизумаба при тяжелом течении COVID-19 Таким образом мы стремились применить подход, направленный одновременно на патогенетические механизмы как ААВ, так и вирусного поражения легких

A brief review of current publications about incidence, outcomes and mechanisms of cardiovascular complications in patients with the new coronaviral disease (COVID-19) is given The possibility of direct deleterious viral effect on the myocardium, negative consequences of cytokine storm, the role of hypoxemia complicating acute respiratory distress syndrome (ARDS), myocardial infarction 1,2 type (MI 1, 2), hypercoagulation, systolic disfunction of right ventricle due to ARDS, recurrent pulmonary embolism (PE) and cardiotoxic effects of drug therapy is discussed Three case reports of cardiac injury in patients on maintenance hemodialysis (MHD) with COVID-19 are presented The first case demonstrated MI 2 type due to ischemic imbalance in a patient with severe ARDS in the absence of obstructive coronary arteries lesion The second case represented coexistent affection of heart as a result of viral myocarditis and cardiotoxic effect of Azithromycin and Plaquenil co-administration The viral myocarditis was proven by postmortem histological and immunohistochemical tests The third case demonstrated the diagnostic quest in a patient with recurrent dyspnea due to sequential severe ARDS, viral hemorrhagic exudative pericarditis with cardiac tamponade and PE progression Currently three basic phenotypes of cardiac injury are distinguished: permanent elevation of myocardial damage markers, MI 1, 2 Type and viral myo/pericarditis Of note, the course of COVID-19 in patients on MHD is more complicated in comparison with the general population The initial vulnerability of these patients is determined not only by severe co-morbidity Some interconfounding pathophysiological processes same to COVID-19 are critically important for the understanding of the current state of the art The crucial role of persistent chronic inflammation, coagulopathy, pulmonary hypertension, permanent hemodynamic stress and fluctuation of volemic status should also be taken into consideration MHD by itself is a powerful risk factor which overburdens the course of COVID-19 Статья содержит краткий обзор текущих публикаций, касающихся распространенности, исходов и механизмов формирования сердечно-сосудистых осложнений у пациентов с новой коронавирусной инфекцией (COVID-19) Обсуждаются возможность прямого повреждающего действия вируса на миокард, негативные последствия цитокинового шторма, роль гипоксемии, осложняющей течение острого респираторного дистресс синдрома (ОРДС), развитие инфарктов миокарда 1 и 2 типов (ИМ 1, 2), гиперкоагуляции, систолической дисфункции правого желудочка на фоне ОРДС, рецидивирующей тромбоэмболии легочной артерии (ТЭЛА) и кардиотоксические эффекты медикаментозной терапии Представлено описание трех клинических случаев поражения сердца у пациентов, находящихся на лечении программным гемодиализом (ПГД) В первом случае продемонстрировано развитие ИМ 2 типа вследствие ишемического дисбаланса у пациента с тяжелым ОРДС без обструктивного поражения коронарных артерий сердца Во втором случае показано сочетанное поражение сердца у пациента с верифицированным вирусным миокардитом и кардиотоксическим эффектом совместного применения азитромицина и плаквенила Вирусный миокардит был подтвержден при аутопсии с последующим проведением гистологического и иммунногистохимического исследований Третий случай демонстрирует диагностический поиск причин рецидивирующего одышечного синдрома у пациента с последовательным развитием тяжелого ОРДС, вирусного геморрагического экссудативного перикардита, осложненного тампонадой сердца, и ТЭЛА В обсуждении клинических случаев подчеркивается широкое распространение поражения сердца при COVID-19 Выделяется 3 основных фенотипа вовлечения сердца в патологический процесс: стойкое повышение концентрации маркеров повреждения миокарда, развитие ИМ 1, 2 типов и вирусные мио/перикардиты Отмечается, что COVID-19 протекает значительно тяжелее у пациентов на ПГД по сравнению с общей популяцией Стартовая уязвимость диализных пациентов для новой коронавирусной инфекции обусловлена не только исходно тяжелой коморбидностью Крайне важным является наличие взаимоотягощающих патофизиологических процессов, синергичных таковым при COVID-19 Решающую роль играют персистирующие в диализной популяции процессы хронического воспаления, коагулопатия, легочная гипертензия, перманентный гемодинамический стресс и колебания волемического статуса ПГД как таковой представляется мощным фактором риска, отягощающим течение COVID-19

Analyzed the features of the surgical treatment of carbuncles. The severity of the purulent-necrotic process was assessed, the significance of the timely diagnosis of the inflammatory stage and the choice of the timing of surgical treatment is shown. The features of the options of surgical tactics - from gentle to radical surgical interventions, methods of intraoperative assessment of tissue viability in the inflammatory focus are described. The necessity of a differentiated approach to the treatment of carbuncles depending on the stage of the disease, the prevalence of the pathological process and its localization is substantiated. The significance of restorative skin-plastic surgery in the replacement of postnecrectomy defects of epithelial tissues in the treatment of extensive carbuncles is shown. Ways of improving the results of treatment of patients with carbuncles are outlined, including timely diagnosis, a differentiated approach to surgical treatment, rational antibacterial therapy, and adequate general treatment.

Introduction. The article analyzes the current situation in the use of outer space, which is characterized by the expansion of outer space activities, increased competition and a dangerous trend of the possible placement of weapons in outer space. After examining the existing international outer space law, the author identifies gaps in international treaties that must be addressed in order to prevent the deployment of weapons in outer space. Particular emphasis is placed on the study on the assessment of effectiveness of international legal efforts of the Russian diplomacy in dealing with this urgent task.Materials and methods. The methodological basis of the study comprises general scientific methods of knowledge: analysis, synthesis, induction/deduction, analogy, as well as special scientific methods: comparative legal, formal legal and statistical methods.Results of the study. It was revealed that international outer space law has been developing from the beginning in the logic of limitations on the military use of outer space. However, they are selective and permit the deployment in outer space of non-nuclear weapon systems. There is a real threat of weapons being deployed in outer space especially because the USA is not even hiding such an intention. A number of negotiating bodies exist to eliminate this threat by international legal means. Russia continues an active diplomatic work in the UN, at the Conference on Disarmament and other locations. The author demonstrates that support for Russian initiatives is growing, but they are persistently confronted by the United States and their allies.Discussion and conclusion. Based on the results of the analysis and expert opinions the author advances specific proposals in support of Russia’s diplomatic efforts to prevent confrontation in outer space. It is recommended that the number of countries which pledged not to be the first to place weapons in outer space should be expanded; that this subject should be included in the BRICS documents; that the second conference on peaceful use of outer space dedicated to the 60th anniversary of the Yuri Gagarin space flight should be to be held in Moscow in 2021.

INTRODUCTION. The article is devoted to practical and legal aspects of floating nuclear power plants (FNPPs). The first ever FNPP “Academic Lomonosov” was built in 2019 in Russia. It is a unique transportable nuclear low-power unit intended for energy and heat supply of remote port cities, industrial enterprises, gas and oil platforms. “Lomonosov” and its successor generations will have a major impact on the global nuclear energy market. The question arises how FNPPs fit into the rules of International Law. MATERIALS AND METHODS. The research was based on the analyses of international conventions on nuclear safety, security and civil liability, Treaty on the Non-Proliferation of Nuclear Weapons, IAEA documents on safeguards and standards, scholarly publications. General and special methods of legal research were used. RESEARCH RESULTS. The authors determined that in the specific case of “Academic Lomonosov” which will operate on the Russian territory no collisions with the rules of International Law are expected. However, if future serial FNPPs go for export, it will be important to analyze their compatibility with international treaties. DISCUSSION AND CONCLUSIONS. This paper concludes that FNPPs are largely compatible with the existing rules of International Law. However, there are some gaps and grey areas, especially in an export scenario. To mitigate those problems, bilateral intergovernmental agreements between the supplying and the importing states shall be concluded on their obligations in all legal and institutional issues prior to FNPP’s international shipment. Safeguards arrangement with the IAEA should be envisaged as well.

Background Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated the reduction of mortality in hospitalized patients with a respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. Methods The study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by 29 clinical and laboratory parameters predicting survival. Results Ruxolitinib treatment in the general cohort of patients was associated with equivalent to dexamethasone mortality rate: 9,6% (95% CI 4,6–14,6%) vs 13,0% (95% CI 7,5–18,5%, superiority p = 0.35, non-inferiority p = 0.0137), respectively. Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated reduced mortality in ruxolitnib-treated patients with febrile fever (OR 0.33, 95%CI 0.11-1.00). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with better safety profile due to reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). Conclusions Ruxolitinib may be an alternative anti-cytokine therapy with comparable efficacy in patients with potential risks of steroid administration. Patients with febrile fever at admission may benefit from ruxolitinib administration.

BackgroundEmerging evidence links morbidity and mortality of pandemic COVID-19 pneumonia to an inflammatory cytokine storm.MethodsEighty nine patients with COVID-19 pneumonia and heightened systemic inflammation (elevated serum C reactive protein and interleukin-6 levels) were treated with Tocilizumab (TCZ), a human monoclonal IgG1 antibody to the interleukin-6 receptor.ResultsClinical and laboratory improvement was seen comparing baseline and 1-2 day post-infusion indices. Among 72 patients not receiving mechanical ventilation, NEWS2 scores fell from 5 to 2 (p < 0.001) C reactive protein levels fell from 95 to 14 mg/L (p < 0.001) and lymphocyte counts rose from 900 to 1000/uL (p = 0.036). Sixty three of 72 patients were discharged from hospital, one patient died, and 8 remained in hospital at time of writing. Among 17 patients receiving mechanical ventilation, despite a rapid decrease in CRP levels from 89 to 35 mg/L (p = 0.014) and early improvements in NEWS2 scores in 10 of 17, ten patients died and seven remain in hospital at time of writing. Overall, mortality was only seen in patients who had markedly elevated CRP levels (>30 mg/L) and low lymphocyte counts (< 1000/uL) before TCZ administration.ConclusionsInflammation and lymphocytopenia are linked to mortality in COVID-19. Inhibition of IL-6 activity by administration of Tocilizumab, an anti IL-6 receptor antibody is associated with rapid improvement in both CRP and lymphocyte counts and in clinical indices. Controlled clinical trials are needed to confirm the utility of IL-6 blockade in this setting. Additional interventions will be needed for patients requiring mechanical ventilation.

The article evaluates the concentration of oil in the atmosphere of Barnaul by an indirect method of measurements which is based on the results of fluorimetric analysis of snow cover. Snow sampling was carried out at the time of maximum snow accumulation in the first decade of March 2013–2017. The concentration of oil in the urban snow cover exceeds the concentration in the control point outside the town by a factor of 2–6, which indicates urban atmosphere pollution. Especially high concentrations of oil are detected at the points located near the intensively loaded urban highways. Analysis shows the decrease of concentration of oil in the atmosphere of Barnaul over the past five years. This is due to the transition of the CHP and to gas heating in private areas, and transition the motor vehicles to environmental fuel of the European standard. The increase in the concentration of oil in the last years is directly related to the growth in the amount of motor vehicles and points to the need to closest attention to the concentration of oil in the snow cover as an indicator of the quality of the urban environment.

The article contains analysis of nuclear environmental problems of the Arctic region under the International Law. It seems important to further develop cooperation to strengthen the international legal framework for nuclear and environmental security in the region, and to improve the Russian national legislation. Such cooperation should be aimed, inter alia, at creating a regional treaty mechanism for responding to potential nuclear accidents by concluding an appropriate intergovernmental agreement on coordination of cooperation under the Conventions on Early Warning Notification and on Assistance in the Case of a Nuclear Accident or Radiological Emergency. Russia is the only state in the world that owns and operates a civilian nuclear icebreaker’s fleet on the Northern Sea Route. In the coming years the first floating nuclear power plant will start operating in the Chukotka Peninsula. In case of its export abroad, it will be required to create additional international legal instruments. Russia has ratified the 1963 Vienna Convention on Civil Liability for Nuclear Damage but has not yet adopted legislation on its financial implementation. It is required to adopt such a law as well as to accede to the revised 1997 Vienna Convention. Nuclear-ecological problems in connection with the elimination of the “nuclear legacy” of the Cold War are still on top of the agenda. That includes the fate of the radioactive stuffs and waste flooded in the Arctic seas. The main conclusion of the article is that the existing international legal base is ipso facto sufficient for the continued solution of Arctic nuclear ecological problems. Additional focused efforts of all interested Arctic partners are required.

Objective to study medical awareness of cardiovascular risk factors (FR) in hospitalized patients of the cardiac and internal medicine units (CU and IMU). Materials and methods A total of 100 patients from CU (n=50) and IMU (n=50) of a Moscow city hospital were included into the survey. The patients were interviewed during the I-II days of hospital stay. A special questionnaire was developed including socio-demographic and clinical indicators, open questions on the knowledge of traditional cardiovascular RFs and their target values. Results Patients of both units did not differ in gender and age. The survey revealed an extremely low awareness of major cardiovascular RFs of patients in both units: practically none of them indicated as RFs for cardiovascular disease elevated cholesterol (0 and 2 %, respectively, p>0.05) and blood pressure (0 % and 2 %, respectively, p>0.05). The majority of patients in both units (74 and 68 %, respectively, p>0.05) reported only 1-2 RFs. Patients in both units often believed that stress is the main cardiovascular RF (66 % and 50 %, respectively, p>0.05). Conclusion The survey revealed a low awareness of cardiovascular RFs in different types of medical patients at time of hospital admission.

This article analyzes the current status of the International Nuclear Law. It contains arguments in support of the assertion that the International Nuclear Law has been already formed as a separate branch of International Law. The article formulates the subject of the International Nuclear Law as the peaceful use of nuclear energy. The author puts forward the argument that nuclear disarmament belongs to another branch of the International Law – the International Security Law. Pressing issues of further development of the International Nuclear Law are set forth: the further analysis of lessons learned from Fukushima NPP accident, and their implementation in national legislations and the IAEA recommendations; establishment of an international mechanism for rapid response in the event of a nuclear accident; strengthening of the nuclear security regime; overcoming the fragmentation of the international liability regime for nuclear damage.