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1. Combined platelet and red blood cell recovery during on-pump cardiac surgery using same™ by i-SEP autotransfusion device: a first-in-human non-comparative study (i-TRANSEP study)

Author: Mansour, Alexandre, Beurton, Antoine, Godier, Anne, Rozec, Bertrand, Zlotnik, Diane, Nedelec, Fabienne, Gaussem, Pascale, Fiore, Mathieu, Boissier, Elodie, Nesseler, Nicolas, Ouattara, Alexandre, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; BACKGROUND: Centrifugation-based autotransfusion devices only salvage red blood cells while platelets are removed. The same™ device (i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage both red blood cells and platelets. We tested the hypothesis that this new device could allow a red blood cell recovery exceeding 80% with a post-treatment hematocrit exceeding 40%, and would remove more than 90% of heparin and 75% of free hemoglobin. METHODS: Adults undergoing on-pump elective cardiac surgery were included in a non-comparative multicenter trial. The device was used intraoperatively to treat shed and residual cardiopulmonary bypass blood. The primary outcome was a composite of cell recovery performance, assessed in the device by red blood cell recovery and post-treatment hematocrit, and of biological safety assessed in the device by the washout of heparin and free hemoglobin expressed as removal ratios. Secondary outcomes included platelet recovery and function and adverse events (clinical and device-related adverse events) up to 30 days after surgery. RESULTS: We included 50 patients of whom 18 (35%) underwent isolated CABG, 26 (52%) valve surgery and 6 (12%) aortic root surgery. The median red blood cell recovery per cycle was 86.1 (25th-75th; 80.8-91.6) % with post-treatment hematocrit of 41.8 (39.7-44.2) %. Removal ratios for heparin and free-hemoglobin were 98.9 (98.2-99.7) % and 94.6 (92.7-96.6) % respectively. No adverse device effect was reported. Median platelet recovery was 52.4 (44.2-60.1) %, with a post-treatment concentration of 116 (93-146) 109.L-1. Platelet activation state and function, evaluated by flow cytometry, was found unaltered by the device. CONCLUSIONS: In this first-in-human study, the sameTM device was able to simultaneously recover and wash both platelets and red blood cell. Compared pre-clinical evaluations, the device achieved a higher platelet recovery of 52% with minimal platelet activation while maintaining platelet ability to be activated in vitro.
Published: 2023

2. Combining thrombopoietin receptor agonists with immunosuppressive drugs in adult patients with multirefractory immune thrombocytopenia, an update on the French experience

Author: Etienne Crickx, Mikael Ebbo, Etienne Rivière, Odile Souchaud‐Debouverie, Louis Terriou, Sylvain Audia, Marc Ruivard, Bouchra Asli, Jean‐Pierre Marolleau, Nadine Méaux‐Ruault, Mathieu Gerfaud‐Valentin, Philippe Audeguy, Mohamed Hamidou, Selim Corm, Xavier Delbrel, Jean Fontan, Delphine Lebon, Christelle Mausservey, Guillaume Moulis, Nicolas Limal, Marc Michel, Bertrand Godeau, Matthieu Mahévas, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Edouard Herriot-Lyon, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne (Med Int - BESANCON), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Medipole De Savoie, Service de Médecine Interne [Pau], Centre hospitalier de Pau, Service d'hématologie, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: ITP, TPO-RA, Hematology, immunosuppressive drug, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, combination therapy
Abstract: International audience; Combining drugs could be an effective option for treating multirefractory ITP, that is, patients not responding to rituximab, thrombopoietin receptor agonists (TPO-RA) and splenectomy. We conducted a retrospective, multicenter, observational study including multirefractory ITP patients who received a combination of a TPO-RA and an immunosuppressive drug. We included 39 patients (67% women, median age 59 years [range 21-96]), with a median ITP duration of 57 months [3-393] and a median platelet count at initiation of 10 × 109 /L [1-35]. The combination regimen was given for a median duration of 12 months [1-103] and included eltrombopag (51%) or romiplostim (49%), associated with mycophenolate mofetil (54%), azathioprine (36%), cyclophosphamide (5%), cyclosporin (3%) or everolimus (3%). Overall, 30 patients (77%) achieved at least a response (platelet count ≥30 × 109 /L and at least doubling baseline during at least 3 months), including 24 complete responses (platelet count >100 × 109 /L during at least 3 months) with a median time to response of 30 days [7-270] and a median duration of response of 15 months [4-63]. Severe adverse event related to ITP treatment was observed in 31%. In conclusion, this study confirms that some patients with multirefractory ITP can achieve long lasting response with this combination.
Published: 2023

3. Examen pelvien en gynécologie et obstétrique : recommandations pour la pratique clinique

Author: Deffieux, Xavier, Rousset-Jablonski, Christine, Gantois, Adrien, Brillac, Thierry, Maruani, Julia, Maitrot-Mantelet, Lorraine, Mignot, Stéphanie, Gaucher, Laurent, Athiel, Yoann, Baffet, Hortense, Bailleul, Alexandre, Bernard, Valérie, Bourdon, Mathilde, Cardaillac, Claire, Carneiro, Yaritza, Chariot, Patrick, Corroenne, Romain, Dabi, Yohann, Dahlem, Laurence, Frank, Sophie, Freyens, Anne, Grouthier, Virginie, Hernandez, Isabelle, Iraola, Elisabeth, Lambert, Marie, Lauchet, Nadege, Legendre, Guillaume, Le Lous, Maela, Louis-Vahdat, Christine, Martinat Sainte-Beuve, Anne, Masson, Marine, Matteo, Caroline, Pinton, Anne, Sabbagh, Emmanuelle, Sallee, Camille, Thubert, Thibault, Heron, Isabelle, Pizzoferrato, Anne-Cécile, Artzner, France, Tavenet, Arounie, Le Ray, Camille, Fauconnier, Arnaud, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Interdisciplinaire sur les enjeux Sociaux - sciences sociales, politique, santé (IRIS), École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord, Institut Curie [Paris], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy]
Subjects: Reproductive Medicine, Obstetrics and Gynecology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics
Abstract: ObjectifÉlaborer des recommandations pour l’examen clinique pelvien en gynécologie et obstétrique.Matériel et méthodesUn groupe de travail multidisciplinaire de 45 experts a été constitué, comprenant des représentants d’associations de patients et d’usagers du système de santé. L’ensemble du processus de ces recommandations a été mené indépendamment de tout financement. Il a été conseillé aux auteurs de suivre les règles du système GRADE® (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer la qualité des preuves. Les limites potentielles de faire des recommandations fortes en présence de preuves de faible qualité ont été soulignées. Le comité a étudié 40 questions dans 4 domaines pour les femmes symptomatiques ou asymptomatiques (urgence, consultation gynécologique, maladies gynécologiques, obstétrique et grossesse). Chaque question a été formulée dans un format PICO (Patients, Intervention, Comparaison, Résultat) et les éléments de preuve ont été détaillés. La revue de la littérature et les recommandations ont été réalisées selon la méthodologie GRADE®.RésultatsLe travail de synthèse des experts et l’application de la méthode GRADE ont abouti à 27 recommandations. Parmi les recommandations formalisées, 17 présentaient un accord fort, 7 un accord faible et 3 un accord professionnel. Treize questions ont donné lieu à une absence de recommandation en raison du manque de preuves (pas de réponse dans la littérature).ConclusionsLes 27 recommandations ont permis de préciser quand un examen clinique est requis pour différentes situations cliniques gynécologiques et obstétricales. Ces recommandations intéressent tout professionnel impliqué dans la santé des femmes. La nécessité de réaliser un examen clinique chez certaines patientes dans certaines situations a été fondée sur des preuves scientifiques. Des recherches supplémentaires sont nécessaires pour étudier les avantages dans d’autres situations.
Published: 2023

4. Phenotypic and genotypic characterization of familial hypercholesterolemia in French adult and pediatric populations

Author: Mélanie Fourgeaud, Louis Lebreton, Khaldia Belabbas, Mathilde Di Filippo, Vincent Rigalleau, Thierry Couffinhal, Yann Pucheu, Pascal Barat, Cécile Ged, Annie M. Bérard, CHU Bordeaux [Bordeaux], Sorbonne Université (SU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and ROSSI, Sabine
Subjects: Adult, Nutrition and Dietetics, Cholestérol LDL, Endocrinology, Diabetes and Metabolism, Cholesterol, LDL, Population pédiatrique, Hyperlipoproteinemia Type II, Hypercholestérolémie familiale, Young Adult, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal Medicine, Humans, Proprotein Convertase 9, Child, Population adulte, Cardiology and Cardiovascular Medicine, maladie monogénique, Retrospective Studies, score DLCN
Abstract: International audience; Contexte : L' hypercholestérolémie familiale (HF) est la maladie génétique la plus courante associée à un risque élevé de maladie cardiovasculaire athéroscléreuse prématurée attribuable à l'augmentation des taux de cholestérol LDL (LDL-C) dès la naissance. L'HF est à la fois sous-diagnostiquée et sous-traitée.Objectif : Nous décrivons les caractéristiques cliniques, biologiques et génétiques de 147 patients en France atteints d'HF clinique (dont un groupe de 26 sujets âgés de < 20 ans) ; nous explorons la meilleure façon de détecter les patients atteints d'HF monogénique.Méthodes : Nous avons examiné rétrospectivement toutes les données disponibles sur les patients subissant des tests génétiques pour l'HF de 2009 à 2019. Les diagnostics d'HF étaient basés sur les scores des adultes du Dutch Lipid Clinics Network (DLCN) et sur les taux élevés de LDL-C chez les sujets de moins de 20 ans. . Nous avons évalué le statut LDLR, APOB et PCSK9.Résultats : Les mutations des adultes (chez 25,6 % de tous les adultes) étaient associées à des scores DLCN indiquant "FH possible", "FH probable et "FH définitive" à des taux de 4 %, 16 % et 53 %, respectivement. les aires sous les courbes ROC du score DLCN et du taux maximal de LDL-C ne différaient pas (p = 0,32).Nous avons constaté que le groupe pédiatrique présentait davantage d'étiologies monogéniques (77 %, augmentant à 91 % lorsqu'un taux élevé de LDL-C était associée à des antécédents familiaux d'hypercholestérolémie et/ou de maladie coronarienne prématurée).Conclusion : Le diagnostic de l'HF monogénique peut être optimisé par le dépistage des enfants en fonction de leur taux de LDL-C, associé à un dépistage en cascade inverse des proches lorsque les enfants servent de cas index.
Published: 2022

5. Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression

Author: Nabeel Abdulrahman, Meram Ibrahim, Jensa Mariam Joseph, Hanan Mahmoud Elkoubatry, Al-Anood Al-Shamasi, Menatallah Rayan, Alain Pierre Gadeau, Rashid Ahmed, Hussein Eldassouki, Anwarul Hasan, Fatima Mraiche, Qatar University, Hamad Medical Corporation [Doha, Qatar], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Saskatchewan [Saskatoon] (U of S), Open Access funding provided by the Qatar National Library. This publication was supported by Qatar University Student Grant No. QUST-2-CPH-2019-9. 'The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.', and INSERM, U1034
Subjects: Angiotensin II, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Empagliflozin, Cardiomegaly, Cell Biology, General Medicine, [SDV] Life Sciences [q-bio], Glucosides, Biochemistry and cell biology, Humans, Medical biochemistry and metabolomics, H9c2 cardiomyoblasts, Myocytes, Cardiac, NHE1, Cardiomyocyte hypertrophy, Benzhydryl Compounds, Molecular Biology, SGLT-1/2
Abstract: Diabetes mellitus (DM)-induced cardiac morbidities have been the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors including empagliflozin (EMPA), which have been approved for the treatment of DM, have gained attention for their cardioprotective effect. The mechanism by which SGLT-2 inhibitors exert their cardioprotective effect remains unclear. Recent studies have suggested that EMPA exerts its cardioprotective effect by inhibiting the Na+/H+ exchanger (NHE), a group of membrane proteins that regulate intracellular pH and cell volume. Increased activity and expression of NHE isoform 1 (NHE1), the predominant isoform expressed in the heart, leads to cardiac hypertrophy. p90 ribosomal s6 kinase (p90 RSK) has been demonstrated to stimulate NHE1 activity. In our study, H9c2 cardiomyoblasts were treated with angiotensin II (ANG) to activate NHE1 and generate a hypertrophic model. We aimed to understand whether EMPA reverses the ANG-induced hypertrophic response and to elucidate the molecular pathway contributing to the cardioprotective effect of EMPA. Our study demonstrated that ANG-induced hypertrophy of H9c2 cardiomyoblasts is accompanied with increased SGLT-1 and NHE1 protein expression, an effect which is prevented in the presence of EMPA. EMPA reduces ANG-induced hypertrophy through the inhibition of SGLT-1 and NHE1 expression.Other Information Published in: Molecular and Cellular Biochemistry License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s11010-022-04411-6
Published: 2022

6. Evaluating the effects of sodium glucose co-transporter -2 inhibitors from a renin–angiotensin–aldosterone system perspective in patients infected with COVID-19: contextualizing findings from the dapagliflozin in respiratory failure in patients with COVID-19 study

Author: Moustafa, Diala Alhaj, Imran, Zainab, Ismail, Roua, Rayan, Menatallah, Gadeau, Alain-Pierre, Eldassouki, Hussein, Abdulrahman, Nabeel, Mraiche, Fatima, Qatar University, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Saskatchewan [Saskatoon] (U of S), Hamad Medical Corporation [Doha, Qatar], Admin, Oskar, INSERM, U1034, and This project was supported by Qatar University Student Grant No: QUST-2-CPH-2020-16. 'The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.'
Subjects: Heart Diseases, [SDV]Life Sciences [q-bio], SGLT-2, Renin-Angiotensin System, Mini Review Article, Double-Blind Method, Glucosides, Sodium-Glucose Transporter 2, Genetics, Humans, Multicenter Studies as Topic, Benzhydryl Compounds, Renin angiotensin aldosterone system, Sodium-Glucose Transporter 2 Inhibitors, Molecular Biology, Randomized Controlled Trials as Topic, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, Drug Repositioning, COVID-19, General Medicine, Dapagliflozin, Mitochondria, [SDV] Life Sciences [q-bio], Oxidative Stress, Clinical Trials, Phase III as Topic, DARE-19, Receptors, Virus, Kidney Diseases, Angiotensin-Converting Enzyme 2, Respiratory Insufficiency, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ACE-2
Abstract: International audience; Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.
Published: 2022

7. Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests

Author: Clement Karsenty, Celine Guilbeau-Frugier, Gaël Genet, Marie-Helene Seguelas, Philippe Alzieu, Olivier Cazorla, Alexandra Montagner, Yuna Blum, Caroline Dubroca, Julile Maupoint, Blandine Tramunt, Marie Cauquil, Thierry Sulpice, Sylvain Richard, Silvia Arcucci, Remy Flores-Flores, Nicolas Pataluch, Romain Montoriol, Pierre Sicard, Antoine Deney, Thierry Couffinhal, Jean-Michel Senard, Celine Galés, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Virginia, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: General Immunology and Microbiology, cardiac hypertrophy, [SDV]Life Sciences [q-bio], General Neuroscience, cardiac postnatal devleopment, General Medicine, General Biochemistry, Genetics and Molecular Biology, cardiomyocyte architecture, developmental biology, subsarcolemmal mitochondria, diatolic function, cell biology, ephrin-B1, rat, mouse
Abstract: International audience; The rod-shaped adult cardiomyocyte (CM) harbors a unique architecture of its lateral surface with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) with unknown role. Here, we investigated the development and functional role of CM crests during the postnatal period. We found in rodents that CM crest maturation occurs late between postnatal day 20 (P20) and P60 through both SSM biogenesis, swelling and crest-crest lateral interactions between adjacent CM, promoting tissue compaction. At the functional level, we showed that the P20-P60 period is dedicated to the improvement of relaxation. Interestingly, crest maturation specifically contributes to an atypical CM hypertrophy of its short axis, without myofibril addition, but relying on CM lateral stretching. Mechanistically, using constitutive and conditional CM-specific knock-out mice, we identified ephrin-B1, a lateral membrane stabilizer, as a molecular determinant of P20-P60 crest maturation, governing both the CM lateral stretch and the diastolic function, thus highly suggesting a link between crest maturity and diastole. Remarkably, while young adult CM-specific Efnb1 KO mice essentially exhibit an impairment of the ventricular diastole with preserved ejection fraction and exercise intolerance, they progressively switch toward systolic heart failure with 100% KO mice dying after 13 months, indicative of a critical role of CM-ephrin-B1 in the adult heart function. This study highlights the molecular determinants and the biological implication of a new late P20-P60 postnatal developmental stage of the heart in rodents during which, in part, ephrin-B1 specifically regulates the maturation of the CM surface crests and of the diastolic function.
Published: 2023

8. Post-cardiac surgery fungal mediastinitis: clinical features, pathogens and outcome

Author: Geoffroy Hariri, Mathieu Genoud, Vincent Bruckert, Samuel Chosidow, Emmanuel Guérot, Antoine Kimmoun, Nicolas Nesseler, Emmanuel Besnier, Fabrice Daviaud, David Lagier, Julien Imbault, David Grimaldi, Adrien Bouglé, Nicolas Mongardon, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Groupe de Recherche Clinique en Anesthésie Réanimation médecine PEriopératoire (GRC 29 - ARPE), Sorbonne Université (SU), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Henri Mondor [Créteil], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Rouen, Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre cardiologique du Nord (CCN), CHU Marseille, CHU Pessac, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IMRB - GEIC2O/'Genetic and Environmental Interactions in COPD, Cystic fibrosis and Other (rare) respiratory diseases' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and None
Subjects: Mediastinitis, Fungus, Nosocomial infection, Aspergillus, Trichosporon, [SDV]Life Sciences [q-bio], Cardiac surgery, Healthcare-associated infection, Critical Care and Intensive Care Medicine, Candida
Abstract: Objectives The occurrence of mediastinitis after cardiac surgery remains a rare and severe complication associated with poor outcomes. Whereas bacterial mediastinitis have been largely described, little is known about their fungal etiologies. We report incidence, characteristics and outcome of post-cardiac surgery fungal mediastinitis. Methods Multicenter retrospective study among 10 intensive care units (ICU) in France and Belgium of proven cases of fungal mediastinitis after cardiac surgery (2009–2019). Results Among 73,688 cardiac surgery procedures, 40 patients developed fungal mediastinitis. Five were supported with left ventricular assist device and five with veno-arterial extracorporeal membrane oxygenation before initial surgery. Twelve patients received prior heart transplantation. Interval between initial surgery and mediastinitis was 38 [17–61] days. Only half of the patients showed local signs of infection. Septic shock was uncommon at diagnosis (12.5%). Forty-three fungal strains were identified: Candida spp. (34 patients), Trichosporon spp. (5 patients) and Aspergillus spp. (4 patients). Hospital mortality was 58%. Survivors were younger (59 [43–65] vs. 65 [61–73] yo; p = 0.013), had lower body mass index (24 [20–26] vs. 30 [24–32] kg/m2; p = 0.028) and lower Simplified Acute Physiology Score II score at ICU admission (37 [28–40] vs. 54 [34–61]; p = 0.012). Conclusion Fungal mediastinitis is a very rare complication after cardiac surgery, associated with a high mortality rate. This entity should be suspected in patients with a smoldering infectious postoperative course, especially those supported with short- or long-term invasive cardiac support devices, or following heart transplantation.
Published: 2023

9. Microrheology and structural quantification of hypercoagulable clots

Author: Wolff-Trombini, L, Ceripa, A, Moreau, J, Galinat, H, James, C, Westbrook, N, Allain, J, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mathematical and Mechanical Modeling with Data Interaction in Simulations for Medicine (M3DISIM), Laboratoire de mécanique des solides (LMS), École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire Charles Fabry (LCF), Institut d'Optique Graduate School (IOGS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Bordeaux [Bordeaux], and ANR-11-EQPX-0029,MORPHOSCOPE 2,Imagerie et reconstruction multiéchelles de la morphogenèse. (Plateforme d'innovation technologique et méthodologique pour l'imagerie in vivo et la reconstruction des dynamiques multiéchelles de la morphogenèse)(2011)
Subjects: Biological Physics (physics.bio-ph), [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], FOS: Physical sciences, Physics - Biological Physics
Abstract: International audience; We propose a combination of microrheological and structural characterizations of fibrin networks to study blood hypercoagulability. Fibrin is the central element of coagulation as its polymerization creates the network of fibers in which platelets and red blood cells are included. This is a controlled process via cascades between various coagulation factors. An alteration in the concentrations of coagulation factors and inhibitors will lead to hypocoagulation or hypercoagulation. These changes in the conditions of polymerization of fibrin lead to the formation of networks with different architectures and thus modify its mechanical behavior. We have performed microrheology by recording Brownian motion of microbeads caught in the network of clots. The structure was quantified under the same polymerization conditions with confocal microscopy images. We have tested our approach by adding fibrinogen to the plasma, which leads to a stiffer, denser network with shorter fibers. The addition of coagulation Factor VIII at 400% induces the same correlated trend between a denser network and a higher modulus. This comparative approach is promising for the study of other conditions altering clot formation and may lead to a new diagnosis approach for hypercoagulability.
Published: 2023
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10. A retrospective study of indications and consequences of monitoring direct oral anticoagulant plasma concentrations on patient care in a university hospital: The Retro-AOD study

Author: Musa Sesay, Laurent Weinmann, Céline Delassasseigne, Thibaud Cavaillez, Christine Mouton, Stéphanie Roullet, Matthieu Biais, Chloé James, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Pyridones, Administration, Oral, Renal function, Context (language use), 030204 cardiovascular system & hematology, Dabigatran, 03 medical and health sciences, 0302 clinical medicine, Rivaroxaban, medicine, Coagulation testing, Humans, 030212 general & internal medicine, Retrospective Studies, Pharmacology, business.industry, Anti-IIa activity, Anti-Xa Activity, Anticoagulants, Retrospective cohort study, Hematology, University hospital, Hospitals, 3. Good health, Emergency medicine, Apixaban, Patient Care, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Direct oral anticoagulant, medicine.drug
Abstract: Introduction The use of direct oral anticoagulants (DOAC) is increasing. Specific concentrations are available and have been proven to be reliable and reproducible in optimising patient care. This retrospective, monocentric study aimed to describe the indications and consequences of monitoring DOAC plasma levels on patient care. Materials and methods We collected data of patients hospitalised at the Bordeaux University Hospital between January 2017 and December 2018. These included demographics, indications, type, dose of DOAC, standard coagulation tests, creatinine clearance and DOAC plasma concentration using specifically calibrated rivaroxaban and apixaban anti-Xa and dabigatran anti-IIa assays. The date of last DOAC intake, the time between intake and plasma level measurement were also collected and analysed. Results A total of 2197 DOAC assays in 1488 patients were obtained in various clinical situations: urgent or elective procedures, context of acute renal failure, suspicion or occurrence of ischemic strokes, intra-cranial and other bleeding sites. Interpretation of these assays led physicians to maintain, postpone or cancel invasive and high haemorrhagic risk procedures in 757, 261 and 56 cases respectively. The remaining 1123 assays were associated with no significant modification of patient care. DOAC plasma concentration was ≤30 ng ml-1 (sensitivity 85.4%, specificity 73.6%, positive predictive value 71.1%, negative predictive value 86.7%, AUC 0.81) after a last intake of at least 2 days. Conclusions Our study is, to date, the largest report of real-life measurement of specific DOAC plasma level at a single institution. Patient care was not modified in more than half of the assays.
Published: 2021

11. Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery:multicentre, randomised, double blind, placebo controlled trial

Author: Emmanuel Futier, Samir Jaber, Matthias Garot, Marie Vignaud, Yves Panis, Karem Slim, Jean-Christophe Lucet, Gilles Lebuffe, Alexandre Ouattara, Younes El Amine, Philippe Couderc, Aurélien Dupré, Audrey De Jong, Sigismond Lasocki, Marc Leone, Julien Pottecher, Bruno Pereira, Catherine Paugam-Burtz, Université de Lille, CHU Lille, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Hôpital Claude Huriez [Lille], Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Middle Aged, Antibiotic Prophylaxis, Anti-Bacterial Agents, Ornidazole, Anti-Infective Agents, Double-Blind Method, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, Surgical Wound Infection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Colorectal Surgery
Abstract: Objective To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery. Design Multicentre, randomised, double blind, placebo controlled trial. Setting 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019. Participants 926 adults scheduled for elective colorectal surgery. Intervention Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision. Main outcome measures The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery. Results Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference −8.6%, 95% confidence interval −13.5% to −3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference −3.2%, 95% confidence interval −6.4% to −0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference −3.4%, −6.7% to −0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference −4.5%, −8.6% to −0.5%). Conclusion Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. Trial registration ClinicalTrials.gov NCT02618720 .
Published: 2022

12. Atypical late diagnosis of Noonan syndrome revealed by bleedings due to platelet dysfunction

Author: Sabine-Marie Castet, Mathieu Fiore, Marie-Christine Alessi, Sophie Naudion, Jean-Claude Bordet, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Pediatrics, medicine.medical_specialty, Delayed Diagnosis, Platelet dysfunction, MEDLINE, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Hematology, business.industry, Noonan Syndrome, medicine.disease, 3. Good health, Late diagnosis, Mutation, Noonan syndrome, Cardiology and Cardiovascular Medicine, business, Recherches cliniques, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2021

13. Body-weight variability and risk of cardiovascular outcomes in patients with type 1 diabetes: a retrospective observational analysis of data from the DCCT/EDIC population

Author: Petria, Iulia, Albuquerque, Samuel, Varoquaux, Gaël, Vie, Jill-Jênn, Venteclef, Nicolas, Mohammedi, Kamel, Roussel, Ronan, Camoin, Marion, Perseghin, Gianluca, Velho, Gilberto, Potier, Louis, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Méthodes computationnelles et mathématiques pour comprendre la société et la santé à partir de données (SODA), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Petria, I, Albuquerque, S, Varoquaux, G, Vie, J, Venteclef, N, Mohammedi, K, Roussel, R, Camoin, M, Perseghin, G, Velho, G, and Potier, L
Subjects: Type 1 diabete, Endocrinology, Diabetes and Metabolism, Body Weight, Myocardial Infarction, Cardiovascular risk, Cardiovascular System, Article clinique, Diabetes Mellitus, Type 1, Weight variation, Risk Factors, Diabetes Mellitus, Humans, Mortality, MED/13 - ENDOCRINOLOGIA, Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Type 1, Retrospective Studies
Abstract: Background Cardiovascular risk and body-weight management are both emerging challenges of type 1 diabetes care. We evaluated the association between intraindividual variability of body-weight and risk of cardiovascular events in people with type 1 diabetes. Methods We analyzed 1,398 participants from the DCCT/EDIC studies. Five indices of intraindividual variability of body-weight were calculated for each participant taking into account body-weight measures obtained during the DCCT follow-up (average 6 ± 2 years). The Average Successive Variability (ASV) index, the main variable of interest, was defined as the average absolute difference between successive body-weight measures. The primary outcome was a composite of major adverse cardiovascular events (MACE: nonfatal myocardial infarction or stroke, or cardiovascular death) occurring during the subsequent EDIC follow-up (20 ± 3 years). All-cause death was a secondary outcome. Risk of outcomes were assessed by Cox proportional hazards regression analyses, adjusted for traditional cardiovascular risks factors, including BMI. Results The cumulative incidence of MACE and all-cause death during follow-up were 5.6% (n = 79) and 6.8% (n = 95), respectively. The adjusted Hazard Ratio (HR) for MACE by every increase of 1 standard deviation (SD) of ASV was 1.34 (95% CI, 1.06–1.66), p = 0.01. For all-cause death, the adjusted HR for 1 SD increase of ASV was 1.25 (1.03–1.50), p = 0.03. Similar results were observed when considering the other indices of intraindividual variability of body-weight. Conclusions High body-weight variability (body-weight cycling) is associated with increased risk of MACE and all-cause death in people with type 1 diabetes, independently of the BMI and traditional cardiovascular risk factors.
Published: 2022

14. Comparison of Surgical Ventricular Septal Reduction to Alcohol Septal Ablation Therapy in Patients with Hypertrophic Cardiomyopathy

Author: Catherine Bourque, Patricia Réant, Anne Bernard, Lionel Leroux, Guillaume Bonnet, Mathieu Pernot, Arnaud Bisson, Julien Herbert, Christophe Saint-Etienne, Stéphane Lafitte, Laurent Fauchier, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de Mathématiques Appliquées - Ecole Polytechnique (CMAP), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Éducation Éthique Santé EA 7505 (EES), and Université de Tours (UT)
Subjects: Ablation Techniques, Treatment Outcome, Ethanol, Humans, Ventricular Septum, Cardiomyopathy, Hypertrophic, Cardiology and Cardiovascular Medicine, ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract: Ventricular septal myectomy (SM) and alcohol septal ablation (ASA), 2 septal reduction therapies (SRTs), are recommended in symptomatic obstructive hypertrophic cardiomyopathy (HCM) despite maximum tolerated medical therapy. Contradictory results between the outcomes of these 2 types of therapies persist to this day. The objective of this study was to compare in-hospital and mid-term outcomes of SM versus ASA, at a nationwide level in France. We collected information on patients who underwent SRT for HCM using the French nationwide Programme de Médicalisation des Systèmes d'Information database between 2010 and 2019. A total of 1,574 patients were identified in the database, including 340 patients in the SM arm and 1,234 patients in the ASA arm. No difference during the median follow-up of 1.3 years between the 2 groups was noted in terms of mortality (adjusted incidence rate ratio 0.687, 95% confidence interval 0.361 to 1.309, p = 0.25). However, there was a significantly lower risk of all-cause stroke (adjusted incidence rate ratio 0.180, 95% confidence interval 0.058 to 0.554, p = 0.003) in the ASA group. In conclusion, in our "real-life" data from France, mortality after SRT in patients with HCM was similar after ASA or SM. Moreover, ASA was more widely used than SM despite European Society of Cardiology guidelines recommendations.
Published: 2022

15. Combined Platelet and Erythrocyte Salvage: Evaluation of a New Filtration-based Autotransfusion Device

Author: Pascale Gaussem, Alexandre Ouattara, Lucie Skreko, Véronique Picard, Benoit Decouture, Isabelle Gouin-Thibault, Christilla Bachelot-Loza, Charles R. Lefèvre, Alexandre Mansour, Nicolas Nesseler, Mikael Roussel, CHU Pontchaillou [Rennes], i-SEP (i-SEP), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), i-SEP (Nantes, France), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Blood transfusion, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Platelet Transfusion, 030204 cardiovascular system & hematology, Blood cell, Andrology, Blood Transfusion, Autologous, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, medicine, Humans, Platelet, Whole blood, medicine.diagnostic_test, business.industry, Albumin, Complete blood count, Equipment Design, Flow Cytometry, Blood proteins, Anesthesiology and Pain Medicine, medicine.anatomical_structure, France, Erythrocyte Transfusion, business, Filtration, Autotransfusion
Abstract: Background The SAME device (i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage and wash both red blood cells and platelets. This study evaluated the device performances using human whole blood with the hypothesis that the device will be able to salvage platelets while achieving a erythrocyte yield of 80% and removal ratios of 90% for heparin and 80% for major plasma proteins without inducing signification activation of salvaged cells. Methods Thirty healthy human whole blood units (median volume, 478 ml) were diluted, heparinized, and processed by the device in two consecutive treatment cycles. Samples from the collection reservoir and the concentrated blood were analyzed. Complete blood count was performed to measure blood cell recovery rates. Flow cytometry evaluated the activation state and function of platelets and leukocytes. Heparin and plasma proteins were measured to assess washing performance. Results The global erythrocyte yield was 88.1% (84.1 to 91.1%; median [25th to 75th]) with posttreatment hematocrits of 48.9% (44.8 to 51.4%) and 51.4% (48.4 to 53.2%) for the first and second cycles, respectively. Ektacytometry did not show evidence of erythrocyte alteration. Platelet recovery was 36.8% (26.3 to 43.4%), with posttreatment counts of 88 × 109/l (73 to 101 × 109/l) and 115 × 109/l (95 to 135 × 109/l) for the first and second cycles, respectively. Recovered platelets showed a low basal P-selectin expression at 10.8% (8.1 to 15.2%) and a strong response to thrombin-activating peptide. Leukocyte yield was 93.0% (90.1 to 95.7%) with no activation or cell death. Global removal ratios were 98.3% (97.8 to 98.9%), 98.2% (96.9 to 98.8%), and 88.3% (86.6 to 90.7%) for heparin, albumin, and fibrinogen, respectively. The processing times were 4.4 min (4.2 to 4.6 min) and 4.4 min (4.2 to 4.7 min) for the first and second cycles, respectively. Conclusions This study demonstrated the performance of the SAME device. Platelets and red blood cells were salvaged without significant impact on cell integrity and function. In the meantime, leukocytes were not activated, and the washing quality of the device prevented reinfusion of high concentrations of heparin and plasma proteins. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2021

16. Effects of capnometry monitoring during recovery in the post-anaesthesia care unit: a randomized controlled trial in adults (CAPNOSSPI)

Author: Stéphanie Roullet, Matthieu Biais, Isabelle Etchebarne, Karine Nouette-Gaulain, Laurent Soubiron, Julien Potvin, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), and Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, medicine.medical_specialty, Health Informatics, Anesthesia, General, Critical Care and Intensive Care Medicine, Hypoxemia, law.invention, Pacu, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Laryngeal mask airway, Capnography, 030202 anesthesiology, law, Anesthesiology, medicine, Humans, General anaesthesia, Prospective Studies, Hypoxia, medicine.diagnostic_test, biology, business.industry, Respiration, 030208 emergency & critical care medicine, Perioperative, Carbon Dioxide, biology.organism_classification, Post-anaesthesia care unit, 3. Good health, Anesthesiology and Pain Medicine, Anesthesia, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose: Continuous capnography should be used on patients admitted to post-anaesthesia care units (PACUs) with endotracheal tubes, but this monitoring is not always performed. Optimized ventilation in the PACU could be part of the global standards of practice to maintain the benefits of perioperative ventilation. The main objective was to study the rate of patients with alveolar hypoventilation before tracheal extubation or Laryngeal Mask Airway (LMA) removal upon the measurement of continuous capnography. Methods: In this prospective, parallel-group, randomized controlled study, we enrolled adult patients admitted to the PACU after general anaesthesia with an endotracheal tube or LMA in place. Patients were randomly assigned to two groups: in the Capno + group, nurses managed the patients with access to the capnometer and end-tidal carbon dioxide pressure (PETCO2) measurements; in the Capno- group, nurses monitored the patients without seeing PETCO2 measurements. The primary outcome was the percentage of patients with PETCO2 measurements above 45 mm Hg during the minute before extubation. Secondary endpoints included the delay in recovering spontaneous breathing, rate of hypoxemia, delay before extubation, and length of stay in the PACU. Results: Forty-eight patients were randomized into the two groups. The percentage of patients with PETCO2 > 45 mm Hg the minute before extubation was significantly decreased in the Capno + group (83.3% versus 54,1% in the Capno- and Capno + groups respectively, p = 0.029). There were no significant differences concerning secondary endpoints. Conclusions: The use of PETCO2 monitoring improves patient safety by decreasing the incidence of CO2 retention during recovery from general anaesthesia. This study suggests that this monitoring should be integrated in the PACU. The risk of hypoxemia can also be prevented through the early recognition of apnoea. Clinical Trial registry: clinicaltrial.gov. identifier: NCT03370081
Published: 2021

17. Differential prognostic burden of cardiovascular disease and lower-limb amputation on the risk of all-cause death in people with long-standing type 1 diabetes

Author: Marion, Camoin, Gilberto, Velho, Pierre-Jean, Saulnier, Louis, Potier, Yawa, Abouleka, Charlyne, Carpentier, Severine, Dubois, Alice, Larroumet, Vincent, Rigalleau, Elise, Gand, Olivier, Bourron, Lyse, Bordier, André, Scheen, Samy, Hadjadj, Ronan, Roussel, Michel, Marre, Kamel, Mohammedi, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Liège, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Admin, Oskar
Subjects: Adult, Male, Endocrinology, Diabetes and Metabolism, Type 1 diabetes mellitus, Lower-limb amputation, Middle Aged, Prognosis, Cardiovascular disease, Amputation, Surgical, Stroke, Myocardial infarction, Diabetes Mellitus, Type 1, Lower Extremity, Cardiovascular Diseases, Risk Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Prospective Studies, Mortality, Cardiology and Cardiovascular Medicine
Abstract: Background Cardiovascular disease (CVD) and nontraumatic lower-limb amputation (LLA) each results in reduced life expectancy in patients with type 1 diabetes, but the differential burden between these conditions is unknown. We compared the effects of CVD and LLA on the risk of mortality in people with type 1 diabetes. Methods We used pooled data from the SURGENE, GENEDIAB, and GENESIS prospective cohorts. Data were divided into: 1/absence of CVD (myocardial infarction and/or stroke) nor LLA, 2/history of CVD alone without LLA, 3/LLA alone without CVD or 4/both conditions at baseline. Participants with baseline history of peripheral artery disease were excluded from groups 1 and 2. The study endpoint was any death occurring during follow-up, regardless of the causes. Results Among 1169 participants (male 55%, age 40 ± 13 years, diabetes duration 23 ± 11 years), CVD, LLA or both were present at baseline in 49 (4.2%), 62 (5.3%) and 20 (1.7%) subjects, respectively. All-cause death occurred in 304 (26%) participants during 17-year follow-up, corresponding to 18,426 person-years and an incidence rate of 16 (95%CI, 15–18) per 1000 person-years. The risk of death increased in individuals with baseline history of CVD (adjusted HR 2.00 [95% CI 1.34–3.01], p = 0.0008) or LLA (2.26 [1.56–3.28], p versus no condition, with an additive effect in people with both conditions (5.32 [3.14–9.00], p versus LLA (0.87 [0.54–1.41]). Compared with no condition, CVD and LLA were similarly associated with reduced life expectancy during follow-up: 2.79 (95% CI 1.26–4.32) and 3.38 (1.87–4.88) years, respectively. Combined conditions expose to 7.04 (4.76–9.31) less years of life expectancy (all p Conclusions CVD and LLA conferred a similar burden regarding mortality in type 1 diabetes population. Our findings encourage a careful consideration of people with type 1 diabetes and LLA as usually recommended for those with CVD, in terms of management of risk factors, treatments and prevention.
Published: 2022

18. Guidelines on enhanced recovery after cardiac surgery under cardiopulmonary bypass or off-pump

Author: Paul-Michel Mertes, Michel Kindo, Julien Amour, Christophe Baufreton, Lionel Camilleri, Thierry Caus, Didier Chatel, Bernard Cholley, Alain Curtil, Jean-Philippe Grimaud, Rémi Houel, Fehmi Kattou, Jean-Luc Fellahi, Catherine Guidon, Pierre-Grégoire Guinot, Guillaume Lebreton, Sandrine Marguerite, Alexandre Ouattara, Sophie Provenchère Fruithiot, Bertrand Rozec, Jean-Philippe Verhoye, André Vincentelli, Hélène Charbonneau, Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Hôpital Privé Jacques Cartier [Massy], MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, CHU Amiens-Picardie, Nouvelle Clinique de Tours Saint Gatien-Alliance [Tours] (CTSGA), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Clinique de la Sauvegarde [Lyon], Clinique Saint Augustin, Hôpital Saint-Joseph [Marseille], Institut Mutualiste de Montsouris (IMM), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital Pontchaillou, CHU Lille, Université de Lille, Clinique Pasteur [Toulouse], DESSAIVRE, Louise, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), École Pratique des Hautes Études (EPHE), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: Adult, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Cardiopulmonary Bypass, Critical Care, Coronary Artery Bypass, Off-Pump, off pump cardiac surgery, General Medicine, Cardiac surgery, Guidelines, Length of Stay, Critical Care and Intensive Care Medicine, Enhanced recovery after surgery (ERAS), Anesthesiology and Pain Medicine, Anesthesiology, Patient Satisfaction, Humans, Anesthesia, Cardiac Surgical Procedures, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objective: To provide recommendations for enhanced recovery after cardiac surgery (ERACS) based on a multimodal perioperative medicine approach in adult cardiac surgery patients with the aim of improving patient satisfaction, reducing postoperative mortality and morbidity, and reducing the length of hospital stay. Design: A consensus committee of 20 experts from the French Society of Anaesthesia and Intensive Care Medicine (Societe francaise d'anesthesie et de reanimation, SFAR) and the French Society of Thoracic and Cardiovascular Surgery (Societe francaise de chirurgie thoracique et cardio-vasculaire, SFCTCV) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guideline process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide the assessment of the quality of evidence. Methods: Six fields were defined: (1) selection of the patient pathway and its information; (2) preoperative management and rehabilitation; (3) anaesthesia and analgesia for cardiac surgery; (4) surgical strategy for cardiac surgery and bypass management; (5) patient blood management; and (6) postoperative enhanced recovery. For each field, the objective of the recommendations was to answer questions formulated according to the PICO model (Population, Intervention, Comparison, Outcome). Based on these questions, an extensive bibliographic search was carried out and analyses were performed using the GRADE approach. The recommendations were formulated according to the GRADE methodology and then voted on by all the experts according to the GRADE grid method. Results: The SFAR/SFCTCV guideline panel provided 33 recommendations on the management of patients undergoing cardiac surgery under cardiopulmonary bypass or off-pump. After three rounds of voting and several amendments, a strong agreement was reached for the 33 recommendations. Of these recommendations, 10 have a high level of evidence (7 GRADE 1+ and 3 GRADE 1-); 19 have a moderate level of evidence (15 GRADE 2+ and 4 GRADE 2-); and 4 are expert opinions. Finally, no recommendations were provided for 3 questions. Conclusions: Strong agreement existed among the experts to provide recommendations to optimise the complete perioperative management of patients undergoing cardiac surgery. (C) 2022 The Authors. Published by Elsevier Masson SAS on behalf of Societe francaise d'anesthesie et de reanimation (Sfar).
Published: 2022

19. Astrocytic junctional adhesion molecule-A regulates T-cell entry past the glia limitans to promote central nervous system autoimmune attack

Author: Mario Amatruda, Candice Chapouly, Viola Woo, Farinaz Safavi, Joy Zhang, David Dai, Anthony Therattil, Chang Moon, Jorge Villavicencio, Alexandra Gordon, Charles Parkos, Sam Horng, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), University of Virginia School of Medicine [US], Perelman School of Medicine, University of Pennsylvania, New York Medical College (NYMC), University of Miami Leonard M. Miller School of Medicine (UMMSM), University of Michigan [Ann Arbor], University of Michigan System, This work was supported by grant funding to S.H.: National Institutes of Health (NIH) National Institute of Neurological Diseases and Stroke (NINDS) K08 NS102507-01A1, NIH R25NS079102, a Career Transition Award by the National Multiple Sclerosis Society and the Conrad N. Hilton Foundation, philanthropic support by the Jayne and Harvey Beker Foundation and a post-doctoral Neuroscience fellowship from the Leon Levy Foundation. F.S. was supported by a post-doctoral Neuroscience fellowship from the Leon Levy Foundation. The Mount Sinai School of Medicine Microscopy and Flow Cytometry Shared Resource Facilities were utilized in this study, core facilities receive support from National Institutes of Health/National Cancer Institute Grant R24 CA095823., and INSERM, U1034
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], General Engineering, experimental autoimmune encephalomyelitis, glia limitans, junctional adhesion molecule-A, astrocyte immune cell cross-talk, multiple sclerosis
Abstract: Contact-mediated interactions between the astrocytic endfeet and infiltrating immune cells within the perivascular space are underexplored, yet represent potential regulatory check-points against CNS autoimmune disease and disability. Reactive astrocytes upregulate junctional adhesion molecule-A, an immunoglobulin-like cell surface receptor that binds to T cells via its ligand, the integrin, lymphocyte function-associated antigen-1. Here, we tested the role of astrocytic junctional adhesion molecule-A in regulating CNS autoinflammatory disease. In cell co-cultures, we found that junctional adhesion molecule-A-mediated signalling between astrocytes and T cells increases levels of matrix metalloproteinase-2, C–C motif chemokine ligand 2 and granulocyte-macrophage colony-stimulating factor, pro-inflammatory factors driving lymphocyte entry and pathogenicity in multiple sclerosis and experimental autoimmune encephalomyelitis, an animal model of CNS autoimmune disease. In experimental autoimmune encephalomyelitis, mice with astrocyte-specific JAM-A deletion (mGFAP:CreJAM-Afl/fl) exhibit decreased levels of matrix metalloproteinase-2, reduced ability of T cells to infiltrate the CNS parenchyma from the perivascular spaces and a milder histopathological and clinical course of disease compared with wild-type controls (JAM-Afl/fl). Treatment of wild-type mice with intraperitoneal injection of soluble junctional adhesion molecule-A blocking peptide decreases the severity of experimental autoimmune encephalomyelitis, highlighting the potential of contact-mediated astrocyte–immune cell signalling as a novel translational target against neuroinflammatory disease.
Published: 2022

20. Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study

Author: Nicolas, Nesseler, Guillaume, Fadel, Alexandre, Mansour, Marylou, Para, Pierre-Emmanuel, Falcoz, Nicolas, Mongardon, Alizée, Porto, Astrid, Bertier, Bruno, Levy, Cyril, Cadoz, Pierre-Grégoire, Guinot, Olivier, Fouquet, Jean-Luc, Fellahi, Alexandre, Ouattara, Julien, Guihaire, Vito-Giovanni, Ruggieri, Philippe, Gaudard, François, Labaste, Thomas, Clavier, Kais, Brini, Nicolas, Allou, Corentin, Lacroix, Juliette, Chommeloux, Guillaume, Lebreton, Michael A, Matthay, Sophie, Provenchere, Erwan, Flécher, André, Vincentelli, James T, Ross, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, Nouvel Hôpital Civil de Strasbourg, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Bicêtre, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Marie-Lannelongue, Groupe Hospitalier Paris Saint-Joseph (hpsj), Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU), Institut Mutualiste de Montsouris (IMM), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, ECMOSARS Investigators: Marc Pierrot, Sidney Chocron, Guillaume Flicoteaux, Philippe Mauriat, Hadrien Roze, Olivier Huet, Marc-Olivier Fischer, Claire Alessandri, Raphel Bellaïche, Ophélie Constant, Quentin de Roux, André Ly, Arnaud Meffert, Jean-Claude Merle, Lucile Picard, Elena Skripkina, Thierry Folliguet, Antonio Fiore, Nicolas d'Ostrevy, Marie-Catherine Morgan, Maxime Nguyen, Lucie Gaide-Chevronnay, Nicolas Terzi, Gwenhaël Colin, Olivier Fabre, Arash Astaneh, Justin Issard, Elie Fadel, Dominique Fabre, Antoine Girault, Iolande Ion, Jean Baptiste Menager, Delphine Mitilian, Olaf Mercier, François Stephan, Jacques Thes, Jerôme Jouan, Thibault Duburcq, Valentin Loobuyck, Sabrina Manganiello, Mouhammed Moussa, Agnes Mugnier, Natacha Rousse, Olivier Desebbe, Roland Henaine, Matteo Pozzi, Jean-Christophe Richard, Zakaria Riad, Christophe Guervilly, Sami Hraiech, Laurent Papazian, Matthias Castanier, Charles Chanavaz, Sebastien Gette, Guillaume Louis, Erick Portocarrero, Nicolas Bischoff, Antoine Kimmoun, Mathieu Mattei, Pierre Perez, Alexandre Bourdiol, Yannick Hourmant, Pierre-Joachim Mahé, Bertrand Rozec, Mickaël Vourc'h, Stéphane Aubert, Florian Bazalgette, Claire Roger, Pierre Jaquet, Brice Lortat-Jacob, Pierre Mordant, Patrick Nataf, Juliette Patrier, Morgan Roué, Romain Sonneville, Alexy Tran-Dinh, Paul-Henri Wicky, Charles Al Zreibi, Bernard Cholley, Yannis Guyonvarch, Sophie Hamada, Claudio Barbanti, Anatole Harrois, Jordi Matiello, Thomas Kerforne, Nicolas Brechot, Alain Combes, Jean Michel Constantin, Cosimo D'Alessandro, Pierre Demondion, Alexandre Demoule, Martin Dres, Muriel Fartoukh, Guillaume Hekimian, Charles Juvin, Pascal Leprince, David Levy, Charles Edouard Luyt, Marc Pineton de Chambrun, Matthieu Schmidt, Thibaut Schoell, Pierre Fillâtre, Nicolas Massart, Roxane Nicolas, Maud Jonas, Charles Vidal, Salvatore Muccio, Dario Di Perna, Bruno Mourvillier, Amedeo Anselmi, Karl Bounader, Maxime Esvan, Claire Fougerou-Leurent, Yoann Launey, Thomas Lebouvier, Alessandro Parasido, Florian Reizine, Philippe Seguin, Emmanuel Besnier, Dorothée Carpentier, Anne Olland, Fanny Bounes, Vincent Minville, Antoine Guillon, Yannick Fedun, James T Ross, Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), CHU Toulouse [Toulouse], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), University of California [San Francisco] (UCSF), University of California, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Cohort Studies, Male, [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, Extracorporeal Membrane Oxygenation, [SDV]Life Sciences [q-bio], COVID-19, Humans, Respiratory Insufficiency, Pandemics, Retrospective Studies
Abstract: Background Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non–COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. Methods The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. Results Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. Conclusions In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2022

21. Impact of intraventricular septal fiber orientation on cardiac electromechanical function

Author: Jairo Rodríguez-Padilla, Argyrios Petras, Julie Magat, Jason Bayer, Yann Bihan-Poudec, Dounia El Hamrani, Girish Ramlugun, Aurel Neic, Christoph M. Augustin, Fanny Vaillant, Marion Constantin, David Benoist, Line Pourtau, Virginie Dubes, Julien Rogier, Louis Labrousse, Olivier Bernus, Bruno Quesson, Michel Haïssaguerre, Matthias Gsell, Gernot Plank, Valéry Ozenne, Edward Vigmond, E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Austrian Academy of Sciences (OeAW), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical University Graz, Medical University of Graz, BioTechMed-Graz, Graz University of Technology [Graz] (TU Graz)-Karl-Franzens-Universität Graz-Medical University Graz, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Graz University of Technology [Graz] (TU Graz), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE19-0007,CARTLOVE,Contrôle des Ablations Radiofréquence par Thermométrie (IRM) pour Les Oreillettes et VEntricules(2017), ANR-19-ECVD-0006,SICVALVES,Multiscale Modeling of Valvular Heart Diseases - Understanding the Mechanisms of Adverse Remodeling to Improve Precision Medicine(2019), and European Project: 680969,H2020,H2020-HCO-2015,ERA-CVD(2015)
Subjects: Mammals, fiber orientation, Sheep, Physiology, Swine, Heart Ventricles, Myocardium, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Ventricular Septum, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Rats, Diffusion Tensor Imaging, Dogs, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [MATH.MATH-DG]Mathematics [math]/Differential Geometry [math.DG], Physiology (medical), intraventricular septum, normal structural discontinuities, electromechanical models, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Animals, Diamond, Cardiology and Cardiovascular Medicine, [MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Abstract: Cardiac fiber direction is an important factor determining the propagation of electrical activity, as well as the development of mechanical force. In this article, we imaged the ventricles of several species with special attention to the intraventricular septum to determine the functional consequences of septal fiber organization. First, we identified a dual-layer organization of the fiber orientation in the intraventricular septum of ex vivo sheep hearts using diffusion tensor imaging at high field MRI. To expand the scope of the results, we investigated the presence of a similar fiber organization in five mammalian species (rat, canine, pig, sheep, and human) and highlighted the continuity of the layer with the moderator band in large mammalian species. We implemented the measured septal fiber fields in three-dimensional electromechanical computer models to assess the impact of the fiber orientation. The downward fibers produced a diamond activation pattern superficially in the right ventricle. Electromechanically, there was very little change in pressure volume loops although the stress distribution was altered. In conclusion, we clarified that the right ventricular septum has a downwardly directed superficial layer in larger mammalian species, which can have modest effects on stress distribution.
Published: 2022

22. Glycaemic Variability and Hyperglycaemia as Prognostic Markers of Major Cardiovascular Events in Diabetic Patients Hospitalised in Cardiology Intensive Care Unit for Acute Heart Failure

Author: Edouard Gerbaud, Ambroise Bouchard de La Poterie, Thomas Baudinet, Michel Montaudon, Marie-Christine Beauvieux, Anne-Iris Lemaître, Laura Cetran, Benjamin Seguy, François Picard, Fritz-Line Vélayoudom, Alexandre Ouattara, Rémi Kabore, Pierre Coste, Pierre Domingues-Dos-Santos, Bogdan Catargi, Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Admin, Oskar, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital [Boston], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), and Hôpital Saint-André
Subjects: [SDV] Life Sciences [q-bio], diabetes, glycaemic variability, acute heart failure, major adverse cardiovascular event, Major adverse cardiovascular event, [SDV]Life Sciences [q-bio], Diabetes, ARTICLE CLINIQUE, Acute heart failure, General Medicine, Glycaemic variability
Abstract: (1) Background: Hyperglycaemia and hypoglycaemia are both emerging risk factors for cardiovascular disease. Nevertheless, the potential effect of glycaemic variability (GV) on mid-term major cardiovascular events (MACE) in diabetic patients presenting with acute heart failure (AHF) remains unclear. This study investigates the prognostic value of GV in diabetic patients presenting with acute heart failure (AHF). (2) Methods: this was an observational study including consecutive patients with diabetes and AHF between January 2015 and November 2016. GV was calculated using standard deviation of glycaemia values during initial hospitalisation in the intensive cardiac care unit. MACE, including recurrent AHF, new-onset myocardial infarction, ischaemic stroke and cardiac death, were recorded. The predictive effects of GV on patient outcomes were analysed with respect to baseline characteristics and cardiac status. (3) Results: In total, 392 patients with diabetes and AHF were enrolled. During follow-up (median (interquartile range) 29 (6–51) months), MACE occurred in 227 patients (57.9%). In total, 92 patients died of cardiac causes (23.5%), 107 were hospitalised for heart failure (27.3%), 19 had new-onset myocardial infarction (4.8%) and 9 (2.3%) had an ischaemic stroke. Multivariable logistic regression analysis showed that GV > 50 mg/dL (2.70 mmol/L), age > 75 years, reduced left ventricular ejection fraction (LVEF < 30%) and female gender were independent predictors of MACE: hazard ratios (HR) of 3.16 (2.25–4.43; p < 0.001), 1.54 (1.14–2.08; p = 0.005), 1.47 (1.06–2.07; p = 0.02) and 1.43 (1.05–1.94; p = 0.03), respectively. (4) Conclusions: among other well-known factors of HF, a GV cut-off value of >50 mg/dL was the strongest independent predictive factor for mid-term MACE in patients with diabetes and AHF.
Published: 2022

23. Trials of mechanical circulatory support with percutaneous axial flow pumps in cardiogenic shock complicating acute myocardial infarction: Mission impossible?

Author: François Roubille, Alexandre Ouattara, Mélanie Gaubert, Laurent Bonello, Guillaume Schurtz, Clément Delmas, Mediterranean Association for Research and Studies in Cardiology (MARS cardio), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Departement de Cardiologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Percutaneous, [SDV]Life Sciences [q-bio], Clinical Decision-Making, Myocardial Infarction, Shock, Cardiogenic, Infarctus du myocarde, Acute myocardial infarction, 030204 cardiovascular system & hematology, Prosthesis Design, law.invention, Prosthesis Implantation, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Randomized controlled trial, Risk Factors, Mechanical circulatory support, law, Étude, Humans, Medicine, 030212 general & internal medicine, Myocardial infarction, Intensive care medicine, Cardiogenic shock, Survival rate, Randomized Controlled Trials as Topic, Trials, business.industry, Patient Selection, Support circulatoire mécanique, Recovery of Function, General Medicine, Evidence-based medicine, Étude clinique randomisée, medicine.disease, 3. Good health, Treatment Outcome, Research Design, Observational study, Heart-Assist Devices, Randomized clinical trials, Cardiology and Cardiovascular Medicine, business, Choc cardiogénique
Abstract: International audience; Cardiogenic shock is a complex clinical entity associated with very high mortality and intensive resource utilization. Despite the widespread use of timely reperfusion and appropriate pharmacotherapy, the survival rate remains at around 50%. Recently, percutaneous axial flow pumps have been integrated into the therapeutic spectrum of cardiogenic shock management. However, most of the literature supporting their use stems from observational studies. To date, attempts to perform randomized controlled trials with percutaneous axial flow pumps have failed. This underlines the challenge of performing a well-conducted randomized controlled trial that provides the highest level of evidence. Such a trial is warranted, because percutaneous axial flow pumps are costly, and are associated with serious complications. The major pitfalls of previous studies were lack of standardized cardiogenic shock definitions according to clinical severity, inappropriate patient and device selection, lack of standardized trial endpoints and high rates of crossovers; these issues must be carefully considered and evaluated. In light of recent trial failures, we aim to summarize the challenges associated with performing randomized controlled trials of percutaneous axial flow pumps in patients experiencing acute myocardial infarction complicated by cardiogenic shock, and to suggest potential means of overcoming them.; Le choc cardiogénique reste une entité clinique complexe associée avec une très haute mortalité et une utilisation intensive de ressource. Malgré la généralisation de la reperfusion précoce et un traitement adapté, le taux de mortalité reste élevée aux alentours de 50 %. Les pompes axiales percutanées ont été récemment intégrées dans l’arsenal thérapeutique du choc cardiogénique. Cependant, la plupart des données de la littérature en faveur de leur utilisation sont de natures observationnelles. À ce jour, les tentatives de réaliser les études cliniques randomisées ont été des échecs. Cela souligne à quel point il reste compliqué de réaliser une étude randomisée bien conduite afin de fournir un niveau de preuve suffisant. Une telle étude est nécessaire car les pompes axiales sont coûteuses et associées avec des complications sérieuses. L’absence de définition standardisée du choc cardiogénique en fonction de sa gravité, une mauvaise sélection des patients ou des interventions, l’absence de critère de jugement validé et le fort taux de crossover sont parmi les écueils majeurs de la réalisation des précédentes études et doivent être prise en compte pour la réalisation des prochaines. À la lumière des échecs récents, nous avons voulu résumer les écueils pour la réalisation d’une étude randomisée utilisant les pompes microaxiales dans le choc cardiogénique secondaire à un IDM et suggérer des voies potentielles de résolution.
Published: 2020

24. Guidelines: Anaesthesia in the context of COVID-19 pandemic

Author: Lionel Velly, Etienne Gayat, Hervé Quintard, Emmanuel Weiss, Audrey De Jong, Philippe Cuvillon, Gérard Audibert, Julien Amour, Marc Beaussier, Matthieu Biais, Sébastien Bloc, Marie Pierre Bonnet, Pierre Bouzat, Gilles Brezac, Claire Dahyot-Fizelier, Souhayl Dahmani, Mathilde de Queiroz, Sophie Di Maria, Claude Ecoffey, Emmanuel Futier, Thomas Geeraerts, Haithem Jaber, Laurent Heyer, Rim Hoteit, Olivier Joannes-Boyau, Delphine Kern, Olivier Langeron, Sigismond Lasocki, Yoan Launey, Frederic le Saché, Anne Claire Lukaszewicz, Axel Maurice-Szamburski, Nicolas Mayeur, Fabrice Michel, Vincent Minville, Sébastien Mirek, Philippe Montravers, Estelle Morau, Laurent Muller, Jane Muret, Karine Nouette-Gaulain, Jean Christophe Orban, Gilles Orliaguet, Pierre François Perrigault, Florence Plantet, Julien Pottecher, Christophe Quesnel, Vanessa Reubrecht, Bertrand Rozec, Benoit Tavernier, Benoit Veber, Francis Veyckmans, Hélène Charbonneau, Isabelle Constant, Denis Frasca, Marc-Olivier Fischer, Catherine Huraux, Alice Blet, Marc Garnier, Assistance Publique - Hôpitaux de Marseille (APHM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Anesthésie et Réanimation [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mutualiste de Montsouris (IMM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie-réanimation, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'anesthésie réanimation chirurgicale [Rennes], Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, CHU Toulouse [Toulouse], Service Anesthésie - Réanimation [Bordeaux], CHU Bordeaux [Bordeaux], Physiopathologie et Pharmacologie Clinique de la Douleur, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Juge - Clinique du sport [Marseille], Pôle d'Anesthésie-Réanimation [CHU Rangueil], CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'anesthésie - réanimation chirurgicale [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'Anesthésie Réanimation, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de réanimation médicale [CHU de Carémeau, Nîmes], Institut Curie [Paris], Réanimation Médico-Chirurgicale, Service d'Anesthésie Réanimation, CHU Necker - Enfants Malades [AP-HP], Département d'anesthésie-réanimation[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Mitochondries, stress oxydant et protection musculaire (Strasbourg), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Groupe d’Anesthésie-Réanimation Chirurgie cardio-thoracique et vasculaire [Toulouse], Clinique Pasteur [Toulouse], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Département d'anesthésiologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-Hôpital Pontchaillou, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Pôle Anesthésie Réanimation [CHU de Toulouse], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Histoire et Cultures de l'Antiquité et du Moyen Âge (HISCANT-MA), Université de Lorraine (UL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Emergency Department, Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin - Bordeaux, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Anaesthesiology, Robert Debré Hospital, Service d'anesthésie réanimation chirurgicale, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie mitochondriale, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Anesthésiologie, Université Pierre et Marie Curie - Paris 6 (UPMC), and Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis - Lariboisière, AP-HP, Paris, France.
Subjects: Infection prevention and control, [SDV]Life Sciences [q-bio], Psychological intervention, Airway management, Context (language use), Critical Care and Intensive Care Medicine, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030202 anesthesiology, Informed consent, Personal protective equipment, Pandemic, Health care, Medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Modalities, SARS-CoV-2, business.industry, COVID-19, 030208 emergency & critical care medicine, General Medicine, Guideline, 3. Good health, Anesthesiology and Pain Medicine, Universal precautions, Anesthesia, Viruses, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Objectives The world is currently facing an unprecedented healthcare crisis caused by the COVID-19 pandemic. The objective of these guidelines is to produce a framework to facilitate the partial and gradual resumption of intervention activity in the context of the COVID-19 pandemic. Methods The group has endeavoured to produce a minimum number of recommendations to highlight the strengths to be retained in the 7 predefined areas: (1) protection of staff and patients; (2) benefit/risk and patient information; (3) preoperative assessment and decision on intervention; (4) modalities of the preanaesthesia consultation; (5) specificity of anaesthesia and analgesia; (6) dedicated circuits and (7) containment exit type of interventions. Results The SFAR Guideline panel provides 51 statements on anaesthesia management in the context of COVID-19 pandemic. After one round of discussion and various amendments, a strong agreement was reached for 100% of the recommendations and algorithms. Conclusion We present suggestions for how the risk of transmission by and to anaesthetists can be minimised and how personal protective equipment policies relate to COVID-19 pandemic context.
Published: 2020

25. Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm

Author: Poisson, Johanne, Tanguy, Marion, Davy, Hortense, Camara, Fatoumata, El Mdawar, Marie-Belle, Kheloufi, Marouane, Dagher, Tracy, Devue, Cécile, Lasselin, Juliette, Plessier, Aurélie, Merchant, Salma, Blanc-Brude, Olivier, Souyri, Michèle, Mougenot, Nathalie, Dingli, Florent, Loew, Damarys, Hatem, Stephane N., James, Chloé, Villeval, Jean-Luc, Boulanger, Chantal M., Rautou, Pierre-Emmanuel, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Gériatrie [Hôpital Européen Georges Pompidou, Paris], Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence des Maladies Vasculaires du Foie [Paris] (FILFOIE), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Phénotypage du petit animal (UMS28), Sorbonne Université (SU), Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie [Paris], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Laboratoire d'Hématologie, Hôpital Haut Lévêque CHU de Bordeaux, Pessac, CHU Bordeaux [Bordeaux], This work was supported by the Agence Nationale pour la Recherche (ANR 14 CE35 0022 03/ JAK-POT) and J.P by the 'poste accueil INSERM'. The proteomic plateform is supported by 'Région Ile-de-France' (2013-2-EML-02-ICR-1) and Fondation pour la Recherche Médicale (DGE20121125630) grants (to D.L.)., Poisson, Johanne, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Simvastatin, Erythrocytes, Cardiology, Aorta, Thoracic, Mice, Transgenic, In Vitro Techniques, Antioxidants, Mice, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell-Derived Microparticles, Animals, Humans, Cancer, Myeloproliferative Disorders, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Janus Kinase 2, Cardiovascular disease, endothelial cells, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Femoral Artery, Mice, Inbred C57BL, Oxidative Stress, Cardiovascular Diseases, Vasoconstriction, Gain of Function Mutation, Research Article
Abstract: International audience; Arterial cardiovascular events are the leading cause of death in patients with JAK2V617F myeloproliferative neoplasms (MPN). However, their mechanisms are poorly understood. The high prevalence of myocardial infarction without significant coronary stenosis or atherosclerosis in patients with MPN suggests that vascular function is altered. Consequences of JAK2V617F mutation on vascular reactivity are unknown. We observe here increased responses to vasoconstrictors in arteries from Jak2V617F mice, resulting from disturbed endothelial nitric oxide pathway and increased endothelial oxidative stress. This response was reproduced in wild-type mice by circulating microvesicles isolated from patients carrying JAK2V617F and by erythrocyte-derived microvesicles from transgenic mice. Microvesicles of other cellular origins had no effect. This effect was observed ex vivo on isolated aortas, but also in vivo on femoral arteries. Proteomic analysis of microvesicles derived from JAK2V617F erythrocytes identified increased expression of myeloperoxidase as the likely mechanism accounting for microvesicles effect. Myeloperoxidase inhibition in microvesicles derived from JAK2V617F erythrocytes supressed their effect on oxidative stress. Antioxidants, such as simvastatin and N-acetyl-cysteine, improved arterial dysfunction in Jak2V617F mice. In conclusion, JAK2V617F MPN are characterized by exacerbated vasoconstrictor responses resulting from increased endothelial oxidative stress caused by circulating erythrocyte-derived microvesicles. Simvastatin appears as promising therapeutic strategy in this setting.
Published: 2020

26. CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine

Author: Sébastien Lepreux, Antoine Dewitte, Julien Villeneuve, Jean Ripoche, Xavier Gauthereau, Alexandre Ouattara, Claire Rigothier, Marion Bouchecareilh, Christian Combe, Dewitte, Antoine [0000-0003-1112-4845], Villeneuve, Julien [0000-0002-5430-1680], Ouattara, Alexandre [0000-0002-7346-7539], Apollo - University of Cambridge Repository, Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anesthésie - Réanimation [Bordeaux], CHU Bordeaux [Bordeaux], Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Service de pathologie [CH Libourne], Centre Hospitalier Libourne, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie-transplantation-dialyse [Bordeaux], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chassande, Olivier, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Article Subject, Cell Survival, [SDV]Life Sciences [q-bio], Blotting, Western, CD40 Ligand, Immunology, Apoptosis, Enzyme-Linked Immunosorbent Assay, Inflammation, Pharmacology, Real-Time Polymerase Chain Reaction, Cell Line, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Pathology, medicine, RB1-214, Humans, Secretion, Platelet activation, Interleukin 6, Cell Proliferation, biology, Interleukin-6, Chemistry, Acute kidney injury, Interleukin, Chloroquine, Epithelial Cells, hemic and immune systems, Cell Biology, Flow Cytometry, medicine.disease, Cell Hypoxia, 3. Good health, [SDV] Life Sciences [q-bio], Kidney Tubules, 030104 developmental biology, Microscopy, Fluorescence, 030220 oncology & carcinogenesis, biology.protein, Kidney disorder, medicine.symptom, Research Article
Abstract: Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear. Here, we studied the control by CD154 of the proinflammatory cytokine interleukin- (IL-) 6 secretion in short-term oxygen (O2) deprivation conditions, using the HK-2 cell line as a kidney tubular epithelial cell (TEC) model. IL-6 secretion was markedly stimulated by CD154 after 1 to 3 hours of hypoxic stress. Both intracellular IL-6 expression and secretion were stimulated by CD154 and associated with a strong upregulation of IL-6 mRNA and increased transcription. Searching for inhibitors of CD154-mediated IL-6 production by HK-2 cells in hypoxic conditions, we observed that chloroquine, a drug that has been repurposed as an anti-inflammatory agent, alleviated this induction. Therefore, CD154 is a potent early stimulus for IL-6 secretion by TECs in O2 deprivation conditions, a mechanism likely to take part in the deleterious inflammatory consequences of platelet activation in kidney tubular injury. The inhibition of CD154-induced IL-6 production by chloroquine suggests the potential usefulness of this drug as a therapeutic adjunct in conditions associated with acute kidney injury.
Published: 2020

27. Crest maturation at the cardiomyocyte surface contributes to a new late postnatal development stage that controls the diastolic function of the adult heart

Author: Clément Karsenty, Céline Guilbeau-Frugier, Gaël Genet, Marie-Hélène Seguelas, Philippe Alzieu, Olivier Cazorla, Alexandra Montagner, Yuna Blum, Caroline Dubroca, Julie Maupoint, Blandine Tramunt, Marie Cauquil, Thierry Sulpice, Sylvain Richard, Silvia Arcucci, Remy Flores-Flores, Nicolas Pataluch, Romain Montoriol, Pierre Sicard, Antoine Deney, Thierry Couffinhal, Jean-Michel Sénard, Céline Galés, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Virginia School of Medicine [US], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Toulouse (UT), and CHU Bordeaux [Bordeaux]
Subjects: [SDV]Life Sciences [q-bio]
Abstract: RATIONALEIn addition to its typical rod-shape, the mammalian adult cardiomyocyte (CM) harbors a unique lateral membrane surface architecture with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) the role of which is still unknown.OBJECTIVETo investigate the development and functional role of CM crests during the postnatal period.METHODS AND RESULTSElectron/confocal microscopy and western-blot of left ventricular tissues from rat hearts indicated a late CM surface crest maturation, between postnatal day 20 (P20) and P60, as shown by substantial SSM swelling and increased claudin-5 cell surface expression. The P20-P60 postnatal stage also correlates with an ultimate maturation of the T-Tubules and the intercalated disk. At the cellular level, we identified an atypical CM hypertrophy characterized by an increase in long- and short-axes without myofibril addition and with sarcomere lateral stretching, indicative of lateral stretch-based CM hypertrophy. We confirmed the P20-P60 hypertrophy at the organ level by echocardiography but also demonstrated a transcriptomic program after P20 targeting all the cardiac cell populations. At the functional level, using Doppler echocardiography, we found that the P20-P60 period is specifically dedicated to the improvement of relaxation. Mechanistically, using CM-specific knock-out mice, we identified ephrin-B1 as a determinant of CM crest maturation after P20 controlling lateral CM stretch-hypertrophy and relaxation. Interestingly, while young adultEfnb1CMspe−/−mice essentially show a relaxation impairment with exercise intolerance, they progressively switch toward heart failure with 100% KO mice dying after 13 months.CONCLUSIONSThis study highlights a new late P20-P60 postnatal developmental stage of the heart in rodents during which the CM surface crests mature through an ephrin-B1-dependant mechanism and regulate the diastolic function. Moreover, we demonstrate for the first time that the CM crest architecture is cardioprotective.
Published: 2022

28. JAK2 V617F polycythemia vera and essential thrombocythemia: dynamic clinical features associated with long-term outcomes

Author: Léa Sureau, Caroline Buors, Jean-Christophe Ianotto, Françoise Boyer, Aline Tanguy-Schmidt, Lydia Roy, Emilie Cayssials, Laura Cailly, Jean-Claude Chomel, Aurélie Chauveau, Corentin Orvain, Olivier Mansier, Dana Ranta, Margot Robles, Emmanuel Gyan, Olivier Hérault, Stanislas Nimubona, Tony Marchand, Eric Lippert, Jérémie Riou, Valérie Ugo, Damien Luque Paz, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Intercommunal de Cornouaille (CHIC), CHU Bordeaux [Bordeaux], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CENTRE HOSPITALIER PÉRIGUEUX (CHP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Canceropole Grand Ouest, Ligue contre le Cancer Grand OuestLigue nationale contre le cancer, French National Institute of Cancer (FIMBANK, INCa BCB 2013), Chard-Hutchinson, Xavier, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Henri Mondor [Créteil]
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Primary Myelofibrosis, Mutation, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Janus Kinase 2, Polycythemia Vera, ComputingMilieux_MISCELLANEOUS, Thrombocythemia, Essential
Abstract: International audience
Published: 2022

29. Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation

Author: Levy, Bruno, Girerd, Nicolas, Amour, Julien, Besnier, Emmanuel, Nesseler, Nicolas, Helms, Julie, Delmas, Clément, Sonneville, Romain, Guidon, Catherine, Rozec, Bertrand, David, Helène, Bougon, David, Chaouch, Oussama, Walid, Oulehri, Hervé, Dupont, Belin, Nicolas, Gaide-Chevronnay, Lucie, Rossignol, Patrick, Kimmoun, Antoine, Duarte, Kevin, Slutsky, Arthur, Brodie, Daniel, FELLAHI, Jean-Luc, Ouattara, Alexandre, Combes, Alain, Mattei, Mathieu, Thivillier, Carine, Auchet, Thomas, Perez, Pierrre, Fritz, Caroline, Maureira, Pablo, Hubert, Maxime, Liu, Yihua, Meziani, Ferhat, Merdji, Hamid, Monnier, Alexandra, Clere-Jehl, Raphaël, Nieszkowska, Ania, Pineton, Marc, Chommeloux, Juliette, Hékimian, Guillaume, Lebreton , Guillaume, Quessard, Astrid, Imbault, Julien, Rémy, Alain, Pernot , Mathieu, Joseph, Pierre, Scollo, Giovanni, Pozzi, Matteo, Escudier, Étienne, MULLER, Michel, Dorez, Didier, Sirodot, Michel, Doguet, Fabien, Scherrer, Vincent, Aludaat, Chadi, Bernasinski, Michael, Zogheib, Elie, Caus, Thierry, Bizouarn, Philippe, Vourc’h, Mickael, Roussel, Jean-Christian, Senage, Thomas, Flecher, Erwan, Verhoye, Jean-Philippe, Roisne, Antoine, Biedermann, Sébastien, Vardon-Bounes, Fanny, Crognier, Laure, Porterie, Jean, Colson, Pascal, Gaudard, Philippe, Rouviere, Philippe, Bouadma, Lila, Sinnah, Fabrice, Nataf, Patrick, Para, Marylou, Dureau, Pauline, Djavidi, Nima, Bouglé, Adrien, Leprince, Pascal, Dessertaine, Géraldine, Durand, Michel, Albaladejo, Pierre, Martin, Cecile, Belon, François, Piton, Gael, Winiszewski, Hadrien, Perroti, Andrea, Tonon, David, Cholley, Bernard, Zlotnik, Diane, Achouh, Paul, Nougue, Hélène, Collange, Olivier, Mertes, Paul Michel, Kindo, Michel, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hôpital Privé Jacques Cartier [Massy], Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Strasbourg (UNISTRA), Hôpital Universitaire de Rangueil, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Amiens-Picardie, Service de Réanimation médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], University of Toronto, Columbia University Irving Medical Center (CUIMC), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Importance: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain.Objective: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO.Design, Setting, and Participants: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for
Published: 2022

30. Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial

Author: Bruno, Levy, Nicolas, Girerd, Julien, Amour, Emmanuel, Besnier, Nicolas, Nesseler, Julie, Helms, Clément, Delmas, Romain, Sonneville, Catherine, Guidon, Bertrand, Rozec, Helène, David, David, Bougon, Oussama, Chaouch, Oulehri, Walid, Dupont, Hervé, Nicolas, Belin, Lucie, Gaide-Chevronnay, Patrick, Rossignol, Antoine, Kimmoun, Kevin, Duarte, Arthur S, Slutsky, Daniel, Brodie, Jean-Luc, Fellahi, Alexandre, Ouattara, Alain, Combes, Michel, Kindo, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Privé Jacques Cartier [Massy], Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Service de Réanimation médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], University of Toronto, Columbia University [New York], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The trial was sponsored and conducted by the Direction de la Recherche Clinique, CHU Nancy, with a grant from the French Ministry of Health., HYPO-ECMO Trial Group and the International ECMO Network (ECMONet): Mathieu Mattei MD, Carine Thivillier MD, Thomas Auchet MD, Pierrre Perez MD, Caroline Fritz MD, Pablo Maureira MD, PhD, Maxime Hubert MD, Yihua Liu MD, PhD, Ferhat Meziani MD, PhD, Hamid Merdji MD, Alexandra Monnier MD, Raphaël Clere-Jehl MD, Ania Nieszkowska MD, Marc Pineton MD, Juliette Chommeloux MD, Guillaume Hékimian MD, Guillaume Lebreton MD, Astrid Quessard MD, Julien Imbault MD, Alain Rémy MD, Mathieu Pernot MD, Pierre Joseph MD, Giovanni Scollo MD, Matteo Pozzi MD, PhD, Étienne Escudier MD, Michel Muller MD, Didier Dorez MD, Michel Sirodot MD, Fabien Doguet MD, Vincent Scherrer MD, Chadi Aludaat MD, Michael Bernasinski MD, Elie Zogheib MD, PhD, Thierry Caus MD, PhD, Philippe Bizouarn MD, PhD, Mickael Vourc'h MD, PhD, Jean-Christian Roussel MD, PhD, Thomas Senage MD, PhD, Erwan Flecher MD, PhD, Jean-Philippe Verhoye MD, PhD, Antoine Roisne MD, Sébastien Biedermann MD, Fanny Vardon-Bounes MD, PhD, Laure Crognier MD, Jean Porterie MD, Pascal Colson MD, PhD, Philippe Gaudard MD, PhD, Philippe Rouviere MD, Lila Bouadma MD, PhD, Fabrice Sinnah MD, PhD, Patrick Nataf MD, PhD, Marylou Para MD, Pauline Dureau MD, Nima Djavidi MD, Adrien Bouglé MD, PhD, Pascal Leprince MD, PhD, Géraldine Dessertaine MD, Michel Durand MD, Pierre Albaladejo MD, Cecile Martin MD, François Belon MD, Gael Piton MD, PhD, Hadrien Winiszewski MD, Andrea Perroti MD, David Tonon MD, Bernard Cholley MD, PhD, Diane Zlotnik MD, Paul Achouh MD, PhD, Hélène Nougue MD, PhD, Olivier Collange MD, PhD, Paul Michel Mertes MD, PhD, Michel Kindo MD, PhD, and Jonchère, Laurent
Subjects: Male, Time Factors, [SDV]Life Sciences [q-bio], Shock, Cardiogenic, Hemorrhage, General Medicine, Middle Aged, Respiration, Artificial, Body Temperature, [SDV] Life Sciences [q-bio], Renal Replacement Therapy, Stroke, Extracorporeal Membrane Oxygenation, Hypothermia, Induced, Sepsis, Confidence Intervals, Intubation, Intratracheal, Heart Transplantation, Humans, Female, France, Heart-Assist Devices, Erythrocyte Transfusion, Original Investigation
Abstract: ImportanceThe optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain.ObjectiveTo determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO.Design, Setting, and ParticipantsRandomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for InterventionsEarly moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166).Main Outcomes and MeasuresThe primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO.ResultsAmong the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, −8.3% [95% CI, −16.3% to −0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.57 (95% CI, 0.36 to 0.90; P = .02) for the moderate hypothermia group compared with the normothermia group and the risk difference was −12.7% (95% CI, −22.3% to −3.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group.Conclusions and RelevanceIn this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive.Trial RegistrationClinicalTrials.gov Identifier: NCT02754193
Published: 2022

31. Plasma Markers of Neutrophil Extracellular Trap Are Linked to Survival but Not to Pulmonary Embolism in COVID-19-Related ARDS Patients

Author: Renaud Prével, Annabelle Dupont, Sylvie Labrouche-Colomer, Geoffrey Garcia, Antoine Dewitte, Antoine Rauch, Julien Goutay, Morgan Caplan, Elsa Jozefowicz, Jean-Philippe Lanoix, Julien Poissy, Etienne Rivière, Arthur Orieux, Denis Malvy, Didier Gruson, Loic Garçon, Sophie Susen, Chloé James, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anesthésie - Réanimation [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Interface sang vaisseaux et réparation cardiovasculaire, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Lille, CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro [Lille], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Université de Bordeaux (UB), Service de médecine interne et maladies tropicales, CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Victor Segalen - Bordeaux 2, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Global Health in the Global South (GHiGS), Institut de Recherche pour le Développement (IRD)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Hématologie [CHU Amiens], Université de Picardie Jules Verne (UPJV), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital cardiologique, University of Salford, and CHU Pessac
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Respiratory Distress Syndrome, neutrophil extracellular trap, Immunology, immunothrombosis, COVID-19, acute respiratory distress syndrome, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Extracellular Traps, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, Humans, Pulmonary Embolism, Biomarkers
Abstract: IntroductionCoronavirus disease 2019 (COVID-19) can cause life-threatening acute respiratory distress syndrome (ARDS). Recent data suggest a role for neutrophil extracellular traps (NETs) in COVID-19-related lung damage partly due to microthrombus formation. Besides, pulmonary embolism (PE) is frequent in severe COVID-19 patients, suggesting that immunothrombosis could also be responsible for increased PE occurrence in these patients. Here, we evaluate whether plasma levels of NET markers measured shorty after admission of hospitalized COVID-19 patients are associated with clinical outcomes in terms of clinical worsening, survival, and PE occurrence.Patients and MethodsNinety-six hospitalized COVID-19 patients were included, 50 with ARDS (severe disease) and 46 with moderate disease. We collected plasma early after admission and measured 3 NET markers: total DNA, myeloperoxidase (MPO)–DNA complexes, and citrullinated histone H3. Comparisons between survivors and non-survivors and patients developing PE and those not developing PE were assessed by Mann–Whitney test.ResultsAnalysis in the whole population of hospitalized COVID-19 patients revealed increased circulating biomarkers of NETs in patients who will die from COVID-19 and in patients who will subsequently develop PE. Restriction of our analysis in the most severe patients, i.e., the ones who enter the hospital for COVID-19-related ARDS, confirmed the link between NET biomarker levels and survival but not PE occurrence.ConclusionOur results strongly reinforce the hypothesis that NETosis is an attractive therapeutic target to prevent COVID-19 progression but that it does not seem to be linked to PE occurrence in patients hospitalized with COVID-19.
Published: 2022

32. Decrease of Pdzrn3 is required for heart maturation and protects against heart failure

Author: Mathieu Pernot, Béatrice Jaspard-vinassa, Alice Abelanet, Sebastien Rubin, Isabelle Forfar, Sylvie Jeanningros, Laura Cetran, Murielle Han-Yee Yu, Elise Balse, Stéphane Hatem, Pascale Dufourcq, Thierry Couffinhal, Cécile Duplàa, Gestionnaire, HAL Sorbonne Université 5, Role de l'ubiquitine ligase E3 PDZRN3 dans le développement des cardiomyopathies hypertrophiques et dans la transition vers l'insuffisance cardiaque - - CardioPDZ2016 - ANR-16-CE17-0001 - AAPG2016 - VALID, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des Maladies Cardiaques et Vasculaires [CHU Bordeaux], This work was supported by Agence National de la Recherche (ANR -16-CE17-0001-01), by the Fédération Française de Cardiologie, Fondation pour le Recherche Médicale (Equipe FRM) and by Inserm funds., ANR-16-CE17-0001,CardioPDZ,Role de l'ubiquitine ligase E3 PDZRN3 dans le développement des cardiomyopathies hypertrophiques et dans la transition vers l'insuffisance cardiaque(2016), Azevedo, Chloe, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Adaptation cardiovasculaire à l'ischemie, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Ubiquitin-Protein Ligases, [SDV]Life Sciences [q-bio], Science, 030204 cardiovascular system & hematology, Article, Basolateral polarity, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Animals, Humans, Myocytes, Cardiac, Protein Kinase C, beta Catenin, 030304 developmental biology, Heart Failure, Mice, Knockout, 0303 health sciences, Multidisciplinary, Molecular medicine, Disease model, Heart, Cardiovascular biology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], Cardiac hypertrophy, Medicine, Cardiomyopathies, Signal Transduction
Abstract: Heart failure is the final common stage of most cardiopathies. Cardiomyocytes (CM) connect with others via their extremities by intercalated disk protein complexes. This planar and directional organization of myocytes is crucial for mechanical coupling and anisotropic conduction of the electric signal in the heart. One of the hallmarks of heart failure is alterations in the contact sites between CM. Yet no factor on its own is known to coordinate CM polarized organization. We have previously shown that PDZRN3, an ubiquitine ligase E3 expressed in various tissues including the heart, mediates a branch of the Planar cell polarity (PCP) signaling involved in tissue patterning, instructing cell polarity and cell polar organization within a tissue. PDZRN3 is expressed in the embryonic mouse heart then its expression dropped significantly postnatally corresponding with heart maturation and CM polarized elongation. A moderate CM overexpression of Pdzrn3 (Pdzrn3 OE) during the first week of life, induced a severe eccentric hypertrophic phenotype with heart failure. In models of pressure-overload stress heart failure, CM-specific Pdzrn3 knockout showed complete protection against degradation of heart function. We reported that Pdzrn3 signaling induced PKC ζ expression, c-Jun nuclear translocation and a reduced nuclear ß catenin level, consistent markers of the planar non-canonical Wnt signaling in CM. We then show that subcellular localization (intercalated disk) of junction proteins as Cx43, ZO1 and Desmoglein 2 was altered in Pdzrn3 OE mice, which provides a molecular explanation for impaired CM polarization in these mice. Our results reveal a novel signaling pathway that controls a genetic program essential for heart maturation and maintenance of overall geometry, as well as the contractile function of CM, and implicates PDZRN3 as a potential therapeutic target for the prevention of human heart failure.
Published: 2022

33. Role of pericytes and endothelial cells in the heart failure

Author: Cornuault, Lauriane, STAR, ABES, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux, and Marie-Ange Renault
Subjects: Insuffisance cardiaque, Péricytes, Dysfonction endothéliale, Heart failure, Endothelial dysfunction, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Pericytes, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: Heart failure (HF) is a major public health issue affecting between 1 to 2% of the general population. Patients with HF with preserved ejection fraction (HFpEF) represent approximately 50% of patients with HF and are often older, female, and frequently have hypertension. The high prevalence of these comorbidities suggests that they play a role in the development of the disease. There is currently no specific treatment for HFpEF, because its pathophysiology remains poorly understood and requires further investigations in order to find new therapeutic targets. Microvascular dysfunction is currently proposed as compromising the perfusion of the heart and participating in the development of diastolic dysfunction. But the role of endothelial dysfunction in the pathophysiology of HFpEF remains to be clarified.Our objective was to better understand the role of vascular cells, pericytes and endothelial cells, in the pathophysiology of HFpEF. More specifically, this thesis aimed (1) to measure the impact of pericyte degeneration on cardiac microvascular integrity and cardiac function, (2) to test whether endothelial dysfunction participates in the development of diastolic dysfunction in a mouse model of HFpEF, and (3) to assess the sexual dimorphism associated with ICFEp.To investigate the role of pericytes in the heart, we have developed a mouse model lacking pericytes, Pdgfrb-Cre/ERT2; Rosa-DTA mice. We demonstrated that cardiac pericytes are required for cardiac microvascular integrity and cardiac function by regulating cardiomyocyte contractility and relaxation. These results suggest that changes in the pericyte phenotype may participate in the pathophysiology of cardiovascular diseases.To test the role of endothelial dysfunction in the pathophysiology of HFpEF, we created a mouse model in which diastolic dysfunction is induced by a high-fat diet (HFD) and by L-NAME, a NO synthase inhibitor. Firstly, we characterized the phenotype of the coronary vasculature in this model in males, females and ovariectomized females to highlight a possible sexual dimorphism. We have demonstrated that diastolic dysfunction was associated with endothelial dysfunction only in ovariectomized females. Secondly, we tested the role of endothelial dysfunction in these mice using a mouse model with preserved endothelial function under stress conditions (CdonECKO mice). This experiment proved that preventing endothelial dysfunction does not prevent diastolic dysfunction induced by an HFD+L-NAME treatment.All of these results demonstrate that the role of endothelial dysfunction in the development of HFpEF remains to be proved., L’insuffisance cardiaque (IC) est un problème de santé publique majeur touchant entre 1 et 2 % de la population générale. Les patients atteints d’IC à fraction d’éjection préservée (ICFEp) représentent environ 50 % des patients ayant une IC et sont souvent plus âgés, de sexe féminin, et présentent fréquemment une HTA. La prévalence élevée de ces comorbidités suggère qu’elles jouent un rôle dans le développement de la maladie. Il n’existe à l’heure actuelle aucun traitement spécifique de l’ICFEp, car sa physiopathologie reste mal comprise et nécessite d’être approfondie afin de trouver de nouvelles cibles thérapeutiques. La dysfonction microvasculaire est actuellement proposée comme compromettant la perfusion du coeur et participant ainsi au développement de la dysfonction diastolique. Mais l’implication de la dysfonction endothéliale dans la physiopathologie de l’ICFEp reste à démontrer. L’objectif de cette thèse était donc de mieux comprendre le rôle des cellules vasculaires, péricytes et cellules endothéliales, dans la physiopathologie de l’ICFEp. Plus précisément, cette thèse a eu pour but (1) de mesurer l’impact de la dégénérescence des péricytes sur l’intégrité microvasculaire cardiaque et sur la fonction cardiaque, (2) de tester si la dysfonction endothéliale participe au développement de la dysfonction diastolique dans un modèle murin d’ICFEp, et (3) d’évaluer le dimorphisme sexuel associé à l’ICFEp.Pour étudier le rôle des péricytes sur le coeur, nous avons développé un modèle de souris dépourvues de péricytes, les souris Pdgfrb-Cre/ERT2 ; Rosa-DTA. Nous avons démontré que les péricytes cardiaques sont nécessaires à l’intégrité microvasculaire cardiaque et à la fonction cardiaque en régulant la contractilité et la relaxation des cardiomyocytes. Ces résultats suggèrent que des modifications du phénotype des péricytes pourraient participer à la physiopathologie de maladies cardiovasculaires. Pour tester le rôle de la dysfonction endothéliale dans la physiopathologie de l’ICFEp, nous avons d’abord mis en place un modèle murin, chez lequel une dysfonction diastolique est induite par un régime riche en lipides (HFD) et par le L-NAME, un inhibiteur de NO synthase. Dans un premier temps, nous avons caractérisé le phénotype de la vasculature coronaire dans ce modèle chez les mâles, les femelles et les femelles ovariectomisées pour mettre en évidence un éventuel dimorphisme sexuel. Nous avons, en effet, mis en évidence que la dysfonction diastolique était associée à une dysfonction endothéliale uniquement chez les femelles ovariectomisées. Dans un second temps, nous avons testé le rôle de la dysfonction endothéliale chez ces souris à l’aide d’un modèle murin présentant une fonction endothéliale préservée dans des conditions de stress (les souris CdonECKO). Cette expérience nous a révélé que prévenir la dysfonction endothéliale ne permet pas de prévenir la dysfonction diastolique induite par le traitement HFD+L-NAME.L’ensemble de ces résultats démontrent que le rôle de la dysfonction endothéliale dans le développement de l’ICFEp reste à prouver.
Published: 2022

34. The ability of Oxygen Reserve Index® to detect hyperoxia in critically ill patients

Author: Hugues de Courson, Thomas Julien-Laferrière, Delphine Georges, Philippe Boyer, Eric Verchère, Matthieu Biais, Admin, Oskar, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oxygen, Hypoxemia, Arterial oxygen tension, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], ORI, Hyperoxia, Critical Care and Intensive Care Medicine
Abstract: Background Hyperoxia is associated with increased morbidity and mortality in the intensive care unit. Classical noninvasive measurements of oxygen saturation with pulse oximeters are unable to detect hyperoxia. The Oxygen Reserve Index (ORI) is a continuous noninvasive parameter provided by a multi-wave pulse oximeter that can detect hyperoxia. Primary objective was to evaluate the diagnostic accuracy of the ORI for detecting arterial oxygen tension (PaO2) > 100 mmHg in neurocritical care patients. Secondary objectives were to test the ability of ORI to detect PaO2 > 120 mmHg and the ability of pulse oximetry (SpO2) to detect PaO2 > 100 mmHg and PaO2 > 120 mmHg. Methods In this single-center study, we collected ORI and arterial blood samples every 6 h for 3 consecutive days. Diagnostic performance was estimated using the area under the receiver operating characteristic curve (AUROC). Results There were 696 simultaneous measurements of ORI and PaO2 in 62 patients. Considering the repeated measurements, the correlation between ORI and PaO2 was r = 0.13. The area under the receiver operating characteristic curve (AUROC), obtained to test the ability of ORI to detect PaO2 > 100 mmHg, was 0.567 (95% confidence interval = 0.566–0.569) with a sensitivity of 0.233 (95%CI = 0.230–0.235) and a specificity of 0.909 (95%CI = 0.907–0.910). The AUROC value obtained to test the ability of SpO2 to detect a PaO2 > 100 mmHg was 0.771 (95%CI = 0.770–0.773) with a sensitivity of 0.715 (95%CI = 0.712–0.718) and a specificity of 0.700 (95%CI = 0.697–0.703). The diagnostic performance of ORI and SpO2 for detecting PaO2 > 120 mmHg was AUROC = 0.584 (95%CI = 0.582–0.586) and 0.764 (95%CI = 0.762–0.766), respectively. The AUROC obtained for SpO2 was significantly higher than that for ORI (p Conclusion In a specific population of brain-injured patients hospitalized in a neurointensive care unit, our results suggest that the ability of ORI to diagnose hyperoxia is relatively low and that SpO2 provides better detection.
Published: 2022

35. Myocardial infarction associated with erenumab: a case report

Author: Justine Perino, Virginie Corand, Elise Laurent, Hélène Théophile, Ghada Miremont‐Salamé, Antoine Pariente, Jean‐Laurent Colas, Thierry Couffinhal, Francesco Salvo, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Polyclinique Bordeaux Nord Aquitaine, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM, U1034, Centre de Pharmacovigilance [CHU Bordeaux] (CP), and Centre de la douleur de Bordeaux (CDB)
Subjects: [SDV] Life Sciences [q-bio], drug safety, migraine disorder, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV]Life Sciences [q-bio], pharmacovigilance, adverse event, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, case report, Pharmacology (medical), calcitonin gene-related peptide
Abstract: International audience; Background: Monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP-mabs) are novel drugs for resistant migraine prophylaxis. As CGRP-mabs cause inhibition of vasodilatation, their use is reserved to patients with no recent history of cardiovascular diseases. We report a case of myocardial infarction associated with erenumab.Case: A 57-year-old woman with a familial history of coronaropathy, was first treated with erenumab 70 mg for 6 months, then increased to 140 mg. Almost five months after, the patient presented chest pain, increased troponin and abnormal electrocardiogram. A myocardial infarction without coronarography abnormality was diagnosed through MRI.Conclusion: Further evidence is needed to assess the risk of myocardial infarction in patients treated with a CGRP-mab. In patients over 40 years of age, the risk of coronary or cardiovascular events should be assessed using risk tables or algorithms to take into account cardiovascular risk factors. This may be complemented by appropriate exams to measure the burden of coronary atherosclerosis, if necessary.
Published: 2022

36. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial

Author: Urs Fischer, Johannes Kaesmacher, Daniel Strbian, Omer Eker, Christoph Cognard, Patricia S Plattner, Lukas Bütikofer, Pasquale Mordasini, Sandro Deppeler, Vitor M Pereira, Jean François Albucher, Jean Darcourt, Romain Bourcier, Guillon Benoit, Chrysanthi Papagiannaki, Ozlem Ozkul-Wermester, Gerli Sibolt, Marjaana Tiainen, Benjamin Gory, Sébastien Richard, Jan Liman, Marielle Sophie Ernst, Marion Boulanger, Charlotte Barbier, Laura Mechtouff, Liqun Zhang, Gaultier Marnat, Igor Sibon, Omid Nikoubashman, Arno Reich, Arturo Consoli, Bertrand Lapergue, Marc Ribo, Alejandro Tomasello, Suzana Saleme, Francisco Macian, Solène Moulin, Paolo Pagano, Guillaume Saliou, Emmanuel Carrera, Kevin Janot, María Hernández-Pérez, Raoul Pop, Lucie Della Schiava, Andreas R Luft, Michel Piotin, Jean Christophe Gentric, Aleksandra Pikula, Waltraud Pfeilschifter, Marcel Arnold, Adnan H Siddiqui, Michael T Froehler, Anthony J Furlan, René Chapot, Martin Wiesmann, Paolo Machi, Hans-Christoph Diener, Zsolt Kulcsar, Leo H Bonati, Claudio L Bassetti, Mikael Mazighi, David S Liebeskind, Jeffrey L Saver, Jan Gralla, Angelika Alonso, Caroline Arquizan, Xavier Barreau, Rémy Beaujeux, Daniel Behme, Tobias Boeckh-Behrens, Christian Boehme, Martí Boix, Grégoire Boulouis, Nicolas Bricout, Nicolas Broc, Carlo W. Cereda, Emmanuel Chabert, Tae-Hee Cho, Alessandro Cianfoni, Vincent Costalat, Christian Denier, Frederico Di Maria, Richard du Mesnil de Rochemont, Patricia Fearon, Anna Ferrier, Sebastian Fischer, Maxime Gauberti, Marie Gaudron, Laetitia Gimenez, Christoph Globas, Michael Görtler, Mayank Goyal, Ruediger Hilker-Roggendorf, Michael D. Hill, Vi Tuan Hua, Lisa Humbertjean, Olav Jansen, Simon Jung, Georg Kägi, Michael E. Kelly, Ilka Kleffner, Michael Knoflach, Krassen Nedeltchev, Lars Udo Krause, Kimmo Lappalainen, Margaux Lefebvre, Joe Leyon, Liang Liao, Jean-Sebastien Liegey, Christian Loehr, Patrik Michel, Stefania Nannoni, Patrick Nicholson, Lorena Nico, Michael Obadia, Julien Ognard, Ayokunle Ogungbemi, Jean-Marc Olivot, Simon Escalard, Marco Pasi, Lissa Peeling, Jane Perez, Martina Petersen, Eike Piechowiak, Roberto Raposo, Silja Räty, Sarah C. Reitz, Sebastià Remollo, Luca Remonda, Ian Rennie, Manuel Requena, Alexander Riabikin, Roberto Riva, Aymeric Rouchaud, Andrea Rosi, Marta Rubiera, Laurent Spelle, Marlena Schnieder, Joanna D. Schaafsma, Tilman Schubert, Jörg B. Schulz, Mohammed Siddiqui, Sébastien Soize, Michael Sonnberger, Emmanuel Touze, Aude Triquenot, Guillaume Turc, Lucy Vieira, Wagih Ben Hassen, Judith N. Wagner, Katrin Wasser, Johannes Weber, Holger Wenz, David Weisenburger-Lile, Fritz Wodarg, Valérie Wolff, Silke Wunderlich, University of Bern, Bern University Hospital [Berne] (Inselspital), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Toulouse [Toulouse], Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux), CHU Bordeaux [Bordeaux], University of Toronto, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de neurologie [Rouen], Helsinki University Hospital [Finland] (HUS), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], University Medical Center Göttingen (UMG), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Interférométrie, In situ et Instrumentation pour la Microscopie Electronique (CEMES-I3EM), Centre d'élaboration de matériaux et d'études structurales (CEMES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Hôpital Foch [Suresnes], Institut de Ciencies del Cosmos (ICCUB), Universitat de Barcelona (UB), Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Environnement, Bioénergie, Microalgues et Plantes (EBMP), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Département de Neuroradiologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Lille, University hospital of Zurich [Zurich], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toronto Western Hospital, Frankfurt University Hospital, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Case Western Reserve University [Cleveland], Alfried Krupp Krankenhaus [Essen], Geneva University Hospitals and Geneva University, Institute of Medical Informatics, Biometrics and Epidemiology [ Essen, Germany] (IMIBE), University Hospital Basel [Basel], University of Basel (Unibas), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of California (UC), SWIFT DIRECT Collaborators: Angelika Alonso, Caroline Arquizan, Xavier Barreau, Rémy Beaujeux, Daniel Behme, Tobias Boeckh-Behrens, Christian Boehme, Martí Boix, Grégoire Boulouis, Nicolas Bricout, Nicolas Broc, Carlo W Cereda, Emmanuel Chabert, Tae-Hee Cho, Alessandro Cianfoni, Vincent Costalat, Christian Denier, Frederico Di Maria, Richard du Mesnil de Rochemont, Patricia Fearon, Anna Ferrier, Sebastian Fischer, Maxime Gauberti, Marie Gaudron, Laetitia Gimenez, Christoph Globas, Michael Görtler, Mayank Goyal, Ruediger Hilker-Roggendorf, Michael D Hill, Vi Tuan Hua, Lisa Humbertjean, Olav Jansen, Simon Jung, Georg Kägi, Michael E Kelly, Ilka Kleffner, Michael Knoflach, Krassen Nedeltchev, Lars Udo Krause, Kimmo Lappalainen, Margaux Lefebvre, Joe Leyon, Liang Liao, Jean-Sebastien Liegey, Christian Loehr, Patrik Michel, Stefania Nannoni, Patrick Nicholson, Lorena Nico, Michael Obadia, Julien Ognard, Ayokunle Ogungbemi, Jean-Marc Olivot, Simon Escalard, Marco Pasi, Lissa Peeling, Jane Perez, Martina Petersen, Eike Piechowiak, Roberto Raposo, Silja Räty, Sarah C Reitz, Sebastià Remollo, Luca Remonda, Ian Rennie, Manuel Requena, Alexander Riabikin, Roberto Riva, Aymeric Rouchaud, Andrea Rosi, Marta Rubiera, Laurent Spelle, Marlena Schnieder, Joanna D Schaafsma, Tilman Schubert, Jörg B Schulz, Mohammed Siddiqui, Sébastien Soize, Michael Sonnberger, Emmanuel Touze, Aude Triquenot, Guillaume Turc, Lucy Vieira, Wagih Ben Hassen, Judith N Wagner, Katrin Wasser, Johannes Weber, Holger Wenz, David Weisenburger-Lile, Fritz Wodarg, Valérie Wolff, Silke Wunderlich., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), St George’s University Hospitals, Vall d'Hebron University Hospital [Barcelona], and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], General Medicine, 610 Medicine & health
Abstract: Background Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. Methods In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0.9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. Findings Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7 .3%, 95% CI -16.6 to 2.1, lower limit of one-sided 95% CI -15.1%, crossing the non-inferiority margin of - 12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy ( risk difference -1.0%, 95% CI -4.8 to 2 .7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [ 91%] of 201 vs 199 [96%] of 207, risk difference -5.1%, 95% CI -10.2 to 0. 0, p=0.047). Interpretation Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
Published: 2022

37. A Glanzmann thrombasthenia family associated with a TUBB1‐related macrothrombocytopenia

Author: Alan T. Nurden, Benoît Guillet, Jacques Caen, Xavier Pillois, Sophie Bayart, Paquita Nurden, CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Académie nationale de médecine, Centre de Traitement des Maladies Hémorragiques [CHU Rennes], Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Rhythmologie et de Modélisation Cardiaque [Bordeaux] (Plateforme Technologique d’Innovation Biomédicale), Hôpital Xavier Arnozan - CHU de Bordeaux, and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV]Life Sciences [q-bio], thrombocytopenia, membrane glycoproteins, 030204 cardiovascular system & hematology, Gene mutation, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Gene expression, Medicine, Platelet, Gene, Sanger sequencing, business.industry, Glanzmann thrombasthenia, Oligogenic Inheritance, Hematology, Phenotype, 3. Good health, Immunology, gene expression, symbols, β-tubulin, Complication, business
Abstract: International audience; Background - Macrothrombocytopenia (MTP) is a rare but enigmatic complication of Glanzmann thrombasthenia (GT), an inherited bleeding disorder caused by the absence of platelet aggregation due to deficiencies of the αIIbβ3 integrin. Objectives - We report a family with type I GT and a prolonged bleeding time but unusually associated with congenital mild thrombocytopenia and platelet size heterogeneity with giant forms. Methods and results - Sanger sequencing of DNA from the propositus identified 2 heterozygous ITGB3 gene mutations: p.P189S and p.C210S both of which prevent αIIbβ3 expression and are causative of GT but without explaining the presence of enlarged platelets. High-throughput screening led to the detection of a predicted disease-causing heterozygous mutation in the TUBB1 gene: p.G146R, encoding β1-tubulin, a component of the platelet cytoskeleton and a gene where mutations are a known cause of MTP. Conclusions - Family screening confirmed that this rare phenotype results from oligogenic inheritance while suggesting that the GT phenotype dominates clinically.
Published: 2019

38. Relationship between variations in cardiac output and end-tidal CO2 after phenylephrine infusion in anaesthetised patients

Author: Delphine Georges, Philippe Boyer, Emmanuel Futier, Hugues de Courson, Matthieu Biais, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cardiac output, medicine.medical_specialty, Haemodynamics, business.industry, Hemodynamics, 030208 emergency & critical care medicine, Monitor, Phenylephrine, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, Internal medicine, Cardiology, medicine, Postoperative outcome, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Hypotension, Postoperative, business, Outcome, End tidal co2, medicine.drug
Published: 2021

39. Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE)

Author: Alexandre Duvignaud, Edouard Lhomme, Racha Onaisi, Rémi Sitta, Ambre Gelley, Julie Chastang, Lionel Piroth, Christine Binquet, Julie Dupouy, Alain Makinson, Benjamin Lefèvre, Jean-Marc Naccache, Caroline Roussillon, Roland Landman, Cédrick Wallet, Sophie Karcher, Valérie Journot, Duc Nguyen, Thierry Pistone, Stéphane Bouchet, Marie-Edith Lafon, Mathieu Molimard, Rodolphe Thiébaut, Xavier de Lamballerie, Jean-Philippe Joseph, Laura Richert, Olivier Saint-Lary, Sarah Djabarouti, Linda Wittkop, Xavier Anglaret, Denis Malvy, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université - Département de médecine générale, Sorbonne Université (SU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe Hospitalier Paris Saint-Joseph (hpsj), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-20-COVI-0040,COVERAGE,Traitement à domicile des personnes infectées par le SRAS-CoV-2 sans signe de gravité mais à risque de complications: un essai randomisé à plusieurs bras et en plusieurs étapes (MAMS) pour évaluer l'efficacité de plusieurs antiviraux(2020), Richert, Laura, Traitement à domicile des personnes infectées par le SRAS-CoV-2 sans signe de gravité mais à risque de complications: un essai randomisé à plusieurs bras et en plusieurs étapes (MAMS) pour évaluer l'efficacité de plusieurs antiviraux - - COVERAGE2020 - ANR-20-COVI-0040 - COVID-19 - VALID, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Toulouse (UT)
Subjects: Microbiology (medical), Male, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Ciclesonide, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Pregnenediones, Outpatients, Adults, Humans, Aged, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Inhaled corticosteroids, SARS-CoV-2, COVID-19, General Medicine, Middle Aged, COVID-19 Drug Treatment, Treatment, Oxygen, Infectious Diseases, Treatment Outcome, Randomized controlled trial, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female
Abstract: International audience; Objectives: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness.Methods: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here.Results: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms.Discussion: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.
Published: 2021

40. Targeting Pdzrn3 maintains adult blood-brain barrier and central nervous system homeostasis

Author: Cécile Duplàa, Bruno Bontempi, Florian Gueniot, Sébastien Rubin, Thierry Couffinhal, Carole Proust, Alice Abelanet, Jean-Luc Morel, P. Bougaran, Pascale Dufourcq, Admin, Oskar, Role de l'ubiquitine ligase E3 PDZRN3 dans le développement des cardiomyopathies hypertrophiques et dans la transition vers l'insuffisance cardiaque - - CardioPDZ2016 - ANR-16-CE17-0001 - AAPG2016 - VALID, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Agence Nationale de la Recherche Grant ANR 16-CE17-0001-01. Institut National de la Santé et de la Recherche Médicale University of Bordeaux, ANR-16-CE17-0001,CardioPDZ,Role de l'ubiquitine ligase E3 PDZRN3 dans le développement des cardiomyopathies hypertrophiques et dans la transition vers l'insuffisance cardiaque(2016), Service des Maladies Cardiaques et Vasculaires [CHU Bordeaux], ANR-18-RHUS-0002,SHIVA,Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease(2018), ANR-20-ECVD-0002,ENRICH,ENdothelial Retinal function as Indicator for vascular Cognitive Health(2020), MOREL, jean-luc, Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease - - SHIVA2018 - ANR-18-RHUS-0002 - RHUS - VALID, and ENdothelial Retinal function as Indicator for vascular Cognitive Health - - ENRICH2020 - ANR-20-ECVD-0002 - ERA-CVD - VALID
Subjects: [SDV.BA] Life Sciences [q-bio]/Animal biology, Ubiquitin-Protein Ligases, Central nervous system, Wnt pathway, Vascular permeability, blood brain barrier, Disease, Blood–brain barrier, Capillary Permeability, Mice, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Alzheimer Disease, Medicine, Animals, Homeostasis, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cognitive impairment, vascular permeability, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.BA]Life Sciences [q-bio]/Animal biology, [SCCO.NEUR] Cognitive science/Neuroscience, Wnt signaling pathway, Endothelial Cells, Biological Transport, Original Articles, Pathophysiology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.anatomical_structure, endothelial tight junction, Neurology, Blood-Brain Barrier, Vascular cognitive impairment, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Neuroscience
Abstract: résumé de communication dans un congrès; International audience; Blood brain barrier (BBB) disruption is a critical component of the pathophysiology of cognitive impairment of vascular etiology (VCI) and associated with Alzheimer's disease (AD). The Wnt pathway plays a crucial role in BBB maintenance, but there is limited data on its role in cognitive pathologies. The E3 ubiquitin ligase PDZRN3 is a regulator of the Wnt pathway. In a murine model of VCI, overexpressing Pdzrn3 in endothelial cell (EC) exacerbated BBB hyperpermeability and accelerated cognitive decline. We extended these observations, in both VCI and AD models, showing that EC-specific depletion of Pdzrn3, reinforced the BBB, with a decrease in vascular permeability and a subsequent spare in cognitive decline. We found that in cerebral vessels, Pdzrn3 depletion protects against AD-induced Wnt target gene alterations and enhances endothelial tight junctional proteins. Our results provide evidence that Wnt signaling could be a molecular link regulating BBB integrity and cognitive decline under VCI and AD pathologies.
Published: 2021

41. High mean arterial pressure target to improve sepsis-associated acute kidney injury in patients with prior hypertension: a feasibility study

Author: Alexandre Ouattara, Jean Ripoche, Sébastien Rubin, Gauthier Bouche, Antoine Dewitte, Gilles Hilbert, Aurore Labat, Pierre-Antoine Duvignaud, Christian Combe, Didier Gruson, Alexandre Boyer, Olivier Joannes-Boyau, Immunology from Concept and Experiments to Translation (ImmunoConcept), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), CHU Bordeaux [Bordeaux], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Mean arterial pressure, Fractional excretion of sodium, Urology, Renal function, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Urine sodium, Norepinephrine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Septic shock, Intensive care, medicine, 10. No inequality, Creatinine, RC86-88.9, business.industry, Research, Acute kidney injury, Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, medicine.disease, chemistry, Blood pressure, Urine osmolality, Kidney concentrating ability, business
Abstract: Background The optimal mean arterial pressure (MAP) in cases of septic shock is still a matter of debate in patients with prior hypertension. An MAP between 75 and 85 mmHg can improve glomerular filtration rate (GFR) but its effect on tubular function is unknown. We assessed the effects of high MAP level on glomerular and tubular renal function in two intensive care units of a teaching hospital. Inclusion criteria were patients with a history of chronic hypertension and developing AKI in the first 24 h of septic shock. Data were collected during two 6 h periods of MAP regimen administered consecutively after haemodynamic stabilisation in an order depending on the patient's admission unit: a high-target period (80–85 mmHg) and a low-target period (65–70 mmHg). The primary endpoint was the creatinine clearance (CrCl) calculated from urine and serum samples at the end of each MAP period by the UV/P formula. Results 26 patients were included. Higher urine output (+0.2 (95%:0, 0.4) mL/kg/h; P = 0.04), urine sodium (+6 (95% CI 0.2, 13) mmol/L; P = 0.04) and lower serum creatinine (− 10 (95% CI − 17, − 3) µmol/L; P = 0.03) were observed during the high-MAP period as compared to the low-MAP period, resulting in a higher CrCl (+25 (95% CI 11, 39) mL/mn; P = 0.002). The urine creatinine, urine–plasma creatinine ratio, urine osmolality, fractional excretion of sodium and urea showed no significant variation. The KDIGO stage at inclusion only interacted with serum creatinine variation and low level of sodium excretion at inclusion did not interact with these results. Conclusions In the early stage of sepsis-associated AKI, a high-MAP target in patients with a history of hypertension was associated with a higher CrCl, but did not affect the kidneys' ability to concentrate urine, which may reflect no effect on tubular function.
Published: 2021

42. Skin autofluorescence predicts mortality in type 1 diabetes

Author: Laurence Blanco, Vincent Rigalleau, Camille Majchrzak, Marie Monlun, Alice Larroumet, Ninon Foussard, Kamel Mohammedi, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Glycated Hemoglobin, Glycation End Products, Advanced, Type 1 diabetes, Pathology, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, General Medicine, Skin autofluorescence, 030204 cardiovascular system & hematology, medicine.disease, Fluorescence, 03 medical and health sciences, Diabetes Mellitus, Type 1, 0302 clinical medicine, Endocrinology, Internal Medicine, Humans, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Diabetic Angiopathies, Skin
Published: 2021

43. Pre-operative peripheral intravenous cannula insertion failure at the first attempt in adults: Development of the VENSCORE predictive scale and identification of risk factors

Author: Alexandre Ouattara, Karine Nouette-Gaulain, Florian Robin, Bertrand Moal, Matthieu Biais, Maxim Roy, Emeline Angles, Stéphanie Roullet, Florence Saillour-Glénisson, Musa Sesay, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, medicine.medical_specialty, Peripheral intravenous, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Catheterization, Peripheral, Medicine, Cannula, Humans, 030212 general & internal medicine, Prospective Studies, Internal validation, Cannula insertion, Vein, business.industry, 030208 emergency & critical care medicine, Pre operative, Confidence interval, 3. Good health, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Anesthesia, Emergency medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Cohort study
Abstract: STUDY OBJECTIVE: Our objective was to develop a clinical scale (the VENSCORE) to predict pre-operative peripheral intravenous cannula (PIVC) insertion failure at the first attempt in adults. DESIGN: This was a prospective multicenter cohort study that included internal validation with bootstrapping. SETTING: The operating rooms of 14 hospitals in southern France from June 2016 to June 2018. PATIENTS: Consecutive adult patients aged 18 years or older were recruited upon arrival to the operating room, regardless of American Society of Anaesthesiology (ASA) physical status. INTERVENTIONS: PIVC insertion on arrival to the OR. MEASUREMENTS: PIVC insertion failure at the first attempt was the outcome of interest. Data collected included the number of PIVC insertion attempts and potential predictors of the risk of failure (including pre-operative patient characteristics and data relative to the procedure). Uni- and multivariable logistic analyses were performed. Based on these results, the VENSCORE scale was developed to predict the risk of failure of the first PIVC insertion. MAIN RESULTS: In total, 3394 patients were included, and 27 were excluded because of protocol violations. The PIVC insertion failure rate at the first attempt was 20.3%. Based on multivariable analysis, a history of difficult PIVC insertions, high-risk surgery, poor vein visibility, and moderate to poor vein palpability were identified as risk factors for insertion failure at the first attempt. The area under the curve of the predictive model was 0.82 (95% confidence interval: 0.80-0.84). A VENSCORE value of 0 points was associated with a failure rate of 7%, versus 97% for a score of 6. CONCLUSIONS: The four-item VENSCORE scale could be useful for prospectively identifying adults at risk of first PIVC insertion attempt failure.
Published: 2021

44. Impact of dexamethasone use to prevent from severe COVID-19-induced acute kidney injury

Author: Sébastien Rubin, Renaud Prevel, Alexandre Boyer, Arthur Orieux, Didier Gruson, Pierre Khan, CHU de Bordeaux Pellegrin [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Admin, Oskar
Subjects: Male, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Treatment outcome, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Severity of Illness Index, Dexamethasone, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Severity of illness, Research Letter, medicine, Humans, Intensive care unit, ComputingMilieux_MISCELLANEOUS, Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, RC86-88.9, business.industry, Acute kidney injury, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, medicine.disease, 3. Good health, Treatment Outcome, Emergency medicine, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience
Published: 2021

45. Impact of a simulation-based training on the experience of the beginning of residency

Author: Sébastien Sanges, Pierre Fesler, Etienne Rivière, Y. Kouchit, C. Mercuzot, J. Galland, B. Debien, N. Martis, Camille Roubille, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, Biocommunication en Cardio-Métabolique (BC2M), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Perceived Stress Scale, Anxiety, medicine.disease_cause, Stress, Simulation training, 03 medical and health sciences, 0302 clinical medicine, MESH: Simulation training, Internship, Humans, Medicine, Psychological stress, 030212 general & internal medicine, Session (computer science), Simulation based, Internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, 030504 nursing, business.industry, Internat, Gastroenterology, Internship and Residency, Enseignement par simulation, MESH: Intership and residency, [SDV] Life Sciences [q-bio], Médecine interne, Generalized anxiety, MESH: Clinical competence, Physical therapy, Clinical Competence, medicine.symptom, 0305 other medical science, business, Anxiété, Stress, Psychological, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction We aimed to evaluate the impact of an immersive simulation session on the experience of the beginning of residency. Methods The interventional group consisted of newly recruited residents in 2019, who participated in the workshop presenting four emergency scenarios frequently encountered during night shifts; the control group comprised residents who had begun their internship in 2018, without having participated in the simulation workshop. The level of psychological stress and self-confidence were self-estimated in the simulation group before and immediately after the workshop. During the second semester of residency, stress, self-efficacy and anxiety were evaluated in both groups with the Perceived Stress Scale (PSS), General Self-efficacy Scale (GSES), and Generalized Anxiety Disorder-7 (GAD-7) scale. Results In the second semester 2020, the PSS, GSES and GAD-7 were 20.71 ± 8.15 and 22.44 ± 5.68 (P = 0.40); 26.88 ± 6.30 and 27.11 ± 3.95 (P = 0.87); 6.94 ± 5.25 and 8.89 ± 4.78 (P = 0.22) for the simulation (n = 17, 89.5% of participation) and control (n = 9, 75%) groups, respectively. In the simulation group, the level of self-confidence had significantly improved from 1.82 ± 0.95 before the session to 2.29 ± 1.16 after the session (P = 0.05). Interestingly, this improvement in self-confidence was significantly correlated with GAD-7 (P = 0.014) and PSS (P = 0.05), and tended to be correlated with GSES (P = 0.09). Conclusion Our study showed a significant improvement in self-confidence between before and after the simulation session. Residents who experienced an improvement in self-confidence saw their stress and anxiety levels decrease during the second semester reevaluation, in favor of a prolonged benefit from the session.
Published: 2021

46. Remission of necrobiosis lipoidica diabeticorum with a JAK1/2 inhibitor: A case report

Author: Pauline Poupon, Kamel Mohammedi, Laurence Blanco, Vincent Rigalleau, O. Cadart, E. Belin, Patrick Blanco, N. Poursac, M. A. Barbet-Massin, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 030203 arthritis & rheumatology, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, General Medicine, medicine.disease, Dermatology, Necrobiosis lipoidica, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal Medicine, medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Published: 2021

47. One-year care pathway after acute myocardial infarction in 2018: Prescription, medical care and medication adherence, using a French health insurance reimbursement database

Author: Karin Martin-Latry, Philippe Latry, Camille Berges, Pierre Coste, Hervé Douard, Yann Pucheu, Thierry Couffinhal, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Caisse primaire d'assurance maladie (CPAM), Sources of funding : none, and Admin, Oskar
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Myocardial Infarction, General Medicine, Reimbursement, Medication Adherence, Cohort Studies, Insurance, Prescriptions, Health, Insurance, Health, Reimbursement, Critical Pathways, Humans, Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aged
Abstract: International audience; Myocardial infarction is a major cause of morbidity and mortality. Guidelines have been published to optimize medical care and involve optimization of the care pathway and hospital-city coordination. To describe the myocardial infarction care pathway during the year following hospital discharge, and the use of and adherence to secondary prevention drugs. A cohort study was conducted using data from the main French health insurance reimbursement database of the ex-Aquitaine region. Information about the medical and pharmaceutical care of hospitalized patients in 2018 was collected for 12 months. Medication adherence was assessed by using the proportion of days covered by the treatment and persistence. A total of 3015 patients were included, and the mean age was 66 years. Almost 76% of the patients had a reimbursement for BAS (combined prescription of beta-blocker/antiplatelet/lipid-lowering drug), BASI (combined prescription of beta-blocker/antiplatelet/lipid-lowering drug/angiotensin-converting enzyme inhibitor) or AS (combined prescription of antiplatelet/lipid-lowering drug) treatment. Medication adherence was around 83% for aspirin and 75% for lipid-lowering drugs for the 1-year persistence. During the same time, the proportion of days covered was suboptimal. Almost 4% of patients died after leaving hospital, 45% went to a cardiac rehabilitation centre and 23% had at least one hospital readmission, whatever the reason. Patients had a mean number of 11 general practitioner consultations during the year. Almost 41% of patients did not have a consultation with a cardiologist, and 38.4% had at least two consultations. Rehabilitation and general practitioner consultations were associated with adherence. These new results provide clear information on the medical care environment of patients, and help us to improve care transition. Close collaboration between healthcare practitioners is very important in the early stages of outpatient follow-up.
Published: 2021

48. Polymicrobial Infections Among Patients with Vascular Q Fever, France, 2004-2020

Author: Marc-Olivier Vareil, Carole Eldin, Sabine Pereyre, Noémie Sauvage, Xavier Berard, Caroline Caradu, Mathilde Puges, Laure Alleman, Charles Cazanave, Fatima M’Zali, Mathilde Carrer, Maïlys Ducours, CHU Bordeaux [Bordeaux], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales A [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Le CHCB, Centre Hospitalier de la Côte Basque, Université de Bordeaux (UB), Université de Bordeaux Ségalen [Bordeaux 2], Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMBE, Isabelle, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Centre Hospitalier de la Côte Basque (CHCB)
Subjects: Epidemiology, vector-borne infections, Infectious and parasitic diseases, RC109-216, medicine.disease_cause, Serology, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, aortoenteric fistula, 030212 general & internal medicine, bacteria, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Coinfection, vascular graft and endograft infections, Dispatch, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Infectious Diseases, Coxiella burnetii, Superinfection, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, France, Q Fever, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Microbiology (medical), polymicrobial infections, Polymicrobial infection, vascular Q fever, 030231 tropical medicine, Aortoenteric fistula, Q fever, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, chronic Q fever, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, In patient, Aortitis, Polymicrobial Infections among Patients with Vascular Q Fever, France, 2004–2020, business.industry, bacterial zoonoses, medicine.disease, biology.organism_classification, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, zoonoses, Immunology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, aortitis
Abstract: International audience; We report 5 cases of vascular Q fever complicated by polymicrobial superinfection in patients who had no risk factors for acute Q fever. Q fever was diagnosed by serologic and molecular assays for Coxiella burnetii. We confirmed additional infections using conventional graft cultures.
Published: 2021

49. Feasibility and postoperative opioid sparing effect of an opioid-free anaesthesia in adult cardiac surgery: a retrospective study

Author: Sébastien Leuillet, Gaspard Cadier, Alexandre Ouattara, Clément Aguerreche, Julien Imbault, Alain Remy, Cédrick Zaouter, Antoine Beurton, Centre de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, CHU Bordeaux [Bordeaux], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Biofortis Mérieux NutriSciences [Saint-Herblain], Université du Québec à Montréal = University of Québec in Montréal (UQAM), Laboratoire de Recherche Magellan, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Malbec, Odile, and Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan)
Subjects: Male, Mean arterial pressure, Lidocaine, [SDV]Life Sciences [q-bio], Remifentanil, Pain, 030204 cardiovascular system & hematology, Loading dose, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Anesthesiology, medicine, Humans, Hypnotics and Sedatives, Ketamine, Anesthesia, RD78.3-87.3, Dexmedetomidine, Cardiac Surgical Procedures, Aged, Retrospective Studies, Opioid-free anaesthesia, Pain, Postoperative, Morphine, Maintenance dose, business.industry, Research, Perioperative, Middle Aged, Cardiac surgery, 3. Good health, Analgesics, Opioid, [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, Feasibility Studies, Female, France, business, medicine.drug
Abstract: Background No previous study investigated the dexmedetomidine-based opioid-free anesthesia (OFA) protocol in cardiac surgery. The main objective of this study was to evaluate the feasibility and the postoperative opioid-sparing effect of dexmedetomidine-based OFA in adult cardiac surgery patients. Methods We conducted a single-centre and retrospective study including 80 patients above 18 years old who underwent on-pump cardiac surgery between November 2018 and February 2020. Patients were divided into two groups: OFA (lidocaine, ketamine, dexmedetomidine, MgSO4) or opioid-based anaesthesia (remifentanil and anti-hyperalgesic medications such as ketamine and/or MgSO4 and/or lidocaine at the discretion of the anesthesiologist). The primary endpoint was the total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours. Secondary outcomes included perioperative hemodynamics, post-operative maximal pain at rest and during coughing and adverse outcomes. Data are expressed as median [interquartile range]. Results Patients in the OFA-group had a higher EuroSCORE II, with more diabetes, more dyslipidemia and more non-elective surgery but fewer smoking history. In the OFA group, the median loading dose of dexmedetomidine was 0.6 [0.4–0.6] μg.kg− 1 while the median maintenance dose was 0.11 μg.kg− 1.h− 1 [0.05–0.20]. In 10 (25%) patients, dexmedetomidine was discontinued for a drop of mean arterial pressure below 55 mmHg. The median total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours was lower in the OFA group (15.0 mg [8.5–23.5] versus 30.0 mg [17.3–44.3], p p = 0.60), the maximal pain score during coughing was lower in OFA group (3.5 [2.0–5.0] versus 5.5 [3.0–7.0], p = 0.04). In OFA group the incidence of atrial fibrillation (18% versus 40%, p = 0.03) and non-invasive ventilation use (25% versus 48%, p = 0.04) were lower. The incidence of bradycardia and the intraoperative use of norepinephrine were similar between both groups. Conclusion Dexmedetomidine-based OFA in cardiac surgery patients is feasible and could be associated with a lower postoperative morphine consumption and better postoperative outcomes. Further randomized studies are required to confirm these promising results and determine the optimal associations, dosages, and infusion protocols during cardiac surgery. Graphical abstract
Published: 2021

50. Changes in dynamic arterial elastance induced by volume expansion and vasopressor in the operating room: a prospective bicentre study

Author: Philippe Boyer, Musa Sesay, Romain Grobost, Matthieu Biais, Romain Lanchon, Karine Nouette-Gaulain, Emmanuel Futier, Hugues de Courson, Service Anesthésie - Réanimation [Bordeaux], CHU Bordeaux [Bordeaux], Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), This study was supported from institutional and departmental sources., Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Boullé, Christelle
Subjects: Cardiac output, medicine.medical_specialty, Mean arterial pressure, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 030202 anesthesiology, Internal medicine, Heart rate, Article CLINIQUE, medicine, Arterial pressure, business.industry, Research, Doppler, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, Stroke volume, lcsh:RC86-88.9, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Pulse pressure, Compliance (physiology), Blood pressure, Cardiology, Arterial line, business
Abstract: Background Dynamic arterial elastance (Eadyn), defined as the ratio between pulse pressure variations and stroke volume variations, has been proposed to assess functional arterial load. We evaluated the evolution of Eadyn during volume expansion and the effects of neosynephrine infusion in hypotensive and preload-responsive patients. Methods In this prospective bicentre study, we included 56 mechanically ventilated patients in the operating room. Each patient had volume expansion and neosynephrine infusion. Stroke volume and stroke volume variations were obtained using esophageal Doppler, and pulse pressure variations were measured through the arterial line. Pressure response to volume expansion was defined as an increase in mean arterial pressure (MAP) ≥ 10%. Results Twenty-one patients were pressure responders to volume expansion. Volume expansion induced a decrease in Eadyn (from 0.69 [0.58–0.85] to 0.59 [0.42–0.77]) related to a decrease in pulse pressure variations more pronounced than the decrease in stroke volume variations. Baseline and changes in Eadyn after volume expansion were related to age, history of arterial hypertension, net arterial compliance and effective arterial elastance. Eadyn value before volume expansion > 0.65 predicted a MAP increase ≥ 10% with a sensitivity of 76% (95% CI 53–92%) and a specificity of 60% (95% CI 42–76%). Neosynephrine infusion induced a decrease in Eadyn (from 0.67 [0.48–0.80] to 0.54 [0.37–0.68]) related to a decrease in pulse pressure variations more pronounced than the decrease in stroke volume variations. Baseline and changes in Eadyn after neosynephrine infusion were only related to heart rate. Conclusion Eadyn is a potential sensitive marker of arterial tone changes following vasopressor infusion.
Published: 2019

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