Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

Associated features in females with an FMR1 premutation

Abstract Changes in the fragile X mental retardation 1 gene (FMR1) have been associated with specific phenotypes, most specifically those of fragile X syndrome (FXS), fragile X tremor/ataxia syndrome (FXTAS), and fragile X primary ovarian insufficiency (FXPOI). Evidence of increased risk for additional medical, psychiatric, and cognitive features and conditions is now known to exist for individuals with a premutation, although some features have been more thoroughly studied than others. This review highlights the literature on medical, reproductive, cognitive, and psychiatric features, primarily in females, that have been suggested to be associated with changes in the FMR1 gene. Based on this review, each feature is evaluated with regard to the strength of evidence of association with the premutation. Areas of need for additional focused research and possible intervention strategies are suggested

Clinical and radiographic results of the Total Condylar III and Constrained Condylar total knee arthroplasty.

The Total Condylar III (Johnson and Johnson, Braintree, MA) and Constrained Condylar (Zimmer, Warsaw, IN) knee prostheses are nonlinked, semi-constrained prosthetic alternatives to rigid or rotating hinge prostheses for use in complex knee reconstructions. Forty-six Total Condylar III or Constrained Condylar prostheses were implanted with cement in 36 patients and followed for a mean of 5 years (range, 2-9 years). There were 25 primary total knee arthroplasties and 21 revision total knee arthroplasties. The knees were evaluated using The Hospital for Special Surgery 100-point knee rating system. Overall, 40 knees (87%) had a good or excellent clinical result, 2 knees (4%) had a fair result, and 4 knees (9%) had a poor result. There was one revision for loosening of a cemented, nonmodular Constrained Condylar prosthesis, and one knee had a debridement for a late, metastatic infection, but the components were retained. There were no mechanical failures in those knees that were primary arthroplasties, but two mechanical failures occurred in those knees that were revision arthroplasties. Radiographic review showed one asymptomatic loosening of a Constrained Condylar tibial component with an uncemented press-fit stem, and only 8 knees had scattered nonprogressive tibial bone-cement radiolucent lines. The Total Condylar III and Constrained Condylar semiconstrained prostheses are successful when used in complex knee reconstructions