Venous thromboembolism (VTE) is the third most frequent cause of death from cardiovascular diseases after myocardial infarction and stroke and the most preventable cause of mortality. VTE is common and potentially life-threatening in patients admitted to ICU, even in spite of preventive care.

The purpose of the review is to justify the necessity of preventive care for venous thromboembolism in ICU patients.

From over 300 initially selected sources of literature databases (Scopus, Web of science, RSCI, etc.), 99 sources were chosen including 69 that were published during the last five years (2015-2020). The exclusion criteria included data of low informative value or disproven data.

The review discusses VTE relevance, risk factors for its development, selection and scope of preventive care depending on the risk of thrombosis and hemorrhage, patient management in different clinical settings (impaired renal function, thrombocytopenia, heparin-induced thrombocytopenia, liver dysfunction, indications for installation of vena cava filter).

In the world literature, however, there is yet no consensus on the matter under discussion that would have been based on meta-analyses or large randomized studies. No agreement has been reached either in respect of use of mechanical and combined prophylaxis of venous thromboses/PATE, application of ultrasound to detect asymptomatic thromboses. There are no studies on efficacy and safety of pharmacological prophylaxis of VTE in patients with significant hepatic impairment.

The review describes that all patients admitted in ICU feature a high risk of VTE development. The scope of preventive care depends not only on VTE risk but also on the risk of a hemorrhage. To prevent the latter, low-molecular weight heparins should be used. For most cases, the choice of heparine dose depends on renal function. When there is a high risk of hemorrhage, mechanical preventive aids are applied.

This paper highlights published hypotheses on the possibility of coronavirus SARS-CoV-2 entry into the bloodstream, its interaction with vascular endothelium, red blood cells, hemoglobin and its fragments. As a result of such interaction, iron ions may be released into the bloodstream and, subsequently, a cytokine storm may occur. In this context, it is important to find a cytoprotective agent capable of blocking such processes. The perfluorocarbon emulsion could be a candidate for this role.

The aim of the paper is to show the feasibility of biophysical methods to study the molecular mechanisms of action of SARS-CoV-2 on human red blood cells and hemoglobin as well as the restorative and cytoprotective effect of the perfluorocarbon emulsion during Fe²⁺ oxidation in heme.

Materials and methods. High resolution spectroscopy, atomic force microscopy, atomic force spectroscopy, electroporation were used. Blood was exposed to oxidizing agents of different nature. Perfluorocarbon emulsion was added in various concentrations and its effect at various incubation times was studied. Concentration of hemoglobin derivatives was calculated considering multicollinearity, and statistical analysis of the results was performed.

Results. The perfluorocarbon emulsion was shown to have an effective restorative and cytoprotective action in iron ion oxidation in the heme: Fe³⁺ was restored to Fe²⁺. The degree of MetHb reduction to HbO₂ and Hb depended on the concentration of the oxidizing agent and incubation time. We observed a change in MetHb content from 80-90% to 5-12%. The perfluorocarbon emulsion in clinical concentrations helped eliminate local membrane defects and restored normal erythrocyte morphology.

Conclusion. In the light of the studied hypotheses, the use of perfluorocarbon emulsion can become an effective method for blocking the consequences of coronavirus effect on the blood cells and restoring a normal gas exchange.

Aquaporins represent proteins contributed to water transport through cell membrane. They are involved in formation and resolution of edema, cell migration and inflammatory reaction. There are only few studies linking the genetic polymorphism of aquaporin 5 (rs3759129 AQP5) and sepsis. At the same time, the apparent heterogeneity of patients along the foci of infection may limit finding the most significant association of AQP5 genotypes with the course of infectious complications of critical conditions and restrict further development of rs3759129 AQP5 as a potentially strong marker of sepsis outcome.

The purpose of the study was to determine whether the preferential localization of the infection affects the prognostic value of the genetic marker AQP5 (1364A/C, rs3759129) in outcome prediction in sepsis (SEPSIS-3, 2016) patients.

Materials and methods. Study groups (n=339) included ICU patients with abdominal sepsis (AS, including pancreatitits, peritonitis, cholecystitis, appendicitis; n=94) sepsis patients with other sources of infections  (n=65) and ICU patients without sepsis (n=180). AQP5 polymorphism was studied by analyzing PCR products in a 2% agarose gel using a AQP5 1364A/C specific tetra primer set.

Result. Distribution of alleles (A and C) and genotypes (AA, AC and CC) AQP5 1364A/C in patients with  sepsis or sepsis subgroups (sepsis with no septic shock and sepsis shock patients) versus control group (healthy  volunteers) did not differ. Although there was a trend to preferential survival of sepsis patients with genotype C AQP5 despite the source of infection, only patients with AQP5 CC or AC genotype and abdominal sepsis (Sepsis-3), or a subgroup of the same AQP5 genotype experiencing septic shock, demonstrated increased 30day survival versus AA homozygotic patients (P=0.002).

Conclusion. The informative value of detecting the AQP5 CC or AC genotype for prognosis of 30-day survival versus AA homozygotic patients is most significant only in abdominal sepsis patients.

Инсульт является второй по частоте причиной смерти в мире после ишемической болезни сердца (ИБС) и третьей по частоте развития инвалидности.

Цель: выявление закономерностей содержания кандидатных молекулярных маркеров в сыворотке крови пациентов в различные стадии геморрагического инсульта.

Материал и методы. Число пациентов с геморрагическим инсультом составило 33, из них мужчин 15, женщин 18. Возраст пациентов — 31-65 лет. Молекулярные маркеры ЦНС в сыворотке крови определяли в острейшей стадии через 1-3 часа, 7, 14 и 30 дней от начала заболевания. Количественную оценку содержания кандидатных молекулярных маркеров повреждения центральной нервной системы (ЦНС) в сыворотке крови у пациентов с геморрагическим инсультом осуществляли методом иммуноферментного анализа в острейшей стадии через 1-3 часа, затем — 7, 14 и 30 дней от начала заболевания. Определяли нейротрофический фактор головного мозга, нейронспецифическую ено-лазу, белок S-100 общий, глиальный нейротрофический фактор, васкулоэндотелиальный фактор роста, сиалированный углеводный антиген, супероксиддисмутазу. Молекулярные маркеры ЦНС выявляли с помощью автоматического микропланшетного иммуноферментного анализатора Immuno-mat ТМ. Контрольную группу составили 20 добровольцев в возрасте 24-58 лет. Статистический анализ полученных данных производили при помощи пакета Statistica 7,0. Использовали параметрические методы статистического анализа, данные представили в виде медианы 25-75 перцентилей (25-75 IQR). Статистически значимым считали различие при p<0,05.

Результаты. По сравнению с группой контроля в сыворотках крови пациентов с геморрагическим инсультом отмечали изменение содержания исследуемых кандидатных молекулярных маркеров. В острейшей стадии геморрагического инсульта (1-3 часа от начала заболевания) регистрировали статистически значимое возрастание содержания белка S100, глиального нейротрофического фактора, фактора роста эндотелия сосудов, супероксиддисмутазы, сиалированного углеводного антигена, а снижение содержания мозгового нейротрофического фактора и повышение содержания нейрон-специ-фической енолазы было статистически недостоверным. В острой стадии геморрагического инсульта (7-14 дней) отмечали статистически значимое снижение содержания мозгового нейротрофического фактора (14 день), повышение содержания фактора роста эндотелия, супероксиддисмутазы, сиалиро-ванного углеводного антигена. В подострой стадии заболевания (30 суток) регистрировали статистически значимое повышение содержания фактора роста эндотелия, супероксиддисмутазы и сиалиро-ваннго углеводного антигена.

Заключение. Изучили динамику содержания кандидатных молекулярных маркеров в сыворотке крови пациентов с геморрагическим инсультом, которая, вероятно, отражает процессы альтерации и регенерации, соответствующие стадиям заболевания. Использование данных кандидатных молекулярных биомаркеров, после соответствующей валидации, перспективно в комплексной диагностике, мониторинге лечения и реабилитационных мероприятий у данной категории пациентов.

Purpose of the study: to evaluate hearing the vagus nerve’s rhythm in patients with paroxysmal atrial fibrillation.

Materials and methods. Observations were carried out in 50 patients with paroxysmal atrial fibrillation who were admitted for catheter-based treatment of arrhythmia. Cardiorespiratory synchronism test was carried out not in atrial fibrillation attack during sinus rhythm with the help of VNS-Micro instrument and software determining the regulatory adaptive status of the human body. The early depolarization zone in the right atrium was mapped using circulatory navigation 20-pole LASSO NAV. Carto-3 system was used to build an electro-anatomic isochronous model of sinus rhythm of the right atrium. The automatic method of annotation of CONFIDENCE module points was applied. At least 500 activation points in the right atrium were set. The observational data and computed values, subject to normal distribution, were processed by parametric statistic techniques using STATISTICA 10.0 software.

Results. It has been established that in subjects with low regulatory adaptive capabilities, the length of atrial fibrillation anamnesis amounted to 5.8±0.7 years, and in case of good and satisfactory capabilities — 2.9±0.5 years. The Pearson correlation coefficient between the area of early depolarization zone in the right atrium and disease duration was equal to 0.92.

Conclusion. The length of atrial fibrillation correlates with the regulatory adaptive status and area of the early depolarization zone in the right atrium.

Coagulopathy always accompanies blood loss, and its transformation into disseminated intravascular coagulation syndrome (DIC) is associated with increased morbidity and mortality.

Objective: to characterize the features of the development and course of DIC during bleeding, as well as identify the main predictors of its formation during surgical interventions in children with oncological diseases.

Material and Methods. A retrospective study of children under 18 years of age with oncological pathology who received surgical treatment for the period from 2017 to 2019 years. Children who received blood transfusion and hemostatic therapy with intraoperative bleeding were selected. The resulting cohort (n=207) was divided into two groups using the modified ISTH assessment system: children with DIC (n=59), without DIC (n=148). Demographic, clinical, and laboratory factors were compared between groups. The final model of multivariate logistic regression included signs that were before the development of DIC on the second day after the operation and were selected as a result of univariate analysis (P<0.05), had less than 10% missing data and were clinically plausible. The prediction accuracy of the multivariate model was checked by analyzing the area under the ROC curve.

Results. DIC was found to develop often in children with cancer during surgical operations in the retroperitoneal space (OR=2.09 [1.07; 4.05]; P=0.03) and liver (OR=3.86 [1.72; 8.67]; P=0.001). Multiple organ failure (MOF) was more severe and was represented by pulmonary, hepatic and renal failure in the group with identified DIC. The development of MOF was accompanied by a decrease in tissue perfusion and an increase in D-dimer. The probability of detecting acute thrombosis after surgery was 4.5 times higher in the group of patients with DIC than in the group without DIC (OR=4.5 [1.4; 14.3]; P=0.01). 90-daily survival was 84.41±6.49% [71.69%; 97.13%] in the group of patients with DIC, and 96.22±3.12 [90.1%; 100%] in the group without DIC. Multivariate analysis showed that age less than 8 years, platelet count less than 150X109/l, hypocalcemia less than 1 mmol/l and the period of intraoperative critical hypotension for more than 25 minutes are predictors of the development of DIC after surgery. ROC analysis showed excellent quality of the obtained predictive model (AUC=0,94 [0,9; 0,97]).

Conclusion. In children with oncological diseases, in the presence of bleeding, coagulopathy in the postoperative period is transformed into a DIC-syndrome, proceeding clinically with the development of organ failure. Age less than 8 years, platelet count less than 150X109/l, hypocalcemia less than 1 mmol/L and a period of intraoperative critical hypotension of more than 25 minutes are predictors of the development of DIC. The extreme expression of the «organ» type DIC is the progression of thrombotic syndrome to life threatening complications, which reduces the 90-day survival by 12%.

Among the major etiological factors that can cause an anaphylactic shock (AS), drugs account for 31.2-46.5%.

Purpose of the work was to identify factors associated with a high AS risk based on 2010-2018 records made in the Republic of Crimea.

Materials and methods. The objects of the study were 112 information reports about adverse reactions (AR) to medicine remedies (MR), which were recorded in the regional database of spontaneous information reports—ARCAD — in the Republic of Crimea during 2010-2018. A retrospective analysis of drug-induced AS cases has been carried out for the following indicators: intake and route of administration of drugs, gender, age, history of allergies.

Results of the study have shown that antimicrobial drugs, local anesthetics, analgesics-antipyretics, X-ray contrast iodine-containing substances, and non-steroidal anti-inflammatory drugs featured the highest AS incidence. Most frequently, AS cases were observed in patients aged 31 to 60 years, with no significant differences between men (57 cases) and women (54 cases). In one case the patient's gender was missed or not stated.

The leader in AS incidence is Ceftriaxone, which application was associated with 22 cases of such AR. In 87 cases, AS was found associated with parenteral administration drugs, the intravenous route of administration being predominant (44 cases). In 97 cases, development of drug-induced AS was life-threatening and required emergency pharmacotherapy; 8 reports contained a lethal outcome record.

Conclusions. Attention should be paid to high incidence, severity, and instant progression rate of adverse reactions in the form of AS. Considering the AS progression rate and facts of ignored past history of drugs and allergies, as well as pharmacological correction errors, additional educational events are worth conducting for physicians specializing in different fields.

The aim of the study is to explore the best intensive care strategies for acute 1,4-butanediol poisoning complicated by post-intoxication delirium.

Materials and methods. The data of the laboratory testing and treatment of 40 men with acute severe poisoning with 1,4-butanediol, complicated by post-intoxication delirium were analyzed. Twenty patients received succinate-containing drug, others were treated with conventional methods. The control group included 18 healthy male patients aged 25 to 40 years. Clinical course of delirium, parameters of glutathione system and lipid peroxidation in patients' red blood cells, oxygen transport function (by indirect calorimetry), gammahydroxybutyric acid level in the biological fluids by gas chromatography/mass spectrometry were evaluated during the study.

Results. An increases in levels of reduced glutathione by 50.3% by day 7 (from 3.68±0.57 to 5.53±0.35 pmol/g), hemoglobin (Hb), antioxidant enzymes and glutathione reduction enzymes were found; glucose-6-phosphate dehydrogenase increased by 17,1% (from 3.68±0.26 to 4.31±0.41 pmol/g Hb) and glutathione reductase increased by 15% (from 174.1±16.3 to 200.2±4.11 pmol/min/g Hb). At the same time, the MDA lipid peroxidation system activation was decreased by 41.9% (from 7.78±1.06 to 4.52±0.28 nmol/g Hb).

Conclusion. The obtained data proved high efficacy of a succinate-containing drug in slowing down the progression of post-intoxication delirium through increasing the level of the main cellular antioxidant, the reduced glutathione.

The aim is to study the effectiveness of lithium chloride for preventing damage to the monolayer of endothelial cells in vitro exposed to serum of patients with septic shock.

Material and methods. Serum samples prepared from blood of 5 septic shock patients selected according to «Sepsis-3» criteria and 5 healthy volunteers (control serum) were used in the study. Blood for experiments was withdrawn within 2 hours after the diagnosis of septic shock. The Ea.hy926 endothelial cells were incubated with the serum of a patient with septic shock (toxic serum) or control serum for 3 hours at 37°C without or with lithium chloride at final concentrations of 0.01 mmol/l, 0.1 mmol/l, 1 mmol/l, 10 mmol/l. Lithium chloride was added 1 hour before the serum change. After incubation, the expressions of actin, VE-cadherin and claudin were assessed by immunofluorescent microscopy; the level and degree of phosphorylation of glycogen synthase kinase 3/1 (GSK-3/3) were determined using western blotting.

Results. Toxic serum significantly inhibited GSK-3/3 phosphorylation, induced cleavage of VE-cadherin and reduced the claudin inendothelial cells. Toxic serum also altered the shape of endothelial cells: they lost their native polygonal shape and became elongated with gaps between them. Incubation of endothelial cells monolayer with lithium chloride at concentrations equal or higher 1.0 mmol/l almost completely prevented cleavage of claudin, actin and VE-cadherin. When studying the in vitro protection of endothelial cells from effects of toxic serum with lithium chloride, pre-incubation with the drug at a concentration of 1 mmol/l for 1 hour prevented inactivation (dephosphorylation) of GSK-3/3 and even to stimulate its phosphorylation in 1-4 hours after exposure to the serum.

Conclusion. The study clearly showed the protective effect of lithium chloride on endothelial cell monolayer by activating phosphorylation of GSK-3/3 (enzyme conversion into inactive form). Moreover, the effect of lithium chloride exhibited a distinct dose-dependent character starting with a concentration of 0.01 mmol/l.