Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.

Своевременная диагностика и выбор оптимальной стратегии лечения острых нарушений мозгового кровообращения (ОНМК) остается актуальной задачей для системы здравоохранения. В мире исследуются возможности применения искусственного интеллекта (ИИ) в диагностике множества заболеваний, в том числе ОНМК. Цель данного обзора — анализ современных представлений об использовании ИИ в диагностике острого нарушения мозгового кровообращения по компьютерно-томографическим изображениям головного мозга. Проведён анализ доступных публикаций за последние 5 лет по ключевым словам: ишемический инсульт, ОНМК, терапевтическое окно, искусственный интеллект, машинное обучение, лучевая диагностика в русскоязычной литературе (e-library) и англоязычных базах данных (PubMed, Scopus, Web of Science). Timely diagnosis and selection of the optimal treatment strategy for acute cerebrovascular accidents (ACVA) remains an urgent task for the healthcare system. The world is exploring the possibilities of using artificial intelligence (AI) in the diagnosis of many diseases, including stroke. The purpose of this review was to analyze modern ideas about the use of AI in the diagnosis of acute cerebrovascular accident using computed tomography images of the brain. An analysis of available publications over the past 5 years was carried out using keywords — ischemic stroke, stroke, therapeutic window, artificial intelligence, machine learning, radiation diagnostics) in Russian-language literature (e-library) and English-language databases (PubMed, Scopus, Web of Science).

Dabigatran etexilate is a prodrug of dabigatran, a direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of promising areas of associated researches of SNV of genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage.

To analyze results of the studies covering modern scientific views on the genetics of familial amyotrophic lateral sclerosis (FALS).We searched for full-text publications containing the key words “amyotrophic lateral sclerosis”, “FALS”, and “genetics” in the literature for the past 10 years in both Russian and English in eLibrary, PubMed, Web of Science, and OMIM databases. In addition, the review includes earlier publications of historical interest.This review summarizes all existing information on four most widespread genes associated with FALS: SOD1, TARDBP, FUS, and C9ORF72. The review also describes the functions of these genes and possible pathogenetic mechanisms of motor neuron death in amyotrophic lateral sclerosis (ALS), such as mitochondrial dysfunction, oxidative stress, glutamate excitotoxicity, damage to axonal transport components, and pathological neurofilament aggregation.As modern methods of molecular genetic diagnostics evolve, our knowledge about multifactorial FALS genetics expands. This information should be taken into consideration in clinical practice of neurologists. Information about the genes associated with ALS and understanding of particular pathogenetic mechanisms of the disease play a key role in the development of effective therapeutic strategies.

Dabigatran etexilate is a prodrug of dabigatran, a oral direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. However, pharmacokinetics and pharmacogenetics of dabigatran are variable. This can affect both effectiveness and safety of anticoagulant therapy. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of associated researches of SNV genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage.Materials and methods. The search for full-text publications in Russian and English languages containing key words “dabigatran etexilate”, “dabigatran”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of dabigatran etexilate are considered in this review. The hypothesis about UDP-glucuronosyltransferase enzymes influence on dabigatran metabolism was examined. Nowadays more than 2000 SNV CES1 and ABCB1 genes are identified, but their potential influence on pharmacokinetics of dabigatran etexilate and its active metabolite (dabigatran) in clinical practice needs to be further researched. Role of SNV UDP-glucuronosyltransferase genes (UGT2B15, UGT1A9, UGT2B7) in dabigatran’s effectiveness and safety is not explored enough. However, UGT2B15 gene can be a potential candidate gene for research on safety of this drug.

Edoxaban is a new generation of oral anticoagulant; it is selective, direct and reversible inhibitor of activated blood coagulation factor X (F Xa), serine protease responsible for thrombin formation. Edoxaban is used to prevent stroke in non-valvular atrial fibrillation, to treat deep vein thrombosis and pulmonary embolism. The purpose of the review is to analyze the associative studies of OHB of CYP3A4 / 5 and ABCB1 genes, as well as to search for new candidate genes reflecting the efficacy and safety of edoxaban. The search for full-text publications in Russian and English over the past two decades was carried out in eLibrary, PubMed, Web of Science, OMIM databases using the following keywords: edoxaban, pharmacokinetics, pharmacogenetics, efficacy, and safety. The review covers pharmacokinetics of edoxaban, as well as pharmacogenetic features of the drug metabolism in details. Candidate genes influencing concentration of edoxaban are genes encoding key enzymes of its metabolism – CES1, CYP3A4 / 5, ABCB1, and, to a lesser extent, SLCO1B1. By present day, numerous NVS of candidate genes have been identified. They potentially affect pharmacokinetics of edoxaban, but their role in real clinical practice requires further study