Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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

Fibrin glue is effective healing perianal fistulas in patients with Crohn's disease.

peer reviewedBACKGROUND & AIMS: Fibrin glue is a therapeutic for fistulas that activates thrombin to form a fibrin clot, which mechanically seals the fistula tract. We assessed the efficacy and safety of a heterologous fibrin glue that was injected into the fistula tracts of patients with Crohn's disease (ClinicalTrials.gov No. NCT00723047). METHODS: This multicenter, open-label, randomized controlled trial included patients with a Crohn's disease activity index < or =250 and fistulas between the anus (or low rectum) and perineum, vulva, or vagina, that drained for more than 2 months. Magnetic resonance imaging or endosonography was performed to assess fistula tracts and the absence of abscesses. Patients were stratified into groups with simple or complex fistulas and randomly assigned to receive fibrin glue injections (n = 36) or only observation (n = 41) after removal of setons. The primary end point was clinical remission at week 8, defined as the absence of draining, perianal pain, or abscesses. At week 8, a fibrin glue injection was offered to patients who were not in remission. RESULTS: Clinical remission was observed in 13 of the 34 patients (38%) of the fibrin glue group compared with 6 of the 37 (16%) in the observation group; these findings demonstrate the benefit of fibrin glue (odds ratio, 3.2; 95% confidence interval: 1.1-9.8; P = .04). The benefit seemed to be greater in patients with simple fistulas. Four patients in the fibrin glue group and 6 in the observation group had adverse events. CONCLUSIONS: Fibrin glue injection is a simple, effective, and well-tolerated therapeutic option for patients with Crohn's disease and perianal fistula tracts

The Clinical Picture of Severe Systemic Capillary-Leak Syndrome Episodes Requiring ICU Admission

International audienc

Clinical phenotype and outcomes of pneumococcal versus meningococcal purpura fulminans: a multicenter retrospective cohort study

International audienceNo abstract availabl

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn’s disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn’s perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn’s disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn’s lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn’s disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn’s disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer

Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial

International audienceEpidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia