[Experience of anticipatory therapy with IL-6 receptor inhibitors and perspectives for its use in the evolution of COVID-19].

The Advisory Board chaired by the chief specialist in infectious diseases of the Ministry of Health of Russian Federation, Professor V.P. Chulanov was held on June 18, 2022 in Saint Petersburg. Aim. The main purpose of the Board was following discussion: the analysis of the real-world data of levilimab as an anticipatory therapy for COVID-19 in hospitalized patients; the review of the experience and perspectives of levilimab as an anticipatory anti-inflammatory option for outpatient patients who meet defined clinical and laboratory criteria. Results. The analyzed data on clinical efficacy and safety formed the basis of recommendations proposed by experts for the use of levilimab in the inpatient and outpatient medical care for COVID-19.

[The dynamics of indices of professional self-evaluation and social status of physicians: the first results of reforms in health care system].

In Russia, an active transformation of national health care system takes place and one of the most important of its activities became approval of the "road map". In 2017, survey of physicians was carried out that revealed a number of patterns and problems in the field of physicians perception of their own lives, social self-implementation. In 2019, survey was re-carried out covered 311 specialists from the Republic of Bashkortostan. The purpose of this study was to analyze the dynamics of indices of professional self-assessment and social status of physicians in 2017-2019. The results testify a number of significant changes that took place by 2019: 1) number of specialists evaluating their own competence as "Excellent" statistically significantly increased (p=0.015); 2) percentage of specialists of second qualification category significantly decreased (p=0.0068) and previously observed relationship between professional self-assessment and qualification category lost its significance; 3) physicians began to statistically significantly more often identify themselves with highest stratum of society (p=0.012); 4) situation associated with lack of free time (p=0.021) and fears of losing job (p=0.044) worsened significantly. The research data mainly testify positive changes in social well-being of physicians in 2017-2019 and can be considered as first results of reform of national health care system. Nevertheless, increase of deficiency of free time and fears of losing job requires development and implementation of appropriate preventive measures.

[The efficacy and safety of eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria. Results of a phase III randomized open-label comparative clinical trial].

AIM: To establish the equivalent efficacy and comparable safety profile of biosimilar Acveris and referent eculizumab product Soliris used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). MATERIALS AND METHODS: Were included in the phase III multicenter 28 PNH patients, open-label clinical trial. Participants were randomized (1:1) into 2 treatment groups: investigational product (Acveris, n=14) and referent product (Soliris, n=14). Patients received eculizumab as the intravenous infusion 600 mg once a week during the first 4 weeks, 900 mg at week 5 and then 900 mg every 14 days (2 days) up to week 27 of the study. The efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of the compared products were analyzed after the end of 27 weeks of the study. The primary efficacy endpoint was the area under the curve LDH concentrationtime (AUCLDH) throughout the study period weeks 527. RESULTS: The difference between the mean AUCLDH values between the Acveris and Soliris groups was 5380.0 [-38 773.87; 49 533.87] U/ldays. The 95% CI limits for the difference in mean AUCLDH values between the groups fit the preset 95% CI [-146 500.9146 500.9] U/ldays and establish the equivalent efficacy of the biosimilar and referent product according to the primary efficacy endpoint. The safety profile of both Acveris and Soliris was expected and comparable according to the proportion of patients with adverse events. The formation of binding antibodies to eculizumab was not detected in both the groups. CONCLUSION: The study established the equivalent efficacy of biosimilar product Acveris and referent eculizumab product with the evidence of effective suppression of intravascular hemolysis in PNH patients along with a comparable favorable safety profile.

[Vascular remodeling with violations of intracardiac hemodynamics in patients older age category, combined with the clinical-cluster, neurocognitive and biomarker heterogeneity in multifocal atherosclerosis].

AIM: Study of the remodeling of the carotid arteries with violation of intracardiac hemodynamics in patients with MFA, and the estimation of the main parameters of dyslipidemia, apoptosis, and oxidative stress in patients with high vascular risk older age group (6175 years) in a Regional vascular center of Ufa. MATERIALS AND METHODS: Depending on the predominant lesion of the vascular pool, patients were divided into 3 clusters by the method of hierarchical analysis of categorical variables according to the clinical manifestation of atherosclerotic lesions of the heart, brain and lower limb arteries confirmed by coronary angiography, ultrasound Doppler of the main arteries of the head and lower extremities. 96 of them were IPA with a primary lesion of the heart (1st cluster), the 96 IPA with a predominance of lesions of the carotid arteries (2nd cluster), 96 patients with ischemia of lower extremities (3rd cluster). At the hospital stage, electrocardiography, echocardiography, magnetic resonance imaging of the chest and abdomen, ultrasound of the OBP and kidneys, if necessary, ultrasound of the pelvis were performed. Determination of 8-ON-deoxyguanosine, annexin-5 (An-5) and Aan-5 in blood by ELISA was performed in all patients with MFA, as well as standard biochemical screening for lipidogram examination. RESULTS: We have found that most often in different combinations and with different degrees of severity according to our data are observed: Clinical manifestation of atherosclerotic heart disease (cluster 1) mainly due to its history in combination with stage III hypertension with increasing thickness of intima-media complex and stenosis of the right WASP, left ventricular dilatation, as well as a higher concentration of Aan-5IgMand LP-A as a risk factor for coronary heart disease, atherosclerosis, atherothrombosis. 2. Hemodynamically significant violations of the main arteries of the head in patients of the 2nd cluster mainly with acute ischemic cerebral circulation, in which there was a development of left ventricular hypertrophy with an increase in the size of the left atrium and the presence of atherosclerotic plaque of the right and left WASP. The higher prevalence of stroke was combined with a marked cognitive deficit among patients of cluster 2 with the lowest level of An-5, an increase in total cholesterol and low-density lipoprotein cholesterol. 3. The total severity of the condition in patients with hemodynamic ischemia with clinical manifestation of vascular lesions of the lower extremities was accompanied by a predominant increase in stable angina with FC2, lerish syndrome with occlusion of the iliac, superficial femoral arteries, the presence of insulin-independent type 2 diabetes, which in this group was established in 59.4% of cases, combined with a higher concentration of the marker of oxidative stress 8-ON-deoxyguanosine and hypertriglyceridemia. CONCLUSION: The construction of a three-cluster model in patients at high vascular risk of the elderly age category showed the interaction of cardio-carotid comorbid background on the clinical diversity of systemic vascular lesions in MFA with the development of remodeling of the main arteries and disorders of intracardiac hemodynamics associated with laboratory changes in the assessment of the main parameters of dyslipidemia, apoptosis markers, oxidative stress.

[Clinical Features of Comorbid Cluster and Premorbidly Manifestations in Patients with High Vascular Risk in the Middle Age Category with the Presence of Multifocal Atherosclerosis].

OBJECTIVE: to study clinical and cluster features of cardiovascular burdening taking into account the comorbid polymorbid background in patients of middle age (45-60 years) with the presence of multifocal atherosclerosis (MFA). MATERIALS AND METHODS: Patients were examined in the Regional Vascular Center of Ufa (RVCU). Depending on the predominant localization of lesions in the vascular bed patients were divided into 3 clusters by the method of hierarchical analysis of categorical variables according to the clinical manifestation of atherosclerotic lesions of the heart, brain and lower limb arteries confirmed by coronary angiography, ultrasound Doppleroscopy of main arteries of the head and lower extremities. Ninety-six patients had predominant lesions in the heart (1st cluster), 96 - in carotid arteries (2nd cluster), and 96 patients had ischemia of lower extremities (3rd cluster). Examination during hospitalization in RVCU included when indicated echocardiography, magnetic resonance imaging of the chest and abdomen, ultrasound studies of abdomen, kidney, and pelvis. RESULTS: According to data obtained the following conditions were most often observed in different combinations and with varying degrees of severity of clinical manifestation.Claster 1. Clinical manifestation of atherosclerotic heart disease mainly due to stage III hypertension, history of myocardial infarction were combined with pneumonia, chronic obstructive pulmonary disease with the outcome in pneumosclerosis and emphysema, as well as the presence of cholecysto-cardial syndrome, chronic gastritis, chronic cholecysto-pancreatitis, abdominal ischemic syndrome, rheumatoid arthritis, diabetes mellitus, and chronic pyelonephritis.Claster 2. Hemodynamically significant lesions of brachiocephalic arteries mainly with acute ischemic disturbance of cerebral circulation were combined with bronchial asthma, (the development of which was associated with prolonged persistent eosinophilic inflammation), worsening of chronic kidney disease with urolithiasis, angionephropathy and iron deficiency anemia, as well as the presence of dorsopathy associated with stenotic atherosclerosis of brain vessels.Claster 3.Hemodynamic ischemia with clinical manifestation of vascular lesions of lower extremities was accompanied by type 2 diabetes, chronic cholecysto-pancreatitis, erosive and ulcerative lesions in the stomach and duodenum, polyosteoarthrosis, abdominal-ischemic syndrome. Type 2 diabetes prevailed in patients with occlusion of right posterior tibial artery and trophic ulcer of the right foot. CONCLUSION: Interdependence of comorbid and polymorbid background and cardiovascular burdening changes their clinical picture and course, increases number of complications and their severity.

[An impact of affective and cognitive impairment on the quality of life in patients with lymphoproliferative diseases]. / Vliianie affektivnykh i kognitivnykh narushenii na kachestvo zhizni u patsientov s limfoproliferativnymi zabolevaniiami.

AIM: To assess the neurological and cognitive status, identify the frequency of anxiety and depression in patients with lymphoproliferative diseases, and analyze their impact on the quality of life of patients. MATERIAL AND METHODS: Fifty-eight patients, including 35 (60.34%) men and 23 (39.66%) women aged from 42 to 86 years, with a diagnosis of chronic lymphocytic leukemia (CLL) or multiple myeloma (MM) were examined. Clinical and anamnestic methods, the Montreal scale of cognitive function assessment, the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Cancer Therapy-General (FACT-G) were administered. RESULTS: Cognitive impairment was observed in 44 (75.86%) patients. Thirty-two (56.14%) patients had no symptoms of depression, clinically diagnosed depression was observed only in 8 (14.04%). In 37 (64.91%) patients, there were no symptoms of anxiety, clinically diagnosed anxiety was revealed in 6 (10.53%). The average score on the FACT-G scale for quality of life was 62.72±23.29 with a maximum score of 108. CONCLUSION: Cognitive impairment was observed in a large number of patients. Symptoms of depression were found in less than half of the patients, and manifestations of anxiety were found in one third. The presence of affective disorders, such as anxiety and depression, reduced quality of life evaluated in all its modules.

[Hygienic evaluation of chronic lymphatic leukemia in Bashkortostan Republic].

Prevalence of chronic lymphatic leukemia increased in Bashkortostan Republic over 1999-2008 with predominance of urban population, male patients, individuals aged 80-84. Reliable correlation was seen between pollutants releases into the ambient air and the morbidity parameters over following 5 years.

[Molecular genetic analysis of the interleukin 6 and tumor necrosis factor alpha gene polymorphisms in multiple myeloma]. / Molekuliarno-geneticheskii analiz polimorfizma genov interleikina 6 i faktora nekroza opukholei al'fa u bol'nykh mnozhestvennoi mielomoi.

The-174G alpha-->C polymorphism of the interleukin 6 (IL-6) gene promoter and the-308G alpha-->A polymorphism of the tumor necrosis factor alpha (TNF alpha) gene promoter were tested for association with multiple myeloma (MM) varying in severity. Of 69 patients, 19 had aggressive MM, 26 had benign MM, and 24 had unidentified MM. The control group (N = 102) matched the test group in age and sex composition. The two groups did not significantly differ in allele and genotype frequencies of the IL-6 and TNF alpha genes. Genotype CC, which determines low-level expression of IL-6, occurred at a frequency of 0.35 in patients with low-progressing MM and was absent from patients with aggressive MM. The TNF alpha gene showed no association with predisposition to MM or clinical variant of the disease. On this evidence, the polymorphic variants of the cytokine genes were assumed to have no effect on predisposition to MM. As for MM progression, genotype CC of the IL-6 gene was associated with milder clinical signs in patients from Bashkortostan.