The COVID-19 outbreak started in December 2019 in China has spread over all countries of the world within few month acquiring a pandemic nature, the incident population counting millions. The pathogenic mechanisms of the new coronaviral infection caused by never-before-seen virus SARS-CoV2 are yet to be studied. Various drugs are used for COVID-19 treatment and guidelines are continuously revised as new experience is acquired. In the current pandemic situation, it is important to provide specialists with latest information concerning efficacy and safety drugs for COVID-19 patients and promising research in this field.

The purpose of the review is to critically analyze published data on outcomes of COVID-19 treatment with various drugs including potentially promising drugs.

The search has been carried out through such databases as PubMed, Scopus, Cyberleninka, https://www.globalclinicaltrialsdata.com, https://clinicaltrials.gov, Cochrane Library; mostly, randomized clinical trials-2020 and papers dedicated to candidate drugs have been considered. The paper is structured based on the drug’s action mechanism and contains parts dedicated to antiviral, immunomodulatory, and antibacterial therapies. Looking for a new promising target in COVID-19 treatment, the authors focus their attention on matrix metalloproteinases (MMP), which abundance results in the destruction of extracellular matrix, epithelial and endothelial basal membranes and leads to secondary lung tissue injury. The paper provides a theoretic justification of MMP inhibitor use by an example of doxycycline and offers an efficacy study protocol for the new approach to COVID-19 therapy.

Conclusion: as of now, there are no drugs which efficacy for COVID 19 has been proven. Drugs possessing multiple mechanisms of action are employed beside their specified indications, often in combinations; in this situation, additive side effects with adverse consequences for the patient can hardly be avoided. Administration of drugs with unproven efficacy may be justified only in clinical trials followed by subsequent analysis and publication of findings demonstrating that in case of success, recommendations for a majority of COVID-19 patients could be confidently issued.

Comparative studies on the efficacy and safety of Inhalation Anesthesia (IA) and Total IntraVenous Anesthesia (TIVA) have been performed for many years, and the results were various.

The aim of this study was to evaluate new data on the clinical efficacy of anesthetic preconditioning, the difference between inhalation and intravenous anesthesia on cardiac protection and clinically relevant outcomes in cancer surgery.

Materials and methods. We carried out a systematic review and meta-analysis on searches and analysis of the literature over the past five years in accordance to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results. Out of the 759 articles which were initially identified, we selected 3 studies regarding the clinical significance of anesthetic cardioprotection and 10 studies comparing IA and TIVA in patients undergoing surgery for malignant diseases.

Two meta-analyses and one multi-regional clinical trial (MRCT) suggest that further studies of the effectiveness of anesthetic cardioprotection is futile.

A meta-analysis of 9 retrospective cohort studies and 1 MRCT showed a detrimental effect of IA on 3-year survival in surgical oncology (Hazard Ratio (HR): 1.73 (1.36; 1.96) Heterogeneity: Q = 8.336, df = 3, I²; f²= 64.01, overall effect analysis: Z = 2.386 (P<0.017)). Analysis of 5-year mortality did not reveal any differences, although it did not remove any doubts about the possible negative effect of the use of IA in surgical oncology.

Conclusion. Due to the futility of the previous efforts, the authors suggest not starting new studies aimed at finding evidence of the effectiveness of anesthetic cardioprotection on clinically relevant outcomes. However, since cohort studies indicate a possible beneficial effect of the use of TIVA in surgical oncology, the authors suggest conducting a serious comparative MRCT in this setting.

Infusion therapy is one of the most frequently prescribed treatments in hospitalized patients. Fluid maintenance and resuscitation is an important strategy in major surgery. Acetate-buffered balanced crystalloid fluids may influence acid-base status, intracellular and extracellular water content, plasma electrolyte composition and have a favorable impact on renal, hepatic, and splanchnic microcirculation.

Aim was to evaluate current evidence of efficacy and safety of acetate-buffered crystalloid solutions for fluid therapy in abdominal surgery in adults.

Materials and methods. Medline, the Cochrane Library, eLIBRARY.ru were searched up to 31 May 2020 (additional search in November 2020) using the key words «acetate» AND «buffers» OR «buffered» AND «crys-talloid solutions» OR «crystalloids». Studies published after 2009 in English and Russian were included. Systematic review was conducted in accordance with PRISMA guidelines using specified PICO(S) criteria.

Results. The total of 62 studies were identified from all databases. Out of them 11 full-text publications were considered eligible, 6 of them were included into the final review. Acetate-buffered crystalloid solutions have a favorable impact on microcirculation. Metabolic alkalosis after the fluid infusion did not occur in all the studies; potassium levels remained stable, also.

Conclusion. Efficacy (based on acid-base status, hemodynamic parameters) of the acetate-buffered crystalloid solutions for fluid therapy during the abdominal surgery in adults patients was confirmed with the A level of evidence.

The aim of the study is to evaluate the efficacy of hyperbaric oxygen therapy and its effect on oxidative stress and apoptosis in patients with new coronavirus infection COVID-19.

Materials and methods. 90 patients diagnosed with new coronavirus infection caused by SARS-CoV-2 virus were examined. Hyperbaric oxygen therapy sessions were conducted in 57 patients (38 in severe condition (CT 3-4), 19 in moderate condition (CT 1-2)). The procedures were performed in 1.4-1.6 ATA mode for 40 minutes, 247 sessions in total were performed. The effect of hyperbaric oxygenation was assessed by measuring the level of oxygen saturation, the severity of oxidative stress and apoptosis of blood lymphocytes.

Results. In all examined patients with new coronavirus infection caused by SARS-CoV-2, positive changes such as dyspnea reduction and improvement of general well-being were registered after hyperbaric oxygen therapy sessions. The level of oxygen saturation after the end of the hyperbaric oxygen therapy course was 95.0±1.6% (before the course — 91.3±5.9%), which allowed to return almost all patients to spontaneous respiration without the need for further oxygenation therapy. Hyperbaric oxygen therapy did not reduce the total antioxidant activity, however, it was associated with a decrease in the blood malone dialdehyde from 4.34±0.52 pmol/l to 3.98±0.48 pmol/l and a decrease in open circuit potential of platinum electrode from -22.78±24.58 mV to -37.69±17.4 mV. Besides, the positive effect of hyperbaric oxygen therapy was manifested in normalization of blood cell apoptosis.

Conclusion. Hyperbaric oxygen therapy in patients with new coronavirus infection caused by the SARS-CoV-2 virus is an effective treatment method with multiple effects resulting in improvement of subjective indicators of the patients' condition, increase of hemoglobin oxygen saturation, decrease of lipid peroxidation intensity, activation of antioxidant system, restoration of pro- and antioxidant balance and apoptosis normalization.

The aim of the study is to summarize the histology and morphometry of cortical neurons in acute clozapine and ethanol poisoning.

Material and methods. Histological examination of the parietal cortical brain samples of 26 patients died during the Day 1 of acute clozapine and ethanol poisoning (23 males and 3 females aged 22-63 years) was performed. The blood ethanol level was 1.4-4.1%o. The level of clozapine in the blood ranged between 0.24 and 5.8 mg%, in the liver between 0.097 and 6.5 mg%, in kidneys between 0.03 and 3.5 mg%. The cortical samples for morphometric examination were placed in 10% neutral paraformaldehyde, the histological sections were done and stained with hematoxylin and eosin, as well as according to Niessl. The morphological analysis was performed using the video light microscopy. The number of damaged neurons (with separate quantification of reversible, intermediate, and irreversible damage) was assessed. The statistical analysis was done using the non-parametric methods.

Results. The signs of brain neuronal damage in acute clozapine and ethanol poisoning, as well as forensic chemical tests, might be used for establishing the direct cause of death.

Aim of the study: to evaluate safety and feasibility of clinical use of an extracorporeal blood adsorber based on a hypercrosslinked styrene-divinylbenzene copolymer with immobilized lipopolysaccharide (LPS)-selective ligand designed to remove endotoxins from the bloodstream to treat patients with septic shock.

Materials and methods. Nine patients (mean age 58 years, 5 men and 4 women, initial median APACHE II score 28 points, SOFA score 10 points) with confirmed Gram-negative bacterial infection and septic shock (SEPSIS-3, 2016) underwent LPS-selective hemoperfusion using an extracorporeal blood adsorber based on a hypercrosslinked styrene divinylbenzene copolymer with immobilized LPS-selective ligand for 6 hours, followed by prolonged veno-venous hemodiafiltration. Before the hemoperfusion (day 0), immediately after it, a day after its end (day 1) and once daily for the next 4 days we assessed the hemodynamic parameters, oxygenation, organ failure signs, white blood cell count, procalcitonin, C-reactive protein, clinical chemistry parameters.

Results. Hemoperfusion resulted in a rapid decrease in the endotoxin activity (EAA test), more than twofold decrease in plasma level of interleukin-1 (immunoenzyme test). At the end of the procedure, the plasma lactate level decreased to normal values by day 3, pH values restored to normal within 1-2 days. The noradrenaline requirement rapidly decreased and completely resolved within 1-3 days, which corresponded to the restoration of mean blood pressure values. The values of the PaO2/FiO2 oxygenation index increased significantly after 24 hours, and the median values of 300 were maintained during all subsequent days of observation. During the first day, hemoperfudion caused a rapid decline in APACHE II and SOFA scores, while acute renal failure (estimated by urea and creatinine levels) resolved gradually by day 5. The hemoperfusion did not affect the unchanged coagulation parameters (prothrombin, fibrinogen, INR). During the first day after the procedure, we observed a short-term 1.5-fold decrease in platelet count with subsequent recovery by days 2-3 in most patients. Two patients, both differing from the rest of the patients prior to treatment in the highest values of APACHE II score (above 30), APTT (above 40) and endotoxin activity in EAA test (above 0.9), died on the 4th and 8th days of treatment. The rest of the patients survived, with clinical improvement in all parameters.

Conclusion. The results of extracorporeal blood purification using Efferon LPS extracorporeal blood adsorber indicate a high therapeutic potential of the method and suggest the need for extended clinical trials to assess its clinical efficacy in ICU to reduce the high mortality in patients with septic shock.

Increasing incidence of ischemic diseases and limited resources for their treatment stimulate increased interest in studying the mechanisms of vascularization and finding new approaches for its promotion. One of these approaches is gene therapy aimed at activating the epicardium to produce the vascular precursor cells and microenvironment for the «assembly» of de novo vessels.

The aim is to investigate the possibility of activating epicardial cells and post infarction cardiac vascularization by injecting a genetic construct encoding PDGFBB.

Material and methods. A model of experimental myocardial infarction in a rat with subsequent intramyocardial injection of normal saline solution, control plasmid and plasmid encoding PDGFBB was used. The study of PDGFBB effect on epicardial cell activity was performed on the ex vivo model, as well as in vitro mesothelial cell culture.

Results. Post infarction injection of plasmid encoding PDGFBB increases the density of the vascular network in the peri-infarct area as well as migration of pericytes to the injured zone. PDGFBB promotes activation of epicardial cell pool and expression of smooth muscle cell markers in them (shown on the ex vivo model), as well as stimulates activation of epithelial-mesenchymal transition (in vitro).

Conclusion. Intramyocardial injection of a genetic construct encoding PDGFBB after an experimental myocardial infarction stimulated vascularization of the peri-infarction zone, which may have been partially due to the activation of the epicardial cell pool.