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 Provenance of the Lithospheric Mantle in Continental Collision Zones: Petrology and Geochemistry of Peridotites in the Ulten-Nonsberg Zone (Eastern Alps)

We report petrographic descriptions, modal mineralogy estimates and major and trace element analyses of whole-rocks and minerals for 36 spinel and garnet–spinel peridotites from the Ulten–Nonsberg Zone (UNZ) in the Eastern Alps in Italy. We seek to constrain the origin and evolution of their source region in the mantle using a comprehensive geochemical dataset on representative, large, modally homogeneous samples from six UNZ sites. This complements earlier work on metamorphism, exhumation history and trace element residence. The samples range from coarse- to dominant fine-grained peridotites affected by syn-tectonic recrystallization and formation of amphibole ± chlorite as well as late-stage alteration (loss on ignition from 0·3 to 8·6 wt %). The UNZ rocks show a rather limited major oxide range (e.g. 1·8–2·8 wt % Al2O3 in ∼80% of the samples) and include neither very fertile nor highly refractory peridotites. Their range and average composition are distinct from those in several massifs from the western Alps, further indicating that the mantle beneath the Alps is heterogeneous, consistent with the tectonically active, plate boundary setting in which mantle domains of different origins may be juxtaposed. Comparison of the Al–Fe–Mg relationships in the UNZ peridotites with experimental data on melting of fertile mantle, together with modelling of REE contents in bulk-rocks, indicates that their mantle protoliths were formed by ∼10–20% polybaric melting in upwelling mantle that began at 2–4 GPa and ended close to the surface, possibly in an oceanic setting. The melting may have started in the presence of garnet, but mainly proceeded in the spinel stability field. Many UNZ peridotites are enriched in silica relative to continental off-craton xenoliths and experimental dry melting trends at similar Al2O3 and MgO. These enrichments are similar to those observed in suprasubduction-zone peridotites, suggesting their potential origin and/or evolution in a subduction-related setting. Modal and cryptic metasomatism is widespread in the UNZ suite, with a broad range of enrichments in incompatible trace elements. It took place mainly in the mantle wedge above a subduction zone, consistent with low high field strength elements and high light rare earth elements, Th, U, Ba and Pb, and probably incorporated slab components. Amphibole is the major host of highly incompatible trace elements whereas garnet, texturally equilibrated with the amphibole, hosts much of heavy rare earth elements and Zr and shows broad grain-to-grain variations of these elements consistent with its growth during tectonic recrystallization and hydrous modal metasomatism

Identification of a muscle-specific isoform of VMA21 as a potent actor in X-linked myopathy with excessive autophagy pathogenesis

Defective lysosomal acidification is responsible for a large range of multi-systemic disorders associated with impaired autophagy. Diseases caused by mutations in the VMA21 gene stand as exceptions, specifically affecting skeletal muscle (X-linked Myopathy with Excessive Autophagy, XMEA) or liver (Congenital Disorder of Glycosylation). VMA21 chaperones vacuolar (v-) ATPase assembly, which is ubiquitously required for proper lysosomal acidification. The reason VMA21 deficiencies affect specific, but divergent tissues remains unknown. Here, we show that VMA21 encodes a yet-unreported long protein isoform, in addition to the previously described short isoform, which we name VMA21-120 and VMA21-101, respectively. In contrast to the ubiquitous pattern of VMA21-101, VMA21-120 was predominantly expressed in skeletal muscle, and rapidly up-regulated upon differentiation of mouse and human muscle precursors. Accordingly, VMA21-120 accumulated during development, regeneration and denervation of mouse skeletal muscle. In contrast, neither induction nor blockade of autophagy, in vitro and in vivo, strongly affected VMA21 isoform expression. Interestingly, VMA21-101 and VMA21-120 both localized to the sarcoplasmic reticulum of muscle cells, and interacted with the v-ATPase. While VMA21 deficiency impairs autophagy, VMA21-101 or VMA21-120 overexpression had limited impact on autophagic flux in muscle cells. Importantly, XMEA-associated mutations lead to both VMA21-101 deficiency and loss of VMA21-120 expression. These results provide important insights into the clinical diversity of VMA21-related diseases and uncover a muscle-specific VMA21 isoform that potently contributes to XMEA pathogenesis

Formes brèves

Les formes brèves sont aujourd'hui un mode de communication et d'expression artistique incontournable, omniprésent dans notre culture mais en même temps méconnu. Mouvant et polymorphe, ce format relève aussi bien de l'art que de la littérature, des sciences de la communication, du cinéma, de l'audiovisuel et de nombreux autres domaines. Il n'a pas pour autant fait l'objet que d'un petit nombre de publications interdisciplinaires. Les textes rassemblés ici selon une perspective interdisciplinaire et internationale envisagent donc les formes brèves dans leur diversité, d'un point de vue diachronique tout autant que synchronique. Ils permettent de nourrir non seulement des analyses ciblées sur ces différents types de formes brèves (au cinéma, en littérature, dans l'art, dans la communication, etc.), mais aussi une réflexion théorique sur les questions de définitions, les enjeux, la modernité, ou encore sur la transgénéricité et la transmédialité qui caractérisent souvent ces formes brèves

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome Associated with COVID-19: An Emulated Target Trial Analysis

International audienc