Antibody interference and response kinetics of isatuximab plus pomalidomide and dexamethasone in multiple myeloma

The ICARIA-MM study was sponsored by Sanofi. The authors thank, Helgi van de Velde, Valérie Boutet, Shujia Dai, Deborah DiNoto, Graziella Engelvin, Olivier Fedeli, Sébastien Hugla, Dominique Mouret, Béatrice Pradeilles, and Alain Roccon, all employees of Sanofi, for their contribution to the study, technology, and comments on the manuscript. The authors thank the participating patients and their families, and the study centers and investigators, for their contributions to the study. The medical writing support was provided by John Clarke, PhD and Stephanie Brillhart, PhD of Elevate Medical Affairs, contracted by Sanofi Genzyme for publication support services

Healthcare-associated infections in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

International audienceBackground Both critically ill patients with coronavirus disease 2019 (COVID-19) and patients receiving extracorporeal membrane oxygenation (ECMO) support exhibit a high incidence of healthcare-associated infections (HAI). However, data on incidence, microbiology, resistance patterns, and the impact of HAI on outcomes in patients receiving ECMO for severe COVID-19 remain limited. We aimed to report HAI incidence and microbiology in patients receiving ECMO for severe COVID-19 and to evaluate the impact of ECMO-associated infections (ECMO-AI) on in-hospital mortality. Methods For this study, we analyzed data from 701 patients included in the ECMOSARS registry which included COVID-19 patients supported by ECMO in France. Results Among 602 analyzed patients for whom HAI and hospital mortality data were available, 214 (36%) had ECMO-AI, resulting in an incidence rate of 27 ECMO-AI per 1000 ECMO days at risk. Of these, 154 patients had bloodstream infection (BSI) and 117 patients had ventilator-associated pneumonia (VAP). The responsible microorganisms were Enterobacteriaceae (34% for BSI and 48% for VAP), Enterococcus species (25% and 6%, respectively) and non-fermenting Gram-negative bacilli (13% and 20%, respectively). Fungal infections were also observed (10% for BSI and 3% for VAP), as were multidrug-resistant organisms (21% and 15%, respectively). Using a Cox multistate model, ECMO-AI were not found associated with hospital death (HR = 1.00 95% CI [0.79–1.26], p = 0.986). Conclusions In a nationwide cohort of COVID-19 patients receiving ECMO support, we observed a high incidence of ECMO-AI. ECMO-AI were not found associated with hospital death. Trial registration number NCT04397588 (May 21, 2020)

Veno-Arterial Extracorporeal Membrane Oxygenation for Circulatory Failure in COVID-19 Patients: Insights from the ECMOSARS Registry

International audienceObjectives: The clinical profile and outcomes of patients with Covid-19 who require veno-arterial or veno-venous-arterial extracorporeal membrane oxygenation (VA-ECMO - VAV-ECMO) are poorly understood. We aimed to describe the characteristics and outcomes of these patients and to identify predictors of both favorable and unfavorable outcomes.Methods: ECMOSARS is a multicenter, prospective, nationwide French registry enrolling patients who require VV/VA-ECMO in the context of Covid-19 infection (652 patients at 41 centers). We focused on 47 patients supported with VA- or VAV-ECMO for refractory cardiogenic shock.Results: Median age was 49. 14% of patients had a prior diagnosis of heart failure. The most common etiologies of cardiogenic shock were acute pulmonary embolism (30%), myocarditis (28%), and acute coronary syndrome (4%). E-CPR (Extracorporeal Cardiopulmonary Resuscitation) occurred in 38%. In-hospital survival was 28% in the whole cohort, and 43% when E-CPR patients were excluded. ECMO cannulation was associated with significant improvements in pH and FiO2 on day one, but non-survivors showed significantly more severe acidosis and higher FiO2 than survivors at this point (p = 0.030 and p = 0.006). Other factors associated with death were greater age (p = 0.02), higher BMI (p = 0.03), E-CPR (p = 0.001), non-myocarditis etiology (p = 0.02), higher serum lactates (p = 0.004), epinephrine (but not noradrenaline) use before initiation of ECMO (p = 0.003), hemorrhagic complications (p = 0.001), greater transfusion requirements (p = 0.001), and more severe SAVE and SAFE scores (p = 0.01 and p = 0.03).Conclusions: We report the largest focused analysis of VA- and VAV-ECMO recipients in Covid-19. Although relatively rare, the need for temporary mechanical circulatory support in these patients is associated with poor prognosis. However, VA-ECMO remains a viable solution to rescue carefully selected patients. We identified factors associated with poor prognosis and suggest that E-CPR is not a reasonable indication for VA-ECMO in this population