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/)

Utilisation de l'ECMO dans le SDRA (l'expérience Aquitaine)

INTRODUCTION : Le SDRA fait partie des pathologies les plus fréquentes d'admission des patients en réanimation. Malgré des progrès récents concernant sa compréhension et sa physiopathologie, le taux de mortalité des patients atteints de SDRA reste très élevé. En cas d'hypoxie extrêmement sévère et réfractaire à une prise en charge optimale conventionnelle, certaines équipes ont recours à l'ECMO pour assurer les échanges gazeux tout en laissant les poumons au repos pour limiter les lésions induites par la ventilation. MATERIELS ET METHODE : Nous rapportons, dans cette étude rétrospective et descriptive, l'expérience bordelaise de l'utilisation de l'ECMO chez les patients atteints de SDRA sévère ainsi que le syuivi de leur qualité de vie à long terme. RESULTATS : Entre 2009 et 2012, 23 patients ont bénéficié de l'ECMO pour SDRA en Aquitaine. La mortalité en réanimation et à 1 an étaient respectivement de 17 % et 21 %. La mise en place de l'ECMO a permis de diminuer significativement les pressions de ventilation. Les principales complications étaient barotraumatiques et hémorragiques, nécessitant d'importants besoins transfusionnels. Au niveau du suivi à long terme, les patients de notre étude avaient une qualité de vie dans l'ensemble jugée inférieure à une population normale de référence, sauf concernant la santé mentale. On retrouve également des troubles respiratoires subjectifs, retentissant sur la qualité de vie, chez la plupart des patients. DISCUSSION : En terme de mortalité, nos résultats sont plutôt positifs, comparables à ceux des études récentes. La fréquence élevée des complications barotraumatiques souligne l'importance de l'utilisation d'une ventilation protectrice, à faible pression de plateau. Concernant le suivi à long terme, dans notre étude, il semblerait que les patients ayant bénéficié de l'ECMO souffrent d'une diminution de leur qualité de vie liée à leur état physique mais sans répercussion significative sur le plan mental et social. Cette diminution de la qualité de vie est comparable à celle des populations de patients en SDRA sévère n'ayant pas bénéficié de l'ECMO, retrouvées dans la littérature. CONCLUSION : Les résultats de notre étude semblent montrer que l'utilisation de l'ECMO pour le SDRA est envisageable. Malgré tout, l'importance des complications prouve que l'ECMO pour le SDRA doit rester une thérapeutique d'exception, réalisée dans des centres expérimentés. Les résultats de notre étude sont limités par le fible nombre de patients inclus et par l'importance du biais de sélection. Des études prospectives, randomisées et comparatives sont nécessaires pour évaluer le bénéfice éventuel de l'utilisation de l'ECMO chez les patients de SDRA sévère.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Registration and segmentation of head and neck volumes in IMRT applications

info:eu-repo/semantics/publishe

Preservation of exopolymeric substances in estuarine sediments

International audienceThe surface of intertidal estuarine sediments is covered with diatom biofilms excreting exopolymeric substances (EPSs) through photosynthesis. These EPSs are highly reactive and increase sediment cohesiveness notably through organo-mineral interactions. In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid–base titrations, and (iii) Fourier transform infrared spectroscopy. EPS-sediment complexes were also imaged using cryo-scanning electron microscopy. EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. Concentrations remained relatively low down to ca. 4.3 m deep. Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. EPS composition did not change substantially from the surface to the bottom of the core. EPS concentrations and acidity were anti-correlated with metabolic activity, but showed no statistical correlation with grain size, TOC, depth or enzymatic activity. Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs

Plasmalogens and cell‐cell communication between retinal glial cells

National audiencePurpose Plasmalogens are glycerophospholipids containing a vinyl‐ether bond at sn‐1 position of their glycerol backbone and polyunsaturated fatty acids (PUFAs) at sn‐2. We have previously shown that plasmalogens are involved in the regulation of perinatal retinal vascular development and particularly in astrocyte template formation (Saab et al, PLoSONE 2012 9(6):e101076). Since retinal Müller cells and astrocytes can communicate through calcium waves and connexin 43‐rich gap junctions, the aim of our study was to determine whether a reduction of plasmalogen levels affects communication between retinal glial cells. Methods Primary Müller cells and astrocyte were isolated from retinas of 9‐days old and cerebral cortex from 21‐days old Wistar rats, respectively. SiRNA against DHAPA‐AT ‐the key enzyme of plasmalogen biosynthesis‐ were used to decrease plasmalogen content of Müller cells before they were co‐cultured with naïve astrocytes. Calcium waves initiated in Müller cells by topical application of ATP were monitored by Fura‐2 calcium imaging. Expression levels of cellular proteins involved in calcium metabolism, including connexin 43, were evaluated by proteomics and Western‐blotting in reponse to Si RNA treatment. Results Treating Müller cells with SiRNA against DHAP‐AT led to a reduction of plasmalogen content of about 60% and to a remodelling of PUFA distribution in cell membranes. The expression of connexion 43 was reduced by more than 50% in Müller cells treated with SiRNA. This was associated with an alteration of calcium waves originating from Müller cells as well as a slowed propagation to neighbouring astrocytes. Conclusions These data suggest that membrane plasmalogens content influences cell‐to‐cell communication between retinal Müller cells and astrocytes. Altered coupling between these cells might be one of the factors influencing perinatal vascular development