Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Le dopage chez les chevaux de sport

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

CD34+ cell dose effects on clinical outcomes after T-cell replete haploidentical allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia using peripheral blood stem cells. A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

partially_open16siPrevious observations have reported controversial conclusions regarding cell dose and survival endpoints after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a retrospective analysis on 414 adult patients (median age 54 years, range, 18-74) with acute myeloid leukemia (AML) in first and second complete remission who received a T-cell replete allogeneic HSCT from haploidentical donors, using peripheral blood stem cells, between 2006-2018. Median number of infused CD34+ was 6.58 x 106 /kg (range, 2.2-31.2). Graft-versus-host disease (GVHD) prophylaxis was post-transplant cyclophosphamide in 293 patients and anti-lymphocyte serum in 121 patients. Conditioning was myeloablative in 179 patients and reduced-intensity in 235 patients. After a median follow-up of 23.3 months (range, 12.1-41.8), 2-year overall survival (OS) was 64.5 % (95% CI 59.3-69.7) with leukemia-free survival (LFS) of 57.3 % (95% CI 51.8-62.7) and non-relapse mortality (NRM) of 23.3 % (95% CI 19-27.7). Grades III-IV acute GVHD day+100 incidence was 14.6 % while extensive chronic GVHD was 14.4% at 2-years. Thirteen (3.2%) patients experienced graft failure. We found the optimal CD34+/kg threshold defining high (n= 334) versus low cell dose (n= 80) at 4.96 x 106 . Recipients of > 4.96 x 106 /kg CD34+ cells experienced less NRM (Hazard ratio [HR] 0.48; 95% CI 0.30-0.76) and prolonged LFS (HR 0.63; 95% CI 0.43-0.91) and OS (HR 0.60; 95% CI 0.40-0.88) compared to those in the lower cell dose cohort. Larger cohort studies are needed to confirm these findings. This article is protected by copyright. All rights reserved.openMaffini, Enrico; Labopin, Myriam; Blaise, Didier; Ciceri, Fabio; Gülbas, Zafer; Deconinck, Eric; Leblond, Veronique; Chevallier, Patrick; Sociè, Gerard; Araujo, Mercedes Colorado; Koc, Yener; Savani, Bipin N; Gorin, Norbert Claude; Lanza, Francesco; Nagler, Arnon; Mohty, MohamadMaffini, Enrico; Labopin, Myriam; Blaise, Didier; Ciceri, Fabio; Gülbas, Zafer; Deconinck, Eric; Leblond, Veronique; Chevallier, Patrick; Sociè, Gerard; Araujo, Mercedes Colorado; Koc, Yener; Savani, Bipin N; Gorin, Norbert Claude; Lanza, Francesco; Nagler, Arnon; Mohty, Mohama

Donor EBV Positive Serostatus Increases the Risk of Chronic GVHD in Patients with Myeloid and Lymphoid Malignancies Other Than Acute Leukemia: Infectious Diseases Working Party EBMT Study

Retrospective analysis on Donor EBV Positive Serostatus and the risk of Chronic GVHD in Patients with Myeloid and Lymphoid Malignancies Other Than Acute Leukemi