[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

[ACTIV SARS-CoV-2 registry (Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients). Assessment of impact of combined original comorbid diseases in patients with COVID-19 on the prognosis].

AIM: Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. MATERIALS AND METHODS: The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. CLINICALTRIALS: gov ID NCT04492384. RESULTS: Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. CONCLUSION: Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

Morphofunctional Characteristics of Erythrocytes and Blood Erythropoietin Level in Patients as Predictors of Severe Course of COVID-19.

Morphological and functional characteristics of erythrocytes, hemoglobin, and erythropoietin level in the venous blood were evaluated by laser interference microscopy, Raman spectroscopy with a short-focus extreme aperture lens monochromator, and by ELISA, respectively, in 30 patients with verified moderate COVID-19 at the time of hospitalization and 30 healthy volunteers. The patients whose course of COVID-19 has worsened to critical by day 5 had already had lower (p<0.001) indicators at the time of hospitalization such as the area and thickness of erythrocytes, the hemoglobin distribution and packing density, hemoglobin conformation index (I1355/I1550)/(I1375/I1580) reflecting its oxygen affinity, and blood erythropoietin content. Our findings suggest that these characteristics of erythrocytes, hemoglobin, and erythropoietin can serve as potential predictors of COVID-19 aggravation in hospitalized patients.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2¼).

Aim      To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods  The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion      In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

[Cardiovascular Risks Associated with the use of Performance-Enhancing Stimulants].

The number of people involved in regular exercise and sports is increasing. Not infrequently, this is associated with intake of sports biologically active food supplements (BAS) and stimulators of physical ability. Data has been reported on the frequency of use of physical ability stimulators among professional athletes and on the use of the most popular food supplements among young people. Special attention is paid to the effect of such use on the cardiovascular system of athletes. This review describes negative cardiac effects and clinical cases of death of athletes due to the use of such supplements and stimulators.

[Using L-carnitine to improve the adaptation of young athletes to physical load and the correction of stress-induced cardiomyopathy].

The mechanisms of L-carnitine action and ergogenic pleiotropic effects of drugs, which play important role in sports medicine are described. Results of a comparative, parallel-group randomized clinical trial of L-carnitine (Elkar, PikFarma) in young athletes (football players, walkers) are reported. Elkar increases the body adaptation to physical stress and has a pronounced therapeutic effect in athletes with stress-induced cardiomyopathy by reducing the representation of potentially dangerous arrhythmia (sinus bradycardia less than 2 - 5 centile, 2nd degree atrioventricular block type II, T-wave inversion in more than 2 leads, and/or ST segment depression) and severity of benign ECG disturbances and hemodynamic changes, and decreasing the concentration of biochemical markers of myocardial damage (troponin, natriuretic peptide, creatine phosphokinase MB fraction) and cortisol. In general, Elkar contributed to a significant reduction in symptoms of cardiac remodeling in 75% of patients and had a weak effect in 25% of patents. It is concluded that the use of Elkar in playing sports and sports coaching quality of endurance is appropriate, especially in terms of myocardial remodeling.

[Changes of QT interval during graded exercise test in healthy adolescents aged 11-15 years].

Aim of the study was determination of physiological limits of QT-intervals and its derivative values in healthy children and adolescents during graded exercise tests. We examined 100 healthy boys and girls aged 11-15 years (mean age 13.4+/-2.1 years) and performed electrocardiography at rest and standard veloergometry (VEM) in all of them. We analyzed corrected intervals according to Bazett (QTc=QT/RR) and Fredericia (FQTc/3RR) formulas. Hysteresis QTc was calculated as difference between QTc durations during recovery and exercise at same heart rate (HR) Baseline HR before VEM exceeded rhythm on resting electrocardiogram by 5-15 bpm (84+/-8 vs 70+/-6, respectively, p<0.05) Increase of HR at exercise (mean 172+/-11 bpm) was similar in both sexes. QT interval decreased by 7-10% (18-31 ms) per each 25 w (p<0.05). Values obtained at determination of FQTc we found values 26-52 ms lower than those calculated by the Bazett formula in the process of whole test. Determination of FQTc compared with calculation by Bazett formula revealed more pronounced (10% from baseline level) shortening of FQT at peak exercise. QT calculated by the Bazett formula at 100 w did not differ from baseline level with tendency to higher level. Corrected QT according to the most often used Bazett formula was maximal at the first stage of exercise (25 w) and did not exceed 450 ms in boys and 460ms in girls. Maximal QTc lengthening in the process of test did not exceed 50 ms in any of the examined persons. Hysteresis of QTc interval was equal to 21+/-6 (15-25) ms. The conclusion was made that algorithm of assessment of QT interval changes during exercise test should include initial values of QTc calculated according to the Bazett formula, maximal QTc value, level of exercise at which it was registered, maximal increase of QTc during exercise, and QTc interval hysteresis.

[The efficacy of the ultrashort-term action insulin-lispro preparation "humalog" and the antioxidant mexidol in the complex treatment of type I diabetes in infants and adolescents].

Monitoring of a group of 96 children with type I diabetes mellitus showed the positive effect of fast-acting insulin analog humalog on the long-term glycemic control and correction of metabolic disturbances in the vegetative nervous system and on the elimination of psychological problems. Additional prescription of the antioxidant drug mexidol promoted restoration of the cardiac rhythm variability, normalization of a daily structure of the heart rate, improvement of memory and attention and decreased the level of anxiety. The observations showed a decrease in the rate of formation of the diabetic cardiac neuropathy and a reduction of expressiveness of cerebroasthenic syndrome.

[Anti-arrhythmia activity of derinat in an experiment]. / Protivoaritmicheskaia aktivnost' derinata v éksperimente.

The acute toxicity of the immunostimulant derinat is very low: the LD50 value for intraperitoneal administration exceeds 1000 mg/kg. The drug effectively prevents from acute arrhythmia development upon occlusion in cats and produces antifibrillator effect on a model of reperfusive arrhythmia in a dose of 7.5 mg/kg. Derinat also exhibits the antiarrhythmic activity on the model of adrenalin-induced rhythm violations, but appears ineffective on the calcium chloride model.

[Effect of mexidol on efficacy of traditional therapy of sick sinus syndrome in adolescents]. / Vliianie meksidola na éffektivnost' traditsionnoi terapii sindroma slabosti sinusovogo uzla u podrostkov.

ECG data obtained with a Holter monitor in a group of 90 adolescent patients with vegetovascular dystonia and sick sinus syndrome (SSS) showed that mexidol, intravenously instilled in a daily dose of 2-4 mg/kg over a period of 10 days in combination with a standard neurometabolic scheme results in the development of a therapeutic effect in 93-100% of patients with clinical-ECG variants I and II of the disorder. In most cases, both clinical state and ECG quality were improved and the functional capacity of myocardium was increased. Repeated courses of mexidol administration increased efficacy of the ambulatory SSS treatment on the average by 20%.

A new method for evaluation of safety of antiarrhythmic drugs.

A new method for preclinical evaluation of safety of antiarrhythmic drugs is proposed. During chronic stress, class I antiarrhythmic preparations increased mortality of test animals. By contrast, class II-IV antiarrhythmic agents and antioxidants produced no significant effect on mortality of experimental mice. These data agree with published results of multicenter studies.

[Effect of mexidol, emoxypine, and dimephosphon on electrophysiological effects of nibentan]. / Issledovanie vliianiia meksidola, émoksipina i dimefosfona na élektrofiziologicheskie éffekty nibentana.

Mexidol, emoxypine, and dimephosphon decrease the acute toxicity of nibentan in mice. In the experiments on cats, these drugs reduced the negative dromotropic action of nibentan and prevented an increase in the effective refractory period of the atrioventricular node and ventricles, in the QT interval length, and in the ventricular excitation threshold.

[Combined administration of mexidol and anti-arrhythmia agents]. / Issledovanie sochetannogo primeneniia maksidola s antiaritmicheskimi preparatami.

The influence of mexidol on the acute toxicity and electrophysiological effects of nibentan, propranolol, and verapamil was experimentally studied. It was found that mexidol potentiates the ability of propranolol and verapamil to inhibit automatism of the sinus node and suppresses the ability of all the three drugs to increase the refractory period of myocardium. It is suggested that these effects are related to the action of mexidol upon ion channels.

[The anti-arrhythmia activity of energy-providing and electron-acceptor compounds]. / Protivoaritmicheskaia aktivnost' nekotorykh énergoobespechivaiushchikh i élektronaktseptornykh soedinenii.

The protective effects of fructose-1, 6-diphosphate, sodium malate and cytochrome C were studied in the experiments on rats with disorders of the cardiac rhythm of various origin. The compounds studied prevent the strophantine and adrenaline-induced cardiac rhythm disturbances, but appeared ineffective on aconitine and calcium chloride models.

[The antiarrhythmic activity of glycolysis and Krebs cycle intermediates in early occlusion and reperfusion arrhythmias in rats]. / Issledovanie protivoaritmicheskoi aktivnosti nekotorykh intermediatov glikoliza i tsikla Krebsa pri rannikh okkliuzionnykh i reperfuzionnykh aritmiiakh u krys.

Acute experiments on unconscious rats have demonstrated that fructose-1,6-diphosphate, phosphoenolpyruvate and malate of sodium produced a marked antiarrhythmic activity in acute occlusive and reperfusion arrhythmias, prevented the development of ventricular fibrillation and tachycardias, considerably reduced the duration of arrhythmia paroxysms, but they were ineffective in ventricular extrasystole.