Background. Immunoinflammatory rheumatic diseases (IIRDs) are a significant medical and social problem leading to high mortality, disability and economic burden for society. These diseases, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylitis (axSpA), significantly reduce the quality of life of patients and increase the financial burden on healthcare systems.

   Objective. The aim of this systematic review is to assess current data on the risk of death in patients with IIRDs and identify factors associated with increased mortality, as well as analyze the effectiveness of biological drugs in reducing this risk.

   Materials and methods. The review includes data from multiple clinical trials and meta-analyses covering the period from 2000 to 2021. The analysis was based on data collected from various sources, including national registries, clinical trials and meta-analyses.

   Results. The main results show that IIRDs such as RA, PsA and axSpA significantly increase the risk of death compared to the general population (SMR 2.02 1.79; 2.29). Disease activity, smoking and comorbid conditions are key factors increasing the risk of mortality. The use of biological agents in therapy reduces the risk of death compared to no biological therapy
(HR 0.52 0.32; 0.86) and compared to methotrexate (HR 0.77 0.60; 0.97). The use of biological agents also reduces the risk of cardiovascular events and the development of dementia.

   Conclusions. Early and active use of biological agents can be a significant factor in reducing the negative consequences of IRDs, including mortality and the progression of cardiovascular diseases.

   Conclusion. The results of the systematic review may be useful for developing strategies for managing IIRDs and optimizing medical care for patients. The introduction of GIBPs into the treatment of IIRDs can significantly improve the prognosis and quality of life of patients, reducing the risk of mortality and other adverse outcomes.

   Cost-effectiveness analysis of medical technologies is essential for making rational decisions in healthcare, which in turn contribute to more efficient allocation of limited budgetary resources and improved quality of care. Clinical economic analysis assesses the cost-benefit ratio of medical technologies, which helps determine their feasibility, taking into account the impact on patient health, quality of services and economic costs. One of the methods for accelerated cost-effectiveness assessment is the use of surrogate endpoints (SEP), which allows for faster and safer assessment of new medical technologies. Their use is important for decision makers in healthcare, especially in conditions of a lack of data on the long-term effectiveness of new technologies. Their use should be justified, with a confirmed statistical relationship between surrogate and clinical endpoints. A recent report summarizing current data on the use of SEP in cost-effectiveness analysis of medical technologies served as the basis for this article.

   Relevance. Optic neuromyelitis spectrum disorders are a severe orphan nosology for which the search for new highly effective therapeutic options is a priority area of medical care. At the same time, due to the nature of this group of diseases, conducting new clinical trials (CT) is significantly complicated not only by the long and complex recruitment of patients and the unethical nature of using a parallel control group without treatment, but also by conducting comparisons with a historical control group or indirect comparisons, for which planning the sample size in the CT for a new therapy option is a separate methodological task.

   Objective. The aim of this study was to estimate the power for the analysis of the primary endpoint in the single-arm BCD-132-6/AQUARELLE trial, which was planned to be performed using an adjusted indirect comparison (AIC) of the study drug divosilimab with published data on the placebo group in the randomized N-MOmentum trial.

   Materials and methods. Using the data of the studies identified using a systematic search, a meta-regression model was estimated for the dependence of the average annual relapse rate (ARR) on therapy (anti-CD20 or placebo), the assessment horizon, and baseline patient characteristics. According to its results, for the expected BCD-132-6/AQUARELLE population, a 6-month ARR of 0.116 (95 % CI: 0.030–0.212) was predicted for anti-CD20 therapy. Next, a stepwise effective sample size (ESS) simulation was performed in the divosilimab group with power assessment.

   Results. The expected ratio of the ARR of divosilimab and placebo at 6 months was 0.117 (90 % CI: 0.045–0.214) with-out weighting and 0.156 (90% CI: 0.050–0.315) after weighting (ESS). The minimum EES required to achieve a power of 90 % when testing the hypothesis of superiority in the ARR at 6 months for divosilimab therapy compared with placebo with a one-sided type I error probability of 0.05 is 35 people.

   Conclusion. The obtained results can be used to support the statistical inference of the BCD-132-6/AQUARELLE study.

   Objective. To compare the efficacy and safety of fifth-generation cephalosporins (ceftaroline fosamil and ceftobiprole) when used in adult in the treatment of infections of various localization.

   Materials and methods. A systematic review of the literature was conducted with a meta-analysis and indirect comparison of the results of studies evaluating the efficacy and safety of ceftobiprole and ceftaroline in adult patients in the treatment of community-acquired pneumonia, as well as skin and soft tissue infections based on the following outcomes: clinical cure rate, frequency of microbiological eradication, mortality, incidence of serious adverse events, the frequency of adverse events (AE), according to researchers, associated with taking the investigational drug (IP), as well as the frequency of diarrhea with the calculation of the odds ratio (OR) of the development of each of the events.

   Results. The systematic review included 12 randomized clinical trials. In the treatment of community-acquired pneumonia, ceftobiprole was also effective in terms of clinical cure, mortality, and microbiological eradication, as ceftaroline and the combination of ceftriaxone with or without linezolid. In the treatment of complicated skin and soft tissue infections, ceftobiprole was comparable to ceftaroline and the combination of beta-lactam and vancomycin in terms of clinical cure and mortality. In terms of the frequency of microbiological eradication, ceftobiprole was comparable to the combination of beta-lactam and vancomycin and was superior to ceftaroline (OR 1.65, 95 % CI 1.11; 2.44, p = 0.01). In the treatment of lower respiratory tract infections, complicated skin and soft tissue infections, and bacteremia, ceftobiprole was also safe in terms of the incidence of SAE (OR = 0.93; 95 % CI 0.71;1.22; p = 0.63) and the incidence of diarrhea (OR 1.23; 95 % CI 0.93;
1.64; p = 0.13) as well as ceftaroline.

   Conclusions. Ceftaroline fosamil and ceftobiprole are comparable in efficacy and safety in the treatment of patients with community-acquired pneumonia and complicated skin and soft tissue infections. In the group of patients with nosocomial pneumonia, only ceftobiprole was proven effective in reducing mortality compared with the combination of ceftazidime and linezolid.

   Relevance. Studying risk factors for the presence of multidrug-resistant pathogens at the regional level, which predetermine multiple resistance, is an important component for personalizing the applied strategies of empirical antimicrobial therapy within the framework of epidemiological safety.

   Objective. To study and analyze factors of polyresistance to optimize the choice of empirical antimicrobial therapy in patients with community-acquired pneumonia at the regional level.

   Materials and methods. Clinical, microbiological and molecular genetic risk factors for the presence of multidrug-resistant pathogens of regional significance were retrospectively assessed in 533 patients with community-acquired pneumonia of inpatient profile. To predict the impact of risk factors on the multidrug resistance of respiratory isolates at the regional level, the method of constructing ROC curves was used.

   Results. The leading respiratory isolates in the etiology of community-acquired pneumonia at the regional level were determined. A high level of associative resistance was demonstrated in respiratory isolates of Klebsiella pneumonia, Haemophylus influenzae, Escherichia coli, requiring mandatory microbiological and molecular genetic testing to select initial antimicrobial therapy. Frequency of carbapenemase production in the leading etiologically significant microorganism Klebsiella pneumonia was 60 %; the presence of multiple resistance mechanisms was 30 %, the presence of metallo-beta-lactamases of the NDM type was 42 %, respectively. In the constructed forecasting models, the following factors became practically significant for the implementation of polyresistance at the regional level: previous hospitalization and antimicrobial therapy, stay in long-term care facilities, prior treatment with carbapenem antibiotics, and associative production of carbapenemase with extended spectrum beta-lactamases.

   Conclusion. The obtained results demonstrate the importance of a comprehensive analysis of clinical and microbiological factors for predicting the polyresistance phenotype in a specific medical organization and optimizing the empirical choice of antimicrobial drugs.

   Introduction. The leading pathogens of implant-associated infection are S. aureus and S. epidermidis, characterized by the ability to biofilm formation, which pose a serious threat to the life and health of patients. Antibiotic therapy is an integral part of the complex treatment of infection, but washing the surgical area after the removal of infected components with antiseptics, including those based on polyhexanide or chlorhexidine, plays a major role.

   Objective. To evaluate the presence of biofilm-forming genes in methicillin-resistant S. aureus and S. epidermidis isolated from patients with orthopedic infection and to perform a comparative analysis of the effect of chlorhexidine and polyhexanide on their biofilms.

   Materials and methods. Cultures were isolated according to the international standards of microbiological research. Identification was performed by MALDI-TOF MS, and antibiotic susceptibility was determined according to EUCAST. DNA was isolated and purified using Auto-Pure S32 and the Magno-Sorb kit. Amplification was performed on a CFX-96 device. Visualization was performed using the ChemiDoc gel documentation system. Biofilms were formed for 48 hours and then treated with polyhexanide or chlorhexidine for 5, 10, 20, 40 minutes. The destructive effect of the antiseptics was determined by staining with gentian violet and subsequent comparison with the control. The presence of live bacterial cells in the biofilm after treatment with the drugs was assessed using a resazurin sodium salt. Statistical analysis was performed in GraphPad Prism 9.0.

   Results. The bap gene was detected, and no ica-operon genes were found. MRSA were characterized by the presence of 3 marker genes, and MRSE strains had one or two marker genes. Polyhexanide was more effective in destroying the biomass of the formed daily biofilms of S. aureus — carriers of the bap, clfA/B genes, in contrast to chlorhexidine. Polyhexanide statistically significantly reduced the biomass with an exposure of more than 10 minutes. A similar pattern was found for the MRSE biofilms. In addition, the drugs almost destroyed the biofilm cells of MRSE, and polyhexanide was more effective against MRSA.

   Conclusion. The study revealed the main genetic determinants of methicillin-resistant S. aureus and S. epidermidis biofilm formation. The established interspecies genetic differences can determine the effectiveness of antiseptics and demonstrate the need for exposure of the studied antiseptic for at least 20 minutes to achieve maximum effect on the biofilm cells of staphylococci.

RETRACTED ARTICLE

   Introduction. CDK4/6 inhibitors in combination with endocrine therapy (ET) are the current standard of care for patients with HR+ HER2- advanced and metastatic breast cancer (eBC and mBC). Evidence of the clinical efficacy of CDK4/6 inhibitors has been obtained in several randomized clinical trials (RCTs), but data on their efficacy in real-world clinical practice (RCP) are contradictory.

   Objective. The aim of the ICEDORA study was to analyze clinical and demographic characteristics, treatment regimens, and clinical outcomes in patients with HR+ HER2- mBC and mBC receiving CDK4/6 inhibitors in a real-world clinical practice in Moscow.

   Materials and methods. ICEDORA is a non-interventional retrospective study based on the analysis of data on patients receiving CDK 4/6 inhibitors in Moscow. Clinical characteristics and treatment details of all patients with HR+ HER2-breast cancer who received ribociclib, palbociclib, or abemaciclib from January 2020 to the end of December 2022 were extracted from primary medical records (outpatient charts and medical histories) by parsing. Overall survival (OS) was calculated from the date of breast cancer diagnosis until patient death using the Kaplan-Meier method, and differences between treatment groups were assessed using the log-rank test. Multivariate logistic regression and Cox proportional hazards models were built to exclude the influence of confounders and systematic errors.

   Results. The analysis included 2051 patients. 58.7 % received palbociclib, 34.7 % — ribociclib, 6.6 % — abemaciclib. The median age in the overall population was 58 years, but it was higher in the abemaciclib group (62 years). In 83.5 % of cases, Her2/neu was negative, the groups were homogeneous in this indicator. The level of estrogen receptors (ER) Ki-67 was significantly higher in the abemaciclib group. In the overall population, patients with primary metastatic breast cancer (stage IV) accounted for 42.1 %. The distribution of stages within each group was comparable. The groups differed significantly in the number of metastases due to a higher proportion of patients with one metastasis in the abemaciclib group (31.9 %) compared to the ribociclib (19.0 %) and palbociclib (16.6 %) groups, where the number of metastatic foci was more than one. Comorbidity was present in 90 % of patients. Differences in the baseline characteristics of patients receiving different drugs require caution when interpreting the study results.

   Conclusion. The ICEDORA study, which included patients taking CDK4/6 inhibitors in real-world clinical practice in Moscow, is one of the largest analyses of clinical and demographic characteristics, treatment regimens, and clinical outcomes in patients with HR+ HER2- mBC and mBC taking CDK4/6 inhibitors in real-life clinical practice in Russia. Comparative analysis of the efficacy of ribociclib, palbociclib, and abemaciclib in real-life clinical practice was not planned or conducted due to differences in the clinical and demographic characteristics of patients. Larger multicenter data with
balanced cohorts and long-term follow-up are needed.

   On April 24-25, 2025, the XII All-Russian Conference with international participation «Topical issues of preclinical and clinical studies of drugs and clinical trials of medical devices» was organized and held. The topic of the conference brought together leading experts in the field of preclinical and clinical research. Participants’ prospects for the development of toxicology, preclinical studies of specific activity and translational models, programs for the preclinical development of biomedical cell products, experience in the clinical application of medical programs using artificial intelligence, a personalized approach to prevention and therapy in psychiatry and narcology, pharmacovigilance, the use of real clinical practice data, regulatory issues of clinical trials in pediatrics, data management, biomedical statistics, and mathematical modeling in preclinical and clinical studies. Following the conference, a Resolution was developed, the text of which we invite you to familiarize yourself with.