Risk factors of adverse outcome of COVID-19 and experience of Tocilizumab administration in patients on maintenance hemodialysis due to diabetic kidney disease

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 <0,001), 3-4 degree of lung damage according to CT data (ОR 6,2; 95% CI 1,803–21,449; р = 0,005), CVE during hospitalization (ОR 18,9; 95% CI 3,631–98,383; р <0,001); CCI ≥10 points (ОR 4,33; 95% CI 1,001–18,767; р = 0,043), level of prandial glycemia at admission ≥10 mmol/l (ОR 10,4; 95% CI 2,726–39,802; р <0,001). For risk identification of upcoming lethal outcome a predictive model was created with the use of discovered RF as variables. The predictive value of this model is 92,45% (positive prognostic value — 96,5%, negative prognostic value — 87,5%).In TCZ treated subgroup the laboratory markers of adverse outcome were detected with application of correlation analysis. Among them: increasing level of CPR 24-48 hours before lethal outcome (r = 0,82), the reduction of lymphocytes count after TCZ administration (r = -0,49), increasing of leukocytes and further reduction of lymphocytes count 24-48 hours before lethal outcome (r = 0,55 и r = -0,52, resp.)).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

Обратимая легочная гипертензия у пациентки после трансплантации почки с длительно функционирующей артериовенозной фистулой

Case report of reversible high pulmonary hypertension (PH) in patient with successful kidney transplantation (KT) is presented. The distinction of the case was the functioning arteriovenous fistula (AVF) with excessive blood flow during 15 years in the absence of indications for hemodialysis. Consequently, PH was complicated by serious congestive heart failure (CHF) with high cardiac output. Surgical closure of AVF resulted in complete regression of clinical, instrumental and laboratory signs and symptoms of PH and CHF within 2 weeks. The pathogenic role of excessive AVF blood flow in PH and CHF formation is a point of discussion. Surgical closure of AVF with excessive blood flow is recommended in cases of presence of symptomatic PH and CHF in patients after successful KT.Представлено описание клинического случая обратимой высокой легочной гипертензии (ЛГ) у пациентки с успешной трансплантацией почки (ТП), особенностью которого было функционирование артериовенозной фистулы (АВФ) с избыточным кровотоком в течение 15 лет при отсутствии показаний к проведению гемодиализа. ЛГ сопровождалась развитием тяжелой застойной сердечной недостаточности (ЗСН) с высоким сердечным выбросом. Лигирование АВФ привело к полному регрессу клинико-инструментальных и лабораторных признаков ЛГ и ЗСН в течение 2 недель. Обсуждается патогенетическая роль избыточного кровотока по АВФ в формировании ЛГ и ЗСН. Рекомендуется лигирование АВФ с избыточным кровотоком в случае формирования симптомной ЛГ у пациентов после успешной ТП

COVID-19-ассоциированный бивентрикулярный синдром Такоцубо, осложнившийся кардиогенным шоком (клиническое наблюдение)

Acute myocardial dysfunction (AMD) remains prominent among extrapulmonary manifestations of COVID-19. Takotsubo syndrome (TS) is one of the causes of AMD development. TS incidence in patients with COVID-19 is currently unknown. The report presents a clinical case of an elderly female patient on maintenance hemodialysis with severe COVID-19. During the session of therapeutic plasma exchange (TPE), the patient had an episode of ventricular fibrillation followed by cardiogenic shock development and ECG changes, similar to myocardial infarction. Echocardiographic (Echo) data showed a distinctive pattern of biventricular TS with a significant systolic function decrease in both ventricles. Emergency CT angiography ruled out obstructive lesions of coronary arteries. Full recovery of both ventricles systolic function, regression of ECG changes, and complete resolution of cardiogenic shock were observed within the next week. The subsequent course of the disease was complicated by sepsis and multiple organ failure which determined the lethal outcome.The autopsy findings excluded coronarogenic and viral myocardial damage. The presented case demonstrates a life-threatening TS pattern in patients with severe COVID-19. TPE procedure should be treated as a possible trigger of TS.Среди внелегочных проявлений COVID-19 важное место занимает острая миокардиальная дисфункция. Одной из причин ее развития является синдром Такоцубо (СТ). Частота встречаемости СТ у пациентов с COVID-19 неизвестна. Представлено клиническое наблюдение пожилой пациентки с тяжелым течением COVID-19, получавшей лечение программным гемодиализом. В ходе сеанса терапевтического плазмообмена развился эпизод фибрилляции желудочков с формированием клинико-инструментальной картины кардиогенного шока, сопровождавшейся инфарктоподобными изменениями ЭКГ. По данным Эхо-КГ выявлен типичный паттерн бивентрикулярного СТ с выраженным снижением систолической функции обоих желудочков. По результатам экстренной коронароангиографии обструктивного поражения коронарного русла не выявлено. В течение последующей недели лечения отмечались полное восстановление систолической функции обоих желудочков, регресс инфарктоподобных изменений ЭКГ и разрешение кардиогенного шока. Дальнейшее течение заболевания осложнилось развитием сепсиса и полиорганной недостаточности, приведших к летальному исходу. По данным аутопсии коронарогенное и вирусное поражение миокарда были исключены.Представленный случай демонстрирует развитие жизнеугрожающего варианта СТ у пациентки с COVID-19. В качестве вероятного триггера следует рассматривать процедуру терапевтического плазмообмена

A Transient "Changing-look'' Active Galactic Nucleus Resolved on Month Timescales from First-year Sloan Digital Sky Survey V Data

We report the discovery of a new ``changing-look'' active galactic nucleus (CLAGN) event, in the quasar SDSS J162829.17+432948.5 at z=0.2603, identified through repeat spectroscopy from the fifth Sloan Digital Sky Survey (SDSS-V). Optical photometry taken during 2020--2021 shows a dramatic dimming of ${\Delta}$g${\approx}$1 mag, followed by a rapid recovery on a timescale of several months, with the ${\lesssim}$2 month period of rebrightening captured in new SDSS-V and Las Cumbres Observatory spectroscopy. This is one of the fastest CLAGN transitions observed to date. Archival observations suggest that the object experienced a much more gradual dimming over the period of 2011--2013. Our spectroscopy shows that the photometric changes were accompanied by dramatic variations in the quasar-like continuum and broad-line emission. The excellent agreement between the pre- and postdip photometric and spectroscopic appearances of the source, as well as the fact that the dimmest spectra can be reproduced by applying a single extinction law to the brighter spectral states, favor a variable line-of-sight obscuration as the driver of the observed transitions. Such an interpretation faces several theoretical challenges, and thus an alternative accretion-driven scenario cannot be excluded. The recent events observed in this quasar highlight the importance of spectroscopic monitoring of large active galactic nucleus samples on weeks-to-months timescales, which the SDSS-V is designed to achieve.Comment: Published in ApJ

A Transient “Changing-look” Active Galactic Nucleus Resolved on Month Timescales from First-year Sloan Digital Sky Survey V Data

We report the discovery of a new “changing-look” active galactic nucleus (CLAGN) event, in the quasar SDSS J162829.17+432948.5 at z = 0.2603, identified through repeat spectroscopy from the fifth Sloan Digital Sky Survey (SDSS-V). Optical photometry taken during 2020-2021 shows a dramatic dimming of Δg ≈ 1 mag, followed by a rapid recovery on a timescale of several months, with the ≲2 month period of rebrightening captured in new SDSS-V and Las Cumbres Observatory spectroscopy. This is one of the fastest CLAGN transitions observed to date. Archival observations suggest that the object experienced a much more gradual dimming over the period of 2011-2013. Our spectroscopy shows that the photometric changes were accompanied by dramatic variations in the quasar-like continuum and broad-line emission. The excellent agreement between the pre- and postdip photometric and spectroscopic appearances of the source, as well as the fact that the dimmest spectra can be reproduced by applying a single extinction law to the brighter spectral states, favor a variable line-of-sight obscuration as the driver of the observed transitions. Such an interpretation faces several theoretical challenges, and thus an alternative accretion-driven scenario cannot be excluded. The recent events observed in this quasar highlight the importance of spectroscopic monitoring of large active galactic nucleus samples on weeks-to-months timescales, which the SDSS-V is designed to achieve

Опыт применения фокусированного ультразвукового исследования сердца у пациентов с COVID-19 в Prone-позиции

Aim of the study. To study the experience of using focused transthoracic echocardiography in patients with COVID-19 in prone position (fEchoPr) in intensive care units (ICU).Materials and methods. The retrospective observational study included 53 patients (period from 15 April to 31 December 2020). Inclusion criteria: confirmed diagnosis of COVID-19, availability of fEchoPr data, outcome certainty (discharge/death). We analyzed electronic medical records. The fEchoPr was performed in patients in the prone position with a bolster under the left side of the chest and left arm raised (‘swimmer’s position’). We assessed the systolic function of the right ventricle (RV) (tricuspid annular plane systolic excursion (TAPSE)), RV size, RV/LV ratio, systolic function of the left ventricle (LV) (left ventricular outflow tract velocity time integral. (LVOT VTI)), and pulmonary hypertension (PH) (tricuspid regurgitation peak gradient (PGTR). Depending on the results, the patients were divided into 2 groups: informative (+fEchoPr) and non-informative (–fEchoPr) examinations.Results. There was no statistically significant difference in the groups (+fEcho n = 35 vs –fEcho n = 18) by age (65.6 ± 15.3 vs 60.2 ± 15.8, p > 0.05), by gender (male: 23 (65.7%) vs 14 (77.8%), p > 0.05), by body mass index (31.3 ± 5.3 kg/m 2 vs 29.5 ± 5.4 kg/m2 , p > 0.05), by mechanical ventilation support (24 (68.6%) vs 17 (94.4%), p = 0.074), by NEWS scale indicators (6.9 ± 3.7 vs 8.5 ± 3.5 points), by mortality (82.8% vs 94.4%, p > 0.05). Correlation analysis revealed a moderate inverse relationship between being on mechanical ventilation and the informative value of the study (Spearman's r = −0.30 at p = 0.033). In the +fEchoPr group, the correct measurement of TAPSE and RV/LV was carried out in 100%: a decrease in RV systolic function was recorded in 5 patients (14%), expansion of the RV in 13 patients (37%). Signs of PH were detected in 11 patients (31%), PGTR could not be measured in 10 patients (28%). LV systolic dysfunction was detected in 7 patients (20%). No pathology was detected in 16 patients (46%). One patient was diagnosed with infective endocarditis of native mitral valve, which was later confirmed by autopsy.Conclusion. In 66% of cases, fEchoPr examinations were informative, especially in terms of assessing the state of the right heart. fEchoPr examination is an affordable, valid and reproducible method to assess and monitor the state of the heart in ICU patients.Цель исследования: изучение опыта применения фокусированного трансторакального эхокардиографического исследования в Prone-позиции (фЭхоPr) в отделениях реанимации и интенсивной терапии (ОРИТ) у пациентов с COVID-19.Материал и методы. В ретроспективное наблюдательное исследование включено 53 пациента (период 15.04–31.12.20). Критерии включения: подтвержденный диагноз COVID-19, наличие данных фЭхоPr, определенность исхода (выписка/смерть). Анализировались электронные истории болезни. фЭхоPr выполнялось в положении пациента на животе с валиком под левой частью грудной клетки и поднятой левой рукой (“поза пловца”). Проводилась оценка систолической функции правого желудочка (ПЖ) (измерение экскурсии фиброзного кольца трикуспидального клапана (TAPSE)), размера ПЖ, систолической функции левого желудочка (ЛЖ) (измерение интеграла линейной скорости кровотока в выходном тракте ЛЖ (VTIвтлж)), параметра ПЖ/ЛЖ, легочной гипертензии (ЛГ) (измерение пикового градиента трикуспидальной регургитации (PGTR)). В зависимости от результатов пациенты были разделены на 2 группы: информативные (+фЭхоPr) и неинформативные (−фЭхоPr) исследования.Результаты. Не выявлено статистически значимой разницы в группах (+фЭхоPr n = 35 vs -фЭхоPr n = 18) по возрасту (65,6 ± 15,3 года vs 60,2 ± 15,8 года, р > 0,05), полу (муж.: 23 (65,7%) vs 14 (77,8%), р > 0,05), индексу массы тела (31,3 ± 5,3 кг/м 2 vs 29,5 ± 5,4 кг/м2 , р > 0,05), нахождению на искусственной вентиляции легких (ИВЛ) (24 (68,6%) vs 17 (94,4%), р = 0,074), показателям шкалы NEWS (6,9 ± 3,7 vs 8,5 ± 3,5 балла), летальности (82,8% vs 94,4%, р > 0,05). Корреляционный анализ выявил умеренную обратную связь между нахождением на ИВЛ и информативностью исследования (r-Спирмена = −0,30 при р = 0,033). В группе +фЭхоPr корректное измерение TAPSE и ПЖ/ЛЖ проведено в 100%: снижение систолической функции ПЖ зафиксировано у 5 (14%), расширение ПЖ у 13 (37%) пациентов. Признаки ЛГ выявлены у 11 (31%), измерить PGTR не удалось у 10 (28%) человек. Систолическая дисфункция ЛЖ выявлена у 7 (20%). Не было выявлено патологии у 16 (46%) пациентов. У одного пациента диагностирован инфекционный эндокардит нативного митрального клапана, подтвердившийся при проведении аутопсии.Заключение. В 66% случаев проведение фЭхоPr было информативным, особенно в части оценки состояния правых отделов сердца. фЭхоPr – доступный, валидный и воспроизводимый метод оценки и мониторинга состояния сердца у пациентов в ОРИТ

Covid-19-associated cardiac damage in patients on maintenance hemodialysis Case reports and review of the literature

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 fi rst 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 infl ammation, coagulopathy, pulmonary hypertension, permanent hemodynamic stress and fl uctuation of volemic status should also be taken into consideration. MHD by itself is a powerful risk factor which overburdens the course of COVID-19

Risk factors of adverse prognosis in patients on maintenance hemodialysis with Covid-19. Focus on cardivascular comorbidity Single center experience

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 fi brillation (20%) and diabetes (45%). Mean CCI was 6.6±2.4. Obesity was observed in 33% of cases. No statistical confi dence 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/m vs 27.1±5.8 kg/m , p>0.05). The total number of CVE - 20 (4 vs 16, p=0.019), MI - 10%, PE - 6%. No statistically signifi cant difference was found in LV myocardial mass index - average index 140±33 g/m (138±36 g/m vs 143±30 g/m2, p>0.05), LA volume index - median 35 (33; 40) ml/m2 - 35 (33; 40) ml/m vs 36 (35; 38) ml/m , 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. 2 2 2 2 2