Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study)

Introduction: Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as “cytokine storm”, and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and Methods: This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients’ condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results: The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001).Conclusion: Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism

Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Studies of an artificially generated electrode effect at ground level

The outdoor experiments, using a metallic grid above the ground surface, have yielded well-defined vertical profiles of the space-charge density. The profiles showed strong evidence for the existence of an electrode effect, which could be named the artificial electrode effect and can serve as a very useful and well-controlled model for the study of atmospheric electric processes in the atmospheric surface layer. The build-up or break-down of an electrode-effect layer occurred in a time of the order of 10 s under the experimental conditions realized. The artificially generated electrode effect is dependent on the electrical field strength supplied, wind speed, turbulent mixing and ion mobilities. Wind speed and ion mobility seem to be the dominant factors, defining space-charge density profiles. A theoretical model for the artificial electrode effect has been developed, taking into account turbulent mixing of charged particles in the air flow with the logarithmic profile of the wind velocity. The numerical analysis of the boundary value problem for the two-dimensional equations for the light ion concentrations has been performed. The model presented shows a qualitative agreement of calculated space-charge profiles with measured ones, and explains the dependence of the artificial electrode effect on the dominant control parameters. The limiting conditions for the developed theory are discussed

Theoretical and Numerical Study of Self-Organizing Processes in a Closed System Classical Oscillator and Random Environment

A self-organizing joint system classical oscillator&ndash;random environment is considered within the framework of a complex probabilistic process that satisfies a Langevin-type stochastic differential equation. Various types of randomness generated by the environment are considered. In the limit of statistical equilibrium (SEq), second-order partial differential equations (PDE) are derived that describe the distribution of classical environmental fields. The mathematical expectation of the oscillator trajectory is constructed in the form of a functional-integral representation, which, in the SEq limit, is compactified into a two-dimensional integral representation with an integrand: the solution of the second-order complex PDE. It is proved that the complex PDE in the general case is reduced to two independent PDEs of the second order with spatially deviating arguments. The geometric and topological features of the two-dimensional subspace on which these equations arise are studied in detail. An algorithm for parallel modeling of the problem has been developed