Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Kalinkin AI, Sigin VO, Nemtsova MV, Strelnikov VV

Breast cancer (BC) is the most frequently diagnosed cancer and one of the major causes of female mortality. The development of prognostic models based on multiomics data is the main goal of precision oncology. Aberrant DNA methylation in BC is a diagnostic marker of carcinogenesis. Despite the existing factors of BC prognosis, introduction of methylation markers would make it possible to obtain more accurate prognostic scores. The study was aimed to assess DNA methylation signatures in various BC subtypes for clinical endpoints and patients' clinicopathological characteristics. The data on methylation of CpG dinucleotides (probes) and clinical characteristics of BC samples were obtained from The Cancer Genome Atlas Breast Cancer database. CpG dinucleotides associated with the selected endpoints were chosen by univariate Cox regression method. The LASSO method was used to search for stable probes, while further signature construction and testing of the clinical characteristics independence were performed using multivariate Cox regression. The dignostic and prognostic potential of the signatures was assessed using ROC analysis and Kaplan–Meier curves. It has been shown that the signatures of selected probes have a significant diagnostic (AUC 0.76–1) and prognostic (p < 0.05) potential. This approach has made it possible to identify 47 genes associated with good and poor prognosis, among these five genes have been described earlier. If the genome-wide DNA analysis results are available, the research approach applied can be used to study molecular pathogenesis of BC and other disorders.

Received: 2022-10-18

Published online: 2022-11-25

DOI: 10.24075/brsmu.2022.056

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VIEWS 2426

Andreevskaya SN, Smirnova TG, Chernousova LN, Larionova EE, Kiseleva EA, Ergeshov A

Fluoroquinolones are the main group of drugs used for treatment of multidrug resistant tuberculosis (MDR-TB). The study was aimed to assess the diversity of mutation in the gyrA gene and to evaluate the association of gyrA mutations with the phenotypic resistance to levofloxacin and the general drug resistance profile of the pathogen. The study involved assessment of diagnostic materials obtained from 2836 patients with pulmonary tuberculosis. TB-BIOCHIP-2 and AmplitubeFQ-RV kits were used for identification of the gyrA mutations. Phenotypic drug susceptibility of M. tuberculosis (MTB) was defined using the BACTEC MGIT 960 test system. It was shown that mutations D94G (41.63%; 95% CI: 38.03–45.32%) and A90V (21.32%; 95% CI: 18.44–24.50%) prevailed in MBT, although some isolates carrying these mutations were obtained from the newly diagnosed patients with pulmonary tuberculosis. It was found that mutation D94A was not strongly associated with the phenotypic resistance to fluoroquinolones. Fluoroquinolone resistance was usually associated with multiple drug resistance (93.52%; 95% CI 91.43–95.12%). In 2.31% (95% CI 1.78–3.00%) of cases, genotypic heteroresistance to fluoroquinolones was detected: mixed populations included 2–4 MTB pools with various structure of the gyrA QRDR. The results obtained lead to the conclusion that resistance to fluoroquinolones that is usually associated with the existing MDR arises in the modern MTB population. MTB carrying gyrA mutations D94G and A90V seems to be the most promising in evolutionary terms.

Received: 2022-10-10

Published online: 2022-10-31

DOI: 10.24075/brsmu.2022.054

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VIEWS 2417

Ermakova DM, Dolgushina NV, Menzhinskaya IV, Lomova NA, Vtorushina VV

Investigation of the effect COVID-19 mediated with autoantibodies has on reproductive outcomes is important. This study aimed to evaluate the profile of antiphospholipid antibodies (aPL) and their association with the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19. The study included 240 patients: 105 of them did not have a history of COVID-19 (group 1) and 135 of them had a history of COVID-19 (group 2) with a mild course (subgroup 2a, n = 85) or moderate course (subgroup 2b, n = 50). With the help of ELISA, serum antibodies (M, G) to cardiolipin, β2-glycoprotein-I, annexin V (AnV), phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylserine/prothrombin complex were determined. The evaluated parameters were the indices of oogenesis, embryogenesis, ART intervention outcomes. In group 2, growing levels of anti-AnV and anti-PE IgG were observed more often (in 28 (20.7%) and 8 (5.9%) patients) than in group 1 (in 10 (9.5%) and 1 (0.95%); p = 0.02 and p = 0.045, respectively). In subgroup 2b we registered a higher level of anti-PE IgG and a higher incidence of early miscarriages (in 6 (12%) patients) than in group 1 (in 3 (2.9%)) (p = 0.024). Weak inverse correlations were found between the level of anti-PE IgG and the number of oocytes and zygotes. The results of this study suggest a negative impact of aPL-mediated COVID-19 on the outcomes of ART programs and the course of early pregnancy.

Received: 2022-09-07

Published online: 2022-10-31

DOI: 10.24075/brsmu.2022.048

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VIEWS 2464

Nuralieva NF, Yukina MYu, Troshina EA, Zhukova OV, Petrov VA, Volnukhin VA

There is evidence in the literature about more frequent association of vitiligo with autoimmune endocrine diseases (AEDs) compared to general population. No full-fledged studies aimed at assessing the prevalence of AEDs in the Russian cohort of adult vitiligo patients have been conducted. The study was aimed to assess the prevalence of AEDs in the cohort of Russian adult vitiligo patients. Patients with vitiligo monitored in two clinics, the Endocrinology Research Centre (Clinic 1; n = 39) and the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology (Clinic 2; n = 26), were enrolled. Along with clinical examination, screening laboratory tests were performed in all patients in order to reveal AEDs. The majority of patients (more than 95% of cases) had nonsegmental vitiligo. Among patients monitored in Clinic 1, AEDs were diagnosed in 85% of cases: isolated AEDs accounted for 39%, while multiple AEDs were found in 46% of cases. Autoimmune thyroid diseases were diagnosed in 69% of cases. Autoimmune adrenal insufficiency was found in 28% of patients, type 1 diabetes mellitus in 21%, hypoparathyroidism in 13%, hypergonadotropic hypogonadism in 10%, endocrine ophthalmopathy in 10% of patients. Among patients monitored in Clinic 2, AEDs were diagnosed in four patients (15% of cases): three patients had primary hypothyroidism in the outcome of autoimmune thyroiditis, one patient had Graves' disease. Thus, the prevalence of AEDs in patients with vitiligo may vary between 15–85%. Vitiligo is most often associated with autoimmune thyroid diseases (15–69%). Vitiligo patients should undergo annual screening aimed at detection of autoimmune endocrine disorders, especially thyroid diseases.

Received: 2022-09-29

Published online: 2022-10-29

DOI: 10.24075/brsmu.2022.055

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VIEWS 2623

Orlova EV, Berdalin AB, Lelyuk VG

Post-stroke lower extremity vein thrombosis can be the reason behind complications of embolic nature and death. This study aimed to investigate the influence of provoking factors, frequency and localization of acute thrombosis, post-thrombotic changes in the lower extremity veins during stroke recovery period. The study involved 1315 patients, 885 (67.3%) male and 430 (32.7%) female, ages 18–94 years, mean age 59.23 ± 13.7 years. All participants underwent lower extremity venous duplex scanning in the early and late stages of stroke recovery period. We found no evidence of interconnections between presence of signs of thrombosis and/or its consequences and the pathogenetic variant of stroke the patient had. Acute deep vein thrombosis was diagnosed significantly more often (p < 0.05) in the early stage of stroke recovery period. The frequency of acute lower extremity vein thrombosis was 7.8%, post-thrombotic changes — 5.6%. Isolated lesion of the lower leg veins was the most common complication associated with deep veins (49.6%). We have discovered a significant relationship between the side of lower extremity paresis (plegia) of and the side of deep vein thrombosis (p < 0.001). No relationship was found between lower extremity superficial and deep vein thrombosis and use of anticoagulants and antiplatelet agents (p > 0.05). Excess body weight was associated with damage to the lower extremity proximal veins (p < 0.05). Women had lower extremity vein thrombosis significantly more often (p < 0.05). Repeated lower extremity venous duplex scanning upon admission to the rehabilitation hospital allowed reducing the risk of venous thromboembolic complications that may develop during the stroke recovery period.

Received: 2022-09-29

Published online: 2022-10-27

DOI: 10.24075/brsmu.2022.053

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VIEWS 2725

Zapesotskaya IV, Sokolyskaya MV, Razuvaeva TN, Borisova SL

The study of neuropsychological features that cause eating disorders may provide a starting point for planning complex studies that allow for integral assessment of the internal and external mechanisms and patterns of eating disorders. The work aims to evaluate the influence of the neuropsychological status on features of the body schema in eating disorders. We conducted an analysis of the subjective and objective indicators of the body image on 51 women aged 20–35 years using face-relative hand position reproduction tests, the "Silhouette" method, measurement of the right hand index finger diameter and of the foot length, and a self-image questionnaire. We carried out qualitative and quantitative assessment of the neuropsychological status using the Luriev test battery. For the analysis of control functions, we used the Wisconsin sorting card test, Cantidad-Numér interference task (Canum), and "Block Span". We found that women with atypical eating behaviors noted the following features associated with a subjective attitude towards their own body: prevalence of dissatisfaction in one's emotional evaluation due to the perception of one's own appearance, stemming from the beliefs and ideas about one's ideal appearance, despite the absence of the abnormalities associated with the objectified ideas of one's own body (weight, size, body proportions). We identified modal-nonspecific control function deficiencies characteristic of different types of eating disorders.

Received: 2022-09-26

Published online: 2022-10-27

DOI: 10.24075/brsmu.2022.051

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VIEWS 2268

Abdraimova NK, Kornienko MA, Bespiatykh DA, Kuptsov NS, Gorodnichev RB, Shitikov EA

Currently, the search for new therapy options for infectious diseases caused by multidrug-resistant Staphylococcus aureus is a priority. Combining antibiotics with virulent (lytic) bacteriophages may be considered a viable alternative to conventional antibiotic therapy. The study was aimed to assess the combined effects of the lytic bacteriophage vB_SauM-515A1 of Herelleviridae family and antibiotics of various classes on the Staphylococcus aureus clinical strains. Strains (n = 4) belong to the clinically significant sequence types ST1, ST8, ST121 and are characterized by multidrug resistance. Efficiency of the combination use of two antibacterial agents was assessed by comparison of optical densities of the test samples and controls after 24 hrs. of incubation. Mutually enhancing activities of bacteriophage used in combination with oxacillin, tetracycline and linezolid were revealed, in contrast to the separate use of each agent. Efficiency generally increased with the selected optimum multiplicity of infection values. No antagonism was revealed when combining the phage with antibiotics. Thus, virulent bacteriophage vB_SauM515A1 can be considered as a possible auxiliary therapeutic agent for antimicrobial-resistant strains of Staphylococcus aureus.

Received: 2022-09-23

Published online: 2022-10-26

DOI: 10.24075/brsmu.2022.052

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VIEWS 2776

Gerasimova AA, Shevchenko YuV, Klimenko PA, Asyrafyan LA

Prediction of ovarian tumor type in pregnant women is of great clinical significance, however, it is vastly difficult. In the last 5–10 years gynecologists were suggested to use RMI (Risk of Malignancy Index) in non-pregnant women, however the value of the test for obstetric practice has yet to be established. The study was aimed to determine RMI-IV and RMI-V during preoperative non-invasive prediction of ovarian tumor type in pregnant women. Retrospective and prospective clinical and laboratory data of 114 pregnant women aged 20–38 were collected. Among them 15 patients had malignant ovarian tumors (MOTs), 28 had borderline ovarian tumors (BOTs), and 71 had benign ovarian tumors. Color Doppler and pulsed wave Doppler ultrasound was performed. The levels of СА-125 were defined by enzyme immunoassay. Models IV, V were used to assess the risk of ovarian cancer. A moderate non-significant increase in blood levels of СА-125 compared to patients with benign ovarian tumors and BOTs was found in pregnant women with MOTs. Patients with BOTs and MOTs showed higher RMI-IV and RMI-V values compared to the group of pregnant women with benign ovarian tumors. Extreme values are required to guarantee the differences in the diagnosis of tumors (RMI-IV > 3500 indicate the presence of MOTs, the values below 100 indicate no malignancy). Similar RMI-V values are 1500 and 60. However, in most cases, availability of RMI-IV and RMI-V is insufficient for decision making, and a comprehensive approach has to be used. Thus, it is difficult to define ovarian mass type in pregnant women using RMI only. Comprehensive clinical assessment with the use of imaging methods is required for preoperative prediction of ovarian mass type in pregnant women, along with the use of prognostic models taking into account the majority of descriptive “morphological” tumor characteristics.

Received: 2022-09-27

Published online: 2022-10-24

DOI: 10.24075/brsmu.2022.050

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VIEWS 2347