Pharmateca

Background: As a rule, the effectiveness of β-blocker therapy is assessed based on its effect on individual structural and functional cardiac parameters. Due to their heterogeneity, a comprehensive assessment of the functional state, including regulatory-adaptive status (RAS), exercise tolerance, and quality of life (QOL), is necessary to monitor the effectiveness of beta-blocker therapy in chronic heart failure (CHF).

Objective: Comparative assessment of the effects of bisoprolol and nebivolol on the functional status of patients with CHF and preserved left ventricular (LV) ejection fraction (EF) associated with stage III arterial hypertension.

Materials and methods: This study enrolled 80 patients with CHF and preserved LVEF ≥ 50%. Participants were randomly assigned to receive bisoprolol or nebivolol. Combination therapy included quinapril, as well as enteric-coated atorvastatin and aspirin (acetylsalicylic acid) if indicated. A comprehensive diagnostic program was administered throughout the 24-week study. A quantitative assessment of RAS was performed using a cardiorespiratory synchronization (CRS) test at baseline and at the end of therapy. Echocardiography, a treadmill test, and a 6-minute walk test were also performed. Patients’ QOL was assessed subjectively; N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined, and 24-hour blood pressure monitoring was performed.

Results: A positive effect on structural and functional parameters of cardiac function was observed in both study groups. Nebivolol demonstrated a more pronounced increase in RAS compared to bisoprolol. Furthermore, it contributed to increased exercise tolerance and improved QOL in patients.

Conclusion: A comparative analysis of the effects of nebivolol and bisoprolol on the functional status of patients with CHF and preserved LVEF associated with stage III arterial hypertension demonstrates that nebivolol has a more pronounced positive effect.

Vericiguat is the first in a new pharmacological class of soluble guanylate cyclase (sGC) stimulators, recently discovered and approved for the treatment of heart failure (HF). Vericiguat has a unique mechanism of action – it specifically targets the NO-sGC-cGMP pathway, which plays a key role in the pathophysiology of HF. By increasing cGMP, vericiguat enhances the natural mechanisms of cardiac contractility and vasodilation, improving cardiac function and alleviating symptoms in patients with HFrEF. This mechanism of action makes vericiguat a valuable adjunct to HF therapy for improving treatment outcomes. Based on the results of large RCTs, vericiguat is considered a second-line therapy for patients with the HF phenotype and low EF as an adjunct to guideline-based therapy. Vericiguat has been approved by the FDA and EMEA as the first sGC-stimulating agent for the treatment of patients with recently worsened CHF with reduced ejection fraction (REF) to reduce the risk of cardiovascular death and hospitalization. The drug has a well-studied biopharmaceutical, pharmacokinetic, and pharmacodynamic profile, allowing for once-daily administration. It also has a limited spectrum of drug interactions and is well-tolerated in CHF patients. With further study, vericiguat has the potential to revolutionize the treatment of CHF by improving outcomes and quality of life.

Background: Diffuse peritonitis complicated by intestinal fistulas is one of the most challenging problems in abdominal surgery, characterized by a vicious cycle of pathophysiology and high mortality rates (up to 40–60%). The management of patients with combined pathology – peritonitis, open abdomen syndrome, and small intestinal fistulas – is particularly challenging.

Objective: Systematization of current understanding of the etiology, pathogenesis, and comprehensive treatment of this patient population.

Methods: A review of domestic and international literature, including clinical guidelines, systematic reviews, and original studies on surgical tactics, intensive care methods, and nutritional support, was conducted.

Results: Treatment success is determined by a staged approach based on the principles of damage control surgery. The primary goal is surgical control of the source of infection and the use of an open-abdomen strategy using negative pressure wound therapy (NPWT). Conservative treatment of fistulas, including active drainage, targeted antimicrobial therapy, pharmacological secretion reduction (octreotide), and individualized nutritional support, is the first-line treatment. Radical interventions are deferred until the patient is stabilized. The choice of strategy should be based on comprehensive classifications (Belokonev-Izmailov, Bjorck) and prognostic scales (SOFA, APACHE II, MPI).

Conclusion: The management of patients with peritonitis and intestinal fistulas requires a multidisciplinary approach, a thorough understanding of pathophysiology, and strict adherence to the appropriate stages. Despite progress, further development and validation of unified algorithms based on evidence-based medicine is required.

The cytochrome P450 (CYP) system is a superfamily of heme-containing enzymes that play a key role in the metabolism of xenobiotics, including the vast majority of drugs, as well as endogenous compounds (steroids, bile acids, fatty acids). Regulation of CYP activity is a complex process influenced by multiple factors. Proinflammatory cytokines such as interleukin-6, interleukin-1β, tumor necrosis factor-alpha, and interferon-gamma are potent suppressors of the expression and activity of major CYP isoforms. This review examines the molecular mechanisms underlying cytokine-mediated CYP regulation, including the suppression of gene transcription through the JAK-STAT, NF-κB, and MAPK pathways and post-transcriptional modifications, and highlights the clinical significance of this phenomenon. Understanding these mechanisms is essential for personalizing pharmacotherapy and developing new strategies for predicting drug interactions in systemic inflammation.

Background: Intra-articular hyaluronic acid (HA) administration is a common method for the symptomatic treatment of knee osteoarthritis (OA). Various HA administration regimens are used in clinical practice; however, the rational choice of treatment frequency, taking into account clinical efficacy and cost effectiveness, remains poorly understood.

Objective: Comparative evaluation of the clinical efficacy and pharmacoeconomic feasibility of single- and triple-dose hyaluronic acid administration regimens in patients with knee osteoarthritis. Material and methods: Data from an observational study including 216 patients with knee OA (108 patients in each group) were analyzed. Patients received HA therapy according to two regimens: a single administration of the cross-linked form and three administrations of the linear form. Efficacy was assessed based on changes in WOMAC scores, the visual analogue scale (VAS), the self-assessment scale, and the EQ-5D-3L. A pharmacoeconomic analysis of direct medical costs was additionally performed, taking into account the cost of medications and the intra-articular injection procedure.

Results: Statistically significant improvements in clinical and functional parameters were noted in both groups. After treatment, a decrease in pain severity according to the VAS, a reduction in the total WOMAC score, and an improvement of quality of life indicators were observed. No intergroup differences in key clinical parameters were found, indicating comparable efficacy of the different treatment regimens. Adverse events were predominantly mild, with no statistically significant differences between the groups. A pharmacoeconomic analysis showed that, with comparable clinical efficacy, a single-dose regimen was associated with reduced direct costs due to a reduced number of procedures. The total cost of treatment with the single-dose regimen was lower compared to the triple-dose regimen.

Conclusion: Single and triple-dose hyaluronic acid administration for knee osteoarthritis exhibit comparable clinical efficacy and safety. Moreover, the single-dose regimen is more cost-effective, which can be considered as a factor in choosing a treatment strategy.

Background: This article describes a three-year clinical follow-up of a 59-year-old patient with severe spastic hemiparesis after an ischemic stroke. He underwent four rehabilitation courses using high-tech rehabilitation methods and botulinum toxin therapy.

Objective: Evaluation of the significance and timeliness of rationally selecting rehabilitation measures for severe post-stroke spastic hemiparesis and the impact of rehabilitation potential on the patient’s recovery and adaptation.

Conclusion: Evaluation of rehabilitation results using clinical scales revealed a reduction in spasticity, a clinically significant increase in muscle strength in the proximal portions of the paretic arm, improved cognitive function and sleep quality, and decreased anxiety and depression. The key outcome of rehabilitation was an improvement in the patient’s quality of life and increased adaptation to the environment, which, in our opinion, is due to a strong motivational focus, timely compensation for affective disorders, and appropriately selected repeated courses of rehabilitation measures.

This article examines vitamin D deficiency in children as a significant risk factor for mineral metabolism disorders, as well as immune and metabolic disorders. Despite the implementation of preventive programs, the high prevalence of vitamin D deficiency in the pediatric population, including in the Russian Federation, is highlighted. Particular attention is paid to children with gastrointestinal diseases, in whom deficiency develops due to impaired absorption of fat-soluble vitamins.

The mechanisms of vitamin D absorption and the role of micellar solubilization involving bile acids are analyzed. It has been shown that micelle formation processes are impaired in cholestasis, malabsorption, and other gastrointestinal pathologies, reducing vitamin D bioavailability and increasing the risk of clinically significant deficiency.

This article examines current approaches to correcting vitamin D deficiency, including the use of micellar and nanoemulsion formulations with improved bioavailability. Clinical and experimental data confirming the efficacy of such formulations, particularly in patients with digestive disorders are presented. It is concluded that innovative vitamin D formulations are beneficial in pediatric practice to enhance the prevention and treatment of deficiency, as well as improve therapy adherence.

Background: Vitiligo is an acquired autoimmune disease characterized by depigmentation of the skin and mucous membranes. It is caused by damage to determined melanocytes by effector cells. Exposomal trigger factors, as well as congenital and adaptive autoimmune activation of the immune system in the skin and mucous membranes, play a key role in the development of the disease. The effectiveness of vitiligo treatment depends on the appropriate choice of treatment method based on the stage of the disease. In the progressive stage of the disease, systemic and topical immunosuppressive agents are typically used, while in the subacute and chronic stages, phototherapy combined with adjuvant therapies aimed at repigmentation of the lesions is effective.

Objective: This article discusses the role of key immunological biomarkers in choosing a treatment method for vitiligo. An analysis of the correlation between increased chemokine levels in the peripheral blood and clinical and morphological signs of disease progression is presented.

Materials and methods: Plasma samples from patients with advanced vitiligo (n = 38) were analyzed. There were 20 men and 18 women. 81.6% (31 patients) had the acute or subacute stage of the disease (progressive vitiligo), while 18.4% (7 patients) had chronic vitiligo. All patients underwent peripheral blood testing for CXCL9, CXCL10, and CXCL11 chemokine levels at different stages of the disease.

Results: Analysis of the obtained data revealed significantly elevated chemokine levels in patients with vitiligo compared to healthy individuals: CXCL9 – 3401.00 pg/ml versus 1138.00 pg/ml, p < 0.001; CXCL10 – 724.00 pg/ml versus 201.30 pg/ml, p < 0.001; CXCL11 – 431.10 pg/ml versus 170.00 pg/ml, p = 0.018. However, when comparing the parameters within the study group, the concentrations of CXCL9, CXCL10, CXCL11 were significantly increased in patients in the acute and subacute stages compared to patients with chronic vitiligo: CXCL9 – 2890.00 pg/ml versus 1683.00 pg/ml, p < 0.001; CXCL10 – 678.00 pg/ml versus 346.00 pg/ml, p < 0.001; CXCL11 – 342.00 pg/ml versus 249.00 pg/ml, p = 0.016. Peripheral blood chemokine levels in patients with chronic vitiligo were slightly elevated compared to healthy control subjects: CXCL9 1683.00 pg/ml vs. 1138.00 pg/ml, p < 0.001; 346.00 pg/ml vs. 201.30 pg/ml, p < 0.001; 249.00 pg/ml vs. 170.00 pg/ml, p = 0.014. Increased peripheral blood CXCL9, CXCL10, and CXCL11 levels were detected during the acute stage of the disease, while in patients with chronic vitiligo, these chemokine levels remained within normal limits.

Conclusion: Increased levels of certain chemokines in peripheral blood may indicate the acute stage of vitiligo, requiring immunosuppressive therapy. Moreover, ultraviolet irradiation of vitiligo lesions during the acute phase will be ineffective and may even worsen the disease.

Objective: Assessment of the risk of abnormal cervical cytology results (atypical squamous cells of undetermined significance) depending on the composition of the vaginal microbiota in patients with chronic endometritis (CE).

Materials and methods: Design: analytical case-control study. Allocation into groups: Group I (n = 496) – patients with CE and ASCUS; Group II (n = 630) – patients with CE and no ASCUS. Examination methods – clinical and laboratory tests – determined the presence of opportunistic bacteria using real-time polymerase chain reaction (PCR) (qualitative and quantitative methods) and viruses (qualitative method), and an oncocytological examination was performed.

Results: In patients with CE, with a positive human papillomavirus (HPV) result, the risk of ASCUS was 15 times higher compared to patients with a negative HPV status (OR = 15.44, 95% CI 4.86–49.02, p < 0.001) in the absence of other indicators. Asymptomatic shedding of the herpes simplex virus (HSV) increased the risk of ASCUS by 6 times compared to its absence (OR = 6.03, 95% CI 1.73–20.95), p < 0.001). On the contrary, in this case, no vaginal dysbiosis was detected in patients, and the risk of ASCUS was the same as in patients with normocenosis (OR = 0.94, 95% CI 0.82–1.80, p = 0.41). However, one in three patients with CE and ASCUS were found to have co-infections, which increased the risk by 2-fold (OR = 2.32, 95% CI 2.08–2.59, p < 0.001) and by 1.5-fold (OR = 1.44, 95% CI 1.12–1.85, p = 0.03) for anaerobic dysbiosis. In the presence of vaginal dysbiosis, the risk of HPV infection was 1.5-fold higher, as was the risk of HSV infection.

Conclusion: In the overall cohort of patients with CE, vaginal dysbiosis, compared with normal vaginal dysbiosis, did not demonstrate an association with ASCUS, regardless of HPV status. The presence of a co-infection in the vagina increases the risk of ASCUS by 2-fold and anaerobic dysbiosis by 1.5-fold.

Background: Modern advances in cancer treatment have significantly increased patient survival; however, side effects of therapy, particularly cardiotoxicity, are becoming a serious problem. The incidence of cancer increases with age, and patients often have pre-existing cardiovascular disease or risk factors for its development. This necessitates the study of the cardiotoxicity of anticancer therapy, as well as the search for an approach to the diagnosis, monitoring, and treatment of cardiovascular complications.

Objective: Review of the literature and identification of the most common types of cardiotoxicity associated with modern anticancer drugs in patients at high cardiovascular risk, discussion of specific diagnostic, monitoring, and treatment options for adverse cardiovascular events.

Methods: From February to April 2025, a search of the PubMed, Google Scholar, and Cyberleninka databases was conducted using the following keywords: anticancer therapy cardiotoxicity, CTRCVD, high cardiovascular risk, cardiotoxicity diagnosis and treatment, and CTRCD diagnosis and treatment.

Results: A literature review identified the most cardiotoxic anticancer drug classes, with a description of the mechanism for the development of this side effect for each. Current methods for assessing the risk of cardiovascular toxicity in cancer patients, as well as approaches to diagnosis, monitoring, and drug prevention of cardiotoxicity in high-risk patients, were also presented.

Conclusion: Cardiologists and oncologists should pay attention to the risks of cardiotoxicity of anticancer therapy and ensure individualization of therapy after a thorough assessment of the benefits of a specific anticancer agent and the possible risk of cardiotoxicity.

Background: Anemia of chronic disease is one of the most common types of anemia worldwide and the most common form in people with chronic diseases. The development of this anemia aggravates the patient’s condition, leads to progression of the underlying disease, and worsens the prognosis; therefore, patients require timely treatment.

Objective: Comparison of the pharmacokinetics of iron supplements in patients with iron deficiency associated with anemia of chronic disease versus patients with isolated iron deficiency anemia.

Materials and methods: A prospective, open-label, cohort, single-center study was conducted in patients with a laboratory-confirmed diagnosis of anemia. One group included patients with iron deficiency anemia, and the other included patients with iron deficiency associated with anemia of chronic disease and elevated hepcidin levels. Blood samples were collected over two days to assess the pharmacokinetics of iron supplements. On the first day, serum endogenous iron concentrations were measured, and on the second day, values were assessed after administration of tablets containing 200 mg of ferrous sulfate and 120 mg of ascorbic acid.

Results: The study included 30 female patients (15 patients in each group) aged 41 to 67 years. There were no statistically significant differences in age or hemoglobin levels between the study groups. Ferritin and hepcidin levels were statistically significantly higher in the group of patients with iron deficiency anemia of chronic disease.

The mean AUC (and standard deviation) after taking the iron supplement, calculated with adjustment for background endogenous iron levels based on pre-treatment data, was 39.80 (19.75) μmol*h/L in the group of patients with iron deficiency anemia of chronic disease and was statistically significantly lower than the AUC value in the group of patients with iron deficiency anemia (p < 0.05), which was 150.19 (71.58) μmol*h/L. The relative bioavailability of iron in the group of patients with iron deficiency in anemia of chronic disease compared to the group of patients with iron deficiency anemia was 26.5%. The mean value of the maximum concentration Cmax after taking the iron preparation in the group of patients with iron deficiency in anemia of chronic disease was also statistically significantly lower than the value in the group of patients with iron deficiency anemia (5.4 [3.5] μmol/L versus 25.2 [7.4] μmol/L, respectively, p < 0.05), and Cmax was achieved in the group of patients with iron deficiency in anemia of chronic disease statistically significantly later (after 6.9 [1.2] hours versus 3.2 [0.9] hours, p < 0.05).

Conclusion: In patients with iron deficiency and elevated hepcidin levels in anemia of chronic disease, iron bioavailability after taking oral preparations containing it is significantly reduced compared to patients with isolated iron deficiency anemia. For patients with anemia of chronic disease, other treatment strategies should be considered.

Treatment adherence is one of the key modifiable factors determining the achievement of clinical goals in chronic and socially significant diseases. The Interdisciplinary Expert Council examined the issue of treatment adherence and proposed a set of measures to its improvement with the aim of reducing the incidence of adverse outcomes in socially significant diseases, increasing life expectancy and quality of life, and optimizing healthcare costs. The Expert Council proposed a number of practical tools that can be integrated into routine doctor visits. Without additional time investment, they have proven effectiveness and can have a significant impact on the quality of communication with patients and the development of adherence. Recommendations for organizational measures, personnel training, improving the status of physicians, and changes at the public policy level are formulated.

Background: In the Russian Federation, diseases associated with spinal osteochondrosis account for approximately 50% of the total morbidity of the population. Half of patients with signs of spinal osteochondrosis experience symptoms of chronic emotional stress, accompanied by pain syndrome (PS). Lumbar osteochondrosis can be caused by various microtraumas sustained during physical activity, poor diet, and a sedentary lifestyle.

Objective: Evaluation of the effectiveness of physical rehabilitation in patients with spinal osteochondrosis.

Materials and methods: The study included 18 men and women, aged 35 to 45 years, with spinal osteochondrosis. All subjects were divided into two groups: an experimental group (9 patients) and a control group (9 patients). Those in the control group used standard physical rehabilitation methods (therapeutic exercise, massage, and physiotherapy). The experimental group used Texnogym exercise machines and block trainers, as well as therapeutic exercise and massage for 30 days.

Results: In experimental group, most patients (92%) reported a reduction in pain after exercise. Complete regression of PS was observed in 82% of cases. Flexibility testing showed a decrease in tension in the posterior functional muscle chains.

Conclusion: After physical rehabilitation, lumbar spine mobility increased. Back muscle strength endurance increased by 75%, and rectus abdominis strength by 65%.