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/)

Étude par spectroscopie infrarouge de l’autoassociation d’éther-alcools en solution, entre 293 et 83 K

Les spectres infrarouge d'éther-alcools en solution ont été étudiés entre 293 K et 83 K dans les régions d'absorption du groupement hydroxyle OH pour la transition fondamentale et la première harmonique.Four le méthoxy-3 butanol-1, le méhtoxy-4 butanol-1 et le méthoxy-5 pentanol-1 on observe à 20 °C, une bande OH libre el une bande OH associée, due à la chélation. Cette dernière bande disparaît progressivement par abaissement de température au profit d'une bande associée, située à plus basse fréquence, due à l’auto-association des éther-alcools. Cette autoassociation s’effectue par l'établissement de pont hydrogène entre les groupes hydroxyle comme le prouvent les expériences de dilution isotopique réalisées à 83 K. A cette température on n'observe pas de liaison intermoléculaire O — H --- O (éther) pour ces trois composés.En revanche, pour l'hydroxyméthyl-2 tétrahydropyranne et l'hydroxyméthyl-2 tétrahydrofuranne, on observe à 83 K entre 3 400 et 3 300 cm-1, deux bandes attribuables à des liaisons intermoléculaires, alcool-éther. Pour expliquer la présence de ces deux bandes nous devons admettre que les espèces auto-associées sont des dimères cycliques.Pour l’hydroxy-3 tétrahydrofuranne et le méthoxy-2 éthanol l’auto-association peut s’effectuer par l’établissement, soit de liaisons hydrogène alcool-alcool, soit de liaisons hydrogène alcool-éther suivant les conditions de concentration et de milieu

Does HEV‐3 subtype play a role in the severity of acute hepatitis E?

International audienceHepatitis E virus genotype 3 (HEV-3) is a major aetiologic agent of acute hepatitis in industrialized countries. Two main HEV-3 subtypes are found in Europe: subtypes 3c and 3f. We have analysed the clinical and biological parameters from 100 French immunocompetent patients with an HEV subtype 3f or subtype 3c infection, included in a prospective multicentre study. Stepwise regression analysis found that infections with HEV subtype 3f were associated with fever (OR: 6.1 95%CI: 1.4-26.1), have a greater virus load (OR: 7.4; 95%CI: 1.3-42.2) and require more frequent hospitalization (OR: 7.6; 95%CI: 1.1-51.4) than those infected with subtype 3c. The directed acyclic graph strengthens the multivariate analyses indicating a direct link between the HEV subtype, HEV RNA concentration, fever and hospitalization. Further studies on patients in other European countries are needed to confirm this relationship and determine the underlying mechanis

A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors

The advent of immune checkpoint-inhibitors (CPI) has transformed treatment for several cancer types. This review was performed to assess the rate of adverse events (AEs) associated with the use of CPI, alone or in combinations. A review of AEs reporting quality was also performed. All publications of Randomized Clinical Trials (RCTs) assessing CPI published before December 2017 were included. To investigate the quality of AEs reporting, a set of items was defined based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, and study-withdrawal related AEs were collected in each treatment category. Specific immune related AEs (irAEs) were also collected when available. Pooled estimates of adverse event rates were calculated by using generalized linear mixed model. A total of 35 RCTs including 16,485 patients were included. The overall quality of AEs reporting was satisfactory, but items pertaining to methods of data collection and analysis were infrequently reported. Grade ≥ 3 AEs were reported for 14% (95% CI 12-16) of patients treated with PD(L)-1 inhibitors, 34% (95% CI 27-42) of patients treated with CTLA-4 inhibitors, 55% (95% CI 51-59) of patients on CPI combinations and 46% (95% CI 40-53) of patients on immunotherapy-chemotherapy combination. The profile of irAEs was different among the treatment categories. The use of CPI, especially in combination, is associated with significant rates of Grade ≥ 3 AEs. Healthcare planning should anticipate the expected high number of patients presenting with irAEs in the future

Rat Hepatitis E Virus: Presence in Humans in South-Western France?

International audienceBackground: Hepatitis E Virus (HEV) is one of the most common causes of hepatitis worldwide, and South-Western France is a high HEV seroprevalence area. While most cases of HEV infection are associated with the species Orthohepevirus-A, several studies have reported a few cases of HEV infections due to Orthohepevirus-C (HEV-C) that usually infects rats. Most of these human cases have occurred in immunocompromised patients. We have screened for the presence of HEV-C in our region. Methods and Results: We tested 224 sera, mostly from immunocompromised patients, for HEV-C RNA using an in-house real time RT-PCR. Liver function tests gave elevated results in 63% of patients: mean ALT was 159 IU/L (normal &lt; 40 IU/L). Anti-HEV IgG (49%) and anti-HEV IgM (9.4%) were frequently present but none of the samples tested positive for HEV-C RNA. Conclusion: HEV-C does not circulate in the human population of South-Western France, despite the high seroprevalence of anti-HEV IgG

Pax Americana

Le XXIe siècle sera-t-il américain ? La question se pose, en effet, au terme d'une décennie marquée par le retour en force de la puissance économique des États-Unis et par l'accélération du processus de mondialisation. Ainsi, alors que s'affirme la suprématie du modèle "anglosaxon", l'instauration d'une pax americana serait-elle l'étape ultime de la marche vers une économie mondialisée ? Les études réunies ici tentent d'apporter des éléments de réponse à cette question. Elles éclairent certaines des facettes actuelles du leadership américain. Plus généralement, elles étudient la dynamique économique anglo-saxonne et en explorent les ressorts idéologiques, juridiques, politiques ou managériaux. Elles placent les évolutions actuelles dans une perspective historique à plus long terme

Mobilization of γδ T Cells and IL-10 Production at the Acute Phase of Hepatitis E Virus Infection in Cytomegalovirus Carriers

International audienceAlterations in the γδ T cell compartment have been reported in immunocompromised individuals infected with hepatitis E virus (HEV)–g3. We now report the analysis of blood γδ T cells from acutely HEV-infected individuals in the absence of immunosuppression. In these patients, non-Vδ2 (ND2) γδ T cells outnumbered otherwise predominant Vδ2 cells selectively in human CMV (HCMV)-seropositive patients and were higher than in HCMVpos controls, mimicking HCMV reactivation, whereas their serum was PCR-negative for HCMV. Stimulation of their lymphocytes with HEV-infected hepatocarcinoma cells led to an HEV-specific response in γδ subsets of HCMVpos individuals. HEV infection was associated with a lowered expression of TIGIT, LAG-3, and CD160 immune checkpoint markers on ND2 effector memory cells in HCMVneg but not in HCMVpos HEV patients. γδ cell lines, predominantly ND2, were generated from patients after coculture with hepatocarcinoma cells permissive to HEV and IL-2/12/18. Upon restimulation with HEV-infected or uninfected cells and selected cytokines, these cell lines produced IFN-γ and IL-10, the latter being induced by IL-12 in IFN-γ–producing cells and upregulated by HEV and IL-18. They were also capable of suppressing the proliferation of CD3/CD28–activated CD4 cells in transwell experiments. Importantly, IL-10 was detected in the plasma of 10 of 10 HCMVpos HEV patients but rarely in controls or HCMVneg HEV patients, implying that γδ cells are probably involved in IL-10 production at the acute phase of infection. Our data indicate that HEV mobilizes a pool of ND2 memory cells in HCMV carriers, promoting the development of an immunoregulatory environment

Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study

International audienceBackground & aims: Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy.Methods: Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA.Results: Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anaemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed.Conclusions: Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viraemia may be the best regimen for this indication