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Vol 32, No 9 (2025)

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Gastroenterology/hepatology

Synergism of iron, vitamin C, and probiotic components in maintaining intestinal microflora and immunity

Mubarakshina O.A., Somova M.N., Batishcheva G.A., Dronova Y.M., Zhdanova O.A., Stepkin D.I., Shcherbova Z.R.

Abstract

This review examines the relationship between iron, vitamin C, intestinal microflora, and the immune system, as well as the rationale for including iron and vitamin C in probiotic complexes. Iron is a key micronutrient involved in respiratory processes, hemoglobin and DNA synthesis, cell cycle regulation, and immune cell function. Iron deficiency is prevalent worldwide and can disrupt both systemic processes and intestinal microbial balance, reducing microbiota diversity and short-chain fatty acid production. Antibiotics used to treat infectious diseases further exacerbate dysbiotic changes by affecting intestinal barrier function and reducing the synthesis of metabolites important for immunity and micronutrient absorption.

Probiotic strains can improve non-heme iron absorption by lowering intestinal pH, stimulating prebiotic fermentation, and influencing the function of transport proteins. Prebiotics such as inulin and galactooligosaccharides also increase mineral bioavailability and support the growth of beneficial microflora. Vitamin C acts as a cofactor, enhancing iron absorption and providing antioxidant protection, while B vitamins influence metabolism and are essential for dysbiotic changes in the microbiota. The combination of iron, vitamin C, and B vitamins with pro- and prebiotic components is characterized by a synergistic effect: it improves the absorption of micronutrients, supports the restoration of microbiota, strengthens barrier mechanisms, and promotes increased immune reactivity. The summarized data emphasize the relevance and effectiveness of this approach for the prevention and correction of deficiency conditions and microbial imbalances.

Pharmateca. 2025;32(9):8-14
pages 8-14 views

Pulmonology/ENT/ARVI

Herpes simplex viruses: from pathogenesis to effective treatment using immunomodulators

Zakharova I.N., Berezhnaya I.V., Pupikina V.V., Churilova V.D.

Abstract

Herpes simplex viruses (HSV) are extremely common infectious agents characterized by a high degree of contagiousness. Infections caused by HSV types 1 and 2 are often asymptomatic but can cause a range of clinical manifestations, including primary and recurrent vesicular lesions of the oral and labial mucosa, ophthalmological and genital lesions, and viral encephalitis. HSV poses a particular danger to patients in high-risk groups. High susceptibility to herpes infections is typical in newborns due to the physiological immaturity of the immune system, as well as in patients with immunodeficiency conditions of various origins. The immunological response to HSV is a complex process that activates components of both innate and adaptive immunity. Recurrent herpesvirus infections are characterized by an immunological imbalance, characterized by a decrease in the number of CD3+ and CD4+ lymphocytes, a decrease in the immunoregulatory coefficient, and suppression of the functional activity of natural killer cells and antibody-dependent cellular cytotoxicity. Over the course of evolution, HSVs have developed adaptive immunomodulatory mechanisms specifically aimed at evading the T-cell immune response, ensuring lifelong persistence of the pathogen in the host body. In pediatric practice, when clinical markers of immune system deficiency are identified, characterized by recurrent infectious and inflammatory conditions and resistance to conventional treatment methods, the use of pharmacological agents with immunotropic properties is justified. This article discusses the mechanisms of action of inosine pranobex and its efficacy against infections caused by HSV types 1 and 2.

Pharmateca. 2025;32(9):15-23
pages 15-23 views

Bronchial asthma in the elderly: diagnostic features, clinical course, and treatment approaches

Gaynitdinova V.V., Aleksandrova A.A., Evdokimova S.A.

Abstract

Globally, the number of elderly patients is growing. It is expected that by 2050, this age group will account for 17% of the global population. As the number of patients over 65 years of age increases, understanding of disease development and clinical features, treatment approaches, and the issue of patient comorbidity are changing. Bronchial asthma in the elderly remains poorly understood. Determining the exact prevalence of bronchial asthma in the elderly is difficult. However, several studies have shown that the prevalence of bronchial asthma in the elderly ranges from 1.8 to 10.9%, is more common in men, and tends to increase over time. This is primarily due to the lack of universal diagnostic criteria in older adults, comorbidity, immunosenescence, heterogeneity of clinical and functional manifestations of the disease, poor patient perception of symptoms, difficulty conducting functional tests, and the lack of response to standard therapy. Therefore, further study of the characteristics of bronchial asthma in this cohort is necessary to improve diagnosis, treatment, and quality of life in elderly patients.

Pharmateca. 2025;32(9):24-30
pages 24-30 views

Occupational chronic obstructive pulmonary disease in its isolated and comorbid course from the perspective of assessing the psychological profile and quality of life

Babanov S.A., Strizhakov L.A., Vostroknutova M.Y., Lavrentyeva N.E., Vasina I.N., Babanov A.S., Artemyeva M.S., Vostrikova M.V.

Abstract

Background: Evaluation of clinical data, psychological profile, and quality of life (QOL) in occupational chronic obstructive pulmonary disease (oCOPD), both with isolated and comorbid course, opens up new possibilities for assessing the development, predicting the course, and personalizing the pharmacotherapy of COPD, as well as for developing individualized strategies for its primary and secondary prevention.

Objective: Determination of the psychological characteristics and QOL in COPD, both isolated and in combination with arterial hypertension (AH).

Material and methods: The study involved 175 patients and 60 controls: Group 1 (control) – 60 healthy volunteers, Group 2 – 35 patients with stage 1 oCOPD (oCOPD I), Group 3 – 50 patients with stage 2 oCOPD, Group 4 – 40 patients with a combination of stage 2 oCOPD and AH, Group 5 – 50 patients with isolated AH. All patients were tested using three methods: the Buss-Durkee Hostility Inventory and the Plutchik-Kellerman-Conte Life Style Index (LSI). Quality of life was also assessed using the SF-36 Health Status Survey. Group data were evaluated using a one-way analysis of variance with between-group comparisons using Dunnett’s test.

Results: For the first time, the characteristics of psychological manifestations and QOL in oCOPD of varying severity, both in isolation and in combination with AH, have been identified.

Conclusion: Exposure to occupational dust is a stress factor leading to the development of severe psychoemotional disorders in oCOPD, both isolated and in combination with AH. We believe that a comprehensive psychological examination, including consultation with a psychologist and the use of the Buss-Durkee Hostility Inventory and the LSI method, as well as QOL assessment, is essential. A QOL assessment was also conducted using the SF-36 questionnaire as part of a program of in-depth periodic medical examinations for individuals working with chemical and fibrogenic industrial aerosols potentially associated with the development of occupational chronic obstructive pulmonary disease (oCOPD). This assessment was also part of a program for providing medical care to patients with COPD, both isolated and comorbid with AH, at pulmonology centers and occupational pathology centers at the federal and regional levels. This assessment took into account the identified psychological changes, decreased QOL, and the need for timely psychological intervention, including the use of pharmacological agents.

Pharmateca. 2025;32(9):40-48
pages 40-48 views

Prospects for modulating the inflammatory process in recurrent ENT diseases

Savlevich E.L., Zurochka A.V., Yastremsky A.P., Kartashova M.K., Kozulina I.E., Tumanova E.A., Popadyuk V.I., Kabanova T.G., Kozlov I.G.

Abstract

Acute and chronic inflammatory ENT-diseases are the most common pathological conditions worldwide. The primary goal of treating acute upper respiratory tract inflammation (URTI) is to reduce the severity of the infection and transform it into a form with mild clinical symptoms, which could prevent the development of complications and long-term effects after a respiratory infection. Acute inflammatory ENT-diseases of the organs should progress through all stages of a typical pathological process, ending in recovery. However, in some situations, the inflammatory process fails to progress to either a complete resolution phase or a chronic proliferative phase. This means the infection cannot resolve, clinically manifesting as a sluggish, torpid course. This condition may be caused by incomplete phagocytosis, an imbalance between the M1 and M2 macrophage fractions, a hypoergic inflammatory process, or pathogen persistence. Targeted stimulation of macrophages toward the M1 phenotype abruptly shifts the system from equilibrium toward acute inflammation. Proinflammatory cytokines IL-1β, IL-6, and TNF-α are released, triggering NETosis, which then stimulates the M1 → M2 macrophage transition, which in turn begins to produce anti-inflammatory cytokines IL-10 and TGF-β. M2 macrophages destroy all cellular debris, stimulating proliferation and the healing process. Thus, it is the stimulation of M1 macrophages and their subsequent transition to the M2 phenotype that effectively helps combat protracted, sluggish inflammation, creating a «proinflammatory flare,» which is the necessary impetus for the full and complete cycle of the inflammatory response. Glucosaminylmuramyl dipeptide (Likopid) exerts its biological activity by binding to the intracellular receptor protein NOD2, triggering phosphorylation of interferon regulatory factor (IRF)-3, thereby increasing IFN-α production and enhancing the production of proinflammatory cytokines IL-1β, IL-6, IL-12, TNF-α, the chemokine CXCL-8, IFNγ, and colony-stimulating factors. Subsequently, the cytosolic NOD2 receptor is translocated to the cytoplasmic membrane and translocated with DUOX2, which encodes dual oxidase type 2, a protein in the hydrogen peroxide generation system, enhancing the bactericidal effect and promoting inflammation regression. The clinical activity of Likopid has been confirmed in recurrent acute and chronic rhinosinusitis, tonsillopharyngitis, including those associated with persistent Epstein-Barr virus (EBV), allergic rhinitis, and in patients with post-COVID syndrome.

Pharmateca. 2025;32(9):31-39
pages 31-39 views

Prevention of severe RSV-associated lower respiratory tract infections in children at high risk of RSV infection: use of palivizumab

Borzakova S.N., Mikheeva A.A., Esmurzieva Z.I.

Abstract

Respiratory syncytial infection (RSVI) is one of the main causes of lower respiratory tract infections in children under 2 years of age. Children born before 35 weeks of gestation, children with bronchopulmonary dysplasia, hemodynamically significant heart defects, and immunodeficiency states are at risk for severe RSVI.

Currently, the most effective and safe method for preventing RSVI is immunization with palivizumab. Palivizumab contains monoclonal IgG1 antibodies against the F protein of the virus, which prevents the virus from attaching to respiratory epithelial cells and prevents severe RSVI. Five injections of palivizumab are required for effective immune protection.

Prophylaxis with palivizumab leads to a significant reduction in the incidence of RSVI after two years of follow-up and reduces the frequency and duration of episodes of bronchial obstruction during one year of follow-up.

Pharmateca. 2025;32(9):49-53
pages 49-53 views

Rheumatology

Sequential therapy for immune reconstitution in multiple sclerosis: a clinical case of use of cladribine tablets after alemtuzumab

Ponevezhskaya E.V., Davydovskaya M.V., Kukushkina A.D., Lysogorskaya E.V., Gosteva V.V., Smirnov A.P.

Abstract

The use of alemtuzumab in the treatment of multiple sclerosis may be limited by the development of autoimmune complications and the persistence of disease activity in some patients. In such situations, the strategy of repeated courses of the drug is not always effective due to the possible formation of neutralizing antibodies, and anti-B-cell therapy has limitations associated with concomitant pathology. The literature describes the possibility of sequential use of two drugs from the class of immune reconstitution therapy - alemtuzumab and cladribine tablets, which allows achieving clinical and neuroimaging stabilization without the need for constant treatment. We present a clinical case of a patient with highly active relapsing-remitting multiple sclerosis, who, after two courses of alemtuzumab, remained active and developed autoimmune complications. Sequential therapy with cladribine tablets ensured control of the disease, stabilization of the neurological status and neuroimaging data, as well as the absence of serious infectious complications. This experience confirms the potential effectiveness and safety of the “alemtuzumab → cladribine tablets” strategy, but emphasizes the need for further accumulation of clinical data to assess its place in the therapeutic arsenal.

Pharmateca. 2025;32(9):54-58
pages 54-58 views

Neurology

Analysis of diagnostic and treatment errors in dementia syndrome in real clinical practice (based on data from an observational study in Novosibirsk)

Duma S.N.

Abstract

Background: The development of dementia significantly impairs the quality of life of patients and their families and places a heavy socioeconomic burden on society as a whole. The medical community faces the clear challenge of diagnosing and treating dementia as early as possible.

Objective: Evaluation of the effectiveness of early diagnosis and a comprehensive approach to prescribing pathogenetically based drug and non-drug therapy.

Materials and method: An observational case-control study was conducted by analyzing the outpatient records of 100 patients diagnosed with chronic cerebral ischemia and dementia syndrome. All patients were referred to the city dementia center for consultation from a healthcare facilities in Novosibirsk. They were examined by a neurologist, assessed for daily activities, and underwent extensive neuropsychological testing, including the Mini-Mental State Examination (MMSE), the «clock,» and literal and categorical associations. All patients underwent neuroimaging (MRI).

Results: Based on the results of an in-depth study, the diagnosis was clarified: 78 patients had moderate Alzheimer’s disease (AD) of mixed origin (neurodegenerative and vascular), 12 patients had mild dementia with Lewy bodies (DLB), and 10 patients had vascular dementia (VD): 6 patients with a mild dementia and 4 with a moderate dementia. The main challenges of early diagnosis and late prescription of antidementia medications are highlighted. A review of non-pharmacological methods for dementia treatment is provided.

Pharmateca. 2025;32(9):60-66
pages 60-66 views

Clinical case report. Severe central nervous system damage in vitamin K deficiency-related late-onset hemorrhagic syndrome

Zizyukina K.S., Burlakova I.M., Sarkisyan E.A., Zhirkova Y.V., Vaynshtein N.P., Romanova D.A., Mitina Y.Y., Shatalov V.G.

Abstract

Objective: Presentation of the clinical case of vitamin K deficiency-related late-onset hemorrhagic syndrome in a full-term girl 43 days old who did not receive vitamin K prophylaxis for late-onset hemorrhagic disease of the newborn.

Key points: Vitamin K deficiency-related late-onset hemorrhagic, better known as late-onset hemorrhagic disease of the newborn (ICD-10: P53), is a condition associated with vitamin K deficiency, leading to blood clotting disorders in children aged 8 days to 6 months. Intracranial hemorrhages, which often lead to residual neurological symptoms and death, pose a particular danger in late-onset vitamin K deficiency-related hemorrhagic syndrome. Contraindications to prophylactic administration of menadione (Vicasol) in the maternity hospital and the lack of availability of phytomenadione in the maternity hospital and outpatient care lead to the risk of developing hemorrhagic disease.

Description of the clinical case: This article presents an observation of child V. with vitamin K deficiency-related late-onset hemorrhagic syndrome and severe hemorrhagic central nervous system damage.

Conclusion: Prevention of vitamin K deficiency-related hemorrhagic syndrome is an essential intervention performed in the first hours of a newborn's life. Lack of vitamin K supplementation can lead to severe consequences, as confirmed by our clinical case. The diagnostic and treatment measures performed immediately after the child's admission to the hospital prevented a fatal outcome and achieved minimal neurological impairment.

Pharmateca. 2025;32(9):67-74
pages 67-74 views

Pediatria

Palliative care for children: definition, content, and prospects (literature review)

Antonova A.A., Kashirskaya E.I., Kondratieva O.A.

Abstract

The number of children requiring palliative care is steadily increasing. Pediatric palliative care is a relatively new field of medicine, bringing together specialists from various fields and volunteers. This article provides an analytical review of current issues and key aspects of the development of pediatric palliative care. Pediatric palliative care aims to improve the quality of life of children with severe, incurable non-oncological and oncological diseases, for whom rehabilitation options are limited or nonexistent. The article presents the main models of palliative care organization. In countries with high levels of economic development, inpatient models (particularly specialized children’s hospice facilities) predominate, characterized by significant resource intensity. In countries with limited financial resources, less expensive but proven effective models have become widespread, among which home palliative care holds a special place. An analysis of the legislative and regulatory framework is conducted. In the Russian Federation (RF), legal regulation of palliative care was implemented in 2011 with the adoption of Federal Law No. 323-FZ «On the Fundamentals of Health Protection of Citizens in the Russian Federation.» In accordance with the provisions of this regulatory act, palliative care was included in the system of types of medical care provided to the population. Further institutional development of the palliative care system occurred in 2012, when Order No. 1183n of the Russian Ministry of Health dated December 20, 2012, «On Approval of the Nomenclature of Positions for Medical and Pharmaceutical Workers» officially introduced the position of «Palliative Care Physician.» The distribution and course of life-threatening childhood diseases, which determine the fundamental differences in palliative care provided to children, are analyzed. A literature search using Scopus, Web of Science, MedLine, PubMed, and E-library databases was conducted.

Pharmateca. 2025;32(9):75-81
pages 75-81 views

Dermatology/allergology

Hyperuricemia in psoriasis. Intersystem interrelationships and clinical significance

Vereshchagin E.I., Svechnikova E.V., Maksimova Y.V., Arutyunyan G.B., Artemieva N.O., Morzhanaeva M.A., Terentyeva L.V., Devyatova A.V., Nelga I.O., Rzhevskaya E.V., Tartanova D.Y.

Abstract

Background: Elevated serum uric acid levels are known to be a cause of a number of chronic diseases, including atherosclerosis, gout, nephritis, obesity, diabetes, and metabolic syndrome. Psoriasis is a chronic inflammatory disease with systemic manifestations that, according to recent studies, affects not only the skin and musculoskeletal system but is also accompanied by metabolic disorders.

Hyperuricemia is associated with severe psoriasis, the presence of psoriatic arthritis, and an increased risk of cardiovascular complications and gout. Despite increased scientific interest in this topic, the clinical significance of uric acid levels in patients with psoriasis remains unresolved.

Objective: Analytical Review of the scientific literature to identify a correlation between uric acid levels and the severity of psoriasis.

Conclusion: The results of this literature review indicate a relationship between hyperuricemia and psoriasis. This association is not limited to the presence of metabolic syndrome, but is evident in patients with psoriasis even in the absence of concomitant metabolic disorders due to accelerated cell turnover. Although elevated uric acid levels can be considered a potential biomarker of systemic inflammation, which characterizes the severity of psoriasis and associated pathologies, the limited number of large-scale studies hinders a definitive interpretation of the prognostic significance of this indicator. Nevertheless, the data obtained suggest that uric acid levels are not simply a marker, but rather an important pathogenetic factor reflecting the severity and chronicity of psoriasis, amplifying the inflammatory cascade through the activation of purine metabolism by cytokines. Further studies in larger cohorts of patients are needed to confirm these findings and clarify the prognostic role of hyperuricemia in psoriasis severity. Understanding the relationship between hyperuricemia and psoriasis may open new perspectives for the development of comprehensive therapeutic strategies aimed at correcting both skin manifestations and systemic metabolic disorders.

Pharmateca. 2025;32(9):82-86
pages 82-86 views

Therapeutic potential of transcranial magnetic stimulation in mental health issues

Svechnikova E.V., Morzhanaeva M.A., Lemytskaya V.E., Rzhevskaya E.V., Gladko V.V., Artemyeva N.O.

Abstract

Transcranial magnetic stimulation (TMS) is a non-invasive stimulation of brain tissue by creating a high- or low-intensity magnetic field that modulates the excitability of the cerebral cortex. Repetitive (rhythmic) transcranial magnetic stimulation (rTMS) involves the application of repeated TMS pulses to a specific area of the brain. rTMS has been studied as a potential treatment for a number of psychiatric and neurological disorders. The neuromodulatory effect depends on a number of stimulation parameters, such as the target area in the brain, frequency, intensity, duration, and number of sessions, as well as patient factors such as age, disease status, medication use, and individual symptoms.

Generally, rTMS is classified as high-frequency (>1 Hz), which increases cortical excitability, and low-frequency (<1 Hz), which suppresses it [1]. A new advancement in TMS is ExoTMS® technology. This technology utilizes a new therapy protocol at three different frequencies with an increased number of magnetic pulses (6,440), which is 2-3 times more than other similar devices. Furthermore, ExoTMS pulses are trapezoidal in shape and, unlike traditional rectangular pulses, gradually deliver increasing electromagnetic energy to neurons and are non-addictive. All this reduces the therapy course to 6 sessions of 24 minutes each, compared to 30 sessions with similar devices. By stimulating the dorsolateral prefrontal cortex (DLPFC), ExoTMS enhances arousal in this region, thereby facilitating the processing and regulation of emotions [2].

rTMS has a stimulating effect on neuronal plasticity processes, in particular on the mechanisms of long-term potentiation and depression, and the regulation of gene expression associated with the synthesis of brain-derived neurotrophic factor (BDNF) [3, 4]. This article presents an overview of current data on transcranial magnetic stimulation and the capabilities of ExoTMS technology.

Pharmateca. 2025;32(9):87-94
pages 87-94 views

A case of onychomycosis caused by the pathogen Trichophyton verrucosum in a patient with concomitant dermatological pathology

Chasnyk A.S., Pozdnyakova O.N., Nemchaninova O.B., Fomenko N.V., Kalymbetova T.V., Shipilova N.A., Sergeeva I.G.

Abstract

Background. Nail pathologies which manifest with similar clinical signs are a common clinical situation in the practice of a dermatovenerologist. The imperfection of laboratory methods for research on fungal infections, the presence of combined lesions of the nail plates with other skin changes in the patient, as well as the growth of atypical pathogens in the etiological structure of onychomycosis complicate diagnosis.

Description of a clinical case. The article presents a clinical observation of a patient with a long-term course of nail mycosis caused by Trichophyton verrucosum, combined with changes in the skin of the face, scalp and perianal area. Repeated microscopic examinations of scrapings from the nail plates showed the presence of single yeast cells and spores, while external etiotropic therapy did not lead to improvement. PCR diagnostics for fungi gave a positive result (Fungi 32.7), but the pathogen was not identified. Subsequent cultural research gave an increase in colonies of the fungus T. verrucosum.

Conclusion. The clinical case demonstrates the need for a personalized approach to patients with long-term dermatoses and reflects the pathomorphosis in the course of skin diseases, including fungal etiology. To finally diagnose nail mycosis caused by a zooanthropophilic pathogen, our patient needed a combination of several laboratory research methods.

Pharmateca. 2025;32(9):95-100
pages 95-100 views

Obstetrics/gynecology

An innovative method of pregravid preparation of the “thin” endometrium during IVF

Shneiderman M.G., Kalinina E.A., Smolnikova V.Y., Alieva K.U., Aksenenko A.A., Kuzemin A.A., Dyuzheva E.V., Gavisova A.A., Fatkhudinov T.K., Afyan A.I., Boris D.A., Apolikhina I.A.

Abstract

Background: In the context of declining fertility and in order to increase the effectiveness of the in vitro fertilization method when diagnosed with hypoplastic (thin) endometrium, the development of a new method of treating this pathology becomes relevant.

Objective: Development of a new effective method of treating hypoplastic (thin) endometrium without the use of standard treatment methods - hormone therapy and physiotherapy used in preparing patients for in vitro fertilization (IVF), and evaluation of the effectiveness and safety of the proposed innovative method.

Material and methods: The study included 260 patients of reproductive age (from 25 to 48 years) with diagnosed primary or secondary infertility and the presence of “thin endometrium” that was not treatable by other methods and did not respond to hormonal stimulation carried out in cycles three or four months before the start of the study. In the control group, 30 women with a clinically confirmed diagnosis of “infertility 1 or infertility 2, thin endometrium” were examined. The procedure for irrigation of the endometrium with carbon dioxide was carried out three times on the 7th, 9th and 11th days of the menstrual cycle. Statistical data processing was carried out using Statistica 10.0 software packages.

Results: After the patients underwent three irrigations of the endometrium with carbon dioxide, there was a clear trend towards an increase in the thickness of the endometrium. This indicates the potential of the method in increasing the number of successful embryo implantations during the IVF procedure.

Conclusion: Our own clinical observations accumulated confirm the high efficiency of using carbon dioxide (CO2) for irrigation of the uterine cavity with thin endometrium, which contributes to a significant increase in the endometrium thickness in the preparatory period before the IVF procedure.

Pharmateca. 2025;32(9):101-107
pages 101-107 views

Oncology

Evolution of antitumor treatment for primary glial CNS tumors

Slugina E.A., Novik V.A., Nekhaeva T.L., Efremova N.A., Kurnosov I.A., Danilova A.B., Baldueva I.A.

Abstract

Gliomas are a group of central nervous system (CNS) tumors originating from glial cells. Despite significant efforts in the field of oncology, gliomas, especially high-grade gliomas, remain one of the most complex and aggressive forms of malignancy. Low-grade diffuse gliomas have a relatively favorable prognosis, while high-grade gliomas, especially glioblastomas, are characterized by an extremely unfavorable course. The overall survival (OS) of patients with glioblastoma ranges from 14 to 20 months, and the 5-year survival rate is only 6%. In patients with newly diagnosed glioblastoma, the 6-month progression-free survival (PFS) is approximately 54%, while in relapsed patients, the 6-month PFS is 30–40%, and the 6-month OS is 57%. For newly diagnosed diffuse glial tumors WHO G3–4, the 1-year PFS is approximately 80%, and the median OS is approximately 25 months. These indicators emphasize the need to search for new treatment approaches. This article presents the main current strategies and approaches to the treatment of diffuse glial CNS tumors. A meta-analysis of the efficacy of the combination of bevacizumab and irinotecan was conducted.

Pharmateca. 2025;32(9):108-118
pages 108-118 views

The problem of drug-induced hepatotoxicity in oncology practice and methods for its correction

Skvortsov V.V., Kolomytsev V.V., Goryunova L.V.

Abstract

Drug-induced liver injury (DILI) is a serious problem in oncology practice due to the low selectivity of anticancer drugs and their metabolites. Improved survival rates for cancer patients and the expansion of the arsenal of chemotherapeutic agents, including targeted agents and immunotherapy, are contributing to the increasing prevalence of DILI, requiring effective approaches to prevention and correction. This review analyzes the mechanisms of chemotherapeutic agent hepatotoxicity, classification, and diagnosis of DILI.

Patient management includes biochemical monitoring, chemotherapeutic dose reduction, and the use of hepatoprotectors. IIt has been shown that among modern approaches to the correction of DILI, an important place is occupied by the use of a multicomponent drug (Remaxol®, INN: Inosine + Meglumine + Methionine + Nicotinamide + Succinic acid). This fixed combination provides a comprehensive pathogenetic effect, including correction of mitochondrial dysfunction, reduction of oxidative stress, stimulation of hepatocyte regeneration, and enhancement of detoxification processes. Clinical trial results demonstrate the efficacy of this preparation for both the prevention and treatment of DILI in cancer patients receiving polychemotherapy.

Pharmateca. 2025;32(9):119-125
pages 119-125 views

Economic aspects of hepatocellular carcinoma treatment

Vlasova N.A., Eliseeva E.V., Apanasevich V.I., Startsev S.S.

Abstract

This study examines the economic aspects of hepatocellular carcinoma (HCC) diagnosis and treatment in Russia and abroad. HCC is the most common primary liver cancer, requiring significant financial expenditures for diagnosis and treatment. The increasing incidence of HCC leads to an increased need for diagnosis and treatment. The aim of this study is to characterize the economic aspects of HCC diagnosis and treatment in Russia and abroad. To achieve this goal, scientific publications on the economic aspects of HCC diagnosis and treatment indexed in the eLibrary, Cyberleninka, PubMed, and Google Scholar electronic libraries, as well as clinical guidelines from the Russian Ministry of Health and the European Association for the Study of the Liver were reviewed. This article examines the economic aspects of various methods for diagnosing and treating HCC in Russia and abroad, including the cost of procedures, the availability of surgical and medical treatment, and the burden on the healthcare system. Particular attention is paid to the cost-effectiveness of preventive measures, such as hepatitis B vaccination and hepatitis C screening. A detailed analysis of the potential economic impact of the disease, the specifics of healthcare financing, and factors influencing the choice of diagnostic and therapeutic measures is provided. As the burden of HCC increases worldwide, concerted efforts to understand the comparative effectiveness of surveillance and treatment strategies are needed, and more comparative studies among patients with cirrhosis and all stages of HCC are required. Although survival remains the most important outcome, quality of life, costs, and ultimately value must be assessed in parallel when considering the clinical utility of interventions. Further research to identify ways to reduce this disparity is needed.

Pharmateca. 2025;32(9):126-137
pages 126-137 views

Risk stratification for opioid analgesia failure in cancer patients using pharmacogenetic markers

Khaytovich E.D., Shikh E.V., Kazakov R.E.

Abstract

Background: Morphine is the drug of choice for pain relief in cancer patients; however, interindividual variability in drug response limits the effectiveness of standard doses. The introduction of pharmacogenetic approaches allows for personalized selection of opioid therapy, improving its safety and efficacy.

Objective: Evaluation of the association between OPRM1 (rs1799971), COMT (rs4680), CYP2D6 (*4, *10), and ABCB1 (rs1045642) gene polymorphisms and the need for morphine dose titration in palliative cancer patients, taking into account pharmacokinetic and clinical parameters.

Materials and methods: The study included 86 palliative care cancer patients receiving morphine as their primary analgesic. All participants underwent genotyping for the aforementioned polymorphisms. Plasma morphine concentrations were determined using HPLC-MS/MS. Pain was assessed using a visual analog scale (VAS) at three time points. Based on a combination of genetic factors, an integrated genetic risk scale (0–7 points) was developed, reflecting the likelihood of standard dose ineffectiveness.

Results: The analysis showed that in patients with a high score (5-7 points), dose titration was required in 81% of cases, compared to only 5% of those with a low score (0-1 point). A weak relationship between pain severity and steady-state morphine concentration was found, indicating genetically determined resistance. Personalized dosage selection based on the pharmacogenetic profile enabled therapeutic concentrations and clinically significant pain reduction (VAS ≤ 3) to be achieved without excessive drug exposure.

Conclusion: Pharmacogenetic profiling based on OPRM1, COMT, CYP2D6, and ABCB1 analysis predicts the risk of insufficient analgesia with a standard dose of morphine in cancer patients. The developed integrated scale can be used to stratify patients and select the starting dose of opioid therapy, thereby increasing its efficacy and safety.

Pharmateca. 2025;32(9):138-143
pages 138-143 views

The impact of p53 protein expression on the achievement of complete pathomorphism in neoadjuvant drug therapy for early HER2-positive breast cancer (results of a retrospective single-center study)

Kuts I.N., Titov K.S., Karseladze D.A., Zakurdaev E.I., Lebedev S.S., Lebedinsky I.N., Chizhikov N.P., Tatarova A.V., Roshchin F.Y.

Abstract

Background: Neoadjuvant therapy (NAT) is currently the gold standard for the treatment of early HER2-positive breast cancer (BC). However, only patients who achieve a complete pathological response (pCR) benefit from overall survival and progression-free survival (OS and PFS). The question of which patients should begin treatment with neoadjuvant therapy (NAT) and which should be treated initially with surgery remains a matter of debate.

Objective: Determination of the role of tumor p53 expression in achieving pCR after NAT in patients with early HER2-positive breast cancer by review prepared histological biopsy specimens for p53 expression determination, followed by a logistic regression analysis of the resulting database to calculate the relationship between achieving complete pathological response and the presence of p53 expression.

Materials and methods: A retrospective analysis of the medical records of 50 patients who received combination or comprehensive treatment for early (cT1-3N0-2M0) HER2-positive breast cancer in the General Oncology Department, S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department, over a 4-year period from 2021 to 2024. All patients were assessed for p53 protein expression in preoperative biopsy specimens using immunohistochemistry assay. The presence or absence of p53 protein expression was analyzed and correlated with the achievement of pCR.

Results: The presence of p53 protein expression significantly increases the likelihood of achieving a complete pathological response (pCR=1). OR=9.33 indicates that patients with p53 expression have a 9-fold higher chance of pCR than patients without it. The result is statistically significant (p=0.0024), confirming the role of p53 protein expression as a strong predictor of response to NAT.

Conclusion: p53 protein expression is a significant predictor of achieving a complete pathological response (RCB = 0) after effective NAT.

Pharmateca. 2025;32(9):144-150
pages 144-150 views

The role of perfusion computed tomography in the diagnosis of kidney cancer

Khasigov A.V., Tebiyev V.T., Timoshenkova A.V.

Abstract

Background: Imaging methods such as ultrasound, computed tomography (CT), positron emission tomography, and magnetic resonance imaging (MRI) play a leading role in the detection of kidney tumors. Renal CT is the standard for diagnosing renal cell carcinoma (RCC). Digital data on perfusion CT (PCT) parameters for the tumor zone and healthy tissue allow to determine normalized «i» values for each RCC parameter (BF – blood flow, BV – blood volume, MTT – mean transit time, TTP – time to peak).

Despite the long history of studying RCC, diagnostic methods, and imaging, CT and/or MRI do not have sufficient specificity. Based on the statistical analysis, PCT has great potential in diagnosing renal masses and may open new perspectives for optimizing surgical tactics due to its high information content in the differential diagnosis of benign and malignant renal masses.

Objective: Determination of the diagnostic value of PCT in optimizing surgical treatment tactics and assessing the functional capacity of the renal parenchyma in RCC.

Materials and methods: The study analyzed data from 119 patients (58.3 ± 12.6 years) with a confirmed diagnosis of RCC who underwent PCT before treatment and at 1 and 3 months after the start of therapy. Four perfusion parameters were evaluated for the diagnosis of RCC: BF, BV, MTT, and TTP.

Results: According to the analysis, 1 month after of treatment, patients (n=45) responding to therapy showed a decrease in BF and BV in tumor tissue (p<0.01). In the group of non-responders (n=34), changes in perfusion parameters were non-significant (p>0.05). In patients responding to therapy after 3 months, perfusion parameters continued to decline. The mean BF was 85.2±15.3 ml/100 g/min, and BV was 10.7±2.1 ml/100 g.

Conclusion: PCT has great potential and opens new perspectives in the diagnosis, assessment, and surgical management of RCC.

Pharmateca. 2025;32(9):152-157
pages 152-157 views

Pruritus in patients with adverse events of anticancer therapy: relationships with anxiety and depression compared with dermatoses and skin neoplasms and preventive care tactics

Michenko A.V., Lvov A.N., Kruglova L.S., Golova A.Y., Allenova A.S., Romanov D.V.

Abstract

Background: Chronic pruritus is a common symptom in dermatology and is often associated with anxiety and depression. The relationship between pruritus and psychological disorders, particularly in patients with dermatoses, melanocytic skin neoplasms, and cutaneous toxic reactions, is poorly understood. Understanding this relationship is important for improving patient care and quality of life.

Objective: Assessment of the prevalence of anxiety and depression symptoms in patients with dermatoses, melanocytic skin neoplasms, and cutaneous toxic reactions and analysis of their relationship with pruritus.

Methods: A cross-sectional, observational, controlled study was conducted in patients with pruritic and non-pruritic dermatoses and melanocytic skin neoplasms. The frequency of pruritus and its relationship with anxiety and depression were assessed. No medical interventions were performed. The study was conducted from February 2021 to January 2025. The primary endpoint of this study was a comparative assessment of the intensity of itching and the level of anxiety-depressive disorders in patients with various dermatological and oncological skin diseases. Itching intensity was assessed using the NRS (0-10 points), GAD-2 (anxiety), PHQ-2 (depression), and PHQ-4 (anxiety and depression).

Results: The main group included patients with itchy (atopic dermatitis, n=106) and non-itchy (psoriasis, n=101, acne, n=104) dermatoses; benign and malignant melanocytic neoplasms (melaniform nevi, n=105, melanoma, n=88); skin toxic reactions associated with antitumor therapy (STR, n=93); the control group included 216 healthy volunteers. Patients with chronic inflammatory dermatoses more often reported suicidal ideation. According to the intergroup comparison, the mean total GAD-2 anxiety and PHQ-2 depression scores differed significantly (p<0.0001). Screening scores for anxiety were highest in patients with acne and atopic dermatitis. Depression was most common in patients with chronic itchy rashes (atopic dermatitis) and lesions of visible skin areas (acne). A significant positive correlation was shown between the intensity of itching and the total PHQ-4 score. Current approaches to the prevention of dermatological adverse events of antitumor therapy are presented.

Conclusion: The study demonstrated a strong association between pruritus and psychological disorders in dermatology patients. These disorders are associated with high levels of anxiety, depression, and suicidal ideation, highlighting the need for a comprehensive approach to patient treatment. An algorithm for preventive dermatological care, taking into account the nature and severity of rashes, is presented. This algorithm forms the basis for dermatological supportive therapy for patients with skin toxic reactions.

Pharmateca. 2025;32(9):158-168
pages 158-168 views

Omitting sentinel lymph node biopsy in patients with cT1–2N0 luminal breast cancer: a retrospective cohort analysis and case reports

Khakimova G.G., Reshetov I.V., Zikiryakhodzhaev A.D., Khakimova S.G., Timoshkin V.O.

Abstract

Background: The need for routine sentinel lymph node biopsy (SLNB) as a component of axillary treatment in patients with early breast cancer and clinically node-negative (cN0) lymph nodes has been debated since the publication of ACOSOG Z0011 data in 2010 [1, 2]. Currently, randomized clinical trials (RCTs) are investigating the possibility of omitting SLNB during breast-conserving surgery with pre- or postoperative chemotherapy and radiation therapy [3, 4]. Prospective RCTs such as SOUND, INSEMA, and BOOG 2013–08 evaluated the oncological safety of omitting sentinel lymph node biopsy with subsequent axillary observation compared to SLNB in patients with cN0 breast cancer [5–7].

Objective: Evaluation of the oncological safety of omitting sentinel lymph node biopsy in patients with luminal cT1–2N0 breast cancer.

Retrospective cohort analysis: The study, conducted at the P.A. Herzen National Medical Research Center of Oncology from 2017 to 2022, included 51 patients with luminal subtypes of primary resectable breast cancer (cT1–2N0) without surgical intervention on the regional lymph node collector. All patients had clinically confirmed cN0 status based on ultrasound imaging. Sentinel lymph node biopsy was not performed; the morphological status of the lymph nodes was designated as pNx. The median age of the patients was 59.1 [51.2; 66.0] years. Stage IA was diagnosed in 44 patients (86.3%), and stage IIA in 7 (13.7%). Left breast cancer was observed in 39 patients (79.5%). Metachronous cancer and multicentricity were detected in 6 patients (11.8%). Invasive ductal carcinoma was diagnosed in 42 patients (82.4%), luminal A subtype in 42 (82.4%), and moderate tumor differentiation in 47 (92.2%). We illustrated various variants of the course of cT1-2N0 breast cancer without intervention on the regional lymph collector with identical baseline patient characteristics.

Results: The median follow-up period was 77.4 [12.6; 78.1] months (range, 12.1 to 80.0). Disease progression was recorded in 5.9% of patients. The regional recurrence rate was 3.9% (n=2). Five-year overall survival and progression-free survival were 100% and 95.2±3.4%, respectively. The median was not reached.

Conclusion: Our study confirms that patients with cT1-2cN0 luminal breast cancer may be candidates for omitting SLNB. No predictors of locoregional recurrence were identified.

Pharmateca. 2025;32(9):169-174
pages 169-174 views

Evaluation of blood carboxyhemoglobin levels in healthy volunteers using ETHS

Abdulhakov S.R., Khabieva N.A., Kiyasov I.A., Gaysina L.R., Oslopova Y.V., Sultanbekova E.A., Valeeva I.K., Timerzyanov M.I., Fayzullin R.I., Kiyasov A.P.

Abstract

Background: Carbon monoxide (CO) is an integral component of smoke that is harmful to the health of not only smokers but also those around them. Therefore, analyzing carboxyhemoglobin levels in the blood of smokers and nonsmokers can be considered not only as a factor reflecting hypoxia but also as a parameter for assessing potential damage to vital body functions.

Objective: Assessment of carboxyhemoglobin (COHb) levels (% of hemoglobin saturation) in the blood of volunteers who switched to using an electronic tobacco heating system (ETHS) compared to volunteers who continued smoking conventional cigarettes (CC) and who quit smoking (SC) following short-term exposure.

Materials and methods: The study included 60 volunteers (M – 48, F –1 2) aged 21 to 65 years (mean age 32.4 years). Volunteers were randomized into three study groups [ETHS: conventional cigarettes (CC): smoking cessation (CS)] in a 2:1:1 ratio, accounting for equal representation in each group of male and female volunteers who smoked 10-19 or more conventional cigarettes per day (data on the number of conventional cigarettes smoked was obtained during screening based on the results of a questionnaire for the previous 4 weeks of smoking).

Results: The blood carboxyhemoglobin levels in volunteers in the CC group remained virtually unchanged throughout the study period, while in the ETHS groups it was statistically lower than the level at Day 0, starting from the first day (Day 1) of the study; in the SC group, a trend toward decreased carboxyhemoglobin levels was observed throughout the study. However, no differences were found at the Day 3, Day 4, and Day 5 study points compared to Day 0.

Conclusion: The results of the data analysis allow to conclude on the likelihood of harm reduction effects of the study product (ETHS) when used during the study period (5 days) based on the volunteer examination methods used, including a complete blood count, urinalysis, blood chemistry, ECG, spirometry, and the results of an objective examination assessing anthropometric parameters (height, weight, BMI) and vital signs (blood pressure, heart rate, respiratory rate, body temperature), and the absence of reported adverse events/severe adverse events.

Pharmateca. 2025;32(9):175-184
pages 175-184 views

The use of chemoimmunotherapy in the first-line treatment of advanced small cell lung cancer: a case report and brief literature review

Yusupova Z.M., Muradova M.B., Zakharova A.M., Golubev P.V., Kuzmina E.S., Kuzmin V.M., Kachmasova A.K., Viderker S.P.

Abstract

Background: Small cell lung cancer (SCLC) is a malignancy with an aggressive course and an extremely poor prognosis. In its advanced form, median survival rarely exceeds 12 months, even with chemotherapy. However, in recent years, the advent of immune checkpoint inhibitors (PD-L1 inhibitors), such as atezolizumab, has improved survival rates while maintaining acceptable toxicity.

Description of the clinical case: This case report presents the experience of treating a patient with disseminated small cell lung cancer. She achieved a significant positive response to combination chemoimmunotherapy (etoposide + carboplatin + atezolizumab) followed by maintenance therapy with an anti-PDL1 inhibitor. A brief overview of clinical trials on the efficacy of PD-L1 blockers in the treatment of SCLC is also provided.

Conclusion: The combination of immunotherapy and chemotherapy has become the standard of care for small cell lung carcinoma. The high efficacy of this combination was demonstrated in our clinical case.

Pharmateca. 2025;32(9):185-189
pages 185-189 views

Алгоритмы

Algorithm for the diagnosis and treatment of non-alcoholic fatty liver disease

Shirokova E.N., Tkach K.V.
Pharmateca. 2025;32(9):190-206
pages 190-206 views

Current approaches to the diagnosis and treatment of metastatic triple-negative breast cancer

Lazakovich A.A., Dashyan G.A., Dzhelyalov E.S., Sereda O.A., Vats A.B., Shaykhelislamova L.F., Zhurov A.S., Akhmedov R.M., Semiletova Y.V., Belousov A.M.

Abstract

Metastatic triple-negative breast cancer (mTNBC) is characterized by an aggressive course and previously limited treatment options. However, in recent years, the treatment paradigm has undergone revolutionary changes, shifting from non-specific chemotherapy to a personalized, biomarker-based approach. This review provides a detailed analysis of current strategies for the diagnosis and treatment of mTNBC. The critical importance of comprehensive molecular testing, including determination of PD-L1 status, germline mutations in the BRCA1/2 genes, and HER2 expression (including HER2-low status) for choosing the optimal strategy is emphasized. This article puts focus on the strategic sequencing of different classes of targeted agents, taking into account their mechanisms of action and application sites. The article provides not only information on available options but also a practical algorithm for decision-making based on the latest evidence-based medicine and a clear hierarchy of biomarkers.

Pharmateca. 2025;32(9):207-216
pages 207-216 views

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