The spontaneous course of human herpesvirus 6 DNA-associated myocarditis and the effect of immunosuppressive intervention

INTRODUCTION: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. RESULTS: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases (n = 79) of which 62% (n = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis (n = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3–12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and -negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs. CONCLUSION: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials

Documenting the Recovery of Vascular Services in European Centres Following the Initial COVID-19 Pandemic Peak: Results from a Multicentre Collaborative Study

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March – May 2020, “period 1”), and then again between May and June (“period 2”) and June and July 2020 (“period 3”). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries’ first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic “normal” by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Exercise Intolerance in Untreated OSA:Role of Pulmonary Gas Exchange and Systemic Vascular Abnormalities

Background: Reduced exercise capacity has been reported previously in patients with OSA hypopnea syndrome (OSAHS), although the underlying mechanisms are unclear. Research Question: What are the underlying mechanisms of reduced exercise capacity in untreated patients with OSAHS? Is there a role for systemic or pulmonary vascular abnormalities? Study Design and Methods: This was a cross-sectional observational study in which 14 patients with moderate to severe OSAHS and 10 control participants (matched for age, BMI, smoking history, and FEV 1) underwent spirometry, incremental cycle cardiopulmonary exercise test (CPET) with arterial line, resting echocardiography, and assessment of arterial stiffness (pulse wave velocity [PWV] and augmentation index [AIx]). Results: Patients (age, 50 ± 11 years; BMI, 30.5 ± 2.7 kg/m 2; smoking history, 2.4 ± 4.0 pack-years; FEV 1 to FVC ratio, 0.78 ± 0.04; FEV 1, 85 ± 14% predicted, mean ± SD for all) had mean ± SD apnea hypopnea index of 43 ± 19/h. At rest, PWV, AIx, and mean pulmonary artery pressure (PAP) were higher in patients vs control participants (P &lt; .05). During CPET, patients showed lower peak work rate (WR) and oxygen uptake and greater dyspnea ratings compared with control participants (P &lt; .05 for all). Minute ventilation (V· E), ventilatory equivalent for CO 2 output (V· E/V·CO 2), and dead space volume (V D) to tidal volume (V T) ratio were greater in patients vs control participants during exercise (P &lt; .05 for all). Reduction in V D to V T ratio from rest to peak exercise was greater in control participants compared with patients (0.24 ± 0.08 vs 0.04 ± 0.14, respectively; P = .001). Dyspnea intensity at the highest equivalent WR correlated with corresponding values of V· E/V·CO 2 (r = 0.65; P = .002), and dead space ventilation (r = 0.70; P = .001). Age, PWV, and mean PAP explained approximately 70% of the variance in peak WR, whereas predictors of dyspnea during CPET were rest-to-peak change in V D to V T ratio and PWV (R 2 = 0.50; P &lt; .001). Interpretation: Patients with OSAHS showed evidence of pulmonary gas exchange abnormalities during exercise (in the form of increased dead space) and resting systemic vascular dysfunction that may explain reduced exercise capacity and increased exertional dyspnea intensity.</p

Position, Navigation, and Timing (PNT) through Low Earth Orbit (LEO) Satellites: A Survey on Current Status, Challenges, and Opportunities

Publisher Copyright: AuthorMore and more satellites are populating the sky nowadays in the Low Earth orbits (LEO). Most of the targeted applications are related to broadband and narrowband communications, Earth observation, synthetic aperture radar, and internet-of-Things (IoT) connectivity. In addition to these targeted applications, there is yet-to-be-harnessed potential for LEO and positioning, navigation, and timing (PNT) systems, or what is nowadays referred to as LEO-PNT. No commercial LEO-PNT solutions currently exist and there is no unified research on LEO-PNT concepts. Our survey aims to fill the gaps in knowledge regarding what a LEO-PNT system entails, its technical design steps and challenges, what physical layer parameters are viable solutions, what tools can be used for a LEO-PNT design (e.g., optimisation steps, hardware and software simulators, etc.), the existing models of wireless channels for satellite-to-ground and ground-to-satellite propagation, and the commercial prospects of a future LEO-PNT system. A comprehensive and multidisciplinary survey is provided by a team of authors with complementary expertise in wireless communications, signal processing, navigation and tracking, physics, machine learning, Earth observation, remote sensing, digital economy, and business models.Peer reviewe