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Your search keyword '"Jacques, Cadranel"' showing total 69 results
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69 results on '"Jacques, Cadranel"'

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. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trialsResearch in context

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Ilias I. Siempos, Andre C. Kalil, Drifa Belhadi, Viviane Cordeiro Veiga, Alexandre Biasi Cavalcanti, Westyn Branch-Elliman, Eleni Papoutsi, Konstantinos Gkirgkiris, Nikoleta A. Xixi, Anastasia Kotanidou, Olivier Hermine, Raphaël Porcher, Xavier Mariette, Philippe Ravaud, Serge Bureau, Maxime Dougados, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Annick Tibi, Elie Azoulay, Jacques Cadranel, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Karine Lacombe, Matthieu Mahevas, Frédéric Pene, Valerie Pourchet-Martinez, Frédéric Schlemmer, Yazdan Yazdanpanah, Gabriel Baron, Elodie Perrodeau, Damien Vanhoye, Cécile Kedzia, Lauren Demerville, Anne Gysembergh-Houal, Alexandre Bourgoin, Nabil Raked, Lakhdar Mameri, Claire Montlahuc, Lucie Biard, St.phanie Alary, Samir Hamiria, Thinhinane Bariz, Hala Semri, Dhiaa Meriem Hai, Moustafa Benafla, Mohamed Belloul, Pernelle Vauboin, Saskia Flamand, Claire Pacheco, Anouk Walter-Petrich, Emilia Stan, Souad Benarab, Corine Nyanou, Robin Charreteur, Céline Dupre, Kévin Cardet, Blandine Lehmann, Kamyl Baghli, Claire Madelaine, Eric D'Ortenzio, Oriane Puéchal, Caroline Semaille, Laurent Savale, Anatole Harrois, Samy Figueiredo, Jacques Duranteau, Nadia Anguel, Arthur Pavot, Xavier Monnet, Christian Richard, Jean-Louis Teboul, Philippe Durand, Pierre Tissieres, Mitja Jevnikar, David Montani, Stephan Pavy, Gaétane Nocturne, Samuel Bitoun, Nicolas Noel, Olivier Lambotte, Lelia Escaut, Stephane Jauréguiberry, Elodie Baudry, Christiane Verny, Edouard Lefevre, Mohamad Zaidan, Domitille Molinari, Gaël Leprun, Alain Fourreau, Laurent Cylly, Lamiae Grimaldi, Myriam Virlouvet, Ramdane Meftali, Soléne Fabre, Marion Licois, Asmaa Mamoune, Yacine Boudali, Clotilde Le Tiec, Céline Verstuyft, Anne-Marie Roques, Sophie Georgin-Lavialle, Patricia Senet, Gilles Pialoux, Angele Soria, Antoine Parrot, Helene François, Nathalie Rozensztajn, Emmanuelle Blin, Pascaline Choinier, Juliette Camuset, Jean-Simon Rech, Antony Canellas, Camille Rolland-Debord, Nadege Lemarié, Nicolas Belaube, Marine Nadal, Martin Siguier, Camille Petit-Hoang, Julie Chas, Elodie Drouet, Matthieu Lemoine, Audrey Phibel, Lucie Aunay, Eliane 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Frank, David Wyles, Heather Young, Myoung-don Oh, Wan Beom Park, Chang Kyung Kang, Vincent Marconi, Abeer Moanna, Sushma Cribbs, Telisha Harrison, Eu Suk Kim, Jongtak Jung, Kyoung-Ho Song, Hong Bin Kim, Seow Yen Tan, Humaira Shafi, MF Jaime Chien, Raymond KC. Fong, Daniel D. Murray, Jens Lundgren, Henrik Nielsen, Tomas Jensen, Barry S. Zingman, Robert Grossberg, Paul F. Riska, Otto O. Yang, Jenny Ahn, Rubi Arias, Rekha R. Rapaka, Naomi Hauser, James D. Campbell, William R. Short, Pablo Tebas, Jillian T. Baron, Susan L.F. McLellan, Lucas S. Blanton, Justin B. Seashore, C. Buddy Creech, Todd W. Rice, Shannon Walker, Isaac P. Thomsen, Diego Lopez de Castilla, Jason W. Van Winkle, Francis X. Riedo, Surinder Kaur Pada, Alvin DY. Wang, Li Lin, Michelle Harkins, Gregory Mertz, Nestor Sosa, Louis Yi Ann Chai, Paul Anantharajah Tambyah, Sai Meng Tham, Sophia Archuleta, Gabriel Yan, David A. Lindholm, Ana Elizabeth Markelz, Katrin Mende, Richard Mularski, Elizabeth Hohmann, Mariam Torres-Soto, Nikolaus Jilg, Ryan C. Maves, Gregory C. Utz, Sarah L. George, Daniel F. Hoft, James D. Brien, Roger Paredes, Lourdes Mateu, Cora Loste, Princy Kumar, Sarah Thornton, Sharmila Mohanraj, Noreen A. Hynes, Lauren M. Sauer, Christopher J. Colombo, Christina Schofield, Rhonda E. Colombo, Susan E. Chambers, Richard M. Novak, Andrea Wendrow, Samir K. Gupta, Tida Lee, Tahaniyat Lalani, Mark Holodniy, Aarthi Chary, Nikhil Huprikar, Anuradha Ganesan, Norio Ohmagari, Ayako Mikami, D. Ashley Price, Christopher J.A. Duncan, Kerry Dierberg, Henry J. Neumann, Stephanie N. Taylor, Alisha Lacour, Najy Masri, Edwin Swiatlo, Kyle Widmer, James D. Neaton, Mary Bessesen, David S. Stephens, Timothy H. Burgess, Timothy M. Uyeki, Robert Walker, G. Lynn Marks, Anu Osinusi, Huyen Cao, Anabela Cardoso, Stephanie de Bono, Douglas E. Schlichting, Kevin K. Chung, Jennifer L. Ferreira, Michelle Green, Mat Makowski, Michael R. Wierzbicki, Tom M. Conrad, Jill Ann El-Khorazaty, Heather Hill, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Teri Lewis, Jing Wang, John H. Beigel, Kay M. Tomashek, Varduhi Ghazaryan, Tatiana Beresnev, Seema Nayak, Lori E. Dodd, Walla Dempsey, Effie Nomicos, Marina Lee, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Tammy Yokum, Janice Arega, Ruth Florese, Jocelyn D. Voell, Richard Davey, Ruth C. Serrano, Zanthia Wiley, Varun K. Phadke, Paul A. Goepfert, Carlos A. Gomez, Theresa A. Sofarelli, Laura Certain, Hannah N. Imlay, Cameron R. Wolfe, Emily R. Ko, John J. Engemann, Nora Bautista Felix, Claire R. Wan, Sammy T. Elmor, Laurel R. Bristow, Michelle S. Harkins, Nicole M. Iovine, Marie-Carmelle Elie-Turenne, Victor F. Tapson, Pyoeng Gyun Choe, Richard A. Mularski, Kevin S. Rhie, Rezhan H. Hussein, Dilek Ince, Patricia L. Winokur, Jin Takasaki, Sho Saito, Kimberly McConnell, PharmD, David L. Wyles, Ellen Sarcone, Kevin A. Grimes, Katherine Perez, Charles Janak, Jennifer A. Whitaker, Paulina A. Rebolledo, John Gharbin, Allison A. Lambert, Diego F. Zea, Emma Bainbridge, David C. Hostler, Jordanna M. Hostler, Brian T. Shahan, Evelyn Ling, Minjoung Go, Fleesie A. Hubbard, Melony Chakrabarty, Maryrose Laguio-Vila, Edward E. Walsh, Faheem Guirgis, Vincent C. Marconi, Christian Madar, Scott A. Borgetti, Corri Levine, Joy Nock, Keith Candiotti, Julia Rozman, Fernando Dangond, Yann Hyvert, Andrea Seitzinger, Kaitlyn Cross, Stephanie Pettibone, Seema U. Nayak, and Gregory A. Deye

Subjects
Acute respiratory distress syndrome, Acute hypoxemic respiratory failure, Pneumonia, Critically ill, Cancer, Medicine (General), R5-920
Abstract

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Published
2024
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3. Fully automated radiolabeling of [68Ga]Ga-EMP100 targeting c-MET for PET-CT clinical imaging

Author

Timofei Rusu, Matthieu Delion, Charlotte Pirot, Amaury Blin, Anita Rodenas, Jean-Noël Talbot, Nicolas Veran, Christophe Portal, Françoise Montravers, Jacques Cadranel, and Aurélie Prignon

Subjects
[68Ga]Ga-radiopharmaceuticals, [68Ga]Ga-EMP100, c-MET, PET imaging, Medical physics. Medical radiology. Nuclear medicine, R895-920, Therapeutics. Pharmacology, RM1-950
Abstract

Abstract Background c-MET is a transmembrane receptor involved in many biological processes and contributes to cell proliferation and migration during cancer invasion process. Its expression is measured by immunehistochemistry on tissue biopsy in clinic, although this technique has its limitations. PET-CT could allow in vivo mapping of lesions expressing c-MET, providing whole-body detection. A number of radiopharmaceuticals are under development for this purpose but are not yet in routine clinical use. EMP100 is a cyclic oligopeptide bound to a DOTA chelator, with nanomolar affinity for c-MET. The aim of this project was to develop an automated method for radiolabelling the radiopharmaceutical [68Ga]Ga-EMP100. Results The main results showed an optimal pH range between 3.25 and 3.75 for the complexation reaction and a stabilisation of the temperature at 90 °C, resulting in an almost complete incorporation of gallium-68 after 10 min of heating. In these experiments, 90 µg of EMP-100 peptide were initially used and then lower amounts (30, 50, 75 µg) were explored to determine the minimum required for sufficient synthesis yield. Radiolysis impurities were identified by radio-HPLC and ascorbic acid and ethanol were used to improve the purity of the compound. Three batches of [68Ga]Ga-EMP100 were then prepared according to the optimised parameters and all met the established specifications. Finally, the stability of [68Ga]Ga-EMP100 was assessed at room temperature over 3 h with satisfactory results in terms of appearance, pH, radiochemical purity and sterility. Conclusions For the automated synthesis of [68Ga]Ga-EMP100, the parameters of pH, temperature, precursor peptide content and the use of adjuvants for impurity management were efficiently optimised, resulting in the production of three compliant and stable batches according to the principles of good manufacturing practice. [68Ga]Ga-EMP100 was successfully synthesised and is now available for clinical development in PET-CT imaging.

Published
2023
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4. International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations

Author

Jean-François David Cadranel, Isabelle Ollivier-Hourmand, Jacques Cadranel, Thierry Thevenot, Honoré Zougmore, Eric Nguyen-Khac, Christophe Bureau, Manon Allaire, Jean-Baptiste Nousbaum, Véronique Loustaud-Ratti, Xavier Causse, Philippe Sogni, Bertrand Hanslik, Marc Bourliere, Jean-Marie Peron, Nathalie Ganne-Carrie, Thong Dao, Dominique Thabut, Bernard. Maitre, Nabil Debzi, Ryad Smadhi, Roger Sombie, Raimi Kpossou, Olivier Nouel, Julien Bissonnette, Isaac Ruiz, Mourad Medmoun, Sergio Negrin Dastis, Pierre Deltenre, Florent Artru, Chantal Raherison, Laure Elkrief, and Tristan Lemagoarou

Subjects
Hepatic hydrothorax, Therapeutic pleural puncture, Albumin infusion, Spontaneous bacterial empyema, Talcage pleurodesis, Indwelling pleural catheter, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. Methods Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. Results Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p

Published
2023
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5. Enhancing antifungal treatment for chronic cavitary pulmonary aspergillosis through the addition of endobronchial valve therapy

Author

Thomas Maitre, Juliette Camuset, Morgane Faure, Christophe Cracco, Georgina Maalouf, Yves Allenbach, Matthias Barral, Arnaud Fekkar, Mihaela Giol, Antoine Parrot, and Jacques Cadranel

Subjects
Diseases of the respiratory system, RC705-779
Abstract

A 62-year-old male experienced anti-MDA5 dermatomyositis with lung involvement, treated with immunosuppressive therapy leading to chronic cavitary pulmonary aspergillosis in left upper lobe. Patient's history was complicated by complete left pneumothorax due to alveolar-pleural fistula occurring because of the rupture of the pulmonary cavitation. Left lung failed to re-expand despite a four-week period of pleural drainage. In addition to antifungal therapy, patient received endobronchial valve therapy in the anterior segmental bronchus of the left upper lobe leading to air leak cessation, left lung re expansion and aspergillosis cavitation closure.

Published
2024
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6. Therapeutic strategies to overcome EGFR mutations as acquired resistance mechanism in ALK-rearranged non-small-cell lung cancer: Case Reports

Author

Lionel Michaux, Alexandre Perrier, Camille Mehlman, Hussa Alshehhi, Antonin Dubois, Roger Lacave, Florence Coulet, Jacques Cadranel, and Vincent Fallet

Subjects
non-small cell lung cancer, ALK rearrangement, tyrosine kinase inhibitors, resistance mutation, EGFR, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

IntroductionALK tyrosine kinase inhibitors (ALK TKIs) have improved prognosis in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC). However, drug resistance mechanisms occur inevitably during the course of treatment leading to disease progression. Activation of epidermal growth factor receptor (EGFR) bypass signaling pathway is an uncommon cause of acquired resistance to ALK TKIs.MethodWe present two patients with EML4-ALK rearranged NSCLC, developing an acquired EGFR resistance mutation after receiving multiple lines of ALK TKIs.ResultsWhile preclinical models have showed encouraging data, there is a critical need for clinical studies on treatment strategies to overcome this drug resistance. Three real-life therapeutic approaches were used in this report: i) using brigatinib, an inhibitor targeting both ALK and EGFR tyrosine kinases; ii) combining two ALK TKIs together; and iii) delivering doublet platinum chemotherapy. In case 1, time to treatment failure (TTF) was 9.5 months with brigatinib; in case 2, TTF was 10 months with combined TKIs (osimertinib and brigatinib), whereas TTF with chemotherapy was only 2 months. Tolerability profile TKIs combotherapy was acceptable.ConclusionThese case reports underline the therapeutic complexity of EGFR-acquired resistance mutation in ALK+ NSCLC and offers some leads to solve this real-life clinical challenge.

Published
2023
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7. 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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9. Anti-PD-1 immune-related adverse events are associated with high therapeutic antibody fixation on T cells

Author

Marianne Gazzano, Christophe Parizot, Dimitri Psimaras, Aurore Vozy, Marine Baron, Baptiste Abbar, Vincent Fallet, Elena Litvinova, Anthony Canellas, Cristina Birzu, Valérie Pourcher, Mehdi Touat, Nicolas Weiss, Sophie Demeret, Damien Roos-Weil, Jean-Philippe Spano, Celeste Lebbe, Joe-Elie Salem, Jacques Cadranel, Baptiste Hervier, Guy Gorochov, and Amélie Guihot

Subjects
biomarker, checkpoint inhibition, irAEs, immune related adverse events, flow cytometry, prediction, Immunologic diseases. Allergy, RC581-607
Abstract

Immune checkpoint inhibitors (ICI) widely improved the treatment of solid and hematologic malignancies. Yet, a remarkable proportion of patients receiving ICI develop immune related adverse events (irAEs) which are difficult to define as treatment-related. This underlines the need to develop a biomarker to guide irAE diagnosis. We developed a novel flow cytometry assay combining measurement of anti-PD-1 (programmed cell death protein-1) occupancy and evaluation of remaining PD-1 receptor availability with anti-IgG4 PE and anti-PD-1 BV421. We prospectively collected blood and biological fluids samples from patients treated by IgG4 anti-PD-1 therapy (nivolumab or pembrolizumab), with (n=18) or without (n=12) current irAE. We analyzed PD-1+ and IgG4+ staining pattern and MFI values of these parameters on CD4 and CD8 T cells, and IgG4+/PD-1+ MFI ratios are calculated. A higher mean fluorescence intensity IgG4+/PD-1+ ratio was measured on peripheral CD4+ T cells of irAE cases, when compared to controls (p=0.003). ICI-related toxicity is therefore associated with increased therapeutic antibody occupancy of PD-1 receptors on CD4+ T cells. Furthermore, in one case of ICI-related pneumonitis, binding of therapeutic antibody was stronger on lung CD4+ T cell than in blood. In another case of ICI-related encephalitis, the PD-1 receptor occupancy was total on CSF CD4 T cells, but only partial on peripherical CD4 T cells. Our results suggest that flow cytometry monitoring of ICI occupancy can be used in patients treated with monoclonal ICI to guide irAE diagnosis.

Published
2022
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10. Impact of COVID-19 and lockdowns on pulmonary embolism in hospitalized patients in France: a nationwide study

Author

Pierre Tankere, Jonathan Cottenet, Pascale Tubert-Bitter, Anne-Sophie Mariet, Guillaume Beltramo, Jacques Cadranel, Lionel Piroth, Philippe Bonniaud, and Catherine Quantin

Subjects
COVID-19, Pulmonary embolism, Medico-administrative data, Hospital, Lockdown, SARS-COV2, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background This study assessed the impact of the COVID-19 epidemic on overall hospitalizations for pulmonary embolism (PE) in France in comparison with previous years, and by COVID-19 and non-COVID-19 status. Methods Hospitalization data (2017–2020) were extracted from the French National Discharge database (all public and private hospitals). We included all patients older than 18 years hospitalized during the 3 years and extracted PE status and COVID-19 status (from March 2020). Age, sex and risk factors for PE (such as obesity, cancer) were identified. We also extracted transfer to an intensive care unit (ICU) and hospital death. The number of PE and the frequency of death in patients in 2019 and 2020 were described by month and by COVID-19 status. Logistic regressions were performed to identify the role of COVID-19 among other risk factors for PE in hospitalized patients. Results The overall number of patients hospitalized with PE increased by about 16% in 2020 compared with 2019, and mortality also increased to 10.3% (+ 1.2%). These increases were mostly linked to COVID-19 waves, which were associated with PE hospitalization in COVID-19 patients (PE frequency was 3.7%; 2.8% in non-ICU and 8.8% in ICU). The final PE odds ratio for COVID-19 hospitalized patients was 4 compared with other hospitalized patients in 2020. The analyses of PE in non-COVID-19 patients showed a 2.7% increase in 2020 compared with the previous three years. Conclusion In 2020, the overall number of patients hospitalized with PE in France increased compared to the previous three years despite a considerable decrease in scheduled hospitalizations. Nevertheless, proactive public policy focused on the prevention of PE in all patients should be encouraged.

Published
2021
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11. Lung cancer in patients with fibrosing interstitial lung diseases: an overview of current knowledge and challenges

Author

Namrata Kewalramani, Carlos Machahua, Venerino Poletti, Jacques Cadranel, Athol U. Wells, and Manuela Funke-Chambour

Subjects
Medicine
Abstract

Patients with progressive fibrosing interstitial lung diseases (fILD) have increased morbidity and mortality. Lung fibrosis can be associated with lung cancer. The pathogenesis of both diseases shows similarities, although not all mechanisms are understood. The combination of the diseases is challenging, due to the amplified risk of mortality, and also because lung cancer treatment carries additional risks in patients with underlying lung fibrosis. Acute exacerbations in fILD patients are linked to increased mortality, and the risk of acute exacerbations is increased after lung cancer treatment with surgery, chemotherapy or radiotherapy. Careful selection of treatment modalities is crucial to improve survival while maintaining acceptable quality of life in patients with combined lung cancer and fILD. This overview of epidemiology, pathogenesis, treatment and a possible role for antifibrotic drugs in patients with lung cancer and fILD is the summary of a session presented during the virtual European Respiratory Society Congress in 2021. The review summarises current knowledge and identifies areas of uncertainty. Most current data relate to patients with combined idiopathic pulmonary fibrosis and lung cancer. There is a pressing need for additional prospective studies, required for the formulation of a consensus statement or guideline on the optimal care of patients with lung cancer and fILD.

Published
2022
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12. Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group

Author

Olivier Hermine, Xavier Mariette, Raphael Porcher, Felix Djossou, Yann Nguyen, Jean-Benoît Arlet, Laurent Savale, Jean Luc Diehl, Sophie Georgin-Lavialle, Jacques Cadranel, Gilles Pialoux, Karine Lacombe, Arsène Mekinian, Hélène Gros, Xavier Lescure, Jade Ghosn, Elisabeth Coupez, Kevin Grapin, Christophe Rapp, Marc Michel, Anne Lise Lecapitaine, Jean Marie Michot, Nathalie Costedoat-Chalumeau, Liem Binh Luong Nguyen, Luca Semerano, François Raffi, Claire Aguillar, Claire Rouzaud, Jacques Eric Gottenberg, Yves Hansmann, Boris Bienvenu, Jonathan London, Franklin Samou Fantchou, Felix Ackermann, Antoine Gros, Alexandre Morel, Nicolas Gambier, Damien Sène, Bruno Mégarbane, Elie Azoulay, Serge Bureau, Maxime Dougados, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Mathieu Mahevas, Frédéric Pène, Frédéric Schlemmer, Valérie Pourcher-Martinez, Annick Tibi, Gabriel Baron, Elodie Perrodeau, Stéphanie Baron, Gabriel Steg, Yazdan Yazdapanah, Tabassome Simon, Matthieu Resche-Rigon, Pierre-Louis Tharaux, and Philippe Ravaud

Subjects
COVID-19, Tocilizumab+Dexamethasone, Randomized clinical trial, Medicine (General), R5-920
Abstract

Summary: Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42–1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19–20–0151, PHRC COVID-19–20–0029], Fondation de l'Assistance Publique – Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale” (FRM). Tocilizumab was provided by Roche.

Published
2022
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14. Brief Report of Anti–Programmed Cell Death Protein-1 in Human Immunodeficiency Virus Setting: Relevant and Breaking Results in First-Line NSCLC Therapy

Author

Lise Bertin, MD, Anthony Canellas, MD, Baptiste Abbar, MD, Marianne Veyri, Jean-Philippe Spano, MD, PhD, Jacques Cadranel, MD, PhD, and Armelle Lavolé, MD

Subjects
HIV, Anti–PD-1, CD4+, Viral load, Lung cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

In the recent past, we observed an increased risk of cancer in the population with human immunodeficiency virus (HIV) owing to the development of antiretroviral therapies that decreased mortality caused by HIV-specific infections. This particularly fragile population is frequently excluded from clinical trials, and up-to-date recommendations for these patients are lacking. Only few cases of patients with HIV suffering from cancer and undergoing first-line immunotherapy have been reported so far. Here, we report the largest known study of patients with HIV with NSCLC (five patients) undergoing first-line immunotherapy by pembrolizumab, after CANCERVIH group selection. Our results are consistent with those of previous case reports concerning safety of immunotherapy in patients with HIV, revealing no severe or fatal toxicity, opportunistic infections, or immune reconstitution inflammatory syndrome. Moreover, pembrolizumab did not seem to modify HIV viral parameters. We also evaluated the effectiveness of immunotherapy in these HIV-immunosuppressed patients: the average survival was 9.8 months, with three patients having rapid progression and two partial response. Nevertheless, besides safety and drug-to-drug interactions, the effectiveness of first-line immunotherapy in people living with HIV needs to be supported by larger studies.

Published
2021
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15. Exposure–Response Analysis of Osimertinib in Patients with Advanced Non-Small-Cell Lung Cancer

Author

Thomas Rodier, Alicja Puszkiel, Evelina Cardoso, David Balakirouchenane, Céline Narjoz, Jennifer Arrondeau, Vincent Fallet, Nihel Khoudour, Monia Guidi, Michel Vidal, Xavier Declèves, Chantal Csajka, Jérôme Alexandre, Jacques Cadranel, Elizabeth Fabre, Marie Wislez, François Goldwasser, and Benoit Blanchet

Subjects
osimertinib, non-small-cell lung cancer, pharmacokinetics, pharmacodynamics, Pharmacy and materia medica, RS1-441
Abstract

High interindividual variability (IIV) of the clinical response to epidermal growth factor receptor (EGFR) inhibitors such as osimertinib in non-small-cell lung cancer (NSCLC) might be related to the IIV in plasma exposure. The aim of this study was to evaluate the exposure–response relationship for toxicity and efficacy of osimertinib in unselected patients with advanced EGFR-mutant NSCLC. This retrospective analysis included 87 patients treated with osimertinib. Exposure–toxicity analysis was performed in the entire cohort and survival analysis only in second-line patients (n = 45). No significant relationship between occurrence of dose-limiting toxicity and plasma exposure was observed in the entire cohort (p = 0.23, n = 86). The median overall survival (OS) was approximately two-fold shorter in the 4th quartile (Q4) of osimertinib trough plasma concentration (>235 ng/mL) than in the Q1–Q3 group (12.2 months [CI95% = 8.0–not reached (NR)] vs. 22.7 months [CI95% = 17.1–34.1]), but the difference was not statistically significant (p = 0.15). To refine this result, the exposure–survival relationship was explored in a cohort of 41 NSCLC patients treated with erlotinib. The Q4 erlotinib exposure group (>1728 ng/mL) exhibited a six-fold shorter median OS than the Q1–Q3 group (4.8 months [CI95% = 3.3-NR] vs. 22.8 months (CI95% = 10.6–37.4), p = 0.00011). These results suggest that high exposure to EGFR inhibitors might be related to worse survival in NSCLC patients.

Published
2022
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16. Impact of Anti PD-1 Immunotherapy on HIV Reservoir and Anti-Viral Immune Responses in People Living with HIV and Cancer

Author

Marine Baron, Cathia Soulié, Armelle Lavolé, Lambert Assoumou, Baptiste Abbar, Baptiste Fouquet, Alice Rousseau, Marianne Veyri, Assia Samri, Alain Makinson, Sylvain Choquet, Julien Mazières, Solenn Brosseau, Brigitte Autran, Dominique Costagliola, Christine Katlama, Jacques Cadranel, Anne-Geneviève Marcelin, Olivier Lambotte, Jean-Philippe Spano, Amélie Guihot, The French Cooperative Thoracic Intergroup (IFCT) CHIVA-2 Investigators, and The ANRS Co 24 OncoVIHAC Study Group

Subjects
immune checkpoint blockade, HIV reservoir, anti-HIV immune responses, compensatory mechanisms, Cytology, QH573-671
Abstract

The role of immune checkpoints (ICPs) in both anti-HIV T cell exhaustion and HIV reservoir persistence, has suggested that an HIV cure therapeutic strategy could involve ICP blockade. We studied the impact of anti-PD-1 therapy on HIV reservoirs and anti-viral immune responses in people living with HIV and treated for cancer. At several timepoints, we monitored CD4 cell counts, plasma HIV-RNA, cell associated (CA) HIV-DNA, EBV, CMV, HBV, HCV, and HHV-8 viral loads, activation markers, ICP expression and virus-specific T cells. Thirty-two patients were included, with median follow-up of 5 months. The CA HIV-DNA tended to decrease before cycle 2 (p = 0.049). Six patients exhibited a ≥0.5 log10 HIV-DNA decrease at least once. Among those, HIV-DNA became undetectable for 10 months in one patient. Overall, no significant increase in HIV-specific immunity was observed. In contrast, we detected an early increase in CTLA-4 + CD4+ T cells in all patients (p = 0.004) and a greater increase in CTLA-4+ and TIM-3 + CD8+ T cells in patients without HIV-DNA reduction compared to the others (p ≤ 0.03). Our results suggest that ICP replacement compensatory mechanisms might limit the impact of anti-PD-1 monotherapy on HIV reservoirs, and pave the way for combination ICP blockade in HIV cure strategies.

Published
2022
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18. Influence of the SARS-CoV-2 outbreak on management and prognosis of new lung cancer cases, a retrospective multicentre real-life cohort study

Author

Sonia Priou, Guillaume Lamé, Gérard Zalcman, Marie Wislez, Romain Bey, Gilles Chatellier, Jacques Cadranel, Xavier Tannier, Laurent Zelek, Christel Daniel, Christophe Tournigand, Emmanuelle Kempf, Laboratoire Génie Industriel (LGI), CentraleSupélec-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP CUP Paris, Theranoscan [CHU Tenon] (GRC 4), 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)-Sorbonne Université (SU), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Hôpital Avicenne [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), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, and Fondation ARC pour la recherche contre le cancer (référence COVID202001343)

Subjects
Cancer Research, Lung Neoplasms, SARS-CoV-2, MESH: Delivery of Health Care, MESH: Routinely Collected Health Data, COVID-19, Prognosis, MESH: Lung Neoplasms, Cohort Studies, Oncology, Communicable Disease Control, MESH: COVID-19, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Quality of Health Care, Pandemics, MESH: Early Cancer Detection, Retrospective Studies
Abstract

International audience; IntroductionThe SARS-CoV-2 pandemic has impacted the care of cancer patients. This study sought to assess the pandemic’s impact on the clinical presentations and outcomes of newly referred patients with lung cancer from the Greater Paris area.MethodsWe retrospectively retrieved the electronic health records and administrative data of 11.4 million patients pertaining to Greater Paris University Hospital (AP-HP). We compared indicators for the 2018-2019 period to those of 2020 in regard to newly referred lung cancer cases. We assessed initial tumor stage, delay between first multidisciplinary tumor board (MTB) and anticancer treatment initiation, and 6-month overall survival (OS) rates depending on the anticancer treatment including surgery, palliative systemic treatment, and best supportive care (BSC).ResultAmong 6,240 patients with lung cancer, 2,179 (35%) underwent tumor resection, 2,069 (33%) systemic anticancer therapy, 775 (12%) BSC, whereas 1,217 (20%) did not receive any treatment. During the first lockdown, the rate of new diagnoses decreased by 32% compared with that recorded in 2018-2019. Initial tumor stage, repartition of patients among treatment categories, and MTB-related delays remained unchanged. The 6-month OS rates of patients diagnosed in 2018-2019 who underwent tumor resection were 98% vs. 97% (HR=1.2; 95% CI: 0.7-2.0) for those diagnosed in 2020; the respective rates for patients who underwent systemic anticancer therapy were 78% vs. 79% (HR=1.0; 95% CI: 0.8-1.2); these rates were 20% vs. 13% (HR=1.3; 95% CI: 1.1-1.6) for those who received BSC. COVID-19 was associated with poorer OS rates (HR=2.1; 95% CI: 1.6-3.0) for patients who received systemic anticancer therapy.ConclusionsThe SARS-CoV-2 pandemic has not exerted any deleterious impact on 6-month OS of new lung cancer patients that underwent active anticancer therapy in Greater Paris University hospitals.

Published
2022
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19. Allergic bronchopulmonary aspergillosis: A multidisciplinary review

Author

Amytis Roboubi, Camille Audousset, Émilie Fréalle, Anne-Laure Brun, François Laurent, Joana Vitte, Geoffrey Mortuaire, Guillaume Lefevre, Jacques Cadranel, Cécile Chenivesse, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Foch [Suresnes], Espaces et Sociétés (ESO), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Le Mans Université (UM)-Université d'Angers (UA)-AGROCAMPUS OUEST-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, Université de Lille, Complexe de recherche interprofessionnel en aérothermochimie (CORIA), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], and Pole Cardio-vasculaire et pulmonaire [CHU Lille]

Subjects
Infectious Diseases, [SDV]Life Sciences [q-bio]
Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease characterized by a complex allergic inflam-matory reaction of airways against Aspergillus affecting patients with chronic respiratory diseases (asthma, cystic fibrosis). Exacerbation is often the way to diagnose ABPA and marks its evolution by its recurrent char-acter leading to cortico-requirement or long-term antifungal treatment. Early diagnosis allows treatment of ABPA at an initial stage, preventing recurrence of exacerbations and long-term complications, mainly repre-sented by bronchiectasis. This review of the literature aims to present the current state of the art in terms of diagnosis and treatment of ABPA from a multidisciplinary perspective. As there is no clinical, biological nor radiological specific sign, diagnostic criteria are regularly revised. They are mainly based on the elevation of total and specific IgE against Aspergillus fumigatus and the presence of suggestive CT abnormalities such as mucoid impaction and consolidations. ABPA management includes eviction of mold and pharmacological therapy. Exacerbations are treated in first line with a moderate dose of oral corticosteroids. Azole antifungal agents represent an alternative for the treatment of exacerbations and are the preferential strategy to reduce the future risk of exacerbations and for corticosteroids sparing. Asthma biologics may be of interest; how-ever, their place remains to be determined. Avoiding complications of ABPA while limiting the side effects of systemic drugs remains a major challenge of ABPA management. Several drugs, including new antifungals and asthma biologics, are currently being tested and may be useful in the future.(c) 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved.

Published
2023
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20. Plain language summary of publication: new information for the potential role of afatinib in treating people with NRG1 gene fusion-positive cancer

Author

Jacques Cadranel

Subjects
Cancer Research, Oncology, mental disorders, General Medicine
Abstract

What is this summary about? This plain language summary reports the findings of a case series, a study which evaluated a small number of people who had a certain type of cancer. This case series looked at how well a drug called afatinib worked in people who have a rare type of cancer called neuregulin-1 (also called NRG1) gene fusion-positive cancer. Six people with NRG1 gene fusion-positive cancer were treated with afatinib, including five with lung cancer and one with gastrointestinal cancer. After treatment, people were monitored regularly to see if their tumors had grown (known as tumor progression). What were the results? After being treated with afatinib for up to 16 months, two people had stable disease (meaning their cancer did not get worse or improve). Three people had a partial response (meaning they showed a decrease in the size of their tumor) for over 18 months. One person had a partial response after being treated with afatinib for 11 months. What do the results mean? Afatinib showed encouraging results which suggest it may be a potential treatment for NRG1 fusion-driven cancers, as it delayed tumor progression and decreased tumor size for some people with NRG1 gene fusion-positive tumors. These case reports warrant the conduct of a clinical trial including a larger number of people to definitively confirm how well afatinib works in treating people with NRG1 gene fusion-positive cancers.

Published
2022
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21. Severe sotorasib-related hepatotoxicity and non-liver adverse events associated with sequential anti-PD(L)1 and sotorasib therapy in KRASG12C-mutant lung cancer

Author

Ali Chour, Julie Denis, Céline Mascaux, Maeva Zysman, Laurence Bigay-Game, Aurélie Swalduz, Valérie Gounant, Alexis Cortot, Marie Darrason, Vincent Fallet, Edouard Auclin, Clémence Basse, Claire Tissot, Chantal Decroisette, Pierre Bombaron, Etienne Giroux-Leprieur, Luc Odier, Solenn Brosseau, Quentin Creusot, Marina Gueçamburu, Corentin Meersseman, Adrien Rochand, Adrien Costantini, Claire Marine Gaillard, Eric Wasielewski, Nicolas Girard, Jacques Cadranel, Claire Lafitte, Fanny Lebossé, and Michael Duruisseaux

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2023
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22. Legends to supplementary figures and tables from RhoB Determines Tumor Aggressiveness in a Murine EGFRL858R-Induced Adenocarcinoma Model and Is a Potential Prognostic Biomarker for Lepidic Lung Cancer

Author

Julien Mazières, Gilles Favre, Julie Milia, Anne Casanova, Michèle Beau-Faller, Jacques Cadranel, Thomas Filleron, Valérie Lauwers-Cances, Emilie Bousquet, Isabelle Rouquette, Isabelle Raymond-Letron, Anne Pradines, and Olivier Calvayrac

Abstract

Legends to supplementary figures and tables. Contains detailed legends for supplementary figures S1-5 and supplementary tables 1 and 2

Published
2023
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23. Supplementary Figure S4 from RhoB Determines Tumor Aggressiveness in a Murine EGFRL858R-Induced Adenocarcinoma Model and Is a Potential Prognostic Biomarker for Lepidic Lung Cancer

Author

Julien Mazières, Gilles Favre, Julie Milia, Anne Casanova, Michèle Beau-Faller, Jacques Cadranel, Thomas Filleron, Valérie Lauwers-Cances, Emilie Bousquet, Isabelle Rouquette, Isabelle Raymond-Letron, Anne Pradines, and Olivier Calvayrac

Abstract

Supplementary Figure S4. Representative images of healthy lungs and lung tumors from EGFR/rhob mice stained with CD34 antibody, and corresponding quantification

Published
2023
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24. Data from First-Line Afatinib plus Cetuximab for EGFR-Mutant Non–Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study

Author

Jacques Cadranel, Marc G. Denis, Sandrine Charpentier, Benjamin Huret, Eric Pichon, Aldo Renault, Hugues Morel, Didier Debieuvre, Lionel Moreau, José Hureaux, Franck Morin, Elodie Amour, Judith Raimbourg, Denis Moro-Sibilot, Isabelle Rault, Josiane Otto, Henri Bérard, Elisabeth Quoix, Olivier Molinier, Etienne Giroux-Leprieur, Anne Madroszyk, and Alexis B. Cortot

Abstract

Purpose:Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non–small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced EGFR-mutant NSCLC.Patients and Methods:In this phase II, randomized, open-label study, patients with stage III/IV EGFR-positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C). Oral afatinib 40 mg was given once daily; cetuximab 250 mg/m² was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m² for 6 months. The primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of EGFR circulating tumor DNA in plasma was performed.Results:Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A + C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A + C), and median TTF was 11.1 (95% CI, 8.5–14.1) and 12.9 (9.2–14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A + C. Allele frequency of the EGFR gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received.Conclusions:These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR-mutant NSCLC.

Published
2023
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25. Supplemental Methods from RhoB Determines Tumor Aggressiveness in a Murine EGFRL858R-Induced Adenocarcinoma Model and Is a Potential Prognostic Biomarker for Lepidic Lung Cancer

Author

Julien Mazières, Gilles Favre, Julie Milia, Anne Casanova, Michèle Beau-Faller, Jacques Cadranel, Thomas Filleron, Valérie Lauwers-Cances, Emilie Bousquet, Isabelle Rouquette, Isabelle Raymond-Letron, Anne Pradines, and Olivier Calvayrac

Abstract

Supplemental Methods. This file contains additional methodology (Tumor/lung ratio quantification, Tumor size measurement and grading, CD34 staining and quantification, lung tissue processing for protein extraction for Western Blotting and PAS diastase staining)

Published
2023
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26. Supplementary Tables from First-Line Afatinib plus Cetuximab for EGFR-Mutant Non–Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study

Author

Jacques Cadranel, Marc G. Denis, Sandrine Charpentier, Benjamin Huret, Eric Pichon, Aldo Renault, Hugues Morel, Didier Debieuvre, Lionel Moreau, José Hureaux, Franck Morin, Elodie Amour, Judith Raimbourg, Denis Moro-Sibilot, Isabelle Rault, Josiane Otto, Henri Bérard, Elisabeth Quoix, Olivier Molinier, Etienne Giroux-Leprieur, Anne Madroszyk, and Alexis B. Cortot

Abstract

Supplementary Tables

Published
2023
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27. Supplementary Table S2 from RhoB Determines Tumor Aggressiveness in a Murine EGFRL858R-Induced Adenocarcinoma Model and Is a Potential Prognostic Biomarker for Lepidic Lung Cancer

Author

Julien Mazières, Gilles Favre, Julie Milia, Anne Casanova, Michèle Beau-Faller, Jacques Cadranel, Thomas Filleron, Valérie Lauwers-Cances, Emilie Bousquet, Isabelle Rouquette, Isabelle Raymond-Letron, Anne Pradines, and Olivier Calvayrac

Abstract

Supplementary Table S2. Kras and EGFR mutations and EGFR expression according to RhoB expression in tumors

Published
2023
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28. Data from RhoB Determines Tumor Aggressiveness in a Murine EGFRL858R-Induced Adenocarcinoma Model and Is a Potential Prognostic Biomarker for Lepidic Lung Cancer

Author

Julien Mazières, Gilles Favre, Julie Milia, Anne Casanova, Michèle Beau-Faller, Jacques Cadranel, Thomas Filleron, Valérie Lauwers-Cances, Emilie Bousquet, Isabelle Rouquette, Isabelle Raymond-Letron, Anne Pradines, and Olivier Calvayrac

Abstract

Purpose: A crucial event in lung adenocarcinoma progression is the switch from an aerogenous spread toward an infiltrating tumor. Loss of RhoB expression has been suggested to be critical for lung cancer invasion. Here, we tested RhoB expression as a prognostic biomarker in non–small cell lung cancer (NSCLC) with a special focus on lepidic pattern.Experimental Design: We analyzed RhoB expression using both IHC and RT-qPCR in two series of operated patients (n = 100 and 48, respectively) and in a series of advanced lepidic adenocarcinoma (n = 31) from different hospitals. Next, we examined the role of RhoB in lung cancer progression in transgenic mice that express inducible EGFRL858R crossed with Rhob null mice.Results: We identified that loss of RhoB expression was strongly associated with worse survival (P = 0.0001) and progression-free survival (P < 0.001) in the first series. We then confirmed these results after multivariate analyses of the second series. In the series of adenocarcinoma with lepidic features issued from a clinical trial (IFCT-0401), we showed that loss of RhoB expression was associated with higher aggressiveness of stage IV. Finally, we showed that EGFRL858R/Rhob+/+ mice developed mainly diffuse lung tumors with a lepidic pattern, whereas EGFRL858R/Rhob+/− and EGFRL858R/Rhob−/− developed a greater number of tumors, and aggressive adenocarcinomas with invasive properties.Conclusions: We showed that RhoB is not only a strong prognostic factor in NSCLC but it is also critical for the acquisition of an aggressive phenotype of adenocarcinoma. Clin Cancer Res; 20(24); 6541–50. ©2014 AACR.

Published
2023
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29. Tailoring maintenance chemotherapy upon response to induction chemotherapy as compared with pemetrexed continuation maintenance in advanced non-squamous NSCLC patients: Results of the IFCT-GFPC-1101 multicenter randomized phase III trial

Author

Alexis B. Cortot, Didier Debieuvre, L. Moreau, Radj Gervais, Jacques Margery, Julien Mazieres, Olivier Molinier, Michel Poudenx, Alexandra Langlais, Nicolas Girard, Patrick Dumont, Gérard Zalcman, Franck Morin, Virginie Westeel, Pierre-Jean Souquet, Eric Pichon, Fabrice Barlesi, Maurice Pérol, Jérôme Dauba, Jacques Cadranel, Clarisse Audigier-Valette, and Denis Moro-Sibilot

Subjects
Adult, Pulmonary and Respiratory Medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Adolescent, Pemetrexed, Maintenance Chemotherapy, Young Adult, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Maintenance chemotherapy, business.industry, Induction chemotherapy, Induction Chemotherapy, Middle Aged, Treatment Outcome, Non squamous, Cisplatin, business, medicine.drug
Abstract

Benefit from maintenance in advanced non-squamous non-small cell lung cancer (NS-NSCLC) might favor switch maintenance after disease stabilization (SD) and continuation after objective response (OR). This trial assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG) with G continuation for patients with OR or switch to pemetrexed (P) for patients with SD as compared with a control arm based on the Paramount regimen.Eligibility criteria: age 18-70 years, ECOG PS 0-1, untreated stage IV NS-NSCLC without EGFR or ALK alteration, ineligibility to bevacizumab. Patients were randomized 1:1 to receive either CG (4 cycles) followed by G maintenance in case of OR followed by P at progression, or switch to P for patients with SD, or 4 cycles of CP followed by P (control arm). Primary endpoint: overall Survival.Between 2012 and 2016, 932 patients were randomized (CG: 467, CP: 465) with well-balanced characteristics. 257 patients (56.7%) in the CG arm received maintenance (G: 142, P: 113) versus 277 patients (59.7%) in the CP arm. Median number of maintenance cycles was 5 for G and P (CG induction) and 4 for P (CP induction). OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p = 0.71) with a median of 10.9 months (CG) versus 10.4 (CP). HR for PFS was 0.95 (95% CI 0.83, 1.09; p = 0.45) with a median of 4.8 months for CG versus 4.5 for CP. Safety profile was as expected.Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome.NCT01631136.

Published
2022
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30. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author

Anatole Harrois, Florence Patin, Anaïs Razurel, Laure Allanic, Grégoire Martin de Frémont, Vincent Jachiet, Gonçalo Boleto, Eric D'Ortenzio, Xavier Mariette, Philippe Dieudé, Etienne Canouï, Z Julia, Nathalie Dournon, Jean-Sébastien Hulot, David Lebeaux, Eric Mariotte, Dorothee Vallois, Laurence Berard, Nicolas Gambier, Christiane Verny, Mathilde Le Marchand, Mitja Jevnikar, Jean-Jacques Mourad, Marjolaine Morgand, Bertrand Guidet, Alexandre Moores, Prissile Bakouboula, Frédéric Pène, Pascal Richette, Martine Meunier, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Mamadou Salif Cisse, Marie-Hélène Legros, Yann Nguyen, Damien Roux, Robin Deleris, Maxence Decavele, Patrice Cacoub, Isabelle Dusanter, Patricia Senet, Nassim Mahtal, Raphael Borie, Philippe Benoit, Blandine Denis, Luca Semerano, Sebastien Abad, Marie Dubert, Marie Lachatre, Marine Livrozet, Nathan Ebstein, Lakhdar Mameri, Adrien Michon, Olivier Sanchez, Aurélien Guffroy, Pierre Dupland, Jérôme Pacanowski, Yasmina Ferfar, Tassadit Hadjam, Anne-Marie Roques, Celine Comparon, Solaya Chalal, A Soria, Isabelle Lehir, Anne Gysembergh-Houal, Stéphanie Alary, Valérie Dejean, Elena Kiouris, Estelle Henry, Sophie Diemunsch, Jonathan London, Fanny Charbonnier, Alexandre Demoule, Louise Bondeelle, Samira Saleh-Mghir, Lise Bernard, Brigitte Sabatier, Anne Jacolot, Aurelie Sautereau, Pierre Faye, Benjamin Fournier, Noémie Abisror, Awa Ndiaye, Ruben Benainous, Damien Sène, Emmanuelle Sacco, Isabelle Debrix, Gabriel Nisand, Régis Peffault de Latour, Anne Sophie Korganow, Kévin Cardet, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Elena Fois, Jean-Benoit Arlet, Christine Broissand, Yaël Amara, Matheus Vieira, Sophie Caillat-Zucman, Madona Sakkal, Juliette Djadi-Prat, Jean-Louis Teboul, Hélène François, Stéphane Renaud, Sylviane Ravato, Alaki Thiemele, Gabrielle Archer, Alain Fourreau, David Boutboul, Arsène Mekinian, Antoine Gros, Morgane Faure, Anne Pattyn, Camille Petit-Hoang, Jessica Krause le Garrec, Antony Canellas, Jean-Michel Molina, Zakaria Ait Hamou, Eric Oksenhendler, Ilias Koumis, Marie-Aude Penet, Catherine Boussard, Vincent Fallet, Guillaume Geri, Loic Kassegne, Bernard Cholley, Lucie Biard, Elodie Perrodeau, Tomas Urbina, David Schmitz, johann Cailhol, Elise Morawiec, Audrey Phibel, Sophie Renet, Emmanuel Weiss, Faouzi Saliba, Kristina Beziriganyan, Abdellatif Tazi, Isabelle Peigney, Bertrand Dunogue, Rémy Gauzit, Damien Bergerot, Bob Heger, Ines Ben-Mabrouk, Jade Ghosn, Benjamin Planquette, Alexis Régent, François Weill, Yasmina Mekid, Rosa Da Silva, Victor Lancon, Marc Michel, Nadia Anguel, Anne Claire Desbois, François Danion, Brigitte Ranque, Mohamed Belloul, Nadège Lemarié, Amélie Cransac, Marine Nadal, Lalia Djaghout, Anne Tréhan, Samy Figueiredo, Hakim Meddah, Aurélie Clan Hew Wai, Julie Delemazure, Soraya Fellahi, Jacques-Eric Gottenberg, Matthieu Uzzan, Jean-Charles Duclos-Vallée, Tabassome Simon, Vanessa Rathouin, Yves Hansmann, Hélène Gros, Syllia Belazouz, Nathalie Marin, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Annabelle Stoclin, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Miguel Alejandro Vasquez-Ibarra, Isabelle Madeleine, Simon Valayer, Anne Adda, Marie-Thérèse Tremorin, Nicolas Meyer, Vixra Keo, Lara Zafrani, Caroline Semaille, Maxime Dougados, Olivier Olivier, Emeline Colomba, Florence Morin, Claire Rouzaud, Paul Michel Mertes, Claire Montlahuc, Anne Blanchard, Valérie Pourchet-Martinez, Constance Delaugerre, Nicolas Carlier, Jacques Cadranel, Nicolas Noel, Kahina Cheref, Bao Phung, Moez Jallouli, Ulrich Clarac, Marthe Rigal, Mireille Adda, Lionel Galicier, Fanny Domont, Lee S. Nguyen, Férial Berbour, Fanny Pommeret, Celine Dupré, Gaël Leprun, Jean-Luc Diehl, Laetitia Languille, Philippe Blanche, Abolfazl Mohebbi, Mathilde Noaillon, Olivier Collange, Paul Jaubert, Anne Daguenel-Nguyen, Sandrine Briois, Anne-Lise Pouliquen, Coralie Bloch Queyrat, Clément Jourdaine, Cédric Pierron, Geoffrey Rossi, Chloe McAvoy, Claire Courtin, Mathias Cornic, C Rioux, Christine Lemagner, Martin Dres, Emmanuelle Guillot, Marc Garnier, Safaa Nemlaghi, Guillaume Grailles, Yazdan Yazdanpanah, Veronique Joly, Thiziri Sadaoui, Marion Bouhris, Vincent Castelain, Muriel Fartoukh, Sébastien Cavelot, Sophie Ohlmann-Caillard, Valentina Isernia, Bruno Crestani, Thinhinane Bariz, Benjamin Chaigne, Emmanuel Andrès, Frédéric Blanc, Alain Wynckel, Louise-Laure Mariani, Yasmine Messaoudi, Naima Sguiouar, Amina Kebir, Asmaa Mamoune, Caroline Gaudefroy, Victoire De Lastours, Pierre Diemunsch, Etienne Lengliné, Claire Tantet, Julien Mayaux, Benjamin G. Chousterman, Arthur Pavot, Anne Rachline, Gwenaël Lorillon, Hassan Joumaa, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Fanny Defrancq, Véronique Vigna, Yves Cohen, Amira Benattia, Martin Siguier, Sophie Georgin-Lavialle, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Olivier Hermine, Mathieu Vautier, Florence Tubach, Marion Licois, Anaïs Codorniu, Fanny Alby-Laurent, Jérémie Zerbit, Aude Jacob, Benedicte Giroux-Leprieur, Carine Karachi, Laurent Cylly, Edouard Flamarion, Gladys Aratus, Charléne Jouve, Robin Dhote, Claire Davoine, Valentin Greigert, Gaelle Leroux, Cécile Kedzia, Guillaume Lefèvre, Catherine Metzger, Olivier Benveniste, Clairelyne Dupin, Marie-Alexandra Alyanakian, Mathieu Oberlin, Julien Poissy, Linda Gimeno, Adrien Contejean, Segolene Toquet, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Virginie Zarrouk, Cécile Yelnik, Mandy Nizard, Mourad Djadel, F-Xavier Lescure, Agnes Maurer, Geoffroy Liégeon, Arthur Neuschwander, Hélène Lafoeste, Gaëtan Deslée, Frédéric De Blay, Claire Pernin, Cloé Comarmond, Anne Hutt, Ridha Belilita, Laurence Lecomte, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Jean-Jacques Tudesq, Benjamin Terrier, Solène Fabre, Lelia Escaut, Eva Chatron, Emmanuelle Blin, Pauline Jouany, Sara Sambin, Chistophe Willekens, Nabil Raked, Jean-Simon Rech, Serge Bureau, Boris Bienvenu, Elisabeth Coupez, Tali-Anne Szwebel, Lydia Suarez, Chaouki Bouras, Kamyl Baghli, Emilia Stan, Valérie Camara-Clayette, Fanette Denies, Nathalie Menage, Paul Legendre, Axelle Fuentes, Oriane Puéchal, Charlotte Kaeuffer, Guillaume Becker, Clara Campos-Vega, Armand Mekontso-Dessaps, Pernelle Vauboin, Yurdagul Uzunhan, F Louni, Marie hélène Pari, Myriam Virlouvet, Nicolas Belaube, Hugues Cordel, Nathalie Chavarot, Olivier Sitbon, Jean-Daniel Lelievre, Matthieu Mahévas, Julie Smati, Olivier Clovet, Marc Bardou, Ada Clarke, Gilles Garcia, Anouk Walter-Petrich, Hala Semri, Vasco Honsel, Giovanna Melica, Pierre Mora, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Céline Verstuyft Verstuyft, Blandine Lehmann, Pascal Martel, Aida Zahrate-Ghoul, Karine Martin, Alexandre Bourgoin, Baptiste Duceau, Philippe Ravaud, Celine Wilpotte, Sylvie Le Gac, Michaël Darmont, Aurélie Durel Maurisse, Younes Keroumi, Aude Rigolet, Julie Chas, Pierre-Louis Tharaux, Caroline Morbieu, Valérie Paquet, Eric Vicaut, Pascaline Choinier, Samir Hamiria, Elsa Feredj, Frédéric Schlemmer, Gilles Pialoux, Zeina Louis, Marion Parisey, David Montani, Jean-Pierre Riveline, Jean-Marie Michot, Pascal Lim, Eliane Bertrand, Gaelle Clavere, Julie Jambon, Stéphane Brin, Saskia Flamand, Jeanne Meunier, Geoffroy Volle, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Caroline Hauw-Berlemont, Gabriel Baron, Jeremy Arzoine, Loren Soyez-Herkert, Maria Pereira, Antoine Parrot, Johanna Oziel, Carole Burger, Eric Noll, Paul Vermes, Jeanne Goupil de Bouille, Xavier Monnet, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Jean-Philippe Bastard, Younes El Amine, Timothee Bironne, Damien Vanhoye, Amine Ghembaza, Laure Berton, Yvon Ruch, Thomas Volpe, Thomas Gorget, Jaouad Benhida, Julien Saussereau, Elodie Issorat, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Laurène Deconinck, A. Dossier, Félix Ackermann, Greggory Ducrocq, Anne Bergeron, Laurence Annonay, Camille Knosp, Laurence Drouard, Adrien Joseph, Hilario Nunes, Hanane Fodil, Sabrine Ouamri, Belkacem Asselate, Julie Fillon, Dominique Dautel, Isabelle Brindele, Robin Charreteur, S Lariven, Elie Azoulay, Sami Kolta, Cédric Sublon, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Bruno Mourvillier, Ewa Kozaliewicz, Vincent Provitolo, Marie Lecronier, Julien Chabert, Matthieu Resche-Rigon, Stéphan Pavy, Naura Gamany, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Corinne Guerin, Pierre Tissieres, Nathalie Costedoat-Chalumeau, Nessima Yelles, Emmanuel Chatelus, Jean-Christophe Corvol, Luc Mouthon, Marie Gilbert, Matthieu Lemoine, Lucie Aunay, Candice Estellat, Laure Choupeaux, Dhiaa Meriem Hai, Bernard Goichot, Céline Louapre, Roza Rahli, Nathalie De Castro, Christian Richard, Malikhone Chansombat, Kamil Chitour, Joseph Emmerich, Elodie Drouet, Julien Pottecher, Eric Demonsant, Alexandra Beurton, Raphaël Porcher, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Pierre-Grégoire Guinot, Nicolas Champtiaux, Caroline Pradon, Annick Tibi, Julien Le Marec, Nawal Derridj, Mohamad Zaidan, Eric Marquis, Mickael Henriques, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Diane Le Pluart, Coralie Gernez, Yacine Boudali, Dimitri Fremont, Pierrick Le Borgne, Corinne Pernot, Mélanie Dehais, Claire Madelaine, Dominique Roulot, Georgina Maalouf, Constance Guillaud, Corine Nyanou, Karine Celli Lebras, Sophie Granville, Sabrina Brahmi, Catherine Le Bourlout, Hassan Tarhini, Asmaa Mabrouki, Hakim Tayebi, Sophie Ismael, Jonathan Marey, Sophie Bayer, Gabriel Steg, Antoine Fayol, Catherine Fauvaux, Delphine Feyeux, Côme Bureau, Alexandre Morel, Agathe Bounhiol, Alexandre Buffet, Souad Benarab, Luc Haudebourg, Pierre Le Guen, Damien Vimpere, Xavier Jaïs, Clotilde Le Tiec Le Tiec, Sophie Bulifon, Pélagie Thibaut, Alison Klasen, Claire Pacheco, Anne Godier, Marie Antignac, Domitille Molinari, Philippe Durand, Olivier Lambotte, Paul Henri Grisot, Anne Lise Jegu, Vincent Poindron, Ruxandra Burlacu, Denis Jesuthasan, Sarah Benghanem, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Sara Virolle, Léa Resmini, Liem Binh Luong Nguyen, Marie Matignon, Céline Leplay, and Claire Aguilar

Subjects
medicine.medical_specialty, business.industry, Immunology, Hazard ratio, Absolute risk reduction, Articles, medicine.disease, law.invention, Clinical trial, Pneumonia, Sarilumab, Rheumatology, Randomized controlled trial, law, Internal medicine, Cohort, medicine, Immunology and Allergy, Adverse effect, business
Abstract

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

Published
2022
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31. 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
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32. Respiratory recovery trajectories after severe-to-critical COVID-19: a 1-year prospective multicentre study

Author

Frédéric Schlemmer, Simon Valentin, Laurent Boyer, Anne Guillaumot, François Chabot, Clairelyne Dupin, Pierre Le Guen, Gwenael Lorillon, Anne Bergeron, Damien Basille, Julia Delomez, Claire Andrejak, Valentine Bonnefoy, Hélène Goussault, Jean-Baptiste Assié, Pascaline Choinier, Anne-Marie Ruppert, Jacques Cadranel, Maria Chiara Mennitti, Mehdi Roumila, Charlotte Colin, Sven Günther, Olivier Sanchez, Thomas Gille, Lucile Sésé, Yurdagul Uzunhan, Morgane Faure, Maxime Patout, Capucine Morelot-Panzini, Pierantonio Laveneziana, Maeva Zysman, Elodie Blanchard, Chantal Raherison-Semjen, Violaine Giraud, Etienne Giroux-Leprieur, Stéfanie Habib, Nicolas Roche, Anh Tuan Dinh-Xuan, Islem Sifaoui, Pierre-Yves Brillet, Camille Jung, Emmanuelle Boutin, Richard Layese, Florence Canoui-Poitrine, Bernard Maitre, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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 Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux Universitaires de Genève (HUG), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Service de Pneumologie [CHI Créteil], CHI Créteil, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Avicenne [AP-HP], Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, CHU Pitié-Salpêtrière [AP-HP], Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Basse-Terre [Guadeloupe], Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de physiologie et explorations fonctionelles [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de radiologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Centre Hospitalier Intercommunal de Créteil (CHIC), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Pulmonary and Respiratory Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

BackgroundSurvivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life.MethodsAdults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study.ResultsAmong 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide (DLCO) and significant radiological sequelae, respectively. During extended follow-up, bothDLCOand forced vital capacity percentage predicted increased by means of +4 points at 6 months and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated withDLCOat 3 months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images.ConclusionsAlthough pulmonary function and radiological abnormalities improved up to 1 year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

Published
2023
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33. Germline Mutations of Telomere-Related Genes are a Major Risk Factor for Liver Disease: A Multicentric Transversal Study

Author

Sabrina Sidali, Raphaël Borie, Flore Sicre de Fontbrune, Kinan El Husseini, Pierre-Emmanuel Rautou, Elodie Lainey, Odile Goria, Bruno Crestani, Jacques Cadranel, Vincent Cottin, Vincent Bunel, Jérôme Dumortier, Emmanuel Jacquemin, Noémi Reboux, Sandrine Hirschi, Arnaud Bourdin, Magdalena Meszaros, Sébastien Dharancy, Sophie Hilaire, Vincent Mallet, Martine Reynaud-Gaubert, Louis Terriou, Frédéric Gottrand, Wadih Abou Chahla, Jean-Emmanuel Kahn, Paul Carrier, Faouzi Saliba, Laura Rubbia-Brandt, John-David Aubert, Laure Elkrief, Victor de Ledinghen, Armand Abergel, Olivier Tournilhac, Pauline Houssel, Stéphane Jouneau, Ludivine Wemeau, Anne Bergeron, Thierry Leblanc, Isabelle Ollivier-Hourmand, Eric Nguyen-Khac, Hélène Morisse-Pradier, Ibrahima Ba, Catherine Boileau, Françoise Roulot-Thoraval, Valérie Vilgrain, Christophe Bureau, Hilario Nunes, Jean-Marc Naccache, François Durand, Claire Francoz, Dominique Roulot, Dominique-Charles Valla, Valérie Paradis, Caroline Kannengiesser, and Aurélie Plessier

Published
2023
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34. Parcours de diagnostic rapide du cancer du poumon : évaluation à un an

Author

D. Moal, S. Guegan, A. Canellas, Armelle Lavolé, F. Millet, A.-M. Ruppert, L. Rosencher, Marie Wislez, M. Baud, Jacques Cadranel, C. Epaud, Vincent Fallet, Jalal Assouad, and Martine Antoine

Subjects
Pulmonary and Respiratory Medicine, Gynecology, medicine.medical_specialty, business.industry, medicine, Lung cancer, medicine.disease, business
Abstract

Resume Introduction Le parcours de soins des patients atteints de cancers du poumon (CP) est complexe. L’objectif du Plan cancer 2014–2019 est la maitrise des delais de prise en charge. En 2016, un parcours diagnostic rapide ambulatoire du CP a ete mis en place dans le service de pneumologie. L’objectif de cette etude est d’evaluer sa faisabilite et son impact sur les delais de prise en charge. Methode Il s’agit d’une etude epidemiologique retrospective realisee au CHU de Tenon entre mai 2016 et mai 2017. Resultats Un diagnostic de CP a ete fait dans 60 % des cas (n = 118). Le delai median d’acces a la prise en charge (D1) (demande-consultation) etait de 4 jours (2–7). Le delai median d’acces a la proposition de traitement (D4) (histologie-RCP) etait de 4 jours (0–8). Le delai d’acces au premier traitement (D5) (RCP-traitement) etait de 10 jours (4–15) pour la chimiotherapie et de 27 jours (16–34) jours pour la chirurgie. Le delai global de pris en charge (D6) (imagerie-traitement) etait de 49 jours (34–70). Conclusion Les delais de prise en charge du CP etaient conformes aux recommandations internationales. L’infirmiere de coordination a occupe un role central organisationnel et dans l’accompagnement du patient.

Published
2021
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35. French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis – 2021 update. Full-length version

Author

Vincent Cottin, Philippe Bonniaud, Jacques Cadranel, Bruno Crestani, Stéphane Jouneau, Sylvain Marchand-Adam, Hilario Nunes, Lidwine Wémeau-Stervinou, Emmanuel Bergot, Elodie Blanchard, Raphaël Borie, Arnaud Bourdin, Cécile Chenivesse, Annick Clément, Emmanuel Gomez, Anne Gondouin, Sandrine Hirschi, François Lebargy, Charles-Hugo Marquette, David Montani, Grégoire Prévot, Sébastien Quetant, Martine Reynaud-Gaubert, Mathieu Salaun, Olivier Sanchez, Bruno Trumbic, Karim Berkani, Pierre-Yves Brillet, Marion Campana, Lara Chalabreysse, Gérard Chatté, Didier Debieuvre, Gilbert Ferretti, Jean-Michel Fourrier, Nicolas Just, Marianne Kambouchner, Bertrand Legrand, Frédéric Le Guillou, Jean-Pierre Lhuillier, Anas Mehdaoui, Jean-Marc Naccache, Catherine Paganon, Martine Rémy-Jardin, Salim Si-Mohamed, Philippe Terrioux, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre national de référence des maladies pulmonaires rares [Lyon] (CRMPM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Pneumologie Soins Intensifs, Appareillage Respiratoire [CHU de Dijon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Avicenne [AP-HP], Institut Coeur Poumon [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pessac, 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 d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Pasteur [Nice] (CHU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Marseille, Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Centre Hospitalier Régional d'Orléans (CHRO), Hospices Civils de Lyon (HCL), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Eure-Seine - Hôpital d'Evreux - Vernon (Evreux), Groupe Hospitalier Paris Saint-Joseph (hpsj), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pulmonary and Respiratory Medicine, Biopsy, Biopsie, [SDV]Life Sciences [q-bio], Fibrose pulmonaire, Pneumopathie interstitielle commune, Interstitial lung disease, Common interstitial lung disease, Pneumopathie interstitielle diffuse, Pulmonary fibrosis
Abstract

National audience; BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients’ association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Published
2022
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36. 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
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38. Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial

Author

Julie Mankikian, Agnès Caille, Martine Reynaud-Gaubert, Marie-Sara Agier, Julien Bermudez, Philippe Bonniaud, Raphael Borie, Pierre-Yves Brillet, Jacques Cadranel, Isabelle Court-Fortune, Bruno Crestani, Marie-Pierre Debray, Emmanuel Gomez, Anne Gondouin, Sandrine Hirschi-Santelmo, Dominique Israel-Biet, Stéphane Jouneau, Karine Juvin, Julie Leger, Mallorie Kerjouan, Charles-Hugo Marquette, Jean-Marc Naccache, Hilario Nunes, Laurent Plantier, Grégoire Prevot, Sébastien Quetant, Julie Traclet, Victor Valentin, Yurdagul Uzunhan, Lidwine Wémeau-Stervinou, Theodora Bejan-Angoulvant, Vincent Cottin, Sylvain Marchand-Adam, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), 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 d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Hôpital Avicenne [AP-HP], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Biologie Intégrative du Tissu Osseux (LBTO), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Pontchaillou, 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 ), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre hospitalier Saint-Joseph [Paris], Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Lille, EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), PHRC national, and This study was supported by a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique) 2015

Subjects
Pulmonary and Respiratory Medicine, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract

BackgroundStandard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first step therapies while rituximab is used as rescue therapy.MethodsIn a randomised, double blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune feature) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinico-biological data and a NSIP-like HRCT pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for six months. The primary endpoint was the change in percent of predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary endpoints included progression-free survival (PFS) up to 6 months and safety.FindingsBetween January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 (se1.13) in the rituximab+MMF group and −2.01 (se1.17) in the placebo+MMF group (between-group difference, 3.60 [95% CI 0.41 to 6.80]; p=0.0273). PFS was better in the rituximab+MMF group (crude HR 0.47 [95%CI 0.23 to 0.96]; p=0.03). Serious adverse events occurred in 26 patients of the rituximab+MMF group (41%) and in 23 of the placebo+MMF group (39%). Nine infections were reported in the rituximab+MMF group (five bacterial infections, 3 viral infections, 1 other) and four bacterial infections in the placebo+MMF group.InterpretationCombination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must consider the risk of viral infection.

Published
2023
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40. Do Female

Author

Vincent, Fallet, Mateo, Sanchis-Borja, Patrick R, Benusiglio, and Jacques, Cadranel

Subjects
BRCA2 Protein, Ovarian Neoplasms, Heterozygote, Lung Neoplasms, BRCA1 Protein, Mutation, Humans, Breast Neoplasms, Female, Genetic Predisposition to Disease
Published
2022

41. Brigatinib for Pretreated, ALK-Positive, Advanced Non-Small-Cell Lung Cancers: Long-Term Follow-Up and Focus on Post-Brigatinib Lorlatinib Efficacy in the Multicenter, Real-World BrigALK2 Study

Author

Renaud Descourt, Maurice Pérol, Gaëlle Rousseau-Bussac, David Planchard, Bertrand Mennecier, Marie Wislez, Jacques Cadranel, Alexis Benjamin Cortot, Florian Guisier, Loïck Galland, Pascal Do, Roland Schott, Éric Dansin, Jennifer Arrondeau, Jean-Bernard Auliac, Margaux Geier, Christos Chouaïd, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Régional de Lutte Contre le Cancer Lyon Rhône-Alpes (CLB), Centre Hospitalier Intercommunal de Créteil (CHIC), Institut Gustave Roussy (IGR), CHU Strasbourg, Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Georges-François-Leclerc, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Cochin [AP-HP], Service de Pneumologie [CHI Créteil], CHI Créteil, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Cancer Research, brigatinib, Oncology, lorlatinib, ALK rearrangment, NSCLC, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Brigatinib is a next-generation ALK inhibitor (ALKi) that shows efficacy in ALK inhibitor naïve and post-crizotinib ALK+ advanced NSCLCs (aNSCLCs). The efficacy of brigatinib was retrospectively assessed in patients with aNSCLCs included in the brigatinib French Early-Access Program (1 August 2016–21 January 2019). The primary endpoint was investigator-assessed progression-free survival (invPFS) and the primary analysis was updated in 2021 with a longer follow-up, focused on post-brigatinib lorlatinib efficacy. Sixty-six centers included 183 patients: median age 60 ± 12.7 years; 78.3% never/former smokers; median of 3 ± 1 previous lines and 2 ± 0.5 ALKis; 37.1% ECOG PS 2 and 55.6% >3 metastatic sites. The median follow-up from brigatinib initiation was 40.4 months (95% CI 38.4–42.4). InvPFS was 7.4 months (95% CI 5.9–9.6), median duration of treatment (mDOT) was 7.3 months (95% CI 5.8–9.4) and median overall survival (mOS) was 20.3 months (95% CI 15.6–27.6). The median DOT and OS from brigatinib initiation tend to decrease with the number of ALK inhibitors used in previous lines of therapy. Based on the data collected, 92 (50.3%) patients received ≥1 agent(s) post-brigatinib and 68 (73.9%) of them received lorlatinib, with 51 (75%) immediately receiving it post-brigatinib, 12 (17.6%) receiving it after one and 5 (7.4%) after ≥2 subsequent treatments. The median follow-up was 29.9 (95% CI 25.7–33.1) months. Lorlatinib mDOT was 5.3 (95% CI 3.6–7.6) months with a median OS from lorlatinib initiation of 14.1 (95% CI 10.3–19.2) months. The results of the brigALK2 study confirm the efficacy of brigatinib in a population of heavily pretreated ALK+ aNSCLC patients and provide new data on the activity of lorlatinib after brigatinib.

Published
2022
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42. Characterization of lung cancers in patients with BRCA germline variants: A multicenter series

Author

Mateo Sanchis-Borja, Vincent Fallet, Elisabeth Fabre, Marie Wislez, Stéphane Culine, Gérard Zalcman, Jean-Philippe Spano, Nathalie Chabbert Buffet, Florence Coulet, Patrick R. Benusiglio, and Jacques Cadranel

Subjects
Pulmonary and Respiratory Medicine, Cancer Research, Germ Cells, Lung Neoplasms, Oncology, BRCA1 Protein, Genes, BRCA2, Humans, Female, Adenocarcinoma, Germ-Line Mutation, Retrospective Studies
Abstract

BRCA1 and BRCA2 (BReast CAncer susceptibility genes) are two tumor-suppressor genes associated with the hereditary breast and ovarian cancer susceptibility syndrome. Recent studies also suggest an increased lung adenocarcinoma risk in carriers.We conducted a multi-center retrospective study in 18 different French pulmonology and/or oncology departments on medico-administrative and clinical data prospectively collected in the Clinical Data Warehouse (CDW) of Greater Paris University Hospitals (Assistance Publique-Hôpitaux de Paris, AP-HP). Clinical characteristics and outcomes of patients with LC and a previously known BRCA1/2gl variant were retrospectively evaluated.17 patients with LC and known BRCA1/2gl variant were included. Patients were most women, former smokers with localized disease and BRCA2 variants. All LC were adenocarcinoma. For patients with medical history of cancer, median time from the first cancer in the BRCA spectrum and the LC occurrence was 20 years. Median disease-free survival (DFS) and overall survival (OS) in localized tumor (Stage I and II) was not reached and 78.6 months, respectively. In advanced cancer (Stade III and IV) median progression free survival was 9.7 months and median OS was 17.8 months. Univariate OS and DFS/PFS analyses by BRCA status did not find significant differences.Results seem to show particular LC features in carriers of BRCA2 variants: adenocarcinoma subtype, woman, former or non-smoker.

Published
2022

43. Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients With Advanced Non–Small-Cell Lung Cancer Harboring HER2 Mutations: Results From the IFCT-1703 R2D2 Trial

Author

Julien Mazieres, Claire Lafitte, Charles Ricordel, Laurent Greillier, Elodie Negre, Gérard Zalcman, Charlotte Domblides, Jeannick Madelaine, Jaafar Bennouna, Céline Mascaux, Denis Moro-Sibilot, François Pinquie, Alexis B. Cortot, Josiane Otto, Jacques Cadranel, Alexandra Langlais, Franck Morin, Virginie Westeel, Benjamin Besse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Hospices Civils de Lyon (HCL), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Multidisciplinary Oncology and Therapeutic Innovations Unit, Hôpital Nord [CHU - APHM], Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Service d’oncologie thoracique et essais précoces [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), CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), 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), Hôpital Foch [Suresnes], Service de Pneumologie [Strasbourg], Université de Strasbourg (UNISTRA)-Nouvel Hôpital Civil, Hospices Civils de Strasbourg, CHU de Grenoble-Alpes, Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Gustave Roussy (IGR), and Département de médecine oncologique [Gustave Roussy]

Subjects
MESH: Aged, MESH: Docetaxel, Cancer Research, MESH: Humans, MESH: Middle Aged, MESH: Mutation, MESH: Survival Rate, MESH: Non-Randomized Controlled Trials as Topic, MESH: Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Follow-Up Studies, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Male, MESH: Prognosis, MESH: Lung Neoplasms, MESH: Receptor, ErbB-2, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH: Aged, 80 and over, Oncology, MESH: Antibodies, Monoclonal, Humanized, MESH: Trastuzumab, MESH: Female, MESH: Carcinoma, Non-Small-Cell Lung
Abstract

PURPOSE HER2 exon 20 insertions and point mutations are oncogenic drivers found in 1%-2% of patients with non–small-cell lung cancer (NSCLC). No targeted therapy is approved for this subset of patients. We prospectively evaluated the effectiveness of the combination of two antibodies against human epidermal growth factor 2 (HER2 [HER2] trastuzumab and pertuzumab with docetaxel; trastuzumab and pertuzumab) and docetaxel. METHODS The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with HER2-mutated, advanced NSCLC who progressed after ≥ 1 platinum-based treatment were enrolled. Patients received pertuzumab at a loading dose of 840 mg and 420 mg thereafter; trastuzumab at an 8 mg/kg loading dose and 6 mg/kg thereafter; and docetaxel at a dose of 75 mg/m2 every 3 weeks. The primary outcome was the objective response rate (ORR). Other end points included the duration of response, progression-free survival, and safety ( NCT03845270 ). RESULTS Forty-five patients were enrolled and treated. The median age was 64.5 years (range, 31-84 years), 35% were smokers, 72% were females, 15% had an Eastern Cooperative Oncology Group performance status of 2, and 30% had brain metastases. The objective response rate was 29% (n = 13), and 58% had stable disease (n = 26). The median progression-free survival was 6.8 months (95% CI, 4.0 to 8.5). The median duration of response in patients with a confirmed response (n = 13) was 11 months (95% CI, 2.9 to 14.9). Grade 3/4 treatment-related adverse events were observed in 64% of the patients. No patient discontinued treatment because of toxicity. The most frequent grade ≥ 3 treatment-related adverse events were neutropenia (33%), diarrhea (13%), and anemia (9%). CONCLUSION Triple therapy with trastuzumab, pertuzumab, and docetaxel is feasible and effective for HER2-mutated pretreated advanced NSCLC. These results highlight the effectiveness of the HER2 antibody-based strategy, which should be considered for these patients.

Published
2022
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44. 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

45. Impact of Gender on the Characteristics of Patients with Idiopathic Pulmonary Fibrosis Included in the RaDiCo-ILD Cohort

Author

Sandrine Hirschi, Sonia Gueguen, M. Chevereau, Serge Amselem, Anne-Sophie Gamez, Martine Reynaud-Gaubert, Philippe Bonniaud, Dominique Israel-Biet, Annick Clement, I. Dufaure-Garé, Sylvain Marchand-Adam, Lidwine Wemeau-Stervinou, David Montani, Vincent Cottin, Jacques Cadranel, Hilario Nunes, Sébastien Quétant, Bruno Crestani, Stéphane Jouneau, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 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), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Strasbourg, Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Lapeyronie [Montpellier] (CHU), CHU Trousseau [APHP], French National Research Agency under the 'cohorts' programme of the Investissements d'Avenir (Investments for the Future) French National Research Agency (ANR) [ANR-10-COHO-0003], ANR-10-COHO-0003,RADICO,Cohorte nationale maladies rares(2010), École pratique des hautes études (EPHE), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-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 )-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 Paris (UP), 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, Centre Constitutif de Référence des Maladies Pulmonaires Rares [AP-HP Tenon], Centre national de référence des maladies pulmonaires rares [Lyon] (CRMPM)-Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], 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 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), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Centre national de référence des maladies pulmonaires rares [Lyon] (CRMPM)-Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], 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 Tenon [AP-HP], UF de Génétique moléculaire [CHU Trousseau], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], 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], Chard-Hutchinson, Xavier, and Cohortes - Cohorte nationale maladies rares - - RADICO2010 - ANR-10-COHO-0003 - COHO - VALID

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Vital capacity, Registry, [SDV]Life Sciences [q-bio], Idiopathic pulmonary fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pulmonary function testing, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Internal medicine, medicine, Humans, 030212 general & internal medicine, Honeycombing, Idiopathic interstitial pneumonia, 10. No inequality, Emphysema, Patient characteristics, business.industry, Interstitial lung disease, Gender, respiratory system, medicine.disease, Confidence interval, 3. Good health, respiratory tract diseases, [SDV] Life Sciences [q-bio], 030228 respiratory system, Cohort, Quality of Life, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, France, business, Lung Diseases, Interstitial
Abstract

Background: There is growing evidence of gender-specific phenotypic differences among patients with idiopathic pulmonary fibrosis (IPF), which may affect patient outcomes. Objectives: We present the characteristics of patients with IPF at inclusion in the French Rare Disease Cohort – Interstitial Lung Disease (RaDiCo-ILD) with the aim of characterizing gender-specific phenotypic differences. Methods: Patients with IPF who were enrolled in the national, multicentre RaDiCo-ILD cohort were included. Demographic characteristics, comorbidities, health-related quality of life (HRQoL) scores, pulmonary function, chest imaging, and IPF treatment were collected at inclusion and described by gender. Results: The cohort included 724 patients with IPF (54% of RaDiCo-ILD cohort), of whom 82.9% were male. The proportion of male and female patients with a prior history of smoking was 75.0% and 26.8%, respectively. Emphysema was present in 17.0% (95% confidence interval [CI]: 10.0, 24.0) of men and 5.4% (95% CI: 1.2, 9.6) of women. At inclusion, females had poorer HRQoL than males based on St. George’s Respiratory Questionnaire scores (48.5 [95% CI: 43.9, 53.0] and 41.5 [39.4, 43.6], respectively). The mean forced vital capacity per cent predicted was 77.7% (95% CI: 76.2, 79.3) and 87.4% (83.4, 91.4) for males and females, respectively. Honeycombing on high-resolution computed tomography (HRCT) was present in 70.8% (95% CI: 61.0, 80.6) of males and 45.8% (95% CI: 35.1, 56.5) of females. Conclusions: This analysis of patients with IPF at inclusion in the RaDiCo-ILD cohort provides evidence that comorbid emphysema, lung volume reduction, and honeycombing on HRCT are more common characteristics of males than females.

Published
2022
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46. Detection of acquired TERT amplification in addition to predisposing p53 and Rb pathways alterations in EGFR-mutant lung adenocarcinomas transformed into small-cell lung cancers

Author

Anne Mc Leer, Matthieu Foll, Marie Brevet, Martine Antoine, Silvia Novello, Julie Mondet, Jacques Cadranel, Nicolas Girard, Matteo Giaj Levra, Pierre Demontrond, Clarisse Audigier-Valette, Eric Letouzé, Sylvie Lantuéjoul, Lynnette Fernandez-Cuesta, and Denis Moro-Sibilot

Subjects
Pulmonary and Respiratory Medicine, CCND1, EGFR, Histological transformation, Lung adenocarcinoma, RB1, Small-cell lung carcinoma, TERT, TP53, Cancer Research, Lung Neoplasms, Adenocarcinoma of Lung, Retinoblastoma Protein, Small Cell Lung Carcinoma, ErbB Receptors, Oncology, Drug Resistance, Neoplasm, Mutation, Humans, Carcinoma, Small Cell, Tumor Suppressor Protein p53, Protein Kinase Inhibitors, Telomerase
Abstract

Among the different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) reported in EGFR-mutated lung adenocarcinoma (EGFR-LUAD) patients, histological transformation into small cell carcinoma (SCLC) occurs in 3-14% of resistant cases, regardless of the generation of EGFR-TKI. In recent studies, bi-allelic inactivation of TP53 and RB1 has been identified in a vast majority of transformed SCLCs. However, the molecular mechanisms driving this histologic transformation remain largely unknown, mainly due to the rarity of samples.Out of an initial cohort of 64 patients, tumor tissues of adequate quality and quantity for whole exome sequencing (WES) analysis were available for nine tumors for six patients: paired pre- and post-SCLC transformation samples for three Patients and post-SCLC transformation samples for three other patients.Mutational analyses showed concurrent TP53 mutations and Rb pathway alterations in five of the six patients analyzed, confirming their suggested role as predisposing genetic alterations to SCLC transformation. In addition, TERT amplification was detected in four of the six patients and found to be an event acquired during SCLC transformation. Clonal history evolution analyses from the paired LUAD/SCLC samples showed different evolution patterns. In two patients, a large proportion of mutations were present in the most recent common ancestor cell of the initial LUAD and the transformed SCLC clones, whereas in the third patient, few clonal mutations were common between the LUAD and SCLC samples and the ancestor clone that lead to SCLC was present at low frequency in the initial LUAD.Despite varied clinical presentations and clonal history evolution patterns, in addition to p53 and Rb pathways alterations, TERT amplification emerged as another common genetic mechanism of EGFR-LUAD to SCLC transformation in our cohort, and could represent a candidate therapeutic target in this subset of SCLC tumors.

Published
2022

47. Impact of the SARS-CoV-2 Epidemic on Lung Cancer Surgery in France: A Nationwide Study

Author

Pierre-Benoit Pages, Jonathan Cottenet, Philippe Bonniaud, Pascale Tubert-Bitter, Lionel Piroth, Jacques Cadranel, Alain Bernard, Catherine Quantin, HAL-SU, Gestionnaire, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital du Bocage, Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Constitutif de Référence des Maladies Pulmonaires Rares [AP-HP Tenon], Centre national de référence des maladies pulmonaires rares [Lyon] (CRMPM)-Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [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)-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), The project was funded by the French Cancer Research Association (Fondation ARC pourla recherche sur le cancer)., Unité pneumologie et oncologie thoracique [CHU Tenon], 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)-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], Centre national de référence des maladies pulmonaires rares [Lyon] (CRMPM)-Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], 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 Tenon [AP-HP], 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], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Cancer Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030204 cardiovascular system & hematology, surgical activity volume, mortality, Article, 3. Good health, 03 medical and health sciences, lung cancer, 0302 clinical medicine, Oncology, administrative data, 030220 oncology & carcinogenesis, hospital, RC254-282, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Simple SummaryFew studies have investigated the link between SARS-CoV-2 and health restrictions and its effects on the health of lung cancer (LC) patients. This study aimed to assess the impact of SARS-CoV-2 on activity volume, postoperative complications and in-hospital mortality (IHM) for LC resections in 2020 at the national level in France. Our study shows a decrease in the volume of LC resections, especially during the first lockdown. We also show that only 0.43% of patients hospitalized for LC surgery during 2020 developed a SARS-CoV-2 infection, but this low rate is counterbalanced by a high IHM (21%) in these 51 patients. Our findings suggest that, even if the IHM is high, LC surgery is feasible during a pandemic provided that the general guidance protocols edited by the surgical societies are respected. Therefore, this study provides further arguments to encourage teams to test for COVID-19 prior to surgery and patients to be vaccinated.AbstractFew studies have investigated the link between SARS-CoV-2 and health restrictions and its effects on the health of lung cancer (LC) patients. The aim of this study was to assess the impact of the SARS-CoV-2 epidemic on surgical activity volume, postoperative complications and in-hospital mortality (IHM) for LC resections in France. All data for adult patients who underwent pulmonary resection for LC in France in 2020, collected from the national administrative database, were compared to 2018–2019. The effect of SARS-CoV-2 on the risk of IHM and severe complications within 30 days among LC surgery patients was examined using a logistic regression analysis adjusted for age, sex, comorbidities and type of resection. There was a slight decrease in the volume of LC resections in 2020 (n = 11,634), as compared to 2018 (n = 12,153) and 2019 (n = 12,227), with a noticeable decrease in April 2020 (the peak of the first wave of epidemic in France). We found that SARS-CoV-2 (0.43% of 2020 resections) was associated with IHM and severe complications, with, respectively, a sevenfold (aOR = 7.17 (3.30–15.55)) and almost a fivefold (aOR = 4.76 (2.31–9.80)) increase in risk. Our study suggests that LC surgery is feasible even during a pandemic, provided that general guidance protocols edited by the surgical societies are respected

Published
2021
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48. 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

49. Editorial: New Advances in Non-small Cell Lung Cancer Management: Immune Modulation and Targeted Therapies

Author

Bogdan Grigoriu, Jacques Cadranel, Thierry Berghmans, Université libre de Bruxelles (ULB), Unité pneumologie et oncologie thoracique [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), Theranoscan [CHU Tenon] (GRC 4), 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)-Sorbonne Université (SU)

Subjects
Medicine (General), medicine.medical_treatment, Targeted therapy, lung, 03 medical and health sciences, 0302 clinical medicine, R5-920, PDL1, medicine, Lung cancer, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Lung, business.industry, Immunotherapy, General Medicine, Immune modulation, medicine.disease, targeted therapy, Sciences biomédicales, 3. Good health, PD1, medicine.anatomical_structure, Editorial, 030220 oncology & carcinogenesis, Cancer research, Medicine, Non small cell, immunotherapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

info:eu-repo/semantics/published

Published
2021
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50. Overexpression of IgG2 in patients resembling IgG4-related disease with normal IgG4

Author

Mathilde Lecuit, Pierre Aucouturier, Aicha Abbas, Jacques Cadranel, Christine Silvain, Jean‐Marie Berthelot, Anne‐Laure Fauchais, Paul Loubet, Claude Bachmeyer, Françoise Montravers, Antoine Dossier, Hilario Nunes, Pascale Cervera, and Paul Coppo

Subjects
Adult, Aged, 80 and over, Male, Biopsy, Immunology, Plasma Cells, General Medicine, Middle Aged, Immunoglobulin G, Humans, Female, Immunoglobulin G4-Related Disease, Lymph Nodes, Aged, Retrospective Studies
Abstract

IgG4-Related Disease (IgG4-RD) results from tissue infiltration by IgG4-expressing plasma cells and lymphocytes, leading to fibrosis and organomegaly. Clinical presentation is remarkably variable according to organ involvement, and high IgG4 serum concentration, initially considered a diagnostic hallmark of IgG4-RD, tends to be forgone as an indispensable criterion for its diagnosis; it can indeed be absent in some patients, highlighting the diversity of presentation of this dysimmune condition. Nevertheless, elevation of IgG4 serum concentration in suggestive settings remains an argument in favour of IgG4-RD, and while other IgG subclasses can be elevated, this biological feature lacks any diagnostic value. We retrospectively studied 9 patients (5 females, 4 males, 31-81 years old) for whom a diagnosis of IgG4-RD had been considered, based on clinical, imaging or histological criteria, but appeared to display abnormally high serum IgG2 while IgG4 levels were normal. Increased serum IgG1 in one case and increased IgG3 in another one were also noticed. Immunohistochemical analyses of intracellular immunoglobulins could be performed on tissue lymph node biopsies from 2 patients, which demonstrated strong infiltration with IgG2-expressing plasma cells. Thus, overexpression of IgG2 subclass may highlight cases of dysimmune disorders resembling IgG4-RD, although the disease trigger might be different, notably infectious. We suggest measuring all serum IgG subclass levels in patients with features consistent with IgG4-RD.

Published
2021

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