[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.

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.

Experimental Approach to Search for Free Neutron-Antineutron Oscillations Based on Coherent Neutron and Antineutron Mirror Reflection.

An observation of neutron-antineutron oscillations (n-n[over ¯]), which violate both B and B-L conservation, would constitute a scientific discovery of fundamental importance to physics and cosmology. A stringent upper bound on its transition rate would make an important contribution to our understanding of the baryon asymmetry of the Universe by eliminating the postsphaleron baryogenesis scenario in the light quark sector. We show that one can design an experiment using slow neutrons that in principle can reach the required sensitivity of τ_{n-n[over ¯]}∼10^{10} s in the oscillation time, an improvement of ∼10^{4} in the oscillation probability relative to the existing limit for free neutrons. The improved statistical accuracy needed to reach this sensitivity can be achieved by allowing both the neutron and antineutron components of the developing superposition state to coherently reflect from mirrors. We present a quantitative analysis of this scenario and show that, for sufficiently small transverse momenta of n/n[over ¯] and for certain choices of nuclei for the n/n[over ¯] guide material, the relative phase shift of the n and n[over ¯] components upon reflection and the n[over ¯] annihilation rate can be small enough to maintain sufficient coherence to benefit from the greater phase space acceptance the mirror provides.

[Risk Factors of Cardiovascular Complications After Beating-Heart Coronary Artery Bypass Grafting in Patients With Type Two Diabetes].

AIM: to determine risk factors of early cardiovascular complications after beating-heart coronary artery bypass grafting (CABG) in patients with ischemic coronary disease (IHD) and type two diabetes (D2). MATERIALS AND METHODS: We included into this study 188 patients (mean age 59 years, 85.1% men) with IHD and D2 who underwent off-pump CABG. The following cardiovascular complications (CVC) registered within 7 days after surgery were analyzed: myocardial infarction (MI), stroke/transient ischemic attack (S/TIA), atrial fibrillation (AF). The control group of patients without CVC was formed by case-control method. In the study groups we compared IHD severity, coronary angiography, brachiocephalic and peripheral arteries duplex ultrasonography data, blood pressure level, glomerular filtration rate, EuroSCORE II risk, preoperative glycemic parameters and hypoglycemic therapy, as well as CABG volume and severity. Factors associated with postoperative CVC were determined by multiple stepwise logistic regression. RESULTS AND CONCLUSIONS: CVC were registered in 47 patients (MI - in 18, S/TIA - in 2, AF - in 27). As compared with the control group patients with CVC had higher Canadian Cardiovascular Society angina class and EuroSCORE II risk, lower left ventricular ejection fraction and glomerular filtration rate; they more frequently had left main coronary artery involvement, total coronary artery occlusions, carotid and peripheral artery disease. Group of patients with CVC had higher levels of glycosylated hemoglobin, serum glucose and its diurnal variability, as well as higher proportion of patients switched preoperatively from oral hypoglycemic agents to rapid-acting insulin. According to logistic regression most informative predictors of CVC were peripheral artery disease (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.7-7.1), diurnal serum glucose variability on admission day (OR 13.2, 95% CI 5.9-30.0 per 0.1 mmol/l) and the day before surgery (OR 1.3, 95%CI 1.2-2.4 per 0.1 mmol/l), and switching from oral hypoglycemic agents to insulin (OR 2.5, 95%CI 1.2-5.5).

[Realities and perspectives of stroke prevention in atrial fibrillation: physician's opinions analysis].

The purpose is to study the opinions of general practitioners and cardiologists on the issue of stroke prevention and the prospects of new oral anticoagulants treatment of patients with atrial fibrillation (AF). 240 physicians, of whom 139 were general practitioners and 101 cardiologists, were questioned. The physicians awareness of stroke as the most dangerous AF complication was 84.6%. Only 39.2% of respondents assess the risk of stroke by CHADS2 or CHA2DS2-VASc scores. 24.2% of respondents express their willingness to assign the oral anticoagulants in case of the stroke risk value of one point of the scale, 61.7%--of two points. 40.4% of physicians will prescribe the oral anticoagulants to AF patient older than 75 years. At the same time acetylsalicylic acid is prescribed unreasonably often to AF patients with stroke risk. 85.0% of respondents believe the complexity of controlling and instability of the international normalized ratio to be the barrier to warfarin prescription. We revealed the differences in the approaches to antithrombotic drugs choice between general practitioners and cardiologists, as well as between subgroups of doctors who use or don't use the stroke risk scale. The majority (64.2%) of respondents are found to be aware of the mechanism of action of new oral anticoagulants (dabigatran etexilate). The arguments for their wide use most often indicated are simplicity of application (78.8%), higher safety (53.8%) and efficacy (29.2%) as compared to warfarin. The analysis of doctors' opinions about the possible effect of financial reasons on the frequency of prescribing new oral anticoagulants was also carried out.

[Electrocardiographic sign of secondary atrial tumor presentation].

Two cases of intravital diagnosis of left atrial tumor secondary to lung cancer and esophagus cancer are presented. The myocardial alteration was caused by direct invasion of primary tumor. In both cases the PQ (PR) segment depression was found on ECG, which could reflect neoplastic lesion of the atrium. We proposed to consider this phenomenon as ECG marker of secondary atrial malignancies.

[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.

[Vascular effects of perindopril arginine and indapamide fixed combination in patients with arterial hypertension].

The aim of the study was to investigate the dynamics of arterial stiffness and endothelial function parameters under the influence of perindopril arginine and indapamide fixed combination in arterial hypertension (AH) patients. 30 persons with 1-3 degree AH were included into the study. The treatment duration was 24 weeks. Central aortic blood pressure (BP), augmentation pressure and index (AIx), carotid-femoral and carotid-radial pulse wave velocity (PWV), brachial artery endothelium-dependent vasodilatation (EDVD), office and ambulatory BP as well as orthostatic BP falls were evaluated under the influence of selected therapy. 27 patients completed the study protocol. Results showed that aortic systolic BP was significantly reduced by 10.7 mmHg, augmentation pressure - by 3.6 mmHg and AIx - by 6.5%. Carotid-radial PWV decreased by 0.8 m/s. Carotid-femoral PWV did not change. We also revealed the EDVD increase by week 12. The EDVD growth was correlated with degree of aortic systolic BP reduction (r=-0.48, p=0.02). Office and ambulatory BP declined by 15.8/10.0 and 10.0/7.5 mmHg respectively. The target BP <140/90 mmHg was achieved in 20 (74.1%) persons. At the same time the orthostatic hypotension did not rise. Conclusion. We concluded that perindopril arginine/indapamide fixed combination improved vascular function in hypertensive patients by wave reflection reduction, peripheral arterial stiffness lowering and endothelial function improvement.

[Pulse pressure and target organs damage in elderly patients with arterial hypertension].

For the purpose of determination of the importance of daily pulse pressure (PP-24) as the heart, vessels and kidneys affection marker in elderly patients with arterial hypertension we studied 260 patients of the age of 73.3 +/- 7.3 years. The multiple logistic regression analysis was carried out. The results showed that PP-24 irrespective to systolic or diastolic blood pressure was associated with left ventricular hypertrophy and left ventricular enlargement as well as elevated aortic stiffness and carotid plaque. Morphofunctional changes in peripheral vessels and kidneys were independent on the level of PP-24.

[Dynamics of pulse pressure in orthostatic test: interrelationships with risk factors and involvement of the heart and vessels in elderly patients with arterial hypertension].

We studied dynamics of arterial pulse pressure (APP) during active orthostatic test (AOT) in relation to cardiac and vascular involvement in 198 elderly patients with arterial hypertension. We measured and compared parameters of hemodynamics, rate of detection of risk factors, signs of affection of the heart and vessels in subgroups with elevation of APP (n=50), lowering of APP by more than 10 mm Hg (n=50) and intermediate deviations of APP (n=98) in orthostasis. In patients with elevation of APP during AOT smoking, increased aortic stiffness, history of myocardial infarction were detected more often and risk of development of cardiovascular diseases according to SCORE system was higher than in patients with lowering of APP or absence of its dynamics. Patients with lowering of APP more than 10 mm Hg significantly more often had cerebrovascular disease appearing as history of cerebral strokes and/or transitory ischemic attacks. The conclusion was made about possible significance of orthostatic increment of APP as supplementary marker of cardiovascular risk in elderly patients with arterial hypertension.

Constraints on Non-Newtonian Gravity From the Experiment on Neutron Quantum States in the Earth's Gravitational Field.

An upper limit to non-Newtonian attractive forces is obtained from the measurement of quantum states of neutrons in the Earth's gravitational field. This limit improves the existing constraints in the nanometer range.

Investigation of the Neutron Quantum States in the Earth's Gravitational Field.

We studied the neutron quantum states in the potential well formed by the Earth's gravitational field and a horizontal mirror. The estimated characteristic sizes of the neutron wave functions in two lowest quantum states correspond to their expectations with an accuracy of ≈25 %. The spatial density distribution in a standing neutron wave above a mirror was measured for a set of a few lowest quantum states. A position-sensitive neutron detector with an extra high spatial resolution of 1 µm to 2 µm was developed and tested for this particular task. Although this experiment was not designed or optimized to search for an additional short-range force, nevertheless it allowed us to slightly improve the published boundary in the nanometer range of characteristic distances. We studied systematical uncertainties in the chosen "flow-through" method as well as the feasibility to improve further the accuracy in this experiment.

[Cavinton forte treatment of cerebral vascular insufficiency in patients with coronary heart disease and arterial hypertension].

Using 48-h Holter monitoring of ECG and ambulatory blood pressure monitoring, 28 patients (13 men, 15 women, mean age 66.6 +/- 7.7 years) with cerebral vascular insufficiency of the I-II stage in combination with chronic coronary heart disease and essential arterial hypertension have been examined. Quantitative parameters of myocardial ischemia episodes and hypotension conditions were calculated and compared before the beginning (the first 24 h of monitoring) and during taking the daily dose of 30 mg of cavinton forte (the second 24 hours of monitoring). The distribution of ischemia and hypotension episodes in the periods of the maximal supposed effect of the drug was analyzed. Cavinton forte neither contributes to the manifestation and average frequency of myocardial ischemia episodes nor influences parameters and the character of short-term arterial hypotension episodes. The drug reduces quantity and duration of blood pressure nocturnal fall. It is concluded that initial cavinton forte treatment of cerebral vascular insufficiency in patients with chronic coronary heart disease in combination with arterial hypertension is safe when combined with hemodynamically active antihypertensive and antiischemic therapy.