Vol 32, No 6 (2025)

Background: Deep vein thrombosis (DVT) is one of the most significant vascular diseases, often complicated by pulmonary embolism (PE). The high risk of recurrent DVT requires long-term secondary prevention, which dictates the need to select optimal anticoagulant therapy and continuously assess the balance between efficacy and safety.

Objective: Review of current strategies for secondary prevention of DVT, assessment of the risks and benefits of prolonged anticoagulant therapy, with an emphasis on the role of new direct oral anticoagulants (DOACs), in particular rivaroxaban and its generic Xyltess.

Results: An analytical review of current international and domestic clinical guidelines, as well as key prospective studies on secondary prevention of venous thromboembolic complications (VTEC) was conducted. Prolonged DOAC therapy showed the greatest effectiveness in preventing recurrent DVT and other VTEC. Idiopathic DVT, thrombophilia, proximal localization and concomitant oncology require an individualized approach to the duration of therapy. The generic drug rivaroxaban Xyltess is completely bioequivalent to the original, has European quality and improved accessibility for patients.

Conclusion: Prolonged secondary prevention of DVT using modern DOACs allows achieving an optimal balance of benefit and safety, reducing the risk of relapse and improving long-term clinical outcomes in most categories of patients.

Background: Optimizing therapy in patients at extremely high cardiovascular risk requires a balance between treatment effectiveness and the risk of polypharmacy. The concept of deprescribing is considered a promising approach to reducing the potential harm of drug therapy, including in patient groups at extremely high cardiovascular risk.

Objective: Critical evaluation of the effectiveness of a personalized approach to reducing polypharmacy by adapting treatment regimens with lipid-lowering agents, proton pump inhibitors, antihypertensive agents, and dual antiplatelet therapy based on a review of the scientific literature with elements of a systematic analysis.

Materials and methods: A search of the PubMed and Google Scholar databases was conducted from February to April 2025. Publications published between March 2019 and March 2025 were included in the analysis; the following set of keywords was used to generate the sample: deprescribing; arterial hypertension; antihypertensives; older adults; proton pump inhibitors; rosuvastatin; atorvastatin; cardiovascular disease; DAPT; prospective study; retrospective study; placebo-controlled.

Results: A pooled analysis of data from randomized and observational studies demonstrates the safety and efficacy of controlled decrease or discontinuation of these medications with strict risk stratification and dynamic monitoring. Targeted deprescribing can lead to a reduction in the incidence of side effects, a decrease in the number of drug interactions, and an improvement in adherence to therapy; however, in some patients, drug discontinuation is associated with the risk of adverse clinical outcomes.

Conclusion: Deprescribing in patients with extremely high cardiovascular risk is a clinically valid strategy for optimizing pharmacotherapy. Safe implementation of this approach requires consideration of the potential risks of drug discontinuation, comorbidities, and the patient’s functional status, as well as dynamic monitoring.

The review examines the possibilities of natural mineral waters rich in magnesium sulfate in functional gastrointestinal disorders. To date, three magnesium sulfate-rich natural mineral waters have been studied in randomized, double-blind, placebo-controlled clinical trials. A comparison of the effectiveness of the three studied mineral waters showed that the mineral water Donat is more effective. The results of a randomized clinical trial of mineral water Donat in the treatment of functional constipation are considered in detail, as well as the experience of its use in domestic studies that have demonstrated the effectiveness and safety of therapeutic mineral water Donat in pediatric practice and in adult patients with functional gastrointestinal disorders and, first of all, functional constipation.

The characteristics of the natural mineral water Donat allow us to consider it as the first choice for the treatment and prevention of functional gastrointestinal disorders in certain categories of comorbid patients. The rationale for the use of mineral water Donat for the treatment and prevention of the syndrome of pathology of the digestive system in connective tissue dysplasia is given. Mineral water Donat in patients with connective tissue dysplasia is an additional source of trace elements, primarily magnesium, which has a positive effect on other clinical manifestations.

Genetically engineered biological therapy (GEBT) of bronchial asthma (BA) is a modern method of treating severe forms of the disease that are uncontrolled by traditional pharmacotherapeutic approaches. Currently, six monoclonal antibody drugs for the treatment of severe bronchial asthma (anti-IgE – omalizumab), interleukin (IL)-5 antagonists (anti-IL-5 – mepolizumab, reslizumab) and its receptor (anti-IL-5Rα – benralizumab), as well as antibodies that selectively bind to the IL-4 and IL-13 receptor (anti-IL-4/13Rα - dupilumab) and tezepelumab, promoting the inhibition of thymic stromal lymphopoietin (TSLP) are registered in Russia.

A special group consists of patients with the eosinophilic phenotype of BA, characterized by a severe uncontrolled course and resistance to standard treatment regimens in accordance with the basic step therapy of the disease.

The article presents a clinical case of the effectiveness of GEBT using benralizumab as an example in a patient with severe uncontrolled bronchial asthma (eosinophilic phenotype).

Background: Varicella Zoster Virus (VZV) is a type III herpesvirus infection. Viral reactivation leading to the development of herpes zoster (HZ) is more common in older individuals, especially those with comorbidities, with the potential for severe disease progression and complications such as bacterial superinfection and postherpetic neuralgia. Suppression of innate and adaptive immunity plays a key role in controlling viral latency and reactivation. Standard treatment for herpes zoster includes etiotropic therapy with the antiviral drug acyclovir. However, given the frequency of herpes zoster recurrences and its immunosuppressive effects, immunomodulatory agents are necessary.

Objective: Evaluation of the effectiveness of herpes zoster therapy with the inclusion of the immunostimulant Superlymph^® in the traditional treatment regimen.

Materials and methods: Peripheral blood samples were analyzed from 40 patients with recurrent herpes zoster, divided into two comparable treatment groups (receiving only the traditional acyclovir regimen or combination therapy with the addition of the immunostimulant Superlymph) and 10 healthy control subjects matched for age and gender. Soluble toll-like receptor (sTLR) levels were determined in serum using ELISA. In addition, T-cell subset characteristics were determined using flow cytometry, and the cytokine profile was analyzed using ELISA.

Results: The study identified a range of key cytokine profile parameters, determined cellular (T-lymphocyte subsets) and innate (sTLR) immunity in patients with herpes zoster, and developed a differentiated approach to selecting immunocorrective therapy as part of the combination treatment of herpes zoster during the acute phase.

Conclusion: Dysfunction of various T-lymphocyte subsets, cytokine profile imbalance, and sTLR activation are important mechanisms for the development of herpes zoster relapses. These laboratory parameters substantiate the effectiveness of using an immunobiological suppository containing a complex of natural antimicrobial peptides and cytokines in combination therapy in at-risk patients.

Osteoarthritis is a disabling disease whose prevalence is constantly growing, resulting in an increasing economic burden on healthcare systems, including in Russia. The high cost of osteoarthritis therapy creates the preconditions for finding the most pharmacoeconomically optimal treatment options for this disease. This article analyzes existing clinical data on the efficacy and safety of the main osteoarthritis therapies, for which pharmacoeconomic studies have been conducted over the last ten years.

Acute insomnia (synonyms: short-term, adaptive, situational) is a disease with a characteristic disorder of sleep initiation and/or maintenance with the development of excessive daytime sleepiness syndrome, loss of daytime activity stimuli, limited in duration to a period from 1–2 weeks to 3 months. Despite the existing strategies of drug and non-drug correction, therapy of acute insomnia in patients with chronic non-communicable diseases (CNCDs) remains highly controversial. In this review, we analyzed the data of systematic meta-analyses and randomized clinical trials (RCTs) that expand our understanding of the mechanisms of acute insomnia development in patients with СNCDs, as well as new strategies for risk modification and correction of sleep disorders that are effective in real-life clinical practice.

Chronic migraine (CM) is a specific form of migraine characterized by headache frequency exceeding 15 days per month, with at least 8 headache days being migrainous. The prevalence of CM in the general population ranges from 1.4 to 2.3%, reaching 6.8% in Russia.

CM significantly impairs patients’ ability to work and their quality of life, causes significant economic losses, and poses a serious problem for both patients and the national healthcare system.

This article presents current literature data reflecting modern understanding of the diagnosis and differential diagnosis of CM, as well as factors that contribute to its chronicity, and discusses current therapeutic approaches. According to the 2024 International Headache Society (IHS) guidelines, migraine-specific (targeted) medications are recommended as the primary treatment for migraine and CM. If necessary, they can be combined with other non-specific oral medications recommended for the treatment of migraine and comorbid conditions due to their different mechanisms of action.

Using the CGRP mAb erenumab, which blocks the CGRP receptor on the postsynaptic membrane and is one of the most effective and safe migraine prophylactic agents, it has been shown to halve the number of migraine days per month after just 3 months of therapy.

Background: Emotional and physical stress in medical students combining university studies with night shift work as nursing staff is accompanied by stress-related changes in the autonomic nervous system, which require early detection and preventive intervention.

Objective: Evaluation of heart rate variability (HRV) and the psychoemotional state of medical students working night shifts to identify early indicators of autonomic imbalance as targets for preventive interventions.

Materials and methods: A short-range HRV study and survey using questionnaires were conducted in 77 students aged 18 to 28 years.

Results: High rates of psychoemotional exhaustion (42.9%), decreased personal achievement (57.1%), and signs of depersonalization (44.2%) were identified. According to HRV data, increased sympathetic tone (SDNN, LF/HF, HI) directly correlated with stress and physical activity levels (SDANN and LF/HF) and inversely correlated with adaptive potential (SDNN, TI, RMSSD, pNN(50)%), while a decrease in overall HRV (LF/HF and HI) was associated with stress levels.

Conclusion: Medical students working night shifts exhibited a high rate of psychoemotional disorders, as well as sympathetic activation with decreased adaptive potential and overall HRV, caused by stress and physical activity. Outpatient HRV studies at short intervals are recommended for the early detection of autonomic imbalance caused by emotional, psychological, or physical stress in young people.

Skin melanoma is one of the most common types of cancer in the world, and the incidence rate continues to grow in many regions. The main risk factor for the development of this disease remains exposure to ultraviolet (UV) radiation, for example, with prolonged exposure to the sun. In addition to damage caused by UV radiation, the development of melanoma is also associated with certain hereditary and acquired genetic changes. The stage of skin melanoma at the time of diagnosis is a key prognostic factor, which is typical for most malignant neoplasms. The development of skin melanoma is facilitated by context-dependent genetic mutations that either weaken tumor suppression mechanisms or activate signaling pathways that stimulate their growth. In addition to external factors such as exposure to ultraviolet radiation, the tumor microenvironment can have a significant impact on the progression, invasive growth and metastasis of melanoma. Malignant melanoma can arise from both benign nevi and de novo – without previous formations. Diagnosis of this disease can be difficult due to the wide variety of precancerous melanocytic changes. Molecular markers and gene expression profiles come to the aid of doctors, facilitating a more accurate definition of the pathology. Since skin melanoma is one of the most metastatic cancers in humans, its early detection opens up the possibility of effective treatment. This creates a need for more accurate methods for predicting the course of the disease, which can be based on modern genetic tests. Treatment of patients at early stages, as well as their subsequent follow-up, play a key role in improving the quality of life of patients and improving long-term treatment results.

Background: The problem of infertility and implantation failures in ART programs is widespread in Russia and the world. The development of medicine and directly methods of assisted reproductive technologies (ART) have had a positive effect on the effectiveness of IVF programs, but the percentage of unsuccessful implantations remains high. The contribution of chronic endometritis as a uterine factor of infertility, reducing the percentage of pregnancy, is underestimated; there is no general concept for managing patients with this diagnosis.

Objective: Evaluation and justification of the effectiveness of complex treatment, including peptide therapy, in patients with chronic endometritis associated with ART programs.

Results: In this study, we substantiated the effectiveness of a comprehensive treatment algorithm for patients and described the contribution of human placenta extract to ART programs with infertility and a confirmed diagnosis of chronic endometritis.

Conclusion: The proposed treatment algorithm for patients with chronic endometritis associated with ART programs, including a combination of physiotherapy and peptide therapy with Melsmon, increases the pregnancy rate in cryopreservation cycles of euploid embryos to 73% and can be recommended for the treatment of uterine infertility.

Background: Aromatase inhibitors (AIs) are currently used for the chemoprevention and treatment of hormone-dependent (HR+) breast cancer (BC). In premenopausal women with HR+ BC at high risk of recurrence, as determined by clinicopathological characteristics, the use of these drugs reduces the risk by 10–15%.

Objective: Review of literature on the incidence and mechanisms of AI-associated arthralgia, as well as methods for preventing musculoskeletal disorders (MSDs) during treatment with these medications.

Results: The studies reviewed in this study demonstrate that over 50% of women experience pain, necessitating further investigation of the underlying mechanisms of these complications and the development of strategies to minimize them. CDK4/6 inhibitors may be an alternative, as they have less pronounced side effects on the musculoskeletal system. Observations also confirm a link between side effects and recurrence rates. Duloxetine has been shown to be effective in reducing the incidence of arthralgia, although its effect in patients with a high body mass index requires further analysis. The risk of osteoporosis associated with AI treatment can be reduced with bisphosphonates, which is also supported by a reduction in fracture rates in high-risk patients. True acupuncture is an effective method for reducing arthralgia associated with AI use in women with HR+ BC. Moderate physical activity is an effective non-pharmacological strategy for relieving arthralgia during AI therapy in BC, associated with a reduction in systemic inflammation and an improvement in quality of life.

Objective: Assessment of the prevalence of clinically significant single nucleotide polymorphisms of the ABCB1 gene (rs1128503, rs2032582, rs1045642) in palliative cancer patients receiving morphine in order to substantiate the prospects of a pharmacogenetic approach to personalized analgesic therapy.

Materials and methods: The study included 86 patients with cancer in the palliative stage and receiving morphine, as well as 100 control patients without cancer. Genotyping of ABCB1 polymorphisms was performed using real-time polymerase chain reaction. The dynamics of pain syndrome was also assessed using a visual analog scale (VAS) at three stages of therapy.

Results: A high frequency of heterozygous CT variants for rs1128503 and rs1045642 polymorphisms was established. VAS analysis showed a decrease in pain syndrome from 8 to 2 points after the start of morphine therapy, which confirms its effectiveness.

Conclusion: ABCB1 gene polymorphisms may play a significant role in the variability of response to morphine in cancer patients. The obtained data emphasize the need for further research to develop personalized pain relief strategies taking into account genetic characteristics.

Background: Oxaliplatin is an important component of first-line chemotherapy (CT) regimens for metastatic colorectal cancer (mCRC), but its use is often limited by the development of peripheral neuropathy (PN). The optimal relative dose intensity (RDI) that achieves a balance between efficacy and toxicity remains unresolved.

Objective: Evaluation of the effect of oxaliplatin RDI on the incidence of PN and treatment response rates in patients with mCRC.

Materials and methods: A retrospective, single-center cohort study was conducted. Electronic medical records of 142 patients with mCRC receiving CT using the mFOLFOX6 regimen were included. The effect of oxaliplatin RDI on the development of neuropathy (grade ≥ 2), objective response rate, progression-free survival (PFS), and overall survival (OS) was assessed. The association was assessed using logistic regression, Kaplan-Meier analysis, and ROC analysis. The median follow-up was 36 months.

Results: An RDI ≥ 78.9% was significantly associated with a higher incidence of oxaliplatin-induced grade ≥ 2 PN (OR = 8.25, 95% CI: 2.56–26.62; p = 0.0004). No effect of high dose intensity on PFS (OR = 1.24; p = 0.276) and OS (OR = 0.87; p = 0.561) was found, as was the effect on the objective response rate.

Conclusion: A higher oxaliplatin RDI is associated with an increased risk of neuropathy but does not improve survival, supporting the rationale for individual dose reduction.

Background: According to GLOBOCAN (2022), 2.3 million new cases of breast cancer (11.6% of all malignant neoplasms) were diagnosed worldwide, with a mortality rate of 665,684 cases, which is equivalent to 6.9% of all cancer deaths. Breast cancer (BC) ranks first in the structure of cancer morbidity in women and the fourth among causes of death from malignant neoplasms in the general population. In the Russian Federation, the majority (72.5%) of breast cancer cases are diagnosed at early stages (I-II), which creates prerequisites for improving surgical tactics. Despite the fact that surgical treatment remains the main method of therapy, in recent years the possibilities of reducing the volume of intervention in the axillary zone have been actively discussed. Quality of life (QOL) is recognized as the second most important criterion for treatment effectiveness after overall survival (OS). Its assessment is included in the design of many randomized clinical trials and is carried out using standardized questionnaires and validated scales.

Objective: Assessment of the effect of the volume of surgical intervention in the axillary zone on the quality of life in patients with early breast cancer (cT1-2N0).

Materials and methods: The study, conducted at the Herzen Moscow Oncology Research Institute in 2017–2022, included 204 patients with luminal subtypes of primary resectable breast cancer (cT1-2N0). In 51 women, treatment was limited to radiotherapy without surgical intervention on regional lymphatic collectors, while 153 patients underwent sentinel lymph node biopsy (SLNB) with pN0 confirmation. Patients were allocated by pseudorandomization in a 3:1 ratio taking into account clinical and morphological characteristics. All patients received adjuvant treatment. The median age was 58.1 years [49.6–65.3]. Stage IA was diagnosed in 164 (80.4%) women and IIA in 40 (19.6%). Invasive ductal carcinoma was found in 173 (84.8%) cases, luminal A subtype – in 149 (73.0%), moderate tumor differentiation – in 183 (89.7%). Multicentric growth was detected in 16 (7.8%) patients.

Results: The median follow-up was 76.4 months (12.1–96.3). During this period, disease progression was recorded in 9 patients (4.4%): three of those who did not undergo intervention in the axillary zone (5.9%) and six of the patients who underwent SLNB (3.9%). Local recurrence was noted in one case (0.7%) after sentinel node biopsy. Regional recurrences developed in three patients (1.5%): two (3.9%) in the group without surgery and one (0.7%) after SLNB (p = 0.155). Distant metastases were detected in five patients (2.5%). Five-year overall survival was 100% regardless of the extent of intervention. Five-year progression-free survival was 95.2 ± 3.4% in patients without surgery and 98.0 ± 1.1% in patients after SLNB; the median value was not reached. According to the EORTC QLQ-BR23 questionnaire, complications in the arm and shoulder during the first year of follow-up were noted in 4% of patients who did not undergo surgery and in 17% of patients after SLNB (p = 0.012). Moreover, in the first group, all complaints were minimal and corresponded to the degree of «mildly expressed», while after SLNB, in 2–3.3% of patients they were assessed as «significant» (moderate or expressed).

Conclusions: Patients with early breast cancer (cT1-2N0) can be considered candidates for refusal to perform sentinel lymph node biopsy, which reduces the incidence of complications and allows maintaining a satisfactory quality of life without worsening oncological results.

Background: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer, with laryngeal cancer accounting for only 0.6%. According to GLOBOCAN estimates (2022), approximately 890,000 new cases of HNSCC are registered worldwide each year, with mortality estimated at 450,000. In Russia in 2023, laryngeal cancer accounted for 2% of all malignant neoplasms among the male population. Despite the treatment, more than 50% of patients experience a relapse of the disease in the first 3 years. Modern methods of treating metastatic or recurrent HNSCC include both standard cytostatics and modern classes of antitumor drugs (targeted and immunotherapy).

Description of a clinical case: This article presents a clinical case of a long-term response to combined chemo-targeted (paclitaxel, carboplatin, cetuximab) therapy in a patient with recurrent squamous cell carcinoma of the larynx.

Conclusion: Combination chemo-targeted therapy (paclitaxel, carboplatin, cetuximab) as first-line treatment for recurrent/metastatic HNSCC demonstrates satisfactory tolerability with comparable oncological outcomes, especially in older patients and/or with significant comorbidities.

Background: The COVID-19 pandemic has been a wave-like process for several years, with each period of increased incidence differing in the rate of spread, the degree of contagiousness of the virus, the population receiving outpatient and inpatient treatment, the characteristics of the clinical picture and the outcomes of the disease.

Objective: to analyze the clinical features of COVID-19 and chronic heart failure (CHF) of ischemic genesis in different periods of increased incidence (2020–2021 and 2022–2023).

Materials and methods: A simple comparative retrospective study included 78 patients hospitalized in the pulmonology department of the Omsk City Clinical Emergency Hospital No. 2 with confirmed diagnoses of COVID-19 and CHF of ischemic genesis, group 1 – 36 patients hospitalized in the period 2020–2021, group 2 – 42 patients treated in 2022–2023.

Results and conclusions: Patients with CHF hospitalized in the period 2022–2023. New coronavirus infection (NCVI) were significantly older than in the period 2020-2021. In 2022–2023, a statistically significantly smaller number of hospitalized patients with CHF had manifestations of respiratory and general intoxication syndromes, 47,62% of patients did not report an increase in body temperature, 30% did not report a decrease in blood saturation >95%, in contrast to the period 2020–2021. However, a marked decrease in physical activity, the presence of tachycardia at normal body temperature, the appearance of pastosity of the shins in patients with CHF in the period 2022–2023 can be considered precisely as a manifestation of CHF decompensation, which became the main reason for hospitalization. Patients with CHF with the development of NCVI in both 2020–2021 and 2022–2023 represent a high-risk group for CHF decompensation, requiring intensive monitoring of respiratory manifestations of NCVI while simultaneously monitoring CHF symptoms to develop individualized approaches to treatment and rehabilitation during the period of viral infection and subsequent minimization of early and late complications.

It is well known that the human intestinal microflora can radically affect the state of health, both physical and mental. The microbiota is connected with the central nervous system via the «gut-brain» axis – a complex bidirectional communication system, including neural, endocrine and immune mechanisms. A number of studies have shown that people diagnosed with major depressive disorder also suffer from dysbiosis (decrease in Lactobacillus and Bifidobacterium, increase in Enterobacteriaceae), and a number of antidepressants can worsen this condition. Such disorders require appropriate correction, and the effect of the multi-strain probiotic not only on metabolic and intestinal disorders, but also on the course of depression is of interest. It is able to restore the balance of microflora, reduce inflammation and stimulate the synthesis of neuroactive substances (serotonin, dopamine, GABA), which makes its use promising in psychiat-ry, compared with traditional approaches focused exclusively on central mechanisms.