The Russian Congress «Pharmacotherapy Safety 360°: NOLI NOCERE!» was successfully held at the Russian Ministry of Health in May 2023, providing a high-level, expert platform to discuss current and topical issues of pharmacovigilance and pharmacotherapy safety for different patient groups, including pediatrics, gerontology and geriatrics, pregnant women, patients with orphan and oncological diseases. Extensive scientific topics covered the most significant aspects of the pharmacotherapy safety in various fields, including cardiology, gastroenterology, pulmonology and allergology, endocrinology, neurology, oncology and psychiatry. Over 280 speakers, moderators and lecturers, Russian and foreign experts including world-renowned scientists participated in the discussion of the key tasks facing modern science. The Congress covered issues promising for the further development of biopharmaceuticals, related to the application of artificial intelligence and neural networks.

Cardiovascular diseases (CVD) are a leading cause of mortality in many countries worldwide. Genetic testing is an integral part of CVD prevention. The most common hereditary diseases in the practice of a cardiologist are cardiomyopathy and channelopathy (arrhythmogenic syndromes), as well as familial hypercholesterolemia, which causes a high risk of atherosclerosis and coronary heart disease (CHD). The total carrier frequency of pathogenic variants is 1:100. Timely genetic diagnosis is necessary for conditions that can lead to sudden cardiac death (for example, long QT syndrome, Brugada syndrome, arrhythmogenic cardiomyopathies). Pharmacogenetic testing is also important in cardiology, since it allows taking into account the role of genetic factors in the formation of a response to therapy. Incorporating individual patient characteristics can increase efficiency and minimize the likelihood of complications. The design of modern targeted cardiopanels must necessarily take into account monogenic and oligogenic forms of dyslipidemia and cardiovascular pathologies, polymorphic markers associated with a violation of the lipid spectrum of blood plasma and the early development of CVD in a particular population, as well as a minimum set of pharmacogenetic markers according to modern recommendations for clinical pharmacologists. In this review we provide a justification for the optimal design of such a panel for use in medical practice and scientific research.

Chronic thromboembolic disease (CTED) and chronic thromboembolic pulmonary hypertension (CTEPH) are the complications that comprise a serious problem for patients with history of pulmonary embolism (PE). Erythrocytes, extracellular microvesicles (EMVs) and miRNAs play a substantial role in the procoagulant states. The aim. To analyze the levels of miR-144-3р, miR-451a, and miR-451b in blood plasma-derived EMVs and erythrocytes in patients with history of PE and in the control group. Materials and Methods. 18 patients with history of PE (13 CTEPH, 5 CTED) and 8 controls were enrolled into the study. All the participants had undergone clinical and biochemical blood tests as well as the coagulogram. We used flow cytometry to assess plasma-derived EMVs (CD9, CD41, CD45, CD235a, CD105). We measured the expression of miR-144-3р, miR-451a, miR-451b by real-time PCR with endogenous control (miR-152-3p) and five exogenous quality controls. Results. The levels of miR-144-3р and miR-451a in patients were lower than in controls, both in EMVs (р = 0.030; р = 0.065) and in erythrocytes (р = 0.023;р = 0.086). In female patients, the levels of miR-144-3р and miR-451a in CTEPH were lower than in CTED (р = 0.087; р = 0.031). Mir-451b in EMVs has not been detected, while in erythrocytes its levels have not differed between the groups. In patients, the levels of miR-144-3р and miR-451a directly correlated with each other both in EMVs (р = 0.004) and in erythrocytes (р = 0.042). In all the participants, the levels of miR-144-3р and miR-451a in EMVs directly correlated with those in erythrocytes (р = 0.002; р = 0.078). The number of erythrocyte-derived EMVs correlated with miR-451a levels both in EMVs (R = 0.472; p = 0.065) and in erythrocytes (R = –0.829; p = 0.011). The level of miR-451a in EMVs correlated with blood plasma levels of factor VIII and fibrinogen (R = 0.584; p = 0.022 and R= –0.489; p = 0.047), and with the International Normalized Ratio (R = 0.894; p = 0.041). Conclusion. The microRNA-144/451 cluster may influence both the hemostasis system and the risk of post-thromboembolic complications development. In the present study, miR-144-3р and miR-451a showed themselves as protective factors in relation to both the development of PE and severity of post-thromboembolic complications.

The interest in the problem of hereditary forms of breast cancer is due not only to the increase in the number of patients, but also to the existing features in relation to the phenotypic characteristics of these tumors, course features, and sensitivity to various therapy options. Unfortunately, the data of clinical trials that exist to date do not provide a complete picture of the course of various forms of hereditary breast cancer, sensitivity to therapeutic agents, adequate examination volumes and preventive measures. In this regard, there is a need to conduct prospective randomized trials to optimize treatment, screening and prevention programs. The rapid development of technologies in the field of molecular biology has made it possible to identify about 20 genes, the presence of mutations in which causes an increased risk of developing breast cancer. The aim of this review was to summarize the available data on the role of structural rearrangements of genes of varying degrees of penetrance associated with hereditary predisposition to breast cancer. The mechanism of hereditary breast cancer forms development is associated with rearrangements in DNA repair genes of varying degrees of penetrance. The identification of these mutations is of strategic importance for early diagnosis and the transition from an empirical to a targeted personalized approach in the treatment of various types of cancer. Understanding the pathogenesis of the disease at the molecular level makes it possible to make a breakthrough in the field of pharmacological innovations in order to create new selective classes of drugs in effective targeted therapy.

Coronary heart disease (CHD) is one of the most common causes of death worldwide. The pharmacokinetic properties of drugs used to treat coronary heart disease depend on genetic factors, including the genotype of CYP2C19, CYP2C9 and CYP4F2. However, existing studies of the genetic basis of the response to treatment in patients with acute coronary syndrome (ACS) have contradictory results, requiring a more detailed study. Goal. In this study, we studied the distribution of the genotypes of CYP2C19*2, CYP2C9*2 and CYP4F2*3 among 59 patients diagnosed with ACS who received dual antiplatelet therapy. Methods. The polymerase chain reaction (PCR) method was used to determine the genotypes of CYP2C19, CYP2C9 and CYP4F2. A correlation analysis of the results of genotype carriage and clinical and laboratory parameters of patients was carried out. Results. The distribution of CYP2C9*2 genotypes was as follows: wild genotype (CC) was found with a frequency of 78 % (45 patients), heterozygotes (CT) — 22 % (12 patients), homozygotes (TT) were not detected. The CYP4F2*3 genotype was distributed as follows: 56.14 % (32 patients) had a wild genotype (CC), 31.5 % (18 patients) were heterozygotes with reduced enzyme activity (CT), 12.36 % (7 patients) were homozygotes for the T (TT) allele. The distribution of alleles and genotypes of CYP2C9 did not correspond to the Hardy-Weinberg equation (χ2 = 21.55; p = 0.044), while the distribution of alleles and genotypes of CYP4F2 corresponded to it (χ2 = 3.61; p = 0.0574). Conclusion. The study showed a high prevalence of the genotypes CYP2C9*2 (CT) and CYP4F2*3 (CT and TT) among patients with acute coronary syndrome. The carriage of CYP2C19*2 was significantly associated with adverse cardiovascular events in patients. These results suggest that genetic testing can provide valuable information for risk stratification and personalized treatment of patients with acute coronary syndrome