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1. Role of Damage-Associated Molecular Patterns in Septic Acute Kidney Injury, From Injury to Recovery

Author

Pierre-Olivier Ludes, Charles de Roquetaillade, Benjamin Glenn Chousterman, Julien Pottecher, and Alexandre Mebazaa

Subjects
DAMPs, clinical features, precision medicine, kidney recovery, acute kidney injury, sepsis, Immunologic diseases. Allergy, RC581-607
Abstract

Damage-associated molecular patterns (DAMPs) are a group of immunostimulatory molecules, which take part in inflammatory response after tissue injury. Kidney-specific DAMPs include Tamm-Horsfall glycoprotein, crystals, and uromodulin, released by tubular damage for example. Non-kidney-specific DAMPs include intracellular particles such as nucleus [histones, high-mobility group box 1 protein (HMGB1)] and cytosol parts. DAMPs trigger innate immunity by activating the NRLP3 inflammasome, G-protein coupled class receptors or the Toll-like receptor. Tubular necrosis leads to acute kidney injury (AKI) in either septic, ischemic or toxic conditions. Tubular necrosis releases DAMPs such as histones and HMGB1 and increases vascular permeability, which perpetuates shock and hypoperfusion via Toll Like Receptors. In acute tubular necrosis, intracellular abundance of NADPH may explain a chain reaction where necrosis spreads from cell to cell. The nature AKI in intensive care units does not have preclinical models that meet a variation of blood perfusion or a variation of glomerular filtration within hours before catecholamine infusion. However, the dampening of several DAMPs in AKI could provide organ protection. Research should be focused on the numerous pathophysiological pathways to identify the relative contribution to renal dysfunction. The therapeutic perspectives could be strategies to suppress side effect of DAMPs and to promote renal function regeneration.

Published
2021
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2. Continuous Pneumatic Regulation of Tracheal Cuff Pressure to Decrease Ventilator-associated Pneumonia in Trauma Patients Who Were Mechanically Ventilated

Author

Olivier Mimoz, Benoit Veber, Matthieu Boisson, Dominique Falcon, Carole Ichai, Claire-Marie Drevet, Lilit Kelesyan, Thiên-Nga Chamaraux-Tran, Laurent Muler, Julien Pottecher, Marc Leone, Abdelouaid Nadji, Hervé Quintard, Claire Dahyot-Fizelier, Belaid Bouhemad, Nicolas Marjanovic, Sigismond Lasocki, Claire Roger, Thomas Kerforne, Jean-Yves Lefrant, Catherine Paugam-Burtz, Marc Ginet, Antoine Roquilly, Elodie Caumon, Emmanuelle Hammad, Florian Grimaldi, Pierre-Olivier Ludes, Jérémy Guenezan, Arnaud Foucrier, Sébastien Leduc, Guillaume Besch, Sabrina Seguin, Russell Chabanne, Karim Asehnoune, Philippe Gouin, Pierre-Gildas Guitard, Denis Frasca, Maxime Léger, Sebastien Pili-Floury, Raphaël Cinotti, Marie-Héléne Po, Joe de Keizer, Soizic Gergaud, Thomas Gaillard, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, 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), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Anesthésie et Réanimation [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Anesthésie-Réanimation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Nice (CHU Nice), Aix Marseille Université (AMU), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Hôpital de Hautepierre [Strasbourg], Université de Strasbourg - Faculté de Médecine [Strabourg] (FMTS), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire [Grenoble] (CHU), Service de soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Clermont-Ferrand, Service d'anesthésie - réanimation chirurgicale [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), AGATE Study Group: Guillaume Besch, Bélaid Bouhemad, Elodie Caumon, Thien-Nga Chamaraux-Tran, Raphael Cinotti, Thomas Gaillard, Soizic Gergaud, Marc Ginet, Philippe Gouin, Florian Grimaldi, Pierre-Gildas Guitard, Emmanuelle Hammad, Lilit Kelesyan, Sébastien Leduc, Maxime Leger, Pierre-Olivier Ludes, Laurent Muler, Abdelouaid Nadji, Catherine Paugam-Burtz, Marie-Héléne Po, Hervé Quintard, Claire Roger, Antoine Roquilly, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Chauzy, Alexia, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Critical Care and Intensive Care Medicine, Tracheal tube, 03 medical and health sciences, 0302 clinical medicine, Intensive care, ventilator-associated, medicine, pneumonia, 030212 general & internal medicine, education, intensive care, Mechanical ventilation, education.field_of_study, business.industry, Tracheal intubation, Ventilator-associated pneumonia, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, infection, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, 030228 respiratory system, Anesthesia, Cuff, tracheal cuff pressure, Injury Severity Score, Cardiology and Cardiovascular Medicine, business
Abstract

International audience; Background: Ventilator-associated pneumonia (VAP) is the most frequent health care-associated infection in severely ill patients, and aspiration of contaminated oropharyngeal content around the cuff of the tracheal tube is the main route of contamination.Research question: Is continuous regulation of tracheal cuff pressure using a pneumatic device superior to manual assessment three times daily using a portable manometer (routine care) in preventing VAP in patients with severe trauma?Study design and methods: In this open-label, randomized controlled superiority trial conducted in 13 French ICUs, adults (age ≥ 18 years) with severe trauma (Injury Severity Score > 15) and requiring invasive mechanical ventilation for ≥ 48 h were enrolled. Patients were randomly assigned (1:1) via a secure Web-based random number generator in permuted blocks of variable sizes to one of two groups according to the method of tracheal cuff pressure control. The primary outcome was the proportion of patients developing VAP within 28 days following the tracheal intubation, as determined by two assessors masked to group assignment, in the modified intention-to-treat population. This study is closed to new participants.Results: A total of 434 patients were recruited between July 31, 2015, and February 15, 2018, of whom 216 were assigned to the intervention group and 218 to the control group. Seventy-three patients (33.8%) developed at least one episode of VAP within 28 days following the tracheal intubation in the intervention group compared with 64 patients (29.4%) in the control group (adjusted subdistribution hazard ratio, 0.96; 95% CI, 0.76-1.20; P = .71). No serious adverse events related to the use of the pneumatic device were noted.Interpretation: Continuous regulation of cuff pressure of the tracheal tube using a pneumatic device was not superior to routine care in preventing VAP in patients with severe trauma.Clinical trial registration: ClinicalTrials.gov; No.: NCT02534974; URL: www.clinicaltrials.gov.

Published
2021
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3. Surgical Support for Severe COVID-19 Patients: A Retrospective Cohort Study in a French High-Density COVID-19 Cluster

Author

Eric Noll, Philippe Liverneaux, Julien Pottecher, Pierre Diemunsch, Girish P. Joshi, Pierre Olivier Ludes, Anaëlle Tchentcheli, Christophe Muccioli, Philippe Clavert, Sophie Diemunsch, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Critical Care, Coronavirus disease 2019 (COVID-19), Advisory Committees, Population, surgical non-technical skills, High density, Disease cluster, intensive care unit, 01 natural sciences, law.invention, 03 medical and health sciences, 0302 clinical medicine, Phone, law, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, View from IRCAD, education, Aged, Retrospective Studies, education.field_of_study, business.industry, 010102 general mathematics, COVID-19, Retrospective cohort study, [PHYS.MECA]Physics [physics]/Mechanics [physics], Middle Aged, medicine.disease, University hospital, Intensive care unit, surgical technical skills, Feasibility Studies, Female, Surgery, France, Medical emergency, business, Surgery Department, Hospital
Abstract

Background. The COVID-19 epidemic has resulted in a massive surge in the need for intensive care unit (ICU) care. To avoid being overwhelmed, hospitals had to adapt and support the ICU teams in structured ICU care including involving surgical teams. This work aims at describing the collaborative efforts between the ICU care team and the Surgical Task Force (STF) during a surge of ICU activity in a University Hospital in a French high-density COVID-19 cluster. Study Design. This retrospective single center study analyzed the STF workflow and the ICU population. The study included 55 patients hospitalized in our ICU, ICU-converted step-down units, and post-anesthesia care units. The primary measure was the global daily STF activity. The secondary measure was the daily activity for each of the 5 tasks accomplished by the STF. Results. The STF attempted 415 phone calls for 55 patients’ families, 237 mobilizations of patients requiring prone positions, follow-up of 20 patients requiring medevac, and contribution to ethical discussion for 2 patients. The mean (SD) daily number of successful phones calls, ethical discussions, mobilizations of patients requiring prone positions and medevac follow-up were 18 (7), .1 (.4), 10 (7), and 2 (3), respectively. No actions for discharge summaries writing were required. The maximum number of daily mobilizations for patients requiring prone positions was 25. The maximum number of daily attempted phone calls and successful phone calls were 37 and 26, respectively. Conclusion. Surgeons’ technical and nontechnical skills represented an effective support for ICU teams during the COVID-19 pandemic.

Published
2020
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4. Extracorporeal Membrane Oxygenation for Critically Ill Patients with COVID-19–related Acute Respiratory Distress Syndrome: Worth the Effort?

Author

Pierre Olivier Ludes, Pierre Emmanuel Falcoz, Francis Schneider, Ferhat Meziani, Stéphanie Perrier, Anne Olland, Marc Puyraveau, P.M. Mertes, Julie Helms, and Alexandra Monnier

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, ARDS, Coronavirus disease 2019 (COVID-19), biology, Critically ill, business.industry, medicine.medical_treatment, MEDLINE, Acute respiratory distress, Critical Care and Intensive Care Medicine, medicine.disease, biology.organism_classification, Pandemic, Correspondence, medicine, Extracorporeal membrane oxygenation, Intensive care medicine, business, Betacoronavirus
Published
2020

5. Mécanismes immunologiques post-traumatiques : de l’attrition tissulaire à la défaillance d’organes

Author

Pierre-Olivier Ludes, Eric Noll, and Julien Pottecher

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030208 emergency & critical care medicine
Abstract

Resume Le traumatisme severe reste greve d’une mortalite et d’une morbidite particulierement elevees, au point de constituer la premiere cause d’annees de vie perdues ponderees par la qualite (QALYs). Si le choc hemorragique et les lesions severes du systeme nerveux central restent les deux premieres causes de mortalite precoce apres un traumatisme grave, 25 a 30 % des deces post-traumatiques surviennent plus tard en reanimation des suites de defaillances d’organes (secondary organ failures ou SOF). Ces SOF font intervenir principalement deux mecanismes physiopathologiques : 1) une reaction exacerbee de l’immunite innee, dont l’intensite est proportionnelle a l’etendue des lesions traumatiques et aux concentrations d’alarmines circulantes (aussi nommees Damage-Associated Molecular Patterns ou DAMPs). Ces alarmines de natures diverses (complement, polynucleaires neutrophiles et leur arsenal proteolytique) vont directement leser les cellules endotheliales et epitheliales des organes vitaux (poumon, foie, rein) aboutissant a des syndromes qui menacent le pronostic vital (ALI, ARDS, AKI, vasoplegie et coagulopathie post-traumatiques…) A cote des lesions tissulaires traumatiques directement liees au stress mecanique et a la destruction des barrieres macro- et microscopiques, le choc hemorragique constitue un facteur aggravant et decuple la liberation de DAMPs par un mecanisme d’hypoperfusion tissulaire et cellulaire. Il en va de meme pour les interventions chirurgicales extensives lorsqu’elles sont realisees en phase inflammatoire a un moment ou elles amplifient la reponse immunitaire innee ; 2) une immunosuppression post-traumatique, qui s’initie dans les suites immediates du traumatisme mais dont les consequences (anergie immunitaire, desactivation monocytaire, reponse de type Th2, reactivations virales, susceptibilite accrue aux infections bacteriennes et fongiques) n’apparaissent qu’apres quelques jours et confinent le patient dans un etat persistant d’inflammation, d’immunosuppression et de catabolisme (PICS syndrome). En plus de conforter le bien-fonde de doctrines deja adoptees (parfois de facon empirique) sur des bases cliniques (damage-control surgery, reanimation hemostatique, administration precoce d’acide tranexamique), ces decouvertes recentes laissent entrevoir des voies therapeutiques nouvelles, ciblant les DAMPs eux-memes (dornase alfa), leurs recepteurs (cyclosporine H) et l’arsenal des polynucleaires ou modulant l’activite de l’immunite innee (glucocorticoides, IFNγ, GM-CSF).

Published
2020
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6. Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study

Author

François Danion, Céline Duval, François Séverac, Philippe Bachellier, Ermanno Candolfi, Vincent Castelain, Raphaël Clere-Jehl, Julie Denis, Laurence Dillenseger, Eric Epailly, Justine Gantzer, Blandine Guffroy, Yves Hansmann, Jean-Etienne Herbrecht, Valérie Letscher-Bru, Pierre Leyendecker, Pauline Le Van Quyen, Pierre-Olivier Ludes, Guillaume Morel, Bruno Moulin, Catherine Paillard, Benjamin Renaud-Picard, Anne-Claude Roche, Marcela Sabou, Francis Schneider, Morgane Solis, Emilie Talagrand-Reboul, Francis Veillon, Marie-Pierre Ledoux, Célestine Simand, Raoul Herbrecht, Pietro Francesco Addeo, Dominique Astruc, Mathieu Baldacini, Karin Bilger, Marie-Pierrette Chenard, Olivier Collange, Tristan Degot, Nadia Dhif, Elise Dicop, Samira Fafi-Kremer, Luc-Matthieu Fornecker, Charline Fuseau, Max Guillot, Mary-Line Harlay, Ralf Janssen-Langenstein, Benoît Jaulhac, Charlotte Kaeuffer, Romain Kessler, Christine Kummerlen, Annegret Laplace, Anne Launoy, Bruno Lioure, Hamid Merdji, Paul-Michel Mertes, Shanti Natarajan-Ame, Gabriel Nisand, Michele Porzio, Julien Pottecher, Maleka Schenck-Dhif, Cécile Sonntag, Elise Toussaint, Anne Zilliox, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Cancérologie de Strasbourg Europe (ICANS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions Hôte pathogène, Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nanomédecine Régénérative (NanoRegMed), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte

Subjects
0301 basic medicine, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Coinfections, Computed tomography, Aspergillosis, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Invasive fungal infections, Internal medicine, medicine, Humans, Leukaemia, 030212 general & internal medicine, Mortality, Child, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, Retrospective Studies, Aspergillus species, Aged, 80 and over, medicine.diagnostic_test, business.industry, Coinfection, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, medicine.disease, 3. Good health, Transplantation, Infectious Diseases, Fungal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Risk factors, Child, Preschool, Hematologic Neoplasms, business
Abstract

Objectives To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. Patients and methods We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. Results Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8–43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2–4.4)), other haematological malignancies (OR 2.1 (1.2–3.8)), other underlying diseases (OR 4.3 (1.4–13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2–3.0)), fever (OR 2.4 (1.5–4.1)), tracheal intubation (OR 2.6 (1.5–4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1–6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3–3.7) and OR 2.2 (1.2–4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1–1.9), p Conclusions Coinfections are frequent in IA patients and are associated with higher mortality.

Published
2021
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7. Combining predictive markers for severe COVID-19: Torquetenovirus DNA load and SARS-CoV-2 RNAemia

Author

Morgane Solis, Floriane Gallais, Sabrina Garnier-Kepka, Nicolas Lefebvre, Ilies Benotmane, Pierre-Olivier Ludes, Vincent Castelain, Ferhat Meziani, Sophie Caillard, Olivier Collange, and Samira Fafi-Kremer

Subjects
Infectious Diseases, COVID-19 Testing, SARS-CoV-2, Virology, COVID-19, Humans, RNA, Viral, DNA, Antibodies, Viral
Abstract

SARS-CoV-2 is the cause of worldwide COVID-19, which severity has been linked to the immune and inflammatory response. Here, we investigate Torquetenovirus (TTV) DNA load - a marker reflecting the intensity of the overall immune response - as well as SARS-CoV-2 RNAemia and IgM/IgG antibodies in COVID-19-positive patients.Two hundred and fifteen COVID-19-positive patients were enrolled, including 87 severe cases and 128 mild-moderate cases. SARS-CoV-2 RNAemia and IgM/IgG antibodies, as well as TTV DNA loads, were measured on longitudinal plasma samples.The rate of severe cases was higher in patients with low TTV DNA load in plasma considering a threshold of 700 copies/mL. In severe patients, SARS-CoV-2 RNAemia positivity rates were higher than those in mild-moderate cases at any timepoint. When combined, TTV DNA load and SARS-CoV-2 RNAemia allowed to predict the outcome of COVID-19 infection, with a higher risk (HR=12.4) of ICU admission in patients with low TTV DNA load and positive SARS-CoV-2 RNAemia.TTV DNA load and SARS-CoV-2 RNAemia may be effective, non-invasive markers reflecting disease severity and poor outcome that could be conveniently measured in a clinical laboratory setting, as soon as COVID-19 diagnosis is made.

Published
2021

8. A novel, automated, quantification of abnormal lung parenchyma in patients with COVID-19 infection: Initial description of feasibility and association with clinical outcome

Author

Luc Soler, Julien Pottecher, Nicolas Meyer, Francis Veillon, Francis Schneider, Bernard Goichot, Elliott Bennett-Guerrero, Eric Noll, Pierre Diemunsch, Mickaël Ohana, Pierre-Olivier Ludes, Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, Nouvel Hôpital Civil de Strasbourg, Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire de pharmacologie et de toxicologie neurocardiovasculaire (LPTNC), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), and Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, ARDS, Time Factors, Supine position, Intraclass correlation, Critical Care and Intensive Care Medicine, computer.software_genre, Severity of Illness Index, Severity assessment, Automation, 0302 clinical medicine, Voxel, Supine Position, Medicine, Lung volumes, 030212 general & internal medicine, Lung, Infectious disease, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, medicine.anatomical_structure, Original Article, Female, Lung Volume Measurements, Algorithms, 03 medical and health sciences, Severity of illness, Humans, Retrospective Studies, business.industry, Reproducibility of Results, COVID-19, 030208 emergency & critical care medicine, Retrospective cohort study, CT-scan, Triage, medicine.disease, Anesthesiology and Pain Medicine, Feasibility Studies, Tomography, X-Ray Computed, business, Nuclear medicine, computer, Software, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objective: Ground-glass opacities are the most frequent radiologic features of COVID-19 patients. We aimed to determine the feasibility of automated lung volume measurements, including ground-glass volumes, on the CT of suspected COVID-19 patients. Our goal was to create an automated and quantitative measure of ground-glass opacities from lung CT images that could be used clinically for diagnosis, triage and research. Design: Single centre, retrospective, observational study. Measurements: Demographic data, respiratory support treatment (synthetised in the maximal respiratory severity score) and CT-images were collected. Volume of abnormal lung parenchyma was measured with conventional semi-automatic software and with a novel automated algorithm based on voxels X-Ray attenuation. We looked for the relationship between the automated and semi-automated evaluations. The association between the ground-glass opacities volume and the maximal respiratory severity score was assessed. Main results: Thirty-seven patients were included in the main outcome analysis. The mean duration of automated and semi-automated volume measurement process were 15 (2) and 93 (41) min, respectively (p=8.05*10-8). The intraclass correlation coefficient between the semi-automated and automated measurement of ground-glass opacities and restricted normally aerated lung were both superior to 0.99. The association between the automated measured lung volume and the maximal clinical severity score was statistically significant for the restricted normally aerated (p=0.0097, effect-size: -385mL) volumes and for the ratio of ground-glass opacities/restricted normally aerated volumes (p=0.027, effect-size: 3.3). Conclusion: The feasibility and preliminary validity of automated impaired lung volume measurements in a high-density COVID-19 cluster was confirmed by our results. Keywords: ARDS; COVID-19; CT-scan; Infectious disease; Severity assessment; Triage.

Published
2021
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9. Bayesian predictive probabilities a good way to monitor clinical trials

Author

Nicolas Meyer, Eric Noll, Pierre Olivier Ludes, David Ferreira, Klaus D. Torp, Pierre Diemunsch, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Mitochondrie, stress oxydant et protection musculaire (MSP), and Université de Strasbourg (UNISTRA)

Subjects
Bayesian probability, Posterior probability, Laryngoscopes, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Frequentist inference, Interim, Statistics, Humans, Medicine, Equivalence (measure theory), Randomized Controlled Trials as Topic, Models, Statistical, Laryngoscopy, business.industry, Bayes Theorem, Equipment Design, Bayesian statistics, Treatment Outcome, Anesthesiology and Pain Medicine, Research Design, Sample size determination, Data Interpretation, Statistical, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Early Termination of Clinical Trials, business
Abstract

Background Bayesian methods, with the predictive probability (PredP), allow multiple interim analyses with interim posterior probability (PostP) computation, without the need to correct for multiple looks at the data. The objective of this paper was to illustrate the use of PredP by simulating a sequential analysis of a clinical trial. Methods We used data from the Laryngobloc trial that planned to include 480 patients to demonstrate the equivalence of success between a laryngoscopy performed with the Laryngobloc® device and a control device. A crossover Bayesian design was used. The success rates of the two laryngoscopy devices were compared. Interim analyses, computed from random numbers of subjects, were simulated. Results The PostP of equivalence rapidly reached the predefined bound of 0.95. The PredP computed with an equivalence margin of 10% reached the efficacy bound between 352 and 409 of the 480 included patients. If a frequentist analysis had been made on the basis of 217 out of 480 subjects, the study would have been prematurely stopped for equivalence. The PredP indicated that this result was nonetheless unstable and that the equivalence was, thus far, not guaranteed. Conclusions Based on these interim analyses, we can conclude with a sufficiently high probability that the equivalence would have been met on the primary outcome before the predetermined end of this particular trial. If a Bayesian approach using PredP had been used, it would have allowed an early termination of the trial by reducing the calculated sample size by 15–20%.

Published
2021
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10. Validation of the translated Quality of Recovery-15 questionnaire in a French-speaking population

Author

Pierre-Olivier Ludes, François Lefebvre, Pierre Diemunsch, François Demumieux, Marko Lujic, Eric Noll, Elliott Bennett-Guerrero, Stony Brook University [SUNY] (SBU), and State University of New York (SUNY)

Subjects
medicine.medical_specialty, Psychometrics, Health Status, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Population, 03 medical and health sciences, Patient safety, 0302 clinical medicine, 030202 anesthesiology, Surveys and Questionnaires, medicine, Humans, Translations, Quality (business), education, Reliability (statistics), media_common, Protocol (science), education.field_of_study, Perioperative medicine, business.industry, Reproducibility of Results, Perioperative, Length of Stay, Clinical trial, Anesthesiology and Pain Medicine, Anesthesia Recovery Period, Quality of Life, Physical therapy, France, business
Abstract

Quality of recovery is an important component of perioperative health status. The 15-item Quality of Recovery (QoR-15) scale is a validated multidimensional questionnaire that measures postoperative quality of recovery. The aim of this study was to translate and assess the psychometric properties of a French version of the QoR-15 scale (QoR-15F) to measure postoperative recovery in French-speaking patients.After translation into French of the original English version of the QoR-15 scale, psychometric validation of the QoR-15F scale to measure postoperative quality of recovery was performed. This psychometric validation included validity, reliability, responsiveness, and feasibility. The QoR-15F scale was administered before operation and on Postoperative day 1 in French-speaking patients. Patient-perceived global recovery assessment was measured at Postoperative day 1 using a VAS.We enrolled 150 patients, and 144 completed the study protocol. The completion rate of administered questionnaires was 100%. Pearson (r) correlation between postoperative QoR-15F and the global recovery assessment by the patient was 0.60 (P0.0001). As expected, there was a significant negative correlation between QoR-15F score and duration of surgery (r=-0.29; P0.01), duration of PACU stay (r=-0.21; P=0.01), and duration of hospital stay (r=-0.34; P0.01). Cronbach's alpha was 0.81, split-half alpha was 0.83, and the global test-retest intra-class coefficient was 0.98 (0.95-0.99).The QoR-15F is a valid and reliable tool to measure postoperative quality of recovery in French-speaking patients. The psychometric properties to measure postoperative quality of recovery were similar to the seminal English version.NCT03578068.

Published
2020
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11. Continuous 4 Percent Albumin Versus Intermittent 20 Percent Albumin in Adults with Septic Shock: A Prospective, Phase IV, Open-label Randomized Trial

Author

Thibaut Fabacher, Pierre-Olivier Ludes, Guillaume Morel, Vincent Castelain, Antoine Poidevin, Anne-Florence Dureau, Marie-Hélène Metz-Boutigue, Nicolas Meyer, Bernard Senger, Francis Schneider, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Strasbourg, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte

Subjects
Randomization, Serum albumin, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, law.invention, Norepinephrine (medication), Randomized controlled trial, law, medicine, Outcome, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, Septic shock, Albumin, Care-related Infection, General Medicine, medicine.disease, Intensive care unit, Septic Shock, Oxidative Stress, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Anesthesia, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SOFA score, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Whether a specific way of infusing albumin affects outcome in patients with major oxidative stress remains uncertain. To determine whether outcome measurements (survival, organ failure and care-related infections) are different according to different regimens of albumin infusion, we conducted a phase IV, randomized, open-label trial to compare the effects of continuous infusion of 4 percent albumin versus intermittent 20 percent albumin on outcome measurements in three third level-hospital intensive care unit (ICU) patients with septic shock. We randomly assigned 125 consecutive patients with septic shock when serum albumin became

Published
2020
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12. Association between hypo- and hyperkalemia and outcome in acute heart failure patients : the role of medications

Author

Christian Mueller, Jin-Joo Park, Johan Lassus, Mikhail Kosiborod, Aldo P. Maggioni, Shiro Ishihara, Patrick Plaisance, Ziad A. Massy, Jiri Parenica, Pierre-Olivier Ludes, Matthieu Legrand, Naoki Sato, Jindřich Špinar, Patrick Rossignol, Òscar Miró, Khalid F. AlHabib, Veli-Pekka Harjola, Dong-Ju Choi, Alain Cohen-Solal, Alexandre Mebazaa, Etienne Gayat, Enrique Fairman, F. Peacock, HUS Heart and Lung Center, Clinicum, Kardiologian yksikkö, Department of Medicine, University of Helsinki, and HUS Emergency Medicine and Services

Subjects
Male, Time Factors, HF, Hyperkalemia, Hemodynamics, 030204 cardiovascular system & hematology, urologic and male genital diseases, GUIDELINES, chemistry.chemical_compound, 0302 clinical medicine, ANTAGONISTS, Prospective Studies, 030212 general & internal medicine, Aged, 80 and over, Hazard ratio, General Medicine, Middle Aged, SPIRONOLACTONE, Hypokalemia, 3. Good health, Europe, Survival Rate, Treatment Outcome, HOSPITALIZATION, Acute Disease, Cohort, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Renal failure, Adrenergic beta-Antagonists, Renal function, Heart failure, 03 medical and health sciences, Internal medicine, medicine, Humans, COHORT, Aged, business.industry, MORTALITY, nutritional and metabolic diseases, medicine.disease, United States, chemistry, 3121 General medicine, internal medicine and other clinical medicine, Spironolactone, Potassium, B-blockers, business, REDUCED EJECTION FRACTION, SERUM POTASSIUM LEVELS, Biomarkers, Follow-Up Studies
Abstract

Background The interaction between chronic medications on admission and the association between serum potassium level and outcome in patients with acute heart failure (AHF) are unknown. Methods Observational intercontinental study of patients admitted with AHF. 15954 patients were included from 12 cohorts in 4 continents. Main outcome was 90-day mortality. Clinical presentation (medication use, hemodynamics, comorbidities), demographic, echocardiographic, and biochemical data on admission were recorded prospectively in each cohort, with prospective adjudication of outcomes. Results Positive and negative linear relationships between 90-day mortality and sK+ above 4.5 mmol/L (hyperkalemia) and below 3.5 mmol/L (hypo-kalemia) were observed. Hazard ratio for death was 1.46 [1.34-1.58] for hyperkalemia and 1.22 [1.06-1.40] for hypokalemia. In a fully adjusted model, only hyperkalemia remained associated with mortality (HR 1.03 [1.02-1.04] for each 0.1 mmol/l change of sK+ above 4.5 mmol/L). Interaction tests revealed that the association between hyperkalemia and outcome was significantly affected by chronic medications. The association between hyperkalemia and mortality was absent for patients treated with beta blockers and in those with preserved renal function. Conclusions In patients with AHF, sK+ > 4.5 mmol/L appears to be associated with 90-day mortality. B-blockers have potentially a protective effect in the setting of hyperkalemia.

Published
2018

13. The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin

Author

A. Mark Richards, Philippe Bizouarn, Pierre-Olivier Ludes, David M. Smadja, Alain Cohen-Solal, Jagmeet P. Singh, Chris J. Pemberton, Nicolas Vodovar, Bernard Cholley, Alexandre Mebazaa, Julien Pottecher, Pamela Ballan, Malha Sadoune, Nicolas Gendron, Jane-Lise Samuel, Hélène Nougué, Jackie Szymonifka, Quynh A. Truong, Jean-Marie Launay, Mattia Arrigo, Christian Latremouille, and Alain Carpentier

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Systole, Heart, Artificial, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Natriuretic Peptide, Brain, medicine, Natriuretic peptide, Humans, 030212 general & internal medicine, Postoperative Period, RNA, Messenger, Natriuretic Peptides, Neprilysin, Coronary sinus, Geographic difference, Aged, Heart Failure, business.industry, Heart, Venous blood, Middle Aged, medicine.disease, Brain natriuretic peptide, Peptide Fragments, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Signal Transduction
Abstract

Aims Heart failure (HF) is accompanied by major neuroendocrine changes including the activation of the natriuretic peptide (NP) pathway. Using the unique model of patients undergoing implantation of the CARMAT total artificial heart and investigating regional differences in soluble neprilysin (sNEP) in patients with reduced or preserved systolic function, we studied the regulation of the NP pathway in HF. Methods and results Venous blood samples from two patients undergoing replacement of the failing ventricles with a total artificial heart were collected before implantation and weekly thereafter until post-operative week 6. The ventricular removal was associated with an immediate drop in circulating NPs, a nearly total disappearance of circulating glycosylated proBNP and furin activity and a marked decrease in sNEP. From post-operative week 1 onwards, NP concentrations remained overall unchanged. In contrast, partial recoveries in glycosylated proBNP, furin activity, and sNEP were observed. Furthermore, while in patients with preserved systolic function (n = 6), sNEP concentrations in the coronary sinus and systemic vessels were similar (all P > 0.05), in patients with reduced left-ventricular systolic function, sNEP concentration, and activity were ∼three-fold higher in coronary sinus compared to systemic vessels (n = 21, all P Conclusion The heart plays a pivotal role as a regulator of the endocrine response in systolic dysfunction, not only by directly releasing NPs but also by contributing to circulating sNEP, which in turn determines the bioavailability of other numerous vasoactive peptides.

Published
2017

14. Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis

Author

Bernard Geny, Quentin Maestraggi, Pierre Diemunsch, Julien Pottecher, Thiên-Nga Chamaraux-Tran, Raphaël Clere-Jehl, Pierre-Olivier Ludes, Benjamin Lebas, Francis Schneider, univOAK, Archive ouverte, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Hautepierre [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Mitochondrie, stress oxydant et protection musculaire (MSP), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Nouvel Hôpital Civil de Strasbourg

Subjects
0301 basic medicine, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Article Subject, Multiple Organ Failure, lcsh:Medicine, Review Article, Biology, Disease-Free Survival, General Biochemistry, Genetics and Molecular Biology, Sepsis, Pathogenesis, 03 medical and health sciences, medicine, Humans, Lymphocytes, Muscle, Skeletal, Wasting, General Immunology and Microbiology, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], Septic shock, lcsh:R, Organ dysfunction, Muscle weakness, Skeletal muscle, General Medicine, medicine.disease, Shock, Septic, Mitochondria, Survival Rate, Intensive Care Units, 030104 developmental biology, medicine.anatomical_structure, Shock (circulatory), Immunology, medicine.symptom
Abstract

Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called “cytopathic hypoxia,” perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system (“immunoparalysis”) translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

Published
2017
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15. Tuméfactions cervico-faciales per et post-opératoires immédiates en chirurgie bucco-dentaire

Author

Fabien Bornert, Caroline Schellenberger, Bartholomeus Calon, Pierre Olivier Ludes, Catherine-Isabelle Gros, and Ahmed Feki

Subjects
Periodontics, Dentistry (miscellaneous), Oral Surgery
Abstract

Il n’est pas rare que le chirurgien-dentiste soit confronte a une tumefaction cervico-faciale (TCF) per ou post-operatoire immediate. Bien qu’il s’agisse generalement d’un phenomene benin, il est souvent source d’inquietude pour le praticien et le patient. Une revue de litterature se propose de presenter les differentes etiologies de tumefactions cervico-faciales per et post-operatoires, et d’apporter les elements pratiques pour leur diagnostic. Parmi ces tumefactions, l’emphyseme sous-cutane est un evenement banal, benin et facile a diagnostiquer mais souvent meconnu, ce dont temoigne le nombre de cas rapportes. Plus rares, mais potentiellement graves, il convient egalement de citer l’hematome du plancher buccal et l’angiœdeme qui peuvent etre la consequence du geste bucco-dentaire ou des medicaments. Dans ce cadre, il est en effet necessaire de savoir reconnaitre les prodromes d’une detresse respiratoire. Enfin, la fasciite necrosante cervico-faciale se doit d’etre reconnue tot du fait de son extreme gravite, d’autant que son incidence parait croissante. Un tableau recapitulatif presente les principales causes de TCF per et post-operatoires apres chirurgie dentaire, leur chronologie, leurs principaux symptomes et les mesures therapeutiques a mettre en œuvre.

Published
2013
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