Sechenov University

Introduction. According to the literature, the detection rate of laterally spreading tumors has increased in recent years due to the constant development of endoscopic diagnosis and treatment technologies. It is reported that these neoplasms account for about 15 % of all colorectal neoplasias. According to the literature, laterally spreading tumors are characterized by a more frequent presence of areas of malignancy compared to polypoid formations. Since such neoplasms are closely correlated with colorectal cancer, it is very important to fully understand the clinical presentation and morphological characteristics to select the optimal treatment strategy. Aim. The development of mapping of samples during morphological examination with subsequent correlation with endoscopic data and search for the most suitable areas for taking a biopsy. Materials and methods. To solve the problem described above, a mapping technology was developed for the morphological study of samples of laterally spreading colon neoplasia, which consists in creating an algorithm of actions, described in more detail in the work. Results. The first step of gross is the correct orientation of the resected specimen. The macroscopic integrity of the removed specimen is described. When describing microscopic data, the first question that the morphologist must answer is whether the process is benign or malignant. In case of malignant processes, the morphologist must answer according to the questionnaire: histological type, degree of differentiation / dysplasia, size (mm), depth of invasion, assessment of resection margins, lymphovascular and perineural invasion, tumor kidneys. Conclusion. The presented technique, when used in everyday pathological practice for neoplastic neoplasms of the colon, can allow a reliable assessment of all prognostic factors and the development of an objective interdisciplinary consensus for further treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.46% of the global population. Conventional therapeutics for RA, including disease‐modifying antirheumatic drugs (DMARDs), nonsteroidal anti‐inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti‐inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface‐modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti‐inflammatory mechanism is associated with the downregulation of pro‐inflammatory cytokines like tumor necrosis factor‐α (TNF‐α) and B‐cell–activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti‐inflammatory cytokines like interleukin‐10 (IL‐10), which has significant anti‐inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

Currently, limited data are available on long-term use of dupilumab to treat atopic dermatitis (AD) in a multinational real-world setting. The aim of this analysis was to report the interim 1-year data for patients with AD enrolled in the GLOBOSTAD registry, including treatment patterns, dupilumab effectiveness and safety, and healthcare burden. GLOBOSTAD is an ongoing, 5-year, multinational, prospective, observational study of adult/adolescent (aged ≥ 12 years at baseline) patients with AD who initiated dupilumab in real-world settings according to their local country-specific prescribing guidelines. Outcomes were evaluated at baseline and at 3, 6 and 12 months and included Eczema Area and Severity Index (EASI) total score, SCORing Atopic Dermatitis (SCORAD) total score, percent body surface area (BSA) affected, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI) total score for adults or Children’s Dermatology Life Quality Index (CDLQI) total score for adolescents and pruritus Numeric Rating Scale (NRS) total score. At the interim 1-year cut-off (March 2023), 955 patients were enrolled in GLOBOSTAD, and follow-up data were obtained from 903 patients. After dupilumab initiation, mean improvements in effectiveness outcome measures from baseline to month 3 were EASI from 25.1 to 6.1, SCORAD 59.3 to 25.3, POEM 19.7 to 8.7, DLQI 13.7 to 5.3, CDLQI 12.2 to 2.7 and pruritus NRS 6.3 to 2.5, with each measure exceeding the minimal clinically important difference. These positive changes in effectiveness outcomes were maintained or further improved through 12 months since treatment initiation. AD-related hospitalizations and emergency room or urgent care facility visits decreased from 11.1% to 1.7% from baseline to month 12. In a multinational real-world setting, dupilumab demonstrated rapid, robust and sustained effectiveness in patients with moderate-to-severe AD across multiple disease domains, including AD signs, symptoms, quality of life and emergency/urgent care visits. Safety was consistent with the known dupilumab safety profile. ClinicalTrials.gov Identifier NCT03992417.

Introduction. In recent years, the attention of researchers has increasingly been attracted by representatives of the genus Rubus, among which the European dewberry (Rubus caesius L.), as one of the most frequently encountered species. There are a number of studies on the chemical composition and pharmacological activity of raw materials of European dewberry. For example, its fruits, leaves, and shoots are rich in compounds of a phenolic nature, have antitumor, antioxidant, and antidiarrheal activity. Consideration of European dewberry as a producing plant of medicinal plant raw materials is relevant. Objective. The study of the composition and content of some groups of biologically active substances (BAS) in the leaves and fruits of European dewberry. Material and methods. The objects of the study were dried leaves and fruits of European dewberry harvested in the Moscow region and the Republic of Bashkortostan in the summer of 2023. The analysis of BAS was carried out according to the methods set out in the Russian State Pharmacopoeia. BAS was detected by qualitative reactions and thin-layer chromatography (TLC). The quantitative determination of BAS was carried out by titrimetry and spectrophotometry (SPM) methods. Results and discussion. During the work, hydrolyzable tannins (10.01 and 5.6%, respectively), organic acids (1.44 and 3.12%, respectively), ascorbic acid (0.068 and 0.11%, respectively) were found in the leaves and fruits of the European dewberry. The amount of anthocyanins in terms of cyanidin-3-5-diglycoside was determined in the fruits of the European dewberry, the value of which was 0.98%. The content of flavonoids in terms of rutin in the leaves of European dewberry was 0.72%. Conclusion. A comparative analysis of BAS in the leaves and fruits of the European dewberry was carried out. The studied objects are promising sources of substances of primary and secondary metabolism.

Introduction. Antibacterial resistance of nosocomial infectious agents is a serious problem. It makes a choice of therapy complicated and worsens the prognosis of the disease significantly. Purpose of the study. The purpose of the study was the pharmacoepidemiological analysis of antibacterial use as a treatment for infections caused by multidrug-resistant pathogens. Material and methods. A retrospective study of medical records was conducted for hospitalized patients at the State Budgetary Institution “City Clinical Hospital named after S.S. Yudin DZM” in 2019–2021. Antibacterial therapy in hospital settings against pathogens of the ESKAPE group was analyzed and the resistance of the detected pathogens was determined. Results. 226 confirmed clinical cases of infection were analyzed. Results of 1422 microbiological studies were studied to determine the resistance of the detected pathogens. The structure of 562 prescriptions of drugs of the group J01 “Antibacterial drugs for systemic use” was studied. In 2020 the total volume of consumption of systemic antibacterials amounted for 85594 DDD. The DU-90% segment by the number of DDDs made up five drugs – meropenem, polymyxin B, tigecycline, amikacin and ampicillin/sulbactam. The intensity of drug consumption was also expressed in DDD/100 bed days. The most prescribed empirically systemic antibiotics for infections treatment have become the group of β-lactam drugs in combination with β-lactamase inhibitors and carbapenems. Tigecycline, polymyxin B and carbapenems are the main drugs for targeted treatment of nosocomial infections at the multidisciplinary hospital of the State Budgetary Institution “City Clinical Hospital named after S.S. Yudin DZM”.

Relevance. The advantages of using clopidogrel for the treatment of atherosclerotic cardiovascular diseases have been demonstrated in many studies. However, the risk of clinically significant bleeding is increased when clopidogrel is used in combination with other drugs. Objective. To investigate the possible relationship between the carriage of CYP2C19 loss-of-function and gain-of-function alleles and bleeding events in patients with coronary heart disease (CHD) ± atrial fibrillation (AF) receiving dual antithrombotic therapy with clopidogrel after acute coronary syndrome (ACS). Materials and methods. A total of 150 patients (median age 65 [60,75;73] years) were studied, including 77 patients with CHD without AF taking clopidogrel + acetylsalicylic acid; and 73 patients with CHD and AF taking clopidogrel + rivaroxaban or apixaban. DNA samples obtained from all patients were genotyped for CYP2C19 rs4244285, rs4986893, and rs12248560. The follow-up period was 16 weeks ± 1 days. Information about bleeding events was obtained using the MCMDM-1 questionnaire. Results. Bleeding occurred in 26 (17.3%) patients. The most common bleeding events were nosebleeds (42.3%), bruises (30.8%), and oral bleeding (26.9%). Among patients with bleeding events compared with those who did not, carriers of the rs12248560 (CYP2C19*17) TT genotype were significantly more common — 19.2% and 3.2%, respectively (p = 0.008). A similar result was obtained in the CHD group without AF (21.4% vs. 3.2%, respectively, p = 0.039). Among patients in the presence of bleeding, ultrarapid metabolizers (*17/*17) were administered significantly more frequently than those without bleeding (p=0.008). Conclusion. Carriage of the rs12248560 (*17) TT genotype and ultrarapid metabolizers (*17/*17) phenotype were associated with hemorrhagic events in patients with ACS receiving dual antithrombotic therapy with clopidogrel.

Introduction. Today, resection margins are assessed in different ways, but in clinical practice, preference is given to the histological method with macro- and microscopic examination of the margins. Assessment of resection margins can be carried out not only during planned histological examination, but also during intraoperative examination. Aim. To evaluate the feasibility of intraoperative assessment of resection margins when performing organ-preserving operations in patients with primary resectable breast cancer. Materials and methods. A retrospective study analyzed data from patients with early breast cancer who underwent surgical treatment at the Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia from June 2020 to May 2022. All patients underwent mammary gland resection with or without intraoperative marginal GI of resection, with sentinel lymph node determination or regional lymphadenectomy at the first stage. Patients included in the final analysis were divided into 2 groups: the study group consisted of patients who underwent intraoperative marginal GI of resection, and the control group consisted of patients who did not undergo intraoperative marginal GI of resection. Marginal GI of resection is performed by a pathologist by measuring the distance from the tumor node to the resection margins on a macropreparation. Frozen sections were always stained with hematoxylin and eosin. Results. The 451 patients with early forms of breast cancer included in the final analysis and subjected to breast resection at the first stage were divided into 2 main groups: the study group consisted of patients ( n = 310) who underwent intraoperative microscopic histological assessment of resection margins, and the control group included patients ( n = 141) who did not undergo intraoperative assessment of resection margins. During intraoperative histological assessment of resection margins, patients with positive resection margins were most often observed with invasive cancer – 20.3 versus 3.9 % with intraductal cancer. Conclusion. Further research is needed to determine the factors influencing the increase in the incidence of positive resection margins and their impact on patient survival rates.

Viruses of soil-dwelling invertebrates remain poorly studied. Viruses of eusocial insects are of special interest as they can serve as a model for studying the spread of viruses via social interactions. In this review, we aim to compile and actualize the available information on the diversity of viruses associated with soil-dwelling social insects, termites and ants. Both groups are among the most functionally important soil invertebrates and include numerous pests and invasive species. We analyzed 93 articles dedicated to viral findings in these groups. Viruses were found in 54 species of ants and 28 species of termites. In sum, 270 viruses and viral genetic variants from over 16 viral orders were found to date in soil-dwelling social insects. Complete information on viruses detected in termites and ants, including insect species, viral name, species, replication status, and GenBank accession number is provided. For most of the novel viruses, replication in the insect was not yet confirmed. We encourage more studies of the virome of ants and termites, which should pay more attention to viral replication and infection symptoms.

This article presents changes to clinical guidelines for the treatment of metastatic colon cancer in 2024. The new provisions in the clinical guidelines are complemented by a brief overview of the research results that underlie them. The changes considered concern not only systemic antitumor treatment, but also surgery and molecular genetic diagnostics. The differences between the recommendations of RUSSCO and the Ministry of Health of Russia are given. The introduction of information to determine the clinical benefit of expensive therapeutic options in relation to the use of the ESMO-MCBS and RUSSCO-MCBS scales is discussed. Aim. Bringing information to a wide range of readers on planned changes in clinical guidelines.

The number of patients with HIV infection in the Russian Federation is increasing, which requires wider implementation of antiretroviral therapy and, accordingly, criteria for assessing its effectiveness. Purpose of the study. To present for consideration a clinical case of tuberculosis combined with HIV infection, with a paradoxically high increase in the number of CD4 lymphocytes in the inflammatory syndrome of immune reconstitution, which does not meet the accepted criteria for assessing the effectiveness of treatment. Materials and methods. Dynamic monitoring of the results of treatment of a patient with tuberculosis combined with HIV infection. Research methods: clinical, radiological, laboratory and microbiological. Results and its discussion. In a patient with tuberculosis combined with HIV infection, a paradoxically high increase in the number of CD4 lymphocytes (15 times) is possible with inflammatory syndrome of immune restoration, followed by a sharp decrease. Conclusion. Approaches to developing criteria for assessing the effectiveness of treatment for patients with tuberculosis combined with HIV infection require further research and additional recommendations.

Industrial fibers and materials, containing industrial fibers, are currently widely used in industrial and civil construction, and many other sectors of the national economy. Methodological approaches for monitoring workers and general population exposure to these fibers in the country should be improved. In this regard, drafts of four new methodical documents were developed, and one of existing methodical document was changed. Two documents are related to the determination of concentrations of industrial fibers in the air of a working zone and environment using phase-contrast optical and scanning electron microscopy. The scanning electron microscopy technique is considered as primary, allowing the determination of the types of industrial fibers in the air, and phase-contrast optical microscopy is the appropriate method for use at the relevant industrial enterprises. Two other interconnected documents contain an algorithm for examining various objects in order to identify potential sources of air pollution by industrial fibers and, also the fact of former air pollutions, which will allow assessing the risks (probability) of workers and general population exposure to industrial fibers. The proposed methods have been tested by field studies and harmonized with similar foreign ones to allow comparison. The current method of measuring of the mass concentration of dust in the air of the working zone does not comply with the current legislation and does not allow comparing the obtained results of measurements of individual types of dust with the existing national standards.

Introduction Sex differences exist in risk factors and comorbidities of older adults (aged ⩾ 65 years) with pulmonary embolism (PE). Clinically relevant sex-based treatment disparities for PE have not been adequately addressed. The few existing show conflicting results due to small sample size (type II error) and suboptimal methods (overreliance on p-value, which may detect differences of small clinical relevance). Methods We assessed sex differences in anticoagulation and advanced therapies for PE in older adults, utilizing data from Registro Informatizado Enfermedad TromboEmbolica (RIETE), a large PE registry with predominant participation from Europe, and data from US Medicare beneficiaries. We prespecified a standardized difference (SRD) > 10% as clinically relevant. RIETE included 33,462 (57.7% female) and Medicare included 102,391 (55.0% female) older adults with PE. Results In RIETE, there were no overall sex differences in the use of anticoagulation (median: 181 vs 180 days, SRD < 1%), fibrinolysis (SRD < 3%), thrombectomy (SRD < 2%), or inferior vena cava (IVC) filters (SRD: 4.4%). However, fibrinolytic therapy (systemic or catheter-based) was less often used in female than male patients with intermediate-risk PE (8.0% vs 12.1%, SRD: 13.6%). No sex differences were noted with advanced PE therapies in Medicare beneficiaries. In unadjusted analyses, fibrinolysis and IVC filter placement were more frequent in Medicare than RIETE participants regardless of sex ( p < 0.001). Conclusion In a predominantly European PE registry and a US study of older adults, there were no overall sex differences in anticoagulation patterns or advanced therapy utilization. Future studies should determine if sex disparities in fibrinolytic therapy for intermediate-risk PE and greater use of advanced therapies in US older adults correlate with clinical outcomes.

Introduction : Playing football (American soccer) at the elite level places extremely high demands on the spine. The choice of treatment for lumbar spinal canal stenosis combined with spondylolysis and anterolisthesis is challenging for surgeons, physicians, and clinicians. Case Presentation : A 28-year-old elite football player from the leading Russian football club is the focus of this case study. Patient complained of constant low back pain radiating to the posterior surface of the right thigh and limited mobility in the lumbar spine. Diagnosis: The patient was diagnosed with degenerative stenosis of the spinal canal at the L5 to S1 level, L4 to L5 disc herniation, spondylolysis, and anterolisthesis of L5 vertebra. Management and Outcomes : Two-stage surgery of combined lumbar spine pathology was performed in May 2021. The first stage of surgical treatment included the spinal and foraminal canals decompression at the L4 to L5 and L5 to S1 levels, as well as posterior fusion with rigid pedicle screws. The second stage involved the subsequent replacement of the rigid to dynamic semirigid rods as signs of the bone defect healing appeared. The athlete returned to team training 6 months after the first stage of surgery and was able to play football at the elite level without restrictions 1 year after the first stage and just 30 days following the second stage of surgical treatment. The athlete continues his career as of the last manuscript’s revision. Conclusions : This method holds potential as an effective approach in the treatment of combined lumbar spine pathology among elite athletes.

The results of a recent extension of the analysis of an ‐conforming method for a model of double‐diffusive flow in porous media introduced in [Bürger, Méndez, Ruiz‐Baier, SINUM (2019), 57:1318–1343] to the time‐dependent case are summarized. These include the efficiency and reliability of residual‐based a posteriori error estimators for the steady, semi‐discrete, and fully discrete problems. The method consists of Brezzi–Douglas–Marini approximations for velocity and compatible piecewise discontinuous pressures, whereas Lagrangian elements are used for concentration and salinity. Novel numerical tests confirm the accuracy of the method and illustrate its application to a salinity‐driven problem of sedimentation.

The thermoreceptor gene TRPM8 (rs7593557) was analyzed in 15 population samples living in different regions of Northern Asia, the Altai-Sayan Highlands and Canada. High frequencies of a rare genotype and allele in the populations of the Altai-Sayan region and Western Siberia were found among the Telengits (22.2 and 41.7% respectively), low among the Siberian Tatars (3.2 and 18.5% respectively), and among the peoples of northern Siberia and the Far East high frequency was found among the Nanais (22.2 and 42.6% respectively), and a low frequency among the Yakuts (1.1 and 10.9% respectively). No deviations from Hardy-Weinberg equilibrium were found. Trans-association of TRPV1, TRPA1 and TRPM8 gene polymorphisms was carried out using the regression analysis method in 14 populations. Of all three pairs, only one, TRPV1/TRPM8, showed a positive correlation (0.55, df = 13, P-value – 0.032). In pairs TRPV1/TRPA and TRPA1/TRPM8, a negative correlation was revealed (–0.545, df = 13, P-value – 0.048) and (–0.46, df = 13, P-value – 0.097) respectively. Our data indicate that the studied polymorphisms of the TRPV1 and TRPM8 genes are correlated with each other and negatively correlated with TRPA. The results obtained may indicate the coevolution of these genes. It was previously shown that TRPV1, as well as TRPM8, was detected with high frequency in the Nanai population. It is likely that these two mutations came simultaneously from East Asia and spread throughout Russia, which explains the fact that they are positively correlated with each other.

Introduction. Surgical treatment of vulvar cancer (VC) entails mental and somatic disturbances due to pain, body image changes, and sexual dysfunction, which are closely associated with impaired social functioning and reduced overall quality of life. However, the results evaluating the impact of rehabilitation programmes on various components of quality of life in these patients remain limited. Aim. to evaluate the effectiveness of rehabilitation programs in relation to the psycho-emotional sphere during 36 months following surgical treatment of early-stage VC. Materials and methods. The randomized controlled study included female patients with VC, divided into two parallel groups of those who received a personalized program of comprehensive rehabilitation (VC-1) and rehabilitation according to the general principles regulated in the national clinical guidelines (VC-2). 36 patients each were randomly assigned to VC-1 and VC-2 groups. The control group included 80 women without female cancer. The VC-2 group was recommended physical activity, psychological support, and anti-edema therapy for lymphostasis. The personalized rehabilitation program in the VC-1 group additionally included lifestyle modification, cognitive-behavioral therapy, intimate hygiene training, magnesium, vitamin B6 and folic acid supplementation, correction of sexual disorders, phytotherapy and physiotherapy from the 3rd month, and climatotherapy and landscape therapy from the 6th month. The “Well-being, Activity, Mood” (WAM) questionnaire was administered at the preoperative visit, 1 week, 1, 3, 6, 12, 24 and 36 months after surgery. Scores were presented as Me [Q25; Q75], differences were considered significant at p 0.05. Results. In the control group, scores on all WAM domains were within normal values throughout the study. In the 1st week after the surgery, well-being and activity decreased to unfavorable values in both VC-1 and VC-2 groups. Mood, however, showed significant positive dynamics compared to baseline. Subsequently, the improvement in the WAM domains was significantly faster and more pronounced in the VC-1 group than in the VC-2 group, reaching the range of favorable values by the 12th month, but not reaching the control group. Conclusion. The personalized comprehensive rehabilitation program showed efficacy on well-being, activity and mood on the WAM questionnaire compared to basic rehabilitation. However, rehabilitation measures should be continued one year after surgery.

Introduction . Patients with diabetes mellitus perform blood glucose measurements daily using their personal glucose meters. The procedure of disinfecting the place of blood sampling with antiseptic solutions or washing hands with soap and drying them thoroughly is recommended to the patients to prevent infections. However, the effects of used antiseptics on the accuracy in blood glucose measurement using glucose meters have not been evaluated. Aim. To evaluate the effects of antiseptic solutions on the accuracy in blood glucose measurement using a personal glucose meter. Materials and methods. We mixed several drops of the control solution (CS) with low “L” or high “H” concentrations, which were developed for the Contour Plus glucose meter, and a drop of one of five antiseptic solutions: chlorhexidine bigluconate (Chlorhexidine), benzyl dimethyl[3-(myristoylamine)-propyl] ammonium chloride monohydrate (Miramistin), salts of fatty acids (liquid soap), ethyl alcohol, hydrogen peroxide. Thereafter, the blood glucose levels were measured with a glucose meter. The results obtained were compared with the reference range for the CS with appropriate concentration. Results. Chlorhexidine solution had no effect on the blood glucose measurements in the CS. Adding Miramistin solution (1/5 of the sample with CS “L” and “H”) and liquid soap (4/5 of the sample with CS “L” and 2/5 of the sample with CS “H”) resulted in underestimating blood glucose measurements. Alcohol solution had no effect on the blood glucose measurements in the CS “L”, but the glucometer failed to measure the blood glucose concentration in half of the cases, requiring the test strip to be replaced (“E11” error); when mixed with CS “H”, the measurements were overestimated in 2/5 of samples. Adding hydrogen peroxide solution (4/5 of the sample with CR “L” and “H”) resulted in overestimating the blood glucose measurements. Discussion. Getting fruit juice on the hands, applying hydroquinone-containing cosmetics to the skin affects the accuracy in glucose measurements. Correct use of alcohol-containing disinfectants does not affect results of the blood glucose measurement using a personal glucose meter. Conclusion . The results of the blood glucose measurement using a glucose meter can be significantly distorted if antiseptic gets into the sample. Traces of antiseptic should be removed before obtaining the sample that will be used to measure the blood glucose level with a glucose meter. Hydrogen peroxide should not be used as antiseptic solution when using a glucose meter.