Background Patients with acute severe stroke requiring mechanical ventilation represent a significant clinical challenge. Identification of mortality predictors is necessary to improve outcomes. Methods Fourteen hospitals located around Russia participated in this prospective multicenter observational clinical study. Patients admitted to ICU between November 1, 2017, and November 1, 2019 with confirmed cerebral stroke, aged 18 to 90 years, and requiring mechanical ventilation were included. The impact of various clinical factors on mortality during the 28-day period after stroke was assessed. Results A total of 1289 patients were included in the registry, and 1144 met the study criteria. The 28-day mortality rate for stroke patients on mechanical ventilation was 64.3%. The most common indications for mechanical ventilation were impaired consciousness (75.7%) and hypoxemia (60.9%). In the cohort of strokes with NIHSS severity greater than 20 points, hypoxemia at the start of ventilation (OR 1.85 [1.21; 2.81], P = 0.004) and the use of hyperventilation mode (OR 1.46 [1.02; 2.06], P = 0.0336) were associated with increased mortality. Pressure-controlled mode as the primary ventilation method (OR 0.36 [0.21; 0.60], P < 0.001) and ICP monitoring (OR 0.23 [0.12; 0.44], P < 0.001) were associated with decreased mortality. Infectious complications were associated with longer mechanical ventilation and ICU stay (P < 0.001). The relationship between probable mortality and the severity of neurological deficit on the NIHSS scale at the start of mechanical ventilation is non-linear. A critical threshold was reached at 16 points NIHSS, where a trend of increasing probable mortality emerged. Conclusion The identified predictors of mortality in stroke patients requiring mechanical ventilation are essential for decision-making in this cohort. They include hypoxemia, hyperventilation (used to control intracranial hypertension), volume-controlled (VC) versus pressure-controlled (PC) initial ventilation, and the use of clinical methods for monitoring ICP alone versus invasive monitoring.

Introduction: Severely ill COVID-19 patients receiving prophylactic-dose anticoagulation exhibit high rates of thrombosis and mortality. The escalation of anticoagulation also does not reduce mortality and has an uncertain impact on thrombosis rates. The reasons why escalated doses fail to outperform prophylactic doses in reducing risks of thrombosis and death in severely ill COVID-19 patients remain unclear. We hypothesized that escalated anticoagulation would not effectively prevent hypercoagulability and, consequently, would not reduce the risk of thrombosis and death in some severely ill patients. Methods: We conducted a prospective multicenter study that enrolled 3860 COVID-19 patients, including 1654 severely ill. They received different doses of low-molecular-weight or unfractionated heparin, and their blood coagulation was monitored with activated partial thromboplastin time, D-dimer, and Thrombodynamics. A primary outcome was hypercoagulability detected by Thrombodynamics. Blood samples were collected at the trough level of anticoagulation. Results: We found that escalated anticoagulation did not prevent hypercoagulability in 28.3% of severely ill patients at the trough level of the pharmacological activity. Severely ill patients with such hypercoagulability had higher levels of inflammation markers and better creatinine clearance compared to severely ill patients without it. Hypercoagulability detected by Thrombodynamics was associated with a 1.68-fold higher hazard rate for death and a 3.19-fold higher hazard rate for thrombosis. Elevated D-dimer levels were also associated with higher hazard rates for thrombosis and death, while shortened APTTs were not. The simultaneous use of Thrombodynamics and D-dimer data enhanced the accuracy for predicting thrombotic events and fatal outcomes in severely ill patients. Conclusions: Thrombodynamics reliably detects hypercoagulability in COVID-19 patients and can be used in conjunction with D-dimer to assess the risk of thrombosis and death in severely ill patients. The pharmacological effect of LMWH at the trough level might be too low to prevent thrombosis in some severely ill patients with severe inflammation and better creatinine clearance, even if escalated doses are used.

Trimodulin (human polyvalent immunoglobulin [Ig] M 23

BACKGROUND:Acute respiratory distress syndrome (ARDS) with COVID-19 has a worse prognosis than ARDS with other diseases. Mortality from ARDS with COVID-19 is 26.0 - 61.5%, and due to other causes - 35.3-37.2%.OBJECTIVE:To find of the correlation between polymorphonuclear leukocytes (PMNs), lymphocytes, and macrophages in the cellular composition of the inflammatory infiltrate at different stages and phases of diffuse alveolar damage (DAD) with COVID-19, analyzing the autopsy material.MATERIAL AND METHODS:The lung tissue of 25 patients who died from ARDS with COVID-19 without a secondary bacterial or mycotic infection, another thanatologically significant pathology of the lungs, was studied. To study the cellular composition of the inflammatory infiltrate and the dynamics of its changes a double immunohistochemical analysis of the expression of antibodies to CD15, CD3, and CD68 was used.RESULTS:The inflammatory infiltrate and intraalveolar exudate in the exudative phase of DAD was represented by 56.8% of PMNs (CD15-positive cells; hereinafter - the average value of the percentage of positive cells to the total number of cells of the inflammatory infiltrate), 6.9% - lymphocytes (CD3-positive cells) and 19.5% macrophages (CD68-positive cells). In the early stage of the proliferative phase: 14.1% PMNs, 38.7% lymphocytes and 13.5% macrophages. In the late stage of the proliferative phase: 11.3% PMNs, 14.5% lymphocytes and 39.3% macrophages.CONCLUSIONS:In the exudative phase of DAD a statistically significant predominance of PMN was revealed, which could determine the main volume of lung damage and the severity of ARDS with COVID-19. In the early stage of the proliferative phase of DAD, a statistically significant change in the composition of the inflammatory infiltrate was revealed to compare with the exudative phase: a significant decrease in the content of PMNs relative to the total number of cells in the inflammatory infiltrate; an increase in the number of lymphocytes, which is probably associated with the start of organization and repair processes. In the late stage of the proliferative phase of DAD, compared with its early stage, was revealed a statistically significant increase in the number of macrophages in ratio.

Levilimab (LVL) is a novel anti-IL6Rmonoclonal antibody against IL6Rα. Cytokine release syndrome plays the key role in the pathogenesis of a range of life-threatening conditions including the acute respiratory distress syndrome in severely ill COVID-19 patients. Thus, the use of LVL could be considered as anti-cytokine therapy with a potency to prevent the complications and progression of respiratory failure in COVID-19.We analyzed the changes in the serum concentrations of inflammatory markers (Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IL-6) in patients treated with LVL or placebo as part of a phase III multicenter randomized double-blind placebo-controlled adaptive-design CORONA clinical study aimed to evaluate the efficacy and safety of LVL in subjects with severe COVID-19 (NCT04397562).A total of 217 patients were enrolled in the study, 206 patients were randomized, and 204 patients received the investigational product (IP, LVL or placebo).Study included men and non-pregnant women aged ≥18 years, hospitalized for severe COVID-19 pneumonia, receiving standard therapy according to the national guidelines. Patients with acute respiratory failure with the need in invasive respiratory support, septic shock, multiple organ failure or life expectancy less than 24 hours could not participate in the study. The use of other monoclonal antibodies and glucocorticoids for the treatment of COVID-19 were not allowed.Subjects were stratified according to the CRP level (CRP ≤ 7 mg/L; CRP > 7 mg/L) and then randomized (1:1) into 2 groups to receive LVL 324 mg or placebo. LVL/placebo were administered as a single subcutaneous injection, investigator and patients were unaware of the received therapy.Among secondary endpoints of the study changes from baseline in ESR, CRP and IL-6 concentrations were assessed. CRP level and ESR were measured before the IP administration and on Days 3, 5, 7, 14, 21, 29 and 30. Blood samples for the measurement of IL-6 concentration were obtained before the IP administration and then every day for 2 weeks after administration.We observed the pronounced decrease of ESR in LVL group compared to Placebo group. The difference was statistically significant on Days 3 and 7: the median ESR change from baseline was -3 mm/h and +3 mm/h on Day 3, -11 mm/h and -3.1 mm/h on Day 7, in LVL and Placebo groups, respectively (p=0.0319 and p=0.0110, Days 3 and 7). The statistically significant difference in the change of CRP level was detected between the groups on Day 3: -26.6±41.9 mg/L and -19.2±58.2 mg/L in LVL and Placebo groups, respectively (p=0.0241). Numerically the same dynamics of ESR and CRP was observed over entire study period.The dynamics of IL-6 serum concentrations in LVL and Placebo groups was strikingly different. After LVL administration we detected the rapid significant increase in IL-6 concentration due to IL-6 receptors inhibition. Maximum change from baseline was observed on Day 3 (+91.9±117.7 pg/mL), on Day 14 the value was +31.9±62.7 pg/mL.In the Placebo group, the IL-6 concentration increased slightly until Day 4 (+5,1±76,5 pg/mL), and then decreased significantly (-39.2±55.1 pg/mL on Day 14) due to clinical improvement in this group.The significant differences in the dynamics of ESR, CRP and IL-6 after LVL administration compared to placebo confirmed the pharmacodynamic effect and its potency to prevent the excessive release of inflammatory substances in severely ill COVID-19 patients.[1]Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29. PMID: 32350134; PMCID: PMC7245089.We thank all contributors to the CORONA study.Nikita Lomakin: None declared, Bulat Bakirov: None declared, Gaziiavdibir Musaev: None declared, Denis Protsenko: None declared, Olga Moiseeva: None declared, Elena Pasechnik: None declared, Vladimir Popov: None declared, Elena Smolyarchuk: None declared, Ivan Gordeev: None declared, Michail Gilyarov: None declared, Daria Fomina: None declared, V Mazurov: None declared, Maria Morozova Employee of: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Dmitrii Bogdan Employee of: JSC BIOCAD, Anton Lutskii Employee of: JSC BIOCAD, Arina Zinkina-Orihan Employee of: JSC BIOCAD, Iulia Linkova Employee of: JSC BIOCAD, Anton Seleznev Employee of: JSC BIOCAD.

Aim. To evaluate the dynamics and prognostic significance of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in patients with severe abdominal sepsis.Methods. We analysed survey data of 54 patients (28 men and 26 women) aged 64.5 years [56.25–78.00] with abdominal sepsis or septic shock. Disease severity scored according to the Acute Physiology and Chronic Health Evaluation II criteria was 16.3 ± 0.8 and according to the Sequential Organ Failure Assessment (SOFA) was 3 [3–6]. Statistical analysis of these data was performed using correlation analysis, logistic regression and receiver operating characteristic analysis.Results. Serum NT-proBNP level during the 1st week following admission to the intensive care unit (ICU) exceeded normal values, i.e. 2,570 [116.25–6,559.5] to 4,600 [1,680–18,200] pg/ml. At all disease stages, serum NT-proBNP level correlated with sepsis severity scores (SOFA), procalcitonin (PCT) levels, lactatemia, mean arterial pressure, heart rate and inotropic and vasoactive–inotropic scales (rho = 0.329–0.433; p < 0.02). On ICU days 3–4, serum NT-proBNP level of >5100 pg/ml was associated with increased risk of mortality [65.6%–88.2%; area under the curve (AUC) = 0.806; р < 0.0001]. Similarly, during this interval, elevated serum NT-proBNP level was associated with the use of inotropic drugs (OR = 1.0001, 95% CI = 1.000–1.0002, p < 0.0059). Notably, we found that 76.9%–79.0% of the patients with serum NT-proBNP level of >5250 pg/ml were receiving inotropic drugs including adrenaline, dopamine and dobutamine. We were unable to identify a specific association between serum NT-proBNP level and norepinephrine administration. On ICU days 7 and 8, among patients with serum NT-proBNP level of >3450 pg/ml, we observed a very close relationship between serum NT-proBNP level and PCT (sensitivity = 63.6%, specificity = 66.7%, AUC = 0.708; р = 0.0041).Conclusion. Serum NT-proBNP level is considerably elevated in patients with abdominal sepsis or septic shock. NT-proBNP level was associated with both traditional indicators of sepsis severity and indicators characterising the state of systemic circulation. Notably, serum NT-proBNP level correlates with cardiac failure and inotropic drug requirement. Although the mechanisms underlying the observed increases in serum NT-proBNP level remain unclear, the present findings indicate that this mediator is clearly a significant biomarker and predictor of adverse outcomes related to abdominal sepsis and septic shock. Received 22 January 2020. Revised 27 January 2020. Accepted 11 February 2020. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Author contributionsConception and study design: I.N. Tyurin, D.N. Protsenko, I.A. KozlovData collection and analysis: I.N. Tyurin, S.A. Rautbart, S.N. ShuryginStatistical analysis: I.N. Tyurin, S.A. RautbartDrafting the article: I.N. Tyurin, D.N. Protsenko, I.A. Kozlov, S.N. ShuryginCritical revision of the article: I.N. Tyurin, I.A. KozlovFinal approval of the version to be published: I.N. Tyurin, S.A. Rautbart, D.N. Protsenko, S.N. Shurygin, I.A. Kozlov

Цель. Изучить динамику и прогностическую значимость NT-proBNP у больных с тяжелым абдоминальным сепсисом. Методы. Проанализировали данные обследования 54 больных (28 мужчин и 26 женщин) в возрасте 64,5 [56,25; 78,00] года с абдоминальным сепсисом или септическим шоком. Тяжесть состояния по APACHE II составила 16,3 ± 0,8 балла, по SOFA — 3 [3; 6] балла. Статистическую обработку данных выполнили с использованием корреляционного анализа, логистической регрессии и ROC-анализа. Результаты. NT-proBNP в течение первой недели пребывания больных в отделении реанимации и интенсивной терапии превышал нормальные значения: от 2 570 [116,25; 6 559,5] до 4 600 [1 680; 18 200] пг/мл. На этапах исследования уровень биомаркера коррелировал с показателями тяжести сепсиса — оценкой по SOFA, уровнем прокальцитонина и лактатемией, а также со средним артериальным давлением, частотой сердечных сокращений, инотропным и вазоактивно-инотропным индексами (rho = 0,329–0,433; p<0,02). На 7–8-е сут. пребывания в отделении реанимации и интенсивной терапии связь между NT-proBNP и прокальцитонином становилась тесной. На риск летальности на 3–4-е сут. пребывания в отделении реанимации и интенсивной терапии указывали NT-proBNP >3 450 пг/мл с чувствительностью и специфичностью 63,6 и 66,7% (площадь под ROC-кривой 0,708; р = 0,0041); на 7–8-е сут. >5 100 пг/мл (65,6 и 88,2%; площадь под ROC-кривой 0,806; р<0,0001). Начиная с 3–4-х сут. NT-proBNP был ассоциирован с потребностью в инотропных препаратах (отношение шансов 1,0001, 95%-й доверительный интервал 1,0000–1,0002, p<0,0059); NТ-proBNP >5 250 пг/мл (76,9 и 79,0%) выделял больных, получающих инотропы (адреналин, допамин, добутамин). Ассоциированность с показателями, учитывающими использование норадреналина, отсутствует либо выражена слабо. Заключение. У больных абдоминальным сепсисом или септическим шоком резко повышен NT-proBNP, который связан как с традиционными показателями тяжести сепсиса, так и с показателями состояния системы кровообращения. Кардиодепрессия подтверждается ассоциированностью уровня NT-proBNP с потребностью в назначении инотропных препаратов. Независимо от причин усиления инкреции, повышение NT-proBNP является предиктором неблагоприятного исхода сепсиса. Поступила в редакцию 22 января 2020 г. Исправлена 27 января 2020 г. Принята к печати 11 февраля 2020 г. Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов. Финансирование. Исследование не имело спонсорской поддержки Вклад авторов Концепция и дизайн работы: И.Н. Тюрин, Д.Н. Проценко, И.А. Козлов Сбор и анализ данных: И.Н. Тюрин, С.А. Раутбарт, С.Н. Шурыгин Статистическая обработка данных: И.Н. Тюрин, С.А. Раутбарт Написание статьи: И.Н. Тюрин, Д.Н. Проценко, И.А. Козлов, С.Н. Шурыгин Исправление статьи: И.Н. Тюрин, И.А. Козлов Утверждение окончательного варианта статьи: все авторы

The problem of the optimal integration of thermoelectrically cooled optoelectronic components into an electronic housing is studied with the emphasis on practical implementation. The lines of 2-stage and 3-stage thermoelectric coolers (TECs) compatible with TO8 housing have been developed, and their parameters are measured in a wide range of heat sink temperatures. The TECs are optimized to receive a temperature difference of 100–110 K under a heat load from 70 mW to 100 mW with minimal power consumption. To fit into a standard housing interior, all the TECs have the same overall dimensions, regardless of the number of stages. Details of the TEC configurations and their performance characteristics are presented and discussed.

No recommendations available concerning protocols of static PV loop and esophageal pressure measurements use set positive end-expiratory pressure (PEEP). The aim of the study was evaluation of the significance of the lower inflection point (LIP) and esophageal pressure monitoring for PEEP adjustment in ALI and ARDS.

Acute respiratory distress syndrome (ARDS) is a frequent complication in critically ill patients. Recruitment maneuver (RM) is a rescue procedure which improves oxygenation [1-3]. However, it is not clear whether improving oxygen delivery (DO2) exists after RM. The aim of this study was to evaluate the effects of RM on hemodynamics and DO2.

Conventional mechanical ventilation (MV) may cause additional lung injury in ALI/ARDS due to overdistention of aerated lung regions (high Vt) and cyclic lung reopening (low PEEP level). Hyperproduction of inflammatory mediators is one of the side effects in these cases. This factor could delay or prevent resolution of respiratory failure [1,2]. However, it is not clear whether conventional mechanical ventilation damages intact lungs. The aim of this study was to evaluate the effects of conventional and protective mechanical ventilation on intact lungs in patients with severe trauma.