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/)

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

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

Evaluation clinique et prise en charge standardisées de l'orbitopathie dysthyroïdienne dans le service d'ophtalmologie du CHU de Rennes de janvier 2011 à janvier 2012 (étude préliminaire)

Introduction: l'orbitopathie dysthyroïdienne est une pathologie invalidante, potentiellement grave, dont le retentissement sur la qualité de vie ne doit pas être sous-estimé. Sa physiopathologie est encore imparfaitement connue et fait toujours l'objet de nombreuses études. Sous l'impulsion de l'EUGOGO ( European Group on Graves' Orbitopathy), son diagnostic et son traitement sont en voie de standardisation. Matériel et méthode: Il s'agit d'un travail préliminaire. Nous avons évalué la prise en charge des vingt patients suivis dans le service d'ophtalmologie du CHU de Rennes de janvier 2011 à janvier 2012. Les données sociodémographiques, les données relatives à la dysthyroïdie et à l'orbitopathie dysthyroïdienne, ainsi que le traitement instauré étaient collectés à partir des dossiers des patients, et comparés à la littérature. Résultats: la moyenne d'âge était de 46 ans, avec un sex ratio de trois femmes pour un homme. L'association à une pathologie auto-immune était retrouvée chez 15% des patients. 40% des patients étaient fumeurs lors du diagnostic. 60% des patients avaient un CAS (Score d'activité clinique) >3/7 relevant donc d'une corticothérapie. Nous retrouvions 30% d'orbitopathies légères, 65% d'atteintes modérées 0 S2V7RES ET 5% d'atteintes graves. 10% des patients ont bénéficié d'une radiothérapie orbitaire. Aucun patient n'a bénéficié d'un traitement chirurgical. Discussion et conclusion: la qualité de la prise en charge de l'orbitopathie dysthyroïdienne dépend de la justesse de l'évaluation clinique initiale. L'EUGOGO recommande une approche pluridisciplinaire, et une standardisation de l'évaluation clinique, afin d'harmoniser le traitement. Cette étude préliminaire a permis d'élaborer un outil de travail utile pour la prise en charge standardisée des patients dans notre service et qui servira de base pour poursuivre l'évaluation.Introduction: Graves' orbitopathy is an incapacitating disease, potentially serious. Its impact on quality of life has to be evaluated. Its physiopathology is still incompletely known. Thanks to the European Group on Graves' Orbitopathy (EUGOGO), its diagnosis and treatment are going to be standardized. Methods: it is a preliminary work. We have studied the management of the 20 patients followed-up in the ophtalmology department of the hospital of Rennes, from january 2011 to january 2012. General data, endocrinal and ophtalmologic data, and treatment were reported, and compared to the other studies. Results: the mean age was 46 year-old, with a sex ratio of three women for one man. The association to another autoimmune disease was found in 15% of the patients. 40% patients smoked at the time of diagnosis. 60% of the patients had a CAS (Clinical Activity Score)> 3/7, which indicates the need of a glucocorticoid therapy. 30% had a mild disease, 65% a moderate to severe disease, and 5% a serious disease. 10% were treated by orbital radiotherapy. None patient had a surgical treatment. Conclusions: the quality of the management of Graves' orbitopathy depends onthe right initial clinical evaluation. EUGOGO advises a multidisciplinary approach and a standardization of the clinical assessment in order to coordinate treatment. This preliminary study permitted to create a useful tool in order to make easier the management of Graves'orbitopathy in our department, and to follow the evaluation.RENNES1-BU Santé (352382103) / SudocSudocFranceF

Nature et origine des dépôts de sulfates dans les régions équatoriales et polaires de Mars (comparaison morphologique et minéralogique entre Aram Chaos et la calotte polaire Nord )

Important sulfate deposits have been detected in some equatorial regions of Mars : in the canyons of Valles Marineris, on chaotic terrains, and on Meridiani plains. In order to explain the chemical composition of these deposits, and the formation of a large volume of sediment displaying the same composition and spreading over various and extensive terrains, one of the latest hypotheses suggests a glacial origin. The aim of this thesis is to evaluate the consistency of this process by an integrated morphological and mineralogical study of sulfates found on the North Polar Cap, and on the equatorial chaotic terrains (Aram Chaos). Analysis of the North Polar Cap reveals that all the superficial sediments contain gypsum. These sulfate-bearing particles havereleased directly from the ice cap by sublimation. Winds are then responsible to the reworking of these sediments and their accumulation in the circumpolar dune field. The analysis of Aram Chaossulfate deposits reveals some bright, layered outcrops, similar to those observed in Valles Marineris and Meridiani Planum, that contain a mixing of monohydrated sulfates, ferric oxides and hydrated minerals. These deposits could also originate from glacial processes because, during the periods of high obliquity, some ice accumulations could have formed in the lower latitudes. Moreover, observation of terrestrial analogs in Antarctica demonstrates that sulfates could be formed in the ice by some post-depositional processes. These processes could reproduce the chemical composition of the martian equatorial deposits if ice and some volcanic materials was accumulated at the same time.D importants dépôts de sulfate ont été détectés dans les régions équatoriales de Mars : dans les canyons de Valles Marineris, sur les terrains chaotiques, et sur les plaines de Meridiani. Afin d expliquer la chimie de ces dépôts, ainsi que la formation d un tel volume de sédiments de même composition, sur des surfaces larges et variées, l une des hypothèses les plus récentes suggère une origine glaciaire. Le but de cette thèse est d évaluer la plausibilité de ce mode de formation, par une étude morphologique et minéralogique complète des sulfates trouvés sur la calotte polaire Nord, et sur les terrains chaotiques (Aram Chaos). L analyse des sédiments superficiels de la calotte polaire montre que ceux-ci sont riches en gypse. Ces particules riches en sulfate sont proviennent directement de la calotte polaire, s accumulent en surface après l ablation de la glace, et sont transportées par le vent dans les dunes circum-polaires. L analyse des affleurements observés à l équateur sur Aram Chaos montre des dépôts stratifiés clairs, semblables à ceux de Valles Marineris et Meridiani Planum, et contenant un mélange de sulfates monohydratés, d oxydes de fer et de minéraux hydratés. Ces dépôts pourraient également avoir une origine glaciaire car, durant les périodes de haute obliquité, d anciennes accumulations de glace ont pu se former aux basses latitudes. De plus, l observation d analogues terrestres en Antarctique révèle que des sulfates se forment effectivement dans la glace par des réactions post-dépôts, et peuvent être compatibles avec la chimie des minéraux observés à l équateur martien si l accumulation de la glace coïncide avec le dépôt de matériaux volcaniques.NANTES-BU Sciences (441092104) / SudocSudocFranceF

Differential respiratory control of the upper airway and diaphragm muscles induced by 5-HT1A receptor ligands.

International audienceBACKGROUND: Serotonin (5-HT) has a role in respiratory function and dysfunction. Although 5-HT affects respiratory drive to both phrenic and cranial motoneurons, relatively little is known about the role of 5-HT receptor subtypes in the control of upper airway muscle (UAM) respiratory activity. MATERIALS AND METHODS: Here, we performed central injections of 5-HT1A agonist (8-OHDPAT) or antagonist (WAY100635) in anesthetized rats and analyzed changes in the electromyographic activity of several UAM and other cardiorespiratory parameters. We also compared the pattern of Fos expression induced after central injection of a control solution or 8-OHDPAT. RESULTS: Results showed that 8-OHDPAT induced a robust increase in UAM activity, associated with either tachypnea under volatile anesthesia or bradypnea under liquid anesthesia. Injection of WAY100635 switched off UAM respiratory activity and led to bradypnea, suggesting a tonic excitatory role of endogenous 5-HT1A receptor activation. Co-injection of the agonist and the antagonist blocked the effects produced by each drug alone. Besides drug-induced changes in respiratory frequency, only slight increases in surface of diaphragm bursts were observed. Significant increases in Fos expression after 5-HT1A receptor activation were seen in the nucleus tractus solitarius, nucleus raphe pallidus, parapyramidal region, retrotrapezoid nucleus, lateral parabrachial, and Kölliker-Fuse nuclei. This restricted pattern of Fos expression likely identified the neural substrate responsible for the enhancement of UAM respiratory activity observed after 8-OHDPAT injection. CONCLUSIONS: These findings suggest an important role for the 5-HT1A receptors in the neural control of upper airway patency and may be relevant to counteract pharyngeal atonia during obstructive sleep apneas

Infiltration graisseuse des muscles pelvi-trochantériens dans l'arthroplastie totale de hanche par abord antérieur mini-invasif

International audienceIntroduction: Le choix de l'abord chirurgical pour la réalisation d'une arthroplastie totale de hanche (ATH) ne fait pas consensus en orthopédie. Il existe un regain d'intérêt ces dernières années pour les voies antérieures mini-invasives (VAMI) dites anatomiques. Cependant, leur retentissement minoré n'a pas été confirmé par des imageries. Aussi nous avons mené une étude prospective destinée à : (1) évaluer l'infiltration graisseuse (IG) des muscles péri-articulaires de hanche, (2) analyser l’évolution de cette IG dans le temps. Hypothèse: Une ATH par VAMI induit une IG sur les muscles péri-articulaires antéro-latéraux adjacents à l'abord. Matériels et méthodes: Une série continue mono-opérateur d'ATH par VAMI sur table orthopédique a été réalisée par un opérateur entraîné. Des IRM (1,5Tesla OPTIMA MR360) ont été réalisées en préopératoire, puis à 3 mois et 1 an de la chirurgie. L'analyse de l'IG musculaire selon la classification de Goutallier était réalisée par un radiologue indépendant sur l'ensemble des muscles péri-articulaires de hanche. La comparaison était effectuée entre les IRM préopératoires et celles à 3 mois et 1 an à l'aide de tests de Wilcoxon. Résultats: Soixante-neuf IRM ont été réalisées sur 23 patients. Deux n’étaient pas interprétables du fait de mouvements du patient lors de l'acquisition préopératoire. Aucune complication peropératoire ni postopératoire n'a été rapportée dans cette série après 1 an de suivi. Tous les patients présentaient des hanches indolores sans boiterie à 1 an de l'intervention. L'analyse de l'IG montrait une aggravation significative de cette dernière entre les IRM préopératoires et celles à 3 mois (p = 0,02) et 1 an (p = 0,0007) au niveau du muscle obturateur interne ainsi qu’à 1 an (p = 0,04) au niveau du muscle piriforme. Aucune différence significative n’était retrouvée sur les autres muscles. Le muscle droit fémoral, les muscles jumeaux supérieurs et inférieurs ainsi que le muscle carré fémoral n’étaient pas analysables. Discussion: Notre hypothèse de départ n’était pas confirmée mais nous avons retrouvé un résultat paradoxal avec la mise en évidence d'une IG musculaire, cependant celle-ci n’était pas antéro-externe mais postérieure au niveau des muscles pelvi-trochantériens à la suite d'ATH par VAMI. Ces lésions pourraient être secondaires à des désinsertions ou des dénervations de ces muscles lors de l’élévation du fémur pour l'implantation fémorale. Niveau de preuve: IV; série prospective de cas

Gene expression profiling of the Peyer's patch mononuclear phagocyte system

International audiencePeyer's patches (PPs) are primary inductive sites of mucosal immunity. The PP mononuclear phagocyte system, which encompasses both dendritic cells (DCs) and macrophages, is essential for the initiation of the mucosal immune response. We recently developed a method to isolate each mononuclear phagocyte subset of PP (Bonnardel et al., 2015). We performed a transcriptional analysis of three of these subsets: the CD11b + conventional DC, the lysozyme-expressing monocyte-derived DC termed LysoDC and the CD11c hi lysozyme-expressing macrophages. Here, we provide details of the gating strategy we used to isolate each phagocyte subset and show the quality controls and analysis associated with our gene array data deposited into Gene Expression Omnibus (GEO) under GSE65514

Gene expression profiling of the Peyer's patch mononuclear phagocyte system

Peyer's patches (PPs) are primary inductive sites of mucosal immunity. The PP mononuclear phagocyte system, which encompasses both dendritic cells (DCs) and macrophages, is essential for the initiation of the mucosal immune response. We recently developed a method to isolate each mononuclear phagocyte subset of PP (Bonnardel et al., 2015). We performed a transcriptional analysis of three of these subsets: the CD11b+ conventional DC, the lysozyme-expressing monocyte-derived DC termed LysoDC and the CD11chi lysozyme-expressing macrophages. Here, we provide details of the gating strategy we used to isolate each phagocyte subset and show the quality controls and analysis associated with our gene array data deposited into Gene Expression Omnibus (GEO) under GSE65514