[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.

The Role of Mitochondrial KATP Channels in the Infarct-Reducing Effect of Normobaric Hypoxia.

We studied the role of KATP channels in the infarct-limiting effect of short-term normobaric hypoxia. Male Wistar rats were subjected to a 45-min coronary artery occlusion followed by a 120-min reperfusion. Normobaric hypoxia was simulated 30 min before coronary artery occlusion: 6 sessions of hypoxia (8% O2, 10 min) and reoxygenation (21% O2, 10 min). The following drugs were administered to rats: glibenclamide, 5-hydroxydecanoate, and HMR1098. It was found that normobaric hypoxia contributes to a decrease in myocardial infarct size by 36%. Preliminary administration of glibenclamide or 5-hydroxydecanoate eliminated the infarct-reducing effect of normobaric hypoxia. Activator of mitochondrial KATP channel diazoxide limited the infarct size. These findings suggest that mitochondrial KATP channels are involved into the cardioprotective effect of normobaric hypoxia.

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.

[International register "Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients (ACTIV SARS-CoV-2)"].

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[High altitude pulmonary edema misdiagnosed as pneumonia].

High altitude pulmonary edema (HAPE) is a relatively rare form of high altitude illness. However, without immediate treatment, HAPE is fatal. Furthermore, HAPE is characterized by non-specific signs and symptoms, and many clinical conditions may mimic it. In the present article, we report a case of HAPE misdiagnosed as pneumonia. We also discuss the issues of prevention and early treatment options in this illness.

[Relationship of Remodeling of Carotid Arteries and Left Ventricular Geometry in Patients With Chronic Glomerulonephritis].

PURPOSE: to study clinical-functional features of remodeling of carotid arteries and its relation to restructuring of the left ventricle (LV) in patients with chronic glomerulonephritis at pre-dialysis stage. MATERIALS AND METHODS: We examined 269 patients (189 men, 80 women) with chronic glomerulonephritis (CGN) aged 17-71 years, at pre-dialysis stages of the disease. We analyzed biochemical parameters of peripheral blood with the determination of daily proteinuria and glomerular filtration rate (GFR). For identification of structural changes of carotid arteries (CA) and LV we used Doppler ultrasound and echocardiography. RESULTS: Atherosclerotic changes of CA were found in 79 patients (29.3 %). Four patients (1.4 %) had history of acute disturbance of cerebral circulation. Concentric type of left ventricular hypertrophy (LVH) was significantly more prevalent among patients with CA remodeling compared with those without (37.84 vs. 18.75 %; p=0.006). Eccentric variant of LVH was significantly more prevalent among patients without atherosclerotic lesions in CA compared with those with CA remodeling (81.25 % vs. 62.16 %; p=0.001). Increased CA intima media thickness positively correlated with body mass index (r=0.273; p=0.014) and negatively - with GFR (r= -0.222; p=0.048). Statistically significant relationships were also found between the presence of carotid atherosclerosis and structural rearrangements of the heart. CONCLUSION: We demonstrated a clear relationship between GFR, restructuring of CA and concentric type of change of LV geometry, regardless of the presence of traditional risk factors.

Relationship of Remodeling of Carotid Arteries and Left Ventricular Geometry in Patients With Chronic Glomerulonephritis.

PURPOSE: to study clinical-functional features of remodeling of carotid arteries and its relation to restructuring of the left ventricle (LV) in patients with chronic glomerulonephritis at pre-dialysis stage. MATERIALS AND METHODS: We examined 269 patients (189 men, 80 women) with chronic glomerulonephritis (CGN) aged 17-71 years, at pre-dialysis stages of the disease. We analyzed biochemical parameters of peripheral blood with the determination of daily proteinuria and glomerular filtration rate (GFR). For identification of structural changes of carotid arteries (CA) and LV we used Doppler ultrasound and echocardiography. RESULTS: Atherosclerotic changes of CA were found in 79 patients (29.3%). Four patients (1.4%) had history of acute disturbance of cerebral circulation. Concentric type of left ventricular hypertrophy (LVH) was significantly more prevalent among patients with CA remodeling compared with those without (37.84 vs. 18.75%; p=0.006). Eccentric variant of LVH was significantly more prevalent among patients without atherosclerotic lesions in CA compared with those with CA remodeling (81.25% vs. 62.16%; p=0.001). Increased CA intima media thickness positively correlated with body mass index (r=0.273; p=0.014) and negatively - with GFR (r= -0.222; p=0.048). Statistically significant relationships were also found between the presence of carotid atherosclerosis and structural rearrangements of the heart. CONCLUSION: We demonstrated a clear relationship between GFR, restructuring of CA and concentric type of change of LV geometry, regardless of the presence of traditional risk factors.

[Diagnosis and treatment of pulmonary hypertension: from the point of view of 2017]. / Diagnostika i lechenie legochnykh gipertonii: vzgliad s pozitsii 2017 g.

Pulmonary hypertension (PH) is a group of diseases characterized by increased pulmonary vascular resistance (PVR). Regardless of its cause, PH leads to right ventricular failure and premature death. Recent advances in the diagnosis and treatment of PH have prompted the elaboration of new guidelines for the diagnosis and treatment of PH. This paper provides a brief overview of major achievements in diagnostic and treatment approaches in patients PH.

[Chronic Reno-Cardial Continuum in Glomerulonephritis].

OBJECTIVES: To elucidate main risk factors contributing to development of cardiovascular pathology at the predialysis stage of chronic glomerulonephritis. MATERIALS AND METHODS: We examined 173 patients (90 men, 83 women, age 15-70, mean age 36.8+/-12.9 years) at predialysis stage of chronic glomerulonephritis. Cardiovascular pathology (coronary heart disease, disturbances of cardiac rhythm, left ventricular hypertrophy, chronic heart failure) was found in 88 patients. Clinical examination included history taking, physical examination with measurement of blood pressure BP and anthropological parameters, laboratory and instrumental investigation for diagnosis verification. Biochemical parameters studied were blood serum levels of cholesterol (Ch), high-density lipoprotein Ch, low-density lipoprotein Ch, fibrinogen, C-reactive protein, total protein, and creatinine. ECG and echocardiography were also performed. RESULTS: Presence of cardiovascular pathology was associated with higher concentration of calcium in blood serum (1.7+/-0.6 vs. 1.4+/-0.5 mmol/l, p<0.05), anemia with lower hemoglobin content, number and volume of erythrocytes, higher creatinine (150 [76-179]) vs. 100 [70-117] mcmol/l; p<0.05) and lower glomerular filtration rate (GFR) (80 [41-104] vs. 100 [69-122] ml/min; p<0.05). CONCLUSION: Main factors, contributing to development of cardiovascular pathology in patients at the predialysis stage of chronic glomerulonephritis were anemia, hypercalcemia, and lowering of GFR with increased serum creatinine.

The quality of sleep and periodic breathing in healthy subjects at an altitude of 3,200 m.

The medical risks of travel and stay at high altitude are well known. Many more people travel for recreation to lower but still significant altitudes. To investigate the quality of sleep and sleep-related breathing disorders (SRBD) at that altitude we performed full polysomnography in nine young volunteers at lowland (760 m above sea level) on the first and sixth night after ascent to 3,200 m. There have been few studies on such populations. The subjects were nonsmoking healthy males aged 20.3 +/- 3.5 years with normal spirometry and arterial blood gas measurements performed at low altitude. Although there was no statistically significant difference in the duration of stages and sleep quality between low altitude night and both nights at high altitude as assessed by percent of sleep spent in stage 1, 2, 3+4 NREM, and REM sleep, total sleep time (TST), and sleep efficiency; the number of arousals and awakenings doubled at high altitude. There was no periodic breathing (PB) during sleep, except in isolated central events of SRBD, at low altitude. PB appeared at altitude mostly during NREM sleep and its intensity remained stable throughout the study period. Individual variations of PB intensity were high, ranging from 0.1 to 24% of TST. There were also some episodes of obstructive apnea and hypopnea during sleep at high altitude (p < 0.001). Mean SaO2 was lower during the study nights at high altitude when compared with low altitude. There were some signs of ventilatory acclimatization as shown by a higher mean SaO2 during the sixth compared with the first night at altitude (p < 0.001). We conclude that the sleep quality at the altitude of 3,200 m remains satisfactory when compared to low altitude. There is high individual variability in intensity of PB at that altitude.

[Quality of sleep and periodic breathing in healthy individuals working at an altitude of 3700 meters]. / Jakosc snu i oddychanie okresowe u ludzi zdrowych pracujacych na wysokosci 3700 metrów.

We performed full polysomnography (PSG) in 7 healthy miners of Kyrghyz origin (mean age 25 +/- 6 years) working in 2 weeks shifts at Kumtor gold mines at the elevation of 4200 m. They slept in comfortable dormitories situated at 3700 m. To avoid acute mountain sickness all subjects received acetazolamide 3 x 0.25 daily during 2 days preceding ascent and during 2 days at altitude: PSG was performed three times: at 760 m (1) and on the 1st (2) and 7th night (3) after rapid ascent (aircraft) to high altitude using SomnoTrac 4250 sleep laboratory. We found that sleep efficiency was good at lowland and in the mountains averaging 81.79% and 84% respectively. Although there were no significant differences in percentage of sleep stages and of total sleep time between lowland and both nights at high altitude, arousals and awakenings were more frequent in the mountains. Episodes of periodic breathing (PB) appeared at high altitude. There was a large individual variability in PB on both nights at altitude. The time spent in PB ranged from 4 to 30 minutes during the first night at altitude and from 3 to 17 minutes during the second one. PB appeared mainly during non-REM sleep and aggravated arterial blood desaturation.

[Quality of sleep and periodic breathing during sleep in healthy persons at a height of 3200 meters]. / Jakosc snu oraz oddychanie okresowe podczas snu u ludzi zdrowych na wysokosci 3200 metrów.

In order to investigate quality of sleep and sleep-related breathing disorders (SRBD) at high altitude we performed full polysomnography in 9 young healthy volunteers at lowland (760 m above see level) and on the 1st and 6th night after the ascent to the altitude of 3200 m. The subjects were non-smoking males aged 20.3 +/- 3.5 years with normal spirometry and arterial blood gas measurements performed at low altitude. We found no statistical difference in sleep quality between low and both nights at high altitude as considered by % of stages 1, 2, 3 + 4 non-REM, and REM sleep, total sleep time, sleep efficiency, and number of awakenings+arousals. There was no periodic breathing (PB) during sleep but some central events of SRBD at low altitude. PB appeared at high altitude mostly during non-REM sleep and remained stable throughout the study period. There were also some obstructive SRBD found during high altitude nights. Mean SaO2 was lower during both nights at high altitude when compared to low altitude (p < 0.00001). It was higher during the 6th than during the 1st night at altitude (p < 0.0001). Minimum SaO2 was comparable during low altitude and 6th night at altitude and was lower during the 1st altitude night (p < 0.02). We conclude that sleep quality at the altitude of 3200 m remains unchanged when compared to lowland. There is high individual variability in PB at altitude and its intensity is negligible.

[Effect of altitude on blood oxygenation during sleep in patients with bronchial asthma]. / Wplyw wysokosci na utlenowanie krwi w czasie snu u chorych na astme oskrzelowa.

The aim of our study was to investigate the severity of overnight arterial blood desaturations in patients with asthma at the altitude of 3200 meters above sea level. 12 asthmatics and 12 healthy controls were investigated. Three overnight pulsoximetries were performed in all subjects, one at the lowland and on the 1st and 5th night at the altitude. Mean SaO2 at the lowland was significantly lower in asthmatics than in the controls (p < 0.01). After the ascent to high altitude severe fall in mean SaO2 was noted in both groups (from 94.3% to 85.8% in asthmatics and from 97.1% to 88.7% in controls) (p < 0.001 for both groups). After few days of acclimatization mean SaO2 rose to 88.8% in asthmatics and to 91.3% in controls, but was still significantly lower than at the lowland (p < 0.001 for both groups). At the altitude differences in mean SaO2 between two groups were not statistically significant. We conclude that severity of overnight desaturations at high altitude do not vary between asthmatics with impaired respiratory function and healthy subjects.