Our results show that cyanoacrylate is more effective and achieves GV obliteration faster than injection sclerotherapy with alcohol. It also appears to be more useful in controlling acute GV bleeding, with less of a need for rescue surgery.

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–...

Both EVL and drug therapy are effective in the prevention of variceal rebleeding. Comparisons between the two modalities are few, and only in cirrhotics. This prospective randomized controlled trial compared EVL with drug therapy (propranolol + ISMN) in the prevention of rebleeds from esophageal varices in cirrhotic and noncirrhotic portal hypertension (NCPH) patients. One hundred thirty-seven variceal bleeders were randomized to EVL (Group I; n = 71) or drug therapy (Group II; n = 66). In Group I, EVL was done every 2 weeks till obliteration of varices. In Group II, propranolol (dose sufficient to reduce heart rate to 55 bpm/maximum tolerated dose) and ISMN (incremental dose up to 20 mg BD) were administered. Group I and II patients had comparable baseline characteristics, follow-up (12.4 vs. 11.1 months), cirrhotics and noncirrhotics [50(70.4%) and 21(29.6%) vs. 51(77.3%) and 15(22.7%)] and frequency of Child's A (35 vs. 27), B (26 vs. 28), and C (9 vs. 11). The mean daily dose was 109 +/- 46 mg propranolol and 34 +/- 11 mg ISMN and was comparable in cirrhotic and NCPH patients. Upper GI bleeds occurred in 10 patients in Group I (5 from esophageal varices) and in 18 patients in Group II (15 from esophageal varices) (P = 0.06). The actuarial probability of rebleeding from esophageal varices at 24 months was 22% in Group I and 37% in Group II (P = 0.02). The probability of bleed was significantly higher in Child's C compared to Child's A/B cirrhotics (P = 0.02). On subgroup analysis, in NCPH patients, the actuarial probability of bleed at 24 months was significantly lower in Group I compared to Group II (25% vs 37%; P = 0.01). In cirrhotics, there was no difference in the probability of rebleeding between patients in Group I and those in Group II (P = 0.74). In Group II, 25.7% patients had adverse effects of drug therapy and 9% patients had to stop propranolol due to serious adverse effects, none required stopping ISMN. There were 10 deaths, 6 in Group I (bleed related, 1) and 4 in Group II (bleed related, 1); the actuarial probability of survival was comparable (P = 0.39). EVL and combination therapy are equally effective in the prevention of variceal rebleeding in cirrhotic patients. EVL is more effective than drug therapy in the prevention of rebleeds in patients with NCPH and, hence, recommended. However, in view of the small number of NCPH patients, further studies are needed before this can be stated conclusively.

Prophylaxis with norfloxacin and cisapride significantly reduces the incidence of SBP in high-risk cirrhosis patients; low serum albumin, low ascitic fluid protein and alcoholic cirrhosis predispose to the development of SBP in high-risk cirrhosis patients; and low ascitic fluid protein should also be considered as a risk factor for the development of SBP requiring prophylaxis.

Severe COVID-19 is a biphasic illness, with an initial viral replication phase, followed by a cascade of inflammatory events. Progression to severe disease is predominantly a function of the inflammatory cascade, rather than viral replication per se. This understanding can be effectively translated to changing our approach in managing the disease. The natural course of disease offers us separate windows of specific time intervals to administer either antiviral or immunomodulatory therapy. Instituting the right attack at the right time would maximize the benefit of treatment. This concept must also be factored into studies that assess the efficacy of antivirals and immunomodulatory agents against COVID-19.