Background/Objectives: Vancomycin remains a cornerstone antibiotic for Gram-positive infections, but its narrow therapeutic window and marked pharmacokinetic variability in critical patients complicate dosing. This study aimed to analyze survival and identify factors associated with mortality in intensive care unit (ICU) patients receiving vancomycin under therapeutic drug monitoring (TDM). Methods: A single-center, retrospective cohort study was conducted at City Clinical Hospital named after I.V. Davydovsky (Moscow, Russia) between December 2021 and January 2026 (IRB protocol VANCO-2021). A total of 190 adult patients from surgical, therapeutic, and cardiac ICUs receiving vancomycin for at least 3–5 days were analyzed; trough concentrations were determined by HPLC-MS/MS. Cox proportional hazards, spline Cox, and segmented (piecewise) Cox models were applied to identify mortality predictors, with bootstrap subsampling assessing threshold robustness. Results: Three independent predictors of mortality were identified: ln(minimum vancomycin concentration) (HR = 1.644, p = 0.028), age (HR = 1.019, p = 0.037), and serum creatinine (HR = 1.004, p < 0.001). A data-driven threshold trough concentration (Ctrough) of 25.5 µg/mL was identified, above which mortality increased substantially (63.0% vs. 26.4%; p < 0.05). The adjusted hazard ratio for Ctrough ≥ 25.5 µg/mL was approximately 1.88 (p = 0.054); bootstrap subsampling yielded an uncertainty interval of 23.2–33.6 µg/mL. Conclusions: Elevated minimum vancomycin concentrations exceeding 25.5 µg/mL are independently and statistically associated with increased mortality in ICU patients, likely reflecting altered drug exposure and illness severity rather than a direct causal effect. Systematic TDM is essential for maintaining vancomycin within the therapeutic range.

Background. Respiratory infections are very common in children. Currently, various studies are being conducted to determine additional markers of high incidence of respiratory infections in children. Polymorphisms of the vitamin D receptor gene (VDR) are associated with the risk of developing various diseases, including infectious diseases. Aim. To assess the relationship between VDR gene polymorphisms and the incidence of respiratory infections in infants. Materials and methods. During the study, we assessed the number of respiratory infection episodes in the first 6 months of a child’s life, determined the FokI (rs2228570) and TaqI (rs731236) polymorphisms of the vitamin D receptor gene. Results. The results of the study showed that the presence of minor TT alleles of the FokI gene is associated with a higher frequency of respiratory infections in children in the first 6 months of life. The risk of developing 4 or more episodes of respiratory infections in the first 6 months of life was 4.8 times higher in children who had this genotype (95% CI 2.19–10.5). Conclusion. The presence of minor TT alleles of the FokI gene is associated with a high frequency (more than 4 episodes) of respiratory infections in children in the first 6 months of life.

Background. More and more data confirm the need for personalized pharmacotherapeutic treatment based on the genetic characteristics of the patient, which will become the main method of future antihypertensive treatment, especially in patients with refractory hypertension, in order to rationally prescribe pharmacotherapy. Aims — to study the pharmacodynamic parameters of the effectiveness of therapy with angiotensin II receptor blockers in the form of monotherapy and as part of combined drugs in patients with hypertension, depending on the genetic characteristics of patients – the genetic polymorphism A1166C of the angiotensin II type 1 receptor gene (AGTR1). Methods. The study included 179 patients from the Moscow region with newly diagnosed arterial hypertension (AH) of 1–2 degrees, among whom 141 (78.8%) women and 38 (21.2%) men aged 32 to 69 years, who were randomly assigned to irbesartan and valsartan groups in the form of mono- or combination therapy with hydrochlorothiazide by a simple randomization method. After 3 weeks of pharmacotherapy, the presence of the rs5186 (A1166C) genetic polymorphism of the type 1 angiotensin II receptor gene (AGTR1) was determined. Results. After 3 months of valsartan therapy, among heterozygotes, the change in office DBP was statistically significantly less pronounced compared to the A/A genotype by an average of 5.4 mmHg (p = 0.009), and there was also a less pronounced decrease by an average of 5.6 mmHg, however, not statistically significant, in heterozygotes compared to the C/C genotype (p = 0.192). There was a tendency in patients with genotype A/C compared with genotype A/A after 3 weeks of using irbesartan in the form of a less pronounced decrease in office SAD by an average of 4.3 mmHg. The decrease in office DBP was less pronounced by an average of 5.2 mmHg (p = 0.019); patients with CC genotype also showed a less pronounced decrease in DBP (by an average of 4.2 mmHg), compared with the A/A genotype, however, this difference was not statistically significant (p = 0.48). Conclusions. The A1166C polymorphism of the AGTR1 gene significantly affects the antihypertensive effect of valsartan in patients with grade 1–2 hypertension, leading to a decrease in DBP and an increase in HR in A/C heterozygotes compared to A/A homozygotes. No association between the polymorphism and the antihypertensive effect of irbesartan was identified; however, patients with A/C and C/C genotypes showed a less pronounced reduction in SBP and DBP. No relationship was found between genotype and the achievement of target BP levels or the need for therapy intensification. Further prospective studies with a larger sample size are required to clarify the genetic factors influencing the antihypertensive efficacy of ARBs.

Introduction. Xa factor inhibitors are a significant treatment option for patients with atrial fibrillation, as they assist in reducing the risk of stroke. However, there has not been enough research into the levels of X-factor in these patients.Aim. To assess the impact of blood clotting factor X on the risk of adverse drug events (ADEs) in patients receiving apixaban or rivaroxaban treatment.Materials and methods. The study involved 102 patients with atrial fibrillation who were administered Xa inhibitors: 56 received rivaroxaban and 46 received apixaban. Adverse drug reactions were documented, which were noted in the patient's medical records during drug administration. The concentration of the X factor was measured using photocolorimetry with reagents designed to determine the concentration of the factor X — AssaySense Human Factor X (FX) Chromogenic Activity Assay Kit (AssayPro, USA).Results. In patients receiving apixaban therapy, the X factor concentration was lower in 32.6% of cases and in 43.5% of patients, it was higher than the reference value. In contrast, in patients receiving rivaroxaban therapy, these indicators were lower in 26.8% of cases and higher in 51.8% of patients. Overall, according to the medical records, there were 37 adverse reactions in 29 patients, including 23 (41.1%) ADEs in 19 patients (33.9%) receiving rivaroxaban and 14 (30,4%) ADEs in 10 patients (21.7%) taking apixaban. The level of X factor was statistically significantly associated with the risk of stroke, with an AUC ROC of 0.720 and p-value of 0.05, and with minor bleeding, with an AUC ROC of 0.735 and p-value 0.003. An increase in the X factor level above 12.6 pg/mL increased the risk of stroke by 9.4-fold (95% CI: 1.9-74.3, p = 0.034), while a decrease below 10.5 pg/mL increased the risk of bleeding by 3.2-fold (95% CI: 1.2-8.7, p = 0.021).Conclusion. The level of the X factor in individuals with atrial fibrillation exhibits a wide range of variability. Deviations from the reference values, either below or above, can significantly impact the risk of experiencing minor bleeding or suffering a stroke, respectively.

Introduction. For the past decades, metformin has been the drug of choice for the treatment of patients with type 2 diabetes mellitus (T2DM). However, its long-term use leads to a number of side effects, such as the development of vitamin B12 deficiency (VB12).Aim. Assess the safety of metformin use in real clinical practice in the treatment of patients with type 2 diabetes based on the analysis of the incidence of VB12 deficiency.Materials and methods. Sixty patients with T2DM aged 27 to 65 years were examined in a city polyclinic. The average anamnestic duration of T2DM was 68 [4; 291] months. All patients were on selected hypoglycemic therapy: 19 patients (31.7%) received metformin monotherapy, and 41 patients (68.3%) received metformin as part of combination therapy. The average duration of metformin therapy was 62 [3; 291] months. All patients underwent analysis of the VB12 content in the blood serum depending on the duration of metformin intake. Results. The average VB12 level in the examined patients was 345 [99; 770] pg/ml. Normal VB12 levels were observed in 51 (85%) patients (386 [221; 770] pg/ml), VB12 deficiency (<200 pg/ml) was detected in 9 (15%) patients (146 [99; 195] pg/ml), the differences between VB12 levels were significant (p < 0.05). At the same time, in 37 (61.7%) patients with normal VB12 levels, its values were assessed as borderline (in the range of 200–450 pg/ml), and amounted to 335 [221; 470] pg/ml. VB12 deficiency developed more often in patients taking metformin for more than 1 year (16.7%), borderline VB12 levels were more often found in patients taking metformin for less than a year (58.3%) and more than 5 years (71%). However, the dependence of VB12 levels on the duration of metformin intake was not significant (p > 0.05).Conclusion. Metformin use results in the development of VB12 deficiency in every sixth patient with T2DM, primarily after one year of treatment.

Differences in the response to pharmacotherapy with angiotensin II receptor blockers may be determined by polymorphisms in the genes responsible for their target of action. In this work, we investigate the pharmacodynamic parameters of daily blood pressure monitoring (DBPM) to assess the efficacy of therapy with angiotensin II receptor blockers in the form of monotherapy and as part of combination therapy in patients with arterial hypertension, depending on their genetic characteristics, i.e., polymorphism A1166C of the angiotensin II type 1 receptor gene (AGTR1). The study included 179 patients in the Moscow Oblast with newly diagnosed arterial hypertension of 1–2 stages. Among them, 141 (78.8%) were women and 38 (21.2%) were men aged 32 to 69 years, randomly assigned to irbesartan and valsartan groups in the form of mono- or combination therapy with hydrochlorothiazide by a simple randomization method. Following three weeks of pharmacotherapy, the presence of the rs5186 (A1166C) genetic polymorphism of AGTR1 gene was determined. DВPM was performed when patients were included in the study and after three months of therapy. The maximum antihypertensive effect was observed in heterozygotes A/C in the group of patients taking valsartan after three months of prescribed angiotensin II receptor blockers pharmacotherapy. This effect was manifested in a decreased average daily systolic blood pressure (SBP) and diastolic blood pressure (DBD), average night SBP, variability of night SBP and DBP. Among patients treated with irbesartan, there was no statistically significant association of the A1166C polymorphism genotype of the AGTR1 gene with these indicators. Heterozygotes showed a statistically significantly more pronounced decrease in the average sleeping heart rate in the group of valsartan patients. At the same time, the average daily heart rate decreased more significantly in C/C homozygotes in both the group of irbesartan and valsartan patients. Thus, when developing personalized treatment plans for patients with newly diagnosed stage 1–2 arterial hypertension using detection of the A1166C genetic polymorphism of the AGTR1 gene, it is advisable to recommend valsartan as a more effective initial therapy with angiotensin II receptor blockers in the form of mono- or combination therapy depending on the risk group for patients in the Moscow Oblast who are carriers of the A/C genotype.

Atrial fibrillation (AF) is the most common heart rhythm disorder in clinical practice. It worsens the quality of life of patients, leads to an increase in the mortality rate because of its association with a high risk of thromboembolic complications. The current pandemic of a new coronavirus infection, which began in March 2020, was marked by an increase in cardiovascular diseases, including an increase in the number of patients with AF. That is why it is extremely relevant to find answers to questions about the association and mutual influence of AF and coronavirus infection to reduce the risk of vascular complications. However, most research in this area has focused on hospital patients. In this study, an electronic database of outpatients with AF, including patients with a history of COVID-19 infection was analyzed in order to assess the most significant risk factors for complications.

The effectiveness of the antihypertensive therapy may be associated with genetic factors that affect not only the degree of a blood pressure elevation but also predetermine an interindividual variability in response to the antihypertensive treatment.The aim of the work was to study pharmacodynamic indices of the effectiveness of therapy with angiotensin II receptor blockers (ARBs) in the form of monotherapy and as a part of combined drugs in patients with an arterial hypertension (AH) depending on genetic features of patients – a polymorphism of the gene encoding aldosterone synthase, the C-344T polymorphism.Materials and methods. The study included 179 patients of the Moscow region with a newly diagnosed 1–2-degree AH (141 (78.8%) women and 38 (21.2%) men) aged from 32 to 69 years who had been randomly allocated to treatment groups with irbesartan and valsartan in the form of the mono- or combined therapy with hydrochlorthiazide by simple randomization. After 3 weeks of pharmacotherapy, the presence of the genetic rs1799998 (C-344T) polymorphism of the aldosterone synthase gene, CYP11B2, and the minimum equilibrium concentration of angiotensin receptor blockers (ARBs) were determined.Results. TT homozygotes in the irbesartan group were characterized by a lower level of the blood pressure (BP) target achievement after 3 weeks of pharmacotherapy and a higher frequency of the need to intensify the antihypertensive therapy compared with CT and TT genotypes. Among the patients taking valsartan, the carriers of the TT genotype were characterized by a higher frequency of achieving the target BP after 3 weeks of pharmacotherapy compared to the CC (p <0.001) and CT genotypes (p=0.084). Herewith, at the end of the study, according to the results of the office BP measurement and daily BP monitoring (DBPM), the achievement of the target BP values was not significantly associated with CYP11B2 C-344T genotype in both irbesartan (p >0.999) and valsartan (p=0.149). There was a trend toward a slightly more pronounced decrease in the daytime HR in the heterozygotes receiving irbesartan by a mean of 1.9 bpm compared to the CC homozygotes (p=0.059). The CT heterozygotes taking valsartan, were characterized by a less pronounced decrease in the HR by a mean of 1.4 bpm compared to the TT homozygotes (p=0.045). Moreover, the minimum drug concentration was not a statistically significant mediator of the effects (p=0.484 and p=0.736, respectively).Conclusion. When personalizing the AH therapy in the patients of the Moscow region, to optimize the achievement of the target BP, the carriers of the TT genotype C-344T on the CYP11B2 gene should be recommend valsartan as the starting therapy of ARBs in the form of the mono- or bicomponent therapy depending on the AH degree.

The synthesis and in silico prediction of the molecular-targeted anti-EGFR inhibitory activity of a novel dihydroacridinone derivative are reported. 9-Aminium-3,3-dimethyl-3,4-dihydroacridin-1(2H)-one L-2-hydroxybutanedioate (LHT-17-19) was obtained 99.8

To evaluate the efficacy of early administration of levilimab for prevention of hospitalizations in outpatients with COVID-19.

The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.

Aim. To study the pharmacodynamic parameters of the effectiveness of therapy with angiotensin II receptor blockers in the form of monotherapy and as part of combination drugs in patients with hypertension, depending on the genetic characteristics of patients — the M235T polymorphism of the angiotensinogen gene (AGT).Material and methods. The study included 179 patients in the Moscow region with newly diagnosed hypertension of 1-2 degrees, among whom 141 (78.8%) women and 38 (21.2%) men aged 32 to 69 years, who were randomly assigned to irbesartan and valsartan groups in the form of mono- or combination therapy with hydrochlorothiazide by a simple randomization method. After 3 weeks of pharmacotherapy, the presence of rs699 (C4072T, M235T) genetic polymorphism of the AGT was determined.Results. Homozygotes СС with the genetic polymorphism M235T of the AGT treated with valsartan had a statistically significantly higher frequency of achieving target blood pressure figures after 3 weeks of pharmacotherapy compared with TT homozygotes (p=0.006) and a statistically significantly lower frequency of the need to increase the dose of the drug compared with heterozygotes and TT homozygotes (p=0.047 and 0.006, respectively). Among patients treated with irbesartan, there was no statistically significant association of the M235T polymorphism genotype of the AGT with these indicators.Conclusion. The data obtained may indicate a faster and more stable antihypertensive effect in homozygotes of CC and TT of the genetic polymorphism M235T of the AGT. When personalizing hypertension therapy for patients of the Moscow region, carriers of homozygous CC and TT genotypes of the M235T genetic polymorphism of the AGT for more effective achievement of target blood pressure figures, it is advisable to recommend valsartan as a starting therapy in the form of mono- or twocomponent therapy, depending on the degree of hypertension.

Introduction. It is now well known that a proportion of patients with COVID-19 develop a pathological systemic inflammatory response with complications resulting in multiple organ failure. The severity and prognosis of the disease, as well as the effectiveness of the treatment provided should be assessed as early as possible. For this purpose, a number of laboratory markers are used, such as C-reactive protein (CRP), IL-6, fibrinogen, ferritin, and changes in these parameters serve as a basis for the disease prognosis.Aim. To evaluate the effectiveness of levilimab in outpatients with COVID-19 based on the analysis of changes in laboratory markers of blood inflammatory activity.Material and methods. A total of 120 patients with COVID-19 receiving standard therapy (ST) were included in the study. The patients were divided into 2 groups: the treatment group of patients who received 2 injections of levilimab, IL-6 receptor blocker, included 47 men and 29 women (average age 46.7 years); the control group, who only received CT, included 21 men and 23 women (average age 46.3 ± 2 years).Results. The treatment group demonstrated a faster normalization of laboratory markers of inflammatory activity. After 14 days of follow-up, the CRP levels in the treatment group decreased significantly by 18.9 (67%) (p < 0.05), and in the control group by 14.3 (46.9%) (p < 0.05). The IL-6 level significantly decreased in patients of the control group, but did not change in the levilimab group. The changes in fibrinogen levels showed that the group of patients, who received levilimab, had a significant decrease in fibrinogen by 35% from baseline (p < 0.05), in contrast to the control group, in which fibrinogen levels virtually did not change (3.8% decrease) (p < 0.05).Conclusion. Levilimab therapy carried out at onset of coronavirus infection results in a faster normalization of laboratory markers of inflammatory activity and helps prevent the severe course of COVID-19.

Острая скелетно-мышечная боль (ОСМБ) в спине – одна из наиболее частых причин обращения за медицинской помощью. Ведение пациентов с ОСМБ – актуальная проблема современной медицины, так как ОСМБ служит причиной временной нетрудоспособности населения. Пациент с ОСМБ в спине должен быть информирован о доброкачественном характере заболевания, благоприятном прогнозе, целесообразности сохранять физическую активность и избегать постельного режима. Наибольшее применение в лечении болевого синдрома в спине получили нестероидные противовоспалительные препараты (НПВП). Также в комплексной терапии широко используют витамины, обладающие нейротропной активностью и антиноцицептивным действием (В1, В6, В12). Исторически сложившаяся клиническая практика совместного назначения витаминов группы В и НПВП набирает все большую доказательную базу. На фоне комплексного применения НПВП и препаратов, содержащих бенфотиамин, пиридоксин и цианокобаламин, у пациентов с ОСМБ значительно снижается интенсивность боли и уменьшается количество потребляемых анальгетиков, что подтверждено клиническими исследованиями и метаанализами. Использование двухступенчатой терапии вита‑ минными препаратами с переходом от инъекционных к таблетированным формам лечебных доз синергично действующих витаминов группы В способствует повышению эффективности фармакотерапии болевого синдрома, сокращению времени нетрудоспособности, удлинению безрецидивного периода и улучшению качества жизни пациента. Acute musculoskeletal pain (AMSP) in the back is one of the most common reasons for seeking medical help. Management of patients with AMSP is an urgent problem of modern medicine, since AMSP causes temporary disability of the population. A patient with AMSP in the back should be informed about the benign nature of the disease, a favorable prognosis, the advisability of maintaining physical activity and avoiding bed rest. Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used in the treatment of back pain. Vitamins with neurotropic activity and antinociceptive effects (B1, B6, B12) are also widely used in complex therapy. The historical clinical practice of co-prescribing B vitamins and NSAIDs is gaining increasing evidence base. With the combined use of NSAIDs and drugs containing benfotiamine, pyridoxine and cyanocobalamin, patients with AMSP significantly reduce pain intensity and reduce the amount of analgesics consumed, which is confirmed by clinical studies and meta-analyses. The use of two-stage therapy with vitamin preparations with a transition from injection to tablet forms of therapeutic doses of synergistically acting B vitamins helps to increase the effectiveness of pharmacotherapy for pain syndrome, reduce the time of disability, lengthen the relapse-free period and improve the patient’s quality of life.

Relevance. Coenzyme Q10 is one of the main components that maintain the balance of the body's redox regulatory system. Although some studies have examined plasma concentrations of CoQ10 in various diseases, the distribution of ubiquinol and ubiquinone, as well as the redox state of CoQ10, remain largely unexplored. The purpose of the study. The purpose of the study was to study the ratio of ubiquinone and ubiquinol concentrations in patients with chronic heart failure (CHF) administrating the antioxidant ethylmethylhydroxypyridine malate and the domestic drug ubidecarenone (CoQ10 drug). Methods. The study included 58 patients with functional class (FC) of CHF 0−III (according to NYHA), who were divided into 2 groups for subsequent assessment of the effect of ethylmethylhydroxypyridine malate and ubidecarenone on endogenous plasma concentrations of total CoQ10, ubiquinol and ubiquinone. The concentrations of the studied substances were determined by HPLC-MS/MS in the multiple reaction monitoring mode. Results. The study revealed that with additional administration of the drug ubidecarenone, there was an increase in the concentration of coenzyme Q10 (+25.0 Δ%), a significant increase in the concentration of ubiquinol (+43.4 Δ%), as well as a sharp increase in redox state (+74.6 Δ%) compared to the control group. During administration of ethylmethylhydroxypyridine malate in addition to standard therapy, patients experienced a statistically significant increase in the concentration of coenzyme Q10 (+20.22 Δ%), a significant increase in the concentration of ubiquinol (+25.0 Δ%) and ubiquinone (+17.7 Δ%) according to compared with a control group receiving standard therapy. Conclusion. With the additional administration of ethylmethylhydroxypyridine malate and ubidecarenone to standard therapy, a statistically significant increase in the concentration of total CoQ10 is observed. However, when administrating ubidecarenone, a sharp increase in the redox state of CoQ10 is observed due to its reduced form — ubiquinol. While during administration of ethylmethylhydroxypyridine malate, it is observed an unreliable but positive trend towards an increase in the redox state of CoQ10 due to a statistically significant increase in the concentration of both ubiquinone and ubiquinol.

According to the World Health Organization, 2 billion people all over the world suffer from infectious diseases every year. Infectious diseases remain among the leading causes of death and the first cause of premature death despite the implementation of vaccination programs. Vitamins and micronutrients are essential in supporting both the cellular and humoral parts of the immune system (IS), increasing resistance to infections. Micronutrient deficiency is a recognized global public health problem, and hypovitaminosis and nutrient deficiency conditions predispose to infections. Micronutrients such as vitamins A, C, D, E, B2, B6, B12, folic acid, selenium, zinc, and iron are necessary to maintain immunocompetency. Both in adulthood and in old age, patients have an increased risk of occurrence and severity of infections due to the high prevalence of hypovitaminosis, a decrease in the function of the IS, and the presence of comorbidities. Nutritional support by vitamin and mineral complexes (VMC) with rational composition is a strategy to correct the immune response. VMCs should complement a healthy diet and contain micronutrients within the recommended amounts at the level of daily food requirement. It is advisable to use a differentiated approach to VMCs to modulate the IS function. Basic nutritional support with vitamins C, D, and zinc is most often sufficient for people without the risks of severe and complicated acute respiratory infections. Various mechanisms of action and different targets of micronutrients that correct the body's immune response and synergistic interactions support the discussion of the hypothesis of a more pronounced effect of multicomponent VMCs. In the presence of chronic diseases, in the case of comorbidity, it is advisable to use expanded formulation VMCs containing, in addition to vitamins C, D, and zinc, other micronutrients, such as vitamins A, E, B, copper, selenium, which helps reduce the risk of severe course and complications of respiratory infections in at-risk groups.

Aim . To compare the antiarrhythmic activity and safety of two Russian-made drugs, Laporitmin (PharmVILAR) and Allapinin (Pharmcenter VILAR) in premature ventricular contractions (PVCs) in patients without structural heart pathology. Material and methods . The study included 100 subjects divided into 2 groups; the follow-up period was 3 weeks. The drug efficacy was assessed based on the results of ECG monitoring and Holter ECG monitoring (ECG-HM). Results . A comparative analysis of the antiarrhythmic activity and safety of the drugs containing lappaconitine hydrobromide showed a comparably high clinical efficacy and good tolerability of the original drug Allapinin and the generic drug Laporitmin for PVCs. According to the results of ECG monitoring, the number of PVCs significantly decreased from 2 (2-6) to 0 (0-1) in patients of the main group (Laporitmin treatment group) and from 2 (2-7) to 0 (0-2) in patients of the control group (Allapinin treatment group) (p>0.05); according to the ECG-HM data, the number of PVCs significantly decreased by 88.2 Δ% in the main group and by 87.5 Δ% in the control group (p <0.01). There were no statistically significant differences in the primary effectiveness criterion between the main and control groups (F statistic = 1.41; p = 0.23). Conclusion . The comparative analysis of the original drug Allapinin and the generic drug Laporitmin for PVCs in patients without structural heart pathology who had indications for antiarrhythmic therapy did not detect statistically significant differences in the primary criterion of effectiveness. Therapy with either drug showed a comparably high efficacy in reducing the number of PVCs by more than 75∆%, which was established as a criterion for primary effectiveness in the clinical trial protocol. Both drugs were well tolerated.

Функциональные заболевания кишечника характеризуются высокой распространенностью и значительно влияют на качество жизни пациентов. В настоящее время значительная роль в их патогенезе отводится нарушению экспрессии зонулина клетками кишечника в связи с нарушением микрофлоры кишечника. Цель исследования – определить влияние пробиотика Лактобаланс® мультипробиотик (Юнифарм) на экспрессию зонулина и гастроэнтерологические симптомы у пациентов с функциональными заболеваниями кишечника. Материал и методы. В исследование было включено 108 пациентов (40 мужчин и 68 женщин) с функциональными заболеваниями кишечника: функциональным запором (ФЗ, n = 26), функциональной диареей (ФД, n = 27), синдромом раздраженного кишечника с диареей (СРК-Д, n = 28) и запором (СРК-З, n = 27). Концентрацию зонулина в кале определяли методом иммуноферментного анализа (Human zonulin ELISA kit zonulin, 96 (BlueGene Biotech Shanghai, КНР)). Изменения уровня зонулина и симптомы функционального заболевания кишечника оценивали на фоне терапии муль‑ тиштаммовым пробиотиком Лактобаланс® мультипробиотик. Результаты. До приема пробиотика медианный уровень зонулина составлял 113,5 (95% доверительный интервал (ДИ) 98,6–122,9) нг/мл. У пациентов с ФД зарегистрирован наиболее высокий уровень зонулина – 130,3 нг/мл. У больных с СРК-Д он составил 121,7 нг/мл, с ФЗ – 105,8 нг/мл, с СРК-З – 98,5 нг/мл. После применения мультипробиотика Лактобаланс® уровень зонулина снизился и варьировал от 13,6 до 173,7 нг/мл (медиана – 82,3 (95% ДИ 73,9–93,9) нг/мл). Изменения уровня зонулина отличались в зависимости от диагноза функционального заболевания кишечника. На 21-й день терапии мультипробиотиком Лактобаланс® у пациентов с СРК-Д отмечалось статистически значимое снижение выраженности болевого синдрома с 12,36 до 4,56 балла по шкале GSRS (в 2,7 раза) и диарейного синдрома с 15,24 до 5,4 балла (в 3 раза), а также уменьшение частоты дефекаций и улучшение характера стула. У больных с СРК-З зарегистрировано статистически значимое снижение выраженности симптомов запора с 15,85 до 4,43 балла (в 3,6 раза) и бо‑ левого синдрома с 13,24 до 3,66 балла (р < 0,05). У больных с ФЗ и ФД болевой синдром был слабым, но при применении мультипробиотика Лактобаланс® отмечалось снижение его частоты и выраженности, хотя динамика значений не была статистически значимой. Наблюдалась положительная динамика в проявлениях диареи у больных ФД и запора у больных ФЗ. Так, выраженность симптомов диареи у больных ФД снизилась с 16,34 до 4,86 балла (р < 0,05), а симптомов запора у больных с ФЗ – с 16,1 до 4,13 балла (р < 0,05). Functional bowel diseases are characterized by high prevalence and significantly affect the quality of life of patients. Currently, a significant role in their pathogenesis is assigned to disruption of the expression of zonulin by intestinal cells due to disruption of the intestinal microflora. Purpose of the study – to determine the effect of the probiotic Laktobalans® multiprobiotic (Unipharm) on the expression of zonulin and gastroenterological symptoms in patients with functional intestinal diseases. Material and methods. The study included 108 patients (40 men and 68 women) with functional bowel diseases: functional constipation (FC, n = 26), functional diarrhea (FD, n = 27), irritable bowel syndrome with diarrhea (IBS-D, n = 28) and constipation (IBS-C, n = 27). The concentration of zonulin in feces was determined by ELISA (Human zonulin ELISA kit zonulin, 96 (BlueGene Biotech Shanghai (China)). Changes in zonulin levels and symptoms of functional intestinal disease were assessed during therapy with a multi-strain probiotic Laktobalans® multiprobiotic. Results. Before probiotic supplementation, the median zonulin level was 113.5 (95% confidence interval (CI) 98.6–122.9) ng/ml. Patients with FD had the highest zonulin values – 130.3 ng/ml, patients with IBS-D – 121.7 ng/ml, patients with FC – 105.8 ng/ml, and patients with IBS-C – 98.5 ng/ml. After using Lactobalance® multiprobiotic, the level of zonulin decreased and ranged from 13.6 to 173.7 ng/ml. Median zonulin values were 82.3(73.9–93.9) ng/ml. Changes in zonulin levels differed depending on the diagnosis of functional bowel disease. On the 21st day of therapy with Lactobalans® multiprobiotic in patients with IBS-D, there was a statistically significant decrease in the severity of pain from 12.36 to 4.56 points by almost 2.7 times, the frequency of stools also decreased and the character of stool improved, the severity of diarrhea syndrome was statistically significant decreased from 15.24 to 5.4 points, i.e. 3 times. In patients with IBS-C, there was a statistically significant manifestation of constipation syndromes by 3.6 times, from 15.85 to 4.43 points, and the severity of pain syndrome from 13.24 to 3.66 times (p < 0.05). In patients with FC and FD, the pain syndrome was mild, but when using Lactobalance® multiprobiotic, a decrease in its frequency and severity was noted; the dynamics of the values were not statistically significant. Good positive dynamics in these patients was noted in the manifestations of diarrhea in patients with FD and constipation in patients with FC, so in patients with FD, the symptoms of diarrhea decreased from 16.34 to 4.86 points (p < 0.05), and the symptoms of constipation in patients with FC decreased from 16.1 to 4.13 points (p < 0.05).

Background. One of the important links in the pathogenesis of irritable bowel syndrome (IBS) is a change in the composition of the microbiota, and therefore, the use of probiotics in complex therapy can be considered as a pathogenetic treatment of this functional disease. Aim. To study the effectiveness of probiotic use on the composition of the intestinal microbiota and the dynamics of symptoms in patients with IBS with predominance of diarrhea (IBS-D) or constipation (IBS-C). Materials and methods. 10 patients with IBS-D and 7 patients with IBS-C who took a probiotic for 28 days, which included: Lactobacillus acidophilus 1.25×109 CFU, Bifidobacterium lactis – 1.25×109 CFU, Lactobacillus paracasei – 1.25×109 CFU, Lactobacillus rhamnosus – 1.25×109 CFU. The dynamics of symptoms was assessed using the Gastrointestinal Symptom Rating Scale, and the composition of the microbiota before and after taking the probiotic was analyzed by sequencing 16S pRNA of stool samples. Results. In both groups, we found a statistically significant decrease in the level of Proteobacteria and an increase in Firmicutes. In patients with IBS-C, there was a decrease in Negativicutes, which, on the contrary, increased in patients with IBS-D. Shannon's diversity index in patients with IBS-C was statistically significantly lower than in patients with IBS-D 1.55 vs 2.74 (p=0.1). Against the background of the application, there was an increase in microbial diversity in patients with IBS-D, it increased to 3.01, and in patients with IBS-C to 2.68. Against the background of changes in the microbiota, there was a positive dynamics of disease symptoms against the background of taking probiotics. Conclusion. The results obtained reflect the positive effect of probiotics in patients with IBS-D and IBS-C, which makes it possible to clarify the role of microbiota in the development of IBS and recommend their use as part of complex therapy for this disease.

BACKGROUND:Ankylosing spondylitis (AS) is a chronic inflammatory disease known for causing pain, stiffness, and reduced mobility in the axial skeleton. Adalimumab, a tumor necrosis factor (TNF) inhibitor, has emerged as a promising therapeutic option for AS. METHODS:This systematic review involved a comprehensive search of randomized controlled trials related to AS treatment, conducted in major databases such as MEDLINE, Google Scholar, and PubMed. The search terms encompassed ankylosing spondylitis, adalimumab, methotrexate, other non-biologic DMARDs, glucocorticoids, NSAIDs, and analgesics. A total of 14 randomized controlled trials with 4,500 participants were included in the review. RESULTS:The review's results revealed that adalimumab demonstrated notable superiority when compared to a placebo. It effectively reduced disease activity, improved physical function, and lowered inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate. Adalimumab demonstrated a favorable safety profile, with adverse events comparable to those observed with placebo. CONCLUSION:Based on the results, adalimumab is deemed an effective treatment for AS, showcasing its potential as a first-line therapeutic option. Notably, no significant increase in adverse events was observed compared to placebo. However, the conclusion emphasizes the need for further studies with extended follow-up durations to ascertain the long-term efficacy and safety of adalimumab in AS management. This systematic review provides valuable insights supporting the use of adalimumab in the treatment of AS and underscores the importance of ongoing investigations into its long-term effects to optimize its clinical utilization in AS patients.