The aim of the study. To study the effect of ley-enkephalin synthetic analogue on the dynamics of inflammatory response markers and organ dysfunction in patients with severe combined trauma.

Materials and methods. A prospective clinical study with historical control from two clinical centers — N. I. Pirogov State Clinical Hospital No. 1 and N.V. Sklifosovsky Clinical and Research Institute for Emergency Medicine — included men and women with severe combined trauma and the ISS scores values of 18–44, aged 18 to 70 years. Diagnostic and therapeutic approaches in all patients followed current international, national& local protocols and 2022 clinical recommendations of the Russian Society of Surgeons «Combined and multiple trauma in combination with shock (Polytrauma)». In the study group, treatment was supplemented with extended (72 hours from the admission) infusion of the test drug through a syringe dispenser following the study protocol. Effects of the test drug prolonged infusion were evaluated for the following laboratory parameters: levels of cortisol, procalcitonin, interleukin 6, NTproBNP and leukocyte count. Laboratory tests were performed at 4 time points: prior to test drug infusion, 24 hours and 72 hours after initiation of infusion, and on Day 7. The study evaluated patient’s dynamics using APACHE II, SOFA and SAPS II scales and percentage of patients developing organ dysfunction (renal, respiratory, cardiovascular), rates of sepsis complications and mortality.

Results. Patients who received the test drug had significantly lower concentrations of systemic inflammatory response markers, i. e. PCT (P=0.001) and IL-6 (P=0.010) after 24 hours of follow-up vs the control group patients. The incidence of ARDS has also decreased in the study group (P=0.011 vs control). Acute kidney injury (AKI) rate was insignificantly higher in the control group (P=0.349). The duration of hospital stay in the control group was 35 (17; 51) days vs 18 (14; 30) days in the study group (P=0.140)

Conclusion. The use of ley-enkephalin synthetic analogue inhibits production of such key systemic inflammatory response markers as PCT and IL-6, and reduces PCT concentrations within 24 hours in patients with severe combined trauma. ARDS developed less frequently in the study group, but there was no significant difference in the incidence of AKI, AHF and infectious complications between the groups.

The mortality rate among patients with acute suppurative lung diseases (ASLD) in the ICU reaches 30%. Early, pathogenetically relevant biomarkers are needed to ensure personification and better efficacy of ASLD treatment. Numeric variations in the counts of immune system cells in patient’s blood can be viewed as such candidate biomarkers.

The aim of the study. Identification of potential markers predicting ASLD outcome after community-acquired pneumonia and COVID-19.

Materials and methods. The study included 216 in-hospital patients aged 18-87 with ASLD after community-acquired pneumonia with (N=81) and without (N=135) COVID-19 history.

Results. Patients survival after COVID-19 was linked to lymphocyte count on Day 1 of hospital stay (hazard ratio, HR=5.9 95%CI 0.9–37.4; P=0.0188, log-rank test). In patients who had not have COVID-19, a difference in survival was associated with lymphocyte (HR=2.9 95%CI 1.0–8.4; P=0.0184, log-rank test; N=135), and monocyte counts (HR=2.7 95% CI 0.8–9.5; P=0.0196, log-rank test) on Day 1 of hospital stay. Patients’ survival after COVID-19 infection depended on SII (systemic immune-inflammation index. HR=9.3 95%CI 1.7–49.8; P=0.0124, log-rank test; N=81, SIRI (systemic inflammatory response index, HR=7.2 95%CI 1.4–36.6; P=0.0339, log-rank test; N=81) and NLR (neutrophil-to-lymphocyte ratio, HR=9.6 95%CI 1.8–52.0; P=0.0108; log-rank test; N=81) values on Day 1 of hospital stay. In patients who did not have COVID-19 SII values had no influence on survival.

Conclusion. The lymphocyte count makes it possible to predict outcomes of pleural empyema, regardless of patient’s history of COVID-19, i. e. a decrease in the lymphocyte count below 1.2×10⁹ in 1 L is associated with fatal outcome. Monocyte count carries prognostic information for cases of pleural empyema without previous COVID-19 infection. As for the relative indicators, SIRI, SII and NLR values measured on Day 1 in the hospital were predictors of ASLD outcome only in patients after COVID-19 infection, i. e., higher values were associated with increased risk of death, with NLR index being the most informative. Overall severity of illness above 10 scores by CIRS was associated with an unfavorable ASLD outcome, regardless of patient’s history of COVID-19.

New subgroups of patients with severe community-acquired pneumonia (SCAP) are hardly predicted by the use of clinical covariates; clusterization may significantly improve diagnostic approaches and facilitate the adaptation of specific treatment modalities to patient’s individual characteristics.

The aim of the study. To identify linking the sepsis phenotype in patients with SCAP and preferable treatment option to forecasting the outcome and improve treatment results.

Materials and methods. Case histories of 664 of intensive care unit (ICU) patients with sepsis (2016–2023) from I. I. Mechnikov Northwestern State Medical University were analyzed. The study included 568 (85.5%) patients with viral SCAP (SCAPv group) and 96 (14.5%) patients with bacterial SCAP (SCAPb group). Sepsis phenotypes were identified using algorithm proposed by Seymour C.W. et al. In SCAP cases associated with COVID-19 infection (n=293, 51.6%) patients received genetically engineered biological therapy (GIBT). The study compared two cohorts of patients: those who received GIBT and did not receive GIBT. Data were statistically processed using the Statistica 10.0 and SPSS software packages.

Results. Analysis revealed 4 sepsis phenotypes: α- (N=323, 48.6%); β- (N=128, 19.3%); γ- (N=87, 13.1%); δ - (N=126, 19%). The majority of SCAPv group patients — 295 (51.9%) — had α-phenotype of sepsis, while δ -phenotype prevailed in the SCAPb group — 53 (55.2%). The proportion of patients receiving GIBT and exhibiting α- sepsis phenotype dominated over other sepsis phenotypes: 61.8% of patientspossesed α- phenotype, whereas β-, γ- and δ -phenotypes were determined in 16% , 12.6%, and 9.6% of GIBT patients, respectivelty (P<0.05). The best effect of using monoclonal antibodies to interleukin-6 receptors as a GIBT was obtained in patients with the α-phenotype sepsis and COVID-19-associated SCAP: 87.5% favorable outcomes, P=0.0419. Rate of bacterial sepsis was significantly lower in patients with α- and δ -phenotypes of sepsis receiving GIBT vs those who did not receive this therapy: 12.71% vs 23.2% of patients with α-phenotype, P=0.0131; 25.0% vs 70.41% of patients with δ -phenotype, P=0.0254, respectively.

Conclusion. Differences in sepsis phenotype between patients with viral or bacterial SCAP may stratify patients for different therapeutic management and more accurately predict potential complications and unfavorable outcome.

Diabetic ketoacidosis (DKA) is the main cause of death and disability in children with type I diabetes mellitus (T1DM). Children’s mortality from T1DM reaches 1% in developed countries and 13% in developing countries. The main cause of death in DKA is cerebral edema, clinical manifestations of which develop in 0.5–0.9% of children with DKA, while mortality riches 24%.

Objective. Developing recommendations to prevent life-threatening complications of children with DKA using analysis of literature data and consolidated opinion of experts on the issues of intensive care in children with T1DM.

Materials and methods. We analyzed and discussed studies in diagnosis and treatment of DKA in children with type 1 diabetes and 1200 literature sources since January 1970, published in Russian peer-reviewed scientific journals and international publications presented in the online repository Medline (Pubmed). The search for publications was carried out using the keywords: «children», «DKA», «DM1», «dehydration», «cerebral edema».

Results. We considered issues of epidemiology, pathogenesis, clinical manifestations, diagnosis, intensive care for DKA, as well as clinical and diagnosis, treatment, prevention of cerebral edema issues in children. Limitations of the study were the small number of modern studies with a high level of evidence (randomized controlled trials, meta-analyses) over the past 5 years on DKA in children.

Conclusion. Taking into account the national and international experience, joint recommendations on a consensus format were developed and formulated for the diagnosis of DKA, its leading complications and treatment recommendations for children with T1DM and DKA. Timely and accurate diagnosis of DKA, intensive therapy options based on proven therapeutic efficacy, laboratory and clinical monitoring are warranted to interrupt the DKA pathogenesis, prevent the development of life-threatening conditions, and improve treatment outcomes for children with DKA.

The majority of asphyxial circulatory arrest (CA) models have a number of disadvantages, such as the lack of uniform criteria for fixing CA and recovery of spontaneous circulation, short duration of CA episode and limited volume of post-resuscitation intensive care, poor similarity with resuscitation measures in current clinical anesthesiology/intensive care settings.

The aim of the study: to improve the experimental model of asphyxicial CA by standardizing experimental procedures and using a complex of resuscitation measures replicating current CA management in clinical anesthesiology-intensive care.

Materials and methods. The experiments were conducted on 34 male Wistar rats, distributed into 2 groups: Group I included animals subjected to sham procedure (SP, N=12) and Group II – animals subjected to asphyxial circulatory arrest (CA, N=22) and subsequent resuscitation. Asphyxia in anesthetized rats was induced by rocuronium bromide injection, followed by recording of electrocardiogram (ECG), parameters of invasive blood pressure (BP) measurement and laser Doppler fluxmetry (LDF) to assess skin perfusion. CA episode was maintained for 2 min, followed by a series of resuscitation measures and intensive therapy for 2 h. Circulatory parameters (ECG, BP, LDF), gas composition and arterial blood acid-base state (ABS) dynamics were evaluated.

Results. Monitored parameters were comparable in both groups at baseline after stabilization period. After exclusion criteria were applied 11 animals from SP group and 18 — from CA were included in the analysis. Tachycardia (heart rate, beats/min–1, SP vs CA) was documented in the CA group: 218 [205; 236] vs 286 [272; 305], P⩽0.0001), as well as recovery of skin perfusion to subnormal parameters in the first minutes after successful resuscitation. At minute 10 in the post-resuscitation period worsening of skin perfusion (M, perfusion units, SP vs CA): 14.7 [12.1; 16.5] vs 10.1 [7.0; 12.5], P=0.0014), and decompensated mixed acidosis (pH, SP vs CA): 7.42 [7.40; 7.43] vs 7.20 [7.13; 7.23], P⩽0.0001) were documented in the CA group, however BP values were comparable (BP, mmHg, SP vs CA): 60 [58; 72] vs 67 [62; 82], P=0.482). At minute 120 post-resuscitation and at the end of intensive care period, both groups demonstrated similar values of the monitored parameters. Three out of 18 animals in the CA group died after resuscitation.

Conclusion. Electromechanical dissociation underlies CA in rats subjected to asphyxia. The use of LDF to assess peripheral blood flow makes it possible to standardize the severity of ischemic reperfusion injuries and improve reproducibility of the model. Series of resuscitation measures in experimental setting is justified from a bioethical point of view, and makes it possible to improve repeatability of preclinical research results in clinical practice.

The aim of the study was to compare the effect of sevoflurane and chloral hydrate on the neurological status and volume of brain damage after trauma and ischemia in experimental models of traumatic brain injury (TBI) and focal ischemic stroke (IS) induced by photothrombosis (PT).

Materials and methods. The experiments were performed on mongrel Wistar rats weighing 250–300 g (N=43). There were 4 groups: the Ischemia + Sevoflurane group (ISSEV) (N=10), the Ischemia + Chloral hydrate group (ISCH) (N=10), TBI + Sevoflurane group (TBISEV) (N=13), and TBI+Chloral hydrate group (TBICH) (N=10). Ischemic brain damage was modelled using Rose Bengal (RB) dye-induced PT, and TBI was modelled using mechanical force-induced concussion.

Results. MRI findings indicate lower volumes of brain damage (mm³) in rats from TBISEV group compared with the TBICH group (19±5 vs. 60±5, P<0.0001), and in the ISSEV group compared with the ISCH group (9.8±1.5 vs. 21.5±2, P=0.0016). Moreover, there was a significant difference between ISSEV and ISCH groups based on the protocol assessment of neurological status on day 14 with higher scores in ISSEV (11.4±1.8 vs. 4.9±2.6, P<0.0001).

Conclusion. Taking into account the data obtained, we recommend a careful choice of anesthesia when modeling ischemic stroke and traumatic brain injury in animals. In particular, the neuroprotective effect of sevoflurane should be taken into account in the PT and TBI models.

Acute pancreatitis (AP) is associated with pancreonecrosis in 30% of patients, who may fall at 80% high risk of death when infected pancreatic necrosis progresses to sepsis. Given the catabolic nature of the disease and the significant influence of nutritional status on its course and outcome, these patients require an adequate nutritional support (NS) based on an adequate assessment and control of nutritional and metabolic status.

The aim of the study: to identify trends in developing new tools for assessment of nutritional and metabolic status, and provision of NS in patients with pancreatic sepsis (PS).

Materials and methods

. Keyword search in the PubMed, Scopus and E-library databases for the period from 2018 to 2023 yielded 95 publications, of which 16 meta-analyses and 6 systematic reviews met the requirements.

Results. all existing to date scales for assessment of nutritional deficiency in patients with PS have low prognostic value. Of them, mNUTRIC scale seems to be the most appropriate assessment tool. Recommended by EPSEN guidelines tools to assess the risk of nutritional deficiency it is not suitable for ICU patients. Indirect calorimetry should be preferred vs routine calculation formulas in assessing patient’s energy needs in case of PS. It was also found that «standard» anthropometric values, such as BMI, are not always informative and prognostically significant in patients with severe AP in the ICU. Analgesia, infusion therapy, as well as detection and correction of intraperitoneal hypertension are not only integral components of intensive care for PS but are indispensable for supplying adequate NS in PS patients. It was found that early enteral nutrition is the preferred method of NS, although questions concerning choice of tube insertion site, as well as all parameters of tube feeding remain unanswered. The optimal composition of enteral nutrition for patients with PS has not been established, which is indirectly confirmed by the variety of enteral mixtures available on the market. The refeeding syndrome that occurs at initiation of NS was characterized as a life-threatening condition.

Conclusion. NS, based on adequate assessment of disorders and control of the nutritional and metabolic status is an integral component of intensive care in PS patients. It can reduce the probability and number of potential complications, time of stay in the ICU, cost of treatment, and improve patient’s prognosis.

Purpose of the study: to develop proposals for improving regulatory documentation on ethical expertise (EE) of gene diagnostics and gene therapy clinical studies.

Materials and methods. We used general philosophical research methods, including the formal-logical, historical method, comparative method, systematic approach and axiological method. We analyzed 10 international acts, including acts of «soft law», 4 documents adopted at the level of interstate integration entities, 7 domestic normative legal acts, and a number of various doctrinal sources on the topic under consideration. In addition, we analyzed the regulatory documents for ethical committees (EC) acivities, including those from a historical perspective.

Results. We formulated the concept of EE, defined the principles and main areas of EE, including the personalized medicine, and suggested the regulatory principles of EE operating.

Conclusion. To improve the regulation of EE, the legal status and requirements for the activities of independent ECs should fit the scope of EE, differentially related to the area of a trial (non-interventional trials, clinical trials with a drug treatment); at the national level, independent ECs conducting EE of drug treatmemnt clinical trials should be institutionalized into a single system; to improve the activities of independent ECs in the field of clinical testing, the development of a special normative regulation is required.