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386 results on '"Rachline, A"'

2. Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design

Author

Aslan, Alexandre, Pintado, Claire, Delaugerre, Constance, Ponscarme, Diane, Dalle, Eve, Chas, Julie, Siguier, Martin, Palich, Romain, Valentin, Marc-Antoine, Yazdanpanah, Yazdan, Lacombe, Karine, Viard, Jean-Paul, Lourenco, Jeremy, Rachline, Anne, Detruchis, Pierre, Diemer, Myriam, Azemar, Laurene, Landowski, Stephanie, Ometsguine, Philippe, Buisson, Martin, Feliho, Philip, Bachelard, Antoine, Phung, Bao, Rioux, Christophe, Proux, Caroline, Le Gac, Sylvie, Schneider, Luminita, Charmak, Aziza, Ktorza, Nadine, Seang, Sophie, Orriere, Thibaut, Sellem, Baptiste, Palacios, Christia, Mebarki, Soraya, Molina, Jean-Michel, Bercot, Beatrice, Assoumou, Lambert, Rubenstein, Emma, Algarte-Genin, Michele, Pialoux, Gilles, Katlama, Christine, Surgers, Laure, Bébéar, Cécile, Dupin, Nicolas, Ouattara, Moussa, Slama, Laurence, Pavie, Juliette, Duvivier, Claudine, Loze, Benedicte, Goldwirt, Lauriane, Gibowski, Severine, Ollivier, Manon, Ghosn, Jade, and Costagliola, Dominique

Published
2024
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3. Phosphorylation of PP2Ac by PKC is a key regulatory step in the PP2A-switch-dependent AKT dephosphorylation that leads to apoptosis

Author

Guy Nadel, Zhong Yao, Avital Hacohen-Lev-Ran, Ehud Wainstein, Galia Maik-Rachline, Tamar Ziv, Zvi Naor, Arie Admon, and Rony Seger

Subjects
PP2A phosphorylation, PP2A switch, PKC, JNK, Apoptosis, Medicine, Cytology, QH573-671
Abstract

Abstract Background Although GqPCR activation often leads to cell survival by activating the PI3K/AKT pathway, it was previously shown that in several cell types AKT activity is reduced and leads to JNK activation and apoptosis. The mechanism of AKT inactivation in these cells involves an IGBP1-coupled PP2Ac switch that induces the dephosphorylation and inactivation of both PI3K and AKT. However, the machinery involved in the initiation of PP2A switch is not known. Methods We used phospho-mass spectrometry to identify the phosphorylation site of PP2Ac, and raised specific antibodies to follow the regulation of this phosphorylation. Other phosphorylations were monitored by commercial antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by a TUNEL assay as well as PARP1 cleavage using SDS-PAGE and Western blotting. Results We identified Ser24 as a phosphorylation site in PP2Ac. The phosphorylation is mediated mainly by classical PKCs (PKCα and PKCβ) but not by novel PKCs (PKCδ and PKCε). By replacing the phosphorylated residue with either unphosphorylatable or phosphomimetic residues (S24A and S24E), we found that this phosphorylation event is necessary and sufficient to mediate the PP2A switch, which ultimately induces AKT inactivation, and a robust JNK-dependent apoptosis. Conclusion Our results show that the PP2A switch is induced by PKC-mediated phosphorylation of Ser24-PP2Ac and that this phosphorylation leads to apoptosis upon GqPCR induction of various cells. We propose that this mechanism may provide an unexpected way to treat some cancer types or problems in the endocrine machinery.

Published
2024
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4. Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial

Author

Attal-Behar, Julie, Beaune, Sébastien, Thierry chinet, Cudennec, Tristan, de Laroche, Marine, de Thezy, Albane, Dumoulin, Jennifer, Dupont, Caroline, Fercot, Elise, Giraut, Violaine, Greffe, Ségolène, Grenet, Julie, Guyot, Caroline, Labrune, Sylvie, Lachatre, Marie, Moulias, Sophie, Naline, Charlotte, Pépin, Marion, Rouveix, Elisabeth, Sahut-D'izarn, Marine, Sefssafi, Abel, Teillet, Laurent, Bru, Jean-Pierre, Gaillat, Jacques, Gautier, Vincent, Janssen, Cécile, Pagani, Leonardo, Vitrat, Virginie, Abderrahmane, Malika, Camuset, Juliette, Legall, Catherine, Longuet-Flandres, Pascale, Menn, Anne-Marie, de Lastours, Victoire, Prevost, Gwenolée, Lecronier, Marie, Burdet, Charles, Derradji, Ouda, Escaut, Lelia, Hinglais, Etienne, Lebras, Philippe, Lefevre, Edouard, Noaillon, Mathilde, Rabier, Pauline, Raphaël, Maurice, Teicher, Elina, Verny, Christiane, Vittecoq, Daniel, Wyplosz, Benjamin, Ben Hayoun, Michèle, Brun-Vezinet, Françoise, Casalino, Enrique, Choquet, Christophe, Dombret, Marie-Christine, Duval, Xavier, Houhou, Nadhira, Joly, Véronique, Lescure, Xavier, Pogliaghi, Manuela, Rioux, Christophe, Yazdanpanah, Yazdan, Barros, Elsa, Begga, Belinda, Boukobza, Sébastien, Bouredji, Houria, Chouahi, Imad, Delacroix, Isabelle, Froissart, Antoine, Garrait, Valérie, Ngwem, Elsa, Phlippoteau, Catherine, Salehabadi, Sepehr, Toper, Cécile, Vinas, Florent, Amsilli, Marie, Epaulard, Olivier, Pavese, Patricia, Pierre, Isabelle, Stahl, Jean-Paul, Aulagnier, Jérôme, Celerier, Julie, Cojocariu, Roxana, Kahn, Jean-Emmanuel, Mathieu, Emmanuel, Rachline, Charlotte, Schoindre, Yoland, Sene, Thomas, Thierry, Christelle, Aparicio, Caroline, Delcey, Véronique, Lopes, Amanda, Pierre, Marjolaine Morgand, Sellier, Simoneau, Guy, Chakvetadze, Catherine, Diamantis, Sylvain, Gauthier, Arnaud, Jidar, Kaoutar, Jourdain, Béatrice, Boitiaux, Jean-Francois, Deschamps, Patrick, Devaud, Edouard, Philippe, Bruno, Calin, Ruxandra-Oana, Chroboczek, Tomasz, Davido, Benjamin, Deconinck, Laurène, de Truchis, Pierre, Lagrange, Aurore, Makhloufi, Sabrina, Matt, Morgan, Mellon, Guillaume, Senard, Olivia, Benhamou, Daniel, Chapuzet, Claire, Chauffrey, Laure, Etienne, Manuel, Joly, Luc-Marie, Obstoy, Bérengère, Salaun, Mathieu, Thiberville, Luc, Tillon, Julie, Bollens, Diane, Bottero, Julie, Campa, Pauline, Cosqueric, Gäelle, Lefebvre, Bénédicte, Ouazene, Zineb, Pacanowski, Jérôme, Pateron, Dominique, Valin, Nadia, Compain, Caroline, Cordel, Hugues, Doumenc, Benoit, Fois, Elena, Gambier, Nicolas, Khuong, Marie-Aude, Pasqualoni, Elisa, Poupard, Marie, Dinh, Aurélien, Duran, Clara, Ropers, Jacques, Bouchand, Frédérique, Calin, Ruxandra, Chinet, Thierry, Renaud, Bertrand, Claessens, Yann-Erick, Labarère, José, Bedos, Jean-Pierre, Aegerter, Philippe, and Crémieux, Anne-Claude

Published
2024
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5. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trialsResearch in context

Author

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 Bertrand, Sylviane Ravato, Marie Vayssettes, Anne Adda, Celine Wilpotte, Pélagie Thibaut, Julie Fillon, Isabelle Debrix, Soraya Fellahi, Jean-Philippe Bastard, Guillaume Lefévre, Jacques-Eric Gottenberg, Yves Hansmann, Frédéric Blanc, Sophie Ohlmann-Caillard, Vincent Castelain, Emmanuel Chatelus, Eva Chatron, Olivier Collange, François Danion, Frédéric De Blay, Pierre Diemunsch, Sophie Diemunsch, Renaud Felten, Bernard Goichot, Valentin Greigert, Aurelien Guffroy, Bob Heger, Charlotte Kaeuffer, Loic Kassegne, Anne Sophie Korganow, Pierrick Le Borgne, Nicolas Lefebvre, Paul-Michel Mertes, Eric Noll, Mathieu Oberlin, Vincent Poindron, Julien Pottecher, Yvon Ruch, François Weill, Nicolas Meyer, Emmanuel Andres, Eric Demonsant, Hakim Tayebi, Gabriel Nisand, Stéphane Brin, Cédric Sublon, Guillaume Becker, Anne Hutt, Tristan Martin, Sophie Bayer, Catherine Metzger, Arsene Mekinian, Noémie Abisror, Amir Adedjouma, Diane Bollens, Marion Bonneton, Nathalie Bourcicaux, Anne Bourrier, Maria Chauchard Thibault Chiarabiani, Doroth.e Chopin, Jonathan Cohen, Ines Devred, Bruno Donadille, Olivier Fain, Geoffrey Hariri, Vincent Jachiet, Patrick Ingliz, Marc Garnier, Marc Gatfosse, Etienne Ghrenassia, Delphine Gobert, Jessica Krause le Garrec, Cecilia Landman, Jean Remy Lavillegrand, Benedicte Lefebvre, Thibault Mahevas, Sandie Mazerand, Jean Luc Meynard, Marjolaine Morgand, Zineb Ouaz.ne, Jerome Pacanowski, S.bastien Riviere, Philippe Seksik, Harry Sokol, Heithem Soliman, Nadia Valin, Thomas Urbina, Chloé McAvoy, Maria Pereira Miranda, Gladys Aratus, Laurence Berard, Tabassome Simon, Anne Daguenel Nguyen, Elise Girault, Cl.mentine Mayala-Kanda, Marie Antignac, Céline Leplay, Jean-Benoit Arlet, Jean-Luc Diehl, Florence Bellenfant, Anne Blanchard, Alexandre Buffet, Bernard Cholley, Antoine Fayol, Edouard Flamarion, Anne Godier, Thomas Gorget, Sophie-Rym Hamada, Caroline Hauw-Berlemont, Jean-Sébastien Hulot, David Lebeaux, Marine Livrozet, Adrien Michon, Arthur Neuschwander, Marie-Aude Pennet, Benjamin Planquette, Brigitte Ranque, Olivier Sanchez, Geoffroy Volle, Sandrine Briois, Mathias Cornic, Virginie Elisee, Jesuthasan Denis, Juliette Djadi-Prat, Pauline Jouany, Ramon Junquera, Mickael Henriques, Amina Kebir, Isabelle Lehir, Jeanne Meunier, Florence Patin, Val.rie Paquet, Anne Tréhan, Véronique Vigna, Brigitte Sabatier, Damien Bergerot, Charléne Jouve, Camille Knosp, Olivia Lenoir, Nassim Mahtal, Léa Resmini, Xavier Lescure, Jade Ghosn, Antoine Bachelard, Anne Rachline, Valentina Isernia, Bao-chau, Phung, Dorothée Vallois, Aurelie Sautereau, Catherine Neukrich, Antoine Dossier, Raphaël Borie, Bruno Crestani, Gregory Ducrocq, Philippe Gabriel Steg, Philippe Dieude, Thomas Papo, Estelle Marcault, Marhaba Chaudhry, Charléne Da Silveira, Annabelle Metois, Ismahan Mahenni, Meriam Meziani, Cyndie Nilusmas, Sylvie Le Gac, Awa Ndiaye, Fran.oise Louni, Malikhone Chansombat, Zelie Julia, Solaya Chalal, Lynda Chalal, Laura Kramer, Jeniffer Le Grand, Kafif Ouifiya, Valentine Piquard, Sarah Tubiana, Yann Nguyen, Vasco Honsel, Emmanuel Weiss, Anais Codorniu, Virginie Zarrouk, Victoire de Lastours, Matthieu Uzzan, Naura Gamany, Agathe Claveirole, Alexandre Navid, Tiffanie Fouque, Yonathan Cohen, Maya Lupo, Constance Gilles, Roza Rahli, Zeina Louis, David Boutboul, Lionel Galicier, Yaël Amara, Gabrielle Archer, Amira Benattia, Anne Bergeron, Louise Bondeelle, Nathalie de Castro, Melissa Clément, Michaël Darmon, Blandine Denis, Clairelyne Dupin, Elsa Feredj, Delphine Feyeux, Adrien Joseph, Etienne Lenglin, Pierre Le Guen, Geoffroy Liégeon, Gwenaël Lorillon, Asma Mabrouki, Eric Mariotte, Grégoire Martin de Frémont, Adrien Mirouse, Jean-Michel Molina, Régis Peffault de Latour, Eric Oksenhendler, Julien Saussereau, Abdellatif Tazi, Jean-Jacques Tudesq, Lara Zafrani, Isabelle Brindele, Emmanuelle Bugnet, Karine Celli Lebras, Julien Chabert, Lamia Djaghout, Catherine Fauvaux, Anne Lise Jegu, Ewa Kozakiewicz, Martine Meunier, Marie-Thérèse Tremorin, Claire Davoine, Isabelle Madelaine, Sophie Caillat-Zucman, Constance Delaugerre, Florence Morin, Damien Sène, Ruxandra Burlacu, Benjamin Chousterman, Bruno Mégarbanne, Pascal Richette, Jean-Pierre Riveline, Aline Frazier, Eric Vicaut, Laure Berton, Tassadit Hadjam, Miguel Alejandro Vazquez-Ibarra, Clément Jourdaine, Olivia Tran, Véronique Jouis, Aude Jacob, Julie Smati, Stéphane Renaud, Claire Pernin, Lydia Suarez, Luca Semerano, Sébastien Abad, Ruben B. nainous, Nicolas Bonnet, Celine Comparon, Yves Cohen, Hugues Cordel, Robin Dhote, Nathalie Dournon, Boris Duchemann, Nathan Ebstein, Thomas Gille, Benedicte Giroux-Leprieur, Jeanne Goupil de Bouille, Hilario Nunes, Johanna Oziel, Dominique Roulot, Lucile Sese, ClaireTantet, Yurdagul Uzunhan, Coralie Bloch-Queyrat, Vincent Levy, Fadhila Messani, Mohammed Rahaoui, Myléne Petit, Sabrina Brahmi, Vanessa Rathoin, Marthe Rigal, Nathalie Costedoat-Chalumeau, Liem Binh Luong, Zakaria Ait Hamou, Sarah Benghanem, Philippe Blanche, Nicolas Carlier, Benjamin Chaigne, Remy Gauzit, Hassan Joumaa, Mathieu Jozwiak, Marie Lachétre, Hélène Lafoeste, Odie Launay, Paul Legendre, Jonathan Marey, Caroline Morbieu, Lola-Jade Palmieri, Tali-Anne Szwebel, Hendy Abdoul, Alexandra Bruneau, Audrey Beclin-Clabaux, Charly Larrieu, Pierre Montanari, Eric Dufour, Ada Clarke, Catherine Le Bourlout, Nathalie Marin, Nathalie Menage, Samira Saleh-Mghir, Mamadou Salif Cisse, Kahina Cheref, Corinne Guerin, Jérémie Zerbit, Marc Michel, Sébastien Gallien, Etienne Crickx, Benjamin Le Vavasseur, Emmanuelle Kempf, Karim Jaffal, William Vindrios, Julie Oniszczuk, Constance Guillaud, Pascal Lim, Elena Fois, Giovanna Melica, Marie Matignon, Maud Jalabert, Jean-Daniel Lelièvre, David Schmitz, Marion Bourhis, Sylia Belazouz, Laetitia Languille, Caroline Boucle, Nelly Cita, Agnés Didier, Fahem Froura, Katia Ledudal, Thiziri Sadaoui, Alaki Thiemele, Delphine Le Febvre De Bailly, Muriel Carvhalo Verlinde, Julien Mayaux, Patrice Cacoub, David Saadoun, Mathieu Vautier, Héléne Bugaut, Olivier Benveniste, Yves Allenbach, Gaëlle Leroux, Aude Rigolet, Perrine Guillaume-Jugnot, Fanny Domont, Anne Claire Desbois, Chloé Comarmond, Nicolas Champtiaux, Segolene Toquet, Amine Ghembaza, Matheus Vieira, Georgina Maalouf, Goncalo Boleto, Yasmina Ferfar, Jean-Christophe Corvol, C.line Louapre, Sara Sambin, Louise-Laure Mariani, Carine Karachi, Florence Tubach, Candice Estellat, Linda Gimeno, Karine Martin, Aicha Bah, Vixra Keo, Sabrine Ouamri, Yasmine Messaoudi, Nessima Yelles, Pierre Faye, Sebastien Cavelot, Cecile Larcheveque, Laurence Annonay, Jaouad Benhida, Aida Zahrate-Ghoul, Soumeya Hammal, Ridha Belilita, Fanny Charbonnier, Claire Aguilar, Fanny Alby-Laurent, Carole Burger, Clara Campos-Vega, Nathalie Chavarot, Benjamin Fournier, Claire Rouzaud, Damien Vimpére, Caroline Elie, Prissile Bakouboula, Laure Choupeaux, Sophie Granville, Elodie Issorat, Christine Broissand, Marie-Alexandra Alyanakian, Guillaume Geri, Nawal Derridj, Naima Sguiouar, Hakim Meddah, Mourad Djadel, Héléne Chambrin-Lauvray, Jean-Charles Duclos-vallée, Faouzi Saliba, Sophie-Caroline Sacleux, Ilias Kounis, Sonia Tamazirt, Eric Rudant, Jean-Marie Michot, Annabelle Stoclin, Emeline Colomba, Fanny Pommeret, Christophe Willekens, Rosa Da Silva, Valérie Dejean, Yasmina Mekid, Ines Ben-Mabrouk, Florence Netzer, Caroline Pradon, Laurence Drouard, Valérie Camara-Clayette, Alexandre Morel, Gilles Garcia, Abolfazl Mohebbi, Férial Berbour, Mélanie Dehais, Anne-Lise Pouliquen, Alison Klasen, Loren Soyez-Herkert, Jonathan London, Younes Keroumi, Emmanuelle Guillot, Guillaume Grailles, Younes El amine, Fanny Defrancq, Hanane Fodil, Chaouki Bouras, Dominique Dautel, Nicolas Gambier, Thierno Dieye, Boris Bienvenu, Victor Lancon, Laurence Lecomte, Kristina Beziriganyan, Belkacem Asselate, Laure Allanic, Elena Kiouris, Marie-Héléne Legros, Christine Lemagner, Pascal Martel, Vincent Provitolo, Félix Ackermann, Mathilde Le Marchand, Aurélie Chan Hew Wai, Dimitri Fremont, Elisabeth Coupez, Mireille Adda, Frédéric Duée, Lise Bernard, Antoine Gros, Estelle Henry, Claire Courtin, Anne Pattyn, Pierre-Grégoire Guinot, Marc Bardou, Agnes Maurer, Julie Jambon, Amélie Cransac, Corinne Pernot, Bruno Mourvillier, Eric Marquis, Philippe Benoit, Damien Roux, Coralie Gernez, Cécile Yelnik, Julien Poissy, Mandy Nizard, Fanette Denies, Helene Gros, Jean-Jacques Mourad, Emmanuelle Sacco, Sophie Renet, F. Ader, Y. Yazdanpanah, F. Mentre, N. Peiffer-Smadja, F.X. Lescure, J. Poissy, L. Bouadma, J.F. Timsit, B. Lina, F. Morfin-Sherpa, M. Bouscambert, A. Gaymard, G. Peytavin, L. Abel, J. Guedj, C. Andrejak, C. Burdet, C. Laouenan, D. Belhadi, A. Dupont, T. Alfaiate, B. Basli, A. Chair, S. Laribi, J. Level, M. Schneider, M.C. Tellier, A. Dechanet, D. Costagliola, B. Terrier, M. Ohana, S. Couffin-Cadiergues, H. Esperou, C. Delmas, J. Saillard, C. Fougerou, L. Moinot, L. Wittkop, C. Cagnot, S. Le Mestre, D. Lebrasseur-Longuet, V. Petrov-Sanchez, A. Diallo, N. Mercier, V. Icard, B. Leveau, S. Tubiana, B. Hamze, A. Gelley, M. Noret, E. D’Ortenzio, O. Puechal, C. Semaille, T. Welte, J.A. Paiva, M. Halanova, M.P. Kieny, E. Balssa, C. Birkle, S. Gibowski, E. Landry, A. Le Goff, L. Moachon, C. Moins, L. Wadouachi, C. Paul, A. Levier, D. Bougon, F. Djossou, L. Epelboin, J. Dellamonica, C.H. Marquette, C. Robert, S. Gibot, E. Senneville, V. Jean-Michel, Y. Zerbib, C. Chirouze, A. Boyer, C. Cazanave, D. Gruson, D. Malvy, P. Andreu, J.P. Quenot, N. Terzi, K. Faure, C. Chabartier, V. Le Moing, K. Klouche, T. Ferry, F, Valour, B. Gaborit, E. Canet, P. Le Turnier, D. Boutoille, F. Bani-Sadr, F. Benezit, M. Revest, C. Cameli, A. Caro, MJ Ngo Um Tegue, Y. Le Tulzo, B. Laviolle, F. Laine, G. Thiery, F. Meziani, Y. Hansmann, W. Oulehri, C. Tacquard, F. Vardon-Bounes, B. Riu-Poulenc, M. Murris-Espin, L. Bernard, D. Garot, O. Hinschberger, M. Martinot, C. Bruel, B. Pilmis, O. Bouchaud, P. Loubet, C. Roger, X. Monnet, S. Figueiredo, V. Godard, J.P. Mira, M. Lachatre, S. Kerneis, J. Aboab, N. Sayre, F. Crockett, D. Lebeaux, A. Buffet, J.L. Diehl, A. Fayol, J.S. Hulot, M. Livrozet, A Mekontso- Dessap, C. Ficko, F. Stefan, J. Le Pavec, J. Mayaux, H. Ait-Oufella, J.M. Molina, G. Pialoux, M. Fartoukh, J. Textoris, M. Brossard, A. Essat, E. Netzer, Y. Riault, M. Ghislain, L. Beniguel, M. Genin, L. Gouichiche, C. Betard, L. Belkhir, A. Altdorfer, V Fraipont Centro, S. Braz, JM Ferreira Ribeiro, R Roncon Alburqueque, M. Berna, M. Alexandre, B. Lamprecht, A. Egle, R. Greil, M. Joannidis, Thomas F. Patterson, Philip O. Ponce, Barbara S. Taylor, Jan E. Patterson, Jason E. Bowling, Heta Javeri, LuAnn Larson, Angela Hewlett, Aneesh K. Mehta, Nadine G. Rouphael, Youssef Saklawi, Nicholas Scanlon, Jessica J. Traenkner, Ronald P. Trible, Jr., Emmanuel B. Walter, Noel Ivey, Thomas L. Holland, Guillermo M. Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Lanny Hsieh, Alpesh N. Amin, Miki Watanabe, Helen S. Lee, Susan Kline, Joanne Billings, Brooke Noren, Hyun Kim, Tyler D. Bold, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Nicole Iovine, Lars K. Beattie, Rebecca Murray Wakeman, Matthew Shaw, Mamta K. Jain, Satish Mocherla, Jessica Meisner, Amneris Luque, Daniel A. Sweeney, Constance A. Benson, Farhana Ali, Robert L. Atmar, Hana M. El Sahly, Jennifer Whitaker, Ann R. Falsey, Angela R. Branche, Cheryl Rozario, Justino Regalado Pineda, José Arturo Martinez-Orozco, David Chien Lye, Sean WX. Ong, Po Ying Chia, Barnaby E. Young, Uriel Sandkovsky, Mezgebe Berhe, Clinton Haley, Emma Dishner, Valeria D. Cantos, Colleen F. Kelley, Paulina A. Rebolledo Esteinou, Sheetal Kandiah, Sarah B. Doernberg, Pierre-Cedric B. Crouch, Hannah Jang, Anne F. Luetkemeyer, Jay Dwyer, Stuart H. Cohen, George R. Thompson, 3rd, Hien H. Nguyen, Robert W. Finberg, Jennifer P. Wang, Juan Perez-Velazquez, Mireya Wessolossky, Patrick E.H. Jackson, Taison D. Bell, Miranda J. West, Babafemi Taiwo, Karen Krueger, Johnny Perez, Triniece Pearson, Catharine I. Paules, Kathleen G. Julian, Danish Ahmad, Alexander G. Hajduczok, Henry Arguinchona, Christa Arguinchona, Nathaniel Erdmann, Paul Goepfert, Neera Ahuja, Maria G. 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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6. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

Author

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

Published
2024
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10. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author

Mariette, Xavier, Hermine, Olivier, Tharaux, Pierre-Louis, Resche-Rigon, Matthieu, Porcher, Raphael, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Dalibey, Sarah, Raked, Nabil, Mameri, Lakhdar, Alary, Stéphanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Montlahuc, Claire, Biard, Lucie, Charreteur, Robin, Dupré, Celine, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Pavot, Arthur, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Bulifon, Sophie, Jaïs, Xavier, Sitbon, Olivier, Pavy, Stéphan, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stéphane, Baudry, Elodie, Verny, Christiane, Noaillon, Mathilde, Lefèvre, Edouard, Zaidan, Mohamad, Le Tiec, Clotilde Le Tiec, Verstuyft, Céline, Roques, Anne-Marie, Grimaldi, Lamiae, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Solène, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Georgin-Lavialle, Sophie, Senet, Patricia, Pialoux, Gilles, Soria, Angèle, Parrot, Antoine, François, Hélène, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadège, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefèvre, Guillaume, Fallet, Vincent, Gottenberg, Jacques-Eric, Hansmann, Yves, Andres, Emmanuel, Bayer, Sophie, Becker, Guillaume, Blanc, Frédéric, Brin, Stéphane, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Demonsant, Eric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurélien, Heger, Bob, Hutt, Anne, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Martin, Tristan, Mertes, Paul Michel, Metzger, Catherine, Meyer, Nicolas, Nisand, Gabriel, Noll, Eric, Oberlin, Mathieu, Ohlmann-Caillard, Sophie, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Sublon, Cédric, Tayebi, Hakim, Weill, François, Mekinian, Arsène, Abisror, Noémie, Jachiet, Vincent, Chopin, Dorothée, Fain, Olivier, Garnier, Marc, Krause le Garrec, Jessica, Morgand, Marjolaine, Pacanowski, Jerome, Urbina, Tomas, McAvoy, Chloe, Pereira, Maria, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Daguenel-Nguyen, Anne, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Penet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Jesuthasan, Denis, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Valérie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, F-Xavier, Ghosn, Jade, BACHELARD, Antoine, BIRONNE, Timothee, BORIE, Raphael, BOUNHIOL, Agathe, BOUSSARD, Catherine, CHAUFFiER, Jeanne, CHALAL, Solaya, CHALAL, Lynda, CHANSOMBAT, Malikhone, CRESPIN, Paul, CRESTANI, Bruno, DACONCEICAO, Olivia, DECONINCK, Laurene, DIEUDE, Philippe, DOSSIER, Antoine, DUBERT, Marie, DUCROCQ, Greggory, FUENTES, Axelle, GERVAIS, Anne, GILBERT, Marie, ISERNIA, Valentina, ISMAEL, Sophie, JOLY, Veronique, JULIA, Zelie, LARIVEN, Sylvie, LE GAC, Sylvie, LE PLUART, Diane, LOUNI, Francoise, NDIAYE, Awa, PAPO, Thomas, PARISEY, Marion, PHUNG, Bao, POURBAIX, Annabelle, RACHLINE, Anne, RIOUX, Christophe, SAUTEREAU, Aurelie, STEG, Gabriel, TARHINI, Hassan, VALAYER, Simon, VALLOIS, Dorothee, VERMES, Paul, VOLPE, Thomas, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anaïs, Zarrouk, Virginie, De Lastours, Victoire, Uzzan, Matthieu, Olivier, Olivier, Rossi, Geoffrey, Gamany, Naura, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, De Castro, Nathalie, Clément, Melissa, Darmont, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lengliné, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asmaa, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Celli Lebras, Karine, Chabert, Julien, Djaghout, Lalia, Fauvaux, Catherine, Jegu, Anne Lise, Kozaliewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madeleine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, SENE, Damien, BURLACU, Ruxandra, CHOUSTERMAN, Benjamin, MEGARBANE, Bruno, RICHETTE, Pascal, RIVELINE, Jean-Pierre, FRAZIER, Aline, VICAUT, Eric, BERTON, Laure, HADJAM, Tassadit, VASQUEZ-IBARRA, Miguel Alejandro, JOURDAINE, Clément, JACOB, Aude, SMATI, Julie, RENAUD, Stéphane, MANIVET, Philippe, PERNIN, Claire, SUAREZ, Lydia, Semerano, Luca, ABAD, Sebastien, Benainous, Ruben, Bloch Queyrat, Coralie, Bonnet, Nicolas, Brahmi, Sabrina, Cailhol, johann, Cohen, Yves, Comparon, Celine, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Jacolot, Anne, Nunes, Hilario, Oziel, Johanna, Rathouin, Vanessa, Rigal, Marthe, Roulot, Dominique, Tantet, Claire, Uzunhan, Yurdagul, COSTEDOAT-CHALUMEAU, Nathalie, Ait Hamou, Zakaria, Benghanem, Sarah, BLANCHE, Philippe, CANOUI, Etienne, CARLIER, Nicolas, CHAIGNE, Benjamin, CONTEJEAN, Adrien, DUNOGUE, Bertrand, DUPLAND, Pierre, DUREL - MAURISSE, Aurélie, GAUZIT, Remy, JAUBERT, Paul, Joumaa, Hassan, Jozwiak, Mathieu, KERNEIS, Solen, LACHATRE, Marie, Lafoeste, Hélène, LEGENDRE, Paul, LUONG NGUYEN, Liem Binh, MAREY, Jonathan, MORBIEU, Caroline, MOUTHON, Luc, NGUYEN, Lee, Palmieri, Lola-Jade, REGENT, Alexis, SZWEBEL, Tali-Anne, TERRIER, Benjamin, GUERIN, Corinne, ZERBIT, Jérémie, CHEREF, Kahina, CHITOUR, Kamil, CISSE, Mamadou Salif, CLARKE, Ada, CLAVERE, Gaelle, DUSANTER, Isabelle, GAUDEFROY, Caroline, JALLOULI, Moez, KOLTA, Sami, LE BOURLOUT, Catherine, MARIN, Nathalie, MENAGE, Nathalie, MOORES, Alexandre, PEIGNEY, Isabelle, PIERRON, Cédric, SALEH-MGHIR, Samira, VALLET, Mathilde, MICHEL, Marc, MELICA, Giovanna, LELIEVRE, Jean-Daniel, FOIS, Elena, LIM, Pascal, MATIGNON, Marie, GUILLAUD, Constance, THIEMELE, Alaki, SCHMITZ, David, BOUHRIS, Marion, BELAZOUZ, Syllia, LANGUILLE, Laetitia, MEKONTSO-DESSAPS, Armand, SADAOUI, Thiziri, Mayaux, Julien, Cacoub, Patrice, Corvol, Jean-Christophe, Louapre, Céline, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aïcha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sébastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Lecronier, Marie, Beurton, Alexandra, Haudebourg, Luc, Deleris, Robin, Le Marec, Julien, Virolle, Sara, Nemlaghi, Safaa, Bureau, Côme, Mora, Pierre, De Sarcus, Martin, Clovet, Olivier, Duceau, Baptiste, Grisot, Paul Henri, Pari, Marie hélène, Arzoine, Jérémy, Clarac, Ulrich, Faure, Morgane, Delemazure, Julie, Decavele, Maxence, Morawiec, Elise, Demoule, Alexandre, Dres, Martin, Vautier, Mathieu, Allenbach, Yves, Benveniste, Olivier, Leroux, Gaelle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Cloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Gonçalo, Ferfar, Yasmina, Charbonnier, Fanny, AGUILAR, Claire, ALBY-LAURENT, Fanny, ALYANAKIAN, Marie-Alexandra, BAKOUBOULA, Prissile, BROISSAND, Christine, BURGER, Carole, CAMPOS-VEGA, Clara, CHAVAROT, Nathalie, CHOUPEAUX, Laure, FOURNIER, Benjamin, GRANVILLE, Sophie, ISSORAT, Elodie, ROUZAUD, Claire, VIMPERE, Damien, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Helene, Duclos-Vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Koumis, Ilias, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Chistophe, Sakkal, Madona, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El Amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Razurel, Anaïs, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Hélène, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Clan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Servettaz, Amélie, Deslée, Gaetan, Wynckel, Alain, Benoit, Philippe, Marquis, Eric, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Hélène, Mourad, Jean-Jacques, Sacco, Emmanuelle, and Renet, Sophie

Published
2022
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11. GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch

Author

Guy Nadel, Zhong Yao, Ehud Wainstein, Izel Cohen, Ido Ben-Ami, Amir Schajnovitz, Galia Maik-Rachline, Zvi Naor, Benjamin A. Horwitz, and Rony Seger

Subjects
AKT, PI3K, PP2A, IGBP1, PKC, Medicine, Cytology, QH573-671
Abstract

Abstract Background G protein-coupled receptors (GPCRs) usually regulate cellular processes via activation of intracellular signaling pathways. However, we have previously shown that in several cell lines, GqPCRs induce immediate inactivation of the AKT pathway, which leads to JNK-dependent apoptosis. This apoptosis-inducing AKT inactivation is essential for physiological functions of several GqPCRs, including those for PGF2α and GnRH. Methods Here we used kinase activity assays of PI3K and followed phosphorylation state of proteins using specific antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by TUNEL assay and PARP1 cleavage. Results We identified the mechanism that allows the unique stimulated inactivation of AKT and show that the main regulator of this process is the phosphatase PP2A, operating with the non-canonical regulatory subunit IGBP1. In resting cells, an IGBP1-PP2Ac dimer binds to PI3K, dephosphorylates the inhibitory pSer608-p85 of PI3K and thus maintains its high basal activity. Upon GqPCR activation, the PP2Ac-IGBP1 dimer detaches from PI3K and thus allows the inhibitory dephosphorylation. At this stage, the free PP2Ac together with IGBP1 and PP2Aa binds to AKT, causing its dephosphorylation and inactivation. Conclusion Our results show a stimulated shift of PP2Ac from PI3K to AKT termed “PP2A switch” that represses the PI3K/AKT pathway, providing a unique mechanism of GPCR-stimulated dephosphorylation. Video Abstract

Published
2022
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12. Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design

Author

Molina, Jean-Michel, primary, Bercot, Beatrice, additional, Assoumou, Lambert, additional, Rubenstein, Emma, additional, Algarte-Genin, Michele, additional, Pialoux, Gilles, additional, Katlama, Christine, additional, Surgers, Laure, additional, Bébéar, Cécile, additional, Dupin, Nicolas, additional, Ouattara, Moussa, additional, Slama, Laurence, additional, Pavie, Juliette, additional, Duvivier, Claudine, additional, Loze, Benedicte, additional, Goldwirt, Lauriane, additional, Gibowski, Severine, additional, Ollivier, Manon, additional, Ghosn, Jade, additional, Costagliola, Dominique, additional, Aslan, Alexandre, additional, Pintado, Claire, additional, Delaugerre, Constance, additional, Ponscarme, Diane, additional, Dalle, Eve, additional, Chas, Julie, additional, Siguier, Martin, additional, Palich, Romain, additional, Valentin, Marc-Antoine, additional, Yazdanpanah, Yazdan, additional, Lacombe, Karine, additional, Viard, Jean-Paul, additional, Lourenco, Jeremy, additional, Rachline, Anne, additional, Detruchis, Pierre, additional, Diemer, Myriam, additional, Azemar, Laurene, additional, Landowski, Stephanie, additional, Ometsguine, Philippe, additional, Buisson, Martin, additional, Feliho, Philip, additional, Bachelard, Antoine, additional, Phung, Bao, additional, Rioux, Christophe, additional, Proux, Caroline, additional, Le Gac, Sylvie, additional, Schneider, Luminita, additional, Charmak, Aziza, additional, Ktorza, Nadine, additional, Seang, Sophie, additional, Orriere, Thibaut, additional, Sellem, Baptiste, additional, Palacios, Christia, additional, and Mebarki, Soraya, additional

Published
2024
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14. JNK Cascade-Induced Apoptosis—A Unique Role in GqPCR Signaling

Author

Guy Nadel, Galia Maik-Rachline, and Rony Seger

Subjects
MAPK, JNK, GqPCR, apoptosis, PP2A switch, AKT, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

The response of cells to extracellular signals is mediated by a variety of intracellular signaling pathways that determine stimulus-dependent cell fates. One such pathway is the cJun-N-terminal Kinase (JNK) cascade, which is mainly involved in stress-related processes. The cascade transmits its signals via a sequential activation of protein kinases, organized into three to five tiers. Proper regulation is essential for securing a proper cell fate after stimulation, and the mechanisms that regulate this cascade may involve the following: (1) Activatory or inhibitory phosphorylations, which induce or abolish signal transmission. (2) Regulatory dephosphorylation by various phosphatases. (3) Scaffold proteins that bring distinct components of the cascade in close proximity to each other. (4) Dynamic change of subcellular localization of the cascade’s components. (5) Degradation of some of the components. In this review, we cover these regulatory mechanisms and emphasize the mechanism by which the JNK cascade transmits apoptotic signals. We also describe the newly discovered PP2A switch, which is an important mechanism for JNK activation that induces apoptosis downstream of the Gq protein coupled receptors. Since the JNK cascade is involved in many cellular processes that determine cell fate, addressing its regulatory mechanisms might reveal new ways to treat JNK-dependent pathologies.

Published
2023
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15. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Bazzalo, Ignacio J., Casas, Marcelo M., Nuñez, Sebastián A., Pere, Yael, Ibarrola, Carlos M., Solis Aramayo, Marco A., Cuesta, Maria C., Duarte, Andrea E., Gutierrez Fernandez, Pablo M., Iannantuono, Maria A., Miyazaki, Erica A., Silvio, Javier P., Scublinsky, Dario G., Bales, Alessandra, Catarino, Daniela, Fiss, Elie, Mohrbacher, Sara, Sato, Victor, Baylao, Antonio, Cavalcante, Adilson, Correa, Francini, de Andrade, Celso A., Furtado, Juvencio, Ribeiro Filho, Nelson, Telles, Valéria, Trevelin, Leopoldo T., Vipich, Ricardo, Boldo, Rodrigo, Borges, Paula, Lobo, Suzana, Luckemeyer, Graziela, Machado, Luana, Alves, Maysa B., Iglessias, Ana C., Lago, Marianna M., Santos, Daniel W., Chapdelaine, Hugo, Falcone, Emilia L., Jamal, Rahima, Luong, Me-Linh, Durand, Madeleine, Doucet, Stephane, Carrier, François-Martin, Coburn, Bryan A., Del Sorbo, Lorenzo, Walmsley, Sharon L., Belga, Sara, Chen, Luke Y., Mah, Allison D., Steiner, Theodore, Wright, Alissa J., Hajek, J., Adhikari, Neill, Fowler, Robert A., Daneman, Nick, Khwaja, Kosar A., Shahin, Jason, Gonzalez, Carolina, Silva, Rafael, Lindh, Marcelo, Maluenda, Gabriel, Fernandez, Patricia, Oyonarte, Maite, Lasso, Martin, Boyer, Alexandre, Bronnimann, Didier, Bui, Hoang-Nam, Cazanave, Charles, Chaussade, Helene, Desclaux, Arnaud, Ducours, Mailys, Duvignaud, Alexandre, Malvy, Denis, Martin, Lisa, Neau, Didier, Nguyen, Duc, Pistone, Thierry, Soubrane-Wirth, Gaetane, Leitao, Julie, Allavena, Clotilde, Biron, Charlotte, Bouchez, Sabelline, Gaborit, Benjamin, Gregoire, Antoine, Le Turnier, Paul, Lecompte, Anne-Sophie, Lecomte, Raphael, Lefebvre, Maeva, Raffi, Francois, Boutoille, David, Morineau, Pascale H., Guéry, Romain, Chatelus, Emmanuel, Dumoussaud, Nathalie, Felten, Renaud, Luca, Florina, Goichot, Bernard, Schneider, Francis, Taquet, Marie-Caroline, Groh, Matthieu, Roumier, Mathilde, Neuville, Mathilde, Bachelard, Antoine, Isernia, Valentina, Lescure, F-Xavier, Phung, Bao-Chau, Rachline, Anne, Sautereau, Aurelie, Vallois, Dorothee, Bleher, Yves, Boucher, Delphine, Coudon, Clémentine, Esnault, Jean, Guimard, Thomas, Leautez-Nainville, Sophie, Merrien, Dominique, Morrier, Marine, Motte-Vincent, Pauline, Gabeff, Romain, Leclerc, Hélène, Cozic, Céline, Decours, Romain, Février, Ronan, Colin, Gwenhael, Abgrall, Sophie, Vignes, Dorothee, Sterpu, Raluca, Kuellmar, Mira, Meersch-Dini, Melanie, Weiss, Raphael, Zarbock, Alexander, Antony, Christiane, Berger, Marc, Brenner, Thorsten, Taube, Christian, Herbstreit, Frank, Dolff, Sebastian, Konik, Margarethe, Schmidt, Karsten, Zettler, Markus, Witzke, Oliver, Boell, Boris, Garcia Borrega, Jorge, Koehler, Philipp, Zander, Thomas, Dusse, Fabian, Al-Sawaf, Othman, Köhler, Philipp, Eichenauer, Dennis, Kochanek, Matthias, Shimabukuro-Vornhagen, Alexander, Mellinghoff, Sibylle, Claßen, Annika, Heger, Jan-Michel, Meyer-Schwickerath, Charlotte, Liedgens, Paul, Heindel, Katrin, Belkin, Ana, Biber, Asaf, Gilboa, Mayan, Levy, Itzchak, Litachevsky, Vladislav, Rahav, Galia, Finesod Wiedner, Anat, Zilberman-Daniels, Tal, Oster, Yonatan, Strahilevitz, Jacob, Sviri, Sigal, Baldissera, Elena M., Campochiaro, Corrado, Cavalli, Giulio, Dagna, Lorenzo, De Luca, Giacomo, Della Torre, Emanuel, Tomelleri, Alessandro, Bernasconi De Luca, Davide, Capetti, Amedeo F., Coen, Massimo, Cossu, Maria V., Galli, Massimo, Giacomelli, Andrea, Gubertini, Guido A., Rusconi, Stefano, Burastero, Giulia J., Digaetano, Margherita, Guaraldi, Giovanni, Meschiari, Marianna, Mussini, Cristina, Puzzolante, Cinzia, Volpi, Sara, Aiello, Marina, Ariani, Alarico, Chetta, Alfredo A., Frizzelli, Annalisa, Ticinesi, Andrea, Tuttolomondo, Domenico, Aliberti, Stefano, Blasi, Francesco B., Di Pasquale, Marta F., Misuraca, Sofia, Pilocane, Tommaso, Simonetta, Edoardo, Aghelmo, Alessio M., Angelini, Claudio, Brunetta, Enrico, Canonica, Giorgio W., Ciccarelli, Michele, Dal Farra, Sara, De Santis, Maria, Ferri, Sebastian, Folci, Marco, Guidelli, Giacomo M., Heffler, Enrico M., Loiacono, Ferdinando, Malipiero, Giacomo, Paoletti, Giovanni, Pedale, Rosa, Puggioni, Francesca A., Racca, Francesca, Zumbo, Aurora, Satou, Morihiko, Honda, Hitoshi, Lisun, Tatyana, Protsenko, Denis, Rubtsov, Nikolay, Beloglazova, Irina, Fomina, Daria, Lysenko, Mariana, Serdotetskova, Sofia, Firstov, Vitali, Gordeev, Ivan, Kokorin, Ilia, Komissarova, Ksenia, Lapochkina, Nina, Luchinkina, Elena, Malimon, Valentin, Mamedguseyinova, Sevinch, Polubatonova, Ksenia, Suvorova, Natalia, Arribas, Jose, Borobia Perez, Alberto M., de la Calle Prieto, Fernando, Figueira, Juan Carlos, Motejano Sanchez, Rocio, Mora-Rillo, Marta, Prados Sanchez, Concepcion, Queiruga Parada, Javier, Fernandez Arnalich, Francisco, Guerro Barrientos, Maria, Bendala Estrada, Alejandro, Caballero Marcos, Aranzazu, Garcia Leoni, Maria E., García-Martínez, Rita, Collado, Ana María, Munoz Garcia, Patricia, Torres do Rego, Ana, Villalba García, María V., Burrillo, Almudena, Valerio Minero, Maricela, Gijon Vidaurreta, Paloma, Infante Herrero, Sonsoles, Velilla, Elena, Machado, Marina, Olmedo, Maria, Pinilla, Blanca, Almirante Gragera, Benito, Cañas Ruano, Maria de la Esperanza, Contreras Medina, Sofia, Cortés Herrera, Alejandro, Falcó Ferrer, Vicenç, Ferrer Roca, Ricard, Nuvials Casals, Xavier, Ribera Pascuet, Esteve, Suanzes Diez, Paula, Rebollo Castro, Pedro, Garcia Alcaide, Felipe, Soriano, Alejandro, Oliver Caldes, Aina, González Cordón, Ana, Cardozo, Celia, De la Mora Cañizo, Lorena, Pena López, Romina, Chamorro, Sandra, Crespillo-Andujar, Clara, Escudero Sanchez, Rosa, Fortún-Abete, Jesús, Monge-Maillo, Begoña, Moreno Zamora, Ana, Norman, Francesca, Sanchez Conde, Matilde, Serrano Villar, Sergio, Vizcarra, Pilar, Lescure, François-Xavier, Fowler, Robert A, Lazar, Jennifer Sloane, Shi, Genming, Wung, Peter, Patel, Naimish, and Hagino, Owen

Published
2021
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16. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author

Tharaux, Pierre-Louis, Pialoux, Gilles, Pavot, Arthur, Mariette, Xavier, Hermine, Olivier, Resche-Rigon, Matthieu, Porcher, Raphael, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Dalibey, Sarah, Raked, Nabil, Mameri, Lakhdar, Alary, Stéphanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Montlahuc, Claire, Biard, Lucie, Charreteur, Robin, Dupré, Celine, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Bulifon, Sophie, Jaïs, Xavier, Sitbon, Olivier, Pavy, Stéphan, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stéphane, Baudry, Elodie, Verny, Christiane, Noaillon, Mathilde, Lefèvre, Edouard, Zaidan, Mohamad, Le Tiec, Clotilde Le Tiec, Verstuyft, Céline Verstuyft, Roques, Anne-Marie, Grimaldi, Lamiae, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Solène, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Georgin-Lavialle, Sophie, Senet, Patricia, Soria, Angèle, Parrot, Antoine, François, Hélène, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadège, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefèvre, Guillaume, Fallet, Vincent, Gottenberg, Jacques-Eric, Hansmann, Yves, Andres, Emmanuel, Bayer, Sophie, Becker, Guillaume, Blanc, Frédéric, Brin, Stéphane, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Demonsant, Eric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurélien, Heger, Bob, Hutt, Anne, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Martin, Tristan, Mertes, Paul Michel, Metzger, Catherine, Meyer, Nicolas, Nisand, Gabriel, Noll, Eric, Oberlin, Mathieu, Ohlmann-Caillard, Sophie, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Sublon, Cédric, Tayebi, Hakim, Weill, François, Mekinian, Arsène, Chopin, Dorothée, Fain, Olivier, Garnier, Marc, Krause le Garrec, Jessica, Morgand, Marjolaine, Pacanowski, Jerome, Urbina, Tomas, McAvoy, Chloe, Pereira, Maria, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Daguenel-Nguyen, Anne, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Penet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Jesuthasan, Denis, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Valérie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, F-Xavier, Ghosn, Jade, BACHELARD, Antoine, BIRONNE, Timothee, BORIE, Raphael, BOUNHIOL, Agathe, BOUSSARD, Catherine, CHAUFFiER, Jeanne, CHALAL, Solaya, CHALAL, Lynda, CHANSOMBAT, Malikhone, CRESPIN, Paul, CRESTANI, Bruno, DACONCEICAO, Olivia, DECONINCK, Laurene, DIEUDE, Philippe, DOSSIER, Antoine, DUBERT, Marie, DUCROCQ, Greggory, FUENTES, Axelle, GERVAIS, Anne, GILBERT, Marie, ISERNIA, Valentina, ISMAEL, Sophie, JOLY, Veronique, JULIA, Zelie, LARIVEN, Sylvie, LE GAC, Sylvie, LE PLUART, Diane, LOUNI, Francoise, NDIAYE, Awa, PAPO, Thomas, PARISEY, Marion, PHUNG, Bao, POURBAIX, Annabelle, RACHLINE, Anne, RIOUX, Christophe, SAUTEREAU, Aurelie, STEG, Gabriel, TARHINI, Hassan, VALAYER, Simon, VALLOIS, Dorothee, VERMES, Paul, VOLPE, Thomas, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anaïs, Zarrouk, Virginie, De Lastours, Victoire, Uzzan, Matthieu, Olivier, Olivier, Rossi, Geoffrey, Gamany, Naura, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, De Castro, Nathalie, Clément, Melissa, Darmont, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lengliné, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asmaa, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Celli Lebras, Karine, Chabert, Julien, Djaghout, Lalia, Fauvaux, Catherine, Jegu, Anne Lise, Kozaliewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madeleine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, SENE, Damien, BURLACU, Ruxandra, CHOUSTERMAN, Benjamin, MEGARBANE, Bruno, RICHETTE, Pascal, RIVELINE, Jean-Pierre, FRAZIER, Aline, VICAUT, Eric, BERTON, Laure, HADJAM, Tassadit, VASQUEZ-IBARRA, Miguel Alejandro, JOURDAINE, Clément, JACOB, Aude, SMATI, Julie, RENAUD, Stéphane, MANIVET, Philippe, PERNIN, Claire, SUAREZ, Lydia, Semerano, Luca, ABAD, Sebastien, Benainous, Ruben, Bloch Queyrat, Coralie, Bonnet, Nicolas, Brahmi, Sabrina, Cailhol, johann, Cohen, Yves, Comparon, Celine, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Jacolot, Anne, Nunes, Hilario, Oziel, Johanna, Rathouin, Vanessa, Rigal, Marthe, Roulot, Dominique, Tantet, Claire, Uzunhan, Yurdagul, COSTEDOAT-CHALUMEAU, Nathalie, Ait Hamou, Zakaria, Benghanem, Sarah, BLANCHE, Philippe, CANOUI, Etienne, CARLIER, Nicolas, CHAIGNE, Benjamin, CONTEJEAN, Adrien, DUNOGUE, Bertrand, DUPLAND, Pierre, DUREL - MAURISSE, Aurélie, GAUZIT, Remy, JAUBERT, Paul, Joumaa, Hassan, Jozwiak, Mathieu, KERNEIS, Solen, LACHATRE, Marie, Lafoeste, Hélène, LEGENDRE, Paul, LUONG NGUYEN, Liem Binh, MAREY, Jonathan, MORBIEU, Caroline, MOUTHON, Luc, NGUYEN, Lee, Palmieri, Lola-Jade, REGENT, Alexis, SZWEBEL, Tali-Anne, TERRIER, Benjamin, GUERIN, Corinne, ZERBIT, Jérémie, CHEREF, Kahina, CHITOUR, Kamil, CISSE, Mamadou Salif, CLARKE, Ada, CLAVERE, Gaelle, DUSANTER, Isabelle, GAUDEFROY, Caroline, JALLOULI, Moez, KOLTA, Sami, LE BOURLOUT, Catherine, MARIN, Nathalie, MENAGE, Nathalie, MOORES, Alexandre, PEIGNEY, Isabelle, PIERRON, Cédric, SALEH-MGHIR, Samira, VALLET, Mathilde, MICHEL, Marc, MELICA, Giovanna, LELIEVRE, Jean-Daniel, FOIS, Elena, LIM, Pascal, MATIGNON, Marie, GUILLAUD, Constance, THIEMELE, Alaki, SCHMITZ, David, BOUHRIS, Marion, BELAZOUZ, Syllia, LANGUILLE, Laetitia, MEKONTSO-DESSAPS, Armand, SADAOUI, Thiziri, Mayaux, Julien, Cacoub, Patrice, Corvol, Jean-Christophe, Louapre, Céline, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aïcha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sébastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Lecronier, Marie, Beurton, Alexandra, Haudebourg, Luc, Deleris, Robin, Le Marec, Julien, Virolle, Sara, Nemlaghi, Safaa, Bureau, Côme, Mora, Pierre, De Sarcus, Martin, Clovet, Olivier, Duceau, Baptiste, Grisot, Paul Henri, Pari, Marie hélène, Arzoine, Jérémy, Clarac, Ulrich, Faure, Morgane, Delemazure, Julie, Decavele, Maxence, Morawiec, Elise, Demoule, Alexandre, Dres, Martin, Vautier, Mathieu, Allenbach, Yves, Benveniste, Olivier, Leroux, Gaelle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Cloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Gonçalo, Ferfar, Yasmina, Charbonnier, Fanny, AGUILAR, Claire, ALBY-LAURENT, Fanny, ALYANAKIAN, Marie-Alexandra, BAKOUBOULA, Prissile, BROISSAND, Christine, BURGER, Carole, CAMPOS-VEGA, Clara, CHAVAROT, Nathalie, CHOUPEAUX, Laure, FOURNIER, Benjamin, GRANVILLE, Sophie, ISSORAT, Elodie, ROUZAUD, Claire, VIMPERE, Damien, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Helene, Duclos-Vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Koumis, Ilias, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Chistophe, Sakkal, Madona, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El Amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Razurel, Anaïs, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Hélène, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Clan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Servettaz, Amélie, Deslée, Gaetan, Wynckel, Alain, Benoit, Philippe, Marquis, Eric, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Hélène, Mourad, Jean-Jacques, Sacco, Emmanuelle, and Renet, Sophie

Published
2021
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17. Applying imaging flow cytometry and immunofluorescence in studying the dynamic Golgi structure in cultured cells

Author

Inbal Wortzel, Ziv Porat, Rony Seger, and Galia Maik-Rachline

Subjects
Cell Biology, Flow Cytometry/Mass Cytometry, Microscopy, Science (General), Q1-390
Abstract

Summary: The Golgi apparatus is subjected to fragmentation under several cellular processes such as mitosis. Here we describe two complementary approaches to analyze different Golgi morphological changes during its mitotic fragmentation, using classical immunofluorescence and imaging flow cytometry. Although fluorescent microscopy provides information on the exact Golgi architecture in distinct cells, the imaging flow cytometry combines the morphological data with the high-throughput quantification of flow cytometry. Taken together, both approaches provide robust and significant unbiased data analysis.For complete details on the use and execution of this protocol, please refer to Wortzel et al. (2021).

Published
2022
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22. Mitotic HOOK3 phosphorylation by ERK1c drives microtubule-dependent Golgi destabilization and fragmentation

Author

Inbal Wortzel, Galia Maik-Rachline, Suresh Singh Yadav, Tamar Hanoch, and Rony Seger

Subjects
cell biology, functional aspects of cell biology, Science
Abstract

Summary: ERK1c is an alternatively spliced isoform of ERK1 that specifically regulates mitotic Golgi fragmentation, which allows division of the Golgi during mitosis. We have previously shown that ERK1c translocates to the Golgi during mitosis where it is activated by a resident MEK1b to induce Golgi fragmentation. However, the mechanism of ERK1c functions in the Golgi remained obscure. Here, we searched for ERK1c substrates and identified HOOK3 as a mediator of ERK1c-induced mitotic Golgi fragmentation, which requires a second phosphorylation by AuroraA for its function. In cycling cells, HOOK3 interacts with microtubules (MTs) and links them to the Golgi. Early in mitosis, HOOK3 is phosphorylated by ERK1c and later by AuroraA, resulting in HOOK3 detachment from the MTs, and elevated interaction with GM130. This detachment modulates Golgi stability and allows fragmentation of the Golgi. This study demonstrates a novel mechanism of Golgi apparatus destabilization early in mitosis to allow mitotic progression.

Published
2021
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23. Alternative Splicing of MAPKs in the Regulation of Signaling Specificity

Author

Galia Maik-Rachline, Inbal Wortzel, and Rony Seger

Subjects
MAPK, alternative splicing, ERK, JNK, p38, ERK1c, Cytology, QH573-671
Abstract

The mitogen-activated protein kinase (MAPK) cascades transmit signals from extracellular stimuli to a variety of distinct cellular processes. The MAPKKs in each cascade specifically phosphorylate and activate their cognate MAPKs, indicating that this step funnels various signals into a seemingly linear pathway. Still, the effects of these cascades vary significantly, depending on the identity of the extracellular signals, which gives rise to proper outcomes. Therefore, it is clear that the specificity of the signals transmitted through the cascades is tightly regulated in order to secure the desired cell fate. Indeed, many regulatory components or processes that extend the specificity of the cascades have been identified. Here, we focus on a less discussed mechanism, that is, the role of distinct components in each tier of the cascade in extending the signaling specificity. We cover the role of distinct genes, and the alternatively spliced isoforms of MAPKKs and MAPKs, in the signaling specificity. The alternatively spliced MEK1b and ERK1c, which form an independent signaling route, are used as the main example. Unlike MEK1/2 and ERK1/2, this route’s functions are limited, including mainly the regulation of mitotic Golgi fragmentation. The unique roles of the alternatively spliced isoforms indicate that these components play an essential role in determining the proper cell fate in response to distinct stimulations.

Published
2021
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27. Prevalence of Mycoplasma genitalium and other sexually transmitted pathogens in male urethritis in a sexual health centre in New Caledonia

Author

Patrick Blanco, Anne Rachline, Arnaud Tarantola, Antoine Biron, Sabine Pereyre, Julie Coutherut, and Marion Patoureau

Subjects
Infectious Diseases, Public Health, Environmental and Occupational Health, Pharmacology (medical), Dermatology
Abstract

Background: The prevalence of sexually transmitted infections (STIs) is high in New Caledonia (NC), but there are no data on Mycoplasma genitalium (MG). However, the syndromic treatment of urethritis used in the territory includes a single dose of azithromycin, which could generate resistance in MG. Methods: We recruited 217 men referred to the Noumea public medical centre (CMP) with signs of urethritis and meeting the inclusion criteria from May 2016 to March 2018. Each was tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and for the first time in NC for MG by polymerase chain reaction (PCR). Results: The prevalence of MG was 10.1% (22/217). Azithromycin resistance of MG (mutation in the 23S rRNA gene) could only be assessed for 10 of the 22 strains. Only one (1/10; 10%) was resistant. The prevalence of other STIs tested was high, as CT, NG and/or TV were associated in 77.3% (17/22) of MG-positive cases. Conclusions: Although co-infections further justify syndromic management, the presence of MG in NC urethritis cases could call treatment guidelines into question.

Published
2022

29. G protein-coupled receptor 37 is a negative regulator of oligodendrocyte differentiation and myelination

Author

Hyun-Jeong Yang, Anna Vainshtein, Galia Maik-Rachline, and Elior Peles

Subjects
Science
Abstract

The molecular mechanism controlling oligodendrocyte differentiation is not fully understood. Here the authors show that G protein coupled receptor 37 acts as a negative regulator of CNS myelination, and this effect is mediated by suppression of ERK signalling.

Published
2016
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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

32. Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients

Author

Nguyen, Yann, primary, Flahault, Adrien, additional, Chavarot, Nathalie, additional, Melenotte, Cléa, additional, Cheminant, Morgane, additional, Deschamps, Paul, additional, Carlier, Nicolas, additional, Lafont, Emmanuel, additional, Thomas, Marion, additional, Flamarion, Edouard, additional, Lebeaux, David, additional, Charlier, Caroline, additional, Rachline, Anne, additional, Guérin, Corinne, additional, Ratiney, Robert, additional, Touchard, Justine, additional, Péré, Hélène, additional, Rozenberg, Flore, additional, Lanternier, Fanny, additional, Arlet, Jean-Benoît, additional, Avouac, Jérôme, additional, Boussaud, Véronique, additional, Guillemain, Romain, additional, Vignon, Marguerite, additional, Thervet, Eric, additional, Scemla, Anne, additional, Weiss, Laurence, additional, and Mouthon, Luc, additional

Published
2022
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36. Nuclear P38: Roles in Physiological and Pathological Processes and Regulation of Nuclear Translocation

Author

Galia Maik-Rachline, Lucia Lifshits, and Rony Seger

Subjects
p38MAPK, nuclear translocation, β-like importins, inflammation, cancer, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

The p38 mitogen-activated protein kinase (p38MAPK, termed here p38) cascade is a central signaling pathway that transmits stress and other signals to various intracellular targets in the cytoplasm and nucleus. More than 150 substrates of p38α/β have been identified, and this number is likely to increase. The phosphorylation of these substrates initiates or regulates a large number of cellular processes including transcription, translation, RNA processing and cell cycle progression, as well as degradation and the nuclear translocation of various proteins. Being such a central signaling cascade, its dysregulation is associated with many pathologies, particularly inflammation and cancer. One of the hallmarks of p38α/β signaling is its stimulated nuclear translocation, which occurs shortly after extracellular stimulation. Although p38α/β do not contain nuclear localization or nuclear export signals, they rapidly and robustly translocate to the nucleus, and they are exported back to the cytoplasm within minutes to hours. Here, we describe the physiological and pathological roles of p38α/β phosphorylation, concentrating mainly on the ill-reviewed regulation of p38α/β substrate degradation and nuclear translocation. In addition, we provide information on the p38α/β ′s substrates, concentrating mainly on the nuclear targets and their role in p38α/b functions. Finally, we also provide information on the mechanisms of nuclear p38α/b translocation and its use as a therapeutic target for p38α/β-dependent diseases.

Published
2020
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37. Le non-nom

Author

François Rachline

Published
2021

41. Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial

Author

Aurélien Dinh, Jacques Ropers, Clara Duran, Benjamin Davido, Laurène Deconinck, Morgan Matt, Olivia Senard, Aurore Lagrange, Sabrina Makhloufi, Guillaume Mellon, Victoire de Lastours, Frédérique Bouchand, Emmanuel Mathieu, Jean-Emmanuel Kahn, Elisabeth Rouveix, Julie Grenet, Jennifer Dumoulin, Thierry Chinet, Marion Pépin, Véronique Delcey, Sylvain Diamantis, Daniel Benhamou, Virginie Vitrat, Marie-Christine Dombret, Bertrand Renaud, Christian Perronne, Yann-Erick Claessens, José Labarère, Jean-Pierre Bedos, Philippe Aegerter, Anne-Claude Crémieux, Julie ATTAL-BEHAR, Sébastien BEAUNE, Thierry CHINET, Tristan CUDENNEC, Marine DE LAROCHE, Albane DE THEZY, Jennifer DUMOULIN, Caroline DUPONT, Elise FERCOT, Violaine GIRAUT, Ségolène GREFFE, Julie GRENET, Caroline GUYOT, Jean-Emmanuel KAHN, Sylvie LABRUNE, Marie LACHATRE, Sophie MOULIAS, Charlotte NALINE, Marion PEPIN, Elisabeth ROUVEIX, Marine SAHUT-D'IZARN, Abel SEFSSAFI, Laurent TEILLET, Jean-Pierre BRU, Jacques GAILLAT, Vincent GAUTIER, Cécile JANSSEN, Leonardo PAGANI, Virginie VITRAT, Malika ABDERRAHMANE, Juliette CAMUSET, Catherine LEGALL, Pascale LONGUET-FLANDRES, Anne-Marie MENN, Victoire DE LASTOURS, Marie LECRONIER, Gwenolée PREVOST, Charles BURDET, Ouda DERRADJI, Lelia ESCAUT, Etienne HINGLAIS, Philippe LEBRAS, Edouard LEFEVRE, Mathilde NOAILLON, Pauline RABIER, Maurice RAPHAEL, Elina TEICHER, Christiane VERNY, Daniel VITTECOQ, Benjamin WYPLOSZ, Michèle BEN HAYOUN, Françoise BRUN-VEZINET, Enrique CASALINO, Christophe CHOQUET, Marie-Christine DOMBRET, Xavier DUVAL, Nadhira HOUHOU, Véronique JOLY, Xavier LESCURE, Manuela POGLIAGHI, Christophe RIOUX, Yazdan YAZDANPANAH, Elsa BARROS, Belinda BEGGA, Sébastien BOUKOBZA, Houria BOUREDJI, Imad CHOUAHI, Isabelle DELACROIX, Antoine FROISSART, Valérie GARRAIT, Elsa NGWEM, Catherine PHLIPPOTEAU, Sepehr SALEHABADI, Cécile TOPER, Florent VINAS, Marie AMSILLI, Olivier EPAULARD, Patricia PAVESE, Isabelle PIERRE, Jean-Paul STAHL, Jérôme AULAGNIER, Julie CELERIER, Roxana COJOCARIU, Emmanuel MATHIEU, Charlotte RACHLINE, Yoland SCHOINDRE, Thomas SENE, Christelle THIERRY, Caroline APARICIO, Véronique DELCEY, Amanda LOPES, Marjolaine MORGAND, Pierre SELLIER, Guy SIMONEAU, Catherine CHAKVETADZE, Sylvain DIAMANTIS, Arnaud GAUTHIER, Kaoutar JIDAR, Béatrice JOURDAIN, Jean-Francois BOITIAUX, Patrick DESCHAMPS, Edouard DEVAUD, Bruno PHILIPPE, Ruxandra-Oana CALIN, Tomasz CHROBOCZEK, Benjamin DAVIDO, Laurène DECONINCK, Pierre DE TRUCHIS, Aurore LAGRANGE, Sabrina MAKHLOUFI, Morgan MATT, Guillaume MELLON, Olivia SENARD, Daniel BENHAMOU, Claire CHAPUZET, Laure CHAUFFREY, Manuel ETIENNE, Luc-Marie JOLY, Bérengère OBSTOY, Mathieu SALAUN, Luc THIBERVILLE, Julie TILLON, Diane BOLLENS, Julie BOTTERO, Pauline CAMPA, Gäelle COSQUERIC, Bénédicte LEFEBVRE, Zineb OUAZENE, Jérôme PACANOWSKI, Dominique PATERON, Nadia VALIN, Caroline COMPAIN, Hugues CORDEL, Benoit DOUMENC, Elena FOIS, Nicolas GAMBIER, Marie-Aude KHUONG, Elisa PASQUALONI, and Marie POUPARD

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, Pneumonia severity index, Incidence (epidemiology), Population, General Medicine, 030204 cardiovascular system & hematology, Amoxicillin, medicine.disease, Placebo, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, Community-acquired pneumonia, Internal medicine, medicine, 030212 general & internal medicine, education, Adverse effect, business, medicine.drug
Abstract

Summary Background Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of β-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. Methods We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with β-lactam therapy were randomly assigned (1:1) to receive β-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. Findings Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of β-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or β-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the β-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0–84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the β-lactam group (between-group difference of 9·42%, 95% CI −0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the β-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI −0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the β-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the β-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the β-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). Interpretation Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing β-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. Funding French Ministry of Health.

Published
2021

42. Nuclear ERK: Mechanism of Translocation, Substrates, and Role in Cancer

Author

Galia Maik-Rachline, Avital Hacohen-Lev-Ran, and Rony Seger

Subjects
mitogen-activated protein kinase (MAPK), Beta-like importins, nuclear translocation, nuclear substrates, negative feedback loop, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

The extracellular signal-regulated kinases 1/2 (ERK) are central signaling components that regulate stimulated cellular processes such as proliferation and differentiation. When dysregulated, these kinases participate in the induction and maintenance of various pathologies, primarily cancer. While ERK is localized in the cytoplasm of resting cells, many of its substrates are nuclear, and indeed, extracellular stimulation induces a rapid and robust nuclear translocation of ERK. Similarly to other signaling components that shuttle to the nucleus upon stimulation, ERK does not use the canonical importinmechanism of nuclear translocation. Rather, it has its own unique nuclear translocation signal (NTS) that interacts with importin7 to allow stimulated shuttling via the nuclear pores. Prevention of the nuclear translocation inhibits proliferation of B-Raf- and N/K-Ras-transformed cancers. This effect is distinct from the one achieved by catalytic Raf and MEK inhibitors used clinically, as cells treated with the translocation inhibitors develop resistance much more slowly. In this review, we describe the mechanism of ERK translocation, present all its nuclear substrates, discuss its role in cancer and compare its translocation to the translocation of other signaling components. We also present proof of principle data for the use of nuclear ERK translocation as an anti-cancer target. It is likely that the prevention of nuclear ERK translocation will eventually serve as a way to combat Ras and Raf transformed cancers with less side-effects than the currently used drugs.

Published
2019
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45. Prevalence of

Author

Patrick, Blanco, Anne, Rachline, Arnaud, Tarantola, Antoine, Biron, Sabine, Pereyre, Julie, Coutherut, and Marion, Patoureau

Subjects
Male, New Caledonia, Urethritis, Prevalence, Sexually Transmitted Diseases, Trichomonas vaginalis, Humans, Chlamydia trachomatis, Mycoplasma Infections, Mycoplasma genitalium, Azithromycin, Sexual Health, Neisseria gonorrhoeae
Abstract

The prevalence of sexually transmitted infections (STIs) is high in New Caledonia (NC), but there are no data onWe recruited 217 men referred to the Noumea public medical centre (CMP) with signs of urethritis and meeting the inclusion criteria from May 2016 to March 2018. Each was tested forThe prevalence of MG was 10.1% (22/217). Azithromycin resistance of MG (mutation in the 23S rRNA gene) could only be assessed for 10 of the 22 strains. Only one (1/10; 10%) was resistant. The prevalence of other STIs tested was high, as CT, NG and/or TV were associated in 77.3% (17/22) of MG-positive cases.Although co-infections further justify syndromic management, the presence of MG in NC urethritis cases could call treatment guidelines into question.

Published
2022

46. Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients

Author

Yann Nguyen, Adrien Flahault, Nathalie Chavarot, Cléa Melenotte, Morgane Cheminant, Paul Deschamps, Nicolas Carlier, Emmanuel Lafont, Marion Thomas, Edouard Flamarion, David Lebeaux, Caroline Charlier, Anne Rachline, Corinne Guérin, Robert Ratiney, Justine Touchard, Hélène Péré, Flore Rozenberg, Fanny Lanternier, Jean-Benoît Arlet, Jérôme Avouac, Véronique Boussaud, Romain Guillemain, Marguerite Vignon, Eric Thervet, Anne Scemla, Laurence Weiss, and Luc Mouthon

Subjects
Microbiology (medical), Cohort Studies, Immunocompromised Host, Infectious Diseases, SARS-CoV-2, Humans, COVID-19, Antibodies, Monoclonal, Pre-Exposure Prophylaxis, General Medicine, COVID-19 Drug Treatment
Abstract

Immunocompromised patients have an increased risk of a severe form of COVID-19. The clinical efficacy of the tixagevimab/cilgavimab monoclonal antibody combination as pre-exposure prophylaxis against BA.1 and BA.2 SARS-CoV-2 Omicron sublineages is unknown. We aimed to describe the incidence and outcomes of COVID-19 among immunocompromised patients receiving tixagevimab/cilgavimab as preexposure prophylaxis during the Omicron wave in France.This was an observational multicentre cohort study of immunocompromised patients receiving tixagevimab/cilgavimab as preexposure prophylaxis between December 28, 2021 and March 31, 2022. Patients received tixagevimab/cilgavimab 150/150 mg intramuscularly if they had impaired vaccine response and a high risk of severe form of COVID-19.Tixagevimab/cilgavimab was administered to 1112 immunocompromised patients. After a median (range) follow-up of 63 (49-73) days, COVID-19 was confirmed in 49/1112 (4.4%) ≥5 days after treatment. During the study period, mean weekly incidence rate was 1669 in 100 000 inhabitants in Ile-de-France and 530 in 100 000 among patients who received tixagevimab/cilgavimab prophylaxis. Among infected patients, 43/49 (88%) had a mild-to-moderate form and 6/49 (12%) had a moderate-to-severe form of COVID-19. Patients with moderate-to-severe illnesses were less likely to have received early therapies than patients with mild forms (53.5% vs. 16.7% respectively) and 2/49 (4%) patients died from COVID-19.Our study reported a low rate of infections and severe illnesses among immunocompromised patients treated with tixagevimab/cilgavimab. A global preventive strategy including vaccines, preexposure prophylaxis with monoclonal antibodies, and early therapies might be effective to prevent severe forms of COVID-19 among severely immunocompromised patients.

Published
2022

47. AKTs do not translocate to the nucleus upon stimulation but AKT3 can constitutively signal from the nuclear envelope

Author

Ehud Wainstein, Galia Maik-Rachline, John Blenis, and Rony Seger

Subjects
Nuclear Envelope, Humans, Proto-Oncogene Proteins c-akt, General Biochemistry, Genetics and Molecular Biology
Abstract

AKT is a central signaling protein kinase that plays a role in the regulation of cellular survival metabolism and cell growth, as well as in pathologies such as diabetes and cancer. Human AKT consists of three isoforms (AKT1-3) that may fulfill different functions. Here, we report that distinct subcellular localization of the isoforms directly influences their activity and function. AKT1 is localized primarily in the cytoplasm, AKT2 in the nucleus, and AKT3 in the nucleus or nuclear envelope. None of the isoforms actively translocates into the nucleus upon stimulation. Interestingly, AKT3 at the nuclear envelope is constitutively phosphorylated, enabling a constant phosphorylation of TSC2 at this location. Knockdown of AKT3 induces moderate attenuation of cell proliferation of breast cancer cells. We suggest that in addition to the stimulation-induced activation of the lysosomal/cytoplasmic AKT1-TSC2 pathway, a subpopulation of TSC2 is constitutively inactivated by AKT3 at the nuclear envelope of transformed cells.

Published
2022

49. Myelin content monitoring by diffusion biomarkers in a therapeutic trial with leriglitazone in men with adrenomyeloneuropathy (P1-1.Virtual)

Author

Perlbarg, Vincent, primary, Pascual, Silvia, additional, Blanco, Bernardo, additional, Barbier, Magali, additional, Yazbeck, Elise, additional, Uriet, Dorothee, additional, Rachline, Julie, additional, Meya, Uwe, additional, Martinell, Marc, additional, Galanaud, Damien, additional, Engelen, Marc, additional, and Mochel, Fanny, additional

Published
2022
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