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1. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

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Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia

Subjects
HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Published
2024
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2. ICU admission for solid cancer patients treated with immune checkpoint inhibitors

Author

Anne-Claire Toffart, Anne-Pascale Meert, Florent Wallet, Aude Gibelin, Olivier Guisset, Frédéric Gonzalez, Amélie Seguin, Achille Kouatchet, Myriam Delaunay, Didier Debieuvre, Boris Duchemann, Gaëlle Rousseau-Bussac, Martine Nyunga, David Grimaldi, Albrice Levrat, Elie Azoulay, and Virginie Lemiale

Subjects
Solid tumor, Immune checkpoint inhibitor, Intensive care, Immune-related adverse event, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. Methods This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. Results 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered “likely” associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2–3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13–18.90, and OR = 3.66, 95% CI 1.33–10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19–9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission “likely” related to irAE. Three patients were subsequently treated with immunosuppressants. Conclusion IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge.

Published
2023
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3. Spontaneous pneumomediastinum: a surrogate of P-SILI in critically ill COVID-19 patients

Author

Alexandre Elabbadi, Tomas Urbina, Enora Berti, Damien Contou, Gaëtan Plantefève, Quintana Soulier, Audrey Milon, Guillaume Carteaux, Guillaume Voiriot, Muriel Fartoukh, and Aude Gibelin

Subjects
Pneumomediastinum, Coronavirus disease 2019, Pneumonia, Intensive care unit, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Spontaneous pneumomediastinum (SP) has been described early during the COVID-19 pandemic in large series of patients with severe pneumonia, but most patients were receiving invasive mechanical ventilation (IMV) at the time of SP diagnosis. In this retrospective multicenter observational study, we aimed at describing the prevalence and outcomes of SP during severe COVID-19 with pneumonia before any IMV, to rule out mechanisms induced by IMV in the development of pneumomediastinum. Among 549 patients, 21 patients (4%) developed a SP while receiving non-invasive respiratory support, after a median of 6 days [4–12] from ICU admission. The proportion of patients requiring IMV was similar. However, the time to tracheal intubation was longer in patients with SP (6 days [5–13] vs. 2 days [1–4]; P = 0.00002), with a higher first-line use of non-invasive ventilation (n = 11; 52% vs. n = 150; 28%; P = 0.02). The 21 patients who developed a SP had persisting signs of severe lung disease and respiratory failure with lower ROX index between ICU admission and occurrence of SP (3.94 [3.15–5.55] at admission vs. 3.25 [2.73–4.02] the day preceding SP; P = 0.1), which may underline potential indirect signals of Patient-self inflicted lung injury (P-SILI). In this series of critically ill COVID-19 patients, the prevalence of SP without IMV was not uncommon, affecting 4% of patients. They received more often vasopressors and had a longer ICU length of stay, as compared with their counterparts. One pathophysiological mechanism may potentially be carried out by P-SILI related to a prolonged respiratory failure, as underlined by a delayed use of IMV and the evolution of the ROX index between ICU admission and the day preceding SP.

Published
2022
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4. Identification of bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome in critically ill COVID-19 patients

Author

Guillaume Voiriot, Karim Dorgham, Guillaume Bachelot, Anne Fajac, Laurence Morand-Joubert, Christophe Parizot, Grigorios Gerotziafas, Dominique Farabos, Germain Trugnan, Thibaut Eguether, Clarisse Blayau, Michel Djibré, Alexandre Elabbadi, Aude Gibelin, Vincent Labbé, Antoine Parrot, Matthieu Turpin, Jacques Cadranel, Guy Gorochov, Muriel Fartoukh, and Antonin Lamazière

Subjects
Medicine, Science
Abstract

Abstract The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30–4.41] vs. 9.53 [2.56–19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.

Published
2022
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5. Causes of acute respiratory failure in patients with small-vessel vasculitis admitted to intensive care units: a multicenter retrospective study

Author

Aude Gibelin, Guillaume Dumas, Sandrine Valade, Marc Pineton de Chambrun, François Bagate, Mathilde Neuville, Francis Schneider, Loredana Baboi, Matthieu Groh, Jean-Herlé Raphalen, Jean-Daniel Chiche, Nicolas De Prost, Charles-Edouard Luyt, Claude Guérin, Eric Maury, Etienne de Montmollin, Alexandre Hertig, Antoine Parrot, Raphaël Clere-Jehl, and Muriel Fartoukh

Subjects
Vasculitis, Diffuse alveolar hemorrhage, Intensive care, Acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Rationale Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion. Methods A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv. Results During the study period, 121 patients [62 (50–75) years; 62% male; median SAPSII and SOFA scores 39 (27–52) and 6 (4–8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n = 47, 39%), whereas the main non-immune cause was pulmonary infection (n = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p = 0.053). Among patients with a known Svv (n = 70), immunosuppression [OR 9.41 (1.52–58.3); p = 0.016], and a low vasculitis activity score [0.84 (0.77–0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure. Conclusions An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies.

Published
2021
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6. Pain and dyspnea control during awake fiberoptic bronchoscopy in critically ill patients: safety and efficacy of remifentanil target-controlled infusion

Author

Margot Caron, Antoine Parrot, Alexandre Elabbadi, Sophie Dupeyrat, Matthieu Turpin, Thomas Baury, Sacha Rozencwajg, Clarisse Blayau, Jean-Pierre Fulgencio, Aude Gibelin, Pierre-Yves Blanchard, Séverine Rodriguez, Daisy Daigné, Marie-Cécile Allain, Muriel Fartoukh, and Tài Pham

Subjects
Flexible fiberoptic bronchoscopy, Remifentanil target-controlled infusion, Intensive care unit, Tolerance, Comfort, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Purpose Flexible fiberoptic bronchoscopy is frequently used in intensive care unit, but is a source of discomfort, dyspnea and anxiety for patients. Our objective was to assess the feasibility and tolerance of a sedation using remifentanil target-controlled infusion, to perform fiberoptic bronchoscopy in awake ICU patients. Materials, patients and methods This monocentric, prospective observational study was conducted in awake patients requiring fiberoptic bronchoscopy. In accordance with usual practices in our center, remifentanil target-controlled infusion was used under close monitoring and adapted to the patient’s reactions. The primary objective was the rate of successful procedures without additional analgesia or anesthesia. The secondary objectives were clinical tolerance and the comfort of patients (graded from “very uncomfortable” to “very comfortable”) and operators (numeric scale from 0 to 10) during the procedure. Results From May 2014 to December 2015, 72 patients were included. Most of them (69%) were hypoxemic and admitted for acute respiratory failure. No additional medication was needed in 96% of the patients. No severe side-effects occurred. Seventy-eight percent of patients described the procedure as “comfortable or very comfortable”. Physicians rated their comfort with a median [IQR] score of 9 [8–10]. Conclusion Remifentanil target-controlled infusion administered to perform awake fiberoptic bronchoscopy in critically ill patients is feasible without requirement of additional analgesics or sedative drugs. Clinical tolerance as well as patients’ and operators’ comfort were good to excellent. This technique could benefit patients’ experience.

Published
2021
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7. Infectious aetiologies of severe acute chest syndrome in sickle-cell adult patients, combining conventional microbiological tests and respiratory multiplex PCR

Author

Julien Lopinto, Alexandre Elabbadi, Aude Gibelin, Guillaume Voiriot, and Muriel Fartoukh

Subjects
Medicine, Science
Abstract

Abstract Acute chest syndrome (ACS) is the most serious complication of sickle cell disease. The pathophysiology of ACS may involve lower respiratory tract infection (LRTI), alveolar hypoventilation and atelectasis, bone infarcts-driven fat embolism, and in situ pulmonary artery thrombosis. One of the most challenging issues for the physicians is to diagnose LRTI as the cause of ACS. The use of a respiratory multiplex PCR (mPCR) for the diagnosis of LRTI has not been assessed in sickle-cell adult patients with ACS. To describe the spectrum of infectious aetiologies of severe ACS, using a diagnostic approach combining conventional tests and mPCR. A non-interventional monocenter prospective study involving all the consecutive sickle-cell adult patients with ACS admitted to the intensive care unit (ICU). Microbiological investigation included conventional tests and a nasopharyngeal swab for mPCR. Altogether, 36 patients were enrolled, of whom 30 (83%) had complete microbiological investigations. A bacterial microorganism, mostly Staphylococcus aureus (n = 8), was identified in 11 patients. There was no pneumonia-associated intracellular bacterial pathogen. A respiratory virus was identified in six patients. Using both conventional tests and nasopharyngeal mPCR, a microbiological documentation was obtained in half of adult ACS patients admitted to the ICU. Pyogenic bacteria, especially S. aureus, predominated.

Published
2021
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9. Randomised trial of first-line bronchial artery embolisation for non-severe haemoptysis of mild abundance

Author

Benjamin Planquette, Vincent Labbe, Tabassome Simon, Alexandra Rousseau, Jacques Cadranel, Antoine Khalil, Emmanuel Bergot, Gérard Zalcman, Guy Meyer, Philippe Cluzel, Vincent Jounieaux, Alexandre Demoule, Muriel Fartoukh, Aude Gibelin, Olivier Sanchez, THOMAS SIMILOWSKI, Claire Andrejak, Valérie Chabbert, Michel Djibré, Sophie Tuffet, Cendrine Godet, Sandrine Pontier-Marchandise, Julien Mayaux, Marc Sapoval, Vincent Le Pennec, Clarisse Blayau, Guillaume Voiriot, Alexandre Duguet, Hélène Prodanovik, Guillaume Briend, Anne Roche, Costantino Del Giudice, Olivier Pellerin, Marie-Pierre Revel, Patrick Courtheoux, Jean Claude Meurice, Elise Antone, and Alexandre Remond

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Background Whereas first-line bronchial artery embolisation (BAE) is considered standard of care for the management of severe haemoptysis, it is unknown whether this approach is warranted for non-severe haemoptysis.Research question To assess the efficacy on bleeding control and the safety of first-line BAE in non-severe haemoptysis of mild abundance.Study design and methods This multicentre, randomised controlled open-label trial enrolled adult patients without major comorbid condition and having mild haemoptysis (onset

Published
2021
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12. Tyrosine Kinase Inhibitors for Acute Respiratory Failure Because of Non–small-Cell Lung Cancer Involvement in the ICU

Author

Damien Contou, Frédéric Gonzalez, Anne-Sophie Moreau, M. Pineton de Chambrun, E. De Montmollin, Romain Persichini, Florent Wallet, Anne Oppenheimer, Aude Gibelin, N. Dufour, Jean-Damien Ricard, Stéphane Gaudry, Julien Mayaux, P. Jaubert, Y. Akrour, Annabelle Stoclin, Alexandre Lautrette, Y. Tandjaoui-Lambiotte, B. Duchemann, F. El Kouari, and Khalil Chaïbi

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, MEDLINE, Adenocarcinoma of Lung, Critical Care and Intensive Care Medicine, law.invention, Erlotinib Hydrochloride, Crizotinib, law, Carcinoma, Non-Small-Cell Lung, Internal medicine, Humans, Medicine, Acute respiratory failure, Lung cancer, Protein Kinase Inhibitors, Aged, Neoplasm Staging, Retrospective Studies, Acrylamides, Aniline Compounds, Noninvasive Ventilation, business.industry, Oxygen Inhalation Therapy, Gefitinib, Middle Aged, medicine.disease, Respiration, Artificial, Intensive care unit, ErbB Receptors, Survival Rate, Intensive Care Units, Female, Non small cell, Respiratory Insufficiency, Cardiology and Cardiovascular Medicine, business, Tyrosine kinase
Published
2022

13. Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Abdellatif Tazi, Aurélie Le Borgne-Krams, Marine Cachanado, Tabassome Simon, Sylvain Marchand-Adam, Morgane Didier, Lidwine Wemeau-Stervinou, Sandrine Hirschi, Frédéric Rivière, Arnaud Bourdin, François Lebargy, Stéphane Dominique, Aude Gibelin, Alexandre Chabrol, Tristan Dégot, Jacques Cadranel, Martine Reynaud-Gaubert, Marie-Pierre Debray, Sylvie Leroy, Frédéric Gagnadoux, Emmanuel Bergot, François-Xavier Blanc, Alexandra Rousseau, Raphael Borie, Pierre Yves Brillet, Guillaume Beltramo, Mallorie Kerjouan, Hilario Nunes, Olivia Freynet, Julie Traclet, Bruno Crestani, Anne-Sophie Gamez, Grégoire Prévot, Jean Pastré, Dominique Israel-Biet, Marie-Christine Dombret, Laurent Plantier, Cécile Chenivesse, Laurence Berard, Ana Nieves, Emmanuel Gomez, Dominique Valeyre, Stéphane Jouneau, Anne Gondouin, Elodie Blanchard, C. Launois, Nathalie Bautin, Jean-Marc Naccache, Vincent Cottin, Antoine Parrot, Philippe Bonniaud, Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Sorbonne Université (SU), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Avicenne [AP-HP], Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Saint-Antoine [AP-HP], 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), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, CHU Dijon, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Lille, Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Université de Lyon, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital JeanMinjoz, CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Rouen, Normandie Université (NU), CHU Tenon [AP-HP], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), CHU Montpellier, Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Roche, Ministere de la Sante et des Solidarites, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, education.field_of_study, Exacerbation, Cyclophosphamide, business.industry, [SDV]Life Sciences [q-bio], Population, medicine.disease, Placebo, 3. Good health, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, 030228 respiratory system, Methylprednisolone, Internal medicine, Clinical endpoint, Medicine, 030212 general & internal medicine, business, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract

Summary Background The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. Methods In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588 . Findings Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. Interpretation In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals.

Published
2022

14. Erratum to 'When targeted therapy for cancer leads to ICU admission. RETRO-TARGETICU multicentric study' [Bull. Cancer 109 (2022) 916–24]

Author

Anne-Pascale Meert, Anne-Claire Toffart, Muriel Picard, Paul Jaubert, Aude Gibelin, Philippe Bauer, Djamel Mokart, Andry Van De Louw, Stefan Hatzl, Gabriel Moreno-Gonzales, Gaelle Rousseau-Bussac, Fabrice Bruneel, Luca Montini, Anne-Sophie Moreau, Dorothée Carpentier, Amelie Seguin, Pleun Hemelaar, Elie Azoulay, and Virginie Lemiale

Subjects
Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Published
2023

15. Lower respiratory tract infection with Staphylococcus aureus in sickle-cell adult patients with severe acute chest syndrome - the STAPHACS Study

Author

Aline Santin, Julien Lopinto, Michel Djibré, Muriel Fartoukh, Anne Tristan, Guillaume Voiriot, François Lionnet, Alexandre Elabbadi, Etienne-Marie Jutant, Charlotte Verdet, François Vandenesch, and Aude Gibelin

Subjects
medicine.medical_specialty, Adult patients, business.industry, Cell, Hematology, medicine.disease, medicine.disease_cause, Acute chest syndrome, medicine.anatomical_structure, Staphylococcus aureus, Lower respiratory tract infection, Internal medicine, medicine, business
Published
2021

16. A Severe COVID-19 Pneumonia Revealing a Lepidic Adenocarcinoma: A Diagnostic Challenge during the Pandemic Period

Author

Guillaume Voiriot, Alexandre Elabbadi, Muriel Fartoukh, Aude Gibelin, Martine Antoine, Anne Fajac, Jacques Cadranel, Service d'Anesthésie réanimation [CHU Tenon], 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), Service d'Anatomie et cytologie pathologiques [CHU Tenon], Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Anatomie et cytologie pathologiques [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'anatomie pathologique [CHU Tenon], and Unité pneumologie et oncologie thoracique [CHU Tenon]

Subjects
Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Lung Neoplasms, Coronavirus disease 2019 (COVID-19), Period (gene), Adenocarcinoma, Acute respiratory failure, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pandemic, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Coronavirus disease 2019, business.industry, COVID-19, Middle Aged, medicine.disease, 3. Good health, Pneumonia, 030228 respiratory system, Female, Lepidic adenocarcinoma, business
Abstract

International audience

Published
2022

17. In-Hospital Mortality-Associated Factors in Patients With Thrombotic Antiphospholipid Syndrome Requiring ICU Admission

Author

Matthieu Jamme, Aude Gibelin, Auguste Dargent, Alain Combes, Rémi Coudroy, Marc Pineton de Chambrun, Jérôme Devaquet, Frédéric Pène, François-Michel Beloncle, Jean-Herlé Raphalen, Nicolas de Prost, Jérémie Lemarié, Pierre Trouiller, Elie Azoulay, Amélie Couteau-Chardon, Vincent Degos, Yacine Tandjaoui-Lambiotte, Julien Mayaux, Stanislas Ledochowski, Stanislas Faguer, Charles-Edouard Luyt, Samuel Gaugain, Zahir Amoura, Damien Contou, Steven Grangé, Romaric Larcher, Laurent Argaud, and Alexis Mathian

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Hazard ratio, Organ dysfunction, Retrospective cohort study, Critical Care and Intensive Care Medicine, Catastrophic antiphospholipid syndrome, medicine.disease, Intensive care unit, Thrombosis, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Antiphospholipid syndrome, law, Internal medicine, medicine, 030212 general & internal medicine, Simplified Acute Physiology Score, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract

Background The antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic events that can require ICU admission because of organ dysfunction related to macrovascular and/or microvascular thrombosis. Critically ill patients with thrombosis and APS were studied to gain insight into their prognoses and in-hospital mortality-associated factors. Methods This French national, multicenter, retrospective study included all patients with APS and any new thrombotic manifestations admitted to 24 ICUs (January 2000-September 2018). Results During the study period, 134 patients (male/female ratio, 0.4) with 152 APS episodes were admitted to the ICU (mean age at admission, 46.0 ± 15.1 years). In-hospital mortality of their 134 last episodes was 35 of 134 (26.1%). The Cox multivariable model retained certain factors (hazard ratio [95% CI]: age ≥ 40 years, 11.4 [3.1-41.5], P Conclusions In-ICU anticoagulation was the only APS-specific treatment independently associated with survival for all patients. Double therapy was independently associated with better survival of patients with definite/probable catastrophic APS. In these patients, further studies are needed to determine the role of triple therapy.

Published
2020

18. Diagnosis and prognosis of acute respiratory distress syndrome related to diffuse pneumonic-type adenocarcinoma: a single-center case series study

Author

Maxens Decavèle, Antoine Parrot, Michaël Duruisseaux, Martine Antoine, Anne Fajac, Audrey Milon, Marie-France Carette, Anthony Canellas, Aude Gibelin, Alexandre Elabbadi, Marie Wislez, Jacques Cadranel, and Muriel Fartoukh

Subjects
Pulmonary and Respiratory Medicine
Abstract

The absence of diagnosis of acute respiratory distress syndrome (ARDS) concerns 20% of cancer patients and is associated with poorer outcomes. Diffuse pneumonic-type adenocarcinoma (P-ADC) is part of these difficult-to-diagnose ARDS, but only limited data are available regarding critically ill patients with diffuse P-ADC. We sought to describe the diagnosis process and the prognosis of P-ADC related ARDS patients admitted to the intensive care unit (ICU).Single-center observational case series study. All consecutive patients admitted to the ICU over a two-decade period presenting with (I) histologically or cytologically proven adenocarcinoma of the lung and (II) ARDS according to Berlin definition were included. Clinical, biological, radiological and cytological features of P-ADC were collected to identify diagnostic clues. Multivariate logistic regression analyses were performed to assess factors associated with ICU and hospital mortality.Among the 24 patients included [70 (61-75) years old, 17 (71%) males], the cancer diagnosis was performed during the ICU stay in 19 (79%), and 17 (71%) required mechanical ventilation. The time between the first symptoms and the diagnosis of P-ADC was 210 days (92-246 days). A non-resolving pneumonia after 2 (2 to 3) antibiotics lines observed in 23 (96%) patients with a 34 mg/L (19 to 75 mg/L) plasma C-reactive protein level at ICU admission. Progressive dyspnea, bronchorrhea, salty expectoration, fissural bulging and compressed bronchi and vessels were present in 100%, 83%, 69%, 57% and 43% of cases. Cytological examination of sputum or broncho-alveolar lavage provided a 75% diagnostic yield. The ICU and hospital mortality rates were 25% and 63%, respectively. The time (in days) between first symptoms and diagnosis [odds ratio (OR) 1.02, 95% confidence interval (95% CI): 1.00-1.03, P=0.046] and the Simplified Acute Physiology Score II (OR 1.16, 95% CI: 1.01-1.33, P=0.040) were independently associated with ICU mortality.Non-resolving pneumonia after several antibiotics lines without inflammatory syndrome, associated with progressive dyspnea, salty bronchorrhea, and lobar swelling (i.e., fissural bulging, compressed bronchi and vessels) were suggestive of P-ADC. Delayed diagnosis of diffuse P-ADC seemed an independent prognostic predictor and disease timely recognition may contribute to prognosis improvement.

Published
2022

19. Identification of bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome in critically ill COVID-19 patients

Author

Guillaume Voiriot, Karim Dorgham, Guillaume Bachelot, Anne Fajac, Laurence Morand-Joubert, Christophe Parizot, Grigorios Gerotziafas, Dominique Farabos, Germain Trugnan, Thibaut Eguether, Clarisse Blayau, Michel Djibré, Alexandre Elabbadi, Aude Gibelin, Vincent Labbé, Antoine Parrot, Matthieu Turpin, Jacques Cadranel, Guy Gorochov, Muriel Fartoukh, and Antonin Lamazière

Subjects
Multidisciplinary, SARS-CoV-2, Critical Illness, COVID-19, Humans, Prospective Studies, Bronchoalveolar Lavage Fluid, Biomarkers
Abstract

The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30–4.41] vs. 9.53 [2.56–19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.

Published
2021

20. Prevalence, characteristics and outcome of cardiac manifestations in critically-ill antiphospholipid syndrome patients

Author

Lévi-Dan Azoulay, Marc Pineton de Chambrun, Romaric Larcher, Frédéric Pène, Laurent Argaud, Julien Mayaux, Matthieu Jamme, Remi Coudroy, Alexis Mathian, Aude Gibelin, Elie Azoulay, Yacine Tandjaoui-Lambiotte, Auguste Dargent, François Beloncle, Jean-Herlé Raphalen, Antoine Troger, Nicolas de Prost, Jérôme Devaquet, Damien Contou, Samuel Gaugain, Pierre Trouiller, Steven Grangé, Stanislas Ledochowski, Jérémie Lemarie, Stanislas Faguer, Vincent Degos, Quentin Moyon, Charles-Edouard Luyt, Mathieu Kerneis, Alain Combes, and Zahir Amoura

Subjects
Adult, Immunology, Humans, Contrast Media, Immunology and Allergy, Female, Stroke Volume, Gadolinium, Middle Aged, Antiphospholipid Syndrome, Ventricular Function, Left, Retrospective Studies
Abstract

Antiphospholipid syndrome (APS) is a rare autoimmune disease defined by thrombotic events occurring in patients with persistent antiphospholipid antibodies. Cardiac manifestations in critically-ill APS patients are poorly investigated. We conducted a study to assess the prevalence, the characteristics and the prognosis of cardiac manifestations in thrombotic APS patients admitted to intensive care unit (ICU).A French, national, multicentre, retrospective study, conducted, from January 2000 to September 2018, including all APS patients admitted to 24 participating centres' ICUs with any new thrombotic (arterial, venous or microvascular) manifestation. Cardiac manifestations were defined as any new cardiac abnormalities relying on clinical examination, cardiac biomarkers, echocardiography, cardiac magnetic resonance (CMR) and coronarography. One hundred and thirty-six patients (female 72%) were included. Mean age at ICU admission was 46 ± 15years. Cardiac manifestations were present in 71 patients (53%). In patients with cardiac involvement, median left ventricular ejection fraction (LVEF) was 40% [28-55], troponin was elevated in 93% patients, coronary angiogram (n = 19, 27%) disclosing a coronary obstruction in 21%. CMR (n = 21) was abnormal in all cases, with late gadolinium enhancement in 62% of cases. Cardiac manifestations were associated with a non-significant increase of mortality (32% vs. 19%, p = 0.08). After 1-year follow-up, median LVEF was 57% [44-60] in patients with cardiac involvement.Cardiac involvement is frequent in critically-ill thrombotic APS patients and may be associated to more severe outcome. Increased awareness on this rare cause of myocardial infarction with or without obstructive coronary artery is urgently needed.

Published
2022

21. Causes of acute respiratory failure in patients with small-vessel vasculitis admitted to intensive care units: a multicenter retrospective study

Author

François Bagate, Matthieu Groh, Etienne de Montmollin, Aude Gibelin, Alexandre Hertig, Loredana Baboi, Guillaume Dumas, Mathilde Neuville, Raphaël Clere-Jehl, Charles-Edouard Luyt, Francis Schneider, Eric Maury, Jean-Herlé Raphalen, Nicolas de Prost, Muriel Fartoukh, Marc Pineton de Chambrun, Sandrine Valade, Claude Guérin, Jean-Daniel Chiche, Antoine Parrot, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], CHU Henri Mondor, Hôpital Foch [Suresnes], CHU Necker - Enfants Malades [AP-HP], Service de réanimation médicale polyvalente [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Service d'Anesthésie réanimation [CHU Tenon], Gestionnaire, HAL Sorbonne Université 5, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Département de Néphrologie [CHU Tenon] (Néphrologie et dialyse), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de Pneumologie, Médecine Intensive et Réanimation - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S)

Subjects
Vasculitis, medicine.medical_specialty, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Acute respiratory failure, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Anesthesiology, Intensive care, medicine, 030212 general & internal medicine, RC86-88.9, Proportional hazards model, business.industry, Diffuse alveolar hemorrhage, Research, Medical emergencies. Critical care. Intensive care. First aid, Immunosuppression, Retrospective cohort study, medicine.disease, Intensive care unit, 3. Good health, 030228 respiratory system, Etiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract

Rationale Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion. Methods A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv. Results During the study period, 121 patients [62 (50–75) years; 62% male; median SAPSII and SOFA scores 39 (27–52) and 6 (4–8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n = 47, 39%), whereas the main non-immune cause was pulmonary infection (n = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p = 0.053). Among patients with a known Svv (n = 70), immunosuppression [OR 9.41 (1.52–58.3); p = 0.016], and a low vasculitis activity score [0.84 (0.77–0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure. Conclusions An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies.

Published
2021

23. Role of super-spreader phenomenon in a Covid-19 cluster among healthcare workers in a Primary Care Hospital

Author

Laurent Menard, Michel Denis, Hélène Goulet, Ludovic Lassel, Gilles Pialoux, Aude Gibelin, Sandra Fournier, Basma Abdi, Marine Nadal, Muriel Farthoukh, Service des maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Bactériologie-Hygiène [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Tenon], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], 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), Service de Néphrologie et Dialyses [CHU Tenon], Service des Urgences [CHU Tenon], and Service de virologie [CHU Pitié-Salpêtrière]

Subjects
Microbiology (medical), 0303 health sciences, 2019-20 coronavirus outbreak, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Primary care, Disease cluster, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Health care, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, Medical emergency, business, Letter to the Editor, Super-spreader, 030304 developmental biology
Abstract

International audience; Role of super-spreader phenomenon in a Covid-19 cluster among healthcare workers in a Primary Care Hospital We read with great interest the recent publication of Majra et al. 1 focusing on "societal" superspreading events (SSE) as a major risk factor for epidemic spread. We report another situation of SSE with a nosocomial cluster amongst healthcare workers (HCW) in Tenon Hospital, Paris, France, a middle-sized hospital of 525 beds, between February 21 and March 6, following the admission of our first confirmed COVID-19 case. A suspected COVID-19 case was someone exhibiting compatible symptoms who had been in direct or indirect contact with the index case. A confirmed case was a suspected case with laboratory confirmation through real time reverse transcriptase polymerase chain reaction (RT-PCR) performed on a nasopharyngeal swab.

Published
2021
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24. Pain and dyspnea control during awake fiberoptic bronchoscopy in critically ill patients: safety and efficacy of remifentanil target-controlled infusion

Author

Matthieu Turpin, Thomas Baury, Sophie Dupeyrat, Antoine Parrot, Jean-Pierre Fulgencio, Margot Caron, Muriel Fartoukh, Alexandre Elabbadi, Daisy Daigné, Marie-Cécile Allain, Clarisse Blayau, Pierre-Yves Blanchard, Tài Pham, Sacha Rozencwajg, Aude Gibelin, Séverine Rodriguez, Service d'Anesthésie réanimation [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)

Subjects
medicine.medical_specialty, medicine.drug_class, Sedation, Remifentanil, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Anesthesiology, medicine, Intensive care unit, Flexible fiberoptic bronchoscopy, Critically ill, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Comfort, 3. Good health, 030228 respiratory system, Sedative, Anesthesia, Anxiety, Observational study, Remifentanil target-controlled infusion, medicine.symptom, business, Tolerance, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Purpose Flexible fiberoptic bronchoscopy is frequently used in intensive care unit, but is a source of discomfort, dyspnea and anxiety for patients. Our objective was to assess the feasibility and tolerance of a sedation using remifentanil target-controlled infusion, to perform fiberoptic bronchoscopy in awake ICU patients. Materials, patients and methods This monocentric, prospective observational study was conducted in awake patients requiring fiberoptic bronchoscopy. In accordance with usual practices in our center, remifentanil target-controlled infusion was used under close monitoring and adapted to the patient’s reactions. The primary objective was the rate of successful procedures without additional analgesia or anesthesia. The secondary objectives were clinical tolerance and the comfort of patients (graded from “very uncomfortable” to “very comfortable”) and operators (numeric scale from 0 to 10) during the procedure. Results From May 2014 to December 2015, 72 patients were included. Most of them (69%) were hypoxemic and admitted for acute respiratory failure. No additional medication was needed in 96% of the patients. No severe side-effects occurred. Seventy-eight percent of patients described the procedure as “comfortable or very comfortable”. Physicians rated their comfort with a median [IQR] score of 9 [8–10]. Conclusion Remifentanil target-controlled infusion administered to perform awake fiberoptic bronchoscopy in critically ill patients is feasible without requirement of additional analgesics or sedative drugs. Clinical tolerance as well as patients’ and operators’ comfort were good to excellent. This technique could benefit patients’ experience.

Published
2021

25. Infectious aetiologies of severe acute chest syndrome in sickle-cell adult patients, combining conventional microbiological tests and respiratory multiplex PCR

Author

Guillaume Voiriot, Aude Gibelin, Muriel Fartoukh, Julien Lopinto, Alexandre Elabbadi, Service d'Anesthésie réanimation [CHU Tenon], 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), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, Male, medicine.medical_specialty, Staphylococcus aureus, Science, Atelectasis, Microbiology, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Medical research, law, 030225 pediatrics, Internal medicine, Lower respiratory tract infection, Acute Chest Syndrome, Pneumonia, Staphylococcal, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Fat embolism, Prospective cohort study, Aged, Multidisciplinary, business.industry, Sickle cell disease, Middle Aged, medicine.disease, Intensive care unit, Acute chest syndrome, 3. Good health, Viral infection, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Respiratory virus, Medicine, Female, Bacterial infection, Complication, business, Multiplex Polymerase Chain Reaction
Abstract

Acute chest syndrome (ACS) is the most serious complication of sickle cell disease. The pathophysiology of ACS may involve lower respiratory tract infection (LRTI), alveolar hypoventilation and atelectasis, bone infarcts-driven fat embolism, and in situ pulmonary artery thrombosis. One of the most challenging issues for the physicians is to diagnose LRTI as the cause of ACS. The use of a respiratory multiplex PCR (mPCR) for the diagnosis of LRTI has not been assessed in sickle-cell adult patients with ACS. To describe the spectrum of infectious aetiologies of severe ACS, using a diagnostic approach combining conventional tests and mPCR. A non-interventional monocenter prospective study involving all the consecutive sickle-cell adult patients with ACS admitted to the intensive care unit (ICU). Microbiological investigation included conventional tests and a nasopharyngeal swab for mPCR. Altogether, 36 patients were enrolled, of whom 30 (83%) had complete microbiological investigations. A bacterial microorganism, mostly Staphylococcus aureus (n = 8), was identified in 11 patients. There was no pneumonia-associated intracellular bacterial pathogen. A respiratory virus was identified in six patients. Using both conventional tests and nasopharyngeal mPCR, a microbiological documentation was obtained in half of adult ACS patients admitted to the ICU. Pyogenic bacteria, especially S. aureus, predominated.

Published
2021

26. Randomised trial of first-line bronchial artery embolisation for non-severe haemoptysis of mild abundance

Author

Benjamin Planquette, Vincent Labbe, Tabassome Simon, Alexandra Rousseau, Jacques Cadranel, Antoine Khalil, Emmanuel Bergot, Gérard Zalcman, Guy Meyer, Philippe Cluzel, Vincent Jounieaux, Alexandre Demoule, Muriel Fartoukh, Aude Gibelin, Olivier Sanchez, THOMAS SIMILOWSKI, Claire Andrejak, Valérie Chabbert, Michel Djibré, Sophie Tuffet, Cendrine Godet, Sandrine Pontier-Marchandise, Julien Mayaux, Marc Sapoval, Vincent Le Pennec, Clarisse Blayau, Guillaume Voiriot, Alexandre Duguet, Hélène Prodanovik, Guillaume Briend, Anne Roche, Costantino Del Giudice, Olivier Pellerin, Marie-Pierre Revel, Patrick Courtheoux, Jean Claude Meurice, Elise Antone, Alexandre Remond, Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), CHU Pitié-Salpêtrière [AP-HP], 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), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Picardie Jules Verne (UPJV), Service de pneumologie [Toulouse], CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Service d'Anesthésie réanimation [CHU Tenon], Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de Radiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Radiologie [CHU Caen], Service de Radiologie [CHU Tenon], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Radiothérapie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP]

Subjects
Adult, Pulmonary and Respiratory Medicine, Hemoptysis, medicine.medical_specialty, Standard of care, First line, Bronchial Arteries, Imaging/CT MRI etc, Pulmonary Vasculature, 030218 nuclear medicine & medical imaging, Diseases of the respiratory system, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Bronchoscopy, medicine.artery, medicine, Humans, Adverse effect, Trial registration, Retrospective Studies, RC705-779, medicine.diagnostic_test, Adult patients, business.industry, Embolization, Therapeutic, 3. Good health, Surgery, Treatment Outcome, 030228 respiratory system, Medicine, business, Bronchial artery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Massive Haemoptysis
Abstract

BackgroundWhereas first-line bronchial artery embolisation (BAE) is considered standard of care for the management of severe haemoptysis, it is unknown whether this approach is warranted for non-severe haemoptysis.Research questionTo assess the efficacy on bleeding control and the safety of first-line BAE in non-severe haemoptysis of mild abundance.Study design and methodsThis multicentre, randomised controlled open-label trial enrolled adult patients without major comorbid condition and having mild haemoptysis (onset ResultsBleeding recurrence at day 30 after randomisation (primary outcome) occurred in 4 (11.8%) of 34 patients in the BAE strategy and 17 (44.7%) of 38 patients in the medical strategy (difference −33%; 95% CI −13.8% to −52.1%, p=0.002). The 90-day bleeding recurrence-free survival rates were 91.2% (95% CI 75.1% to 97.1%) and 60.2% (95% CI 42.9% to 73.8%), respectively (HR=0.19, 95% CI 0.05 to 0.67, p=0.01). No death occurred during follow-up and no bleeding recurrence needed surgery.Four adverse events (one major with systemic emboli) occurred during hospitalisation, all in the BAE strategy (11.8% vs 0%; difference 11.8%, 95% CI 0.9 to 22.6, p=0.045); all eventually resolved.ConclusionIn non-severe haemoptysis of mild abundance, BAE associated with medical therapy had a superior efficacy for preventing bleeding recurrences at 30 and 90 days, as compared with medical therapy alone. However, it was associated with a higher rate of adverse events.Trial registration numberNCT01278199

Published
2020

27. Destructive pulmonary fibrosis after severe COVID-19 pneumonia

Author

Aude Gibelin, Alice Letellier, Muriel Fartoukh, Michel Djibré, and Guillaume Voiriot

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Pulmonary cavity, lcsh:Infectious and parasitic diseases, Pulmonary fibrosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Internal medicine, medicine, Medical Imagery, lcsh:RC109-216, 030212 general & internal medicine, Diffuse alveolar damage, COVID – 19 pneumonia, Lung, biology, business.industry, Interstitial lung disease, Achromobacter xylosoxidans, General Medicine, Citrobacter koseri, medicine.disease, biology.organism_classification, Pneumonia, medicine.anatomical_structure, Infectious Diseases, chemistry, business
Abstract

This case report describes the clinical course and management of a 65-year-old man was admitted to the intensive care unit (ICU) of Tenon hospital, a university teaching hospital in Paris, France, for severe confirmed COVID-19 pneumonia Acute cavitary lung lesions are usually related to mycobacterial, parasitic, fungal, or bacterial infection, particularly Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacilli In this case, despite VAP due to Citrobacter koseri and Achromobacter xylosoxidans, this hypothesis is unlikely because neither radiological changes nor signs of necrotizing pneumonia were present on successive chest x-rays Other causes of lung cavitation, such as autoimmune disorder or genetic mutations, were not investigated but the speed of the development of cavitary lesion in a few days was considered atypical In the last hypothesis, although interleukin 6 (IL-6) inhibitor-induced interstitial lung disease has already been described, cavitation related to tocilizumab has not been reported, thus it should be reported as a related side adverse event Severe COVID-19 pneumonia may progress to pulmonary fibrosis related to diffuse alveolar damage, but the association with lung cavitation is uncommon and may significantly impair the outcome

Published
2020
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28. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study

Author

Alexandra Beurton, Abdelmalek Abdelkrim, Nicolas Bréchot, Alexandre Elabbadi, Juliette Chommeloux, Martin De Sarcus, Thomas Urbina, Elodie Baron, Thibaut Schoell, Paris Meng, Charlotte Du Fayet De La Tour, Sofica Marin, Victoria Lepere, Elise Morawiec, Eric Maury, Bertrand Guidet, Pierre Romain Delmotte, Enora Berti, Pierre Bay, Alain Combes, Hafid Ait Oufella, Muriel Fartoukh, Jean Luc Baudel, Samia Abbas, David Levy, Matthieu Turpin, David Hajage, Cossimo D'Alessandro, Pascal Leprince, Corinne Vezinet, Charles Edouard Luyt, Robin Deleris, Martin Dres, Jean Michel Constantin, Alexandre Demoule, Marc Pineton de Chambrun, Mona Assefi, Guillaume Hékimian, Cyrielle Desnos, Pierre Demondion, Guillaume Voiriot, Bao Long Nguyen, Arthur James, Harold Bonvallot, Safaa Nemlaghi, Nathalie Nardonne, Julien Mayaux, Vincent Bonny, Guillaume Lebreton, Cyril Quemeneur, Sara Virolle, Emmanuelle Guerin, Matthieu Schmidt, Aude Gibelin, Julien Le Marec, Charles Juvin, Guillaume Savary, Jean Remi Lavillegrand, Antoine Monsel, Jeremy Arzoine, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Réanimation Médicale [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Trousseau [APHP], 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 Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Réanimation et USC Médico-Chirurgicale [CHU Tenon], CHU Tenon [AP-HP], 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), Service de Pneumologie, Médecine Intensive et Réanimation - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), 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), 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], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Service de Réanimation et USC Médico-Chirurgicale = Médecine intensive réanimation [CHU Tenon], Service de Médecine Intensive et Réanimation - R3S [CHU Pitié-Salpêtrière], and Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158)

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, ARDS, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pneumonia, Viral, Context (language use), Betacoronavirus, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Intensive care, medicine, Extracorporeal membrane oxygenation, Humans, 030212 general & internal medicine, Pandemics, Survival rate, Retrospective Studies, Respiratory Distress Syndrome, SARS-CoV-2, Proportional hazards model, business.industry, COVID-19, Retrospective cohort study, Middle Aged, medicine.disease, Survival Rate, Intensive Care Units, surgical procedures, operative, 030228 respiratory system, Respiratory failure, Emergency medicine, Female, France, Coronavirus Infections, business
Abstract

Summary Background Patients with COVID-19 who develop severe acute respiratory distress syndrome (ARDS) can have symptoms that rapidly evolve to profound hypoxaemia and death. The efficacy of extracorporeal membrane oxygenation (ECMO) for patients with severe ARDS in the context of COVID-19 is unclear. We aimed to establish the clinical characteristics and outcomes of patients with respiratory failure and COVID-19 treated with ECMO. Methods This retrospective cohort study was done in the Paris–Sorbonne University Hospital Network, comprising five intensive care units (ICUs) and included patients who received ECMO for COVID-19 associated ARDS. Patient demographics and daily pre-ECMO and on-ECMO data and outcomes were collected. Possible outcomes over time were categorised into four different states (states 1–4): on ECMO, in the ICU and weaned off ECMO, alive and out of ICU, or death. Daily probabilities of occupation in each state and of transitions between these states until day 90 post-ECMO onset were estimated with use of a multi-state Cox model stratified for each possible transition. Follow-up was right-censored on July 10, 2020. Findings From March 8 to May 2, 2020, 492 patients with COVID-19 were treated in our ICUs. Complete day-60 follow-up was available for 83 patients (median age 49 [IQR 41–56] years and 61 [73%] men) who received ECMO. Pre-ECMO, 78 (94%) patients had been prone-positioned; their median driving pressure was 18 (IQR 16–21) cm H2O and PaO2/FiO2 was 60 (54–68) mm Hg. At 60 days post-ECMO initiation, the estimated probabilities of occupation in each state were 6% (95% CI 3–14) for state 1, 18% (11–28) for state 2, 45% (35–56) for state 3, and 31% (22–42) for state 4. 35 (42%) patients had major bleeding and four (5%) had a haemorrhagic stroke. 30 patients died. Interpretation The estimated 60-day survival of ECMO-rescued patients with COVID-19 was similar to that of studies published in the past 2 years on ECMO for severe ARDS. If another COVID-19 outbreak occurs, ECMO should be considered for patients developing refractory respiratory failure despite optimised care. Funding None.

Published
2020

29. Hémorragies intra-alvéolaires

Author

A Parrot, A. Canellas, J.-M. Nacacche, Muriel Fartoukh, Guillaume Voiriot, Aude Gibelin, and Jacques Cadranel

Subjects
Emergency Medicine, Emergency Nursing
Abstract

L’hémorragie intra-alvéolaire (HIA), maladie rare, est une urgence thérapeutique, car elle peut conduire rapidement vers une insuffisance respiratoire aiguë asphyxiante avec décès. La triade, hémoptysie–anémie–infiltrat radiologique, suggère le diagnostic d’HIA, mais elle peut manquer dans deux tiers des cas, y compris chez des patients en détresse respiratoire. La tomodensitométrie thoracique peut aider dans les formes atypiques. Le diagnostic d’HIA repose sur la réalisation d’un lavage bronchoalvéolaire. Les étiologies en sont très nombreuses. Il importera de séparer, en urgence, les HIA d’origine non immune, avec un dépistage de celles d’origine septique qui doivent bénéficier d’une enquête microbiologique ciblée et cardiovasculaire avec la réalisation d’une échographie cardiaque, des HIA immunes (les vascularites liées aux anticorps anticytoplasme des polynucléaires neutrophiles, les connectivites et le syndrome de Goodpasture), avec la recherche d’autoanticorps et la réalisation de biopsies au niveau des organes facilement accessibles. La biopsie pulmonaire doit rester exceptionnelle. En cas d’HIA immune inaugurale, un traitement par stéroïdes et cyclophosphamide peut être débuté. Les indications du rituximab commencent à être mieux établies. Le bénéfice des échanges plasmatiques est débattu. En cas de réapparition d’infiltrats pulmonaires, chez un patient suivi pour une HIA immune, on s’efforcera d’écarter une infection dans un premier temps.

Published
2018

30. Transcatheter embolotherapy of pulmonary artery aneurysms as emergency treatment of hemoptysis in Behcet patients: experience of a referral center and a review of the literature

Author

Marie-France Carette, Guillaume Voiriot, Muriel Fartoukh, Antoine Khalil, Antoine Parrot, Martine Antoine, Samuel P. Haddad, and Aude Gibelin

Subjects
Adult, Male, Hemoptysis, medicine.medical_specialty, Behcet's disease, Pulmonary Artery, 030204 cardiovascular system & hematology, Emergency treatment, Statistics, Nonparametric, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, Internal Medicine, medicine, Humans, Prospective Studies, Major complication, Emergency Treatment, Secondary Care Centers, 030203 arthritis & rheumatology, Pulmonary artery aneurysm, business.industry, Behcet Syndrome, Immunosuppressive regimen, biochemical phenomena, metabolism, and nutrition, medicine.disease, Aneurysm, Embolization, Therapeutic, Surgery, Pulmonary artery, Emergency Medicine, Referral center, Female, France, Complication, business
Abstract

Hemoptysis is a life-threatening complication of Behcet's disease that is likely related to pulmonary artery aneurysm (PAA). Vascular interventional radiology may offer effective emergency therapeutic option, but has not been thoroughly investigated in this setting. A case series of a French referral center for hemoptysis combined with a literature review of case reports was conducted. Between 1995 and 2016, 12 patients were referred to our center for hemoptysis revealing or complicating the course of Behcet's disease. Pulmonary artery aneurysm (PAA) was the mechanism of hemoptysis in ten patients, nine of whom were treated by a transcatheter embolotherapy. Combining an additional 8 case reports from the literature, 17 patients treated by transcatheter embolotherapy for PAA were analyzed. The duration of the course of Behcet's disease was 22 months [IQR 3-45] at the time of PAA diagnosis. Transcatheter embolotherapy of PAA was successful for immediately controlling hemoptysis in all patients, without major complication except for one. Hemoptysis recurred in seven patients (41%) within 5 months [IQR 1-12]. The use of coils for transcatheter embolotherapy was associated with hemoptysis recurrence. A bronchosystemic hypervascularization related to the previously occluded PAA was the main mechanism of bleeding recurrence, leading to bronchosystemic artery embolization in four patients and surgery in two patients. Behcet's disease-related hemoptysis is mainly due to PAA. Transcatheter embolotherapy should be considered as the first-line emergency treatment for PAA-related hemoptysis, in association with the immunosuppressive regimen. Hemoptysis may recur in half of the cases, involving preferentially a bronchosystemic arterial mechanism.

Published
2018

31. Toxicité pulmonaire des médicaments : ce que le réanimateur doit connaître ?

Author

Muriel Fartoukh, Antoine Parrot, Jacques Cadranel, Aude Gibelin, Guillaume Voiriot, Michel Djibré, Jean-Marc Naccache, and T. Issoufaly

Subjects
Emergency Medicine, Emergency Nursing
Abstract

Le diagnostic d’insuffisance respiratoire aigue d’origine medicamenteuse est un veritable defi. Les traitements a l’origine d’une toxicite pulmonaire sont tres nombreux. Les nouveaux traitements, notamment en oncohematologie (therapie ciblee, immunotherapie), ne sont pas en reste. L’expression clinique tres heterogene est sous-tendue par des mecanismes lesionnels tres differents. Apres avoir ecarte une infection ou un œdeme pulmonaire, il faut savoir evoquer une pneumopathie medicamenteuse. La realisation d’un scanner thoracique et d’une fibroscopie bronchique avec lavage bronchoalveolaire peut etre utile pour exclure une pathologie infectieuse et suggerer une pathologie medicamenteuse. Le traitement est l’arret du medicament et repose frequemment dans ces formes graves sur une corticotherapie.

Published
2018

32. Benralizumab: A potential tailored treatment for life-threatening DRESS in the COVID-19 era

Author

Aude Gibelin, Guillaume Voiriot, Cédric Rafat, Delphine Staumont Salle, Matthieu Groh, Angèle Soria, Farah Mesli, Maëlle Dumont, Matthieu Turpin, Cyrielle Desnos, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), 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), Hôpital Foch [Suresnes], CHU Lille, and Université de Lille

Subjects
2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Tailored treatment, Benralizumab, chemistry.chemical_compound, chemistry, Immunology and Allergy, Medicine, business, Intensive care medicine
Abstract

International audience; No abstract available

Published
2021

33. Simultaneous Left and Right Ventricular Thrombi Caused by Catastrophic Antiphospholipid Syndrome

Author

Michel Djibré, Aude Gibelin, Stéphane Ederhy, Guillaume Voiriot, Sophie Lalevée, Muriel Fartoukh, Vincent Labbé, Florie Akdime, Pierre Antoine Allain, and Clarisse Blayau

Subjects
Pulmonary and Respiratory Medicine, Left and right, Male, medicine.medical_specialty, Heart Diseases, business.industry, Thrombosis, Middle Aged, Critical Care and Intensive Care Medicine, Catastrophic antiphospholipid syndrome, Antiphospholipid Syndrome, Echocardiography, Internal medicine, Cardiology, medicine, Humans, business
Published
2019

34. Non-invasive ventilation versus high-flow nasal cannula oxygen therapy with apnoeic oxygenation for preoxygenation before intubation of patients with acute hypoxaemic respiratory failure: a randomised, multicentre, open-label trial

Author

Jean-Pierre Frat, Jean-Damien Ricard, Jean-Pierre Quenot, Nicolas Pichon, Alexandre Demoule, Jean-Marie Forel, Jean-Paul Mira, Rémi Coudroy, Guillaume Berquier, Benoit Voisin, Gwenhaël Colin, Bertrand Pons, Pierre Eric Danin, Jérome Devaquet, Gwenael Prat, Raphaël Clere-Jehl, Franck Petitpas, Emmanuel Vivier, Keyvan Razazi, Mai-Anh Nay, Vincent Souday, Jean Dellamonica, Laurent Argaud, Stephan Ehrmann, Aude Gibelin, Christophe Girault, Pascal Andreu, Philippe Vignon, Laurence Dangers, Stéphanie Ragot, Arnaud W Thille, Delphine Chatellier, Florence Boissier, Anne Veinstein, René Robert, Céline Deletage-Métreau, Morgane Olivry, Claire Dahyot-Fizelier, Auguste Dargent, Audrey Large, Emmanuelle Begot, Claire Mancia, Maxence Decavele, Martin Dres, Samuel Lehingue, Laurent Papazian, Marine Paul, Nathalie Marin, Matthieu Le Meur, Mohammed Laissy, Anaita Rouzé, Saad Nseir, Matthieu Henry-Lagarrigue, Aihem Yehia, Frédéric Martino, Charles Cerf, Pierre Bailly, Julie Helms, Jean Baptiste Putegnat, Armand Mekontso-Dessap, Thierry Boulain, Pierre Asfar, Séverin Cabasson, Florent Wallet, Kada Klouche, Frédéric Bellec, Centre hospitalier universitaire de Poitiers (CHU 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), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne (UB), Hôpital Dupuytren [CHU Limoges], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Charles Foix [AP-HP], Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), GHU AP-HP Centre Université de Paris, Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hôpital Foch [Suresnes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Nouvel Hôpital Civil de Strasbourg, Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), Centre hospitalier Saint Joseph - Saint Luc [Lyon], CHU 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 Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - HCL], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche sur le Handicap Ventilatoire (GRHV), Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-CHU Rouen, Normandie Université (NU), CHU Rouen, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Delphine Chatellier, Florence Boissier, Anne Veinstein, René Robert, Céline Deletage-Métreau, Morgane Olivry, Claire Dahyot-Fizelier, Auguste Dargent, Audrey Large, Emmanuelle Begot, Claire Mancia, Maxence Decavele, Martin Dres, Samuel Lehingue, Laurent Papazian, Marine Paul, Nathalie Marin, Matthieu Le Meur, Mohammed Laissy, Anaita Rouzé, Saad Nseir, Matthieu Henry-Lagarrigue, Aihem Yehia, Frédéric Martino, Charles Cerf, Pierre Bailly, Julie Helms, Jean Baptiste Putegnat, Armand Mekontso-Dessap, Thierry Boulain, Pierre Asfar, Séverin Cabasson, Florent Wallet, Kada Klouche, Frédéric Bellec, Delphine Chatellier, Florence Boissier, Anne Veinstein, René Robert, Céline Deletage-Métreau, Morgane Olivry, Maxence Decavele, Martin Dres, Samuel Lehingue, Laurent Papazian, Matthieu Le Meur, Mohammed Laissy, Anaita Rouzé, Saad Nseir, Matthieu Henry-Lagarrigue, Aihem Yehia, Charles Cerf, Armand Mekontso-Dessap, Thierry Boulain, Pierre Asfar, CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation, Hôpital Jean Bernard, CHU de Poitiers, Poitiers, France, Equipe LIPNESS (LNC - U1231) (LIPNESS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Coordination des Prélèvements d’Organes et de Tissus (CHPOT), CHU Limoges, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire pluridisciplinaire de recherche en ingénierie des systèmes, mécanique et énergétique (PRISME), Université d'Orléans (UO)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation Médicale [Strasbourg], Institut universitaire des systèmes thermiques industriels (IUSTI), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale [Hôpital de l’Archet], Centre Hospitalier Universitaire de Nice (CHU de Nice)-Hôpital de l'Archet, Service de Réanimation Médicale, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France, parent, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and CHU Henri Mondor [Créteil]

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Nose, medicine.disease_cause, Catheterization, 03 medical and health sciences, 0302 clinical medicine, Fraction of inspired oxygen, Intensive care, Oxygen therapy, medicine, Intubation, Intratracheal, Intubation, Humans, Oximetry, Hypoxia, Noninvasive Ventilation, medicine.diagnostic_test, business.industry, Tracheal intubation, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, Middle Aged, Respiration, Artificial, 3. Good health, [SDV] Life Sciences [q-bio], Pulse oximetry, 030228 respiratory system, Respiratory failure, Anesthesia, Acute Disease, Female, business, Respiratory Insufficiency, Nasal cannula
Abstract

International audience; BACKGROUND: Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation. METHODS: The FLORALI-2 multicentre, open-label trial was done in 28 intensive care units in France. Adult patients undergoing tracheal intubation for acute hypoxaemic respiratory failure (a partial pressure of arterial oxygen [PaO2] to fraction of inspired oxygen [FiO2] ratio of \textless/=300 mm Hg) were randomly assigned (1:1; block size, four participants) to non-invasive ventilation or high-flow oxygen during preoxygenation, with stratification by PaO2/FiO2 ratio (\textless/=200 mm Hg vs \textgreater200 mm Hg). Key exclusion criteria were intubation for cardiac arrest, altered consciousness (defined as a Glasgow coma score of less than eight points), other contraindications to non-invasive ventilation (recent laryngeal, oesophageal, or gastric surgery, and substantial facial fractures), pulse oximetry not available, pregnant or breastfeeding women, and refusal to participate. The primary outcome was the occurrence of severe hypoxaemia (pulse oximetry \textless80%) during the procedure, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02668458. FINDINGS: Between April 15, 2016, and Jan 8, 2017, 2079 patients were intubated in the 28 participating units, and 322 were enrolled. We excluded five patients with no recorded data, two who withdrew consent or were under legal protection, one who was not intubated, and one who had a cardiac arrest. Of the 313 patients included in the intention-to-treat analysis, 142 were assigned to non-invasive ventilation and 171 to high-flow oxygen therapy. Severe hypoxaemia occurred in 33 (23%) of 142 patients after preoxygenation with non-invasive ventilation and 47 (27%) of 171 with high-flow oxygen (absolute difference -4.2%, 95% CI -13.7 to 5.5; p=0.39). In the 242 patients with moderate-to-severe hypoxaemia (PaO2/FiO2 \textless/=200 mm Hg), severe hypoxaemia occurred less frequently after preoxygenation with non-invasive ventilation than with high-flow oxygen (28 [24%] of 117 patients vs 44 [35%] of 125; adjusted odds ratio 0.56, 0.32 to 0.99, p=0.0459). Serious adverse events did not differ between treatment groups, with the most common immediate complications being systolic arterial hypotension (70 [49%] patients in the non-invasive ventilation group vs 86 [50%] patients in the high-flow oxygen group) and chest infiltrate on x-ray (28 [20%] vs 33 [19%]), and the most common late complications being death at day 28 (53 [37%] vs 58 [34%]) and ventilator-associated pneumonia during ICU stay (31 [22%] vs 35 [20%]). INTERPRETATION: In patients with acute hypoxaemic respiratory failure, preoxygenation with non-invasive ventilation or high-flow oxygen therapy did not change the risk of severe hypoxaemia. Future research should explore the effect of preoxygenation method in patients with moderate-to-severe hypoxaemia at baseline. FUNDING: French Ministry of Health.

Published
2019

35. CAPS criteria fail to identify most severely-ill thrombotic antiphospholipid syndrome patients requiring intensive care unit admission

Author

Nicolas de Prost, Romaric Larcher, Damien Contou, Rémi Coudroy, Alain Combes, Zahir Amoura, Laurent Argaud, Pierre Trouiller, François-Michel Beloncle, Jean-Herlé Raphalen, Elie Azoulay, Stanislas Ledochowski, Marc Pineton de Chambrun, Yacine Tandjaoui-Lambiotte, Alexis Mathian, Charles-Edouard Luyt, Auguste Dargent, Alexandre Demoule, Amélie Couteau-Chardon, Steven Grangé, Matthieu Jamme, Aude Gibelin, Vincent Degos, Samuel Gaugain, Frédéric Pène, Stanislas Faguer, Jérôme Devaquet, Jérémie Lemarié, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Réanimation Médicale, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France, parent, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre hospitalier universitaire de Poitiers (CHU 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), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares[CHU Pitié Salpêtrière], Service de médecine interne [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Equipe LIPNESS (LNC - U1231) (LIPNESS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Mécanique des Matériaux et des Structures (M2S), Géomécanique, Matériaux et Structures (GEOMAS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Université de Lyon-Institut National des Sciences Appliquées (INSA), Laboratoire Sciences Analytiques, Bioanalytiques, et Miniaturisation (LSABM), ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS), Service de médecine physique et de réadaptation [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-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)-Université de Montpellier (UM), Chimie-Biologie-Innovation (UMR 8231) (CBI), 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 de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-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 de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon, and Institut National des Sciences Appliquées (INSA)-Université de Lyon

Subjects
0301 basic medicine, Adult, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Catastrophic antiphospholipid syndrome, law.invention, 03 medical and health sciences, 0302 clinical medicine, Systemic lupus erythematosus, law, Antiphospholipid syndrome, medicine, Prevalence, Immunology and Allergy, Humans, Intensive care unit, Diagnostic Errors, Catastrophic Illness, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Microvascular thrombosis, Retrospective cohort study, Mean age, Thrombosis, Middle Aged, medicine.disease, Prognosis, Survival Analysis, 3. Good health, Icu admission, Intensive Care Units, 030104 developmental biology, Antibodies, Antiphospholipid, Female, France, Probability of survival, business
Abstract

International audience; PURPOSE : Catastrophic antiphospholipid syndrome (CAPS), the most severe manifestation of antiphospholipid syndrome (APS), is characterised by simultaneous thromboses in multiple organs. Diagnosing CAPS can be challenging but its early recognition and management is crucial for a favourable outcome. This study was undertaken to evaluate the frequencies, distributions and ability to predict mortality of "definite/probable" or "no-CAPS" categories of thrombotic APS patients requiring admission to the intensive care unit (ICU).METHOD : This French national multicentre retrospective study, conducted from January 2000 to September 2018, included all APS patients with any new thrombotic manifestation(s) admitted to 24 ICUs. RESULTS : One hundred and thirty-four patients (male/female ratio: 0.4; mean age at admission: 45.4+/-15.0 years), who experienced 152 CAPS episodes, required ICU admission. The numbers of definite, probable or no-CAPS episodes, respectively, were: 11 (7.2%), 60 (39.5%) and 81 (53.3%). No histopathological proof of microvascular thrombosis was the most frequent reason for not being classified as definite CAPS. Overall, 35/152 (23.0%) episodes were fatal, with comparable rates for definite/probable CAPS and no CAPS (23% vs. 28.8% respectively, p=0.4). The Kaplan-Meier curve of estimated probability of survival showed no between-group survival difference (log-rank test p=0.5). CONCLUSIONS : In this study, CAPS criteria were not associated with mortality of thrombotic APS patients requiring ICU admission. Further studies are need evaluate the adequacy of CAPS criteria for critically-ill APS patients.

Published
2019

36. Rare respiratory diseases in the ICU: when to suspect them and specific approaches

Author

Muriel Fartoukh, Aude Gibelin, Nicolas de Prost, and Antoine Parrot

Subjects
ARDS, medicine.medical_specialty, Respiratory Distress Syndrome, Lung, medicine.diagnostic_test, business.industry, Biopsy, Acute respiratory distress, Critical Care and Intensive Care Medicine, medicine.disease, Intensive Care Units, Bronchoalveolar lavage, medicine.anatomical_structure, Risk Factors, Epidemiology, medicine, Humans, Risk factor, Respiratory system, Intensive care medicine, business
Abstract

Purpose of review A prompt identification of the cause of acute respiratory failure (ARF)/acute respiratory distress syndrome (ARDS) is required in order to initiate a targeted treatment. Yet, almost 10% of ARDS patients have no identified ARDS risk factor at ARDS diagnosis. Numerous rare causes of ARF have been reported in this setting. The purpose of this review is to delineate the main rare causes of ARF/ARDS and to provide clinicians with a pragmatic diagnostic work-up. Recent findings Recent epidemiological data have proposed the identification of a subgroup of ARDS patients lacking exposure to common risk factors. These can be categorized as having immune, drug-induced, malignant and idiopathic diseases. A standardized diagnostic work-up including chest imaging, the objective assessment of left heart filling pressures, bronchoalveolar lavage fluid microbiological investigations and cytological analysis, immunological tests and search for pneumotoxic drugs may allow for identifying the cause of ARF in most cases. Open lung biopsy should be considered in other cases. Summary A prompt identification of the cause of ARF is required to initiate a targeted treatment. Patients with no identified ARDS risk factor should undergo a comprehensive and hierarchized diagnostic work-up.

Published
2018

37. Hémoptysies graves 2009–2019 admises en réanimation: description

Author

V. Labbé, M. Dijbre, Aude Gibelin, Muriel Fartoukh, J. Dessajan, G. Voiriot, and Antoine Parrot

Subjects
Pulmonary and Respiratory Medicine
Abstract

Introduction En France, aucune donnee recente sur les caracteristiques cliniques, etiologiques ni sur la prise en charge specifique des formes graves des hemoptysies admises en reanimation n’est disponible. Les objectifs de l’etude sont donc: la description clinique, etiologique, microbiologique et therapeutique des patients admis en reanimation pour hemoptysies graves L’etude de la mortalite intra-hospitaliere. L’identification des facteurs pronostics de mortalite intra-hospitaliere. Methodes Cohorte retrospective monocentrique de patients admis en reanimation entre mars 2009 et mars 2019 dans le service de reanimation. Recueil des donnees epidemiologiques, cliniques, biologiques, radiologiques et de prise en charge traitement et de mortalite. Seul le premier episode est decrit. Resultats Notre etude retrospective rapporte une description de 945 patients admis pour hemoptysie en reanimation entre 2009 et 2019. Il s’agit d’une population jeune (âge moyen 53 ans) plutot de type masculin et en bon etat general (PS ≥ 1 84%). Le volume d’hemoptysie moyen a l’admission est de 215 ± 184 ml. Pres de 13% des patients sont ventiles. Le cancer pulmonaire est devenu la premiere etiologie des hemoptysies graves. Les pneumonies sont en augmentation croissante avec pres de 14% entre 2015–2019. Le mecanisme etait systemique chez 872 (92%) des patients et arteriel pulmonaire dans 110 cas (12%). Ce mecanisme arteriel pulmonaire etait surtout retrouve dans les pneumonies (23%), le cancer pulmonaire (20%) ou a une maladie aspergillaire (20%). La radiologie interventionnelle confirme son role cle dans la prise en charge dans plus de 80% des cas. La chirurgie en urgence dans les 24 h represente moins de 1% des patients. La mortalite hospitaliere est de 8.7%. La comparaison avec une periode anterieure de 14 ans (1995–2009), revele une augmentation de la mortalite et du diagnostic de mecanisme arteriel pulmonaire. Les facteurs predictifs independants de mortalite hospitaliere sont le tabac, le PS ≥ 1, l’atteinte d’au moins de 2 cadrans radiologiques, la ventilation mecanique a 24 h et les etiologies cancer et aspergillose. Conclusion Cette etude confirme que le cancer est devenu la premiere cause d’hemoptysie, la place croissante des pneumonies infectieuses non tuberculeuses. L’augmentation de la frequence de l’atteinte vasculaire pulmonaire provient du recours systematique a l’angioscanner thoracique multibarette. La mortalite hospitaliere reste inchangee.

Published
2021

38. Pulmonary Vascular Dysfunction and Cor Pulmonale During Acute Respiratory Distress Syndrome in Sicklers

Author

Bernard Maitre, Aude Gibelin, Jérôme Cecchini, Florence Boissier, Keyvan Razazi, Armand Mekontso Dessap, Nicolas de Prost, Christian Brun-Buisson, Frédéric Galactéros, and Guillaume Carteaux

Subjects
Adult, Male, medicine.medical_specialty, ARDS, Anemia, Hemodynamics, Anemia, Sickle Cell, Disease, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Pulmonary heart disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pulmonary Heart Disease, Internal medicine, Acute Chest Syndrome, medicine, Humans, Young adult, Intensive care medicine, Retrospective Studies, Respiratory Distress Syndrome, business.industry, Retrospective cohort study, medicine.disease, Acute chest syndrome, Logistic Models, 030228 respiratory system, Echocardiography, Emergency Medicine, Cardiology, Female, business
Abstract

Acute chest syndrome (ACS) is the most common cause of death among sickle cell disease (SCD) adult patients. Pulmonary vascular dysfunction (PVD) and acute cor pulmonale (ACP) are common during acute respiratory distress syndrome (ARDS) and their prevalence may be even more important during ARDS related to ACS (ACS-ARDS). The objective of this study was to evaluate the prevalence and prognosis of PVD and ACP during ACS-ARDS.This was a retrospective analysis over a 10-year period of patients with moderate-to-severe ARDS. PVD and ACP were assessed by echocardiography. ARDS episodes were assigned to ACS-ARDS or nonACS-ARDS group according to whether the clinical insult was ACS or not, respectively. To evaluate independent factors associated with ACP, significant univariable risk factors were examined using logistic regression and propensity score analyses.A total of 362 patients were analyzed, including 24 ACS-ARDS. PVD and ACP were identified, respectively, in 24 (100%) and 20 (83%) ACS-ARDS patients, as compared with 204 (60%) and 68 (20%) nonACS-ARDS patients (P 0.0001). The mortality did not differ between ACS-ARDS and nonACS-ARDS patients. Both the crude (odds ratio [OR], 19.9; 95% confidence interval [CI], 6.6-60; P 0.0001), multivariable adjustment (OR, 27.4; 95% CI, 8.2-91.5; P 0.001), and propensity-matched (OR, 11.7; 95% CI, 1.2-110.8; P = 0.03) analyses found a significant association between ACS-ARDS and ACP.All SCD patients presenting with moderate-to-severe ARDS as a consequence of ACS experienced PVD and more than 80% of them exhibited ACP. These results suggest a predominant role for PVD in the pathogenesis of severe forms of ACS.

Published
2016

39. Alveolar lymphocytosis with plasmacytosis in severe COVID-19

Author

Guillaume Voiriot, Aude Gibelin, Anne Fajac, Muriel Fartoukh, and Antoine Parrot

Subjects
Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, Lymphocytosis, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Bronchoalveolar lavage fluid, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Plasmacytosis, COVID-19, Pneumonia, medicine.disease, Virology, Article, Critical care, Pandemic, medicine, medicine.symptom, business
Published
2020

40. Disparity of the 'screen-and-isolate' policy for multidrug-resistant organisms: A national survey in French adult ICUs

Author

Michel Djibré, Guillaume Voiriot, Muriel Fartoukh, Vincent Labbé, Jean Pierre Fulgencio, Aude Gibelin, Clarisse Blayau, and Zoé Coppere

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Isolation (health care), Epidemiology, health care facilities, manpower, and services, 030106 microbiology, Variable screening, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, Drug Resistance, Multiple, Bacterial, Surveys and Questionnaires, medicine, Humans, Icu stay, 030212 general & internal medicine, Infection Control, business.industry, Health Policy, Data Collection, Public Health, Environmental and Occupational Health, Bacterial Infections, Intensive care unit, Organizational Policy, Anti-Bacterial Agents, Intensive Care Units, Infectious Diseases, Contact precautions, Emergency medicine, France, business
Abstract

Background The prevalence of multidrug-resistant organisms (MDROs) has dramatically increased. The aim of this survey was to describe and analyze the different screening and isolation policies regarding MDROs in French adult intensive care units (ICUs). Materials and Methods A multicenter online survey was performed among French ICUs, including 63 questions distributed into 4 parts: characteristics of the unit, MDRO screening policy, policy regarding contact precautions, and ecology of the unit. Results From April 2015 to June 2016, 73 of 301 ICUs (24%) participated in the survey. MDRO screening was performed on admission in 96% of ICUs, for at least 1 MDRO (78%). MDRO screening was performed weekly during ICU stay in 83% of ICUs. Preemptive isolation was initiated on admission in 82% of ICUs, mostly in a targeted way (71%). Imported and acquired MDRO rates >10% were reported in 44% and 27% of ICUs, respectively. An MDRO outbreak had occurred within the past 3 years in 48% of cases. Conclusion French ICUs have variable screening and isolation approaches for MDROs, as up to 10 combinations were met. Discrepancies with the 2009 national guidelines were observed. Very few ICUs practice without some form of screening and isolation of patients upon admission.

Published
2018

41. Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition

Author

Aude Gibelin, Bernard Maitre, Christian Brun-Buisson, Nicolas de Prost, Antoine Parrot, Muriel Fartoukh, Armand Mekontso Dessap, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pôle Thorax Voies aériennes, Groupe Hospitalier des Hôpitaux Universitaires de l’Est Parisien, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Collégium Gallilée, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, ARDS, Pediatrics, medicine.medical_specialty, artificial, Idiopathic pulmonary fibrosis, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Pulmonary edema, Intensive care, Internal medicine, Prevalence, medicine, Risk of mortality, Humans, Respiratory distress syndrome adult, Diffuse alveolar damage, Lung diseases, Aged, Retrospective Studies, Aged, 80 and over, Respiratory Distress Syndrome, medicine.diagnostic_test, business.industry, Respiration, Organ dysfunction, 030208 emergency & critical care medicine, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Bronchoalveolar lavage, 030228 respiratory system, Female, France, medicine.symptom, business
Abstract

International audience; PurposeSome patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDSCRF−) in comparison with others (ARDSCRF+).MethodsRetrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012.ResultsThe prevalence of ARDSCRF− was 7.5 % (95 % CI [5.5–9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDSCRF− patients had a lower logistic organ dysfunction score (4 [3–8] vs. 10 [6–13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46–74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02–4.18]; p = 0.044). Among ARDSCRF− patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03–0.62]) was associated with ICU survival.ConclusionsThe absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

Published
2015

42. Bronchial Dieulafoy’s Disease: Visualization of Embolization Particles in Bronchial Aspirate

Author

Valentine Bonnefoy, Aude Gibelin, Martine Antoine, Jalal Assouad, Muriel Fartoukh, Marc Garnier, and Sebastian Tavolaro

Subjects
Male, Pulmonary and Respiratory Medicine, Hemoptysis, medicine.medical_specialty, Computed Tomography Angiography, Critical Illness, medicine.medical_treatment, Radiography, Treatment outcome, MEDLINE, Pulmonary disease, Bronchial Arteries, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Risk Assessment, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Text mining, Recurrence, Bronchoscopy, medicine, Humans, Embolization, Pneumonectomy, Aged, business.industry, Follow up studies, Combined Modality Therapy, Embolization, Therapeutic, Intensive Care Units, Treatment Outcome, 030228 respiratory system, Radiography, Thoracic, Dieulafoy s disease, Radiology, business, Follow-Up Studies
Published
2018

43. Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure

Author

Pierre Bailly, Jean-Pierre Frat, Gael Pradel, Nicolas Terzi, Nicolas Deye, Arnaud W. Thille, Hodanou Nanadoumgar, Alexandre Lautrette, Mai-Anh Nay, Rémi Coudroy, Stéphanie Ragot, Aude Gibelin, Maxens Decavèle, Christine Lebert, Anahita Rouzé, François Beloncle, Grégoire Muller, Emmanuel Vivier, Guillaume Lacave, Adel Maamar, Laurence Dangers, Jean-Damien Ricard, Jeremy Bourenne, Anthony Le Meur, Alexandre Demoule, Romain Sonneville, Arnaud Gacouin, Séverin Cabasson, Jean Dellamonica, Caroline Sabatier, Guillaume Barberet, Keyvan Razazi, Stephan Ehrmann, Lassane Zanre, Christophe Girault, René Robert, and Pierre-Eric Danin

Subjects
Mechanical ventilation, business.industry, medicine.medical_treatment, 010102 general mathematics, General Medicine, Airway Extubation, 01 natural sciences, Intensive care unit, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Randomized controlled trial, Respiratory failure, law, Anesthesia, medicine, Breathing, Intubation, 030212 general & internal medicine, 0101 mathematics, business, Nose
Abstract

Importance High-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal strategy of ventilation to avoid reintubation. Objective To determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU. Design, Setting, and Participants Multicenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018. Interventions Patients were randomly assigned to high-flow nasal oxygen alone (n = 306) or high-flow nasal oxygen with NIV (n = 342) immediately after extubation. Main Outcomes and Measures The primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality. Results Among 648 patients who were randomized (mean [SD] age, 70 [10] years; 219 women [34%]), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, −6.4% [95% CI, −12.0% to −0.9%];P = .02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, −8.7% [95% CI, −15.2% to −1.8%];P = .01) and reintubation rates up until ICU discharge (12% vs 20%, difference −7.4% [95% CI, −13.2% to −1.8%];P = .009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, −2.4% [95% CI, −6.7% to 1.7%];P = .25). Conclusions and Relevance In mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial Registration ClinicalTrials.gov Identifier:NCT03121482

Published
2019

44. Aspergillus-positive lower respiratory tract samples in patients with the acute respiratory distress syndrome: a 10-year retrospective study

Author

Christian Brun-Buisson, Guillaume Carteaux, Armand Mekontso Dessap, Aude Gibelin, Damien Contou, Françoise Botterel, Françoise Foulet, Keyvan Razazi, Nicolas de Prost, Frédéric Schlemmer, Matthieu Dorison, and Jérémy Rosman

Subjects
medicine.medical_specialty, ARDS, Invasive pulmonary aspergillosis, Critical Care and Intensive Care Medicine, Aspergillosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Risk of mortality, Medicine, 030212 general & internal medicine, Diffuse alveolar damage, Aspergillus, Acute respiratory distress syndrome, biology, business.industry, Research, Incidence (epidemiology), 030208 emergency & critical care medicine, medicine.disease, biology.organism_classification, Surgery, Pneumonia, medicine.anatomical_structure, business, Immunosuppression, Respiratory tract
Abstract

Background The detection of Aspergillus spp. in endotracheal aspirate cultures of mechanically ventilated patients may reflect either colonization or infection. However, little is known about the prevalence and the impact on outcome of respiratory tract sample positive for Aspergillus during the acute respiratory distress syndrome (ARDS). Methods We conducted a monocentric, retrospective study over a 10-year period (January 2006–December 2015) in the ICU of a university hospital. All consecutive adult patients with ARDS were included, and the diagnosis of invasive pulmonary aspergillosis was assessed using a previously validated algorithm. Results In total, 423 ARDS patients were included with 35 patients [8.3 %, 95 % CI (5.4–10.6)] having at least one respiratory tract sample positive for Aspergillus (Aspergillus+ patients) after a median delay of 3 days (1–11) following ICU admission. Comorbidities did not differ between Aspergillus+ and Aspergillus− patients except for more frequent immunosuppression in Aspergillus+ patients (40 vs. 22 %; p = 0.02). There was no difference between Aspergillus− and Aspergillus+ patients regarding in-ICU mortality, ventilator-free days at day 28, and incidence of ventilator-associated pneumonia, but need for renal replacement therapy was higher in Aspergillus+ patients than in others (49 vs. 27 %; p = 0.01). Seventeen [4.0 %, 95 % CI (2.1–5.9)] patients had putative/proven aspergillosis. After adjusting on covariates associated with ICU mortality, putative/proven aspergillosis was associated with in-ICU mortality [aOR = 9.58 (1.97–46.52); p = 0.005], while Aspergillus colonization was not [aOR = 0.64 (0.21–1.99); p = 0.44]. Conclusions Eight percent of ARDS patients had Aspergillus spp.-positive respiratory tract cultures. These had a higher risk of mortality only when categorized as having putative or proven invasive pulmonary aspergillosis.

Published
2016

45. Acute respiratory distress syndrome in a young soccer player: search obturator internus primary pyomyositis. A reverse Lemierre syndrome

Author

Aude Gibelin, Muriel Fartoukh, Michel Djibré, Damien Contou, Vincent Labbé, and A. Parrot

Subjects
Male, medicine.medical_specialty, Pyomyositis, Acute respiratory distress, Iliac Vein, Suction, Methicillin, Young Adult, Soccer, medicine, Humans, Lemierre Syndrome, Respiratory Distress Syndrome, business.industry, Heparin, Anticoagulants, General Medicine, medicine.disease, Combined Modality Therapy, Respiration, Artificial, Surgery, Anti-Bacterial Agents, Obturator internus, Emergency Medicine, business, Pulmonary Embolism, Tomography, X-Ray Computed
Published
2014

46. Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

Author

Aude Gibelin, Christian Brun-Buisson, and Nicolas de Prost

Subjects
medicine.medical_specialty, Chest Pain, Fever, Lung abscess, Chest pain, digestive system, Article, Young Adult, Risk Factors, Internal medicine, medicine, Humans, Lung Abscess, Risk factor, Intensive care medicine, Abscess, skin and connective tissue diseases, Empyema, Pleural, business.industry, Anti-Inflammatory Agents, Non-Steroidal, General Medicine, Pneumonia, Pneumococcal, medicine.disease, Empyema, digestive system diseases, Anti-Bacterial Agents, Pneumonia, Pneumococcal pneumonia, Female, medicine.symptom, business, Complication
Abstract

Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.

Published
2013

47. Le benralizumab : une perspective thérapeutique dans le DRESS ?

Author

Guillaume Lefèvre, Maud Garinat, Cécile Brin, Cyrielle Desnos, Aude Gibelin, Matthieu Turpin, Angèle Soria, Guillaume Voiriot, Matthieu Groh, Cédric Rafat, Staumont-Salle Delphine, Maëlle Dumont, and Farah Mesli

Subjects
SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Ocean Engineering, Benralizumab, P031, chemistry.chemical_compound, chemistry, Immunology and Allergy, Medicine, DRESS, Safety, Risk, Reliability and Quality, business, Humanities
Abstract

Introduction Le traitement du syndrome d’hypersensibilité médicamenteuse ou drug reaction with eosinophilia and systemic symptoms (DRESS) est difficile. En cas d’atteinte viscérale, une corticothérapie systémique est le plus souvent proposée en première intention malgré l’absence d’essai clinique. En l’absence de réponse, le traitement de deuxième ligne n’est pas codifié. Récemment, le benralizumab un anticorps monoclonal ciblant le récepteur de l’interleukine 5 a été utilisé pour traiter deux patients avec une infection sévère à COVID-19 ayant un DRESS résistant à une corticothérapie à forte dose. Nous rapportons le cas d’un patient infecté par le COVID-19 atteint d’un DRESS avec engagement du pronostic vital traité par benralizumab. Matériel et méthodes Un patient de 43 ans, sans antécédent, hospitalisé pour un syndrome de détresse respiratoire aigu lié à une infection à COVID-19 a présenté un DRESS sévère associant une hyperéosinophilie (6660/mm3), de la fièvre, une polyadénopathie, un exanthème maculopapuleux avec œdème du visage, une insuffisance rénale aiguë, une hépatite et une pneumopathie à éosinophiles. Les médicaments les plus imputables étaient la ciprofloxacine et le céfépime. Le traitement initial de ce DRESS sévère a comporté une corticothérapie locale et systémique. Une aggravation hémodynamique a motivé un traitement par immunoglobulines intraveineuses. Devant une atteinte pluriviscérale associée à une majoration du taux d’éosinophiles (10 000/mm3) et des critères biologiques de syndrome d’activation macrophagique avec engagement du pronostic vital, une injection de benralizumab 30 mg en sous-cutanée a été réalisée après concertation multidisciplinaire. Résultats (si adapté) : l’évolution a été très rapidement favorable avec une chute du nombre d’éosinophiles sanguins en 48 heures et une amélioration globale des dysfonctions d’organes et des lésions cutanées. Une deuxième injection de benralizumab a été réalisée quatre semaines plus tard en raison de la réascension modérée des éosinophiles à la décroissance de la corticothérapie générale, sans récidive. Discussion La physiopathologie du DRESS est complexe, elle met en jeu des réponses lymphocytaires T spécifiques et souvent des réactivations virales. Aucune réplication des virus fréquemment rencontrés dans le DRESS (HSV1, HSV2, VZV, CMV, EBV et HHV6) n’a été trouvée chez notre patient. Mais, la mise en évidence d’une réplication du SARS-CoV 2 à distance de l’infection initiale (plus de 60 jours après la 1re PCR SARS-CoV2 positive) pourrait suggérer un rôle potentiel inducteur du SARS-CoV2 dans le DRESS. Le rôle précis des éosinophiles dans la physiopathologie du DRESS n’est pas élucidé, mais l’efficacité et la bonne tolérance du benralizumab chez notre patient plaide en faveur de l’intérêt d’une thérapie anti-IL5 récepteur chez les patients atteints de DRESS sévère corticorésistant ou avec besoin d’une alternative aux corticoïdes systémiques.

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