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1. Mortality and functional outcomes 18 months after hospitalization for COVID-19 in geriatric patients: a multicentric cohort study

Author

Marion Claes, Bastien Genet, Audrey Rouet, Léa Boutitie, Philippine Parramore, Émilie Hardy, Caroline Thomas, Lorène Zerah, and Hélène Vallet

Subjects
SARS-CoV2, Older, Long-term mortality, Prognosis, Geriatrics, RC952-954.6
Abstract

Abstract Background Few data are available on the long-term mortality and functional status of geriatric patients surviving after hospitalization for COVID-19. We compared the mortality and functional status 18 months after hospitalization for geriatric patients who were hospitalized for COVID-19 or another diagnosis. Methods This was a multicentric cohort study in Paris from January to June 2021. We included patients aged 75 years and over who were hospitalized with COVID-19 or not during this period and compared their vital and functional status 18 months after hospitalization. Results We included 254 patients (63 hospitalized for COVID-19). As compared with patients hospitalized for other reasons, those hospitalized for COVID-19 were younger (mean [SD] age 86 [6.47] vs. 88 [6.41] years, p = 0.03), less frail (median Clinical Frailty Scale score 5 [4–6] vs. 6 [4–6], p 0.007) and more independent at baseline (median activities of daily living score 5.5 [4–6] vs. 5 [3.5–6], p 0.03; instrumental activities of daily living score 3 [1–4] vs. 2 [0–3], p 0.04). At 18 months, 50.8% (n = 32/63) of COVID-19 patients had died versus 66% (n = 126/191) of non-COVID-19 patients (p 0.03). On multivariate analysis, COVID-19 positivity was not significantly associated with 18-month mortality (adjusted hazard ratio 0.67, 95% confidence interval 0.40 to 1.13). At 18 months, the two groups did not differ in activities of daily living or frailty scores. Conclusions In this multicenter study of long-term mortality in geriatric patients discharged alive after hospitalization, positive COVID-19 status was not associated with excess mortality.

Published
2024
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2. Innate immune response in acute critical illness: a narrative review

Author

Laure Stiel, Alexandre Gaudet, Sara Thietart, Hélène Vallet, Paul Bastard, Guillaume Voiriot, Mehdi Oualha, Benjamine Sarton, Hatem Kallel, Nicolas Brechot, Louis Kreitmann, Sarah Benghanem, Jérémie Joffre, Youenn Jouan, and la Commission de Recherche Translationnelle de la Société de Réanimation en Langue Française

Subjects
Innate immunity, Immunothrombosis, Immunosenescence, Trained immunity, Acute critical illness, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies. Main text Understanding the underlying biological concepts supporting therapeutic strategies modulating immune response is essential in decision-making. We will develop the multiple facets of innate immune response, especially its cellular aspects, and its interaction with other defense mechanisms. We will first describe the pathophysiological mechanisms of initiation of innate immune response and its implication during ACI. We will then develop the amplification of innate immunity mediated by multiple effectors. Our review will mainly focus on myeloid and lymphoid cellular effectors, the major actors involved in innate immune-mediated organ failure. We will third discuss the interaction and integration of innate immune response in a global view of host defense, thus considering interaction with non-immune cells through immunothrombosis, immunometabolism and long-term reprogramming via trained immunity. The last part of this review will focus on the specificities of the immune response in children and the older population. Conclusions Recent understanding of the innate immune response integrates immunity in a highly dynamic global vision of host response. A better knowledge of the implicated mechanisms and their tissue-compartmentalization allows to characterize the individual immune profile, and one day eventually, to develop individualized bench-to-bedside immunomodulation approaches as an adjuvant resuscitation strategy.

Published
2024
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3. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author

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

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

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

Published
2024
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4. In-hospital mortality of older patients with COVID-19 throughout the epidemic waves in the great Paris area: a multicenter cohort study

Author

Sara Thietart, Antoine Rozes, Florence Tubach, Stéphane Marot, Anne-Geneviève Marcelin, Mathieu Raux, Hélène Vallet, Bruno Riou, Jacques Boddaert, and Lorène Zerah

Subjects
COVID-19, In-hospital mortality, Geriatric, Waves, Omicron, Geriatrics, RC952-954.6
Abstract

Abstract Background Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19. Methods This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group’s data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type. Results Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 [IQR 79–90] years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 [95%CI 1.21–1.66] and 1.56 [95%CI 1.33–1.83] respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 [95% CI 1.12 to 1.49] for wave 1, aOR 1.25 [95% CI 1.08 to 1.45] for wave 2 and aOR 1.56 [95% CI 1.36 to 1.79] for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants. Conclusions Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as “milder” but not “mild”. This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.

Published
2023
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5. The impact of age-related syndromes on ICU process and outcomes in very old patients

Author

Hélène Vallet, Bertrand Guidet, Ariane Boumendil, Dylan W. De Lange, Susannah Leaver, Wojciech Szczeklik, Christian Jung, Sigal Sviri, Michael Beil, and Hans Flaatten

Subjects
Critical care, Intensive care unit, Old patients, Comprehensive geriatric assessment, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract In this narrative review, we describe the most important age-related “syndromes” found in the old ICU patients. The syndromes are frailty, comorbidity, cognitive decline, malnutrition, sarcopenia, loss of functional autonomy, immunosenescence and inflam-ageing. The underlying geriatric condition, together with the admission diagnosis and the acute severity contribute to the short-term, but also to the long-term prognosis. Besides mortality, functional status and quality of life are major outcome variables. The geriatric assessment is a key tool for long-term qualitative outcome, while immediate severity accounts for acute mortality. A poor functional baseline reduces the chances of a successful outcome following ICU. This review emphasises the importance of using a geriatric assessment and considering the older patient as a whole, rather than the acute illness in isolation, when making decisions regarding intensive care treatment.

Published
2023
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6. Expression of immune checkpoint on subset of monocytes in old patients

Author

Luca Royer, Manon Chauvin, Jamila Dhiab, Eric Pedruzzi, Jacques Boddaert, Delphine Sauce, and Hélène Vallet

Subjects
Immune checkpoint, Monocytes, Older, Medicine, Biology (General), QH301-705.5
Abstract

Background: Immune checkpoints and their ligands are important actors of lymphocytes and monocytes activation's regulation. Their expression level within T cells changes with aging. Despite the major impact of aging on monocytes, there is no data about the expression of ICs on monocytes from old patients. The objective of our study is to describe the expression of ICs and their ligands on monocytes from young individuals compared to old patients. Methods: We included 18 old control (>75 years old), 10 young control (

Published
2023
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7. IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture

Author

Chrystel Marton, Alix Minaud, Charles-Antoine Coupet, Manon Chauvin, Jamila Dhiab, Hélène Vallet, Jacques Boddaert, Nadine Kehrer, Bérangère Bastien, Geneviève Inchauspe, Luc Barraud, and Delphine Sauce

Subjects
immunosenescence, hip fracture, immunotherapy, virotherapy, interleukin-7, t-cell functions, trauma, immunosuppression, cytokine, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

Following acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adaptative immune homeostasis in these patients. We assessed the impact of this encoded hIL-7 on the ex vivo immune functions of T cells from PBMC of immunosenescent patients with or without hip fracture. T-cell ex vivo phenotyping was characterized in terms of senescence (CD57), IL-7 receptor (CD127) expression, and T cell differentiation profile. Then, post stimulation, activation status, and functionality (STAT5/STAT1 phosphorylation and T cell proliferation assays) were evaluated by flow cytometry. Our data show that T cells from both groups display immunosenescence features, express CD127 and are activated after stimulation by virotherapy-produced hIL-7-Fc. Interestingly, hip fracture patients exhibit a unique functional ability: An important T cell proliferation occurred compared to controls following stimulation with hIL-7-Fc. In addition, stimulation led to an increased naïve T cell as well as a decreased effector memory T cell proportions compared to controls. This preliminary study indicates that the produced hIL-7-Fc is well recognized by T cells and initiates IL-7 signaling through STAT5 and STAT1 phosphorylation. This signaling efficiently leads to T cell proliferation and activation and enables a T cell “rejuvenation.” These results are in favor of the clinical development of the hIL-7-Fc expressing virotherapy to restore or induce immune T cell responses in immunosenescent hip fracture patients.

Published
2023
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8. Impact on 6-month outcomes of hospital trajectory in critically ill older patients: analysis of the ICE-CUB2 clinical trial

Author

Sara Thietart, Ariane Boumendil, Dominique Pateron, Bertrand Guidet, Hélène Vallet, and the ICE-CUB2 Study Network

Subjects
Geriatrics, Outcome, Functional status, Intensive care, Critical care, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Little is known about the impact of hospital trajectory on survival and functional decline of older critically ill patients. We evaluate 6-month outcomes after admission to: intensive care units (ICU), intermediate care units (IMCU) or acute medical wards (AMW). Methods Data from the randomised prospective multicentre clinical trial ICE-CUB2 was secondarily analysed. Inclusion criteria were: presenting at emergency departments in critical condition; age ≥ 75 years; activity of daily living (ADL) ≥ 4; preserved nutritional status; and no active cancer. A Cox model was fitted to compare survival according to admission destination adjusting for patient characteristics. Sensitivity analysis using multiple imputation for missing data and propensity score matching were performed. Results Among 3036 patients, 1675 (55%) were women; median age was 85 [81–99] years; simplified acute physiology score (SAPS-3) 62 [55–69]; 1448 (47%) were hospitalised in an ICU, 504 in IMCU (17%), and 1084 (36%) in AMW. Six-month mortality was 629 (44%), 155 (31%) and 489 (45%) after admission in an ICU, IMCU and AMW (p

Published
2022
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9. Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients

Author

Manon Chauvin, Martin Larsen, Bibiana Quirant, Paul Quentric, Karim Dorgham, Luca Royer, Hélène Vallet, Amelie Guihot, Béhazine Combadière, Christophe Combadière, Jaume Barallat, Julien Mayaux, Charles-Edouard Luyt, Alexis Mathian, Zahir Amoura, Jacques Boddaert, Fernando Armestar, Guy Gorochov, Eva Martinez-Caceres, and Delphine Sauce

Subjects
SARS-CoV-2, biomarker, neopterin, clinical outcome, death, Microbiology, QR1-502
Abstract

HighlightsInnate immune activation during Covid-19 infection is associated with pernicious clinical outcome.BackgroundCoronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.MethodsWe measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.ResultsSevere and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.ConclusionWe propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.

Published
2021
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10. Devenir des patients âgés après la réanimation : « dis-moi ton passé et je te dirai ton avenir »

Author

Bertrand Guidet, Céline Bianco, and Hélène Vallet

Subjects
Emergency Medicine, Emergency Nursing
Abstract

La proportion de patients âgés admis en réanimation est en constante augmentation depuis deux décennies. Ces patients représentent une population spécifique de par leur vulnérabilité face au stress. Cette vulnérabilité résulte du vieillissement physiologique des organes et des systèmes mais également de la fréquence des comorbidités. La réanimation représente un stress majeur en raison de la gravité des pathologies qui y conduisent mais également, de manière intrinsèque, par les techniques de suppléance d’organe. De ce fait, l’impact en termes de mortalité et de perte d’autonomie à long terme peut être lourd. Tout l’enjeu de la réanimation du patient âgé réside dans : 1. L’identification dès l’admission des patients les plus à même de survivre dans de bonne condition à un séjour en réanimation 2. Une prise en charge spécialisée de ces patients en sortie de réanimation dans le cadre d’une filière structurée. Cette prise en charge relève de l’expertise conjointe des réanimateurs et des gériatres. L’évolution démographique actuelle rend indispensable le développement de cette collaboration et pourrait donner lieu à une nouvelle spécialité : la géronto-réanimation. L’objectif de cette mise au point est de rappeler les spécificités du patient âgé, de faire un point sur le pronostic vital et fonctionnel après un séjour en réanimation et d’aborder le sujet des filières de réanimation-gériatrique.

Published
2022

11. Corticosteroid Therapy in COVID-19 Associated With In-hospital Mortality in Geriatric Patients: A Propensity Matched Cohort Study

Author

Valentine Lidou-Renault, Edouard Baudouin, Pauline Courtois-Amiot, Celine Bianco, Hélène Esnault, Audrey Rouet, Margaux Baque, Charlotte Tomeo, Antonio Rainone, Sara Thietart, Romain Veber, Clementine Ayache, Marion Pepin, Carmelo Lafuente-Lafuente, Emmanuelle Duron, Pierre-Emmanuel Cailleaux, Didier Haguenauer, Nadège Lemarié, Elena Paillaud, Agathe Raynaud-Simon, Caroline Thomas, Jacques Boddaert, Lorène Zerah, and Hélène Vallet

Subjects
Aged, 80 and over, Male, Aging, SARS-CoV-2, COVID-19, Cohort Studies, Adrenal Cortex Hormones, Activities of Daily Living, Humans, Female, Hospital Mortality, Geriatrics and Gerontology, Aged, Retrospective Studies
Abstract

Background Few data are available on the prognosis of older patients who received corticosteroids for COVID-19. We aimed to compare the in-hospital mortality of geriatric patients hospitalized for COVID-19 who received corticosteroids or not. Methods We conducted a multicentric retrospective cohort study in 15 acute COVID-19 geriatric wards in the Paris area from March to April 2020 and November 2020 to May 2021. We included all consecutive patients aged 70 years and older who were hospitalized with confirmed COVID-19 in these wards. Propensity score and multivariate analyses were used. Results Of the 1 579 patients included (535 received corticosteroids), the median age was 86 (interquartile range 81–91) years, 56% of patients were female, the median Charlson Comorbidity Index (CCI) was 2.6 (interquartile range 1–4), and 64% of patients were frail (Clinical Frailty Score 5–9). The propensity score analysis paired 984 patients (492 with and without corticosteroids). The in-hospital mortality was 32.3% in the matched cohort. On multivariate analysis, the probability of in-hospital mortality was increased with corticosteroid use (odds ratio [OR] = 2.61 [95% confidence interval (CI) 1.63–4.20]). Other factors associated with in-hospital mortality were age (OR = 1.04 [1.01–1.07], CCI (OR = 1.18 [1.07–1.29], activities of daily living (OR = 0.85 [0.75–0.95], oxygen saturation < 90% on room air (OR = 2.15 [1.45–3.17], C-reactive protein level (OR = 2.06 [1.69–2.51], and lowest lymphocyte count (OR = 0.49 [0.38–0.63]). Among the 535 patients who received corticosteroids, 68.3% had at least one corticosteroid side effect, including delirium (32.9%), secondary infections (32.7%), and decompensated diabetes (14.4%). Conclusions In this multicentric matched-cohort study of geriatric patients hospitalized for COVID-19, the use of corticosteroids was significantly associated with in-hospital mortality.

Published
2022

13. In-hospital mortality of older patients with COVID-19 throughout the epidemic waves in the Great Paris Area: A multicenter cohort study

Author

Sara Thietart, Antoine Rozes, Florence Tubach, Stéphane Marot, Anne-Geneviève Marcelin, Mathieu Raux, Hélène Vallet, Bruno Riou, Jacques Boddaert, and Lorène Zerah

Abstract

Background Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19. Methods This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group’s data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type. Results Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 [IQR 79–90] years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 [95%CI 1.21–1.66] and 1.56 [95%CI 1.33–1.83] respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 [95% CI 1.12 to 1.49] for wave 1, aOR 1.25 [95% CI 1.08 to 1.45] for wave 2 and aOR 1.56 [95% CI 1.36 to 1.79] for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants. Conclusions Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as “milder” but not “mild”. This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.

Published
2022

18. Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8+ T Cells in Elderly Humans

Author

Francesco Nicoli, Mariela P. Cabral-Piccin, Laura Papagno, Eleonora Gallerani, Mathieu Fusaro, Victor Folcher, Marion Dubois, Emmanuel Clave, Hélène Vallet, Justin J. Frere, Emma Gostick, Sian Llewellyn-Lacey, David A. Price, Antoine Toubert, Loïc Dupré, Jacques Boddaert, Antonella Caputo, Riccardo Gavioli, and Victor Appay

Subjects
immunosenescence, Aging, naive T cells, Immunology, Immunology and Allergy, Aging, fatty acids, immunosenescence, naive T cells, fatty acids, NO
Abstract

Aging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activation. Importantly, reversal of the bioenergetic anomalies with lipid-altering drugs, such as rosiglitazone, almost completely restored the Ag responsiveness of naive CD8+ T cells. Interventions that favor lipid catabolism may therefore find utility as adjunctive therapies in the elderly to promote vaccine-induced immunity against targetable cancers and emerging pathogens, such as seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Published
2022

19. Critical care beyond organ support: the importance of geriatric rehabilitation

Author

Jeremy M. Jacobs, Ana Rahamim, Michael Beil, Bertrand Guidet, Helene Vallet, Hans Flaatten, Susannah K. Leaver, Dylan de Lange, Wojciech Szczeklik, Christian Jung, and Sigal Sviri

Subjects
Critical care, Old patients, Geriatric rehabilitation, Comprehensive geriatric assessment, Frailty, Post-ICU syndrome, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Very old critically ill patients pose a growing challenge for intensive care. Critical illness and the burden of treatment in the intensive care unit (ICU) can lead to a long-lasting decline of functional and cognitive abilities, especially in very old patients. Multi-complexity and increased vulnerability to stress in these patients may lead to new and worsening disabilities, requiring careful assessment, prevention and rehabilitation. The potential for rehabilitation, which is crucial for optimal functional outcomes, requires a systematic, multi-disciplinary approach and careful long-term planning during and following ICU care. We describe this process and provide recommendations and checklists for comprehensive and timely assessments in the context of transitioning patients from ICU to post-ICU and acute hospital care, and review the barriers to the provision of good functional outcomes.

Published
2024
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20. Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8

Author

Francesco, Nicoli, Mariela P, Cabral-Piccin, Laura, Papagno, Eleonora, Gallerani, Mathieu, Fusaro, Victor, Folcher, Marion, Dubois, Emmanuel, Clave, Hélène, Vallet, Justin J, Frere, Emma, Gostick, Sian, Llewellyn-Lacey, David A, Price, Antoine, Toubert, Loïc, Dupré, Jacques, Boddaert, Antonella, Caputo, Riccardo, Gavioli, and Victor, Appay

Subjects
Adult, Male, Aging, Apoptosis, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Cancer Vaccines, Rosiglitazone, Young Adult, MART-1 Antigen, Fenofibrate, Neoplasms, HLA-A2 Antigen, Influenza, Human, Humans, Single-Blind Method, Aged, Hypolipidemic Agents, Aged, 80 and over, Vaccination, COVID-19, Viral Vaccines, Middle Aged, Lipid Metabolism, Peptide Fragments, Glucose, Female, Immunocompetence, Cell Division
Abstract

Aging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8

Published
2021

21. The Very Old Critically Ill Patients

Author

Hans Flaatten, Bertrand Guidet, Hélène Vallet, Hans Flaatten, Bertrand Guidet, and Hélène Vallet

Subjects
Anesthesiology, Nursing, Critical care medicine, Geriatrics
Abstract

This book, part of the European Society of Intensive Care Medicine (ESICM) textbook series, provides detailed up-to-date information on the care of the critical ill very old (≥80 years) patients in the ICU.The very old are expanding fast in our populations, and this is mirrored in our hospitals and ICUs as well. During the last decade, a lot more information about the group of critical ill elderly has been published, and several large networks cooperate in performing multinational studies in this field, one of them with roots in the ESICM. This book will give readers knowledge about the current epidemiology of elderly ICU patients, in patients centered outcomes and factors affecting these outcomes. A large part is devoted to age related changes in vital organ functions, and the specific geriatric “syndromes” like frailty, cognitive decline, reduced activity of daily living, sarcopenia and immunosenecence. This is all important for the practicing intensivists to know about. In addition, specific groups of the elderly in the ICU are also described like the elderly patients with trauma or sepsis.The book is written jointly by intensivists and geriatricians, often working in teams and originating from many different countries. This herald a new era in the collaboration between these two groups in order to improve care and rehabilitation. We have a lot to learn from each other, as both groups have a holistic view of our patients although with different perspectives. This book should be of value for all working in adult ICUs, physicians as well as nurses. It will hopefully lead to a better understanding of the particular challenges posed by this important sub-group of ICU patients and how to manage his group in a way that combine respect for life as well as death and includes patients and caregivers in this process.

Published
2022

22. Retrospective Evaluation of a Restrictive Transfusion Strategy in Older Adults with Hip Fracture

Author

Lorene, Zerah, Lucile, Dourthe, Judith, Cohen-Bittan, Marc, Verny, Mathieu, Raux, Anthony, Mézière, Frédéric, Khiami, Cendrine, Tourette, Christian, Neri, Yannick, Le Manach, Bruno, Riou, Hélène, Vallet, and Jacques, Boddaert

Subjects
Male, Hip Fractures, Anemia, Perioperative Care, Postoperative Complications, Cardiovascular Diseases, Fracture Fixation, Humans, Blood Transfusion, Female, France, Geriatric Assessment, Aged, Retrospective Studies
Abstract

To compare the association between a restrictive transfusion strategy and cardiovascular complications during hospitalization for hip fracture with the association between a liberal transfusion strategy and cardiovascular complications, accounting for all transfusions from the emergency department to postacute rehabilitation settings.Retrospective study.Perioperative geriatric care unit.All individuals aged 70 and older admitted to the emergency department for hip fracture and hospitalized in our perioperative geriatric care unit (N=667; n=193 in the liberal transfusion group, n=474 in the restrictive transfusion group) from July 2009 to April 2016.A restrictive transfusion strategy (hemoglobin level threshold ≥8 g/dL or symptoms) used from January 2012 to April 2016 was compared with the liberal transfusion strategy (hemoglobin level threshold ≥10 g/dL) used from July 2009 to December 2011.Primary endpoint was in-hospital acute cardiovascular complications (heart failure, myocardial infarction, atrial fibrillation or stroke).The change to a restrictive transfusion strategy was associated with fewer acute cardiovascular complications (odds ratio=0.45, 95% confidence interval (CI)=0.31-0.67, p.001), without any noticeable difference in in-hospital or 6-month mortality. The change also led to a reduction in packed red blood cell units used per participant (median 1, interquartile range (IQR) 0-2 in restrictive vs median 2, IQR 0-3 in liberal transfusion strategy, P.001). In rehabilitation settings, the frequency of transfusion was greater with the restrictive transfusion strategy than the liberal transfusion strategy (18% vs 9%, P.001).A restrictive transfusion strategy in older adults with hip fracture was found to be safe and was associated with fewer cardiovascular complications but more transfusions in rehabilitation settings. Prospective studies are needed to confirm these findings.

Published
2018

23. Prognostic Value of Serum Procalcitonin After Orthopedic Surgery in the Elderly Population

Author

Camille Chenevier-Gobeaux, Cédric Villain, Judith Cohen-Bittan, Loïc Epelboin, Patrick Ray, Bruno Riou, Jacques Boddaert, Hélène Vallet, Marc Verny, F. Khiami, Biologie et Pathologie du Neurone (Brain-C), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Calcitonin, Male, Aging, medicine.medical_specialty, Population, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Procalcitonin, Hip fracture, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Internal medicine, Medicine, Humans, Orthopedic Procedures, 030212 general & internal medicine, Prospective Studies, Young adult, Prospective cohort study, education, Aged, 80 and over, education.field_of_study, business.industry, Mortality rate, 030208 emergency & critical care medicine, Odds ratio, medicine.disease, Prognosis, 3. Good health, Surgery, Elderly Population, Orthopedic surgery, Female, Geriatrics and Gerontology, business, Biomarkers
Abstract

International audience; Background: Orthopedic surgery is more and more frequent in the older patients and is associated with a high mortality rate. Although serum procalcitonin levels are associated with prognosis in young adults, data are still lacking in the elderly population, and especially after surgery. The main objective of this study was to determine the prognostic value of procalcitonin levels in a large geriatric orthopedic population, and we compared it with clinical variables and biomarkers. Methods: This is a prospective study including patients admitted in our dedicated geriatric postoperative unit, after orthopedic surgery with immediate postoperative measured procalcitonin levels. Collected data included age, sex, medical history, functional status (activities of daily living [ADL]), fracture type, Cumulative Illness Rating scale (CIRS), postoperative complications, and biological data. The primary endpoint was the 30-day mortality. Results: 436 patients (age 85 +/- 6 years) were included. Hip fracture surgery was the most frequent (n = 310; 71%), and the 30-day mortality rate was 6.9%. Compared with C-reactive protein (CRP), albumin, CIRS, and ADL, procalcitonin had the highest area under the receiver operating characteristic curve for predicting 30-day mortality (0.74; 95% CI: 0.70-0.78). Using a cutoff at 1 mu g/L, procalcitonin was more specific than CIRS to predict 30-day mortality (92 vs 77%; p

Published
2017

24. Isolated cardiac troponin rise does not modify the prognosis in elderly patients with hip fracture

Author

Hélène, Vallet, Alice, Breining, Yannick, Le Manach, Judith, Cohen-Bittan, Anthony, Mézière, Mathieu, Raux, Marc, Verny, Bruno, Riou, Frédéric, Khiami, and Jacques, Boddaert

Subjects
Aged, 80 and over, Male, Hip Fractures, Troponin I, Observational Study, biomarkers, Recovery of Function, Prognosis, elderly, Postoperative Complications, hip fracture, Activities of Daily Living, Humans, Female, Acute Coronary Syndrome, Perioperative Period, Aged, Research Article
Abstract

Perioperative myocardial infarction remains a life-threatening complication in noncardiac surgery and even an isolated troponin rise (ITR) is associated with significant mortality. Our aim was to assess the prognostic value of ITR in elderly patients with hip fracture. In this cohort study, all patients admitted between 2009 and 2013 in our dedicated geriatric postoperative unit after hip fracture surgery with a cardiac troponin I determination were included and divided into Control, ITR, and acute coronary syndrome (ACS) groups. The primary end point was a composite criteria defined as 6-month mortality and/or re-hospitalization. Secondary end points included 30-day mortality, 6-month mortality, and 6-month functional outcome. Three hundred twelve patients were (age 85 ± 7 years) divided into Control (n = 217), ITR (n = 50), and ACS (n = 45) groups. There was no significant difference for any postoperative complications between ITR and Control groups. In contrast, atrial fibrillation, acute heart failure, hemorrhage, and ICU admission were significantly more frequent in the ACS group. Compared to the Control group, 6-month mortality and/or rehospitalization was not significantly modified in the ITR group (26% vs. 28%, P = 0.84, 95% confidence interval [CI] of the difference -13%–14%), whereas it was increased in the ACS group (44% vs. 28%, P = 0.02, 95% CI of the difference 2%–32%). ITR was not associated with a higher risk of new institutionalization or impaired walking ability at 6 months, in contrast to ACS group. In elderly patients with hip fracture, ITR was not associated with a significant increase in death and/or rehospitalization within 6 months.

Published
2017

25. Causes of coma and their evolution in the medical intensive care unit

Author

Emmanuel Guerot, Jean-Yves Fagon, Nicolas Weiss, Guillaume Taldir, Hélène Vallet, Lucille Regard, Jean-Luc Diehl, Charles Vidal, and Yosu Luque

Subjects
Adult, Male, medicine.medical_specialty, Encephalopathy, Epidemiology, medicine, Humans, Glasgow Coma Scale, Coma, Intensive care medicine, Aged, Neuroradiology, Aged, 80 and over, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Intensive Care Units, Neurology, Emergency medicine, Cohort, Disease Progression, Population study, Female, Neurology (clinical), medicine.symptom, business
Abstract

Epidemiological data regarding the frequency of the different causes of coma and their evolution over time in the ICU are scarce [1–4]. In the 1970s, Plum and Posner [2] described the causes of 500 successive cases of coma. However, since then no specific study focusing on the causes of coma and their evolution over time has been published although the ICU management of brain injuries has progressed tremendously. Some data are available from prospective and retrospective studies assessing coma outcome [3–8], but the different causes of coma were excluded in these studies. These studies, therefore, do not provide a global description of the causes of coma and their evolution. The aim of this study was to describe the causes of coma and their evolution over an 8-year time period in a medical ICU. From January 2001 to December 2008, we retrospectively identified patients who presented with coma in the first 24 h of ICU admission, defined as a Glasgow Coma Scale below 8 in the absence of sedative drugs, and we retrieved their demographic data (supplementary Table). For statistical purposes, four time periods of 2 years each were defined. A total of 2,189 out of 4,482 patients were evaluated. Baseline characteristics of the patients can be found in the supplementary Table. Detailed causes of coma, initial Glasgow Coma Scale and ICU survival are shown Table 1. The frequency of anoxo-ischemic encephalopathy and shock of any origin increased as the causes of coma over the 8-year time period is shown in Table 2. At the same time, the frequency of the other causes of coma remained stable. Among the 2,189 comatose patients, 1,139 (52%) survived to ICU discharge (Table 1). Survival rates according to each cause of coma are given in the Table 1. To our knowledge, this is the largest existing cohort that focused on the causes of coma and their evolution. The study population was comparable in age, sex ratio, and the Glasgow Coma Scale score to previously reported populations of comatose patients as in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) cohort. SUPPORT, the largest previously available cohort of 596 non-traumatic comatose patients, studied factors such as high risk of death and severe disability [1–8]. However, the SUPPORT cohort excluded drug intoxication and metabolic causes of coma [4]. Plum and Posner [2] found that the most common causes of coma were drug poisons (30%), cerebral hemorrhage including intracerebral, epidural, and subdural hemorrhages (15%), and brainstem infarction (8%). Cardiac arrest represented only 2% in the Plum and Posner cohort. This discrepancy could be somewhat explained by the fact that the Plum and Posner’s study was performed in a neurological ICU, whereas our study was performed in a general medical ICU. Moreover, our study was subject to regular updates of the guidelines for cardiac arrest resuscitation which has improved immediate survival over the last 30 years. This hypothesis is corroborated by the findings of the other previous reports [4–8]. The reason for the Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-6388-z) contains supplementary material, which is available to authorized users.

Published
2012

26. [An essential multi-disciplinary approach in geriatric perioperative units]

Author

Judith, Cohen-Bittan, Hélène, Vallet, Catherine, Sagot, and Jacques, Boddaert

Subjects
Patient Care Team, Hip Fractures, Humans, France, Hospital Units, Perioperative Care, Aged
Abstract

A hip fracture, often a surgical emergency, is a geriatric as much as an orthopaedic pathology. A multi-disciplinary approach is essential especially in the management of complications. The geriatric perioperative unit of Pitié-Salpétrière-Charles Foix hospital has demonstrated the benefits of such a dedicated care pathway.

Published
2015

27. [Lifelines of proximal femur fracture in the elderly]

Author

Judith, Cohen-Bittan, Hélène, Vallet, Anthony, Mézière, Frédéric, Khiami, Bruno, Riou, and Jacques, Boddaert

Subjects
Aged, 80 and over, Patient Care Team, Critical Pathways, Humans, Orthopedic Procedures, Aged, Femoral Neck Fractures
Published
2015

28. Tocilizumab in severe and refractory non-infectious uveitis

Author

Matthias, Papo, Philip, Bielefeld, Hélène, Vallet, Pascal, Seve, Bertrand, Wechsler, Patrice, Cacoub, Phuc, Le Hoang, Thomas, Papo, Bahram, Bodaghi, and David, Saadoun

Subjects
Adult, Male, Uveitis, Treatment Outcome, Behcet Syndrome, Anti-Inflammatory Agents, Drug Resistance, Humans, Female, Middle Aged, Antibodies, Monoclonal, Humanized, Severity of Illness Index, Aged
Abstract

To report the safety and efficacy of tocilizumab in patients with severe and refractory non-infectious uveitis.Eight consecutive unselected patients with severe and refractory non-infectious uveitis [Birdshot chorioretinopathy (n=1), Behçet's disease (n=1) and idiopathic bilateral panuveitis (n=6)] treated with tocilizumab (8mg/kg every 4 weeks intravenously) were included. The primary outcome was the response to treatment, defined by decrease of inflammatory ocular signs.Four (50%) patients were of female gender and the median (IQR) age was 41 (31-47) years. The median number of previous immunosupressants was of 5.5 (4-6.7). Seven patients had been previously treated with anti-TNF-α [infliximab (n=5) and adalimumab (n=2)]. The immunosupressive drugs used in association with tocilizumab were azathioprine (n=2), mycophenolate mofetil (n=2) and methotrexate (n=2). After a median follow-up of 8 months (6-25), 6/8 (75%) improved under tocilizumab and 2 (25%) were non-responders. The visual acuity improved in five patients. The median dose of prednisolone decreased from 16mg/day (10.6-20.5) to 10 mg/day (10-13.7), at baseline and at the end of follow-up, respectively. Tolerance of tocilizumab was satisfactory and side effects included bronchitis (n=1) and grade 1 leukopenia (n=1) and thrombocytopenia (n=1).Tocilizumab seems to be a safe and promising therapy in severe and refractory non-infectious uveitis.

Published
2014

29. Cytomegalovirus Colitis and Hypo-IgG After Rituximab Therapy for Rheumatoid Arthritis

Author

Alexandre Azria, Ronan Houitte, Hélène Vallet, and Xavier Mariette

Subjects
business.industry, Immunology, Congenital cytomegalovirus infection, Cytomegalovirus colitis, medicine.disease, Etanercept, Rheumatology, Prednisone, Rheumatoid arthritis, medicine, Adalimumab, Immunology and Allergy, Rituximab, Methotrexate, business, medicine.drug
Abstract

To the Editor: Rituximab (RTX) is an anti-CD20 antibody used in patients with rheumatoid arthritis (RA) after failure of anti-tumor necrosis factor (anti-TNF) therapy. Side effects are mainly infectious, probably related to B cell lymphopenia. However, opportunistic infections are not frequent with use of RTX. We describe a case of cytomegalovirus (CMV) colitis in a patient with RA with hypo-IgG after 2 cycles of RTX. A 66-year-old woman was followed for 18 years for RA with positive anticitrullinated protein antibodies and structural erosions. She was successively treated with methotrexate (MTX) alone for 17 years and then in combination with anti-TNF-α for 9 months (adalimumab, then etanercept), without success. She improved after a first course of RTX (1 gram twice) in 2007 associated with low-dose corticosteroid therapy (prednisone 10 mg daily) and MTX 10 mg. In July 2008, the serum IgG level was found to be low: 5.25 g/l; IgG level was not monitored … Address correspondence to Prof. Mariette; E-mail: xavier.mariette{at}bct.aphp.fr

Published
2011

30. Hip Fracture Leads to Transitory Immune Imprint in Older Patients

Author

Héléne Vallet, Charles Bayard, Héléne Lepetitcorps, Jessica O'Hana, Soléne Fastenackels, Tinhinane Fali, Judith Cohen-Bittan, Frédéric Khiami, Jacques Boddaert, and Delphine Sauce

Subjects
acute stress, immune response, aging, inflammation, regulation loop, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Hip fracture (HF) is common in the geriatric population and is associated with a poor vital and functional prognosis which could be impacted by immunological changes. The objective here is to decipher immune changes occurring in the 1st days following HF and determine how phenotype, function, and regulation of innate and adaptive compartments adapt during acute stress event.Methods: We included HF patients, aged over 75 years. For each patient, blood samples were taken at five different timepoints: four in the perioperative period (day 0 to hospital discharge) and one at long term (6–12 months). Phenotypical and functional analysis were performed longitudinally on fresh blood or cryopreserved PBMCs. Clinical data were prospectively collected.Results: One-hundred HF patients and 60 age-matched controls were included. Innate compartment exhibits pro-inflammatory phenotypes (hyperleukocytosis, increase of CD14+ CD16+ proportion and CCR2 expression), maintaining its ability to produce pro-inflammatory cytokines. Adaptive compartment extends toward a transitory immunosuppressive profile (leucopenia) associated with an active T-cell proliferation. Furthermore, increases of LAG-3 and PD-1 and a decrease of 2-B4 expression are observed on T-cells, reinforcing their transitory suppressive status. Of note, these immune changes are transitory and sequential but may participate to a regulation loop necessary for homeostatic immune control at long term.Conclusion: HF is associated with several transitory immunological changes including pro-inflammatory phenotype in innate compartment and immunosuppressive profile in adaptive compartment. A comprehensive assessment of immune mechanisms implicated in the patient's prognosis after HF could pave the way to develop new immune therapeutics strategies.

Published
2020
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31. Caring for the critically ill patients over 80: a narrative review

Author

Bertrand Guidet, Helene Vallet, Jacques Boddaert, Dylan W. de Lange, Alessandro Morandi, Guillaume Leblanc, Antonio Artigas, and Hans Flaatten

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background There is currently no international recommendation for the admission or treatment of the critically ill older patients over 80 years of age in the intensive care unit (ICU), and there is no valid prognostic severity score that includes specific geriatric assessments. Main body In this review, we report recent literature focusing on older critically ill patients in order to help physicians in the multiple-step decision-making process. It is unclear under what conditions older patients may benefit from ICU admission. Consequently, there is a wide variation in triage practices, treatment intensity levels, end-of-life practices, discharge practices and frequency of geriatrician’s involvement among institutions and clinicians. In this review, we discuss important steps in caring for critically ill older patients, from the triage to long-term outcome, with a focus on specific conditions in the very old patients. Conclusion According to previous considerations, we provide an algorithm presented as a guide to aid in the decision-making process for the caring of the critically ill older patients.

Published
2018
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33. Etude des signes cliniques associés au diagnostic d’infection urinaire dans un contexte d’examen cytobactériologique des urines positif chez les sujets âgés de plus de 75 ans en médecine ambulatoire à Paris

Author

Baque, Margaux, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Hélène Vallet

Subjects
MESH: Urinary tract infections, MESH: Aged, Infection urinaire, General practice, Sujet âgé, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: General practice
Abstract

Urinary tract infection in the elderly is a common cause of consultation in general practice but the diagnosis remain complicated without clear recommandations. The aim of our study was to determinate the clinical signs associated with the diagnosis of urinary tract infection in an ambulatory population over 75 years in Paris. From june to october 2017, bacteriological urinary analysis from patients over 75 years old performed in an ambulatory laboratory were included.The primary objective was to determine clinical signs associated with urinary infections.. Secondary objective were to determinate the incidence of asymptomatic bacteriuria in an ambulatory elderly population, to determinate the bacteriological ecology and to describe the treatment. 98 bacteriological urinary analysis were included for analysis. Urinary burning was the only clinical sign associated with the diagnosis of urinary tract infection (OR 4.12 [1.1-16.1], p=0.04). The incidence of asymptomatic bacteriuria was 13.7%. Escherichia Coli was the main germ found. Treatment guidelines in this particular population were not applied. As conclusion, only urinary burning was associated with the diagnosis of urinary tract infection in an ambulatory population of patients over 75 years in Paris.; L’infection urinaire du sujet âgé est un problème fréquent en médecine de ville mais son diagnostic reste compliqué dans cette population sans qu’il existe des recommandations claires. L’objectif de notre étude était de rechercher les signes cliniques associés au diagnostic d’infection urinaire dans un contexte d’ECBU positif chez les sujets de plus de 75 ans en ambulatoire à Paris. De juin à octobre 2017, ont été inclus les patients de plus de 75 ans, ayant un résultat positif d’ECBU pratiqué dans un laboratoire de ville à Paris avec au moins 1 germe identifié. L’objectif principal était de déterminer les signes cliniques associés au diagnostic d’infection urinaire. Les objectifs secondaires étaient de déterminer le taux de colonisation urinaire en ambulatoire, déterminer l’écologie microbiologique et de décrire le type d’antibiothérapie utilisée. Au total, 98 ECBU ont été inclus pour analyse. Les brûlures mictionnelles ont été le seul signe clinique statistiquement associé au diagnostic d’infection urinaire (OR 4.12 [1.1-16.1] avec p=0.04). Aucun signe dit « atypique » n’a été retrouvé dans notre population. Le taux de colonisation urinaire retrouvé a été de 13.7%. Une prédominance d’Eschérichia Coli a été retrouvée dans les ECBU analysés. Les recommandations de prise en charge thérapeutiques dans cette population « à risque de complications » ne sont pas encore parfaitement appliquées. Au total, seules les brûlures mictionnelles sont significativement associées au diagnostic d’infection urinaire dans la population âgée de plus de 75 ans en ambulatoire à Paris.

Published
2018

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