To assess the biology of the lethal endpoint in patients with SARS-CoV-2 infection, we compared the transcriptional response to the virus in patients who survived or died during severe COVID-19. We applied gene expression profiling to generate transcriptional signatures for peripheral blood mononuclear cells (PBMCs) from patients with SARS-CoV-2 infection at the time when they were placed in the Intensive Care Unit of the Pavlov First State Medical University of St. Petersburg (Russia). Three different bioinformatics approaches to RNA-seq analysis identified a downregulation of three common pathways in survivors compared with nonsurvivors among patients with severe COVID-19, namely, low-density lipoprotein (LDL) particle receptor activity (GO:0005041), important for maintaining cholesterol homeostasis, leukocyte differentiation (GO:0002521), and cargo receptor activity (GO:0038024). Specifically, PBMCs from surviving patients were characterized by reduced expression of PPARG, CD36, STAB1, ITGAV, and ANXA2. Taken together, our findings suggest that LDL particle receptor pathway activity in patients with COVID-19 infection is associated with poor disease prognosis.

Strains of microorganisms characterized by resistance to antimicrobial drugs used in medical organizations continue to spread In most regions of the world including Russia. It is clear that it affects both the effectiveness of antimicrobial therapy and tactics and strategy of its use not only in adults patients but also in children. The pandemic of coronavirus infection, in addition, highlighted the growing problems in treatment of invasive mycoses, the dose adjustment of antibiotics during sorption and dialysis therapy methods. These circumstances made it necessary to make adjustments to Guidelines on Diagnostics and Antimicrobial Therapy of Infections Caused by Multiresistant Strains of Microorganisms, which were prepared by a group of leading Russian experts in 2020 [1]. The submitted version of the recommendations was approved on 25.03.2022 at a joint meeting of the working group with representatives of public organizations: Association of Anesthesiologists-Intensivists, the Interregional Non-Governmental Organization Alliance of Clinical Chemotherapists and Microbiologists, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC), and NGO Russian Sepsis Forum. These recommendations reflect an interdisciplinary consensus opinion on approaches to the diagnosis and antimicrobial therapy of infections caused by multiresistant microorganisms. They are based on data from publications obtained from randomized trials as well as based on international clinical guidelines with a high degree of evidence.It is rational to use the Guidelines for determining the tactics of empirical and etiotropic therapy of the most severe infections.

Острое повреждение почек (ОПП)-относительно новое понятие (внедрено в практику с 2012 г�), которое на сегодняшний день трактуют как быстрое снижение функции почек (в течение 48 ч) с нарастанием абсолютных значений креатинина сыворотки крови на 26,5 мкмоль/л или более, относительным повышением концентрации креатинина, равным или превышающим 50% (т� е� в 1,5 раза) по сравнению с исходным уровнем, либо как документированную олигурию при диурезе менее 0,5 мл/кг массы тела/ч в течение 6 ч� Частота ОПП с каждым годом нарастает, особенно у пациентов, подвергающихся тяжелым хирургическим вмешательствам� В рутинной практике значение острой почечной патологии часто недооценивается, что может приводить к повышению летальности� Общепризнанные алгоритмы профилактики и лечения ОПП отсутствуют� В обзоре рассматриваются аспекты диагностики ОПП, принципы периоперационного ведения� Ключевые слова: острое повреждение почек, острая дисфункция почек, почечная недостаточность Для цитирования: Соколов Д� В�, Полушин Ю� С� Острое почечное повреждение в периоперационном периоде // Вестник анестезиологии и реаниматологии�-2018�-Т� 15, № 1�-С� 46-54�

Background: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Both janus kinase (JAK) inhibitor, baricitinib, and dexamethasone demonstrated the reduction of mortality. In this matched control study we compared dexamethasone to another JAK 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. 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. Funding: Ruxolitinib was obtained from Novartis through Managed Access Program (MAP).

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 a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. Methods The matched cohort 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 main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. Results Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6–14.6%]) vs 13.0% (95% CI [7.5–18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31–1.57]). 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 a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (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 a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8–16 mg dexamethasone). Conclusions Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date