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/)

Determinants of physical activity commitment in adolescents and young adults with cancer: sociological protocol for a hospital-based mixed methods study (ETAPE-AJA)

International audienceIntroduction Adolescents and young adults (AYA) with cancer undergo physical transformations due to disease and treatments occurring alongside puberty and adolescence. Although physical activity is recommended for its benefits, its practice among AYA with cancer remains insufficient. The aim of the Éducation Thérapeutique et Activité Physique: Engagement des Adolescents et Jeunes Adultes atteints de cancer study is to identify the evolution of AYA with cancer medical knowledge and powers (power to act, to express oneself) over life and cancer care, and their role in commitment in adapted physical activity (APA) and therapeutic patient education during and after oncological treatments. Methods and analysis This prospective mixed methods monocentre study will be conducted in a French comprehensive cancer centre. Observations will be conducted two times a week during medical consultations, APA interventions and therapeutic education sessions for AYA with cancer. Semidirective interviews will involve 70 participants, including AYA with cancer aged 15–25, health professionals, APA teachers and parents. Quantitative data will be collected on AYA’s social characteristics and participation in physical activity intervention and therapeutic education sessions. A correspondence factor analysis will supplement inductive analysis of ethnographic qualitative data, involving patient coresearchers. The results will help to improve the understanding of AYAs’ medical knowledge and powers, their commitment in physical activity and to develop strategies to increase their participation. Ethics and dissemination This study complies with reference methodology MR004 of the French National Data Protection Authority and was registered by the Data Protection Officer of the Leon Berard Cancer Center on the activity registry of the institution (Ref. N°R201-004-259; 5 July 2022). Ethics approval has been obtained from the Centre Léon Bérard ethics board (Ref. N°2022–006; 20 July 2022). Oral informed consent will be obtained from all participants before data collection. The results of this study will be published in peer-reviewed scientific journals, national and international conferences

Silica and Zirconia supported olefin metathesis pre-catalysts: Synthesis, catalytic activity and multiple-use in dimethyl carbonate

International audienceThis study is aimed at designing and synthesising new olefin metathesis catalysts grafted onto porous solid supports and using them in dimethyl carbonate (DMC) an eco-friendly solvent. Two hybrid organic-inorganic Hoveyda-type catalysts were prepared in a few steps by initial grafting of a tailor-made ligand by sol-gel process onto porous silica and zirconia. The new hybrid organic-inorganic catalysts were then engaged in a series of model ring closing metathesis reactions (RCM) in the eco-friendly solvent DMC and their multiple-use was studied

Modélisation spatialisée des besoins, de la production, et des flux de fourrages en vue de la création d’une filière « Fourrages » sur l’île de La Réunion

International audienceIn the early 2010s, cattle breeding cooperatives in Reunion Island resorted to importing hay from France, as an emergency response to a shortage in forages caused by episodes of severe drought. These events highlighted the vulnerability of the livestock farms in terms of self sufficiency. With a view to improve the self-sufficiency of livestock farms, CIRAD was asked to quantify the supply of and demand for fodder and to propose scenarios for structuring a conserved fodder sector (hay, wrapped fodder, straw) at the island level. CIRAD has therefore developed a dynamic and spatially explicit forage flow simulation model integrating a fine geolocation of herbivore farms and all the island's grasslands and sugarcane plots. The annual fodder production of the department was evaluated at 114,050 tons of dry matter. The annual fodder requirement of livestock was evaluated at 110,550 tons of dry matter. The fodder balance highlights the under-use of unharvested grass in the summer season, leading to tensions over the availability of conserved fodder in the winter season in particular. The seasonal balances are also contrasted according to the island's sub-regions due to a strong spatial and temporal variability of fodder supply and demand. The simulations made it possible to quantify the necessary flows between sub-regions, to represent the networks of actors and to evaluate the improvement of the coverage of needs according to the implementation of new practices at the level of production and the positioning of storage places. This study led to technical and logistical recommendations; these results were taken up and developed by a consultancy agency in the context of an expert appraisal aimed at evaluating the technical and economic feasibility of such a fodder sector in Reunion Island.Au début des années 2010, les coopératives d'élevage de bovins à La Réunion ont eu recours à l'importation de foin depuis la France métropolitaine, pour répondre en urgence à un déficit de fourrage associé à des épisodes de sécheresse marquée. Ces événements ont mis en lumière la fragilité des élevages en termes d'autonomie fourragère. Dans l'optique d'accroître l'autonomie des élevages, il a été demandé au CIRAD de quantifier l'offre et la demande en fourrages et de proposer des scénarios de structuration d'une filière de fourrages conservés (foin, enrubanné, paille) à l'échelle de l'île. Le CIRAD a donc développé un modèle dynamique et spatialisé de simulation des flux de fourrages intégrant une géolocalisation fine des élevages d'herbivores et de l'ensemble des parcelles de prairies et de canne à sucre de l'île. La production fourragère annuelle du département a été évaluée à 114 050 tonnes de matière sèche. Le besoin annuel en fourrages des cheptels a lui été évalué à 110 550 tonnes de matière sèche. Le bilan fourrager, met en avant une sous-valorisation de l'herbe sur pied en saison des pluies qui conduit à des tensions autour de la disponibilité des fourrages conservés en saison sèche plus particulièrement. Les bilans saisonniers sont également contrastés selon les sous-régions de l'île du fait d'une forte variabilité spatiale et temporelle de l'offre et de la demande en fourrages. Les simulations ont permis de quantifier les flux nécessaires entre sous-régions, de représenter les réseaux d'acteurs et d'évaluer l'amélioration de la couverture des besoins en fonction de la mise en place de nouvelles pratiques au niveau de la production et du positionnement des lieux de stockages. Cette étude a abouti à des préconisations techniques et logistiques ; ces résultats ont été repris et valorisés par un bureau d'étude dans le cadre d'une expertise visant à évaluer la faisabilité technico-économique d'une telle filière de fourrages à La Réunion

Proteoliposomes as new tool to select active VHH binders by phage display technology

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An intracellular VHH targeting the Luteinizing Hormone receptor modulates G protein-dependent signaling and steroidogenesis

International audienceLuteinizing hormone (LH) is essential for reproduction, controlling ovulation and steroidogenesis. Its receptor (LHR) recruits various transducers leading to the activation of a complex signaling network. We recently identified iPRC1, the first variable fragment from heavy-chain-only antibody (VHH) interacting with intracellular loop 3 (ICL3) of the follicle-stimulating hormone receptor (FSHR). Because of the high sequence similarity of the human FSHR and LHR (LHCGR), here we examined the ability of the iPRC1 intra-VHH to modulate LHCGR activity. In this study, we demonstrated that iPRC1 binds LHCGR, to a greater extent when the receptor was stimulated by the hormone. In addition, it decreased LH-induced cAMP production, cAMP-responsive elementdependent transcription, progesterone and testosterone production. These impairments are not due to Gs nor β-arrestin recruitment to the LHCGR. Consequently, iPRC1 is the first intra-VHH to bind and modulate LHCGR biological activity, including steroidogenesis. It should help further understand signaling mechanisms elicited at this receptor and their outcomes on reproduction

A single‐domain intrabody targeting the follicle‐stimulating hormone receptor impacts FSH ‐induced G protein‐dependent signalling

International audienceIntracellular variable fragments of heavy‐chain antibody from camelids (intra‐VHH) have been successfully used as chaperones to solve the 3D structure of active G protein‐coupled receptors bound to their transducers. However, their effect on signalling has been poorly explored, although they may provide a better understanding of the relationships between receptor conformation and activity. Here, we isolated and characterized iPRC1, the first intra‐VHH recognizing a member of the large glycoprotein hormone receptor family, the follicle‐stimulating hormone receptor (FSHR). This intra‐VHH recognizes the FSHR third intracellular loop and decreases cAMP production in response to FSH, without altering Gαs recruitment. Hence, iPRC1 behaves as an allosteric modulator and provides a new tool to complete structure/activity studies performed thus far on this receptor