[Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen].

Рost-COVID-19 syndrome (PS) is one of the medical and social problem. According to WHO, 10-20% of COVID-19 patients suffer from PS. The use of medical gases - inhaled nitric oxide (iNO) and molecular hydrogen (iH2) - may influence on the mechanisms of development PC. AIM: To evaluate the safety and efficacy of the combined inhalation of NO and H2 (iNO/iH2) in patients with respiratory manifestations of PS. MATERIALS AND METHODS: 34 patients with PS (11 men/23 women, 60.0±11.7 years) were included in the prospective open-label controlled study in parallel groups: the main group (n=17) received iNO/iH2 for 90 minutes once a day for 10 days (concentration of NO 60 ppm, H2<4% in the gas mixture), the control group (n=17) didn't receive inhalations. The period from the confirmation of COVID-19 to the start of the study was 641.8±230.5 days. The groups did not differ in the baseline parameters. The clinical symptoms (from the self-observation diary and mMRC questionnaires, "dyspnea language"), FAS, HADS, SF-36 scores, 6-minute walk test, the blood serum parameters of oxidative stress, the dynamics of the microcirculation in the eye bulbar conjunctiva were evaluated. The individual dose of iNO has chosen during a 15-minute test (the positive dynamics of the microcirculation have indicated that the dose was selected correctly). RESULTS: The decrease the symptoms severity, such as dyspnea, cough, fatigue and palpitations (p<0.005), the increase in SF-36 questionnaire scores (p=0.006) and a reducing of FAS score (p=0.001), as well as the anxiety component of HADS (p=0.02) were revealed at the end of treatment in the main group compared to the control group. We observed an improvement in distance walked (p=0.01) and the values SpO2 (p=0.04) in 6-minute walk test, the increase in the volumetric blood flow velocity in venules (p<0.001), and the date in oxidative damage (p<0.001) and antioxidant activity (p=0.03) parameters in the blood serum. CONCLUSION: The results of the study demonstrate clinical efficacy iNO/iH2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS.

[The determinants of vaccination against the new coronavirus infection (COVID-19) of residents of the circumpolar region of Russia].

The maintenance of health of residents of the Northern Regions of Russia, including those living in the Arctic zone of the cbountry, is a condition of its advance development in XXI century. The percentage of Russian citizen vaccinated against the new coronavirus infection (COVID-19) does not exceed 50% after beginning of implementation of vaccination program. It can be conditioned by lower level of both of credence of citizen to health care system and health literacy.Purpose of the study is to establish determinants of vaccination of population against COVID-19 in circumpolar region of Russia as exemplified by the Arkhangelsk Oblast.The sociological survey was carried out using the interview technique of patients of medical organizations (n=433) and conditionally healthy residents of the Arkhangelsk Oblast (n=139). To evaluate the level of general health literacy the Russian version of questionnaire HLS19 - Q22-RU was applied. The most of conditionally healthy respondents and consumers of medical services looked for information about methods of prevention and treatment (80.4% and 58.2% correspondingly), had an experience of vaccination against COVID-19 (79% and 56.3% correspondingly). The relative chances of conditionally healthy respondents, women, and respondents having no children and no credence to national health care system to independently look for information related to COVID-19 is higher at 2.94, 2.08, 1.55 and 1.48-1.57 times correspondingly. The relative chances of conditionally healthy respondents having no children in family and assessing one's economic status as "higher than average" to be vaccinated against COVID-19 is higher at 4.02, 1.52, 1.53 times correspondingly. Availability of experience of vaccination against COVID-19 is conditioned by higher level of general health literacy.In the Arkhangelsk Oblast and other circumpolar regions of Russia the programs of increasing loyalty of citizen to measures of population prevention, including vaccine prevention, is to be implemented with consideration of established determinants of of vaccinations against COVID-19.

[Hydrogen effect on the mechanisms of mucosal immunity in patients with COVID-19].

AIM: To study the inhalation of an active form of hydrogen effect to mucosal and system immunity in a rehabilitation program for health workers. MATERIALS AND METHODS: The study involved patients that survived COVID-19 after therapy with inhaled hydrogen for 90 minutes (n=30), and a control group of patients treated according to standard protocol for managing patients that survived COVID-19 during the rehabilitation period (n=30). Biomaterial was carried out in 2 stages: on the first day of the study, before the accepted therapy and on the 10th day of the study. The indicators of humoral and cellular immunity were studied. The levels of secretory immunoglobulin A (sIgA) and IgG were investigated using the method of enzyme-linked immunosorbent assay. Phagocytosis was assessed on a Beckman Coulter FC-500 flow cytometer. Statistical data processing was carried out in the GraphPad Prism 7.00 software using nonparametric methods. RESULTS: It was shown that the phagocytic index (PI) of monocytes in nasal scrapings after inhaled hydrogen treatment did not significantly change relative to the first day of treatment and control, while the PI of granulocytes in nasal scrapings significantly increased relative to the first day by 2.5 times (p=0.000189), as well as relative to the control by 1.1 times (p=0.047410). PI of monocytes in pharyngeal scrapings showed a significant increase relative to the first day of treatment by 2.8 times (p=0.041103), however, did not differ relative to the control. PI of granulocytes of pharyngeal scraping did not differ significantly relative to the first day and control. PI of granulocytes and blood monocytes of the studied group did not change significantly. PI of granulocytes and monocytes of peripheral blood relative to control during therapy did not change. The sIgA level in nasal scrapings significantly increased by 2.9 times, while in pharyngeal scrapings the level of sIgA significantly decreased by 2 times. Сonclusion. We have shown an increase in granulocytes PI in the nasal cavity and oral monocytes, as well as in the level of sIgA in the nasal cavity during therapy with active hydrogen. The data obtained indicate the effectiveness of therapy, which can be used both in the treatment of COVID-19, and in post-COVID syndrome as an additional therapy. The absence of changes in blood parameters, as well as individual links in nasal and pharyngeal scrapings, requires further study to develop ways to overcome treatment tolerance.

[Comments on the article by Professor Dmitry D. Pletnev "Hypertension (the experience of analyzing its genesis)"].

The purpose of the comments is the analysis of Professor Dmitry D. Pletnev's article Hypertension (experience in analyzing its genesis) from the point of view of modern ideas about arterial hypertension. Currently, a small number of publications of Professor D.D. Pletnev, a Russian scientist and clinician, unjustly convicted in 1937, have been preserved. The small work includes not only a deep and critical analysis of the pathogenetic mechanisms of this disease, but also an assessment of diagnostic methods, as well as a detailed description of the clinical picture. The paper, published in 1935, remains relevant and of interest to clinicians and medical historians.

The medical demographic characteristic of group of citizen injured in road accidents on the Federal Highway.

The role of citizen of elderly age in road accidents on the Federal Highway was principally passive since passengers of vehicles predominated (p<0,0001). The most of victims of elderly age (66,7%) suffered of combined lesions. Considering gender of victim, presence of ethanol in blood at the moment of hospitalization, the role of victim of road accident and degree of severity of lesions in citizen of elderly age was in overall higher than in citizen of able-bodied age up to 2.3-2.9 points according ISS scale. The established medical demographic characteristics of victims of elderly age condition necessity of development of differentiated approaches to their medical care support, planning of measures of population prevention of medical sanitary aftermaths of road traumatism.

[Biological activity of interferons in the novel coronavirus infection COVID-19].

INTRODUCTION: The immunopathogenesis of the novel coronavirus infection COVID-19 is usually associated with the development of imbalance in the immune response to its causative agent, SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). This is manifested, in particular, by interferons' (IFNs) deficiency at the beginning of the disease followed by hyperproduction of pro-inflammatory cytokines. The virus causes a decrease in IFN types I (α/ß) and III (λ) levels; changes in IFN type II (γ) are less studied. In this regard, it is relevant to assess the functional bioactive IFN (interferon status) in COVID-19. The aim of the study was to assess the antiviral potential of the body by testing the biologically active IFNs in COVID-19. MATERIAL AND METHODS: We used biological serum samples of COVID-19 patients taken in the acute phase (110 patients on the 1-5 days of the disease) and during rehabilitation (47 patients during 1-3 months after the disease onset). Assessment of interferon status was performed according to the technique developed by the authors and described earlier. RESULTS: The IFN status of patients with COVID-19 in the acute period and in the phase of post-infection rehabilitation was studied вduring the observation period. It was found that SARS-CoV-2 causes a pronounced inhibition of biological activity of IFN types I and II compared to the reference values by more than 20 and 7 times, respectively. During the post-COVID period, incomplete recovery of the IFN system activity was registered, which proceeded very slowly. No cases of reaching physiological indicators of interferon status were identified during the observation period. CONCLUSION: The obtained data on deficiency of the functional biologically active IFN confirm the hypothesis about the predominant role of impaired IFN production of different types in the immunopathogenesis of the novel coronavirus infection.

[The development of first medical care support to victims of road traffic accidents: The publications review].

The medical and demographic losses because of road traffic accidents continue to be significant in most of economically developed and developing countries. The national strategies of reducing medical and demographic losses include two groups of measures, depending on object of exposure: (1) targeted to decreasing risk of road traffic accidents and (2) targeted to timely and adequate medical care support of victims. Beyond this classification are activities targeted to developing and improving in participants of road traffic skills of first self-care and mutual assistance. The availability of mentioned skills is important for saving lives and preventing permanent disability of victims of road traffic accidents.

[Evaluation of the relationship between the parameters of peripheral skeletal and respiratory muscles in patients with chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) is a group of diseases with high levels of comorbidity. Pathological changes of peripheral skeletal and respiratory muscles in COPD patients, which are often underestimated, occupy a special place. AIM: To study the relationship between functional and quantitative parameters of the peripheral (limb muscle) and respiratory muscles in COPD patients. MATERIALS AND METHODS: 127 patients (98 men/29 women, mean age 67.68.2 years) were under observation without acute COPD. All COPD patients were classified according to GOLD (2019) into groups A, B, C, D. The algorithm of the European Working Group on Sarcopenia in Older People (EWGSOP2) was used to diagnose sarcopenia. The muscle mass was measured using dual energy X-ray absorptiometry (DXA) and the appendicular lean mass index (ASM) was estimated. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured by body plethysmograph MasterScreen Body. Quantitative assessment of thoracic muscle cross-sectional areas were performed using the CT scan using Vidar Dicom Viewer software. RESULTS: Sarcopenia was diagnosed in 43.3% of COPD patients. Respiratory muscle dysfunction was determined in 66.1% of patients with COPD, its probability increased in groups C and D in comparison with groups A and B [chance ratio 6.6 (95% confidence interval 2.915.0); p0.0001]. Correlations between the functional parameters of sarcopenia and respiratory muscle strength as well as between the mass of peripheral skeletal muscles and respiratory muscle area have been established according to the data of computerized tomography (р0.01). Sarcopenia as well as respiratory muscle dysfunction was observed more frequently in persons with severe and extremely severe airway obstruction and in patients with predominantly emphysematic COPD phenotype (p0.01). CONCLUSION: Sarcopenia is a frequent comorbidity in COPD and its development is connected with the severity of the course of the main disease. Correlation between parameters of peripheral (limb muscle) and respiratory muscles in patients with COPD has been determined.

Pulmonary vasculitis: diagnosis and treatment.

Pulmonary vasculitis is a group of rapidly progressing severe diseases characterized by vascular inflammation, destruction and necrosis of the pulmonary tissue. The pathological process in the lungs varies from diffuse alveolar hemorrhage to inflammation of the parenchyma, pleural effusion, thrombotic and thromboembolic complications. Depending on the size of the affected vessels, vasculites are divided into vasculites of large, medium and small vessels. Most frequently the lung is found in the small vessels vasculitis, including ANCA-associated vasculitis [granulomatosis with polyangiitis (GP), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA)] and the disease is glomerular basement membrane (goodpasture syndrome). Clinical examination of other systems and organs involved in the pathological process, including the skin and kidneys, as well as the detection of autoantibodies can improve approaches to early diagnosis and treatment of vasculitis. Treatment of life-threatening pulmonary bleeding and irreversible damage to organs, especially the kidneys, requires rapid diagnosis of these conditions. Vasculitis is a rare disease with lesions of many organs, and methods of their treatment, including biological, are rapidly developing, which requires the cooperation of doctors of various specialties and specialized centers to achieve better control of the disease.

[Analysis of the state-of-the-art of consulting medical care to patients with glucocorticoid-induced osteoporosis or its risk according to the data of a questionnaire survey (GLUCOST study)].

AIM: To analyze the state-of-the-art of consulting medical care to Russian patients with glucocorticoid-induced osteoporosis (GCOP) or its risk. SUBJECTS AND METHODS: This GLUCOST study was organized and conducted by the Russian Association of Osteoporosis. A total of 1129 patients with chronic inflammatory diseases, who had been taking oral glucocorticosteroids (OGCSs) a long time (3 months or more), were examined. The patients filled out an anonymous questionnaire on their own. Whether the measures taken to diagnose, prevent, and treat GCOP complied with the main points of Russian clinical guidelines was assessed. RESULTS: 61.8% of the patients knew that the long-term treatment of GCOP might cause osteoporosis. 48.1% of the respondents confirmed the results of bone densitometry; 78.1% of the patients reported that they had been prescribed calcium and vitamin D supplements by their physician, but their regular intake was confirmed by only 43.4%; 25.4% of the patients had sustained one low-energy fracture or more. Treatment for GCOP was prescribed for 50.8% of the patients at high risk for fractures, but was actually received by 40.2%. Therapeutic and diagnostic measures were implemented in men less frequently than in women. When the patient was aware of GCOP, the probability that he/she would take calcium and vitamin D supplements rose 2.7-fold (95% Cl; 2.1 to 3.5; p = 0.001) and that he/she would follow treatment recommendations did 3.5-fold (95% Cl; 2.3 to 5.3; p = 0.001). Bone densitometry increased the prescription rate for antiosteoporotic medication and patient compliance. CONCLUSION: According to the data of Russia's large-scale GLUCOST survey, every four patients with chronic inflammatory disease who are on long-term OGCS therapy have one low-energy fracture or more. Due to inadequate counseling, the patients are little aware of their health and do not get the care required to prevent the disease. Less than 50% of patients who have GCOP and a high risk for fractures undergo examination and necessary treatment aimed at preventing fractures.

[Current approaches to the diagnosis and treatment of postmenopausal osteoporosis].

Postmenopausal osteoporosis (OP) is a disease afflicting every three women above 50 years of age. The sociomedical significance of OP is determined by the development of fracture in minimal injuries resulting in disability and, occasionally, death. The review presents a new management strategy described in the European and Russian guidelines. Particular emphasis is laid on the early identification and treatment of patients at high risk for fractures. The current requirements for drugs used to treat OP are described, by using as an example strontium ranelate, one of the first-line agents for the treatment of postmenopausal OP.

[Preclinical diagnosis of cardiovascular diseases in workers engaged into industries with radiation danger].

The authors presented results of single-stage cross study of randomized select from a cohort of long seniority workers of isotope separation plant in Siberian Chemical Enterprise, with studies of inflammation markers, vascular and platelet hemostasis, serum lipid parameters, calculated atherogeneity coefficient, homocysteine levels. Serum atherogeneity coefficient and inflammation markers levels (fibrinogen, C-reactive protein) could be considered as the most informative laboratory indicators of underlying cardiovascular diseases in individuals without ischemic heart disease. Among a list of standard inductors of platelet aggregation, collagen and epinephrine should be considered preferential. Increased platelet aggregation requires disaggregant therapy, especially in smokers. Increased homocysteine level is associated with high frequency of atherosclerotic plaques and smoking.

[Bone mineral density and risk factors for developing osteoporosis in bronchial asthma patients]. / Mineral'naia plotnost' kostnoi tkani i faktory riska razvitiia osteoporoza u bol'nykh bronkhialnoi astmoi.

AIM: To estimate mineral bone tissue density (MBTD) and risk factors for osteoporosis in patients with bronchial asthma (BA). MATERIAL AND METHODS: A cross-sectional study included 119 patients (48 males and 71 females) aged 18 to 49 years who had no diseases or states that can induce MBTD, except BA. The patients were divided into 3 groups: 1) those untreated with glucocorticoids (GC); 2) those who received inhaled GC; and 3) those who permanently took oral and inhaled GC. The patients underwent questionnaire survey, double-power X-ray absorption of the lumbar vertebral column and proximal femur, and X-ray study; forced expiratory volume per sec and peak expiratory function were measured. RESULTS: In Group 1 patients, there was a high incidence of osteopenia that increased with the severity of BA. About 2.5-year therapy with inhaled GC in large and small doses had no impact on MBTD. The prolonged use of systemic GC caused a marked reduction in MBTD and led to the development of osteoporetic fractures. Changes were detected in both the lumbar spine and proximal femur. In males and females, MBTD decreases were equal. MBTD correlated with the duration of GC therapy and with age at its initiation, but not with the daily dose of GC. In 15.4% of the patients, MBTD remained in the normal range despite the prolonged use of GC in large doses. Osteoporetic fractures were observed at the values of MBTD, which had not reached the stage of osteoporosis according to the WHO criteria, which was indicative of qualitative GC-induced bone tissue changes. CONCLUSION: GC is an important, but not alone, risk factor for osteoporosis in asthmatic patients. The high rate of low MBTD among the patients receiving no GC suggests that it is necessary to make an early diagnosis and to perform rational treatments.

[The effect of low doses of a synthetic analog of a quinoid radiotoxin on the viability of normal and gamma-irradiated animals]. / Vliianie malykh doz sinteticheskogo analoga khinoidnogo radiotoksina na zhiznesposobnost' normal'nykh i gamma-obluchennykh zhivotnykh.

The method for a production of synthetic quinoid radiotoxins in vitro has been developed and described. Synthetic quinoid radiotoxins like quinoid radiotoxins (qRT) which are being produced from irradiated tissues of the organisms have demonstrated high toxicity at relatively high qRT concentrations. However, when synthetic qRT is introduced into the organisms in ultra-small concentrations, one can observe the opposite action: the resistance of the organism increases and a number of essential functions are activated. Quinoid radiotoxins are assumed to take part in regulatory processes responsible for radiation hormesis.

[An intranasal method of administration of calcitrin to steroid-dependent patients with bronchial asthma]. / Endonazal'nyi sposob vvedeniia kal'tsitrina steroid-zavisimym bol'nym bronkhial'noi astmoi.

The efficacy of endonasal calcitrin was studied against that of intramuscular. The drug was given endonasally in a dose of 3 units twice a day during 1--1.5 months. The effect on the calcium-regulating system (total calcium, calcitonin, parathyroid hormone), external respiration, its analgetic action were similar to such of the intramuscular mode. Endonasal calcitrin is recommended for outpatient use.