Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov , NCT04501978 . Findings Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–...

Background The small incisions of minimally invasive surgery have the proposed benefit of less surgical trauma, less pain, and faster recovery. This study was done to compare minimally invasive techniques for aortic valve replacement, including right anterior mini-thoracotomy and mini-sternotomy, to conventional sternotomy. Methods We retrospectively reviewed 503 patients who underwent isolated aortic valve replacement at our institution from 2012 to 2015 using one of three techniques: 1) Mini-thoracotomy, 2) Mini-sternotomy, 3) Conventional sternotomy. Demographics, operative morbidity, mortality, and postoperative complications were compared. Results Of the 503 cases, 267 (53.1%) were mini-thoracotomy, 120 (23.8%) were mini-sternotomy, and 116 (23.1%) were conventional sternotomy. Mini-thoracotomy patients, compared to mini-sternotomy and conventional sternotomy, had significantly shorter bypass times [82 (IQ 67–113) minutes; vs. 117 (93.5–139.5); vs. 102.5 (85.5–132.5), respectively ( p < 0.0001)], a lower incidence of prolonged ventilator support [3.75% vs. 9.17 and 12.9%, respectively ( p = 0.0034)], and required significantly shorter ICU and postoperative stays, resulting in an overall shorter hospitalization [6 (IQ 5–9) days; vs. 7 (5–14.5); vs 9 (6–15.5), respectively ( p < 0.05)]. Incidence of other postoperative complications were lower in the mini-thoracotomy group compared to mini-sternotomy and conventional sternotomy, without significance. Minimally invasive techniques trended towards better survival [mini-thoracotomy 1.5%, mini-sternotomy 1.67%, and conventional sternotomy 5.17% ( p = 0.13)]. Conclusions Minimally invasive aortic valve replacement approaches are safe, effective alternatives to conventional sternotomy. The mini-thoracotomy approach showed decreased operative times, decreased lengths of stay, decreased incidence of prolonged ventilator time, and a trend towards lower mortality when compared to mini-sternotomy and conventional sternotomy.

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BackgroundA significant proportion of patients presenting for isolated aortic valve replacement (AVR) demonstrate some degree of functional mitral regurgitation (fMR). Guidelines addressing concomitant mitral valve intervention in those patients with moderate fMR lack strong evidence-based support. Our aim is to determine the effect of untreated moderate fMR at the time of AVR on long-term survival.MethodsAll patients undergoing isolated AVR from 2000 to 2013 at our institution were retrospectively reviewed. Patients were stratified according to severity of preoperative fMR; 0–1+ MR (Group NoMR, n = 1826) and 2–3+ MR (Group MR, n = 330). All patients in Group MR were propensity-matched with patients in Group NoMR to control for differences in baseline characteristics. The primary outcome of interest was overall survival.ResultsPropensity analysis matched 330 patients from each group. Mean age was 77.9 ± 10.0 years and 50.6% were male. There were no differences in baseline demographics, echocardiographic parameters, or co-morbidities between groups. Kaplan-Meier analysis showed significantly worse medium and long-term survival in Group MR compared to Group NoMR (log-rank p = 0.02). Follow-up echocardiography showed slightly more severe MR in Group MR (1.1 ± 0.7 MR vs. 0.8 ± 0.7 NoMR, p = 0.03) at 1 year.ConclusionsPatients undergoing isolated AVR with concomitant 2–3+ fMR experience poorer long-term survival than those patients with no or mild fMR. This suggests that mitral valve intervention may be necessary in patients undergoing AVR with clinically significant fMR.