Introduction. Thrombo-inflammatory changes in the alveolar-capillary membrane are significant links in the pathogenesis of respiratory failure in COVID-19. This study investigates whether leukocyte-platelet aggregates contribute to its development and, if so, the mechanisms involved. Aim. To examine the quantitative changes in leukocyteplatelet aggregates in patients with COVID-19 receiving different levels of oxygen support. Materials and methods. The study included 134 COVID-19 patients of varying severity and 20 volunteers examined in the pre-pandemic period. The criterion for dividing the studied patients into groups was the ratio of blood oxygen saturation to its inhaled fraction, investigated by pulse oximetry. Three groups were formed depending on the value of the index: in the first (n=48), the SpO2/FiO2 index was above 450%, in the second (n=55) it ranged from 370 to 449%, and in the third (n=51) the index was up to 369%. The enumeration of blood cells, major leukocyte populations, lymphocyte subpopulations, and plateletleukocyte complexes was performed using the CytoFLEX LX flow cytometer (Beckman Coulter, USA). Results. In the third group, there was a decrease in the number of monocytic aggregates (p<0.001) and their subfractions, as well as the number of lymphocyte rosettes (p=0.015), while the number of lymphocytes (p<0.001) and neutrophil interactions (p=0.05) increased in parallel. In the second group, there was a statistically significant decrease in the total number of monocytic aggregates (p=0.038), and in the third, the number of aggregates with classical monocytes (p=0.012). Conclusion. The number of lymphocyte-platelet and monocyte-platelet aggregates decreased in patients with different types of oxygen support, while neutrophil-platelet aggregates increased and correlated with the SpO2/FiO2 ratio.

AIM:To study the dynamics of cystatin C in patients after procedures on retroperitoneal viscera using laparoscopic and retroperitoneal access. MATERIAL AND METHODS:A prospective study of serum and urine cystostatin C levels in 162 patients with renal cysts using laparoscopic (n=83) and retroperitoneal access (n=79) was carried out. Patients were divided into four groups depending on the duration of the procedure and the gas level. For determination of cystatin C level in serum and urine, flow cytometry was performed using Human Kidney Function Panel 2 Mix and Match Subpanel (for Serum/Plasma Samples). RESULTS:A significant increase in the serum and urine level of cystatin C in groups 3 and 4 was seen on the 1st day after laparoscopic procedures in case of pneumoperitoneum pressure above 12 mm Hg., regardless of its duration. For retroperitoneoscopic procedures, similar changes were found only in group 4 with a gas pressure above 12 mm Hg and duration of the intervention of more than 30 minutes. By day 3, cystatin C levels returned to baseline values in all groups. CONCLUSION:The most significant risk factor for acute kidney injury after laparoscopic and retroperitoneoscopic procedures is the gas pressure. The second most important factor is the duration of the intervention. Pneumoperitoneum has a greater effect on cystatin C levels compared to retropneumoperitoneum.

INTRODUCTION. The severe acute respiratory syndrome-related coronavirus-2 (SARS-Cov2) virus is able to interfere with the interaction of angiotensin-converting enzyme with its receptor. Pronation can affect not only the state of gas exchange during Coronavirus disease 2019 (COVID-19), but also blood circulation, as well as the exchange of vasoactive substances. Hemocirculation disorders are essential in the pathogenesis of severe COVID-19.The OBJECTIVE was to assess the level of vascular biomarkers in patients with pneumonia caused by SARS-CoV-2 during proning against the background of various respiratory supportMETHODS AND MATERIALS. The study included 3 groups of patients depending on respiratory support. The first group consisted of 16 patients who received respiratory support with oxygen at a flow of 5–7 liters per minute. The second group included 15 patients who underwent non-invasive lung ventilation. The third group of 16 patients underwent invasive lung ventilation. Blood tests of endothelin-1, B-natriuretic hormone were performed using an enzyme immunoassay kit. The amount of nitrite (NO2) and nitrates (NO3) was determined by the method based on the enzymatic conversion of nitrate to nitrite with the participation of the enzyme nitrate reductase. The reaction recorded the colorimetric concentration of nitrite using the azo dye formed in the Griess reaction.RESULTS. In patients with respiratory oxygen support during pronation, a decrease in the blood level of brain natriuretic peptide was detected. During the prone position maneuver in patients on mechanical ventilation, the concentration of nitrites increased. In an intergroup comparison, in patients of group 3 relative to groups 1 and 2, NO2 and NO3 indicators changed against the background of proning.СONCLUSION. The increased invasiveness of respiratory support in patients with COVID-19 when performing prone positioning is associated with changes in blood levels of nitrites and nitrates.

INTRODUCTION: The forensic medical examination of “medical criminal cases” is the “cornerstone” on the conclusions of which the results of the trial and the further fate of our colleagues largely depend. Therefore, the medical community wants the conclusion of experts (including anesthesiologists and ICU physicians) to be completely objective, scientifically based, not biased and based not on the subjective opinion of an expert, but on specific regulatory documents. OBJECTIVE: To identify typical errors and improve the quality of expert assessment of medical care in the field of “anesthesiology-intensive care”. MATERIALS AND METHODS: The analysis of some forensic medical examinations in criminal cases with the participation of an anesthesiologist and ICU physicians part of the experts was carried out. RESULTS: As a result of the analysis of the conclusions of the forensic medical examinations under consideration, significant shortcomings were identified that could have a significant impact on the results of the consideration of criminal cases and contribute to the imposition of unjustified convictions. CONCLUSIONS: It is necessary to create a legal mechanism for certification of doctors of specialties to allow them as experts to conduct complex forensic medical examinations and state control over the quality of their work.

The search for domestic publications on this publication was conducted in the database on the RSCI website, and foreign ones in the PubMed and Google Scholar databases in the period 2022-2023. Their analysis showed that actively studied approaches to the immunocorrection of sepsis are aimed at changing the content or activity of cytokines, growth factors, the use of immune checkpoint inhibitors, as well as myeloid suppressor cells. When modulating the action of cytokines, a variety of approaches are used, such as changing the affinity of cytokines to their receptors, extending the half-life of cytokines and «fine-tuning» the action of cytokines. For the safe and effective use of bioregulators for immunocorrection in sepsis, additional multicenter studies of their clinical effectiveness are needed, including taking into account the stratification of patients into individual endotypes and the mechanisms of action of bioregulators.

Most patients with critical illness, regardless of the cause, develop activation of innate and adaptive immunity. This is often a critical process leading to organ dysfunction. The aim of the review is to systematize information on monitoring the immune system in critical illness for physicians of different specialties (anesthesiology and intensive care, surgery, general practice, obstetrics and gynecology). The review includes information from 83 recent national and international publications (mostly from 2023), available in the public domain and found by keyword search. We have summarized the current understanding of the relationship between infections and the human immune system, as well as the clinical application of traditional markers of immune status. We provided data on novel promising markers for the assessment of immunity in patients with various diseases. Limitations of the studies reviewed include the need for additional large-scale clinical trials of even the most promising markers, as well as a synthesis of the evidence for their performance. In addition, immune monitoring is likely to increase the cost of patient care, necessitating the development of more affordable research methods. Conclusion. Almost all disorders in critically ill patients are associated with changes in the immune system. Management of patients based on their immune profile requires determination of a personalized strategy for immune modulation, treatment, and prevention of infection. Advanced monitoring of immune system functions will contribute to the personalization of medicine, and the continuous development of biological technologies will allow to improve its methods.

The objective was to determine the attitude of anesthesiologists and intensivists to the possibility of a complete transition to the use of domestic equipment for mechanical ventilation instead of imported ones.Materials and methods. An anonymous survey of members of the Association of anesthesiologists-intensivists, doctors with experience working on ventilators (code 232870 and 232890), using the Google Forms software service. The survey involved 227 specialists from different regions of the country working in hospitals with both more and less than 1000 beds.Results. At the workplaces of respondents, imported equipment predominates (91.6 %). The majority of experts (92.6 %) believe that the capabilities of domestic equipment relative to imported ones are lower, 0.4 % – higher, 7 % do not see any differences. The main complaints about modern domestic equipment: less reliability (84.1 %), fewer capabilities (71.4 %), worse interface work (60.4 %), worse service (25.6 %). 92.1 % do not consider it advisable to refuse to import devices, although 63.9 % of respondents do not work with domestically produced ventilators at all.Conclusion. Domestic anesthesiologists and intensivists are not ready to use exclusively domestically produced devices in their practical work. It is necessary to improve the interaction of the professional community with manufacturers of domestic respiratory equipment in order to disseminate the positive information about it.

Background. Cold injury is one of the most significant problems for the northern regions of the Russian Federation. Frostbite is defined as a complex of changes caused by the action of low temperatures, which lead to morphological changes in damaged tissue structures. As a result, the skin with underlying tissues and the intercellular matrix, the components of which are collagen fibers, are damaged, which eventually leads to remodeling and a protracted course of the wound process. Morphometric studies in combination with quantitative analysis of microphotographs (histological specimens) using GIS technologies make it possible to distinguish altered collagen fibers under the influence of low temperatures from relatively healthy tissues. The aim of the study. To assess the possibility of using computer analysis of microphotographs in a complex of morphometric studies of collagen fibers in local cold injury. Materials and methods. The study included 84 patients with III and IV degree frostbite of the lower extremities. Morphological study of tissues and microphotography were performed using Leica DM2500 microscope (Leica, Germany). The thickness of collagen fibers was measured based on visual measurements of characteristic areas of the microphotograph. Computer analysis of tissue microphotographs of the zone of cryoinjury was performed using the ArcINFO software (Esri, USA). Statistical processing of the study results was carried out using the SPSS Statistics software package (IBM Corp., USA). Graphs and diagrams were constructed using MS Office Excel (Microsoft Corp., USA). Results. With frostbite, severe tissue damage occurs, accompanied by the destructive processes of the extracellular matrix components. Low temperatures contribute to changes in the width and orientation of collagen fibers in the damaged area. In this regard, a change in the texture of the histological specimen image leads to achange in the numerical characteristics of the standard deviation of the curvature coefficient in the studied area of the microphotograph. Thus, in the late reactive period, the described complex of morphometric studies makes it possible to classify particular microphotograph as having pathological signs or as a sample of healthy tissue.

АКТУАЛЬНОСТЬ: Ведущее место в структуре послеоперационных осложнений занимает послеоперационная пневмония. Учитывая распространенность послеоперационной пневмонии и рост числа хирургических процедур, прогнозирование ее развития является актуальной задачей, позволяющей принять меры по снижению частоты ее возникновения, путем оптимизации периоперационного периода. Несмотря на свою ценность, существующие шкалы прогнозирования послеоперационной пневмонии не обеспечивают отечественных специалистов надежным и постоянным методом, с помощью которого можно стратифицировать риск развития послеоперационной пневмонии в нашей популяции. ЦЕЛЬ ИССЛЕДОВАНИЯ: разработка модели прогнозирования послеоперационной пневмонии на основе выявления факторов риска ее развития. МАТЕРИАЛЫ И МЕТОДЫ: Многоцентровое проспективное исследование, 6844 пациента старше 18 лет, подвергающиеся плановым оперативным вмешательствам на органах брюшной полости. Оценивали 30-дневную летальность и послеоперационную пневмонию. На первом этапе исследования проводилось сравнение между группой с пневмонией и группой без пневмонии исходных данных пациентов, а также факторов, связанных с операцией и анестезией. На втором этапе исследования проводился логистический регрессионный анализ для оценки вклада факторов в развитие послеоперационной пневмонии. На третьем этапе исследования выполнялось построение модели прогнозирования послеоперационной пневмонии по данным многомерного логистического регрессионного анализа. На заключительном этапе производилось сравнение полученной модели с моделями прогнозирования других авторов, встречающихся в мировой литературе. РЕЗУЛЬТАТЫ: Пневмония выявлена у 53 пациентов (0,77 %). Летальный исход наблюдался у 39 пациентов: у пациентов с пневмонией в 15 случаях (28,3 %), а без пневмонии — в 24 случаях (0,4 %). Ретроспективно с учетом полученной модели к группе высокого риска развития пневмонии были отнесены 933 пациента, частота развития пневмонии составляла 4,5 %. В группе низкого риска развития пневмонии — 5911 пациентов, частота развития пневмонии составляла 0,19 %. ВЫВОДЫ: Выявлены восемь независимых переменных, связанных с послеоперационной пневмонией: длительность операции, курение, полная функциональная зависимость, периоперационная анемия, требующая применения препаратов железа, интраоперационное применение вазопрессоров, III функциональный класс по классификации Американского общества анестезиологов, применение бронходилатирующих препаратов по поводу хронической обструктивной болезни легких, высокий операционный риск. Модель прогнозирования послеоперационной пневмонии имеет отличную прогностическую значимость (AUROC = 0,904).

Местная холодовая травма протекает с повреждением всех тканевых структур, в том числе и поперечно-полосатой мышечной ткани. Известно, что продукты деградации миоцитов оказывают существенное влияние на эндотелий и периферическую гемодинамику. Цель исследования – изучение в динамике уровня миоглобина, особенностей микроциркуляции и показателей биоэлектрической активности мышц у пациентов с отморожениями. Методика. В исследование включены данные 44 пациентов с отморожениями нижних конечностей III–IV степени в позднем реактивном периоде и периоде гранулирования и эпителизации. Измерения биоэлектрической активности мышц и уровня периферического миоглобина выполнялись на 5-е и 30-е сут от момента получения травмы. Для оценки состояния микроциркуляторного русла использован неинвазивный метод ЛДФ с помощью аппарата ЛАКК-02 (НПП «Лазма», Россия). Измерение уровня свободного миоглобина выполнялось также на 5-е и 30-е сут с момента получения травмы у одних и тех же пациентов с помощью мультиплексного анализа сыворотки крови набором реагентов фирмы Biomedical. Результаты. Установлено, что на 5-е сут с момента криоповреждения концентрация миоглобина в крови была выше в 35,6 раза по сравнению с группой контроля, в тоже время отмечались более низкие (в 5,0 раз) значения амплитуды М-ответа на фоне увеличения резидуальной латентности в 1,7 раза. Показатель микроциркуляции снизился в 1,6 раза. На 30-е сут уровень миоглобина был выше по сравнению с группой контроля в 7,0 раз, амплитуда М-ответа ниже в 1,8 раза, резидуальная латентность выше показателя группы контроля в 1,5 раза, значение показателя микроциркуляции – ниже в 1,3 раза. Заключение. У пациентов с отморожением происходит резкое повышение уровня миоглобина в ранние сроки криотравмы. Высокая концентрация свободного миоглобина сопровождается нарушением микроциркуляции и формирует локальную нейропатию. У пострадавших с местной холодовой травмой снижается амплитуда М-ответа и повышается резидуальная латентность. Выявленные изменения регистрируются в позднем реактивном и в периоде гранулирования и эпителизации. Local cold injury is associated with damage to all tissue structures, including striated muscles. Myocyte degradation products are known to impact significantly peripheral hemodynamics and endothelial metabolism. The aim of this work was to study the dynamics of myoglobin concentration, microcirculation, and variables of the bioelectric muscle activity in patients with frostbite. Methods. This study included 44 patients with degree III–IV frostbite of the lower extremities in the late reactive period and the period of granulation and epithelization. Bioelectric activity of muscles and concentration of peripheral myoglobin were measured on the 5th and 30th days after injury. To assess the state of microcirculation, non-invasive laser Doppler flowmetry was performed with a LAKK-02 (Lazma, Russia) apparatus. Concentration of free myoglobin was also measured on the 5th and 30th days after injury in the same patients using a multiplex analysis of blood serum with a Biomedical reagent kit. Results. On the 5th day after cryoinjury, blood concentration of myoglobin was 3460% higher compared to the control group whereas M-response amplitude was 80% lower, residual latency was 70% increased, and microcirculation index was 37.5% decreased. On the 30th day, myoglobin concentration was 600% higher than in the control group, M-response amplitude was 44.4% lower, residual latency was 50% higher, and microcirculation index was 23.1% lower than in the control group. Conclusions. In patients with frostbite, the myoglobin concentration sharply increases at early stages of cryoinjury. A high concentration of free myoglobin is associated with microcirculatory disorders to induce local neuropathy. In patients with local cold injury, the M-response altitude decreases and the residual latency increases. These changes are observed in the late reactive period and the period of granulation and epithelization.

— Long COVID-19 is a chronic disease that continues to be studied. Data on epidemiology and the main symptoms typical for long COVID-19 are presented. Issues related to the pathogenesis of the disease are discussed. At the same time, special attention is paid to the inflammation process (including of the vascular wall endothelium), the state of the immune system (cytokine storm), the hemostasis system (the mechanism for the development of microangiopathy and thrombosis), and oxidative stress. During the analysis, a special place is given to central nervous system disorders (including organic brain damage) and disorders of cognitive functions. In addition, currently known complications from the cardiovascular system and respiratory organs are described. The treatment and rehabilitation of patients with long COVID-19 is not only a medical, but also a significant social problem.

Long-COVID-19 is a long disease, its duration can be more than four weeks. The analysis was made of epidemiology and of symptoms of Long-COVID-19. The pathogenesis of disease is discased, particularly the inflammation processes, immune system state (cytokine storm), hemostasis system (mechanism of the thrombosis development) and oxidative stress. The disturbances of the central nervous system, including the brain organic diseases and the cognitive functions disturbances, plays a great role by the Long-COVID-19. Besides the damages of heart-vessel system and of breath organs are described. The treatment and rehabilitation of the patients with Long-COVID-19 is not only medical, but also great social problem.

Цель исследования. Определить частоту встречаемости полиморфизма гена TLR9 (T1237C) и установить его вклад в развитие органной недостаточности у больных тяжёлой пневмонией на фоне гриппа A/H1N1. Материалы и методы. Обследованы 100 больных пневмонией. Из них 45 пациентов с тяжёлой пневмонией, 55 – с нетяжёлой пневмонией. Возраст пациентов составил 53 [37; 65] года. Мужчины составляли 48%, а женщины – 52%. Больные тяжёлой пневмонией были поделены на 2 группы: 1 группа – с оценкой по шкале SOFA < 2 баллов, 2 группа – SOFA ≥ 2 баллов. Определение SNP генов осуществлялось методом ПЦР с использованием стандартных наборов НПФ «Литех» (Москва). Амплификацию фрагментов гена TLR3 проводили в термоциклере (модель «Бис»-М111, ООО «Бис-Н», Новосибирск). Анализу подвергалась геномная ДНК, выделенная из лейкоцитов цельной крови с помощью реагента «ДНК экспресс-кровь», затем проводилась реакция амплификации. Детекцию продукта амплификации проводили в 3% агарозном геле. Сравнение частот генотипов в группах проводили с помощью критерия χ2 с поправкой Йейтса на непрерывность с использованием таблицы сопряженности; если ожидаемых явлений в одной из ячеек было меньше 5, применяли точный критерий Фишера. Для оценки ассоциации генотипов с тяжестью заболевания производили расчет отношения шансов (ОШ; Odds Ratio), c 95%-ми доверительными интервалами (ДИ) по генетическим моделям (кодоминантной, доминантной, рецессивной, сверхдоминантной). Результаты. Установлено, что носительство аллеля –1237C чаще регистрируется у больных тяжёлой пневмонией. При анализе распределения частот генотипов гена TLR9 (T1237C) выявлена ассоциация с пневмонией, согласно кодоминантной (ОШ (95% ДИ) 0,422 (0,219 – 0,815) (p = 0,026)), доминантной (ОШ (95% ДИ) 0,436 (0,237 – 0,802) (p = 0,011)) и сверхдоминантной (ОШ (95% ДИ) 0,450 (0,236 – 0,861) (p = 0,023)) генетическим моделям. Заключение. Полученные данные позволяют рассматривать TLR9 как потенциальную точку фармакологического ингибирования, поскольку через пути TLR, включая TLR9, экспрессируются провоспалительные факторы, выступающие потенциальными «виновниками» так называемого цитокинового шторма и тромботических осложнений, лежащих в основе полиорганной недостаточности при тяжёлой пневмонии. Aims of the study. To determine the frequency of occurrence of the TLR9 (T1237C) gene polymorphism and establish its contribution to the development of organ failure in patients with severe pneumonia due to influenza A/H1N1. Materials and methods. 100 patients with pneumonia were examined. Of these, 45 patients with severe pneumonia, 55 with non-severe pneumonia. The age of the patients was 53 [37; 65] year. Men made up 48% and women 52%. Patients with severe pneumonia were divided into 2 groups: group 1 – with a SOFA score <2 points, group 2 – SOFA ≥2 points. Determination of SNP genes was carried out by PCR using standard kits from NPF Litech (Moscow). Amplification of TLR3 gene fragments was carried out in a thermal cycler (model “Bis”-M111, LLC “Bis-N”, Novosibirsk). Genomic DNA isolated from whole blood leukocytes using the “DNA Express Blood” reagent was analyzed, then an amplification reaction was carried out. Detection of the amplification product was carried out in a 3% agarose gel. Comparison of genotype frequencies in groups was carried out using the χ2 test with Yates’ correction for continuity using a contingency table; if the expected events in one of the cells were less than 5, Fisher’s exact test was used. To assess the association of genotypes with disease severity, odds ratios (OR; Odds Ratio) were calculated with 95% confidence intervals (CI) for genetic models (codominant, dominant, recessive, overdominant). Results. It has been established that carriage of the –1237C allele is more often recorded in patients with severe pneumonia. When analyzing the frequency distribution of TLR9 gene genotypes (T1237C), an association with pneumonia was revealed, according to codominant (OR (95% CI) 0.422 (0.219 – 0.815) (p=0.026)), dominant (OR (95% CI) 0.436 (0.237 – 0.802) (p=0.011)) and overdominant (OR (95% CI) 0.450 (0.236 – 0.861) (p=0.023)) genetic models. Conclusion. The data obtained allow us to consider TLR9 as a potential point of pharmacological inhibition, since proinflammatory factors are expressed through TLR pathways, including TLR9, which are potential “culprits” of the so-called cytokine storm and thrombotic complications underlying multiple organ failure in severe pneumonia.

Введение. Холодовая альтерация мышечной ткани сопровождается поступлением в кровоток цитотоксичных продуктов распада миоцитов. Производные миоцитолиза не являются специфическими маркерами миоальтерации; единственным подтверждением деструкции мышц считается свободный миоглобин. Доказана роль миоглобина в патогенезе любого повреждения и в последствиях миоглобин-ассоциированной цитодеструкции. Однако работ, посвященных участию свободного миоглобина в патогенезе криотравмы, нет. Цель исследования: изучить уровень миоглобина и показатели биоэлектрической активности мышц у пациентов с местной холодовой травмой. Материалы и методы. Проведено одноцентровое проспективное открытое нерандомизированное контролируемое интервенционное исследование, в которое были включены 88 пациентов — 50 мужчин и 38 женщин в возрасте от 30 до 40 лет с отморожениями нижних конечностей III–IV степени. В зависимости от объема пораженных холодом тканей пациенты были распределены на 3 группы: группа I с поражением на уровне фаланг пальцев (n = 20), группа II c поражением до уровня плюсны (n = 24), группа III с поражением стопы и нижней трети голени (n = 44). Пострадавшие с самыми тяжелыми поражениями (группа III) были разделены на 2 подгруппы: подгруппа IV — 22 человека в позднем реактивном периоде (5-е сутки с момента травмы), подгруппа V — 22 человека в периоде гранулирования и эпителизации (30-е сутки). Контрольную группу составили 28 относительно здоровых лиц в возрасте от 27 до 40 лет. У всех обследованных определяли уровень периферического миоглобина, оценивали биоэлектрическую активность мышц неинвазивной электронейромиографией и состояние микроциркуляторного русла неинвазивным методом лазерной доплеровской флоуметрии. Результаты. У пациентов в подгруппе IV (5-е сутки с момента криоповреждения) концентрация миоглобина в крови была выше в 35,6 раз, значение амплитуды М-ответа меньше в 5 раз, резидуальная латентность выше в 1,7 раз, показатель микроциркуляции меньше в 1,6 раз по сравнению с контрольной группой. У пациентов в подгруппе V (30-е сутки с момента криоповреждения) уровень миоглобина крови был выше в 7,0 раз, амплитуда М-ответа ниже в 1,8 раза, резидуальная латентность выше в 1,5 раза, показатель микроциркуляции ниже в 1,3 раза по сравнению с контрольной группой. У пациентов в подгруппе V по сравнению с подгруппой IV установлено снижение уровня миоглобина в 3,9 раз и резидуальной латентности в 1,7 раза, а амплитуда М-ответа и показатель микроциркуляции были выше в 3,8 раза и в 1,8 раза соответственно. Анализ зависимости снижения показателей биоэлектрической активности мышц и повышения уровня периферического миоглобина от объема пораженных холодом тканей в сравнении с контрольной группой установил, что у пациентов группы I амплитуда М-ответа снижена в 3 раза и уровень миоглобина повышен в 3 раза; у пациентов группы II амплитуда М-ответа снижена в 4,8 раз и значения миоглобина повышены в 6 раз; у пациентов группы III амплитуда М-ответа снижена в 7 раз, содержание миоглобина повышено в 38 раз. Резидуальная латентность повышена в сравнении с контрольной группой у пациентов группы I в 1,4 раза, у пациентов группы II — в 1,7 раза, у пациентов группы III — в 2,4 раза. Заключение. У пациентов с глубокими отморожениями происходит резкое повышение уровня миоглобина в ранние сроки криотравмы, при этом миоглобинемия сохраняется в отдаленные сроки травмы. Высокая концентрация свободного миоглобина сопровождается нарушениями микроциркуляции и формированием локальной нейропатии. У пациентов с отморожениями снижается амплитуда М-ответа и повышается резидуальная латентность. Introduction. Cold alteration of muscle tissue is associated with the entry of cytotoxic degradation products of myocytes into the bloodstream. Myocytolysis derivatives are not specific markers of myoalteration, while free myoglobin is considered the only confirmation of muscle destruction. The role of myoglobin in the pathogenesis of any injury and in the effects of myoglobin-induced cytodestruction have been demonstrated. However, there are no works focused on the involvement of free myoglobin in the pathogenesis of cryotrauma. Aim: to study the level of myoglobin and indicators of bioelectrical activity in the muscles of patients with local cold injury. Materials and Methods. The single-center prospective open-label non-randomized controlled trial included 88 patients (50 men and 38 women, aged 30–40 years) with III–IV degree frostbite of the lower extremities. Patients were divided into three groups based on the extent of cold-induced tissue damage: those with lesions at the level of the phalanges of the fingers (n = 20), those with lesions up to the level of the metatarsus (n = 24), and those with lesions of the foot and lower third of the leg (n = 44). Patients with the most severe injuries were identified and divided into 2 subgroups: subgroup IV — 22 individuals in the late reactive period (Day 5 after injury), subgroup V — 22 individuals in the granulation and epithelization period (Day 30). The control group consisted of 28 relatively healthy individuals aged from 27 to 40 years. In all examined perrsons we measured the level of peripheral myoglobin, evaluated the bioelectric activity of the muscles via non-invasive electroneuromyography, and assessed the state of the microcirculatory bed via non-invasive laser doppler flowmetry. Results. On day 5 following the cryoinjury, the myoglobin blood level of subgroup IV patients was 35.6 times higher than that of the control group. At the same time, these patients demonstrated a 5-fold decrease in the M-response amplitude, a 1.7-fold increase in the residual latency, and a 1.6-fold decrease in the microcirculation index compared with the control group. On Day 30 following cryoinjury, patients in subgroup V exhibited a myoglobin blood level 7.0 times greater than that of the control group, the M-response amplitude 1.8 times lower, a residual latency 1.5 times higher, and a microcirculation indicator value 1.3 times lower. On Day 30 following cryoinjury, patients in subgroup V exhibited a 3.9-fold decrease in myoglobin levels as well as a 1.7-fold decrease in residual latency when compared to group IV. The amplitude of the M-response and the microcirculation index exhibited an increase on Day 30 relative to Day 5 following cryoinjury (by 3.8-fold and 1.8-fold, respectively). Depending on the volume of tissues affected by cold, there was a decrease in the bioelectrical activity of muscles and an increase in the level of peripheral myoglobin in comparison to the control group. In group I patients, the amplitude of the M-response decreased by 3 times while the level of myoglobin increased by 3 times. In group II patients, the amplitude of the M-response decreased by 4 times. The amplitude of the M-response was decreased by 7 times, while myoglobin values increased by 6 times in all groups. In addition, group III exhibited an increase of 38 times in myoglobin levels. The residual latency was also increased in comparison to the control group, with patients in group I exhibiting an increase of 1.4 times, 1.7 times for patients in group II, and 2.4 times for patients in group III. Conclusion. In patients with deep frostbite, there is a rapid elevation in myoglobin levels during the early stages of cryoinjury, with myoglobinemia persisting in the long term after the injury. A high concentration of free myoglobin is linked with microcirculatory disorders and the development of localized neuropathy. Additionally, patients with frostbite experience a decrease in the amplitude of the M-response and an increase in residual latency.

При развитии тяжелых состояний у больных COVID-19 развивается выраженная гиперкоагуляция, что приводит к возникновению тромбоэмболических осложнений и полиорганной недостаточности, являющихся основной причиной смерти. При этом, наряду с классическим путем, возбудитель COVID-19 ‑ коронавирус SARS-CoV-2 приводит к развитию так называемых альтернативных путей механизмов свёртывания крови и фибринолиза. Альтернативные пути развития и регуляции системы гемостаза и тромбообразования связаны с влиянием шиповидного белка S (англ. spike protein, PROS1) и папаиноподобной протеазы (англ. papain-like protease, PLpro) коронавируса SARS-CoV-2, с действием фрагментов комплемента и мембраноатакующего комплекса, активацией ренин-ангиотензин-альдостероновой и калликреин-кининовой систем, гиперстимуляцией иммунного ответа, приводящего к цитокиновому шторму, с влиянием маннозосвязывающих лектин-ассоциированных сериновых протеаз (англ. mannose-binding lectin-associated serine proteases, MASPs) активированных нейтрофилов с образованием внеклеточных ловушек нейтрофилов (англ. neutrophil extracellular traps, NЕTs), микровезикул различного происхождения, с влиянием повышенной концентрации триптаз, главным образом трипсина и других, пока еще мало изученных факторов. Для успешной терапии тяжелобольных COVID-19 и предотвращения тромбообразования требуется ликвидация цитокинового шторма, что в значительной степени может быть достигнуто применением ингибиторов цитокинов или иммунокорректоров на основе пептидов тимуса (тималин), а также матричных антител к коронавирусу SARS-CoV-2. В связи с «протеолитическим взрывом» у тяжелобольных COVID-19 целесообразно использовать α1-антитрипсин или другие антипротеазные препараты. Высказывается предположение, что альтернативные механизмы системы гемостаза проявляются не только при COVID-19, но и при других заболеваниях и даже в физиологических условиях, но при этом их влияние на свертываемость крови и фибринолиз невелико. Severe conditions in patients with COVID-19 are associated with severe hypercoagulability, which leads to thromboembolic complications and multiple organ failure as the main cause of death. At the same time, along with the classical pathway, the causative agent of COVID-19, SARS-CoV-2 coronavirus, leads to the development of so-called alternative pathways for the mechanisms of blood coagulation and fibrinolysis. Alternative pathways for the development and regulation of hemostasis and thrombogenesis are associated with the impact of the spike protein S (PROS1) and papain-like protease (PLpro) of SARS-CoV-2 coronavirus, the action of complement fragments and the membrane attack complex, and the activation of renin-angiotensin-aldosterone and kallikrein-kinin systems, hyperstimulation of the immune response leading to a cytokine storm, the influence of mannose-binding lectin-associated serine proteases (MASPs), activated neutrophils with the formation of neutrophil extracellular traps (NЕTs), microvesicles of various origins, the influence of an increased concentration of tryptases, mainly trypsin and others, so far little studied factors. Successful therapy of serious COVID-19-patients and prevention of thrombosis requires the elimination of the cytokine storm, which can be largely achieved by using cytokine inhibitors or thymus peptides (thymalin) as immunocorrectors, as well as anti-SARS-CoV-2 matrix antibodies. Due to the “proteolytic explosion” alpha-1-antitrypsin or other antiprotease drugs should be used in serious COVID-19 patients. Alternative hemostatic mechanisms are suggested to develop not only in COVID-19, but also in other diseases and even in normal conditions, but their effect on blood coagulation and fibrinolysis are small.

The review highlights the mechanism of development of hypercoagulation and thrombosis in severe forms of COVID-19. The introduction of the SARS-CoV-2 virus into the host organism is carried out by the interaction of the spike protein S with the angiotensin-converting enzyme ACE-2, which is located in type 2 alveocytes, vascular endothelium, kidneys, liver, and other organs. In the event of a serious condition in patients with COVID-19, both nonspecific and adaptive immunity are activated. Stimulation of the complement system with the appearance of C3a, C3b, and C5a fragments and the membrane attack complex (MAC) creates conditions for the development of hypercoagulability. The involvement of the renin-angiotensin-aldosterone system in this process and the appearance of angiotensin 2 (Ang-2) further increase the intensity of hypercoagulability. When the SARS-CoV-2 virus enters cells, the protective reaction of the adaptive immune system can turn into a pathological one (a cytokine storm develops), characterized by a high level of pro-inflammatory cytokines (IL-1α, IL-6, IL-8, TNF-α, IL-17, etc.) and chemokines (CCL-2, CCL-11, etc.), which ultimately leads to the development of thromboangiopathy or otherwise immunothrombosis in seriously ill patients with COVID-19. Patients with more severe lesions may develop a condition similar to DIC. At the same time, patients with COVID-19 have mild thrombocytopenia and elevated levels of fibrinogen, D dimer, and fibrinogen degradation products (FDP), which indicates intense thrombus formation, as well as short PT and APTT, due to a largely increased level of FVIII. In COVID-19, along with the classical one, an alternative pathway (bypassing thrombin) of regulation of the hemostasis system and thrombus formation appears, mainly associated with the influence of the spike protein S (PS, PROS1) of the SARS-CoV-2 virus and papain-like protease (PROS1). Protein S directly affects the conversion of fibrinogen to fibrin, as well as the activation of individual plasma coagulation factors. The alternative pathway of blood coagulation is also due to the activation of the complement system via the lectin pathway with the inclusion of metalloproteinases MASP-1, -2, and -3. In addition, the S protein activates tPA, which may be accompanied by hyperfibrinolysis. In seriously ill patients with COVID-19, platelets play an important role in the occurrence of thromboembolic complications. During the release reaction, platelets are released from the cytoplasm into the blood α-granules and dense granules containing inflammatory cytokines and chemokines, which enhances the cytokine storm and, consequently, thrombus formation. By acting on the spike protein S, platelets enhance an alternative way of regulating the hemostasis system and thrombus formation.

Background . A significant proportion of patients infected with the SARS-CoV-2 virus had a severe course of the disease required hospitalization and intensive care The objective was to analyze the defects allowed during intensive care of patients with SARS-CoV-2, and to assess the causes of their occurrence. Materials and methods . An analytical study was made on the basis of expert opinions on 60 case histories of deceased patients in the intensive care unit with the main diagnosis: “COVID-19. Community-acquired bilateral polysegmental viral pneumonia ARDS”. To identify the reasons that led to defects in the diagnosis and treatment of patients with NCI COVID-19 in intensive care units, an anonymous survey of 92 anesthesiologists-resuscitators who worked in the “red zone” during the COVID-19 pandemic was conducted. Results . The defects identified by experts can be divided into two main groups: diagnostic defects and treatment defects. ARDS in 25%, PE in 8% of cases were not diagnosed. There was no ECG control and cardiac monitoring in 22%, lung CT in 6.7%, echocardiography in 10% of cases. Consultations of specialized specialists were not held in 11.7% of patients. There were defects in the correction of EBV and ABS in 30%, unreasonable prescribing of drugs in 58%, defects in vasopressor support in 10%, defects associated with mechanical ventilation in 40% of cases. The survey of physicians showed that the defects were based on insufficient knowledge of the governing documents and the limited capabilities of medical organizations to implement the necessary research. Conclusion . The obtained results made it possible to demonstrate the limitations and subjectivity of the existing assessment of the quality of medical care, which sometimes does not take into account the existing conditions for treating patients and the material and technical capabilities of a medical organization.

Оценка эффективности иммунокорригирующей терапии у больных с тяжелым течением COVID-19 является актуальнейшей задачей, так как позволяет прогнозировать характер течения и исход заболевания. Цель исследования -- прогнозирование с помощью ROC-анализа изменений в составе тромбоцитов, лейкоцитов и их популяций, а также их взаимосвязи между собой при использовании иммунокорректоров тоцилизумаба и тималина. на 6-е сут после начала их применения. Методика. Проведено исследование общего анализа крови и соотношения отдельных форменных элементов у 159 пациентов с тяжелым течением COVID-19. Сформировано 3 группы: 1-я группа – контроль, 44 человека, возраст 62±13,4 г. (базовая схема лечения), 2-я – 81 пациент, возраст 58±10,9 г. (базовая схема лечения + тоцилизумаб 4-8 мг/кг однократно внутривенно), и 3-я группа – 34 больных, возраст 61,3±10,1 г. (базовая схема лечения + тималин 10 мг, 1 раз в сут в течение 5 сут внутримышечно). Исследования показателей крови проведены на 1-е 6-е сут терапии в контроле, после однократного введения тоцилизумаба и на следующий день после отмены тималина. При этом общепринятая терапия осуществлялась до конца пребывания больного в стационаре. Результаты. В контрольной группе все исследуемые форменные элементы крови, а также их соотношение располагались в зонах шкалы, соответствующих неудовлетворительной или слабой оценке, что не находило отражения на результатах терапии. При использовании тоцилизумаба на 6-е сут отмечалось значительное увеличение числа эозинофилов и тромбоцитов, что по шкале оценки AUC следует расценивать как «хороший» эффект. Кроме того, в этой группе у пациентов выявлено увеличение показателей, характеризующих соотношение «тромбоциты/лейкоциты» в 1,6 раза и «тромбоциты/лимфоциты» в 1,4 раза, что может расцениваться как предиктор неблагоприятного исхода COVID-19. Под действием тималина на 6-е сут терапии у пациентов в 2 раза повышалось количество лимфоцитов, тогда как соотношение тромбоциты/лимфоциты снижалось в 1,4 раза, а нейтрофилы/лимфоциты – в 2 раза. При этом в 1,3 раза повышалось количество лейкоцитов, в 2 раза – число моноцитов и в 1,5 раза – количество тромбоцитов. Полученные данные указывают на комплексное иммунопротекторное действие тималина у пациентов с тяжелым течением COVID-19. Заключение. С помощью ROC-анализа у больных с тяжелым течением COVID-19 выявлены изменения (в 1-е на 6-е сут лечения) в содержании и соотношении отдельных форменных элементов крови в контроле (лечение по протоколу) и на фоне стандартной терапии иммунокорректорами (тоцилизумаб, тималин). Визуализированные графики позволяют эффективно оценить структуру и значимость сдвигов при различных терапевтических подходах. Evaluating the effectiveness of immunocorrective therapy in patients with severe COVID-19 is an urgent task, as it predicts the future course and outcome of the disease. Aim: To use the ROC analysis for prediction of changes in the composition of platelets, leukocytes and their populations as well as their interrelations on the 6th day after the start of using the immunocorrectors, tocilizumab and thymalin. Methods. Blood cell count and their ratios were analyzed for 159 patients with severe COVID-19. The patients were divided into three groups: 1, control, basic treatment regimen, 44 patients, age 62 ± 13.4 yrs; 2, basic treatment regimen plus tocilizumab, 4-8 mg/kg, iv, once, 81 patients, age 58±10.9 yrs; 3, basic treatment regimen plus thymalin, 10 mg, im, once per day for 5 days, 34 patients, age 61.3±10.1 yrs. Blood components were analyzed on the 1st and 6th days of therapy in the control group, after a single injection of tocilizumab, and on the day following withdrawal of thymalin. Conventional therapy was continued until the patients were discharged from the hospital. Results. In the control group, all the blood count values, as well as their ratios, were in the scale zone corresponding to unsatisfactory or weak assessment. There was no consistency with the results of therapy. On the 6th day of tocilizumab treatment, there was a significant increase in the number of eosinophils and platelets, which should be regarded as a “good effect” according to the AUC scale. In this group, the ratio of platelets/leukocytes increased by 1.6 times and platelets/lymphocytes by 1.4 times. This can be regarded as a predictor of an unfavorable outcome of COVID-19. Under the influence of thymalin on the 6th day of therapy, the number of lymphocytes increased by 2 times, while the platelet/lymphocyte ratio decreased by 28.6% and neutrophils/ lymphocytes by 50%. Furthermore, the number of leukocytes increased 1.3 times, the number of monocytes increased 2 times, and the number of platelets increased 1.5 times. These data indicate a complex immunoprotective effect of thymalin in patients with severe COVID-19. Conclusion. Using ROC analysis in patients with severe COVID-19, changes from the 1st to the 6th day of treatment were found in the count and ratios of blood cells in control (treatment as per protocol) and in patients treated with the immunocorrectors, tocilizumab and thymalin. Presented graphs enable effective assessment of the structure and significance of changes in various therapeutic approaches.

INTRODUCTION: Taking into account the prevalence of postoperative pneumonia and the increase in the number of surgical procedures, forecasting its development is an urgent task that allows taking measures to reduce the frequency of its occurrence by optimizing the perioperative period. Despite their value, the existing scales for predicting postoperative pneumonia do not provide domestic specialists with a reliable and consistent method by which to stratify the risk of developing postoperative pneumonia in our population. OBJECTIVE: To develop a model for predicting postoperative pneumonia based on the identification of risk factors for its development. MATERIALS AND METHODS: A multicenter prospective study of 6844 patients over 18 years of age undergoing elective abdominal surgery. 30-day mortality and postoperative pneumonia were assessed. In the first phase of the study, a comparison was made between the pneumonia and non-pneumonia group of baseline patient data, as well as factors associated with surgery and anesthesia. At the second stage of the study, a logistic regression analysis was performed to assess the contribution of factors to the development of postoperative pneumonia. At the third stage of the study, a model for predicting postoperative pneumonia was built according to the data of multivariate logistic regression analysis. At the final stage, the obtained model was compared with the forecasting models of other authors found in the world literature. RESULTS: Pneumonia was detected in 53 patients (0.77 %). A lethal outcome was observed in 39 patients: in patients with pneumonia in 15 cases (28.3 %), and without pneumonia in 24 cases (0.4 %). Retrospectively, taking into account the obtained model, 933 patients were assigned to the high-risk group for developing pneumonia, the incidence of pneumonia was 4.5 %. In the low-risk group for developing pneumonia — 5911 patients, the incidence of pneumonia was 0.19 %. CONCLUSIONS: Eight independent variables associated with postoperative pneumonia were identified: duration of surgery, smoking, complete functional dependence, perioperative anemia requiring iron supplementation, intraoperative use of vasopressors, American Society of Anesthesiologists classification 3 functional class, use of bronchodilators for chronic obstructive pulmonary disease, and high operative risk. The postoperative pneumonia prediction model has excellent predictive value (AUROC = 0.904).