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8 results on '"IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [Créteil] (U955 Inserm - UPEC)"'

1. Veno-Arterial Extracorporeal Membrane Oxygenation for Circulatory Failure in COVID-19 Patients: Insights from the ECMOSARS Registry

Author

Anselmi, Amedeo, Mansour, Alexandre, Para, Marylou, Mongardon, Nicolas, Porto, Alizée, Guihaire, Julien, Morgant, Marie-Catherine, Pozzi, Matteo, Cholley, Bernard, Falcoz, Pierre-Emmanuel, Gaudard, Philippe, Lebreton, Guillaume, Labaste, François, Barbanti, Claudio, Fouquet, Olivier, Chocron, Sidney, Mottard, Nicolas, Esvan, Maxime, Fougerou-Leurent, Claire, Flecher, Erwan, Vincentelli, André, Nesseler, Nicolas, Pierrot, Marc, Flicoteaux, Guillaume, Mauriat, Philippe, Ouattara, Alexandre, Roze, Hadrien, Huet, Olivier, Fischer, Marc-Olivier, Alessandri, Claire, Bellaïche, Raphel, Constant, Ophélie, Roux, Quentin, Ly, André, Meffert, Arnaud, Merle, Jean-Claude, Picard, Lucile, Skripkina, Elena, Folliguet, Thierry, Fiore, Antonio, d'Ostrevy, Nicolas, Morgan, Marie-Catherine, Guinot, Pierre-Grégoire, Nguyen, Maxime, Gaide-Chevronnay, Lucie, Terzi, Nicolas, Colin, Gwenhaël, Fabre, Olivier, Astaneh, Arash, Issard, Justin, Fadel, Elie, Fabre, Dominique, Girault, Antoine, Ion, Iolande, Menager, Jean Baptiste, Mitilian, Delphine, Mercier, Olaf, Stephan, François, Thes, Jacques, Jouan, Jerôme, Duburcq, Thibault, Loobuyck, Valentin, Moussa, Mouhammed, Mugnier, Agnes, Rousse, Natacha, Manganiello, Sabrina, Desebbe, Olivier, Fellahi, Jean-Luc, Henaine, Roland, Richard, Jean-Christophe, Riad, Zakaria, Guervilly, Christophe, Hraiech, Sami, Papazian, Laurent, Castanier, Matthias, Chanavaz, Charles, Cadoz, Cyril, Gette, Sebastien, Louis, Guillaume, Portocarrero, Erick, Brini, Kais, Bischoff, Nicolas, Levy, Bruno, Kimmoun, Antoine, Mattei, Mathieu, Perez, Pierre, Bourdiol, Alexandre, Hourmant, Yannick, Mahé, Pierre-Joachim, Rozec, Bertrand, Vourc’h, Mickaël, Aubert, Stéphane, Bazalgette, Florian, Roger, Claire, Jaquet, Pierre, Lortat-Jacob, Brice, Mordant, Pierre, Nataf, Patrick, Patrier, Juliette, Provenchere, Sophie, Roué, Morgan, Sonneville, Romain, Tran-Dinh, Alexy, Wicky, Paul-Henri, Al Zreibi, Charles, Guyonvarch, Yannis, Hamada, Sophie, Bertier, Astrid, Harrois, Anatole, Matiello, Jordi, Kerforne, Thomas, Lacroix, Corentin, Brechot, Nicolas, Combes, Alain, Schmidt, Matthieu, Chommeloux, Juliette, Constantin, Jean Michel, D’alessandro, Cosimo, Demondion, Pierre, Demoule, Alexandre, Dres, Martin, Fadel, Guillaume, Fartoukh, Muriel, Hekimian, Guillaume, Juvin, Charles, Leprince, Pascal, Levy, David, Luyt, Charles Edouard, Pineton de Chambrun, Marc, Schoell, Thibaut, Fillâtre, Pierre, Massart, Nicolas, Nicolas, Roxane, Jonas, Maud, Vidal, Charles, Allou, Nicolas, Muccio, Salvatore, Di Perna, Dario, Ruggieri, Vito-Giovanni, Mourvillier, Bruno, Bounader, Karl, Launey, Yoann, Lebouvier, Thomas, Parasido, Alessandro, Reizine, Florian, Seguin, Philippe, Besnier, Emmanuel, Carpentier, Dorothée, Clavier, Thomas, Olland, Anne, Villard, Marion, Bounes, Fanny, Minville, Vincent, Guillon, Antoine, Fedun, Yannick, Ross, James, 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], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, 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), IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [Créteil] (U955 Inserm - UPEC), 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), Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, 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), 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 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), 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), 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), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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
Heart Failure, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, VA-ECMO, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Outcomes, Covid-19
Abstract

International audience; Objectives: The clinical profile and outcomes of patients with Covid-19 who require veno-arterial or veno-venous-arterial extracorporeal membrane oxygenation (VA-ECMO - VAV-ECMO) are poorly understood. We aimed to describe the characteristics and outcomes of these patients and to identify predictors of both favorable and unfavorable outcomes.Methods: ECMOSARS is a multicenter, prospective, nationwide French registry enrolling patients who require VV/VA-ECMO in the context of Covid-19 infection (652 patients at 41 centers). We focused on 47 patients supported with VA- or VAV-ECMO for refractory cardiogenic shock.Results: Median age was 49. 14% of patients had a prior diagnosis of heart failure. The most common etiologies of cardiogenic shock were acute pulmonary embolism (30%), myocarditis (28%), and acute coronary syndrome (4%). E-CPR (Extracorporeal Cardiopulmonary Resuscitation) occurred in 38%. In-hospital survival was 28% in the whole cohort, and 43% when E-CPR patients were excluded. ECMO cannulation was associated with significant improvements in pH and FiO2 on day one, but non-survivors showed significantly more severe acidosis and higher FiO2 than survivors at this point (p = 0.030 and p = 0.006). Other factors associated with death were greater age (p = 0.02), higher BMI (p = 0.03), E-CPR (p = 0.001), non-myocarditis etiology (p = 0.02), higher serum lactates (p = 0.004), epinephrine (but not noradrenaline) use before initiation of ECMO (p = 0.003), hemorrhagic complications (p = 0.001), greater transfusion requirements (p = 0.001), and more severe SAVE and SAFE scores (p = 0.01 and p = 0.03).Conclusions: We report the largest focused analysis of VA- and VAV-ECMO recipients in Covid-19. Although relatively rare, the need for temporary mechanical circulatory support in these patients is associated with poor prognosis. However, VA-ECMO remains a viable solution to rescue carefully selected patients. We identified factors associated with poor prognosis and suggest that E-CPR is not a reasonable indication for VA-ECMO in this population.

Published
2023

2. Low-dose corticosteroid therapy for cardiogenic shock in adults (COCCA): study protocol for a randomized controlled trial

Author

Armand Mekontso Dessap, François Bagate, Clément Delmas, Tristan Morichau-Beauchant, Bernard Cholley, Alain Cariou, Benoit Lattuca, Mouhamed Moussa, Nicolas Mongardon, Damien Fard, Matthieu Schmidt, Adrien Bouglé, Mathieu Kerneis, Emmanuel Vivier, François Roubille, Matthieu Duprey, Véronique Decalf, Thibaud Genet, Messaouda Merzoug, Etienne Audureau, Pierre Squara, 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 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), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), CHU Tenon [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 Henri Mondor, CHU Toulouse [Toulouse], Centre cardiologique du Nord (CCN), 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Lille, IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [Créteil] (U955 Inserm - UPEC), 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), Hôpital Henri Mondor, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Grand Hôpital de l'Est Francilien (GHEF), Centre Hospitalier René Dubos [Pontoise], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CMC Ambroise Paré [Neuilly-sur-Seine], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and MORNET, Dominique

Subjects
Adult, Hypothalamo-Hypophyseal System, Medicine (General), Hydrocortisone, [SDV]Life Sciences [q-bio], Shock, Cardiogenic, Pituitary-Adrenal System, Medicine (miscellaneous), 030204 cardiovascular system & hematology, Study Protocol, 03 medical and health sciences, R5-920, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Multicenter Studies as Topic, Corticosteroid, Pharmacology (medical), 030212 general & internal medicine, Cardiogenic shock, Randomized Controlled Trials as Topic, SARS-CoV-2, COVID-19, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Treatment Outcome, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Fludrocortisone, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Adrenal insufficiency
Abstract

Background Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. Method/design This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 μg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. Discussion This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. Trial registration ClinicalTrials.gov, NCT03773822. Registered on 12 December 2018

Published
2022

3. Factors associated with remission at 5-year follow-up in recent-onset axial spondyloarthritis: results from the DESIR cohort

Author

Philippe Le Corvoisier, Salah Ferkal, Daniel Wendling, Philippe Goupille, Bijan Ghaleh, Emilie Sbidian, Laura Pina Vegas, Pascal Claudepierre, Alain Luciani, Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, EPI-PHARE (EPI-PHARE), Caisse nationale d'assurance maladie des travailleurs salariés [CNAMTS]-Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Epigénétique des infections virales et des maladies inflammatoires (UR 4266) (EPILAB), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Hôpital Henri Mondor, 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 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 Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Plateforme de Ressources Biologiques [Henri Mondor AP-HP, Créteil] (PRB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), CHI Créteil, IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [Créteil] (U955 Inserm - UPEC), 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 VO, alexandra

Subjects
Male, medicine.medical_specialty, MESH: Spondylarthritis, Logistic regression, Severity of Illness Index, remission, Rheumatology, MESH: Severity of Illness Index, Internal medicine, Spondylarthritis, medicine, Humans, Spondylitis, Ankylosing, Pharmacology (medical), Mass index, prognostic factor, Recent onset, BASDAI, MESH: Treatment Outcome, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Ankylosing spondylitis, MESH: Humans, business.industry, cohort, MESH: Axial Spondyloarthritis, MESH: Follow-Up Studies, Odds ratio, spondyloarthritis, MESH: Spondylitis, Ankylosing, medicine.disease, MESH: Male, Confidence interval, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Cohort, MESH: Tumor Necrosis Factor Inhibitors, Female, Tumor Necrosis Factor Inhibitors, business, MESH: Female, Axial Spondyloarthritis, Follow-Up Studies
Abstract

Objective The factors contributing to long-term remission in axial SpA (axSpA) are unclear. We aimed to characterize individuals with axSpA at the 5-year follow-up to identify baseline factors associated with remission. Methods We included all patients from the DESIR cohort (with recent-onset axSpA) with an available Ankylosing Spondylitis Disease Activity Score–CRP (ASDAS-CRP) at 5-year follow-up. Patients in remission (ASDAS-CRP Results Overall, 111/449 patients (25%) were in remission after 5 years. Among those never exposed to TNFi, 31% (77/247) were in remission compared with 17% (34/202) of those exposed to TNFi. Patients in remission after 5 years were more likely to be male, HLA-B27+, have a lower BMI, and a higher education level. Baseline factors associated with 5-year remission in patients never exposed to TNFi included lower BASDAI [adjusted odds ratio (ORa) 0.9, 95% CI: 0.8, 0.9) and history of peripheral arthritis (ORa 2.1, 95% CI: 1.2, 5.3). In those exposed to TNFi, remission was associated with higher education level (ORa 2.9, 95% CI: 1.6, 5.1), lower enthesitis index (ORa 0.8, 95% CI: 0.7, 0.9), lower BASDAI (ORa 0.9, 95% CI: 0.9, 0.9) and lower BMI (ORa 0.8, 95% CI: 0.7, 0.9). Conclusion This study highlights the difficulty in achieving 5-year remission in those with recent-onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.

Published
2021

4. Coronary Flow Assessment Using 3-Dimensional Ultrafast Ultrasound Localization Microscopy

Author

Oscar Demeulenaere, Zulma Sandoval, Philippe Mateo, Alexandre Dizeux, Olivier Villemain, Romain Gallet, Bijan Ghaleh, Thomas Deffieux, Charlie Deméné, Mickael Tanter, Clément Papadacci, Mathieu Pernot, Physique pour la médecine (PhysMed Paris), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [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), Demeulenaere, Oscar, Physique pour la médecine (UMR 8063, U1273), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)

Subjects
Adenosine, [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], ultrasound, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, imaging, microcirculation, volumetric imaging, X-Ray Microtomography, Coronary Vessels, Rats, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Coronary Circulation, microscopy, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Animals, blood flow, Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine, [PHYS.MECA.ACOU] Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], coronary
Abstract

International audience; ObjectivesThe purpose of this study was to demonstrate 3-dimensional (3D) coronary ultrasound localization microscopy (CorULM) of the whole heart beyond the acoustic diffraction limit (1000 images/s).BackgroundDirect assessment of the coronary microcirculation has long been hampered by the limited spatial and temporal resolutions of cardiac imaging modalities.MethodsCorULM was performed in isolated beating rat hearts (N = 6) with ultrasound contrast agents (Sonovue, Bracco), using an ultrasonic matrix transducer connected to a high channel–count ultrafast electronics. We assessed the 3D coronary microvascular anatomy, flow velocity, and flow rate of beating hearts under normal conditions, during vasodilator adenosine infusion, and during coronary occlusion. The coronary vasculature was compared with micro-computed tomography performed on the fixed heart. In vivo transthoracic CorULM was eventually assessed on anaesthetized rats (N = 3).ResultsCorULM enables the 3D visualization of the coronary vasculature in beating hearts at a scale down to microvascular structures (

Published
2022

5. Dysregulated phenylalanine catabolism plays a key role in the trajectory of cardiac aging

Author

Didier Morin, Gabor Czibik, Nadine Suffee, Serge Adnot, Costin Radu, Stéphane N. Hatem, Hao Liang, Marielle Breau, Juliette Bréhat, Ophélie Marion, Suzain Naushad, Maria Pini, Azania Abatan, Dogus Murat Altintas, Yanyan Zhang, Daigo Sawaki, Zaineb Mezdari, Rizwan Sarwar, Arash Yavari, Maissa Halfaoui, Thaïs Delmont, Thomas d’Humieres, Cécile Martel, Geneviève Derumeaux, IMRB - SMCD/'Senescence, Metabolism and Cardiovascular 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), IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [Créteil] (U955 Inserm - UPEC), Département de physiologie (CHU Henri Mondor), Hôpital Henri Mondor, CHU Henri Mondor AP-HP/UPEC, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Experimental Therapeutics, Radcliffe Department of Medicine (R.S., A.Y.), University of Oxford, 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), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IMRB - VHC/'Viruses-Hepatology-Cancers' [Créteil] (U955 Inserm - UPEC), Département de Physiologie, Hôpital Henri Mondor, AP-HP, DHU A-TVB, Créteil, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Mitologics S.A.S., Hôpital Robert Debré Paris, University of Oxford, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), and Azevedo, Chloe

Subjects
Senescence, Male, medicine.medical_specialty, Aging, senescence, Heart Diseases, [SDV]Life Sciences [q-bio], Phenylalanine, Diastole, 030204 cardiovascular system & hematology, Phenylalanine catabolism, Interstitial fibrosis, Models, Biological, Catalysis, 03 medical and health sciences, Mice, 0302 clinical medicine, Metabolomics, Physiology (medical), Internal medicine, medicine, Animals, Humans, Myocytes, Cardiac, Amino Acids, Cellular Senescence, 030304 developmental biology, chemistry.chemical_classification, Mice, Knockout, 0303 health sciences, business.industry, Myocardium, Biopterin, Amino acid, Rats, [SDV] Life Sciences [q-bio], Disease Models, Animal, Endocrinology, chemistry, Liver, Cardiac hypertrophy, Disease Susceptibility, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

Background: Aging myocardium undergoes progressive cardiac hypertrophy and interstitial fibrosis with diastolic and systolic dysfunction. Recent metabolomics studies shed light on amino acids in aging. The present study aimed to dissect how aging leads to elevated plasma levels of the essential amino acid phenylalanine and how it may promote age-related cardiac dysfunction. Methods: We studied cardiac structure and function, together with phenylalanine catabolism in wild-type (WT) and p21 −/− mice (male; 2–24 months), with the latter known to be protected from cellular senescence. To explore phenylalanine’s effects on cellular senescence and ectopic phenylalanine catabolism, we treated cardiomyocytes (primary adult rat or human AC-16) with phenylalanine. To establish a role for phenylalanine in driving cardiac aging, WT male mice were treated twice a day with phenylalanine (200 mg/kg) for a month. We also treated aged WT mice with tetrahydrobiopterin (10 mg/kg), the essential cofactor for the phenylalanine-degrading enzyme PAH (phenylalanine hydroxylase), or restricted dietary phenylalanine intake. The impact of senescence on hepatic phenylalanine catabolism was explored in vitro in AML12 hepatocytes treated with Nutlin3a (a p53 activator), with or without p21-targeting small interfering RNA or tetrahydrobiopterin, with quantification of PAH and tyrosine levels. Results: Natural aging is associated with a progressive increase in plasma phenylalanine levels concomitant with cardiac dysfunction, whereas p21 deletion delayed these changes. Phenylalanine treatment induced premature cardiac deterioration in young WT mice, strikingly akin to that occurring with aging, while triggering cellular senescence, redox, and epigenetic changes. Pharmacological restoration of phenylalanine catabolism with tetrahydrobiopterin administration or dietary phenylalanine restriction abrogated the rise in plasma phenylalanine and reversed cardiac senescent alterations in aged WT mice. Observations from aged mice and human samples implicated age-related decline in hepatic phenylalanine catabolism as a key driver of elevated plasma phenylalanine levels and showed increased myocardial PAH-mediated phenylalanine catabolism, a novel signature of cardiac aging. Conclusions: Our findings establish a pathogenic role for increased phenylalanine levels in cardiac aging, linking plasma phenylalanine levels to cardiac senescence via dysregulated phenylalanine catabolism along a hepatic-cardiac axis. They highlight phenylalanine/PAH modulation as a potential therapeutic strategy for age-associated cardiac impairment.

Published
2021

6. Preliminary pragmatic lessons from the SARS-CoV-2 pandemic in France

Author

Olivier Langeron, T. Gauss, Jean-Michel Constantin, Olivier Joannes-Boyau, Pierre Pasquier, Pierre Bouzat, Julien Pottecher, Université Paris Cité (UPCité), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital d'Instruction des Armées du Val de Grâce, Magellan Medico-Surgical Center [Bordeaux], CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Grenoble, Université Grenoble Alpes (UGA), Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Université de Paris (UP), IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [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), Service d'Anesthésie-Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)

Subjects
surge capacity, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, Health Services Accessibility, Professional Staff Committees, 0302 clinical medicine, Professional-Family Relations, Pandemic, Medicine, Bed Conversion, 030212 general & internal medicine, Surge Capacity, General Medicine, Continuity of Patient Care, Checklist, 3. Good health, Practice Guidelines as Topic, Workforce, France, Patient Safety, Coronavirus Infections, Next of kin, Health Personnel, Pneumonia, Viral, Disaster Planning, World Health Organization, Article, 03 medical and health sciences, Patient safety, Betacoronavirus, Nursing, Intensive care, Humans, Human resources, Pandemics, Health Services Needs and Demand, business.industry, SARS-CoV-2, pandemic, COVID-19, Social Support, 030208 emergency & critical care medicine, Triage, critical care, Anesthesiology and Pain Medicine, recommendations, Interdisciplinary Communication, business
Abstract

International audience; The first wave of the SARS-CoV-2 pandemic required an unprecedented and historic increase in critical care capacity on a global scale in France. Authors and members from the ACUTE and REANIMATION committees of the French Society of Anaesthesia and Intensive Care (SFAR) wished to share experience and insights gained during the first weeks of this pandemic. These were summarised following the World Health Organization Response Checklist and detailed according to the subsequent subheadings: 1. Command and Control, 2. Communication, 3. Safety and Security, 4. Triage, 5. Surge Capacity, 6. Continuity of essential services, 7. Human resources, 8. Logistics and supply management, 9. Training/Preparation, 10. Psychological comfort for patients and next of kin, 11. Learning and 12. Post disaster recovery. These experience-based recommendations, consensual across all members from both committees of our national society, establish a practical framework for medical teams, either spared by the first wave of severe COVID patients or preparing for the second one.

Published
2020

7. Quantitative imaging of coronary flows using 3D ultrafast Doppler coronary angiography

Author

David Maresca, Alain Bizé, Olivier Villemain, Mathieu Pernot, Guillaume Goudot, Lucien Sambin, Mafalda Correia, Mickael Tanter, Bijan Ghaleh, Physique pour la médecine (UMR 8063, U1273), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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), IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [Créteil] (U955 Inserm - UPEC), 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), Physique pour la médecine (PhysMed Paris), and Goudot, Guillaume

Subjects
medicine.medical_specialty, Time Factors, Heartbeat, Swine, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Coronary Angiography, Doppler imaging, Flow measurement, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Coronary circulation, symbols.namesake, 0302 clinical medicine, Imaging, Three-Dimensional, Internal medicine, Coronary Circulation, coronary perfusion, Medicine, Animals, Radiology, Nuclear Medicine and imaging, Reactive hyperemia, Radiological and Ultrasound Technology, business.industry, Ultrasound, ultrafast ultrasound, volumetric imaging, Coronary Vessels, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Cardiology, symbols, Feasibility Studies, business, Doppler effect, Blood Flow Velocity, Artery
Abstract

Coronary flow rate remains complex to assess in clinical practice using non-invasive, non-ionizing imaging tools. In this study, we introduce 3D ultrafast Doppler coronary angiography (3D UDCA), an ultrasound-based method to assess coronary blood flows in three-dimensions at high volume-rate and in one single heartbeat. We demonstrate that 3D UDCA can visualize the coronary vasculature with high temporal and spatial resolution and quantify the absolute flow. The feasibility of the technique was demonstrated in an open-chest swine model. The flow rate of the left-anterior descending artery (LAD) assessed by 3D UDCA was reconstructed successfully at the early diastolic and late diastolic phases and was in good agreement with an invasive gold-standard flowmeter during baseline, reactive hyperemia and coronary stenosis (r2 = 0.84). Finally, we demonstrate that a coronary stenosis on the LAD can be visualized as well as its associated flow acceleration.

Published
2020

8. Cigarette smoking induces human CCR6+Th17 lymphocytes senescence and VEGF-A secretion

Author

Indoumady Baskara, Sabine Le Gouvello, Maude Guillot-Delost, Claude Baillou, Didier Morin, Stéphane Kerbrat, Jorge Boczkowski, Mathieu Surenaud, Maylis Dagouassat, Hoang Quy Nguyen, François M. Lemoine, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Recherche Translationnelle en Oncogénèse Génito-Urinaire [Equipe 7] (Inserm U955 - IMRB - UPEC), Institut Curie [Paris], Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), IMRB - 'From pathophysiology towards immune-basedinterventions in HIV infection' [Créteil] (U955 Inserm - UPEC), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), IMRB - PROTECT/'Pharmacologie et Technologies pour les Maladies Cardiovasculaires' [Créteil] (U955 Inserm - UPEC), Pôle de Biologie-Pathologie [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, This work was supported by the Institut National de la Santé et de la Recherche Médicale, by the Leg Poix, and by private donators. I. Baskara was supported by a PhD scholarship from the Fondation de Recherche en Santé Respiratoire/Fondation du Souffle., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Bodescot, Myriam, Sorbonne Université (SU), and Dieu-Nosjean, Marie-Caroline

Subjects
0301 basic medicine, Senescence, [SDV]Life Sciences [q-bio], lcsh:Medicine, Inflammation, chemical and pharmacologic phenomena, C-C chemokine receptor type 6, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, medicine.disease_cause, Systemic inflammation, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Psoriasis, medicine, Secretion, lcsh:Science, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Multidisciplinary, Lung, business.industry, lcsh:R, hemic and immune systems, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, lcsh:Q, medicine.symptom, business, Oxidative stress
Abstract

Chronic exposure to environmental pollutants is often associated with systemic inflammation. As such, cigarette smoking contributes to inflammation and lung diseases by inducing senescence of pulmonary cells such as pneumocytes, fibroblasts, and endothelial cells. Yet, how smoking worsens evolution of chronic inflammatory disorders associated with Th17 lymphocytes, such as rheumatoid arthritis, psoriasis, Crohn’s disease, and multiple sclerosis, is largely unknown. Results from human studies show an increase in inflammatory CD4+ Th17 lymphocytes at blood- and pulmonary level in smokers. The aim of the study was to evaluate the sensitivity of CD4+ Th17 lymphocytes to cigarette smoke-induced senescence. Mucosa-homing CCR6+ Th17- were compared to CCR6neg -and regulatory T peripheral lymphocytes after exposure to cigarette smoke extract (CSE). Senescence sensitivity of CSE-exposed cells was assessed by determination of various senescence biomarkers (β-galactosidase activity, p16Ink4a- and p21 expression) and cytokines production. CCR6+ Th17 cells showed a higher sensitivity to CSE-induced senescence compared to controls, which is associated to oxidative stress and higher VEGFα secretion. Pharmacological targeting of ROS- and ERK1/2 signalling pathways prevented CSE-induced senescence of CCR6+Th17 lymphocytes as well as VEGFα secretion. Altogether, these results identify mechanisms by which pro-oxidant environmental pollutants contribute to pro-angiogenic and pathogenic CCR6+Th17 cells, therefore potential targets for therapeutic purposes.

Published
2020

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