Том 32, № 4 (2025)

Sildenafil and tadalafil are selective PDE5 inhibitors for the treatment of erectile dysfunction (ED) that have vasodilatory properties mediated through NO and cGMP via smooth muscle relaxation. PDE5 inhibitors are approved for the treatment of ED, but only tadalafil is approved for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia. The association between ED, LUTS, and cardiovascular disease (CVD) has been established. Due to the expression of PDE5 in the cardiovascular system, potential mechanisms of PDE5 inhibitors include improvement of endothelial function, vasodilation with modest reductions in BP and afterload, direct myocardial protection, and anti-inflammatory and antiplatelet effects, which support the beneficial effects of PDE5 inhibitors in CVD. In experimental models, PDE5 inhibitors reduced myocardial ischemic reperfusion injury and arrhythmia, confirming their cardioprotective effect. Early clinical trials examined the effect of PDE5 inhibitors in patients with concomitant diabetes mellitus and showed a reduction in the incidence of myocardial infarction and mortality. Recent large cohort studies examined the long-term effects of PDE5 inhibitors on the risk of CVD and cardiovascular events. Two studies showed a significant reduction in the risk of MACE with tadalafil therapy by 19% (OR=0,81) and the risk of MACE/venous thromboembolism by 41% (OR=0,59). In a new study, the use of sildenafil and tadalafil led to a 34% and 44% reduction in the risk of mortality (OR=0,76 and OR=0,66), as well as a significant reduction in the risk of myocardial infarction, stroke, venous thromboembolism and even dementia in patients with ED and LUTS, with tadalafil having an advantage over sildenafil. According to the results of a meta-analysis of 16 studies, PDE5 inhibitors reduced the risk of MACE by 22% (OR=0,78) and the risk of overall mortality by 30% (OR=0,70).

Thus, new data on PDE-5 inhibitors were obtained, confirming not only the safety of the cardiovascular system, but also showing the presence of important cardioprotective properties.

Finerenone is the first non-steroidal antagonist of mineralocorticoid receptors (MCR), which has high affinity and selectivity for MCR, as well as significant differences from steroid analogs in physicochemical, pharmacodynamic and pharmacokinetic properties. A number of studies confirm the protective role of finerenone due to its anti-inflammatory, antifibrotic and antiremodeling effects in cardiac and renal tissues, which ensures clinical efficacy in reducing the incidence of cardiovascular outcomes. Clinical studies have demonstrated not only the renal-protective effect of finerenone, slowing the progression of chronic kidney disease (CKD), as assessed by the composite renal outcomes/death from renal causes, but also a reduction in the incidence of cardiovascular outcomes (including cardiovascular mortality, hospitalization for heart failure, non-fatal myocardial infarction and non-fatal stroke). Special studies have demonstrated a favorable effect of finerenone on the development of new-onset chronic heart failure (CHF) and CHF-related outcomes, regardless of the presence of CHF in the anamnesis. In addition, the effectiveness of finerenone in patients with CHF is observed across the entire range of ejection fraction (EF), reducing the risk of cardiovascular death and the incidence of hospitalization for CHF. All available data indicate that finerenone, being safe and well tolerated, has a high potential for preventing morbidity and mortality in a wide range of cardiorenal-metabolic syndrome conditions.

Background: Gastritis is a histological diagnosis, although its prevalence is decreasing in developed countries along with the prevalence of Helicobacter pylori infection. We identified H. pylori-positive (Hp+) and H. pylori-negative (Hp-) gastritis variants to analyze relationships that have not been adequately studied in previous studies.

Objective: Evaluation of the clinical, laboratory, and histological changes in the gastric mucosa in Hp+ and Hp- gastritis.

Materials and methods: We examined 122 patients (62 with Hp+ and 60 with Hp- gastritis) aged 20 to 65 years. In addition to conventional clinical and biochemical tests, the laboratory tests included the Gastropanel. For the diagnosis of Helicobacter pylori, 2-3 available methods were used for each patient. All study participants underwent esophagogastroduodenoscopy with morphological examination of biopsy specimens according to OLGA/OLGIM criteria. The vegetative status of the examined patients was assessed. All patients were prescribed treatment for gastritis, depending on the presence of Hp infection. Differences between the comparison parameters were considered statistically different at p≤0.05.

Results: Hp- gastritis was more often verified in the antral section, while Hp+ gastritis almost always affected both the antral section and the stomach body. Metaplasia according to OLGIM 0–I was observed only in 9 patients with Hp+ gastritis (p>0.05). In the vegetative status, vagotonia prevailed, in contrast to the control (p>0.05). All patients with Hp+ gastritis were prescribed anti-Helicobacter therapy. A number of patients chose a combination composition with the commercial name Pilobact^® AM and bismuth tripotassium dicitrate for 14 days, had an eradication level of 87.4%. We conducted a pharmacochemical comparative analysis of the drugs included in Pilobact^® AM with reference drugs and obtained their high comparability.

Conclusion: Significant differences in clinical and laboratory parameters in patients with Hp+ Hp- gastritis were revealed only in morphological data. One of the anti-Helicobacter treatment options can be the Pilobact^® AM combination, which has proven both its high efficiency in clinical observations and pharmacochemical comparability with reference drugs.

Background: Currently, significant importance is attached to comorbidity in gastrointestinal diseases. Comorbidity of gastroesophageal reflux disease and irritable bowel syndrome is associated with the presence of common pathophysiological mechanisms and is associated with a decrease in the quality of life.

Description of the clinical case: The article considers a clinical case of overlap syndrome of gastroesophageal reflux disease with erosive esophagitis and irritable bowel syndrome in a 37-year-old patient, as well as the effectiveness of therapy using a proton pump inhibitor and a selective myotropic antispasmodic in this case.

Conclusion: The combination of a PPI (pantoprazole) and a selective myotropic antispasmodic (mebeverine hydrochloride) can be considered when choosing therapy in comorbid patients.

Hassall’s corpuscles are unique epithelial structures of the thymus medulla. Despite the long history of thymic corpuscle research, their functions and structural features still require further study. This review analyzes modern literature data on the structure, origin, and functional role of Hassall’s corpuscles in health and various pathologies. It is shown that the main structural component of the corpuscles are medullary thymic epithelial cells (mTEC) at the terminal stages of differentiation, which undergo keratinization similar to epidermal cells. In addition to mTEC, the bodies include microenvironment cells: dendritic cells, macrophages, myoid cells, and lymphocytes. Modern studies using single-cell RNA sequencing and spatial transcriptomics have shown that «aging» mTEC of Hassall’s corpuscles produce a wide range of cytokines, chemokines, and antimicrobial peptides, forming a specific proinflammatory microenvironment of the thymus medulla. The interaction of secreted factors with cells of innate and adaptive immunity plays an important role in the processes of negative selection of autoreactive thymocytes and differentiation of regulatory T-lymphocytes. Structural and functional changes in Hassall’s corpuscles observed in age-related thymus involution and various pathological conditions can lead to a violation of central immunological tolerance and the development of autoimmune diseases. Thus, Hassall’s corpuscles are not only morphological markers of thymus involution, but also functionally active structures involved in maintaining thymic homeostasis. Further studies of the molecular mechanisms that control the morphogenesis and activity of Hassall’s corpuscles may open up new possibilities for developing approaches to correcting age-related changes in the immune system.

Background: Bromdihydrochlorophenylbenzodiazepine is a domestic benzodiazepine tranquilizer used in the treatment of alcohol withdrawal syndrome (AWS). Therapeutic drug monitoring (TDM) of bromdihydrochlorophenylbenzodiazepine has not been sufficiently studied.

Objective: Analysis of the associations of phenazepam and oxyphenazepam TDM parameters with the development of adverse reactions (ARs) during the treatment of AWS in men, taking into account pharmacogenetic and clinical factors.

Materials and methods: The study included 102 male patients diagnosed with AWS (F10.30 according to ICD-10). All patients were prescribed bromdihydrochlorophenylbenzodiazepine. On the 6th day, the presence of ARs was assessed using the UKU Side-Effects Rating Scale. Venous blood samples were obtained from each patient for TDM and pharmacogenetic testing of polymorphic variants of CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3 and CYP2C19*17.

Results: The mean age of 100 participants (2 samples spoiled) was 41.42±8.5 years. The mean concentrations of bromdihydrochlorophenylbenzodiazepine (216.04±144.68 ng/ml) and oxybromdihydrochlorophenylbenzodiazepine (59.34±42.98 ng/ml) were determined among patients. The dose-normalized concentrations were 38.15±28.44 ng/ml for bromdihydrochlorophenylbenzodiazepine and 10.47±34.11 ng/ml for the metabolite, respectively. The concentration of bromdihydrochlorophenylbenzodiazepine was significantly higher in patients with the AR “Constipation” (72.5 [37.75; 154.5] versus 34 [16.25; 46] ng/ml; p=0.034). The presence of the ARs “Asthenia/lethargy/fatigue” and “Constipation” was associated with a higher concentration of oxybromdihydrochlorophenylbenzodiazepine (10 [7; 14] vs. 8 [5; 11] ng/ml; p=0.013 and (27 [9.25; 43.25] vs. 9 [6, 12] ng/ml; p=0.03), respectively. The AR “Depression”, on the contrary, was more often observed among patients with a lower concentration of bromdihydrochlorophenylbenzodiazepine (27 [12; 34] vs. 38 [23; 47.5] ng/ml; p=0.023). No associations were found between polymorphic variants of CYP3A5*3, CYP2C9*2, *3, CYP2C19*2, *3, *17 and TDM data of phenazepam.

Conclusion: In this study, the blood bromdihydrochlorophenylbenzodiazepine and oxybromdihydrochlorophenylbenzodiazepine concentrations in patients with AWS was determined for the first time. Increased plasma concentration of oxybromdihydrochlorophenylbenzodiazepine was associated with an increase in the frequency of any adverse reactions (subjectively and objectively), separately the frequencies of the adverse reactions «Asthenia / lethargy / increased fatigue» and «Constipation». In patients with complaints of depression, a lower concentration of bromdihydrochlorophenylbenzodiazepine was noted.

Background: Application of therapeutic exercises after stroke helps to restore movement of the affected limb and muscle strength, eliminate motor disorders and lost social and everyday functions, improve the psychological state, activate the patient, and reduce the risk of recurrent stroke. For rehabilitation of patients after a stroke, the use of robot-assisted devices provides verticalization of patients, elimination or reduction of paresis and paralysis of the limbs.

Objective: Assessment and restoration of the motor activity of the upper limb and social and everyday skills in people aged 55–60 years after a stroke.

Methods: All patients received standard therapy, including neuromuscular electrical myostimulation, limb massage and individual therapeutic exercise sessions to improve and restore fine motor skills. Also, training using the Armeo robotic complex was included in rehabilitation program of 6 patients of the experimental group. Before and after rehabilitation, the functions of the affected upper limb (abduction/adduction, flexion/extension of the shoulder and elbow joint, rotational and rotary movements of the hand) were assessed in both groups of post-stroke patients.

Results: The use of therapeutic exercises in passive and passive-active modes allowed to reduce muscle tone, improve abduction and adduction of the shoulder joint, flexion and extension of the shoulder and elbow joints, and stimulate more active movements due to the reflex influence of afferent impulses arising in the muscles and joints of the paralyzed limb. The use of the Armeo robotic complex allowed to increase the range of motion, compensate for movement deficiencies, the strength of the affected limb, reduce neurological deficit, and improve the psychoemotional state.

Conclusion: In order to restore impaired functions of the upper limb, robot-assisted therapy was used, which allowed to increase the effectiveness of rehabilitation through repetitive cyclic exercises, improve the activity and quality of life of patients. After rehabilitation with the use of therapeutic exercises, social and everyday skills significantly expanded in both groups of patients.

Anxiety disorders are the most common type of mental illness. Due to their high prevalence (3.3% of the global disease burden), chronic course and a large number of comorbidities, anxiety disorders are among the nine leading causes of disability. The presence of anxiety in heart disease, cancer or lung disease negatively affects the quality of life, treatment adherence, prognosis and treatment costs. Anxiety disorders are treated using psychotherapy, pharmacotherapy or a combination of both. Benzodiazepines are an effective treatment for anxiety, if prescribed as directed and with control over adverse events, some of which are described in the article. Unlike SSRIs, which are first-line drugs for treating anxiety disorders, the anxiolytic effect of which develops only after 2–4 weeks of use, benzodiazepines provide a rapid pharmacological response with reduction of anxiety symptoms within a short time. In this regard, their use is advisable in short courses for rapid symptom relief. Diamidazepam, a member of the benzodiazepine group, combines a powerful anti-anxiety effect with an activating and anti-asthenic effect, while being virtually devoid of the side effects of classic benzodiazepines in the form of excessive sedation, drowsiness, and muscle relaxation.

Background: Manifestation of psoriasis is attributable to the genetic predisposition and the influence of environmental agents (pesticides, sulfur and nitrogen dioxide, heavy metals, hydrocarbons). Psoriasis is associated with a persistent tendency to the formation of comorbid pathology, such as joint, cardiovascular, endocrine, renal, hepatic, neurological, as well as uveitis and metabolic disorders. In connection with the above mentioned, an integrated interdisciplinary approach is necessary in the follow-up care of patients with psoriasis and a personalized selection of a treatment regimen.

Objective: Development of mechanisms for preventing relapses and complications of psoriasis occurring against the background of multiple organ pathology and environmental stress.

Materials and methods: The study included 84 patients with psoriasis living in nine municipalities of the Republic of Dagestan - in five districts and four cities.

Results: The study group had a high frequency of arthropathy (from 45.5% to 80.0%) and pain syndrome in one of the joints (from 45.5% to 100.0%). Combination therapy for arthralgia included nonsteroidal anti-inflammatory drugs (NSAIDs) (34.52%, CI 95%: 24.8–45.0%) and glucocorticosteroids (30.95%, CI 95%: 21.6–41.2%). Topical therapy and physiotherapy were used for stabili-zing and regressing the skin process and preventing arthropathy. Restoration of liver function was necessary in 53.57% (CI 95%: 42.9–64.1%) of patients. In an ecologically safe municipality (Khiva district), 32.0% of patients with psoriasis were removed from the follow-up care register in 2020–2023 due to long-term remission and the absence of relapses. In areas with a tense environment, for example, in the city of Khasavyurt, the proportion of those removed from the register was 3.2%, in the Derbent district – 1.7%, the differences with the Khiva district were statistically significant in all cases (p<0.001). The above mentioned trend was recorded in all administrative units with a tense environment.

Conclusion: In conditions of environmental pollution and multimorbidity, resistance to therapy and the development of psoriasis complications are noted. An interdisciplinary approach to dynamic monitoring with the involvement of leading specialists contributes to the prevention of disabling psoriasis complications.

The prevalence of allergic rhinitis (AR) in Russia depends on the region, climate zone and occupies from 18 to 33.2% in the structure of respiratory allergic diseases. Against the background of an increase in the number of patients with respiratory allergies, a tendency towards aggravation of symptoms is noted. Thus, among patients with allergic rhinitis, 62.7% have moderate and severe forms. About 35-40% of patients, despite adequate treatment, according to the recommendations of medical specialists, do not achieve control over the symptoms of allergic rhinitis. Symptoms of allergic rhinitis, such as nasal congestion, nasal discharge, sneezing and itching, can significantly affect everyday life, quality of sleep and lead to psychological and social problems. The growing trend in the number of patients with uncontrolled symptoms of AR indicates the need to optimize approaches to therapy and implement the principles of personalized medicine in order to achieve a higher level of symptom control, increase patient compliance and satisfaction with treatment. One of the approaches that meets modern requirements for efficacy and safety in patients with uncontrolled severe symptoms of allergic rhinitis is the use of genetically engineered biological drugs. The efficacy and safety of biological drugs is confirmed by clinical examples from real practice. The article presents a series of clinical cases of severe uncontrolled symptoms of AR against the background of standard pharmacotherapy. The addition of biological drugs to standard pharmacotherapy, in particular omalizumab, allows for faster control of AR symptoms, increased treatment effectiveness and reduced need for symptomatic therapy. High efficacy and good tolerability and safety profile of omalizumab, as well as long-term experience of use in children and adults, make it an optimal choice for additional therapy of moderate-severe seasonal AR symptoms, allowing to maintain a good quality of life of patients during the palination season.

A literature review of the pathogenesis, classification, clinical manifestations, diagnostics and treatment principles of hereditary palmoplantar keratoderma is conducted. Two clinical cases are presented. The first case is a 3-year-old girl and her mother with diffuse palmoplantar keratoderma type Unna-Thost (according to the patients words, similar lesions were found in the eldest daughter and grandfather). The second case is a 67-year-old patient with punctate palmoplantar keratoderma (Buschke-Fischer syndrome) in combination with bilateral cataracts and moderate neuropsychiatric disorders.

Gastric cancer is one of the most pressing problems in modern oncology. Surgery is currently the main treatment for resectable gastric cancer, but overall survival rates remain unsatisfactory. To date, combination therapy is the standard approach. Modern drug therapy, in addition to chemotherapy, includes targeted and immunotherapy, and it has changed significantly over the past few years. At the same time, perioperative chemotherapy regimens differ. In recent years, perioperative therapy using new agents such as targeted drugs and immune checkpoint inhibitors (ICIs) has also been investigated with promising results. Perioperative therapy has become an integral part of treatment strategies and requires further study. This review demonstrates modern perioperative therapy regimens, their recent achievements and presents future prospects.

Background: Arterial hypertension (AH) is the most common chronic non-infectious disease, against the background of which acute respiratory viral infection (ARVI) can occur.

Objective: Evaluation of the clinical features of AH in patients with ARVI of various etiologies (COVID-19, influenza, unspecified).

Material and methods: The retrospective comparative study included 373 patients. Patients with AH + ARVI of unspecified etiology (group 1A) – 98 people; AH + COVID-19 (group 1B) – 192 patients; AH + influenza (group 1B) – 12 patients. A group of patients with AH (group 2) was recruited as a control group – 71 patients, comparable by gender, age, AH stage and degree, the presence of complications. Statistical analysis was carried out using the STATISTICA 10.0 software packages.

Results: Against the background of acute respiratory viral infection, regardless of the etiological factor, patients showed an increase in both systolic and diastolic blood pressure (BP), more – with acute respiratory viral infection of unspecified etiology (80%) and COVID-19 (70% of patients), significantly less – with influenza (16.7%). This required treatment adjustments, in particular, a switch from monotherapy to combination antihypertensive therapy. In all patients with arterial hypertension, the course of ARVI was accompanied by tachycardia.

Conclusion: Early intensification of antihypertensive therapy during the development of ARVI of various etiologies in patients with AH history will help maintain control over the disease and prevent the development of vascular accidents.

Objective: Evaluation of the features of professional burnout in general practitioners and general and specialized surgeons.

Materials and methods: The study was carried out within the framework of the complex topic of the Department of Occupational Diseases and Clinical Pharmacology named after Honored Scientist of the Russian Federation Professor V.V. Kosarev, Samara State Medical University, «Problems of polymorbidity, diagnostics, prognosis and prevention of occupational and work-related diseases in workers with isolated combined exposure to factors of the production environment and the work process» (registration number 124053000016-4, date of registration 05/30/2024). The study included: Group 1 – gastroenterologists (n=52), Group 2 – cardiologists (n=58), Group 3 – oncologists of the therapeutic (T) profile (n=48), Group 4 – general surgical (GS) profile (n=71), Group 5 – cardiovascular surgeons (n=30), Group 6 – surgical oncologists (S) profile (n=65), Group 7 (control) – workers of engineering and technical and economic profiles, not related by the profile of their activities to work in medical organizations (healthy) (n=75). The level of professional burnout in medical workers was assessed using the MBI method developed by K. Maslach, S. Jackson, as adapted by N.E. Vodopyanova. Statistical analysis was performed using the RStudio programming language and environment (R v.4.4.1, RStudio 2024.09.1+394). Descriptive statistics for continuous data were calculated as the mean, 95% confidence intervals (CI), for nonparametric data – the median, 25% and 75% quartiles and interquartile range. Although the data did not correspond to a normal distribution, the groups were larger than 30 observations, which, according to the central limit theorem, allowed to use the mean and 95% CI to describe the variables. The χ² test was used to compare percentages. When assessing differences in nonparametric data groups, the Mann-Whitney criteria for two comparison groups and the Kruskal-Wallis tests for more than 2 groups were used.

Results: The professional activity of doctors of T and S profiles was associated with the impact of chronic professional stress, leading to the development of professional burnout.

Conclusion Thus, the obtained data indicated the need to use specialized rehabilitation measures for doctors using relaxation techniques, art therapy, as well as professional adaptation programs, physiotherapeutic techniques such as electrosleep and reflexology, if possible, spa treatment in sanatoriums-preventoriums, local sanatoriums, etc. with visits to psychotherapeutic offices, as well as psychopharmacological drugs when identifying risk factors for increasing the level of professional burnout in medical workers provi-ding medical care in hospitals of therapeutic, general surgical and specialized profiles.

Mine-blast injuries (MBI) are a serious medical problem in the context of modern military conflicts and terrorist attacks. The most common and severe complication of MBI is hearing loss, which significantly reduces the quality of life of victims, limiting their communication capabilities, contributing to social isolation, deterioration of cognitive functions and psychological state. Hearing loss in MBI develops as a result of the impact of shock and sound waves on the auditory apparatus, which leads to damage to the structures of the middle and inner ear, as well as the auditory nerve. There are conductive, sensorineural and mixed forms of hearing loss, each of which has its own pathogenesis features and requires specific approaches to diagnosis and treatment. Clinical manifestations vary from acute to chronic forms and are accompanied by varying degrees of hearing loss. Hearing loss resulting from MBI is caused by complex mechanical and pathophysiological processes occurring in the auditory apparatus under the influence of a shock wave. The shock wave, interacting with the tissues of the body, causes mechanical damage that affects the structures of the inner ear and the auditory nerve. Understanding the pathogenesis and clinical manifestations of hearing loss allows to develop effective methods of prevention, diagnosis and treatment, which helps improve the quality of medical care.