The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability. METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT. RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT. DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.

Background: The role of remdesivir inThe primary outcome was in-hospital 24.8% and 28.2%, respectively (95% CI the treatment of patients in hospital mortality. Secondary outcomes 0.72 to 1.07). For patients not mechanwith COVID-19 remains ill defined in a included changes in clinical severity, ically ventilated at baseline, the need for global context. The World Health Organ-oxygen-and ventilator-free days (at mechanical ventilation was 8.0% in those ization Solidarity randomized controlled 28 d), incidence of new oxygen or assigned remdesivir, and 15.0% in those trial (RCT) evaluated remdesivir in mechanical ventilation use, duration of receiving standard of care (RR 0.53, 95% CI patients across many countries, with hospital stay, and adverse event rates. 0.38 to 0.75). Mean oxygen-free and Canada enrolling patients using anWe performed a priori subgroup analy-ventilator-free days at day 28 were 15.9 expanded data collection format in the ses according to duration of symptoms (± standard deviation [SD] 10.5) and 21.4 Canadian Treatments for COVID-19 before enrolment, age, sex and severity (± SD 11.3) in those receiving remdesivir (CATCO) trial. We report on the Canad-of symptoms on presentation. and 14.2 (± SD 11) and 19.5 (± SD 12.3) in ian findings, with additional demo-those receiving standard of care (p = 0.006 graphics, characteristics and clinical Results: Across 52 Canadian hospitals, and 0.007, respectively). There was no difoutcomes, to explore the potential for we randomized 1282 patients between ference in safety events of new dialysis, differential effects across different Aug. 14, 2020, and Apr. 1, 2021, to remde-change in creatinine, or new hepatic dyshealth care systems.sivir (n = 634) or standard of care (n = function between the 2 groups. 648). Of these, 15 withdrew consent or Methods: We performed an open-label, were still in hospital, for a total sample of Interpretation: Remdesivir, when compragmatic RCT in Canadian hospitals, in 1267 patients. Among patients assigned pared with standard of care, has a modest conjunction with the Solidarity trial. We to receive remdesivir, in-hospital mortal-but significant efect on outcomes imporrandomized patients to 10 days of rem-ity was 18.7%, compared with 22.6% in tant to patients and health systems, such desivir (200 mg intravenously [IV] on day the standard-of-care arm (relative risk as the need for mechanical ventilation. 0, followed by 100 mg IV daily), plus[RR] 0.83 (95% confidence interval [CI] Trial registration: ClinicalTrials.gov, no. standard care, or standard care alone. 0.67 to 1.03), and 60-day mortality was NCT04330690.

Probiotic microorganisms have been documented over the past two decades to play a role in cholesterol-lowering properties via various clinical trials. Several mechanisms have also been proposed and the ability of these microorganisms to deconjugate bile via production of bile salt hydrolase (BSH) has been widely associated with their cholesterol lowering potentials in prevention of hypercholesterolemia. Deconjugated bile salts are more hydrophobic than their conjugated counterparts, thus are less reabsorbed through the intestines resulting in higher excretion into the feces. Replacement of new bile salts from cholesterol as a precursor subsequently leads to decreased serum cholesterol levels. However, some controversies have risen attributed to the activities of deconjugated bile acids that repress the synthesis of bile acids from cholesterol. Deconjugated bile acids have higher binding affinity towards some orphan nuclear receptors namely the farsenoid X receptor (FXR), leading to a suppressed transcription of the enzyme cholesterol 7-alpha hydroxylase (7AH), which is responsible in bile acid synthesis from cholesterol. This notion was further corroborated by our current docking data, which indicated that deconjugated bile acids have higher propensities to bind with the FXR receptor as compared to conjugated bile acids. Bile acids-activated FXR also induces transcription of the IBABP gene, leading to enhanced recycling of bile acids from the intestine back to the liver, which subsequently reduces the need for new bile formation from cholesterol. Possible detrimental effects due to increased deconjugation of bile salts such as malabsorption of lipids, colon carcinogenesis, gallstones formation and altered gut microbial populations, which contribute to other varying gut diseases, were also included in this review. Our current findings and review substantiate the need to look beyond BSH deconjugation as a single factor/mechanism in strain selection for hypercholesterolemia, and/or as a sole mean to justify a cholesterol-lowering property of probiotic strains.

BackgroundKnowledge of the impact of the gut microbiome on conditions other than Clostridium difficile infection has been rapidly increasing, and the potential usefulness of fecal microbiota transplantation (FMT) in these indications is being explored. The need to exclude donors with an increased risk of these diseases has left uncertainties regarding the cost and feasibility of donor screening. The aim of this study was to compare our experience to other donor-screening programs and report the costs associated with establishing a donor-screening program, for the treatment of metabolic syndrome-related conditions.MethodsForty-six potential donors (PDs) had their medical histories and physical examinations undertaken by a physician. Blood, stool, and urine were screened for 31 viral, bacterial, fungal, and protozoan agents in addition to biochemical characteristics. The price of advertising, doctor’s visits and diagnostic tests were calculated to determine the cost of finding a donor.ResultsOf the PDs screened, 5 of 46 passed the history, examination, blood, stool, and urine tests. The most common reasons for exclusion included a body mass index >25 or the detection of Blastocystis hominis, Dientamoeba fragilis, or Helicobacter pylori. Four of five eligible donors had subsequent travel or illness that contraindicated donation, so only 1 of 46 PDs was suitable. The total cost for finding a single suitable donor was $15190 US dollars. This screening was performed in Canada, and costs in the United States would be substantially higher.ConclusionsNew potential therapeutic uses for FMT have created a demand for stricter exclusion criteria for donors. This study illustrates that screening many individuals to find a donor and the subsequent associated costs may make central processing and shipment a more reasonable alternative.