Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS.

BACKGROUND: Glycyrrhizin, an active component of liquorice root extract, exhibits antiviral and immunomodulatory properties by direct inhibition of the pro-inflammatory alarmin HMGB1 (High-mobility group box 1). OBJECTIVE: The aim of this study was to explore the role of liquorice intake on the viral entry receptor ACE2 (angiotensin-converting enzyme 2) and the immunoregulatory HMGB1 in healthy individuals and to explore HMGB1 expression in coronavirus disease 2019 (COVID-19) or non-COVID-19 in ARDS (acute respiratory distress syndrome patients). MATERIAL AND METHODS: This study enrolled 43 individuals, including hospitalised patients with i) acute respiratory distress syndrome (ARDS) due to COVID-19 (n = 7) or other underlying causes (n = 12), ii) mild COVID-19 (n = 4) and iii) healthy volunteers (n = 20). Healthy individuals took 50 g of liquorice (containing 3% liquorice root extract) daily for 7 days, while blood samples were collected at baseline and on day 3 and 7. Changes in ACE2 and HMGB1 levels were determined by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Additionally, HMGB1 levels were measured in hospitalised COVID-19 patients with mild disease or COVID-19 associated acute respiratory distress syndrome (ARDS) and compared with a non-COVID-19-ARDS group. RESULTS: Liquorice intake significantly reduced after 7 days both cellular membranous ACE2 expression (-51% compared to baseline levels, p = 0.008) and plasma HMGB1 levels (-17% compared to baseline levels, p<0.001) in healthy individuals. Half of the individuals had a reduction in ACE2 levels of at least 30%. HMGB1 levels in patients with mild COVID-19 and ARDS patients with and without COVID-19 were significantly higher compared with those of healthy individuals (+317%, p = 0.002), but they were not different between COVID-19 and non-COVID-19 ARDS. CONCLUSIONS: Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.

Model-Based Analysis of SARS-CoV-2 Infections, Hospitalization and Outcome in Germany, the Federal States and Districts.

The coronavirus disease 2019 (COVID-19) pandemic challenged many national health care systems, with hospitals reaching capacity limits of intensive care units (ICU). Thus, the estimation of acute local burden of ICUs is critical for appropriate management of health care resources. In this work, we applied non-linear mixed effects modeling to develop an epidemiological SARS-CoV-2 infection model for Germany, with its 16 federal states and 400 districts, that describes infections as well as COVID-19 inpatients, ICU patients with and without mechanical ventilation, recoveries, and fatalities during the first two waves of the pandemic until April 2021. Based on model analyses, covariates influencing the relation between infections and outcomes were explored. Non-pharmaceutical interventions imposed by governments were found to have a major impact on the spreading of SARS-CoV-2. Patient age and sex, the spread of variant B.1.1.7, and the testing strategy (number of tests performed weekly, rate of positive tests) affected the severity and outcome of recorded cases and could reduce the observed unexplained variability between the states. Modeling could reasonably link the discrepancies between fine-grained model simulations of the 400 German districts and the reported number of available ICU beds to coarse-grained COVID-19 patient distribution patterns within German regions.

Effects of surgical and FFP2 masks on cardiopulmonary exercise capacity in patients with heart failure.

AIMS: Surgical and FFP2 masks are recommended to reduce transmission of SARS-CoV-2. The cardiopulmonary effects of facemasks in patients with chronic heart failure are unknown. This prospective, cross-over study quantified the effects of wearing no mask (nm), surgical mask (sm), and FFP2 mask (ffpm) in patients with stable heart failure. METHODS: 12 patients with clinically stable chronic heart failure (HF) (age 63.8±12 years, left ventricular ejection fraction (LVEF) 43.8±11%, NTProBNP 573±567 pg/ml) underwent spiroergometry with and without masks in a randomized sequence. Comfort/discomfort was assessed using a standardized questionnaire. RESULTS: Maximum power was reduced with both types of masks (nm: 108.3 W vs. sm: 101.2 W vs. ffpm: 95.6 W, p<0.01). Maximum respiratory oxygen uptake (1499ml/min vs. 1481 ml/min vs. 1300 ml/min, p = 0.95 and <0.01), peak ventilation (62.1 l/min vs. 56.4 l/min vs. 50.3 l/min, p = 0.15 and p<0.05) and O2-pulse (11.6 ml/beat vs. 11.8 ml/beat vs. 10.6 ml/beat, p = 0.87 and p<0.01) were significantly changed with ffpm but not sm. Discomfort was moderately but significantly increased (nm: 1.6 vs. sm: 3.4 vs. ffpm: 4.4, p<0.05). CONCLUSION: Both surgical and FFP masks reduce exercise capacity in heart failure patients, while FFP2 masks reduce oxygen uptake and peak ventilation. This reduction in cardiopulmonary performance should be considered in heart failure patients whose daily life activities are often just as challenging as exercise is for healthy adults.

Comparison of immersive and non-immersive virtual reality videos as substitute for in-hospital teaching during coronavirus lockdown: a survey with graduate medical students in Germany.

As a consequence of the continued Covid-19 lockdown in Germany, in-hospital teaching for medical students was impossible. While lectures and other theoretical training were relatively easily converted into online sessions using platforms such as Moodle, Zoom and Microsoft Teams, this was not the case for practical skills and clinical interventions, such as bronchoscopy or colonoscopy. This study describes a workaround that was implemented at the Saarland University Hospital utilizing virtual reality equipment to convey the impressions of shadowing clinical procedures to the students without physical presence. To achieve this, 3D 180° videos of key clinical interventions of various internal medicine specialities were recorded, cut, and censored. The videos were uploaded to the e-learning YouTube channel of our institution and shared with the students via the private share function. The students could choose whether to use a VR-viewer to watch the videos immersively or to watch them without a viewer on a screen non-immersively. At the end of the course after 1 week, the students completed a questionnaire anonymously focusing on learning-success regarding the presented topics, a self-assessment, and an evaluation of the course. A total of 27 students watched the videos with a VR-Viewer and 74 watched non-immersively. Although the VR-viewer group self-assessed their expertise higher, there was no significant difference between the two groups in the learning-success test score. However, students in the VR-viewer group rated the learning atmosphere, comprehensibility, and overall recommendation of the course significantly higher. They also agreed significantly more to the statement, that they gained a better conception of the presented procedures, and that virtual reality might be an appropriate tool for online teaching. Video-assisted teaching facilitates learning and might be a valuable add-on to conventional teaching.Abbreviations: Covid-19: severe acute respiratory syndrome coronavirus 2; 3D: three-dimensional; 2D: Two-dimensional; VR: virtual reality.

Effects of Medical Face Masks on Physical Performance in Patients With Coronary Artery Disease or Hypertension.

In this randomized, prospective monocentric study, 40 subjects with coronary artery disease or hypertension (cardiovascular disease [CVD] group) were assigned to either surgical mask (SM) or class 2 filtering facepiece mask (FFP2). They performed cycle ergometry exercise tests with progressive intensity until exhaustion with the assigned mask and another test with no mask (NM) in random order. A control group of 10 healthy subjects randomly performed 3 exercise tests with NM, SM, and FFP2, respectively. Blood pressure, heart rate, 12-lead electrocardiogram, exertion, shortness of breath, and capillary blood gases from the earlobe were documented. Across all groups, exercise testing with face masks resulted in a significantly reduced peak power output in watts compared with testing with NM (CVD group: SM vs NM: -5.0 ± 7.0%, p = 0.005; FFP2 vs NM: -4.7 ± 14%, p = 0.03; control group: SM vs NM: -6.8 ± 4.4%, p = 0.008; FFP2 vs NM: -8.9 ± 6.3%; p = 0.01) without differences in hemodynamic parameters, such as maximum heart rate and systolic blood pressure. Wearing an FFP2 compared with NM resulted in significant higher carbon dioxide partial pressure (CVD group: FFP2: 36.0 ± 3.2 mm Hg vs NM: 33.3 ± 4.4 mm Hg, p = 0.019; control group: FFP2: 32.6 ± 2.8 mm Hg vs NM: 28.1 ± 1.7 mm Hg, p <0.001) with corresponding differences in hydrogen carbonate and base excess, but not to a clinically critical extent. In conclusion, exercise testing with SM and FFP2 resulted in a significant reduction of peak power output without differences in hemodynamic parameters in subjects with preexisting CVD and in healthy subjects.

Arterial hypertension - Clinical trials update 2021.

AIM: This review aims to summarize and discuss some of the most relevant clinical trials in epidemiology, diagnostics, and treatment of hypertension published in 2020 and 2021. DATA SYNTHESIS: The trials included in this review are related to hypertension onset age and risk for future cardiovascular disease, reliability of different blood pressure monitoring methods, role of exercise-induced hypertension, treatment of hypertension in patients with SARS-CoV-2 infection, management of hypertension high-risk patient groups, e.g., in the elderly (≥80 years) and patients with atrial fibrillation, and the interplay between nutrition and hypertension, as well as recent insights into renal denervation for treatment of hypertension. CONCLUSIONS: Hypertension onset age, nighttime blood pressure levels and a riser pattern are relevant for the prognosis of future cardiovascular diseases. The risk of coronary heart disease appears to increase linearly with increasing exercise systolic blood pressure. Renin-angiotensin system blockers are not associated with an increased risk for a severe course of COVID-19. In elderly patients, a risk-benefit assessment of intensified blood pressure control should be individually evaluated. A J-shaped association between cardiovascular disease and achieved blood pressure could also be demonstrated in patients with atrial fibrillation on anticoagulation. Salt restriction and lifestyle modification remain effective options in treating hypertensive patients at low cardiovascular risk. Sodium glucose co-transporter 2 inhibitors and Glucagon-like peptide-1 receptor agonists show BP-lowering effects. Renal denervation should be considered as an additional or alternative treatment option in selected patients with uncontrolled hypertension.

Effects of face masks on performance and cardiorespiratory response in well-trained athletes.

BACKGROUND: During the COVID-19 pandemic, compulsory masks became an integral part of outdoor sports such as jogging in crowded areas (e.g. city parks) as well as indoor sports in gyms and sports centers. This study, therefore, aimed to investigate the effects of medical face masks on performance and cardiorespiratory parameters in athletes. METHODS: In a randomized, cross-over design, 16 well-trained athletes (age 27 ± 7 years, peak oxygen consumption 56.2 ± 5.6 ml kg-1 min-1, maximum performance 5.1 ± 0.5 Watt kg-1) underwent three stepwise incremental exercise tests to exhaustion without mask (NM), with surgical mask (SM) and FFP2 mask (FFP2). Cardiorespiratory and metabolic responses were monitored by spiroergometry and blood lactate (BLa) testing throughout the tests. RESULTS: There was a large effect of masks on performance with a significant reduction of maximum performance with SM (355 ± 41 Watt) and FFP2 (364 ± 43 Watt) compared to NM (377 ± 40 Watt), respectively (p < 0.001; ηp2 = 0.50). A large interaction effect with a reduction of both oxygen consumption (p < 0.001; ηp2 = 0.34) and minute ventilation (p < 0.001; ηp2 = 0.39) was observed. At the termination of the test with SM 11 of 16 subjects reported acute dyspnea from the suction of the wet and deformed mask. No difference in performance was observed at the individual anaerobic threshold (p = 0.90). CONCLUSION: Both SM and to a lesser extent FFP2 were associated with reduced maximum performance, minute ventilation, and oxygen consumption. For strenuous anaerobic exercise, an FFP2 mask may be preferred over an SM.

Research Output and International Cooperation Among Countries During the COVID-19 Pandemic: Scientometric Analysis.

BACKGROUND: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has instigated immediate and massive worldwide research efforts. Rapid publication of research data may be desirable but also carries the risk of quality loss. OBJECTIVE: This analysis aimed to correlate the severity of the COVID-19 outbreak with its related scientific output per country. METHODS: All articles related to the COVID-19 pandemic were retrieved from Web of Science and analyzed using the web application SciPE (science performance evaluation), allowing for large data scientometric analyses of the global geographical distribution of scientific output. RESULTS: A total of 7185 publications, including 2592 articles, 2091 editorial materials, 2528 early access papers, 1479 letters, 633 reviews, and other contributions were extracted. The top 3 countries involved in COVID-19 research were the United States, China, and Italy. The confirmed COVID-19 cases or deaths per region correlated with scientific research output. The United States was most active in terms of collaborative efforts, sharing a significant amount of manuscript authorships with the United Kingdom, China, and Italy. The United States was China's most frequent collaborative partner, followed by the United Kingdom. CONCLUSIONS: The COVID-19 research landscape is rapidly developing and is driven by countries with a generally strong prepandemic research output but is also significantly affected by countries with a high prevalence of COVID-19 cases. Our findings indicate that the United States is leading international collaborative efforts.

Correction to: Off­the­shelf barrier for emergency intubation in the cardiac catheterization laboratory during the coronavirus disease 2019 (COVID­19) pandemic.

During submission the author name Andreas Link was unfortunately omitted. The correct author list reads as follows.

Decline of emergency admissions for cardiovascular and cerebrovascular events after the outbreak of COVID-19.

BACKGROUND: The spread of the novel coronavirus SARS-CoV-2 and the guidance from authorities for social distancing and media reporting lead to significant uncertainty in Germany. Concerns have been expressed regarding the underdiagnosing of harmful diseases. We explored the rates of emergency presentations for acute coronary syndrome (ACS) and acute cerebrovascular events (ACVE) before and after spread of SARS-CoV-2. METHODS: We analyzed all-cause visits at a tertiary university emergency department and admissions for ACS and ACVE before (calendar weeks 1-9, 2020) and after (calendar weeks 10-16, 2020) the first coronavirus disease (COVID-19) case in the region of the Saarland, Germany. The data were compared with the same period of the previous year. RESULTS: In 2020 an average of 346 patients per week presented at the emergency department whereas in 2019 an average of 400 patients presented up to calendar week 16 (p = 0.018; whole year 2019 = 395 patients per week). After the first COVID-19 diagnosis in the region, emergency department visit volume decreased by 30% compared with the same period in 2019 (p = 0.0012). Admissions due to ACS decreased by 41% (p = 0.0023 for all; Δ - 71% (p = 0.007) for unstable angina, Δ - 25% (p = 0.42) for myocardial infarction with ST-elevation and Δ - 17% (p = 0.28) without ST-elevation) compared with the same period in 2019 and decreased from 142 patients in calendar weeks 1-9 to 62 patients in calendar weeks 10-16. ACVE decreased numerically by 20% [p = 0.25 for all; transient ischemic attack: Δ - 32% (p = 0.18), ischemic stroke: Δ - 23% (p = 0.48), intracerebral haemorrhage: Δ + 57% (p = 0.4)]. There was no significant change in ACVE per week (p = 0.7) comparing calendar weeks 1-9 (213 patients) and weeks 10-16 (147 patients). Testing of 3756 samples was performed to detect 58 SARS-CoV-2 positive patients (prevalence 1,54%, thereof one patient with myocardial and two with cerebral ischemia) up to calendar week 16 in 2020. CONCLUSIONS: The COVID-19 pandemic was associated with a significant decrease in all-cause admission and admissions due to cardiovascular events in the emergency department. Regarding acute cerebrovascular events there was a numerical decrease but no significant difference.

Off-the-shelf barrier for emergency intubation in the cardiac catheterization laboratory during the coronavirus disease 2019 (COVID-19) pandemic.

With the spread of SARS-CoV-2, it is expected that cases of acute coronary syndrome in the setting of coronavirus disease 2019 (COVID-19) develop. As expensive and sophisticated protection devices are not widely available, we have been working on a simple, off-the-shelf protection device for endotracheal intubation of potentially infected patients. For this purpose, we used a large transparent plastic bag (such as the sterile protective cover of the lead glass shield) for protection from airborne infections. The cover is moved over the patient's head from cranial to caudal, covering the catheter table including the torso with no need for patient mobilization. The intubation is done conventionally under direct visual control.