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/)

Probable Interaction Between an Oral Vitamin K Antagonist and Turmeric (Curcuma longa)

We report a probable interaction between a vitamin K antagonist, fluindione, and the herbal medicine turmeric that resulted in the elevation of the international normalized ratio (INR). The case presented here underlines the importance of considering potential exposure to herbal medications when assessing adverse effects

CONTEXTE PALÉOENVIRONNEMENTAL ET CHRONOLOGIQUE DES OCCUPATIONS NÉANDERTALIENNES DE LA GROTTE DES RAMANDILS (PORT-LA-NOUVELLE, AUDE, FRANCE) : APPORT DES RESTES DE GRANDS MAMMIFÈRES

International audience. The Ramandils Cave has yielded abundant Mousterian lithic industries, hominin teeth and faunal remains (ungulates, carnivores, lagomorphs, microvertebrates and malacofauna), revealing a large species diversity in a coastal environmental context. Studies of large mammals, coupled with recent palynological analyses of coprolites, allow attribution of the whole of the deposits to the beginning of the Late Pleistocene and more precisely to marine oxygen isotope stage (MIS) 5, in agreement with the available radiometric dating. The study of these assemblages, especially for the richer stratigraphic units, III and II, suggests various continental environments related to a temperate climate influenced by a Mediterranean coastal context. Fluctuations are perceptible throughout the sequence, as indicated by variations in species and pollen abundance, both taxonomically and quantitatively, with a general trend of opening landscapes in the upper levels. Large mammals from Ramandils Cave, corresponding to a post-Eemian fauna, represent different Neanderthal occupations phases and give an insight into palaeobiodiversity on the northwestern Mediterranean territory during the Late Pleistocene.a livré de nombreuses pièces d'industries lithiques moustériennes, des dents humaines ainsi que des restes fauniques (ongulés, carnivores, lagomorphes, microvertébrés et malacofaune) reflétant une grande diversité spécifique en milieu côtier. L'étude des grands mammifères, couplée aux récentes analyses palynologiques de coprolithes, permet d'attribuer l'ensemble du remplissage au Pléistocène supérieur et plus précisément au stade isotopique marin (SIM) 5, en accord avec les datations radiométriques disponibles. L'analyse de ces assemblages, en particulier pour les ensembles stratigraphiques III et II, les plus riches, a permis de reconstituer le cadre paléoenvironnemental et paléoclimatique de ces niveaux et de mettre en évidence une certaine variété de paysages continentaux, liés à un climat tempéré, influencé par une situation côtière méditerranéenne. Des fluctuations sont cependant perceptibles tout au long de la séquence au sein du cortège faunique et pollinique, tant au niveau taxonomique que quantitatif, montrant une tendance à l'ouverture du milieu dans la partie supérieure des dépôts. Les grands mammifères de la grotte des Ramandils, correspondant à une faune du SIM 5 postérieure à l'Eemien, représentent différentes phases d'occupations néandertaliennes et illustrent une partie de la paléobiodiversité sur le territoire nord-ouest méditerranéen au Pléistocène supérieur

Contexte paléoenvironnemental et chronologique des occupations néandertaliennes de la grotte des Ramandils (Port-La-Nouvelle, Aude, France) : apport des restes de grands mammifères

La grotte des Ramandils (Port-La-Nouvelle, Aude, France) a livré de nombreuses pièces d’industries lithiques moustériennes, des dents humaines ainsi que des restes fauniques (ongulés, carnivores, lagomorphes, microvertébrés et malacofaune) reflétant une grande diversité spécifique en milieu côtier. L’étude des grands mammifères, couplée aux récentes analyses palynologiques de coprolithes, permet d’attribuer l’ensemble du remplissage au Pléistocène supérieur et plus précisément au stade isotopique marin (SIM) 5, en accord avec les datations radiométriques disponibles. L’analyse de ces assemblages, en particulier pour les ensembles stratigraphiques III et II, les plus riches, a permis de reconstituer le cadre paléoenvironnemental et paléoclimatique de ces niveaux et de mettre en évidence une certaine variété de paysages continentaux, liés à un climat tempéré, influencé par une situation côtière méditerranéenne. Des fluctuations sont cependant perceptibles tout au long de la séquence au sein du cortège faunique et pollinique, tant au niveau taxonomique que quantitatif, montrant une tendance à l’ouverture du milieu dans la partie supérieure des dépôts. Les grands mammifères de la grotte des Ramandils, correspondant à une faune du SIM 5 postérieure à l’Eemien, représentent différentes phases d’occupations néandertaliennes et illustrent une partie de la paléobiodiversité sur le territoire nord-ouest méditerranéen au Pléistocène supérieur.The Ramandils Cave has yielded abundant Mousterian lithic industries, hominin teeth and faunal remains (ungulates, carnivores, lagomorphs, microvertebrates and malacofauna), revealing a large species diversity in a coastal environmental context. Studies of large mammals, coupled with recent palynological analyses of coprolites, allow attribution of the whole of the deposits to the beginning of the Late Pleistocene and more precisely to marine oxygen isotope stage (MIS) 5, in agreement with the available radiometric dating. The study of these assemblages, especially for the richer stratigraphic units, III and II, suggests various continental environments related to a temperate climate influenced by a Mediterranean coastal context. Fluctuations are perceptible throughout the sequence, as indicated by variations in species and pollen abundance, both taxonomically and quantitatively, with a general trend of opening landscapes in the upper levels. Large mammals from Ramandils Cave, corresponding to a post-Eemian fauna, represent different Neanderthal occupations phases and give an insight into palaeobiodiversity on the northwestern Mediterranean territory during the Late Pleistocene

Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium cell dedifferentiation

International audienceBackgroundThe retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE cell morphology and key functions in vitro.MethodsPrimary porcine RPE cells were exposed to TNFα (at 0.8, 4, or 20 ng/ml per day) for 10 days. RPE cell morphology, phagocytosis, barrier- and immunosuppressive-functions were assessed.ResultsChronic (10 days) exposure of primary RPE cells to TNFα increases RPE cell size and polynucleation, decreases visual cycle gene expression, impedes RPE tight-junction organization and transepithelial resistance, and decreases the immunosuppressive capacities of the RPE. TNFα-induced morphological- and transepithelial-resistance changes were prevented by concomitant Transforming Growth Factor β inhibition.ConclusionsOur results indicate that chronic TNFα-exposure is sufficient to alter RPE morphology and impede cardinal features that define the differentiated state of RPE cells with striking similarities to the alterations that are observed with age in neurodegenerative diseases such as age-related macular degeneration

Influence of centre expertise on the diagnosis and management of hypertrophic cardiomyopathy A study from the French register of hypertrophic cardiomyopathy (REMY)

International audienceBackground - Our knowledge of hypertrophic cardiomyopathy (HCM) mainly originates from quarternary centres. The objective is to assess the current management of HCM patients in a large multicentre French register according to the level of expertise. Methods and results - A total of 1431 HCM patients were recruited across 26 (11 expert and 15 non-expert) centres in REMY, a prospective hospital-based register of adult HCM patients. A sarcomeric origin was suspected in 1284 (89.7%) patients [261 (20.3%) with a reported gene mutation, 242 (18.8%) genotype-negative], while 107 (7.5%) had a diagnosis of non-sarcomeric HCM. Patients managed in non-expert centres were older (P < 0.01) and presented more often with NYHA III/IV class dyspnoea (P < 0.01), congestive heart failure (P < 0.01), low LEVF (P < 0.01), less often with a syncope history (P < 0.01) and lower LV obstruction (P < 0.01) than patients in expert centres. Genotype positive sarcomeric aetiologies were less frequent in non-expert centres (P < 0.01). The use of diagnostic and prognostic tests as cardiac MRI (P < 0.001), genetic (P < 0.001) and alpha-galactosidase A enzyme level testing (P < 0.001), Holter ECG (P < 0.001), and exercise test (P < 0.001), was lower in non-expert centres. Septal ablation procedures using alcohol (P < 0.001) or myectomy (P < 0.001) were more frequent in expert centres. Conclusion - In real life practice, only a minority of HCM patients are identified as sarcomere positive as per genetic testing. The management of HCM patients varies according to the centre's level of expertise, with less access to diagnostic and prognostic tests in non-expert centres. Non-sarcomeric HCM may therefore be overlooked despite specific treatment in some aetiologies