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Type 1 diabetes mellitus (DM) is one of the most common autoimmune disease that is treated with lifelong insulin therapy. Non-target indicators of glycemic control, which are observed in 71% of patients, lead to the formation and progression of diabetes complications, early disability and mortality. In this regard, the search for new approaches to the treatment and prevention of type 1 DM seems to be relevant. Various methods of immunological prophylaxis for the development of type 1 DM have been studied, in particular, the use of monoclonal antibodies. Thus, in November 2022, teplizumab was approved to slow down the clinical progression of the stage of type 1 DM. The prospects for the use of new options for islet cell transplantation are being studied — in June 2023, an allogeneic donor β-cell transplant obtained from the pancreas of donors after death was approved. Another pathogenetically substantiated method for the prevention and treatment of autoimmune diseases is high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HDIT-HSCT). HDIT-HSCT demonstrated its effectiveness and cost-effectiveness in various clinical trials. This review provides up-to-date information on modern methods of immunological prophylaxis of type 1 DM.

SCIENTIFIC RELEVANCE. The pandemic of novel coronavirus infection (COVID-19) led to a drastic increase in the use of medicinal products of various therapeutic groups and increased spontaneous reporting of adverse drug reactions (ADRs). Therefore, it is necessary to analyse the reported information to identify potential safety signals.AIM. This study aimed at systematisation and quantitative analysis of data on the safety of COVID-19 medicinal products from the Russian pharmacovigilance database.MATERIALS AND METHODS. This retrospective analysis included spontaneous ADR reports submitted to the Russian pharmacovigilance database from 1 January 2020 to 31 December 2022. The authors applied disproportionality analysis to generate safety signals.RESULTS. During the stated period, the database website published 873 spontaneous reports on 1,636 ADRs associated with COVID-19 treatment. Most ADRs were associated with favipiravir (493 reports), hydroxychloroquine (87 reports), and olokizumab (85 reports). The most common ADRs included 273 (16.7%) abnormal investigation results, 203 (12.4%) hepatobiliary disorders, and 191 (11.6%) gastrointestinal disorders. The majority of adverse events, 674 (77%) cases, had favourable outcomes. Using frequency-based disproportionality analysis, the authors identified 23 potential safety signals based on disproportionately reported ADRs for azithromycin, dexamethasone, levilimab, lopinavir+ritonavir, molnupiravir, olokizumab, tofacitinib, tocilizumab, umifenovir, and favipiravir.CONCLUSIONS. The new safety signals require additional assessment of ADR reporting forms for causal relationship analysis, validation, prioritisation, and clinical interpretation. The frequency-based method did not identify safety signals for hydroxychloroquine, remdesivir, baricitinib, sarilumab, and anti-COVID-19 human immunoglobulin, but this does not rule out the possibility of detecting new causal relationships.

This study presents the findings of the magnetic resonance morphometric analysis of brain subcortical structures in patients with remitting relapsing multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) phenotypes in comparison with the control group. The study revealed significant differences between the volume of the left nucleus accumbens [control:RRMS= 570,108 ± 100,024:487,851 ± 124,174; F(p) ANOVA=

Objective. The purpose of this study is to systematize and comprehensively evaluate safety data on the drug favipiravir using the national pharmacovigilance database of the Russian Federation. Materials and Methods. The report is based on spontaneous reports in the national automated information system of pharmacovigilance of the Russian Federation for the reporting period from 01.01.2020 – 04.07.2022. To identify safety signals we used disproportionality analysis, to estimate consumption of favipiravir – indicator of the number of consumed DDDs, we additionally performed review of concomitant therapy as a risk factor for serious adverse reactions. Results. A total of 412 reports of 585 adverse reactions was included in the analytic phase. The largest number of reports referred to liver and biliary tract disorders – 166 (38%), gastrointestinal disorders – 93 (16%), changes in laboratory and instrumental data – 53 (9%), and immune system disorders – 44 (7%). A total consumption of oral favipiravir expressed in the number of maintenance daily doses for 2021 was 46,417,274.87, i.e. 30 times the consumption of remdesivir and 6 times the consumption of hydroxychloroquine. One potential statistical safety signal such as hypercreatininemia was identified. Conclusions. Development of hypercreatininemia is a potential statistical safety signal of favipiravir, which requires further validation.

Introduction. Modern transplantation and biological therapy methods are associated with a wide range of adverse events and complications. Incidence and variety of neurological complications mostly depend on myelo- and immunosuppression severity and duration as well as on donor's and recipient's characteristics. The most frequent complications involving the nervous system include neurotoxic reactions, infections, autoimmune and lymphoproliferative diseases, and dysmetabolic conditions as well as cerebrovascular complications that potentially affect transplantation outcomes. Objective. To evaluate the impact of post-transplantation cerebrovascular events (CVEs) on transplantation outcomes in patients with hematologic malignancies. Materials and methods. We analyzed 899 transplantations performed at the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology, and Transplantation, Pavlov First Saint Petersburg State Medical University, from 2016 to 2018. We assessed transplantation parameters and donor's and recipient's characteristics by intergroup comparison, pseudo-randomization (propensity score matching), KaplanMeier survival analysis, and log-rank tests. Results. Post-transplantatively, CVEs developed in 2.6% (n = 23) of cases: 13 (1.4%) ischemic strokes and 11 (1.2%) hemorrhagic strokes or intracranial hemorrhages were diagnosed. CVEs developed on days 99.5 39.2 post hematopoetic stem cell transplantation (HSCT). There were more patients with non-malignant conditions in the CVE group as compared to the non-CVE group (21.7% vs 7.9%; p = 0.017). Patients with CVE had a significantly lower Karnofsky index (75.6 21.3 vs 85.2 14.9; p = 0.008). Statistically, we also note some non-significant trends: patients with CVE more often underwent allogenic HSCT (82.6% vs 64.0%; p = 0.077) while donors were more often partially (rather than totally) HLA compatible for recipients (39.1% vs 21.1%; p = 0.33). Patients with CVE more often had a history of venous thromboses (13.3% vs 4.2%; p = 0.077). Post-HSCT stroke decreased post-transplantation longevity by approximately 3 times (331.8 81.6 vs 897.9 25.4 post HSCT; p = 0.0001). In the CVE group, survival during first 180 days post HSCT (landmarks post-HSCT Day+60 and Day+180) was significantly lower as compared to that in the CVE-free group. If CVE developed during first 30 days and 100 days post HSCT, vascular catastrophe did not affect post-HSCT survival significantly. Conclusion. Whereas ischemic stroke is a long-term HSCT complication (beyond D+100 post transplantation), hemorrhagic stroke is a short-term complication (D0D+100 post HSCT). CVEs affect survival in patients with hematologic malignancies, especially those developed between D+60 and D+180 post HSCT. History of venous abnormalities, low Karnofsky index at HSCT initiation, and the type of allogenic HSCT, especially from half-matched donors, can be considered as negative outcome risk factors in post-HSCT CVE.

The lecture discusses some aspects of anesthetic and intesive care for patients with blast injuries based on the experience of local conflicts and man-made disasters of recent decades generalized by national and foreign experts.Such casualties are difficult to treat due to potential significant anatomical damage and development of severe functional disorders. Understanding the role of damaging factors facilitates the choice of diagnostic and therapeutic tactics.

Aim. To conduct a retrospective assessment of the clinical and laboratory data of patients with severe forms of COVID-19 hospitalized in the intensive care and intensive care unit, in order to assess the contribution of various indicators to the likelihood of death. Materials and methods. A retrospective assessment of data on 224 patients with severe COVID-19 admitted to the intensive care unit was carried out. The analysis included the data of biochemical, clinical blood tests, coagulograms, indicators of the inflammatory response. When transferring to the intensive care units (ICU), the indicators of the formalized SOFA and APACHE scales were recorded. Anthropometric and demographic data were downloaded separately. Results. Analysis of obtained data, showed that only one demographic feature (age) and a fairly large number of laboratory parameters can serve as possible markers of an unfavorable prognosis. We identified 12 laboratory features the best in terms of prediction: procalcitonin, lymphocytes (absolute value), sodium (ABS), creatinine, lactate (ABS), D-dimer, oxygenation index, direct bilirubin, urea, hemoglobin, C-reactive protein, age, LDH. The combination of these features allows to provide the quality of the forecast at the level of AUC=0.85, while the known scales provided less efficiency (APACHE: AUC=0.78, SOFA: AUC=0.74). Conclusion. Forecasting the outcome of the course of COVID-19 in patients in ICU is relevant not only from the position of adequate distribution of treatment measures, but also from the point of view of understanding the pathogenetic mechanisms of the development of the disease.

In our study, we aimed to evaluate the significance of specific cytokines in blood plasma as predictive markers of COVID-associated mortality. Materials and methods. In plasma samples of 29 patients with PCR-confirmed COVID-19 we measured the concentrations of 47 molecules. These molecules included: interleukins and selected pro-inflammatory cytokines (IL-1, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL 13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFN2, IFN, TNF, TNF/Lymphotoxin-(LTA)); chemokines (CCL2/MCP-1, CCL3/MIP-1, CCL4/MIP-1, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GRO, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine); anti-inflammatory cytokines (IL-1Ra, IL-10); growth factors (EGF, FGF-2/FGF-basic, Flt-3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGFAB/BB, TGF, VEGF-A); and sCD40L. We used multiplex analysis based on xMAP technology (Luminex, USA) using Luminex MagPix. As controls, we used plasma samples of 20 healthy individuals. Based on the results, we applied Receiver Operating Characteristic (ROC) analysis and Area Under Curve (AUC) values to compare two different predictive tests and to choose the optimal division point for disease outcome (survivors/non-survivors). To find optimal biomarker combinations, we as used cytokines concentrations as dependent variables to grow a regression tree using JMP 16 Software.Results. Out of 47 studied cytokines/chemokines/growth factors, we picked four pro-inflammatory cytokines as having high significance in evaluation of COVID-19 outcome: IL-6, IL-8, IL-15, and IL-18. Based on the results received, we assume that the highest significance in terms of predicting the outcome of acute COVID-19 belongs to IL-6 and IL-18. Conclusion. Analyzing concentrations of IL-6 and IL-18 before administering treatment may prove valuable in terms of outcome prognosis.

The objective: to evaluate the feasibility of using dexamethasone and lidocaine to potentiate the effect of anesthesia in patients with chronic polypous rhinosinusitis during functional endoscopic sinus surgery (FESS) interventions.Subjects and Methods. Clinical data, blood serum samples were collected prospectively from 52 patients who underwent FESS intervention. The patients were divided into 3 groups: Control Group ‒ C (n = 26), anti-inflammatory drugs were not administered; Dexamethasone Group ‒ D (n = 13), dexamethasone was administered (0.10‒0.15 mg/kg); and Lidocaine Group ‒ L (n = 13), a 1% solution of lidocaine was administered intravenously. The following parameters were studied: IL-6, IL-10, IL-18, alpha1-antitrypsin, and ferritin.Results. An increase of IL-6, IL-6/IL-10 was observed in Group C. An increase of IL-10 and a decrease of IL-6, IL-6/IL-10 were noted in Group D. In Group L, IL-6, IL-6/IL-10 did not change significantly. The intensity of bleeding was lower in Groups L (p < 0.001) and D (p < 0.05) versus Group C. Relative changes in the concentration of biomarkers within the normal range were detected in all groups.Conclusions. Changes in the cytokine profile are insignificant in patients with chronic polyposis rhinosinusitis during FESS performed under combined anesthesia.No convincing data on the need for intraoperative use of dexamethasone or intravenous lidocaine have been received.

An approach to the preparation of pullulan-graft-poly(2-methyl-2-oxazoline)s based on Cu-catalyzed azide–alkyne cycloaddition with polyoxazoline-azide was applied. All of the obtained polymers were characterized through classical molecular hydrodynamic methods and NMR. The formation of graft copolymers was accomplished by oxidative degradation of pullulan chains. Nevertheless, graft copolymers were obtained as uniform products with varied side chain lengths and degrees of substitution.

Introduction. In recent years, much attention has been paid to the study of extracellular microparticles (microvesicles and exosomes) and their role in the pathogenesis of human diseases.The objective of this study was to determine the number and size of plasma extracellular microparticles (PEMP) in patients with severe and extremely severe COVID-19 and correlate these data with the markers of hemostasis activation, inflammation, and tissue damage.Methods and Materials. The study included 29 patients with severe and extremely severe COVID-19. Concentration and size of PEMP were determined by nanoparticle trajectory analysis (NTA). All patients underwent the complete blood count and the thromboelastometry (TEM). Hemostatic, biochemical, and immunological parameters were assessed including fibrinogen, prothrombin time, activated partial thromboplastin time, D-dimer, C-reactive protein, lactate dehydrogenase, procalcitonin, von Willebrand factor antigen, interleukin 6, and interleukin 18.Results. There were 14 patients (48.3 %) discharged from the ICU with improvement (group 1— survived patients), and 15 patients (51.7 %) with lethal outcomes (group 2 — lethal outcome); the PEMP concentration did not differ between these groups. In group 2, there were heterogeneity of PEMP population, and a tendency to the larger PEMP size (p=0.074). In all patients, the PEMP concentration correlated negatively with both prothrombin time and the number of large platelets; the size of PEMP correlated negatively with the level of von Willebrand factor antigen, and positively with the fibrinogen. In group 1, the PEMP concentration had a direct correlation with both the level of interleukin 18 and maximum clot lysis in TEM; the PEMP size had a direct correlation with the maximum clot lysis in TEM and an inverse correlation with both the level of procalcitonin and maximum clot density in TEM.Conclusion. Our study confirms the importance of the process of extracellular microparticles formation in the COVID-19 pathogenesis. Our findings are consistent with the hypothesis that the parameters of PEMP population can be predictive biomarkers of the COVID-19 severity.

Introduction. More than 50,000 haematopoietic stem cell transplantations (HSCTs) are performed worldwide each year to treat malignant blood cancers, solid tumours, bone marrow aplasia, primary immunodeficiency conditions, autoimmune disorders, and storage disorders. The success of HSCTs depends on many factors, including patient's past medical history. Purpose. To assess the effect of an acute cerebrovascular accident (CVA) that occurred before the HSCT on the transplantation outcome in patients with blood cancer. Materials and methods. We examined the results of 899 transplantations conducted between 2016 and 2018 at the R.M. Gorbacheva Research Institute for Pediatric Oncology, Haematology and Transplantation of the Pavlov First Saint Petersburg State Medical University. We analysed transplantation parameters, as well as donor and recipient characteristics. Apart from intergroup comparisons, pseudo-randomization was performed using the Propensity Score Matching method. The survival rate analysis was conducted using the KaplanMeier estimate and the log rank test. Results. Sixteen patients (1.8%) had cerebrovascular events in their past history before the HSCT: ischaemic stroke in 0.4% of cases and haemorrhagic stroke or intracerebral haemorrhage in 1.4% of cases. Patients with a history of cerebrovascular events included more people with leukaemia (p = 0.02), had more often received an allogenic transplant (р = 0.01), the donors more often had a partial rather than a full HLA match with the recipient (р = 0.06), had a lower body mass index (р = 0.02), and a lower Karnofsky/Lansky score (р = 0.01) than patients in the control group. The presence of a cardiovascular event had a statistically significant association with reduced overall survival rate of HSCT recipients (р = 0.0012). Conclusion. Patients with blood cancer and stroke preceding the transplantation do not typically have any 'classical' risk factors (diabetes mellitus, venous system disorders, decreased cardiac output, significant atherosclerotic changes in precerebral arteries), therefore, secondary prevention guidelines for CVA during treatment of the main disease may not be effective and cannot be relied on. This article discusses the most likely causes of CVA in patients with blood cancer. A history of CVA before HSCT may have a significant effect on the transplantation outcome, but is not a contraindication for this treatment method. Recipient selection is a very important stage in HSCT planning. A multidisciplinary team should find a balance between the indications and contraindications for performing HSCT from an unrelated donor.

There is an increase in the incidence of multiple sclerosis in the world. Only in half of the cases, standard therapy allows for a short time to achieve control over this disease. High-dose immunosuppressive therapy and autologous hematopoietic stem cells transplantation is a promising and effective method of treating autoimmune diseases, including multiple sclerovsis. Over the past 20 years, progress has been made in understanding the immune mechanisms of the method. At present, the frequency and severity of adverse events of therapy significantly decreased by reducing the intensity of conditioning regimens. The objective of this review was to analyze scientific publications on the effectiveness of the method, and the data on the optimal conditions and criteria for its use in multiple sclerosis.

The objective: to conduct a comparative assessment of the severity of intraoperative bleeding with different methods of airway management (using a laryngeal mask and endotracheal tube) during endoscopic rhinosinussurgical procedures.Subjects and Methods. A prospective randomized cohort single-center study of 160 cases of endoscopic rhinosinussurgical procedures under general anesthesia was conducted.Tracheal intubation (TI) was used in 79 cases (Group 1), a laryngeal mask (LM) – in 81 (Group 2). The evaluation criteria in the groups included the bleeding intensity (BI) by 6-point scale of average categories (Fromme-Boezaart Score), indicators characterizing the state of blood circulation during surgery: HR, BPsys., BPdiast., MAP, and perfusion index.Results. Significantly lower BI values were observed in Group 2 at all time points of the study (at the 10th, 30th and 60th minute of surgery). This was due both to using a laryngeal mask, and to lower HR, BPsys., BPdiast, and MAP.Conclusion. The use of a laryngeal mask for airway management during general anesthesia in endoscopic rhinosinussurgical procedures helps to reduce the intensity of surgical field bleeding.

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.

The safety and effectiveness of endoscopic rhinological operations in the treatment of chronic inflammatory diseases, as well as neoplasms of the paranasal sinuses, are largely achieved by reducing bleeding in the area of the surgical field. Even a small amount of blood can disrupt the view during endoscopy and prevent the intervention from being performed, thereby increasing the risk of complications.The review presents modern methods of reducing the risk of intraoperative bleeding under general anesthesia. Each approach has its own characteristics, therefore, the benefit-risk ratio should be assessed for each patient before choosing a specific method for controlling intraoperative bleeding.

In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) after autoHCT (HR 0.6, 95% CI 0.4–0.7, p < 0.0001) due to reduced cumulative incidence of relapse in the last five years (56% in 2010–2014 vs. 38% in 2015–2022). An improvement in EFS after alloHCT over time was observed (HR 0.33, 95% CI 0.23–0.48, p < 0.0001), which was due to reduced non-relapse mortality. No difference in cumulative relapse incidence was observed over the last decade for allografted patients. Survival after autoHCT improved in Hodgkin’s disease (HR 0.1, 95% CI 0.1–0.3), multiple myeloma (HR 0.4, 95% CI 0.2–0.7) and solid tumors (HR 0.2, 95% CI 0.2–0.4), while after alloHCT, improvement was observed in acute myeloid leukemia (HR 0.3, 95% CI 0.1–0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1–0.5), Hodgkin’s disease (HR 0.1, 95% CI 0.0–0.4), non-Hodgkin’s lymphomas and chronic lymphocytic leukemia (HR 0.2, 95% CI 0.0–0.6), inborn diseases (HR 0.2, 95% CI 0.2–0.4) and acquired aplastic anemia with matched related donors and matched unrelated donors (HR 0.3, 95% CI 0.2–0.8).

This paper studies the working principles of antagonistic magneto-rheological (MR) actuators, i.e., a combination of an electric motor and a pair of MR clutches in an antagonistic configuration, for compliant actuation in robotics. The study focuses on the unique boundedness property exhibited by MR actuators, which limits the output torques delivered to the load, independent of the received input torque and/or control commands. This inherent property is of significant importance for ensuring human safety in human–robot interaction applications. Through a comprehensive analysis, we provide analytical proof of the inherent output boundedness of antagonistic MR actuators and validate our findings through experimental results. Our research demonstrates that these actuators are well-suited for safe operations in robotic applications, eliminating the need for additional sensor measurements or complex control strategies. This promising capability enables the avoidance of trade-offs between actuator performance, complexity, and cost. The insights gained from this study contribute to advancing compliant actuation technology, paving the way for high-performance and human-safe robotic systems.

The mechanisms of development of nosocomial infectious complications in COVID-19 and the contribution of bacterial and mycotic superinfection to the formation of extremely high mortality among patients with severe and extremely severe course of this disease have not yet been fully revealed. The objective: to study epidemiology, risk factors for the development of nosocomial superinfection, and its effect on the severity and outcome of the disease in patients with COVID-19.Subjects and Methods. 383 cases of severe and extremely severe COVID-19 were retrospectively analyzed. Demographic data, the presence of concomitant diseases, community-acquired co-infection at the time of hospitalization, data on the methods used to treat new coronavirus infection, severity of the course of the disease, developed infectious complications and their etiology, and the disease outcome were studied. Risk factors for the development of secondary infectious complications and the contribution of nosocomial superinfection to the severity of COVID-19 and the disease outcome were evaluated.Results. Risk factors for the development of secondary infectious complications include age over 65 years (OR 1.04; 95% CI 1.03–1.06; p < 0.0001), concomitant cardiovascular pathology (OR 3.82; 95% CI 2.02‒7.19; p < 0.0001), chronic kidney disease, including requiring renal replacement therapy (OR 2.01; 95% CI 1.33–3.02; p = 0.0007), and glucocorticoid therapy (OR 1.62; 95% CI 1.02–2.69; p = 0.04). The development of nosocomial infectious complications in patients with COVID-19 is associated with a more severe course of the disease and unfavorable prognosis (OR 13.44; 95% CI 8.23‒21.92; p < 0.0001).Conclusion. Identification of risk factors for the development of secondary infectious complications in COVID-19 allows developing differentiated approaches to the pathogenetic treatment of patients with severe COVID-19, increasing alertness in terms of the development of nosocomial infections, ensuring their timely diagnosis and treatment.

Changes in classification criteria and active introduction of biomarkers of acute kidney injury (KDIGO, 2012) are changing approaches to diagnosis and treatment of postoperative renal dysfunction including cardiac surgery patients operated with cardiopulmonary bypass (CPB). The objective: to compare the detection rate of AKI after surgery with CPB with the use of biomarkers and kidney disease improving global outcomes criteria, as well as to evaluate the cause and localization of structural changes of the nephron.Subjects and Methods. A monocenter observational study among elective cardiac surgery patients (n = 97) was conducted. Inclusion criteria: age over 18 years, duration of surgery (coronary bypass surgery, prosthetic heart valves) from 90 to 180 minutes, no signs of end stage kidney disease. AKI was diagnosed based on changes in serum creatinine and biomarkers (NGAL, IgG, albumin in urine). The studied parameters were recorded 15 minutes after the start and end of anesthesia, as well as 24 and 48 hours after surgery. Retrospectively, the group was divided into three subgroups: 1) patients without AKI after surgery; 2) patients in whom signs of AKI were detected after 24 hours but regressed by the 48th hour; 3) patients in whom AKI persisted during all 48 hours of follow-up.Results. 24 hours after surgery, AKI based on KDIGO criteria was recorded in 56.3% of patients. Using biomarkers, signs of tubular damage (NGAL) at the end of anesthesia were detected in 95.9% of patients; after 24 hours, they were registered in 73.2% of cases. In a subgroup where AKI persisted for more than 24 hours, glomeruli were damaged in addition to tubules which was manifested not only by selective but also by non-selective proteinuria. The duration of CPB, hemodilution (Hb < 90 g/l), the release of free hemoglobin in the blood (> 1.5 mg/l) at low (< 1 g/l) values of haptoglobin were significantly associated with AKI development.Conclusion. The KDIGO criteria do not allow detecting a subclinical form of renal dysfunction which may occur in about 40% of patients after surgery with CPB. AKI can be caused by damage to both the tubular part of the nephron and glomeruli in cases of prolonged CPB with the development of hemolysis, the release of free hemoglobin in the blood, and persisting anemia at the end of the surgery. The NGAL assessment makes it possible to detect subclinical kidney injury in the absence of elevated serum creatinine levels.

Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway in lethal COVID-19 caused by SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2). Last data suggested the possible role of extracellular vesicles in COVID-19 pathogenesis. The aim of the present study was to retrospectively evaluate parameters of cholesterol metabolism and newly identified EVs, exomeres, as possible predictors of fatal outcome of COVID-19 patients infected by the Alpha and the Delta variants of SARS-CoV-2 virus. Blood from 67 patients with severe COVID-19 were collected at the time of admission to the intensive care unit (ICU) and 7 days after admission to the ICU. After 30 days patients were divided into two subgroups according to outcome-34 non-survivors and 33 survivors. This study demonstrated that plasma low- and high-density lipoprotein cholesterol levels (LDL-C and HDL-C) were decreased in non-survivors compared to controls at the time of admission to the ICU. The conjoint fraction of exomeres and LDL particles measured by dynamic light scattering (DLS) was decreased in non-survivors infected by the Alpha and the Delta variants compared to survivors at the time of admission to the ICU. We first showed that reduction of exomeres fraction may be critical in fatal outcome of COVID-19.

Abstract 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

Currently, due to the lack of specific etiotropic therapy, rituximab is widely used for the treatment of most autoimmune diseases of the central and peripheral nervous system. Rituximab is a chimeric monoclonal antibody with specificity for CD20, the antigen found on the surface of normal and malignant B-lymphocytes. It is used mainly in hematological practice. It is used off-label for the treatment of neurological diseases. The world literature describes the use of rituximab for the treatment of such pathologies as autoimmune encephalitis, neuromyelitis optica spectrum disorder, multiple sclerosis, primary angiitis of the central nervous system, immune-mediated inflammatory polyneuropathy, myasthenia gravis, refractory to basic immunosuppressive therapy. This article provides an overview of the world literature on the use of rituximab in neurological practice, describes our own experience of its use on the basis of the Department of Neurology № 1 of Pavlov University (Saint Petersburg, Russia).

Objective: complex assessment of clinical and economic effectiveness as well as saving of the state budget assets within the therapy of patients with sepsis/septic shock based on different technologies of blood purification.Methods. Evaluation of direct and indirect costs of the eight blood purifcation methods. The target population includes adult patients 18+ with septic acute kidney injury. The study was conducted in compliance with acting Standards on Clinical Economic Studies used in the Russian Federation.The study methods included evaluation of existing randomized clinical studies and trials with data from network meta-analyses and systematic reviews of the target technologies. The direct medical and indirect non-medical costs were calculated and analyzed in respect of cost-effectiveness and budget impact analyses.Results. Direct and indirect costs were calculated for the sorption devices oXiris (Baxter International Inc.), Toraymyxin (Toray Medical Co.), Alteco LPS Adsorber (Alteco Medical AB), Toxipak (POKARD NPF), Desepta.LPS (BIOTECH M NPP), CytoSorb (CytoSorbents Inc.), HA330 (Jafron Biomedical Co.), Desepta (BIOTECH M NPP) for two time-horizons: 1-year period and 5-years period with discounting. For both periods, the use of oXiris hemoflter results in the least economic burden for the state budget.Conclusion. The use of blood purifcation in septic patients therapy is associated with considerable direct and indirect fnancial expenses, the amount of which and consequential budget saving depend on the technology of blood purifcation applied. The actual tariff compensation policy evidently demands revising.

Objective: to analyze available publications assessing efficacy of the Mozart effect in patients with epilepsy.Material and methods. A search for scientific publications has been performed in PubMed, Scopus and eLibrary databases by retrieving inquiries "Mozart effect" and "epilepsy" in paper title, resume and keywords. As a result, 18 studies matching inclusion and exclusion criteria were selected. The data obtained were systematized into four categories: 1) whether a single listening of Mozart’s Sonata for Two Pianos in D major, K.448 affect interictal epileptiform activity (IEA) immediately during an event; 2) whether a repeated (course) of listening K.448 affect IEA; 3) is there a delayed effect on IEA after a single or repeated listening of K.448; 4) how does the Mozart effect act on rate of epileptic seizures during ongoing therapy course of listening K.448 or afterwards.Results. It was found that therapy with Mozart’s sonata K.448 may lower IEA index during a single listening of this musical composition and shortly afterwards. A lowered IEA index during a course listening of K.448 lasting for some time afterwards may be observed as well. Moreover, a repeated listening of K.448 may reduce rate of epileptic seizures within entire music course.Conclusion. The analysis revealed that there are currently some reasons to consider the Mozart effect as a means of neurostimulation impacting on rate of epileptic seizures and IEA.

Impaired microcirculation due to endothelial dysfunction in COVID-19 is considered to be the most important link in the pathogenesis of this disease. However, due to the complexity of its instrumental assessment in critically ill patients, the data available in the literature on specific manifestations of endothelial dysfunction are very contradictory.The objective: to determine the most characteristic capillaroscopic signs of microvascular disorders and to assess the state of microcirculation regulation in patients with severe COVID-19.Subjects and Methods. When admitted to the intensive care unit, 60 patients with COVID-19 and 12 patients with chronic cardiovascular pathology without COVID-19 (Comparison Group) were examined. All patients underwent microscopy of the microcirculatory bed of finger nail bed; the following parameters were assessed: diameters of the venous, arterial and transitional parts of capillaries, height of capillary loops, density of capillaries per 1 mm of the length of the perivascular zone, the average linear velocity of capillary blood flow (LVCBF), and thickness of the perivascular zone. The presence of avascular zones, the number of capillaries in the visualized field with circulating aggregates in the lumen, and the shape of capillaries were taken into account. In addition, an occlusion test using laser Doppler flowmetry was performed in 32 patients with COVID-19. The maximum post-occlusive increase in blood flow at the moment of cuff deflation was assessed, as well as changes in the mean value of post-occlusive blood flow relative to the baseline within 3 minutes after cuff deflation.Results. In 53 (88.3%) patients with COVID-19, abnormalities corresponding to chronic microcirculatory changes in the form of predominance of pathological capillary forms were detected. Microaggregates in the lumen of capillaries and decreased linear velocity of blood flow were revealed in 100% of cases. When comparing groups of patients with different outcomes, statistically significant differences were revealed between the LVCBF parameters (in the survivors - 354.35 ± 44.78 pm/sec, in the deceased - 278.4 ± 26.59 pm/sec), as well as between the values of the perivascular zones thickness (95.35 ± 15.96 microns versus 159.93 ± 19.90 microns). The results of the post-occlusion test revealed a significant difference between the groups in terms of the maximum post-occlusion gain (39.42 ± 3.85 BPU in the group with a favorable outcome, 27.69 ± 3.19 BPU in the group with an unfavorable outcome, 47.23 ± 1.78 BPU in the control group). In both groups, there was no increase in this parameter relative to the initial blood flow. At the same time, in the control group, the average index of post-occlusive blood flow was higher than the initial level.Conclusions. Acute microcirculation disorders with decreased linear velocity of capillary blood flow, circulation of aggregates, increased thickness of the perivascular zone were detected in all patients with severe COVID-19 but especially in those with unfavorable outcomes. Vascular tone regulation disorders were manifested by the absence of reactive hyperemia in response to acute ischemia, as well as a decrease in maximal flow-induced increase. These changes fit into the concept of endothelial dysfunction. Signs of chronic microcirculation disorders in most patients increase the risk of severe COVID-19.

Ferritin is one of the biomarkers requiring special attention; its blood level increases significantly especially in the severe course of COVID-19. Information on the effect of hyperferritinemia on the disease outcome is very contradictory as are the ideas about the causes of its development.The objective: to study the effect of hyperferritinemia on the disease outcome and analyse the possible causes of its development in severe COVID-19.Subjects and Methods. Data on 479 patients with severe course of coronavirus infection treated in intensive care units (ICU) were retrospectively analyzed. Of them, the proportion of patients with a favorable outcome (Group 1) was 51.0% (n = 241), and with an unfavorable outcome (Group 2) - 49.0% (n = 235). The following parameters were assessed: the levels of ferritin, C-reactive protein, fibrinogen, IL-6, IL-10, IL-18, procalcitonin, complement C5a, total, direct and indirect bilirubin, ALT, AST, and the blood level of lactate dehydrogenase (LDH). The changes of erythrocyte count and hemoglobin blood level were also monitored. In order to form a clear view of iron metabolism, free iron, transferrin, and myoglobin levels were assessed in several patients with high ferritin values (more than 1,500 pg/L).Results. In the unfavorable outcome, ferritin levels increase very significantly, reaching maximum by day 6 of patients' stay in ICU. The difference in the level of ferritin between the groups of survivors and deceased during this period is clear and significant (p = 0.0013). The association of ferritin values with the outcome is detected as early as day 1, but by day 4 it becomes highly significant (the cut-off point is 1,080 pg/l). No data have been obtained that would indicate the association of hyperferritinemia with impaired iron metabolism, the development of hepatic dysfunction, or cellular destruction. In contrast to survivors, those who died on day 6 had elevated IL-6 while C5a level remained unchanged. Conclusions. The rapid increase in ferritin blood levels to 1,000 pg/L or higher is an unfavorable prognostic sign indicating a high probability of a lethal outcome. When assessing genesis of hyperferritinemia in COVID-19, the crucial significance should be attributed to the cytokine storm rather than disorders of iron metabolism or hemotoxic effects of the virus. The persistent increase of ferritin level in blood during 4-6 days of stay in ICU should be considered as a reason to intensify anticytokine therapy.

Estimations of the frequency of acute kidney injury in SARS-CoV-2 (COVID-19) coronavirus disease are very diverse. The literature data is highly inconsistent and shows AKI ranging from 0.5 to 80%.The objective: to analyze the incidence of renal dysfunction in COVID-19 patients and assess the significance of systemic inflammation for its development.Subjects and methods: The analysis was performed basing on data of 3,806 patients with COVID-19 treated at the Pavlov State Medical University, 395 of them were admitted to the intensive care units (ICU). The criterion for establishing renal dysfunction (RD) is the increase in blood creatinine level above the upper limit of reference values (0.115 mmol/l). Patients with end-stage chronic kidney disease who needed to continue routine long-term dialysis were not included in the study. We analyzed the incidence of renal dysfunction, changes in blood levels of creatinine, urea, and electrolytes during 8 days. In addition, glomerular filtration rate, diuresis volume, levels of hematocrit, hemoglobin, LDH, CRP, ferritin, and procalcitonin were evaluated.Results. The frequency of RD among all patients was 19.0%, among patients in the ICU – 41.0%. In 79% and 81%, respectively, it was detected on the first day of hospitalization. The increase in the number of patients with RD and the aggravation of the existing dysfunction occurred after 6 days. At the initial stage of the disease, the manifestations of RD in most cases were not expressed even in those with an unfavorable course of the disease but the level of creatinine showed a weak but significant (p < 0.5) correlation with changes in CRP (r = 0.110), ferritin (r = 0.137), and procalcitonin (PCT, r = 0.418). The difference in the level of creatinine in patients with PСT level above and below 0.5 ng/ml was observed on the first day only; the value of this parameter returned to normal faster in the subgroup of patients whose procalcitonin level did not exceed 0.5 ng/ml.Conclusion. In case of the signs indicative of RD, it is advisable to distinguish between primary and secondary injury. In the first case, it is primarily due to systemic inflammation, in the second case it is caused by additional impact of other aggressive factors. This will make it possible to clarify the renal and non-renal indications for renal replacement therapy (RRT) in patients with COVID-19, and to evaluate the results adequately since the effectiveness of RRT at different stages of the disease cannot be the same.

The constant mutation of the virus and the complicated epidemiological situation in other countries keep the probability of a third wave of the pandemic in the Russian Federation fairly high. It is important to summarize the gained experience as fast as possible to use it appropriately once it is needed.The objective: to analyze the specific parameters of care for critically ill patients with the novel coronavirus infection in Pavlov Multidisciplinary Medical Center.Subjects and methods. This is a result-based report on the work performed by the Infection Center, which was deployed twice in Pavlov Multidisciplinary Medical Center (from 28.04.2020 to 03.08.2020 and from 01.11.2020 to 15.03.2021). Totally, 3,830 patients with SARS-CoV-2 were managed (1,680 patients during the first deployment and 2,150 patients during the second one). In the preparatory period, the operation of the emergency department based on the inpatient emergency medical department (EMD) had been simulated to clarify its staff structure and the procedure for admission, examination, and treatment of patients. Here we compare the organizational approaches during the first and second waves of the pandemic and present the characteristics of the demographic data of the treated patients, the incidence of certain complications, and outcomes.Results. The overall lethality in the Center made 6.2%. Despite the experience gained in the first wave, the results of treatment during the second wave (autumn-winter) did not improve (5.7% died in the first wave and 6.7% in the second one). Lethality in ICU and EMD was 40.0% and 49.6%, in ICU only – 38.5% and 46.9% respectively. A moderate lethality increase in ICU was due to the concentration of critically ill and most critically ill patients. There were 51.4% of patients with comorbidities and 53.5% were above 65 years of age. Refinement and differentiation of tasks performed by departments, simulation of the operation of the Center before opening made it possible to increase the throughput of the medical unit avoiding rush during admission and deterioration the quality of treatment.Conclusion. Certain aspects of the organization of medical care affect the performance of a multidisciplinary medical institution transformed into an infectious diseases hospital. The experience gained under such circumstances can be useful in other emergencies with a large number of victims and patients.

The use of high-adsorption membrane hemofiltration in COVID-19 positive patients to reduce the severity of a cytokine storm is clearly beneficial but at the same time, there are no certain procedures for its practical use.The objective: to study the change in the levels of IL-6 and IL-18 in response to prolonged (24-72 hours) high-adsorption membrane hemofiltration.Subjects and methods. We retrospectively analyzed the data on IL-6 and IL-18 levels and their changes in 69 patients who were COVID-19 positive and had different degrees of lung damage, they had received high-adsorption membrane hemofiltration during their stay at the intensive care unit. The extent of lung lesions was the following: 4 people had CT-2, 44 people had CT-3, and 21 patients had CT-4. 18 patients had an unfavorable outcome of the disease. High-adsorption membrane hemofiltration (Prismaflex) was used in the group of patients who had clinical signs of the rapid progression of the disease and also such laboratory findings as elevated values of C-reactive protein (above 100 mg/L), ferritin (more than 600 μg/L), and progression of lymphopenia. This intervention lasted for 24 hours at CT-2/3, and 48 hours at CT-4. The effluent dose was 30.0 ± 6.4 ml/kg/h. The levels of IL-6, IL-18, and procalcitonin were tested before and after the completion of the intervention, and the difference between their concentration before and after high-adsorption membrane hemofiltration was calculated. The potential association between received data (IL-6, IL-18, delta of IL-6, delta of IL-18) and degree of lung damage and outcomes was analyzed.Results. It was detected that the more the lungs were affected, the lower levels of IL-6 and IL-18 were and vice versa and this correlation was not associated with the use of tocilizumab (used in 44 people). The maximum decrease in the level of cytokines was observed in the group of patients with CT-2. There was a significant association between the delta of IL-6 (F = 6.69; p ≤ 0.05) and the outcome which was especially pronounced in people with a favorable outcome.Conclusion. As the inflammation progresses in the lungs, the levels of IL-6 and IL-18 decrease which may be a manifestation of the depletion of the cytokine storm. The use of prolonged high-adsorption membrane hemofiltration (24-48 h) allows reducing the level of cytokines. The delta value reflects a decrease in IL-6 concentration, it significantly correlates with the outcome which indicates the importance of using this method in a continuous mode.

Acute symptomatic epileptic seizures are one of the complications of hematopoietic stem cell transplantation. The etiological factors leading to the development of this complication differ from those in the general population, while the significance of each of them is different depending on the time after transplantation. We analyze the literature data on the role of drugs, metabolic disorders and infectious complications, as well as the structural pathology of the brain substance in the development of acute symptomatic seizures in patients with oncohematological pathology. We also consider the clinical features of symptomatic epileptic seizures and the possible prognostic significance of their development in patients who underwent hematopoietic stem cell transplantation.

Thrombophilia, as well as multiple organ dysfunction, are typical manifestations of the severe new coronavirus infection that closely resemble the clinical signs of catastrophic antiphospholipid syndrome (CAPS). The objective: to assess whether catastrophic antiphospholipid syndrome is an essential manifestation of severe forms of COVID-19.Subjects and methods. 45 patients diagnosed with the new coronavirus infection (SARS-CoV-2) and a severe course of viral pneumonia (more than 3 points on the NEWS score by the admission, CT 3-4, oxygenation index below 100, the need for at least high-flow oxygen therapy). They were assessed for the development of CAPS due to signs of progressing organ dysfunction despite the ongoing intensive therapy, suspected pulmonary embolism and progressing venous thrombosis of a lower extremity or subclavian vein. It was an essential provision that they should have no signs of bacterial infection (blood procalcitonin should be below 0.5 μg/l). The antiphospholipid syndrome was diagnosed based on the detection of antibodies to β-2-glycoprotein in the blood (A/t β-2-GP1 IgGAM, A/t β-2-GP1 IgM, A/t β-2-GP1 IgG) and to cardiolipin (A/t CL IgM , A/t CL IgG) by ELISA tests. The course of the disease was monitored using other routine clinical (temperature, complete blood and urine counts) tests and blood panel tests reflecting the severity of the systemic inflammatory response (ferritin, CRP, interleukins 6 and 18), and the state of the hemostatic, respiratory, circulatory, liver and kidney systems.Results. Antiphospholipid antibodies (aAPL) moderately exceeding the reference values were detected in 9 out of 45 patients (20%), mainly due to IgA and IgM isotypes to β-2-glycoprotein and IgM isotype to cardiolipin. The assessment of the antibody titer in 5 patients over time (after 7 days) revealed a decrease, but it did not affect the outcome (four of them died). In 36 patients, some traces of aAPL were found that did not reach the lower limit of the norm, despite the uniformity of the clinical signs and similarity of biochemical parameters reflecting the severity of organ disorders. The absence of antibodies did not prevent the development of thrombotic complications (thrombosis of large vessels and pulmonary embolism in 5 patients). There were no other manifestations often associated with CAPS (thrombocytopenia, hemolytic anemia, decreased fibrinogen concentration in the blood). Conclusion. Catastrophic antiphospholipid syndrome is not inevitable in severe COVID-19 cases, however, it can develop as one of the manifestations of thrombophilia that occurs in such patients.

Microcirculation disorders caused by thrombosis are the most important factor determining the pathogenesis of organ damage in severe COVID-19 including the absence of obvious macrohemodynamic instability. However, there are very few publications demonstrating the results of intravital visualization of changes in the microcirculation system in this disease.The objective: to assess the state of microcirculation in patients with viral pneumonia associated with COVID-19 using nail bed microscopy.Subjects and methods. Eleven patients with COVID-19 were examined; they were admitted to the intensive care unit due to progressing acute respiratory failure. Vital microscopy of the microcirculatory bloodstream in the fingers’ nail bed was performed by admission and over time. When assessing microcirculation, the presence of aggregates in the lumen of capillaries and avascular zones, and the linear velocity of blood flow were taken into account. The results were summarized taking with the outcome consideration (6 people recovered, 5 died). Results. Microcirculation disorders were objectively confirmed in all patients. In 100% of cases, microaggregates were detected in the capillary lumen. The values of the mean linear velocity of capillary blood flow turned out to be extremely variable. However, the values of the maximum linear velocities of capillary blood flow in the patients who subsequently died were significantly lower versus survivors (190 μm/sec (135.5; 237) and 387 μm/sec (329.3; 407.5), p = 0.018). The irregularity of blood flow in the visualized field was revealed: when the value of the maximum linear velocity in some capillaries was less than 180 µm/sec, in others, disturbances in the form of pendulum-like movement were already noted. Further slowing down of the blood flow velocity led to the development of stasis and the formation of avascular zones.Conclusion. Impaired microcirculation (decreased blood flow rate in the capillaries, the presence of microaggregates and a lower number of perfused capillaries in the form of avascular zones) develops in all patients with severe COVID-19.

Subjects and methods. The retrospective study included 37 patients (n = 37) diagnosed with severe viral pneumonia (SARS-CoV2) who were treated in the intensive care unit of Pavlov First Saint Petersburg State Medical University. To assess the significance of PADM as a biomarker of bacterial infection, patients were divided into two groups: the group of patients with viral pneumonia without sepsis (n = 24) and the group of those who developed sepsis and septic shock complicating the course of the new coronavirus infection (n = 13). PADM was assessed as a criterion for the severity of the disease in the groups of deceased (n = 19) and survivors (n = 18). Data were statistically processed in the computer mathematics system R, version 3.6.2, the prognostic significance of PADM was assessed using linear regression.Results. The median PADM in the group without sepsis was higher than the reference value – 1.1 (0.5; 4.3) nmol/L, in patients with sepsis that complicated the course of viral pneumonia – 2.8 (1.1; 5.7) nmol/L (p = 0.0019). Significant differences were revealed between the baseline levels of PADM in patients with different outcomes: in the surviving group, the median was 0.99 (0.5; 3.14) nmol/L, and in the group of deceased – 2.70 (0.94; 5.86 ) nmol/L. In surviving patients, the changes in PADM levels had a linear distribution throughout the entire period of stay in the intensive care unit. In deceased patients, within 20 days before death, PADM tended to grow significantly and reached its maximum by the time of the outcome.Conclusion. The assessment of the PADM blood level can be used to clarify the addition of a bacterial infection in patients with pneumonia caused by the SARS-CoV2 virus. The study of changes in its level makes it possible to objectify the prediction of the course of COVID-19 – favorable or unfavorable. Data accumulation is required to clarify specific PADM values that predict the outcome in COVID-19 patients.

The authors reviewed the literature and presented results of their own research of post-operative cognitive dysfunction confirming its social importance. The development of post-operative cognitive dysfunction is to be perceived as a real fact despite the differences in the published epidemiological data. Currently, there are no grounds to correlate it directly with the general anesthesia given to patients, and there is no evidence that a certain method of anesthesia or a certain drug can reduce the frequency of post-operative clinical decline. There are numerous factors within genesis of post-operative cognitive decline and they are not studied well. All suspected mechanisms (neurotoxicity of the used agents, and other factors of anesthesia and surgery; impairment of information neuro-transmission mechanisms; neuroinflammation developing as a response to trauma) can initiate the complex neuro-physiological reactions causing cognitive dysfunction.The authors presented experimental data about morphofunctional changes in neurons and cerebellar cortex microglia after laparotomy and anesthesia with sevoflurane followed by the exposure to it in a special box for 6 hours (induction of 8 vol. % with the air flow of 2 l/min., maintaining 2 vol. % of sevoflurane with the air flow of 1 l/min.). They demonstrated that neuroinflammation was not the key factor of the detected neuronal damage. Purkinje neurons were damaged the most, since they were fairy sensitive to energy metabolic disorders, promoting the death of other neurons of the molecular layer. Neurons of the granular layer with the low level of energy metabolism were the most resistant to the impact provided by surgery/anesthesia. These data confirmed the importance of multifactorial approach when assessing the genesis of cognitive dysfunction. This research is to be continued and aimed to find out predictors of post-operative cognitive decline and to optimize anaesthesiologic support of surgery and other invasive interventions to provide a balance between their aggressiveness and effectiveness of protection, especially in senile patients who already have some cognitive dysfunctions.

Introduction. Under the conditions of circulatory disorders and coronary heart disease (CHD), amino acids acquire additional value as a source of intermediates of Krebs cycle, participating in cell energetics. If there is a disturbance of energy metabolism, the level of amino acids in the blood can change, including the minor non-encoding amino acid homoarginine (hArg).The objective of this study was to compare the shifts in the levels of hArg and other amino acids in the venous blood flowing from the tissues of the heart and brain versus their levels in blood plasma from the cubital vein in patients with CHD.Methods and materials. The study used plasma samples of 58 patients (46 men and 12 women) aged 62 (57 — 66) years with CHD and heart failure of functional class III (NYHA). The level of hArg and the spectrum of 22 other amino acids were determined by the reversed-phase high-performance liquid chromatography (HPLC). Besides, the levels of lactic acid (LA) were determined by spectrophotometric method, as well as routine biochemical parameters were determined using standard kits.Results. Patients with CHD had compensated, without significant deviations, biochemical data of glucose level, lipid and nitrogen metabolism profiles. The level of hArg in the patient group of 1.4 (1.0—1.9) p.M was significantly lower compared to the reference interval, and the level of total homocysteine was increased, although there were no differences depending on the venous basin. The highest concentrations of LA, alanine and glutamine were detected in the plasma from the internal jugular vein. At the same time, lower concentrations of arginine, lysine and alanine corresponded to the lowest values of hArg.Conclusion. In patients with CHD and heart failure, a significant increase in the levels of glutamine and alanine in plasma from the internal jugular vein and coronary sinus in comparison with plasma from the cubital vein was accompanied by profound dysregulation of energy metabolism with the decrease in hArg levels.

It has been found out that methylation of nucleic acids, proteins and low-molecular substrates is necessary to renew cellular structures, their restoration and cytoprotection. Methionine plays the most important role in this process but whether its metabolism changes during anesthesia and how different anesthetics affect it, has not yet been studied.The objective: to study the metabolism of methionine during cardiopulmonary bypass when the direct myocardial revascularization is performed and the impact of the anesthetics used (propofol, desflurane, and sevoflurane) on methionine metabolism.Subjects and methods: 74 patients who underwent surgery due to coronary heart disease with cardiopulmonary bypass were enrolled in the study. The patients were divided into three groups by the anesthetic used (desflurane, sevoflurane, propofol). Levels of methionine, homocysteine, cysteine, and taurine were tested in the blood collected from veins and jugular vein before the aorta clamping and after the release of clamps.Results. In all three groups, lower levels of methionine and a higher level of homocysteine were observed after the release of clamps from the aorta, especially in the jugular vein. The most significant consumption of methionine was noted when propofol was used. In the same group, the exocytic release of homocysteine into the blood and the formation of cysteine were significantly lower. No significant difference was observed in the effect of desflurane and sevoflurane on methylation.Conclusion. During the anoxia, the consumption of methionine increases significantly but the intensity of demethylation/remethylation depends on the anesthetics used during anesthesia. The most significant decrease in the level of methionine as well as the remethylation of homocysteine into methionine occurs with the use of propofol, rather than inhalation anesthetics which may be a consequence of desflurane and sevoflurane cytoprotective properties.

It is very important to observe all the parameters of cardioplegia when protecting myocardium during cardiac surgery. To perform this task, it is necessary to have clear understanding of properties of the elements of the extracorporeal circuit of cardiopulmonary bypass.The objective: to develop a test model and using it to evaluate technical capabilities of blood cardioplegic system reducing the filling volume of the heat exchange chamber and the system supplying solution to the myocardium.Subjects and methods. A model of a neonatal cardiopulmonary bypass circuit was tested, it included an oxygenator and the cardioplegic system with a 7-ml heat exchange chamber; changes in the pressure and temperature in key nodes of the extracorporeal and cardioplegic circuits were assessed when the pump velocity, ambient temperature and fluid temperature in the main circuit were changed.Results. This modification provides a wide range of liquid volumetric velocities. Maintaining the selected variant of blood cardioplegia and safe pressure within the cardioplegic circuit is ensured at the perfusion rate of up to 350 ml/min. With normothermal circulation and air temperature in the operating room of 23°C, parameters of the cardioplegic circuit and solution delivery system allows maintaining the solution temperature within the range from 16 to 19°C. When the solution is cooled in a heat exchanger down to 4°C, the temperature of the final cardioplegic solution is maintained within 12-17°C; and with normothermal perfusion, air temperature in the operating room of 15°C and the solution temperature in the heat exchange chamber of 4°C, the temperature of the final cardioplegic solution can be within 6‒13°C. With perfusion in the mode of moderate hypothermia (32°C), air temperature in the operating room 15°C and temperature in the heat exchange chamber 4°C, the final cardioplegic solution can be delivered at the temperature from 5 to 9°C.Conclusions. The proposed test model allows investigating aimed to find out additional characteristics of the cardioplegic circuit.Ambient air temperature, cardioplegic pump velocity and main circuit fluid temperature are the main factors influencing the final cardioplegic solution temperature.When using the studied variant of the cardioplegic circuit assembly, the maintenance of the selected variant of blood cardioplegia and safe pressure inside the cardioplegic circuit are ensured at a perfusion rate of up to 350 ml/min.

The objective: to identify laboratory markers of systemic perfusion in newborns with functional single ventricle on mechanical ventilation after surgical correction. Subjects and methods. Blood gas parameters were retrospectively analyzed in 52 newborns with congenital heart defects with univentricular hemodynamic after surgical correction. All samples were divided into three groups based on arterial blood saturation (SaO2): Group 1 – hypoxia (SaO2 ≤ 65%); Group 2 – normoxemia (SaO2 = 65-85%); Group 3 – hyperoxemia (SaO2 > 85%). Stroke volume and cardiac index were evaluated with echocardiography. The oxygen consumption and carbon metabolism were evaluated by arterial and venous blood gases. Results. The mixed central venous pO2 (PvO2) > 29.5 mm Hg, mixed central venous O2 (SvO2) > 54.5%, arteriovenous difference in saturation (Sa-vO2) < 15.8%, total oxygen content in venous blood (CvO2) > 119 ml/l, oxygen extraction ratio (O2ER) < 19% and the arteriovenous difference in partial pressure of carbon dioxide (dPCO2) < 5.4 mm Hg are cut off criteria for adequate systemic perfusion. PvO2 < 26 mm Hg, SvO2 < 44.5%, Sa-vO 2 > 27%, CvO2 < 88 ml/l, O2ER > 27.7%, dPCO2> 7.9 mm Hg have been associated with decreased systemic perfusion. The logistic regression model including combination of O2ER and dPCO2 predicts adequate systemic flow accuracy of 94.3% (sensitivity 87.5%, specificity 94.7%, p = 0.001). Graphics allow to adapt the mathematical model to clinical practice to verify systemic hypoperfusion in newborns with functional single ventricle. Conclusion: The following cut off parameters allow to assess systemic perfusion in newborns with functional single ventricle: PvO2, SvO2, CvO2, Sa-vO 2, O2ER, and dPCO2. The model for predicting the adequacy of systemic perfusion can be used as an effective tool to monitor hemodynamic status in newborns with functional single ventricle.

The editorial considers the results and development trends of anesthesiology and resuscitation in this country after the 2nd Congress On Topical Issues of Critical Care Medicine which was held last year. Special attention is paid to the practical implementation of the concepts of enhanced recovery of the patient and perioperative medicine as well as acute kidney injury. It is noted that a change in the conceptual understanding of renal dysfunction results in re-consideration of principles of management of critically ill patients with special emphasis on factors that can cause (aggravate) kidney injury. The article focuses on the fact that the mechanistic implementation of any new techniques without regard to the consequences can bring not only benefits but also harm. It emphasizes that the prevention of the cohort of patients with chronic kidney disease from growing and adequate timely use of modern dialysis technologies can result in reduction of public spending on hemodialysis after discharge from the hospital. The effectiveness of interdisciplinary interaction of various professional communities jointly searching for solutions is illustrated by the example of the management of the antibiotic resistance problem.

The article tells about Armen A. Bunyatyan, the outstanding Soviet and Russian scientist, anesthesiologist, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences (September 30, 1930 – February 19, 2020). It presents his background and reflects his contribution to the development of the specialty and science of anesthesiology and resuscitation.

Introduction. Strains of microorganisms resistant to antimicrobial agents are commonly found in medical units throughout most regions of the world, including Russia. This leads to lower antimicrobial therapy efficacy when treating nosocomial infections. In this regard, the timely implementation of adequate antibiotic therapy is of great importance.The objective of the guidelines: To provide summarized information on contemporary approaches to microbiological diagnostics and the assessment of results, as well as the principles of rational use of antimicrobial and antifungal agents, including treatment of infections caused by multiple drug-resistant strains of microorganisms.Subjects and methods. These guidelines are based on published data obtained in the course of randomized trials, as well as information presented in the provisions of international guidelines supported by high-level evidence. The guidelines were prepared by a working group of Russian experts with extensive experience in research and practical work in this area. On October 11, 2019, the final version of the guidelines was reviewed and approved at a joint meeting of the working group and representatives of the public organizations which initiated the development of these guidelines (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), NGO Russian Sepsis Forum).Conclusion. The guidelines reflect an interdisciplinary consensus of approaches to the diagnostics and antibiotic therapy of infections caused by multiresistant microorganisms. The provisions set forth should be used to decide on the strategy of empirical and etiotropic therapy of the most severe infections.

Introduction. Currently, there is a tendency for a number of post-intubation patients to develop post-tracheostomic cicatricial stenosis of the trachea. This dictates a need for the improvement of surgical and anaesthesiologic approaches to intubation management. Objective: Analysis of the specific parameters of anesthesia for cervical tracheal resection in patients with stenosis of the trachea without its intubation.Subjects and methods. We analyzed 12 cases of circular resection of the trachea due to benign stenosis. The degree of anesthetic risk was as follows: 11 patients – ASA 3, 1 patient – ASA 4. Tracheal stenosis persisted for 14±6 months before it was resected (Me 4, Min 1, Max 67). The length of the resected part of the trachea was 27±3 mm (Me 25, Min 15, Max 40), duration of surgery – 159±9 min (Me 160, Min 65, Max 240). The anesthesia strategy included the insertion of the I-Gel supraglottic airway device with a jet ventilation catheter put through the I-Gel. Temporary stenting of the stenosis zone of the trachea before surgery (if necessary) instead of bougienate was an important component of the anesthesia strategy. Mandatory use of sedation (dexmedetomidine) is suggested before and within 12 hours after surgery.Results. This strategy can be successfully implemented if the minimum diameter of the tracheal stenosis exceeds 7 mm (the jet ventilation catheter is necessary to be applied through this lumen and a fine bronchoscope used to monitor the state of the catheter tip). Preliminary stenting with metal stents was performed in 5 patients. The I-Gel lumen was wide enough to manipulate a flexible endoscope, a catheter guide was inserted for jet ventilation, and then the catheter itself was placed. The use of high-frequency ventilation mask it advisable to ensure adequate gas exchange at all stages of the surgery. Sedation with dexmedetomidine reduced the patient’s discomfort after the surgery due to the fixation of the patient’s head with stitches in a “nodding” position, which reduced anastomosis tension. In all 12 patients, this anesthesia strategy was successful and provided a more favorable environment for surgeons compared to the classical approach with the use of an endotracheal tube. In all patients, anastomosis healed by primary tension with no complications.Conclusion. The use of a supraglottic airway device, dexmedetomidine, and temporary stenting of the stenotic part of the trachea allow the surgeon to avoid tracheal intubation during circular resection and expand the range of anesthesiological tools during tracheal surgery.

Дорогие друзья!В канун Нового, 2022 года прежде всего хочу поблагодарить всех членов редколлегии, экспертов, выступавших в роли рецензентов, авторов статей и, конечно же, читателей за приверженность Журналу и большой совместный труд по повышению его рейтинга и привлекательности. Мы и далее будем работать над тем, чтобы в «Вестнике…» публиковалась интересная и актуальная для практических врачей информация.К сожалению, из-за пандемии коронавирусной инфекции уходящий год, так же как и предыдущий, для всех оказался не самым простым. Редакция и редколлегия старались максимально оперативно размещать на страницах Журнала материалы, отражающие накопленный опыт лечения таких больных, рассчитывая, что он окажется полезным для совершенствования лечебной тактики при этой весьма неприятной болезни. В то же время мы старались не забывать и о «нековидных» вопросах, поскольку сегодня по-прежнему важно обращать внимание и на другие аспекты нашей повседневной работы. Они ведь никуда не исчезли из нашей жизни, и поле деятельности анестезиолога-реаниматолога никак не сократилось.Дорогие друзья, от имени сотрудников редакции и членов редколлегии поздравляю вас с наступающим 2022 годом! Пусть Новый год принесет нам благополучие, стабильность, удачу, а все наши планы и мечты исполнятся!Главный редакторакадемик РАН, профессорЮ. С. Полушин

Purpose: The aim of this research is to develop an accurate and interpretable aggregated score not only for hospitalization outcome prediction (death/discharge) but also for the daily assessment of the COVID-19 patient's condition.Patients and Methods: In this single-center cohort study, real-world data collected within the first two waves of the COVID-19 pandemic was used (27.04.2020–03.08.2020 and 01.11.2020–19.01.2021, respectively). The first wave data (1,349 cases) was used as a training set for the score development, while the second wave data (1,453 cases) was used as a validation set. No overlapping cases were presented in the study. For all the available patients' features, we tested their association with an outcome. Significant features were taken for further analysis, and their partial sensitivity, specificity, and promptness were estimated. Sensitivity and specificity were further combined into a feature informativeness index. The developed score was derived as a weighted sum of nine features that showed the best trade-off between informativeness and promptness.Results: Based on the training cohort (median age ± median absolute deviation 58 ± 13.3, females 55.7%), the following resulting score was derived: APTT (4 points), CRP (3 points), D-dimer (4 points), glucose (4 points), hemoglobin (3 points), lymphocytes (3 points), total protein (6 points), urea (5 points), and WBC (4 points). Internal and temporal validation based on the second wave cohort (age 60 ± 14.8, females 51.8%) showed that a sensitivity and a specificity over 90% may be achieved with an expected prediction range of more than 7 days. Moreover, we demonstrated high robustness of the score to the varying peculiarities of the pandemic.Conclusions: An extensive application of the score during the pandemic showed its potential for optimization of patient management as well as improvement of medical staff attentiveness in a high workload stress. The transparent structure of the score, as well as tractable cutoff bounds, simplified its implementation into clinical practice. High cumulative informativeness of the nine score components suggests that these are the indicators that need to be monitored regularly during the follow-up of a patient with COVID-19.