Assessment of Autonomic Nervous System Dysfunction in the Early Phase of Infection With SARS-CoV-2 Virus

BackgroundWe are facing the outburst of coronavirus disease 2019 (COVID-19) defined as a serious, multisystem, disorder, including various neurological manifestations in its presentation. So far, autonomic dysfunction (AD) has not been reported in patients with COVID-19 infection.AimAssessment of AD in the early phase of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus).Patients and methodsWe analyzed 116 PCR positive COVID-19 patients. After the exclusion of 41 patients with associate diseases (CADG), partitioned to patients with diabetes mellitus, hypertension, and syncope, the remaining patients were included into a severe group (45 patients with confirmed interstitial pneumonia) and mild group (30 patients). Basic cardiovascular autonomic reflex tests (CART) were performed, followed by beat-to-beat heart rate variability (HRV) and systolic and diastolic blood pressure variability (BPV) analysis, along with baroreceptor sensitivity (BRS). Non-linear analysis of HRV was provided by Poincare Plot. Results were compared to 77 sex and age-matched controls.ResultsAD (sympathetic, parasympathetic, or both) in our study has been revealed in 51.5% of severe, 78.0% of mild COVID-19 patients, and the difference compared to healthy controls was significant (p = 0.018). Orthostatic hypotension has been established in 33.0% COVID-19 patients compared to 2.6% controls (p = 0.001). Most of the spectral parameters of HRV and BPV confirmed AD, most prominent in the severe COVID-19 group. BRS was significantly lower in all patients (severe, mild, CADG), indicating significant sudden cardiac death risk.ConclusionCardiovascular autonomic neuropathy should be taken into account in COVID-19 patients’ assessment. It can be an explanation for a variety of registered manifestations, enabling a comprehensive diagnostic approach and further treatment

Consensus on the assessment of systemic sclerosis-associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment

INTRODUCTION: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. METHODS: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. RESULTS: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. CONCLUSION: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Physical Activity in Systemic Lupus Erythematosus Physical Activity Program Is Helpful for Improving Quality of Life in Patients with Systemic Lupus Erythematosus

Given the crucial events in systemic lupus erythematosus (SLE) such as joint and muscle pain, fatigue, depression, obesity and osteoporosis, the very thought of exercising can be challenging. This prospective study included 60 patients diagnosed with SLE in stable condition. A randomly selected group of 30 women had aerobic training on a bicycle ergometer for a period of 15 minutes, 3 times per week for 6 weeks, while the second group of 30 women performed isotonic exercises (to stretch and lengthen muscles and improve the range of motion) for 30 minutes, 3 times per week during the same period. Fatigue Severity Scale (FSS), Short Form 36 (SF36) questionnaire on the quality of life and Beck depression inventory (BDI) were analyzed at baseline and after 6 weeks. At baseline FSS score was 53.8 ± 5.7 and after the physical activity FSS score was 29.1 ± 7.8 (FSS ≥ 36; fatigue is present). The largest number of patients (66.7%) was in a moderate depressed state at the baseline, while after physical activities 61.7% of patients, had a mild mood disturbance. There were significant differences (p < 0.001) in values of all areas of quality of life questionnaire SF36 before and after the implementation of physical activity. The type of physical activity had no influence in FSS and BDI values. Continuous physical activity, regardless of its type, significantly improved quality of life of SLE patients. We recommend regular physical activity as an integral part of modern therapeutic approach in this patient population

Immunohistochemical analysis of the arterial supply and mast cells of the trigeminal ganglion

The aim of this study was to quantify the distribution of microvessels and mast cells in all three parts of the trigeminal ganglion (TG). Statistical analyses were applied to investigate possible micromorphological regional differences in their density. Five serially sectioned human TGs were prepared for CD34 and mast cell tryptase immunostaining. The following quantifications were performed in microscopic fields of three parts of the TG: microvessel density (MVD), mast cell density (MCD) and ganglionic cell count. The density of CD34-positive microvessels was not significantly different in any of the three observed parts of the TG. The distribution of neurons showed no significant statistical difference in three parts of the TG. There was no difference in the density of tryptase-positive mast cells within the TG, but there was an abundant presence of mast cells in the periganglionic dural and subdural tissues, a finding hitherto not reported. We can say that there is a homogenous vascular pattern within the TG which excludes local predominance in pathogenesis of trigeminal neuralgia. Second, and more important, the finding of peri-trigeminal mast cells indicates their important role in migraine pain and confirms their degranulation as the main therapeutic goal for this condition

Molecular Aspects of MAFLD—New Insights on Pathogenesis and Treatment

Metabolic-associated liver disease (MAFLD) affects up to 70% of overweight and more than 90% of morbidly obese people, and its pathogenesis is rather complex and multifactorial. The criteria for MAFLD include the presence of hepatic steatosis in addition to one of the following three criteria: overweight or obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. If the specific criteria are present, the diagnosis of MAFLD can be made regardless of alcohol consumption and previous liver disease. The pathophysiological mechanisms of MAFLD, including inflammation, lipotoxicity, mitochondrial disfunction, and oxidative stress, as well as the impact of intestinal gut microbiota, are constantly being elucidated. Treatment strategies that are continually emerging are based on different key points in MAFLD pathogenesis. Yet, the ideal therapeutic option has still not been found and future research is of great importance, as MAFLD represents a multisystemic disease with numerous complications

Chronic or Changeable Infarct Size after Spontaneous Coronary Artery Dissection

Spontaneous coronary artery dissection (SCAD) could be the cause of acute myocardial infarction (AMI) and sudden cardiac death. Clinical presentations can vary considerably, but the most common is the elevation of cardiac biomarkers associated with chest discomfort. Different pathological etiology in comparison with Type 1 AMI is the underlying infarct size in this population. A 42-year-old previously healthy woman presented with SCAD. Detailed diagnostical processing and treatment which were performed could not prevent myocardial injury. The catheterization laboratory was the initial place for the establishment of a diagnosis and proper management. The management process can be very fast and sometimes additional imaging methods are necessary. Finding predictors of SCAD recurrence is challenging, as well as predictors of the resulting infarct scar size. Patients with recurrent clinical symptoms of chest pain, ST elevation, and complication represent a special group of interest. Therapeutic approaches for SCAD range from the ”watch and wait” method to complete revascularization with the implantation of one or more stents or aortocoronary bypass grafting. The infarct size could be balanced through the correct therapeutical approach, and, proper multimodality imaging would be helpful in the assessment of infarct size

An Integrative in Silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

Aims: An infectious disease (COVID-19) caused by the coronavirus SARS-CoV-2 emerged in Wuhan, China in December 2019. Currently, SARS-CoV-2 infected more than 9 million people and caused more than 450 000 deaths. Considering the urgent need for novel therapeutics, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we investigated an integrative in silico drug repurposing approach as a valuable tool for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro).Main methods: To screen FDA-approved drugs, we designed an integrative in silico drug repurposing approach implementing structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data-mining analysis of drug-gene-COVID-19 association.Key findings: Through the presented approach, 43 candidates with potential inhibitory effect on Mpro were selected and further evaluated according to the predictions of tissue disposition, drug-gene-COVID-19 associations and potential pleiotropic effects. We singled out 9 FDA approved drugs as the most promising for their profiling in COVID-19 drug discovery campaigns. Our results were in agreement with current experimental findings, which validate the applied integrative approach and may support clinical decisions for a novel epidemic wave of COVID-19.Significance: To the best of our knowledge, this is the first integrative in silico repurposing study for COVID-19 with a clear advantage in linking structure-based molecular modeling of Mpro inhibitors with predictions of tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.</div

Population pharmacokinetics of 25-hydroxy Vitamin D in non-elderly postmenopausal women

© 2019 Polish Pharmaceutical Society. All Rights Reserved. Vitamin D is one of the keys to bone health, and the serum levels of this vitamin are a major concern for postmenopausal women. The aims of this study were to develop a population pharmacokinetic (PPK) model for the clearance of 25-hydroxy vitamin D in non-elderly postmenopausal women and to identify the factors which have a significant influence on its clearance. The study population consisted of postmenopausal women who had been referred for evaluation of bone mineral density (BMD) by DEXA (dual-energy x-ray absorptiometry) scanner. The population pharmacokinetics modeling was conducted using the ADVAN 1 subroutine from a non-linear mixed effects (NONMEM) program, and thirty-two covariates were assessed. A total of 75 serum concentrations were obtained from the same number of postmenopausal women and used for PPK analysis. The mean value of the participantsí age was 57.92 ± 3.93 years and their body weight was 69.76 ± 11.49 kg. A wide range of 25-hydroxy vitamin D concentrations was observed (from 3.41 to 61.92 ng/mL) with a mean value of 26.19 ± 10.95 ng/mL. A total of 32 covariates were examined and preliminary results suggested the influence of six covariates on 25-hydroxy vitamin D clearance. In the final PPK model, however, only one covariate was shown to have a significant impact on the clearance value ñ the mean daily dietary intake dose of vitamin D (DD). These findings offer a preliminary basis on which to determine the level of vitamin D supplementation required by individual postmenopausal women. It could prove particularly important in achieving optimal serum levels of vitamin D in this vulnerable population