Author: "Adrien Joseph" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Adrien Joseph"' showing total 126 results

Start Over Author "Adrien Joseph"

126 results on '"Adrien Joseph"'

1. Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance

Author: Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Lisa Derosa, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Rafael Mena-Osuna, Irene Herranz-Montoya, Nabil Djouder, Sylvain Baulande, Hui Pan, Adrien Joseph, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Tarek Ben Ahmed, Olivier Caron, Pierre Busson, David Boulate, Mélanie Deschasaux-Tanguy, Nathalie Arnault, Jonathan G. Pol, Eliane Piaggio, Mathilde Touvier, Laurence Zitvogel, Suzette Delaloge, Isabelle Martins, and Guido Kroemer
Subjects: Precocious detection, Neuroendocrine factors, Non-small cell lung cancer, Immunosurveillance, Immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. Methods We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. Results Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. Conclusion These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.
Published: 2024
Full Text: View/download PDF

2. Correction: COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants

Author: Pierre Bay, Etienne Audureau, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Matthieu Turpin, Laurence Morand-Joubert, Sébastien Jochmans, Aurélia Pitsch, Sylvie Meireles, Damien Contou, Amandine Henry, Adrien Joseph, Marie-Laure Chaix, Fabrice Uhel, Damien Roux, Diane Descamps, Malo Emery, Claudio Garcia-Sanchez, David Levy, Sonia Burrel, Julien Mayaux, Antoine Kimmoun, Cédric Hartard, Frédéric Pène, Flore Rozenberg, Stéphane Gaudry, Ségolène Brichler, Antoine Guillon, Lynda Handala, Fabienne Tamion, Alice Moisan, Thomas Daix, Sébastien Hantz, Flora Delamaire, Vincent Thibault, Bertrand Souweine, Cecile Henquell, Lucile Picard, Françoise Botterel, Christophe Rodriguez, Armand Mekontso Dessap, Jean-Michel Pawlotsky, Slim Fourati, Nicolas de Prost, and the SEVARVIR investigators
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2024
Full Text: View/download PDF

3. COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants

Author: Pierre Bay, Etienne Audureau, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Matthieu Turpin, Laurence Morand-Joubert, Sébastien Jochmans, Aurélia Pitsch, Sylvie Meireles, Damien Contou, Amandine Henry, Adrien Joseph, Marie-Laure Chaix, Fabrice Uhel, Damien Roux, Diane Descamps, Malo Emery, Claudio Garcia-Sanchez, David Levy, Sonia Burrel, Julien Mayaux, Antoine Kimmoun, Cédric Hartard, Frédéric Pène, Flore Rozenberg, Stéphane Gaudry, Ségolène Brichler, Antoine Guillon, Lynda Handala, Fabienne Tamion, Alice Moisan, Thomas Daix, Sébastien Hantz, Flora Delamaire, Vincent Thibault, Bertrand Souweine, Cecile Henquell, Lucile Picard, Françoise Botterel, Christophe Rodriguez, Armand Mekontso Dessap, Jean-Michel Pawlotsky, Slim Fourati, Nicolas de Prost, and the SEVARVIR investigators
Subjects: COVID-19, Invasive pulmonary aspergillosis, Intensive care unit, SARS-CoV-2, Omicron, COVID-19 associated pulmonary aspergillosis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. Methods This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. Results 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4–7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. Conclusion This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.
Published: 2024
Full Text: View/download PDF

4. Correction: Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance

Author: Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Lisa Derosa, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Rafael Mena-Osuna, Irene Herranz-Montoya, Nabil Djouder, Sylvain Baulande, Hui Pan, Adrien Joseph, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Tarek Ben Ahmed, Olivier Caron, Pierre Busson, David Boulate, Mélanie Deschasaux-Tanguy, Nathalie Arnault, Jonathan G. Pol, Eliane Piaggio, Mathilde Touvier, Laurence Zitvogel, Suzette Delaloge, Isabelle Martins, and Guido Kroemer
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2024
Full Text: View/download PDF

5. Right ventricular injury in patients with COVID-19-related ARDS eligible for ECMO support: a multicenter retrospective study

Author: Matthieu Petit, Misylias Bouaoud, Edouard Jullien, Adrien Joseph, Bruno Evrard, Cyril Charron, Anousone Daulasim, Annick Legras, Maeva Gourraud, Marine Goudelin, Philippe Vignon, and Antoine Vieillard-Baron
Subjects: Acute respiratory distress syndrome, COVID-19, Right ventricle, Extracorporeal membrane oxygenation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been proposed in this setting, but optimal criteria to select target patients remain unknown. Our hypothesis is that evaluation of right ventricular (RV) function could be helpful. The aims of our study were to report the incidence and outcomes of patients eligible for ECMO according to EOLIA criteria, and to identify a subgroup of patients with RV injury, which could be a target for ECMO. Methods Retrospective observational study involving 3 French intensive care units (ICUs) of teaching hospitals. Patients with confirmed SARS-CoV-2 infection between March 2020 and March 2021, presenting ARDS and with available echocardiography, were included. Patients were classified in three groups according to whether or not they met the EOLIA criteria and the presence of RV injury (RVI) (“EOLIA −”, “EOLIA + RVI −” and “EOLIA + RVI + ”). RVI was defined by the association of RV to left ventricular end-diastolic area ratio > 0.8 and paradoxical septal motion. Kaplan–Meier survival curves were used to analyze outcome as well as a Cox model for 90 day mortality. Results 915 patients were hospitalized for COVID-19, 418 of them with ARDS. A total of 283 patients with available echocardiography were included. Eighteen (6.3%) patients received ECMO. After exclusion of these patients, 107 (40.5%) were classified as EOLIA −, 126 (47.5%) as EOLIA + RVI −, and 32 (12%) as EOLIA + RVI + . Ninety-day mortality was 21% in the EOLIA-group, 44% in the EOLIA + RVI-group, and 66% in the EOLIA + RVI + group (p
Published: 2024
Full Text: View/download PDF

6. Critically Ill Patients with Visceral Nocardia Infection, France and Belgium, 2004–2023

Author: Lucas Khellaf, Virginie Lemiale, Maxens Decavèle, Marc Pineton de Chambrun, Alexandra Beurton, Toufik Kamel, Anabelle Stoclin, Djamel Mokart, Fabrice Bruneel, Clara Vigneron, Achille Kouatchet, Benoît Henry, Jean-Pierre Quenot, Grégoire Jolly, Nahema Issa, Matthieu Bellal, Julien Poissy, Claire Pichereau, Julien Schmidt, Nathalie Layios, Maxime Gaillet, Elie Azoulay, and Adrien Joseph
Subjects: Nocardia, immunocompromised, intensive care, bacteria, France, Belgium, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: We studied 50 patients with invasive nocardiosis treated during 2004–2023 in intensive care centers in France and Belgium. Most (65%) died in the intensive care unit or in the year after admission. Nocardia infections should be included in the differential diagnoses for patients in the intensive care setting.
Published: 2024
Full Text: View/download PDF

7. Severe infections requiring intensive care unit admission in patients receiving ibrutinib for hematological malignancies: a groupe de recherche respiratoire en réanimation onco-hématologique (GRRR-OH) study

Author: Louise Baucher, Virginie Lemiale, Adrien Joseph, Florent Wallet, Marc Pineton de Chambrun, Alexis Ferré, Romain Lombardi, Laura Platon, Adrien Contejean, Charline Fuseau, Laure Calvet, Frédéric Pène, Achille Kouatchet, Djamel Mokart, Elie Azoulay, and Antoine Lafarge
Subjects: Ibrutinib, Opportunistic infections, Intensive care, Lymphoproliferative disease, Targeted drugs, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020. Results Median time from ibrutinib initiation was 6.6 [3–18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5–11] vs. 4 [3–7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1–2] vs. 0 [0–2]; p
Published: 2023
Full Text: View/download PDF

8. Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study

Author: Nicolas de Prost, Etienne Audureau, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Pierre Bay, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Guillaume Voiriot, Laurence Morand-Joubert, Sébastien Jochmans, Aurélia Pitsch, Sylvie Meireles, Damien Contou, Amandine Henry, Adrien Joseph, Marie-Laure Chaix, Fabrice Uhel, Diane Descamps, Malo Emery, Claudio Garcia-Sanchez, Charles-Edouard Luyt, Stéphane Marot, Frédéric Pène, Anne-Sophie Lhonneur, Stéphane Gaudry, Ségolène Brichler, Lucile Picard, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, Slim Fourati, and the SEVARVIR investigators
Subjects: SARS-CoV-2, Omicron, Sublineage, COVID-19, Acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. Results The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as “BA.2” (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as “BA.4/BA.5”, and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as “BQ.1.1”. The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. Conclusions Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.
Published: 2023
Full Text: View/download PDF

9. 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
Full Text: View/download PDF

10. Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis

Author: Julie Le Naour, Léa Montégut, Yuhong Pan, Sarah Adriana Scuderi, Pierre Cordier, Adrien Joseph, Allan Sauvat, Valerio Iebba, Juliette Paillet, Gladys Ferrere, Ludivine Brechard, Claire Mulot, Grégory Dubourg, Laurence Zitvogel, Jonathan G. Pol, Erika Vacchelli, Pierre-Laurent Puig, and Guido Kroemer
Subjects: Bone marrow-derived dendritic cells, chemotaxis, immunogenic chemotherapy, immunosurveillance, tumor microenvironment, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: ABSTRACTFormyl peptide receptor-1 (FPR1) is a pattern recognition receptor that is mostly expressed by myeloid cells. In patients with colorectal cancer (CRC), a loss-of-function polymorphism (rs867228) in the gene coding for FPR1 has been associated with reduced responses to chemotherapy or chemoradiotherapy. Moreover, rs867228 is associated with accelerated esophageal and colorectal carcinogenesis. Here, we show that dendritic cells from Fpr1−/− mice exhibit reduced migration in response to chemotherapy-treated CRC cells. Moreover, Fpr1−/− mice are particularly susceptible to chronic ulcerative colitis and colorectal oncogenesis induced by the mutagen azoxymethane followed by oral dextran sodium sulfate, a detergent that induces colitis. These experiments were performed after initial co-housing of Fpr1−/− mice and wild-type controls, precluding major Fpr1-driven differences in the microbiota. Pharmacological inhibition of Fpr1 by cyclosporin H also tended to increase intestinal oncogenesis in mice bearing the ApcMin mutation, and this effect was reversed by the anti-inflammatory drug sulindac. We conclude that defective FPR1 signaling favors intestinal tumorigenesis through the modulation of the innate inflammatory/immune response.
Published: 2023
Full Text: View/download PDF

11. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Author: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stéphane Gaudry, Ségolène Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Louise-Marie Jandeaux, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Djillali Annane, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, and Slim Fourati
Subjects: Science
Abstract: SARS-CoV-2 variant Omicron has been suggested to cause less severe disease. This prospective study shows that the clinical phenotype in patients infected with Omicron differs from patients infected with Delta but no association between Delta and Omicron including sublineages and mortality was observed.
Published: 2022
Full Text: View/download PDF

12. Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index

Author: Adrien Joseph, Hui Chen, Gerasimos Anagnostopoulos, Léa Montégut, Antoine Lafarge, Omar Motiño, Maria Castedo, Maria Chiara Maiuri, Karine Clément, Safae Terrisse, Anne Laure Martin, Ines Vaz-Luis, Fabrice Andre, Franziska Grundler, Françoise Wilhelmi de Toledo, Frank Madeo, Laurence Zitvogel, François Goldwasser, Benoit Blanchet, Frédéric Fumeron, Ronan Roussel, Isabelle Martins, and Guido Kroemer
Subjects: Cytology, QH573-671
Abstract: Abstract In mice, the plasma concentrations of the appetite-stimulatory and autophagy-inhibitory factor acyl-coenzyme A binding protein (ACBP, also called diazepam-binding inhibitor, DBI) acutely increase in response to starvation, but also do so upon chronic overnutrition leading to obesity. Here, we show that knockout of Acbp/Dbi in adipose tissue is sufficient to prevent high-fat diet-induced weight gain in mice. We investigated ACBP/DBI plasma concentrations in several patient cohorts to discover a similar dual pattern of regulation. In relatively healthy subjects, ACBP/DBI concentrations independently correlated with body mass index (BMI) and age. The association between ACBP/DBI and BMI was lost in subjects that underwent major weight gain in the subsequent 3–9 years, as well as in advanced cancer patients. Voluntary fasting, undernutrition in the context of advanced cancer, as well as chemotherapy were associated with an increase in circulating ACBP/DBI levels. Altogether, these results support the conclusion that ACBP/DBI may play an important role in body mass homeostasis as well as in its failure.
Published: 2021
Full Text: View/download PDF

13. Elevated plasma levels of the appetite-stimulator ACBP/DBI in fasting and obese subjects

Author: Sijing Li, Adrien Joseph, Isabelle Martins, and Guido Kroemer
Subjects: metabolism, obesity, diazepam binding protein, appetite, starvation, autophagy, Medicine, Biology (General), QH301-705.5
Abstract: Eukaryotic cells release the phylogenetically ancient protein acyl coenzyme A binding protein (ACBP, which in humans is encoded by the gene DBI, diazepam binding inhibitor) upon nutrient deprivation. Accordingly, mice that are starved for one to two days and humans that undergo voluntary fasting for one to three weeks manifest an increase in the plasma concentration of ACBP/DBI. Paradoxically, ACBP/DBI levels also increase in obese mice and humans. Since ACBP/DBI stimulates appetite, this latter finding may explain why obesity constitutes a self-perpetuating state. Here, we present a theoretical framework to embed these findings in the mechanisms of weight control, as well as a bioinformatics analysis showing that, irrespective of the human cell or tissue type, one single isoform of ACBP/DBI (ACBP1) is preponderant (~90% of all DBI transcripts, with the sole exception of the testis, where it is ~70%). Based on our knowledge, we conclude that ACBP1 is subjected to a biphasic transcriptional and post-transcriptional regulation, explaining why obesity and fasting both are associated with increased circulating ACBP1 protein levels.
Published: 2021
Full Text: View/download PDF

14. Cancer cell-autonomous overactivation of PARP1 compromises immunosurveillance in non-small cell lung cancer

Author: Adrien Joseph, Guido Kroemer, Antoine Lafarge, Oliver Kepp, Jonathan Pol, Sylvere Durand, Marion Leduc, Pan Juncheng, Florine Obrist, Judith Michels, Maria Castedo, Allan Sauvat, Giulia Cerrato, Isabelle Martins, Ester Saavedra, Sijing Li, Sarah Lévesque, Fanny Aprahamian, and Nitharsshini Nirmalathansan
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2022
Full Text: View/download PDF

15. Immune‐mediated thrombotic thrombocytopenic purpura prognosis is affected by blood pressure

Author: Adrien Joseph, Martin Eloit, Elie Azoulay, Gilles Kaplanski, François Provot, Claire Presne, Alain Wynckel, Steven Grangé, Éric Rondeau, Frédéric Pène, Yahsou Delmas, Alexandre Lautrette, Christelle Barbet, Christiane Mousson, Jean‐Philippe Coindre, Pierre Perez, Matthieu Jamme, Jean‐François Augusto, Pascale Poullin, Frédéric Jacobs, Khalil El Karoui, Cécile Vigneau, Marc Ulrich, Tarik Kanouni, Moglie Le Quintrec, Mohamed Hamidou, Simon Ville, Anne Charvet‐Rumpler, Mario Ojeda‐Uribe, Pascal Godmer, Véronique Fremeaux‐Bacchi, Agnès Veyradier, Jean‐Michel Halimi, and Paul Coppo
Subjects: ADAMTS13, blood pressure, complement, hemolytic uremic syndrome, hypertension, prognosis, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Abstract Background The prevalence, prognostic role, and diagnostic value of blood pressure in immune‐mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear. Methods Using a national cohort of iTTP (n = 368), Shigatoxin‐induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension‐related thrombotic microangiopathy (n = 25), we sought to compare the cohort’s blood pressure profile to assess its impact on prognosis and diagnostic performances. Results Patients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118–143] vs 161 [IQR 142–180] mmHg) and diastolic (76 [IQR 69–83] vs 92 [IQR 79–105] mmHg, both p
Published: 2022
Full Text: View/download PDF

16. Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit

Author: Adrien Joseph, Audrey Simonaggio, Annabelle Stoclin, Antoine Vieillard-Baron, Guillaume Geri, Stéphane Oudard, Jean-Marie Michot, Olivier Lambotte, Elie Azoulay, and Virginie Lemiale
Subjects: Cancer, Outcome, Adverse event, Immunotherapy, Intensive care, Immune-related adverse events, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Immune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown. This retrospective multicentric study aims to describe the characteristics of patients admitted to the intensive care units of 4 academic hospitals in Paris area while receiving immune checkpoint inhibitor treatment between January 2013 and October 2019. Results Over the study period, 112 cancer patients who received immune checkpoint inhibitors were admitted to the intensive care unit within 60 days after the last dose. ICU admission was related to immune-related adverse events (n = 29, 26%), other intercurrent events (n = 39, 35%), or complications related to tumor progression (n = 44, 39%). Immune-related adverse events were pneumonitis (n = 8), colitis (n = 4), myocarditis (n = 3), metabolic disorders related to diabetes (n = 3), hypophysitis (n = 2), nephritis (n = 2), meningitis or encephalitis (n = 2), hepatitis (n = 2), anaphylaxis (n = 2) and pericarditis (n = 1). Primary tumors were mostly melanomas (n = 14, 48%), non-small-cell lung cancers (n = 7, 24%), and urothelial carcinomas (n = 5, 17%). Diagnosis of melanoma and a neutrophil/lymphocyte ratio
Published: 2020
Full Text: View/download PDF

17. Acute kidney injury in patients with SARS-CoV-2 infection

Author: Adrien Joseph, Lara Zafrani, Asma Mabrouki, Elie Azoulay, and Michael Darmon
Subjects: Acute kidney injury, COVID-19, Complement system proteins, Interleukin-6, Outcome, Intensive care units, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Acute Kidney Injury (AKI) is a frequent complication of severe SARS-CoV-2 infection. Multiple mechanisms are involved in COVID-19-associated AKI, from direct viral infection and secondary inflammation to complement activation and microthrombosis. However, data are limited in critically-ill patients. In this study, we sought to describe the prevalence, risk factors and prognostic impact of AKI in this setting. Methods Retrospective monocenter study including adult patients with laboratory confirmed SARS-CoV-2 infection admitted to the ICU of our university Hospital. AKI was defined according to both urinary output and creatinine KDIGO criteria. Results Overall, 100 COVID-19 patients were admitted. AKI occurred in 81 patients (81%), including 44, 10 and 27 patients with AKI stage 1, 2 and 3 respectively. The severity of AKI was associated with mortality at day 28 (p = 0.013). Before adjustment, the third fraction of complement (C3), interleukin-6 (IL-6) and ferritin levels were higher in AKI patients. After adjustment for confounders, both severity (modified SOFA score per point) and AKI were associated with outcome. When forced in the final model, C3 (OR per log 0.25; 95% CI 0.01–4.66), IL-6 (OR per log 0.83; 95% CI 0.51–1.34), or ferritin (OR per log 1.63; 95% CI 0.84–3.32) were not associated with AKI and did not change the model. Conclusion In conclusion, we did not find any association between complement activation or inflammatory markers and AKI. Proportion of patients with AKI during severe SARS-CoV-2 infection is higher than previously reported and associated with outcome.
Published: 2020
Full Text: View/download PDF

18. Improved Swiss-rolling method for histological analyses of colon tissue

Author: Julie Le Naour, Léa Montégut, Adrien Joseph, Kévin Garbin, Erika Vacchelli, Guido Kroemer, Jonathan G. Pol, and Maria Chiara Maiuri
Subjects: Intestinal murine tissue, Swiss-rolling technique, Ex vivo method, Histological tissue preparation, Science
Abstract: Since the introduction of the Swiss-rolling technique by Reilly and Kirsner in 1965, various methodological approaches have been developed for histological analyses of intestinal tissues. Here, we describe an improved protocol for the processing of freshly harvested murine colons that can be extended to other intestinal tissues. With simple tools, this technique allows to tightly wrap the organ throughout the whole length and to keep it in place before fixation, avoiding excessive stiffness of the tissue. Unlike the original method which relies on frozen samples, processing of the biological samples right after resection preserves epitopes integrity for subsequent immunohistochemical analyses. Ultimately, this method provides a reproducible workflow to capture the entire colon length in a unique histological section in order to assess several features such as intestinal inflammation and tumorigenesis.• Easily include freshly isolated tissues• Shorten preparation time using a few affordable tools• Prevent unrolling and preserve tissue integrity
Published: 2022
Full Text: View/download PDF

19. Acute Kidney Injury in Cancer Immunotherapy Recipients

Author: Adrien Joseph, Antoine Lafarge, Elie Azoulay, and Lara Zafrani
Subjects: immunotherapy, acute kidney injury, immune checkpoint inhibitors, chimeric antigen receptor T cell therapy, cancer, Cytology, QH573-671
Abstract: Cancer immunotherapy has now entered clinical practice and has reshaped the standard of care for many cancer patients. With these new strategies, specific toxicities have emerged, and renal side effects have been described. In this review, we will describe the causes of acute kidney injury in CAR T cell, immune checkpoint inhibitors and other cancer immuno-therapy recipients. CAR T cell therapy and bispecific T cell engaging antibodies can lead to acute kidney injury as a consequence of cytokine release syndrome, tumor lysis syndrome, sepsis or specific CAR T cell infiltration. Immune checkpoint blockade most often results in acute tubular interstitial nephritis, but glomerular diseases have also been described. Although the pathophysiology remains mostly elusive, we will describe the mechanisms of renal damage in these contexts, its prognosis and treatment. As the place of immunotherapy in the anti-cancer armamentarium is exponentially increasing, close collaboration between nephrologists and oncologists is of utmost importance to provide the best standard of care for these patients.
Published: 2022
Full Text: View/download PDF

20. Author Correction: Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Author: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stéphane Gaudry, Ségolène Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Louise-Marie Jandeaux, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Djillali Annane, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, and Slim Fourati
Subjects: Science
Published: 2022
Full Text: View/download PDF

21. Metabolic features of cancer cells impact immunosurveillance

Author: Christophe Klein, Diane Damotte, Alexandra Leary, Adrien Joseph, Sebastien Gouy, Marco Alifano, Marie-Caroline Dieu-Nosjean, Guido Kroemer, Eric Deutsch, Antoine Lafarge, Philippe Morice, Julien Adam, Patricia Pautier, Cyrus Chargari, Isabelle Cremer, Catherine Genestie, Pan Juncheng, Michele Mondini, Nizar Labaied, Mauro Loi, Valentina Astesana, Florine Obrist, Norma Bloy, Gautier Stoll, Nicolas Signolle, and Maria Castedo
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background Tumors rewire their metabolism to achieve robust anabolism and resistance against therapeutic interventions like cisplatin treatment. For example, a prolonged exposure to cisplatin causes downregulation of pyridoxal kinase (PDXK), the enzyme that generates the active vitamin B6, and upregulation of poly ADP-ribose (PAR) polymerase-1 (PARP1) activity that requires a supply of nicotinamide (vitamin B3) adenine dinucleotide. We investigated the impact of the levels of PDXK and PAR on the local immunosurveillance (ie, density of the antigen presenting cells and adaptive immune response by CD8 T lymphocytes) in two different tumor types.Methods Tumors from patients with locally advanced cervical carcinoma (LACC) and non-small cell lung cancer (NSCLC) were stained for PAR, PDXK, dendritic cell lysosomal associated membrane glycoprotein (DC-LAMP) and CD8 T cell infiltration. Their correlations and prognostic impact were assessed. Cisplatin-resistant NSCLC cell clones isolated from Lewis-lung cancer (LLC) cells were evaluated for PAR levels by immunoblot. Parental (PARlow) and cisplatin-resistant (PARhigh) clones were subcutaneously injected into the flank of C57BL/6 mice. Tumors were harvested to evaluate their immune infiltration by flow cytometry.Results The infiltration of tumors by CD8 T and DC-LAMP+ cells was associated with a favorable overall survival in patients with LACC (p=0.006 and p=0.008, respectively) and NSCLC (p
Published: 2021
Full Text: View/download PDF

22. Pyridoxal kinase and poly(ADP-ribose) affect the immune microenvironment of locally advanced cancers

Author: Adrien Joseph, Juncheng Pan, Judith Michels, Guido Kroemer, and Maria Castedo
Subjects: tumor microenvironment, immune escape, metabolism, vitamin b, immunotherapy, cd8+ t cells, dendritic cells, survival, cervical cancer, non-small cell lung cancer, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Malignant cells adapt to the hostile tumor microenvironment by escaping from, or actively suppressing, anticancer immune responses. In the past, we reported that reduced synthesis of active vitamin B6 (due to downregulation of pyridoxal kinase) or overactivation of poly(ADP-ribose) polymerase confers resistance to chemotherapy with cisplatin. Recently, we found that these prognostically adverse alterations in oncometabolism also correlate with the rarefaction of immune effectors in the tumor bed.
Published: 2021
Full Text: View/download PDF

23. Metabolic enzymes expressed by cancer cells impact the immune infiltrate

Author: Gautier Stoll, Margerie Kremer, Normal Bloy, Adrien Joseph, Maria Castedo, Guillaume Meurice, Christophe Klein, Lorenzo Galluzzi, Judith Michels, and Guido Kroemer
Subjects: dc-lamp, dendritic cells, cytotoxic t lymphocytes, myeloid cells, treg cells, tumor microenvironment, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: The expression of two metabolic enzymes, i.e., aldehyde dehydrogenase 7 family, member A1 (ALDH7A1) and lipase C, hepatic type (LIPC) by malignant cells, has been measured by immunohistochemical methods in non-small cell lung carcinoma (NSCLC) biopsies, and has been attributed negative and positive prognostic value, respectively. Here, we demonstrate that the protein levels of ALDH7A1 and LIPC correlate with the levels of the corresponding mRNAs. Bioinformatic analyses of gene expression data from 4921 cancer patients revealed that the expression of LIPC positively correlates with abundant tumor infiltration by myeloid and lymphoid cells in NSCLC, breast carcinoma, colorectal cancer and melanoma samples. In contrast, high levels of ALDH7A1 were associated with a paucity of immune effectors within the tumor bed. These data reinforce the notion that the metabolism of cancer cells has a major impact on immune and inflammatory processes in the tumor microenvironment, pointing to hitherto unsuspected intersections between oncometabolism and immunometabolism.
Published: 2019
Full Text: View/download PDF

24. Shiga Toxin-Associated Hemolytic Uremic Syndrome: Specificities of Adult Patients and Implications for Critical Care Management

Author: Benoit Travert, Cédric Rafat, Patricia Mariani, Aurélie Cointe, Antoine Dossier, Paul Coppo, and Adrien Joseph
Subjects: Shiga toxin, Escherichia coli, hemolytic uremic syndrome, thrombotic microangiopathy, Medicine
Abstract: Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a form of thrombotic microangiopathy secondary to an infection by an enterohemorrhagic E. coli. Historically considered a pediatric disease, its presentation has been described as typical, with bloody diarrhea at the forefront. However, in adults, the clinical presentation is more diverse and makes the early diagnosis hazardous. In this review, we review the epidemiology, most important outbreaks, physiopathology, clinical presentation and prognosis of STEC-HUS, focusing on the differential features between pediatric and adult disease. We show that the clinical presentation of STEC-HUS in adults is far from typical and marked by the prevalence of neurological symptoms and a poorer prognosis. Of note, we highlight knowledge gaps and the need for studies dedicated to adult patients. The differences between pediatric and adult patients have implications for the treatment of this disease, which remains a public health threat and lack a specific treatment.
Published: 2021
Full Text: View/download PDF

25. Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

Author: Adrien Joseph, Aurélie Cointe, Patricia Mariani Kurkdjian, Cédric Rafat, and Alexandre Hertig
Subjects: shiga toxin, escherichia coli, hemolytic uremic syndrome, thrombotic microangiopathy, Medicine
Abstract: The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure.
Published: 2020
Full Text: View/download PDF

26. Severe infections in recipients of cancer immunotherapy: what intensivists need to know

Author: Adrien, Joseph, Antoine, Lafarge, Asma, Mabrouki, Moustafa, Abdel-Nabey, Yannick, Binois, Romy, Younan, and Elie, Azoulay
Subjects: Administration, Intravesical, Urinary Bladder Neoplasms, Adrenal Cortex Hormones, Humans, Immunotherapy, Critical Care and Intensive Care Medicine
Abstract: Given the increased number of cancer patients admitted in the ICU and the growing importance of immunotherapy in their therapeutic arsenal, intensivists will be increasingly confronted to patients treated with immunotherapies who will present with complications, infectious and immunologic.Apart from their specific immunologic toxicities, cancer immunotherapy recipients also have specific immune dysfunction and face increased infectious risks that may lead to intensive care unit admission.Chimeric antigen receptor T-cell therapy is associated with profound immunosuppression and the risks of bacterial, fungal and viral infections vary according to the time since infusion.Immune checkpoint blockers are associated with an overall favorable safety profile but associations of checkpoint blockers and corticosteroids and immunosuppressive drugs prescribed to treat immune-related adverse events are associated with increased risks of bacterial and fungal infections.The T-cell engaging bispecific therapy blinatumomab causes profound B-cell aplasia, hypogammaglobulinemia and neutropenia, but seems to be associated with fewer infectious adverse events compared with standard intensive chemotherapy.Lastly, intravesical administration of Bacillus Calmette-Guérin (BCG) can lead to disseminated BCGitis and severe sepsis requiring a specific antibiotherapy, often associated with corticosteroid treatment.
Published: 2022
Full Text: View/download PDF

27. Predictors of acute ischemic cerebral lesions in immune-mediated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Author: Lisa Neuman, Adrien Joseph, Raïda Bouzid, Mickael Lescroart, Eric Mariotte, Stéphane Ederhy, Sophie Tuffet, Jean-Luc Baudel, Ygal Benhamou, Lionel Galicier, Steven Grangé, François Provôt, Antoine Neel, Frédéric Pène, Yahsou Delmas, Claire Presne, Pascale Poullin, Alain Wynckel, Pierre Perez, Christelle Barbet, Jean-Michel Halimi, Valérie Chatelet, Jean-Michel Rebibou, Mario Ojeda-Uribe, Cécile Vigneau, Laurent Mesnard, Agnès Veyradier, Elie Azoulay, Paul Coppo, and Hugues Chabriat
Abstract: BackgroundThe immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known.AimThe prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and shigatoxin-producingEscherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study.MethodsUnivariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions.ResultsAmong 73 TMA cases (mean age 46.89 ± 15.99 years (range: 21-87 years) with iTTP (n = 57) or HUS (n= 16), one third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, 3 factors predicted the occurrence of acute ischemic lesions on cerebral MRI: 1) the presence of old infarcts on cerebral MRI, 2) the level of blood pulse pressure, 3) the diagnosis of iTTP.ConclusionCerebral MRI is crucial to detect both symptomatic and covert ischemic lesions at the acute phase of iTTP and HUS and helps identify patients with old infarcts, at the highest risk of neurological worsening. The diagnosis of iTTP further increases the risk of ischemic lesions but also an increased level of blood pressure that may represent a potential target to further improve the therapeutic management of these conditions.Key points-One third of patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) or the hemolytic uremic syndrome (HUS) present with acute ischemic cerebral lesions on magnetic resonance imagery (MRI);-The cerebral manifestations on MRI did not differ between iTTP and HUS;-The presence of old infarcts on cerebral MRI, the level of blood pulse pressure and a diagnosis of iTTP predict the occurrence of acute ischemic lesions on cerebral MRI.
Published: 2023
Full Text: View/download PDF

28. 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
Full Text: View/download PDF

29. High plasma concentrations of acyl‐coenzyme A binding protein ( <scp>ACBP</scp> ) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of <scp>ACBP</scp>

Author: Léa Montégut, Adrien Joseph, Hui Chen, Mahmoud Abdellatif, Christoph Ruckenstuhl, Omar Motiño, Flavia Lambertucci, Gerasimos Anagnostopoulos, Sylvie Lachkar, Silvia Dichtinger, Maria Chiara Maiuri, François Goldwasser, Benoit Blanchet, Frédéric Fumeron, Isabelle Martins, Frank Madeo, and Guido Kroemer
Subjects: Aging, Cell Biology
Abstract: Autophagy defects accelerate aging, while stimulation of autophagy decelerates aging. Acyl-coenzyme A binding protein (ACBP), which is encoded by a diazepam-binding inhibitor (DBI), acts as an extracellular feedback regulator of autophagy. As shown here, knockout of the gene coding for the yeast orthologue of ACBP/DBI (ACB1) improves chronological aging, and this effect is reversed by knockout of essential autophagy genes (ATG5, ATG7) but less so by knockout of an essential mitophagy gene (ATG32). In humans, ACBP/DBI levels independently correlate with body mass index (BMI) as well as with chronological age. In still-healthy individuals, we find that high ACBP/DBI levels correlate with future cardiovascular events (such as heart surgery, myocardial infarction, and stroke), an association that is independent of BMI and chronological age, suggesting that ACBP/DBI is indeed a biomarker of "biological" aging. Concurringly, ACBP/DBI plasma concentrations correlate with established cardiovascular risk factors (fasting glucose levels, systolic blood pressure, total free cholesterol, triglycerides), but are inversely correlated with atheroprotective high-density lipoprotein (HDL). In mice, neutralization of ACBP/DBI through a monoclonal antibody attenuates anthracycline-induced cardiotoxicity, which is a model of accelerated heart aging. In conclusion, plasma elevation of ACBP/DBI constitutes a novel biomarker of chronological aging and facets of biological aging with a prognostic value in cardiovascular disease.
Published: 2022
Full Text: View/download PDF

30. Post-traumatic stress disorder and quality of life alterations in survivors of immune-mediated thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome

Author: Elie Azoulay, Virginie Souppart, Nancy Kentish-Barnes, Ygal Benhamou, Bérangère S. Joly, Lara Zafrani, Adrien Joseph, Emmanuel Canet, Claire Presne, Maximilien Grall, Yoann Zerbib, François Provot, Jehane Fadlallah, Eric Mariotte, Tomas Urbina, Agnès Veyradier, and Paul Coppo
Subjects: Critical Care and Intensive Care Medicine
Published: 2023
Full Text: View/download PDF

31. Effectiveness of third-generation cephalosporins or piperacillin compared with cefepime or carbapenems for severe infections caused by wild-type AmpC β-lactamase-producing Enterobacterales: A multi-centre retrospective propensity-weighted study

Author: Alexis Maillard, Tristan Delory, Juliette Bernier, Antoine Villa, Khalil Chaibi, Lélia Escaut, Adrien Contejean, Beatrice Bercot, Jérôme Robert, Fatma El Alaoui, Jacques Tankovic, Hélène Poupet, Gaëlle Cuzon, Matthieu Lafaurie, Laure Surgers, Adrien Joseph, Olivier Paccoud, Jean-Michel Molina, and Alexandre Bleibtreu
Subjects: Microbiology (medical), Infectious Diseases, Pharmacology (medical), General Medicine
Published: 2023
Full Text: View/download PDF

32. Predictive Scores for Early Identification of Immune-Mediated Thrombotic Thrombocytopenic Purpura: Room for Improvement?

Author: Adrien Joseph, Benoit Brilland, Laure Burguet, Martin Eloit, Nicolas Fage, Jean-François Augusto, Yahsou Delmas, Agnès Veyradier, Jean-Michel Halimi, and Paul Coppo
Subjects: Nephrology
Published: 2022

33. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron, sublineages BA.1, BA.1.1, BA.2 and impact of mutational patterns in critically ill French patients with COVID-19

Author: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tai Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stephane Gaudry, Segolene Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Jandeaux Louise-Marie, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Christophe Rodriguez, Djillali Annane, Elie Azoulay, Armand Mekontso-Dessap, Jean-Michel Pawlotsky, and Slim Fourati
Abstract: Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with a rarer occurrence of severe disease requiring intensive care. However, a substantial number of patients infected with variant Omicron still experienced severe COVID-19. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 participating intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients for whom SARS-CoV-2 variant lineage was determined, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) was different from that in those infected with variant Delta (n = 111). We observed no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35–1.32]; p = 0.253). Among Omicron-infected patients, 43.2% were immunocompromised, most of whom had received two doses of vaccine or more (85.9%) but displayed a poor humoral response to vaccination (mean difference in serum anti-spike IgG antibody titers between vaccinated and non-vaccinated immunocompromised patients: 1078 BAU/mL [-319.4; 2475.0]; p = 0.160). The mortality rate of immunocompromised patients infected with variant Omicron was significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there was no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms or mutational profile and the 28-day mortality.
Published: 2022
Full Text: View/download PDF

34. The Specificities of Thrombotic Thrombocytopenic Purpura at Extreme Ages: A Narrative Review

Author: Adrien Joseph, Bérangère S. Joly, Adrien Picod, Agnès Veyradier, and Paul Coppo
Subjects: General Medicine
Abstract: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy (TMA) related to a severe ADAMTS13 deficiency, the specific von Willebrand factor (VWF)-cleaving protease. This deficiency is often immune-mediated (iTTP) and related to the presence of anti-ADAMTS13 autoantibodies that enhance its clearance or inhibit its VWF processing activity. iTTP management may be challenging at extreme ages of life. International cohorts of people with TTP report delayed diagnoses and misdiagnoses in children and elderly people. Child-onset iTTP shares many features with adult-onset iTTP: a female predominance, an idiopathic presentation, and the presence of neurological disorders and therapeutic strategies. Long-term follow-ups and a transition from childhood to adulthood are crucial to preventing iTTP relapses, in order to identify the occurrence of other autoimmune disorders and psychosocial sequelae. In contrast, older iTTP patients have an atypical clinical presentation, with delirium, an atypical neurological presentation, and severe renal and cardiac damages. They also have a poorer response to treatment and prognosis. Long-term sequelae are highly prevalent in older patients. Prediction scores for iTTP diagnoses are not used for children and have a lower sensitivity and specificity in patients over 60 years old. ADAMTS13 remains the unique biological marker that is able to definitely confirm or rule out the diagnosis of iTTP and predict relapses during follow-ups.
Published: 2023
Full Text: View/download PDF

35. Cancer cell-autonomous overactivation of PARP1 compromises immunosurveillance in non-small cell lung cancer

Author: Pan Juncheng, Adrien Joseph, Antoine Lafarge, Isabelle Martins, Florine Obrist, Jonathan Pol, Ester Saavedra, Sijing Li, Allan Sauvat, Giulia Cerrato, Sarah Lévesque, Marion Leduc, Oliver Kepp, Sylvère Durand, Fanny Aprahamian, Nitharsshini Nirmalathansan, Judith Michels, Guido Kroemer, and Maria Castedo
Subjects: Pharmacology, Cancer Research, Lung Neoplasms, Immunology, Poly(ADP-ribose) Polymerase Inhibitors, Mice, Oncology, Monitoring, Immunologic, Carcinoma, Non-Small-Cell Lung, Tumor Microenvironment, Molecular Medicine, Immunology and Allergy, Animals, Cisplatin
Abstract: BackgroundHigh activity of poly(ADP-ribose) polymerase-1 (PARP1) in non-small cell lung cancer (NSCLC) cells leads to an increase in immunohistochemically detectable PAR, correlating with poor prognosis in patients with NSCLC, as well as reduced tumor infiltration by cytotoxic T lymphocytes (CTLs). Intrigued by this observation, we decided to determine whether PARP1 activity in NSCLC cells may cause an alteration of anticancer immunosurveillance.MethodsContinuous culture of mouse NSCLC cells in the presence of cisplatin led to the generation of cisplatin-resistant PARhigh clones. As compared with their parental controls, such PARhigh cells formed tumors that were less infiltrated by CTLs when they were injected into immunocompetent mice, suggesting a causative link between high PARP1 activity and compromised immunosurveillance. To confirm this cause-and-effect relationship, we used CRISPR/Cas9 technology to knock out PARP1 in two PARhigh NSCLC mouse cell lines (Lewis lung cancer [LLC] and tissue culture number one [TC1]), showing that the removal of PARP1 indeed restored cisplatin-induced cell death responses.ResultsPARP1 knockout (PARP1KO) cells became largely resistant to the PARP inhibitor niraparib, meaning that they exhibited less cell death induction, reduced DNA damage response, attenuated metabolic shifts and no induction of PD-L1 and MHC class-I molecules that may affect their immunogenicity. PARhigh tumors implanted in mice responded to niraparib irrespective of the presence or absence of T lymphocytes, suggesting that cancer cell-autonomous effects of niraparib dominate over its possible immunomodulatory action. While PARhigh NSCLC mouse cell lines proliferated similarly in immunocompetent and T cell-deficient mice, PARP1KO cells were strongly affected by the presence of T cells. PARP1KO LLC tumors grew more quickly in immunodeficient than in immunocompetent mice, and PARP1KO TC1 cells could only form tumors in T cell-deficient mice, not in immunocompetent controls. Importantly, as compared with PARhigh controls, the PARP1KO LLC tumors exhibited signs of T cell activation in the immune infiltrate such as higher inducible costimulator (ICOS) expression and lower PD-1 expression on CTLs.ConclusionsThese results prove at the genetic level that PARP1 activity within malignant cells modulates the tumor microenvironment.
Published: 2022

36. A phase transition for the heights of a fragmentation tree.

Author: Adrien Joseph
Published: 2011
Full Text: View/download PDF

37. Convalescent plasma therapy for B-cell–depleted patients with protracted COVID-19

Author: Stanislas Faguer, Pierre Tiberghien, Etienne Crickx, Fanny Pommeret, David Veyer, Claire Rouzaud, Fabrice Camou, Olivier Hermine, Elie Azoulay, Pierre Gallian, Cécile Pouderoux, Deborah Eshagh, Jonathan London, Fatiha Merabet, Philippe Petua, David Boutboul, Laure Anne Raillon, Valérie Zeller, Hélène Péré, Benjamin Planquette, Jérôme Pacanowski, Adrien Joseph, Marc Michel, Martin Martinot, Matthieu Mahévas, Lucienne Chatenoud, Karine Lacombe, Anne Lise Beaumont, David Ghez, Amani Ouedrani, Tali Anne Szwebel, Arsène Mekinian, Florence Ader, Thomas Hueso, Marc Garnier, and Sébastien Clerc
Subjects: 0301 basic medicine, Clinical Trials and Observations, Immunology, Pneumonia, Viral, Context (language use), 030204 cardiovascular system & hematology, Biochemistry, Immunoglobulin G, Serology, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Agammaglobulinemia, medicine, Humans, Adverse effect, Pandemics, COVID-19 Serotherapy, Autoimmune disease, B-Lymphocytes, biology, business.industry, SARS-CoV-2, Brief Report, Bacterial pneumonia, Immunization, Passive, COVID-19, Cell Biology, Hematology, medicine.disease, 3. Good health, Pneumonia, 030104 developmental biology, biology.protein, Antibody, business, Coronavirus Infections
Abstract: There is a Blood Commentary on this article in this issue., Key Points As a proof of concept, COVID-19 convalescent plasma represents an interesting approach in B-cell–depleted patients with protracted COVID-19.COVID-19 convalescent plasma induces a decrease in temperature and inflammatory parameters within 1 week associated with oxygen weaning., Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti–SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2., Visual Abstract
Published: 2020

38. Multifaceted modes of action of the anticancer probiotic Enterococcus hirae

Author: Marion Leduc, Didier Raoult, Laura Mondragón, Kristina Iribarren, Anne-Gaëlle Goubet, Diane Derrien, Satoru Yonekura, Noélie Bossut, Valerio Iebba, Nicola Segata, Guo Chen, Ivo G. Boneca, Lisa Derosa, Adrien Joseph, Fabrice Andre, Sylvère Durand, Aurélie Fluckiger, Maryam Tidjani Alou, Fanny Aprahamian, Richard J. Wheeler, Maryse Moya-Nilges, Eugenie Pizzato, Bo Qu, Guido Kroemer, Oliver Kepp, Nicolas Pons, Romain Daillère, Fabien Lemaitre, Laurence Zitvogel, Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Shanghai Jiao Tong University [Shanghai], Institut Gustave Roussy (IGR), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, UMR 1015 Immunologie des tumeurs et immunothérapie contre le cancer (ITIC), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Trento [Trento], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Karolinska University Hospital [Stockholm], Fondation pour la Recherche Médicale, Ligue contre le Cancer (équipes labellisées), Leducq Foundation, Seerave Foundation, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), SIRIC Cancer Research and Personalized Medicine (CARPEM), Fondation ARC pour la Recherche sur le Cancer, Région Ile-de-France, Chancellerie des universités de Paris (Legs Poix), FRM, European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR), Gustave Roussy Odyssea, Fondation Carrefour, High-end Foreign Expert Program in China: GDW20171100085 and GDW20181100051, Institut National du Cancer (INCA) France, Inserm (HTE), Institut Universitaire de France, ANR-10-COHO-0004,CANTO,Etude des toxicités chroniques des traitements anticancéreux chez les patientes porteuses cancer(2010), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 680969,H2020,H2020-HCO-2015,ERA-CVD(2015), European Project: 825410, H2020-EU.3.1., H2020-EU.3.1.2.,ONCOBIOME (2019), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Ligue Nationale Contre le Cancer (LNCC), Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Goubet, A. -G., Wheeler, R., Fluckiger, A., Qu, B., Lemaitre, F., Iribarren, K., Mondragon, L., Tidjani Alou, M., Pizzato, E., Durand, S., Derosa, L., Aprahamian, F., Bossut, N., Moya-Nilges, M., Derrien, D., Chen, G., Leduc, M., Joseph, A., Pons, N., Le Chatelier, E., Segata, N., Yonekura, S., Iebba, V., Kepp, O., Raoult, D., Andre, F., Kroemer, G., Boneca, I. G., Zitvogel, L., Daillere, R., Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Université Paris Cité (UPC), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), and European Project: 825410,ONCOBIOME
Subjects: 0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], microbiome, law.invention, Probiotic, Mice, 0302 clinical medicine, Cancer immunotherapy, Enterococcus hirae, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neoplasms, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, CD137, 3. Good health, Bifidobacterium animalis, Anti-Bacterial Agents, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, immunotherapy, Immunotherapy, microbiota, cancer, tumor, probiotic, intratumoral IFNγ, Biology, Article, Microbiology, 03 medical and health sciences, Memory T Cells, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Microbiome, Molecular Biology, Probiotics, Autophagy, Cell Biology, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, Mice, Inbred C57BL, 030104 developmental biology, Dysbiosis
Abstract: International audience; A deviated repertoire of the gut microbiome predicts resistance to cancer immunotherapy. Enterococcus hirae compensated cancer-associated dysbiosis in various tumor models. However, the mechanisms by which E. hirae restored the efficacy of cyclophosphamide administered with concomitant antibiotics remain ill defined. Here, we analyzed the multifaceted modes of action of this anticancer probiotic. Firstly, E. hirae elicited emigration of thymocytes and triggered systemic and intratumoral IFN gamma-producing and CD137-expressing effector memory T cell responses. Secondly, E. hirae activated the autophagy machinery in enterocytes and mediated ATG4B-dependent anticancer effects, likely as a consequence of its ability to increase local delivery of polyamines. Thirdly, E. hirae shifted the host microbiome toward a Bifidobacteria-enriched ecosystem. In contrast to the live bacterium, its pasteurized cells or membrane vesicles were devoid of anticancer properties. These pleiotropic functions allow the design of optimal immunotherapies combining E. hirae with CD137 agonistic antibodies, spermidine, or Bifidobacterium animalis. We surmise that immunological, metabolic, epithelial, and microbial modes of action of the live E. hirae cooperate to circumvent primary resistance to therapy.
Published: 2021
Full Text: View/download PDF

39. Shiga Toxin-Associated Hemolytic Uremic Syndrome: Specificities of Adult Patients and Implications for Critical Care Management

Author: Aurélie Cointe, Antoine Dossier, Paul Coppo, Patricia Mariani, Benoit Travert, Cédric Rafat, Adrien Joseph, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and Gestionnaire, Hal Sorbonne Université
Subjects: Adult, medicine.medical_specialty, Pediatrics, Thrombotic microangiopathy, Critical Care, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Disease, Review, Toxicology, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Escherichia coli, Humans, 030212 general & internal medicine, Child, Escherichia coli Infections, 0303 health sciences, biology, Shiga-Toxigenic Escherichia coli, 030306 microbiology, business.industry, Public health, Outbreak, Shiga toxin, medicine.disease, Prognosis, 3. Good health, thrombotic microangiopathy, [SDV] Life Sciences [q-bio], Hemolytic-Uremic Syndrome, biology.protein, hemolytic uremic syndrome, Medicine, Bloody diarrhea, Presentation (obstetrics), business
Abstract: International audience; Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a form of thrombotic microangiopathy secondary to an infection by an enterohemorrhagic E. coli. Historically considered a pediatric disease, its presentation has been described as typical, with bloody diarrhea at the forefront. However, in adults, the clinical presentation is more diverse and makes the early diagnosis hazardous. In this review, we review the epidemiology, most important outbreaks, physiopathology, clinical presentation and prognosis of STEC-HUS, focusing on the differential features between pediatric and adult disease. We show that the clinical presentation of STEC-HUS in adults is far from typical and marked by the prevalence of neurological symptoms and a poorer prognosis. Of note, we highlight knowledge gaps and the need for studies dedicated to adult patients. The differences between pediatric and adult patients have implications for the treatment of this disease, which remains a public health threat and lack a specific treatment.
Published: 2021
Full Text: View/download PDF

40. Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index

Author: Hui Chen, Fabrice Andre, Gerasimos Anagnostopoulos, Frédéric Fumeron, Isabelle Martins, Antoine Lafarge, François Goldwasser, Franziska Grundler, Frank Madeo, Maria Castedo, Benoit Blanchet, Safae Terrisse, Ines Vaz-Luis, Adrien Joseph, Omar Motiño, Françoise Wilhelmi de Toledo, Ronan Roussel, Laurence Zitvogel, Karine Clément, Anne Laure Martin, Maria Chiara Maiuri, Léa Montégut, Guido Kroemer, HAL-SU, Gestionnaire, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Gustave Roussy (IGR), Université Paris-Saclay, Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UNICANCER, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Direction de la recherche [Gustave Roussy], Buchinger Wilhelmi Clinic, Karl-Franzens-Universität Graz, Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of Chinese Academy of Sciences [Beijing] (UCAS), Karolinska University Hospital [Stockholm], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Karl-Franzens-Universität [Graz, Autriche], Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and University of Graz
Subjects: Male, Cancer Research, medicine.medical_specialty, Immunology, Adipose tissue, Context (language use), Article, Body Mass Index, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, 0302 clinical medicine, Overnutrition, Internal medicine, Germany, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, 030304 developmental biology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, Diazepam Binding Inhibitor, Mice, Knockout, 0303 health sciences, QH573-671, Chemistry, Binding protein, Body Weight, Diagnostic markers, Cell Biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Mice, Inbred C57BL, Endocrinology, Female, France, medicine.symptom, Cytology, Body mass index, Diazepam binding inhibitor, Weight gain, 030217 neurology & neurosurgery, Homeostasis
Abstract: In mice, the plasma concentrations of the appetite-stimulatory and autophagy-inhibitory factor acyl-coenzyme A binding protein (ACBP, also called diazepam-binding inhibitor, DBI) acutely increase in response to starvation, but also do so upon chronic overnutrition leading to obesity. Here, we show that knockout of Acbp/Dbi in adipose tissue is sufficient to prevent high-fat diet-induced weight gain in mice. We investigated ACBP/DBI plasma concentrations in several patient cohorts to discover a similar dual pattern of regulation. In relatively healthy subjects, ACBP/DBI concentrations independently correlated with body mass index (BMI) and age. The association between ACBP/DBI and BMI was lost in subjects that underwent major weight gain in the subsequent 3–9 years, as well as in advanced cancer patients. Voluntary fasting, undernutrition in the context of advanced cancer, as well as chemotherapy were associated with an increase in circulating ACBP/DBI levels. Altogether, these results support the conclusion that ACBP/DBI may play an important role in body mass homeostasis as well as in its failure.
Published: 2021
Full Text: View/download PDF

41. 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: Mathieu Vautier, Florence Tubach, Marion Licois, Estelle Henry, Marie-Alexandra Alyanakian, Julien Poissy, Solaya Chalal, Anne Gysembergh-Houal, Stéphanie Alary, Sophie Diemunsch, Jonathan London, Camille Petit-Hoang, Ruben Benainous, Catherine Metzger, Olivier Benveniste, Hala Semri, Charléne Jouve, Robin Dhote, johann Cailhol, Elise Morawiec, Kristina Beziriganyan, Mathieu Oberlin, Paul Legendre, Hélène François, Claire Davoine, F Louni, Myriam Virlouvet, Stéphane Renaud, Christiane Verny, Bertrand Guidet, Bob Heger, Lara Zafrani, Pierre-Louis Tharaux, Mandy Nizard, Adrien Contejean, Segolene Toquet, Ulrich Clarac, Sylviane Ravato, Gaëtan Deslée, Frédéric De Blay, Christian Richard, Raphaël Porcher, Malikhone Chansombat, Marie Lachatre, Ines Ben-Mabrouk, Matthieu Uzzan, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Fanny Charbonnier, Pierre-Grégoire Guinot, Alexandre Demoule, Nicolas Champtiaux, Nicolas Belaube, Jean-Pierre Riveline, Kamil Chitour, Joseph Emmerich, Arthur Neuschwander, Mickael Henriques, Anne Hutt, Arthur Pavot, Anne Rachline, Elena Fois, Audrey Phibel, Xavier Monnet, Jean-Charles Duclos-Vallée, Félix Ackermann, Maria Pereira, Anne Sophie Korganow, Elodie Drouet, Tabassome Simon, Morgane Faure, Anne Pattyn, Aida Zahrate-Ghoul, Karine Martin, Jean-Jacques Tudesq, Gladys Aratus, Kévin Cardet, Julien Pottecher, Eric Demonsant, Arsène Mekinian, Rémy Gauzit, Julie Smati, Robin Deleris, Jean-Simon Rech, Boris Bienvenu, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Alexis Régent, François Weill, Lalia Djaghout, Anne Tréhan, Isabelle Lehir, Elena Kiouris, Sophie Renet, Yasmina Mekid, Vanessa Rathouin, David Montani, Annick Tibi, Anne Blanchard, Fanette Denies, Nathalie Menage, Guillaume Becker, Valérie Camara-Clayette, Loic Kassegne, Nathalie Chavarot, Aurélie Clan Hew Wai, Jeremy Arzoine, Louise Bondeelle, Mohamad Zaidan, S Lariven, Laurent Cylly, Edouard Flamarion, Chaouki Bouras, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Marie hélène Pari, Lionel Galicier, Valérie Dejean, Delphine Feyeux, Naima Sguiouar, Anne Bergeron, Laurence Annonay, Anouk Walter-Petrich, Camille Knosp, Laurence Drouard, Thiziri Sadaoui, Julie Delemazure, Antoine Parrot, Carole Burger, Laurence Berard, Nicolas Gambier, Eric Marquis, Isabelle Madeleine, Gwenaël Lorillon, Matthieu Resche-Rigon, Yves Hansmann, Claire Rouzaud, Hélène Gros, Sophie Caillat-Zucman, Bernard Cholley, Celine Wilpotte, Chistophe Willekens, Lydia Suarez, Syllia Belazouz, Valérie Pourchet-Martinez, Dhiaa Meriem Hai, Olivier Collange, Paul Jaubert, Marie-Thérèse Tremorin, Nathalie Marin, Diane Le Pluart, Madona Sakkal, Juliette Djadi-Prat, Alexandre Morel, Agathe Bounhiol, Xavier Jaïs, Nicolas Meyer, Vixra Keo, Michaël Darmont, Benedicte Giroux-Leprieur, Anatole Harrois, Anne Adda, Yaël Amara, Fanny Pommeret, Antony Canellas, Matheus Vieira, Clotilde Le Tiec Le Tiec, Corinne Pernot, Bernard Goichot, Céline Louapre, Roza Rahli, Anne Jacolot, Anne Daguenel-Nguyen, Marie Dubert, Anaïs Razurel, Aurelie Sautereau, Mitja Jevnikar, Pierre Faye, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Florence Patin, Kahina Cheref, Mélanie Dehais, Paul Michel Mertes, Caroline Morbieu, Valérie Paquet, Dominique Roulot, Giovanna Melica, Pauline Jouany, Frédéric Schlemmer, Blandine Lehmann, Pascal Martel, Tomas Urbina, Yazdan Yazdanpanah, Veronique Joly, Damien Bergerot, Claire Courtin, Benjamin Fournier, Guillaume Grailles, Asmaa Mamoune, Caroline Gaudefroy, Charlotte Kaeuffer, Bruno Crestani, Thinhinane Bariz, C Rioux, Karine Celli Lebras, Sophie Granville, Marion Bouhris, Hugues Cordel, Jean-Marie Michot, Mohamed Belloul, Nadège Lemarié, Philippe Dieudé, Sylvie Le Gac, Matthieu Mahévas, Pascal Richette, Anaïs Codorniu, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Vincent Castelain, Aude Rigolet, Valentin Greigert, Gaelle Leroux, Simon Valayer, Eliane Bertrand, Eric Vicaut, Stéphane Brin, Jacques-Eric Gottenberg, Olivier Clovet, Marc Bardou, Muriel Fartoukh, Valentina Isernia, Ada Clarke, Bao Phung, Grégoire Martin de Frémont, Jeanne Meunier, Gonçalo Boleto, David Lebeaux, Hassan Tarhini, Asmaa Mabrouki, Pascaline Choinier, Etienne Canouï, Eric D'Ortenzio, Constance Guillaud, Corine Nyanou, Alexandre Moores, Linda Gimeno, Victoire De Lastours, F-Xavier Lescure, Claire Montlahuc, Sophie Georgin-Lavialle, A Soria, Xavier Mariette, Sophie Ismael, Prissile Bakouboula, Olivier Lambotte, Jérémie Zerbit, Aude Jacob, Z Julia, Nathalie Dournon, Marthe Rigal, Mireille Adda, Nathan Ebstein, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Hélène Lafoeste, Coralie Bloch Queyrat, Sabrina Brahmi, Catherine Le Bourlout, Nicolas Noel, Emmanuelle Guillot, Hakim Tayebi, Sandrine Briois, Anne-Lise Pouliquen, Lakhdar Mameri, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Lelia Escaut, Clément Jourdaine, Cédric Pierron, Marc Garnier, Yves Cohen, Abdellatif Tazi, Maxence Decavele, Paul Henri Grisot, Patrice Cacoub, Laure Allanic, Amira Benattia, Martin Siguier, Luca Semerano, Jean-Sébastien Hulot, Jean-Jacques Mourad, Sara Sambin, Miguel Alejandro Vasquez-Ibarra, Nabil Raked, Christine Lemagner, Martin Dres, Clara Campos-Vega, Tali-Anne Szwebel, Benjamin Chaigne, Emmanuel Andrès, Gabriel Steg, Frédéric Blanc, Isabelle Peigney, Catherine Fauvaux, Côme Bureau, Samira Saleh-Mghir, Julie Jambon, Pierre Dupland, Anne Lise Jegu, Mamadou Salif Cisse, Damien Roux, Moez Jallouli, Philippe Blanche, Sébastien Cavelot, Sophie Ohlmann-Caillard, Louise-Laure Mariani, Adrien Michon, Alain Wynckel, Saskia Flamand, Safaa Nemlaghi, Benjamin G. Chousterman, Geoffroy Volle, Cécile Kedzia, Fanny Domont, Lee S. Nguyen, Férial Berbour, Pierre Diemunsch, Celine Dupré, Etienne Lengliné, Claire Tantet, Gaël Leprun, Sara Virolle, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Mathilde Le Marchand, Vincent Poindron, Victor Lancon, Ruxandra Burlacu, Guillaume Lefèvre, Kamyl Baghli, Emilia Stan, Yann Nguyen, Olivier Sanchez, Olivier Sitbon, Loren Soyez-Herkert, Fanny Defrancq, Véronique Vigna, Aurélien Guffroy, Martine Meunier, Pierre Mora, Léa Resmini, Liem Binh Luong Nguyen, Jean-Luc Diehl, Johanna Oziel, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Marie Matignon, Mourad Djadel, Yasmine Messaoudi, Hassan Joumaa, Isabelle Dusanter, Sarah Benghanem, Julien Mayaux, Marc Michel, Claire Pernin, Antoine Gros, Nassim Mahtal, Philippe Benoit, Cloé Comarmond, Laurence Lecomte, Patricia Senet, Sebastien Abad, Jérôme Pacanowski, Céline Leplay, Claire Aguilar, Cédric Sublon, Jesuthasan Denis, Régis Peffault de Latour, Gabrielle Archer, Alain Fourreau, Emmanuelle Blin, Lise Bernard, Alexandra Beurton, Alexandre Buffet, Pierre Le Guen, Clairelyne Dupin, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Alexandre Bourgoin, Agnes Maurer, Eric Noll, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Carine Karachi, Samy Figueiredo, Hakim Meddah, Greggory Ducrocq, Jeanne Goupil de Bouille, Awa Ndiaye, Jessica Krause le Garrec, Maxime Dougados, Yasmina Ferfar, Damien Vimpere, Olivier Olivier, Annabelle Stoclin, Jean-Louis Teboul, Ridha Belilita, Serge Bureau, Naura Gamany, Emeline Colomba, Baptiste Duceau, Philippe Ravaud, Corinne Guerin, Florence Morin, Pélagie Thibaut, Younes Keroumi, Julie Chas, Elisabeth Coupez, Laetitia Languille, Mathias Cornic, Jean-Michel Molina, Caroline Pradon, Alison Klasen, Zakaria Ait Hamou, Armand Mekontso-Dessaps, Yurdagul Uzunhan, Samir Hamiria, Anne Godier, Elsa Feredj, Nessima Yelles, Jean-Benoit Arlet, Christine Broissand, Belkacem Asselate, Jaouad Benhida, Julien Le Marec, Nawal Derridj, Laurène Deconinck, A. Dossier, Eric Oksenhendler, Eva Chatron, Lucie Aunay, Candice Estellat, Julie Fillon, Marie Antignac, Jade Ghosn, Ilias Koumis, David Schmitz, Domitille Molinari, Soraya Fellahi, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Vincent Provitolo, Marie Lecronier, Dimitri Fremont, Pierrick Le Borgne, Emmanuel Weiss, Faouzi Saliba, Stéphan Pavy, Geoffrey Rossi, Chloe McAvoy, Eric Mariotte, Dorothee Vallois, Sabrine Ouamri, Pierre Tissieres, Luc Mouthon, Blandine Denis, Celine Comparon, Emmanuelle Sacco, Frédéric Pène, Marjolaine Morgand, Vasco Honsel, Laure Choupeaux, Bruno Mourvillier, Ewa Kozaliewicz, Marie-Hélène Legros, Isabelle Debrix, Gabriel Nisand, Julien Chabert, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Marine Livrozet, Lucie Biard, Elodie Perrodeau, Brigitte Sabatier, Raphael Borie, Rosa Da Silva, Nathalie Costedoat-Chalumeau, Emmanuel Chatelus, Jean-Christophe Corvol, Nathalie De Castro, David Boutboul, Benjamin Planquette, Anne Claire Desbois, François Danion, Brigitte Ranque, Amélie Cransac, Marine Nadal, Coralie Gernez, Yacine Boudali, Claire Madelaine, Georgina Maalouf, Jonathan Marey, Sophie Bayer, Antoine Fayol, Souad Benarab, Luc Haudebourg, Sophie Bulifon, Claire Pacheco, Philippe Durand, Olivier Hermine, Fanny Alby-Laurent, Geoffroy Liégeon, Axelle Fuentes, Jean-Daniel Lelievre, Gilles Garcia, Céline Verstuyft Verstuyft, Marie-Aude Penet, Constance Delaugerre, Nicolas Carlier, Aurélie Durel Maurisse, Gilles Pialoux, Zeina Louis, Marion Parisey, Pascal Lim, Gaelle Clavere, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Adrien Joseph, Hilario Nunes, Hanane Fodil, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Isabelle Brindele, Robin Charreteur, Elie Azoulay, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Marie Gilbert, Matthieu Lemoine, Abolfazl Mohebbi, Mathilde Noaillon, Amina Kebir, Virginie Zarrouk, Cécile Yelnik, Benjamin Terrier, Solène Fabre, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Oriane Puéchal, Pernelle Vauboin, Caroline Hauw-Berlemont, Gabriel Baron, Paul Vermes, Yvon Ruch, Dominique Dautel, Tassadit Hadjam, Anne-Marie Roques, Jean-Philippe Bastard, Younes El Amine, Damien Sène, Alaki Thiemele, Catherine Boussard, Vincent Fallet, Timothee Bironne, Damien Vanhoye, Guillaume Geri, Amine Ghembaza, Bertrand Dunogue, Nadia Anguel, Laure Berton, Caroline Semaille, Thomas Volpe, Jacques Cadranel, Thomas Gorget, Julien Saussereau, Elodie Issorat, Sami Kolta, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Porcher, Raphaël
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Hazard ratio, Articles, Middle Aged, Intensive care unit, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Treatment Outcome, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, Critical Care Outcomes, Aged, Mechanical ventilation, Anakinra, SARS-CoV-2, business.industry, Comment, COVID-19, Bayes Theorem, Pneumonia, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Interleukin 1 Receptor Antagonist Protein, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Interleukin-1
Abstract: International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.
Published: 2021
Full Text: View/download PDF

42. Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit

Author: Antoine Vieillard-Baron, Jean-Marie Michot, Stéphane Oudard, Elie Azoulay, Virginie Lemiale, Olivier Lambotte, Adrien Joseph, Guillaume Geri, Audrey Simonaggio, Annabelle Stoclin, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Gustave Roussy (IGR), Service de Réanimation Médicale, Hôpital Saint Louis, Paris, France, Université Paris-Saclay, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Paris (UP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Oncology, Adverse event, medicine.medical_specialty, Immune checkpoint inhibitor, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Immune-related adverse events, Intensive care, Anesthesiology, Internal medicine, medicine, Adverse effect, 030304 developmental biology, Pneumonitis, Cancer, Outcome, Hepatitis, 0303 health sciences, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, medicine.disease, Intensive care unit, 3. Good health, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, business, Meningitis
Abstract: Background Immune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown. This retrospective multicentric study aims to describe the characteristics of patients admitted to the intensive care units of 4 academic hospitals in Paris area while receiving immune checkpoint inhibitor treatment between January 2013 and October 2019. Results Over the study period, 112 cancer patients who received immune checkpoint inhibitors were admitted to the intensive care unit within 60 days after the last dose. ICU admission was related to immune-related adverse events (n = 29, 26%), other intercurrent events (n = 39, 35%), or complications related to tumor progression (n = 44, 39%). Immune-related adverse events were pneumonitis (n = 8), colitis (n = 4), myocarditis (n = 3), metabolic disorders related to diabetes (n = 3), hypophysitis (n = 2), nephritis (n = 2), meningitis or encephalitis (n = 2), hepatitis (n = 2), anaphylaxis (n = 2) and pericarditis (n = 1). Primary tumors were mostly melanomas (n = 14, 48%), non-small-cell lung cancers (n = 7, 24%), and urothelial carcinomas (n = 5, 17%). Diagnosis of melanoma and a neutrophil/lymphocyte ratio n = 7), mechanical ventilation (n = 6), and extra-corporeal membrane oxygenation (n = 2). One-year survival was significantly higher for patients admitted for irAE compared to patients admitted for other reasons (p = 0.004). Conclusions Admission to the intensive care unit related to immune-related adverse event was associated with better outcome in cancer patients treated with immune checkpoint inhibitors. Our results support the admission for an intensive care unit trial for patients with suspected immune-related adverse events.
Published: 2020
Full Text: View/download PDF

43. Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI)

Author: Frank Bellivier, Christine Passerieux, Julien Dubreucq, Isabelle Martins, Antoine Lafarge, Pierre-Michel Llorca, Delphine Capdevielle, Ludovic Samalin, Caroline Dubertret, Franck Oury, Valentina Sica, Stéphanie Moriceau, Fabrice Berna, Raymond Schwan, Guido Kroemer, Face-Sz, Christophe Magnan, Sébastien Gard, José Manuel Bravo-San Pedro, Marion Leboyer, Paul Roux, Bruno Etain, Emilie Olié, Jasmina Mallet, David Misdrahi, Raoul Belzeaux, Maria Chiara Maiuri, Adrien Joseph, Jonathan Pol, Philippe Courtet, Guillaume Fond, Franck Schürhoff, D' Amato Thierry, Joséphine Loftus, Gerasimos Anagnostopoulos, Mircea Polosan, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Gustave Roussy (IGR), Université Paris-Saclay, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Fondation FondaMental [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lapeyronie [Montpellier] (CHU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Charles Perrens, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Psychothérapique de Nancy (CPN), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Service de Biologie [Hôpital Européen Georges Pompidou, APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Karolinska University Hospital [Stockholm], Association pour la Recherche sur le Cancer, ARC ANR-18-IDEX-0001 Ligue Contre le Cancer Chancellerie des UniversitÃ©s de Paris Fondation pour la Recherche MÃ©dicale, FRM Agence Nationale de la Recherche, ANR: UMS3655 Institut National Du Cancer, INCa Institut Universitaire de France, IUF Fondation Leducq Association pour la Recherche sur le Cancer, ARC GDW20171100085, The authors thank Maxime Perez for establishing contacts among dispersed investigators. The authors thank the CRC Core Facilities for the technical support. G.K. is supported by the Ligue contre le Cancer (équipe labellisée), Agence National de la Recherche (ANR)—Projets blancs, ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, AMMICa US23/CNRS UMS3655, Association pour la recherche sur le cancer (ARC), Association 'Le Cancer du Sein, Parlons-en!', Cancéropôle Ile-de-France, Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM), a donation by Elior, European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR), Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome, Fondation Carrefour, High-end Foreign Expert Program in China (GDW20171100085), Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno-Oncology (ANR-18-IDEX-0001), the RHU Torino Lumière, the Seerave Foundation, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), and the SIRIC Cancer Research and Personalized Medicine (CARPEM). J.M.B-S.P. is supported by a Ramon y Cajal contract funded by the Spanish Government., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Joseph, A., Moriceau, S., Sica, V., Anagnostopoulos, G., Pol, J., Martins, I., Lafarge, A., Maiuri, M. C., Leboyer, M., Loftus, J., Bellivier, F., Belzeaux, R., Berna, F., Etain, B., Capdevielle, D., Courtet, P., Dubertret, C., Dubreucq, J., Thierry, D. A., Fond, G., Gard, S., Llorca, P. -M., Mallet, J., Misdrahi, D., Olie, E., Passerieux, C., Polosan, M., Roux, P., Samalin, L., Schurhoff, F., Schwan, R., Magnan, C., Oury, F., Bravo-San Pedro, J. M., Kroemer, G., Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), École Pratique des Hautes Études (EPHE), CHU Henri Mondor [Créteil], Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], and Centre Psychothérapique de Nancy [Laxou] (CPN)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Immunology, Appetite, Article, Body Mass Index, Immobilization, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Orexigenic, medicine, Extracellular, Animals, lcsh:QH573-671, Psychiatry, Receptor, Swimming, Diazepam Binding Inhibitor, Metabolic Syndrome, 2. Zero hunger, Behavior, Animal, biology, lcsh:Cytology, Chemistry, Mental Disorders, Binding protein, Endocrine system and metabolic diseases, Feeding Behavior, Cell Biology, Darkness, Receptors, GABA-A, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, biology.protein, Antibody, Psychiatric disorders, Diazepam binding inhibitor, 030217 neurology & neurosurgery, Intracellular, Behavioural despair test, medicine.drug
Abstract: Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABAAR). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.
Published: 2020
Full Text: View/download PDF

44. Corrigendum to: Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group

Author: Antoine, Lafarge, Adrien, Joseph, Christian, Pagnoux, Xavier, Puéchal, Pascal, Cohen, Maxime, Samson, Mohamed, Hamidou, Alexandre, Karras, Thomas, Quemeneur, Camillo, Ribi, Matthieu, Groh, Luc, Mouthon, Loïc, Guillevin, and Benjamin, Terrier
Subjects: Rheumatology, Pharmacology (medical)
Published: 2020

45. Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

Author: Alexandre Hertig, Aurélie Cointe, Cédric Rafat, Adrien Joseph, Patricia Mariani Kurkdjian, Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Robert Debré, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Bacterial Zoonoses, Thrombotic microangiopathy, escherichia coli, Health, Toxicology and Mutagenesis, lcsh:Medicine, Virulence, Review, Toxicology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Escherichia coli, Animals, Humans, Effective treatment, Escherichia coli Infections, 030304 developmental biology, Hydration status, 0303 health sciences, Shiga-Toxigenic Escherichia coli, biology, 030306 microbiology, business.industry, lcsh:R, Outbreak, Shiga toxin, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, thrombotic microangiopathy, Bacterial virulence, Hemolytic-Uremic Syndrome, Immunology, biology.protein, hemolytic uremic syndrome, Narrative review, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure. Key Contribution: We review here the current understanding of the mechanisms of virulence of Shiga toxin-producing Escherichia coli; in particular how infection can lead to thrombotic microangiopathy and acute kidney injury. A modern procedure for differential diagnosis is also provided.
Published: 2020
Full Text: View/download PDF

46. Early Differentiation of Shiga Toxin–Associated Hemolytic Uremic Syndrome in Critically Ill Adults With Thrombotic Microangiopathy Syndromes

Author: Lara Zafrani, Agnès Veyradier, Eric Mariotte, Cédric Rafat, Adrien Joseph, Alexandre Hertig, Elie Azoulay, Eric Rondeau, and Patricia Mariani-Kurkdjian
Subjects: Adult, Male, medicine.medical_specialty, Thrombotic microangiopathy, Anemia, Critical Illness, medicine.medical_treatment, Thrombotic thrombocytopenic purpura, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Gastroenterology, Shiga Toxin, Cohort Studies, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Atypical hemolytic uremic syndrome, medicine, Humans, 030212 general & internal medicine, Renal replacement therapy, Aged, Atypical Hemolytic Uremic Syndrome, Retrospective Studies, Purpura, Thrombotic Thrombocytopenic, Shiga-Toxigenic Escherichia coli, biology, Thrombotic Microangiopathies, business.industry, Shiga toxin, Syndrome, Middle Aged, medicine.disease, Diarrhea, Early Diagnosis, Hemolytic-Uremic Syndrome, biology.protein, Female, medicine.symptom, business
Abstract: OBJECTIVES Thrombotic microangiopathy syndromes are a heterogeneous group of severe diseases that often require ICU admission. Prompt initiation of targeted therapies is required for atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, whereas there is no specific consensus therapy for Shiga toxin-associated hemolytic uremic syndrome. We sought to compare the characteristics of Shiga toxin-associated hemolytic uremic syndrome, atypical hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura patients at admission in the ICU to allow early differentiation of Shiga toxin-associated hemolytic uremic syndrome from other thrombotic microangiopathy syndromes and help to tailor initial treatment. DESIGN Retrospective cohort study. SETTING Two ICUs part of the French reference center for thrombotic microangiopathy syndromes. PATIENTS Adult patients presenting with features of thrombotic microangiopathy syndromes. Other causes than Shiga toxin-associated hemolytic uremic syndrome, atypical hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura were excluded. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS From September 2003 to January 2017, 236 thrombotic microangiopathy syndrome patients were admitted, including 12 Shiga toxin-associated hemolytic uremic syndrome, 21 atypical hemolytic uremic syndrome, and 91 thrombotic thrombocytopenic purpura. Shiga toxin-associated hemolytic uremic syndrome patients were older than other thrombotic microangiopathy syndromes patients (64 yr [interquartile range, 50-72 yr] vs 42 yr [31-54 yr]; p = 0.007) and presented with more frequent digestive symptoms (92% vs 42%; p < 0.001), especially nonbloody diarrhea and vomiting. Biologically, Shiga toxin-associated hemolytic uremic syndrome patients displayed higher fibrinogen (490 mg/dL [460-540 mg/dL] vs 320 mg/dL [240-410 mg/dL]; p = 0.003) and creatinine levels (2.59 mg/dL [2.12-3.42 mg/dL] vs 1.26 mg/dL [0.61-1.90 mg/dL]; p < 0.001), and less marked anemia (hemoglobin level, 9.7 g/dL [8.7-11.9 g/dL] vs 7.7 g/dL [6.3-9.1 g/dL]; p < 0.001). Forty-two percent (n = 5) required renal replacement therapy, and 83% (n = 10) were treated with plasma exchange before the distinction from other thrombotic microangiopathy syndromes could be made. CONCLUSIONS Adult Shiga toxin-associated hemolytic uremic syndrome patients are older, present more frequently with digestive symptoms and display higher hemoglobin and fibrinogen levels than other thrombotic microangiopathy syndromes. However, overlap across the three thrombotic microangiopathy syndromes remains substantial, putting forward the need to implement early plasma therapy until thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome can be ruled out.
Published: 2018
Full Text: View/download PDF

47. External validation and comparison of formulae estimating 24-h sodium intake from a fasting morning urine sample

Author: Emmanuelle Vidal-Petiot, Anne Boutten, Martin Flamant, Jimmy Mullaert, Adrien Joseph, Matthieu Resche-Rigon, François Vrtovsnik, Marie-Pia d’ Ortho, and Ph. Gabriel Steg
Subjects: Adult, Male, medicine.medical_specialty, Physiology, Population, Urology, Renal function, Blood Pressure, Urine, 030204 cardiovascular system & hematology, Urine sodium, Urine collection device, Excretion, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, education, Aged, Urine Specimen Collection, Morning, education.field_of_study, business.industry, Sodium, Sodium, Dietary, Fasting, Mathematical Concepts, Middle Aged, Confidence interval, Endocrinology, Creatinine, Female, Cardiology and Cardiovascular Medicine, business
Abstract: OBJECTIVE The relationship between sodium intake and cardiovascular events is controversial, but most large epidemiological studies estimated sodium intake using formulae based on single urine samples, the validity of which is debated. We evaluated sodium intake estimating formulae in a large cohort of adult patients. DESIGN AND METHODS Patients were asked to collect 24-h urine the day before admission. Validity of the 24-h urine collection was assessed by comparing creatinine clearance from this collection to the mean creatinine clearance from six fractionated urine samples. Only collections with creatinine clearance within ±15% of fractionated clearance were considered valid. The Kawasaki, INTERSALT and Tanaka formulae, using a morning fasting urine sample obtained upon admission, were compared with 24-h urine sodium excretion. The relationship between sodium intake, either measured or estimated, and blood pressure was assessed. RESULTS Amongst 2278 patients referred to our physiology department between September 2006 and August 2016, 1018 had complete 24-h urine collections and were included in this analysis. Mean age was 51 ± 14 years and mean sodium excretion was 3624 ± 1614 mg/day. The intraclass correlation coefficient was higher for the Kawasaki (0.54; 95% confidence interval, 0.48-0.60), than for the INTERSALT (0.38; 0.33-0.42, P
Published: 2018
Full Text: View/download PDF

48. Risk of malignancy in patients treated for systemic necrotising vasculitis

Author: Antoine Lafarge, Mohamed Hamidou, Matthieu Groh, Pacal Cohen, Alexandre Karras, Christian Pagnoux, Camillo Ribi, Xavier Puéchal, Benjamin Terrier, Luc Mouthon, Thomas Quemeneur, Loïc Guillevin, Maxime Samson, and Adrien Joseph
Subjects: 0301 basic medicine, medicine.medical_specialty, Cyclophosphamide, Immunology, Population, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Clinical endpoint, Immunology and Allergy, education, Necrotising vasculitis, 030203 arthritis & rheumatology, education.field_of_study, Cumulative dose, business.industry, Cancer, medicine.disease, 030104 developmental biology, Rituximab, Vasculitis, business, medicine.drug
Abstract: Reduction in cyclophosphamide cumulative dose and introduction of newer immunosuppressive drugs may reduce the malignant burden of systemic necrotising vasculitis (SNV).1 2 This study aimed to describe malignancies recorded in five randomised controlled trials in SNV conducted by the French Vasculitis Study Group and to identify predictive factors. CHUSPAN, CHUSPAN 2, WEGENT, CORTAGE and MAINRITSAN trials evaluated different therapeutic strategies, summarised in online supplementary table S1, for the treatment of newly diagnosed or relapsing SNV. Informations regarding methods and references are provided in the online supplementary materials. The primary endpoint was the occurrence of malignancy.### Supplementary data [annrheumdis-2019-216452supp001.pdf] A total of 733 patients included between 1993 and 2012 were pooled. Baseline characteristics of the population are summarised in table 1. During a 4485.9 person-years (PY) observation period, 39 (5.3%) patients developed malignancies (869.5 per 100 000 PY), including solid cancers in 34 (4.6%) cases (757.9 per 100000 PY) and haematological malignancies in 5 …
Published: 2019
Full Text: View/download PDF

49. Renal recovery after severe acute kidney injury in critically ill myeloma patients: a retrospective study

Author: Claire Pichereau, Adrien Joseph, Lara Zafrani, Eric Mariotte, Emmanuel Canet, Elie Azoulay, Sandrine Valade, Marion Venot, Akli Chermak, and Stephanie Harel
Subjects: medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, urologic and male genital diseases, law.invention, 03 medical and health sciences, AKI, 0302 clinical medicine, law, Intensive care, Internal medicine, medicine, Renal replacement therapy, Intensive care medicine, Dialysis, Transplantation, Univariate analysis, business.industry, Acute kidney injury, medicine.disease, Intensive care unit, Nephrology, SOFA score, business
Abstract: Background Despite substantial improvements in the management of multiple myeloma, renal failure remains an important burden that tremendously impairs prognosis. The purpose of this study was to describe the characteristics and to establish prognostic factors of renal recovery in myeloma patients admitted to the intensive care unit (ICU) for acute kidney injury (AKI) Stage 3 treated with renal replacement therapy (RRT). Methods A retrospective single-centre cohort study was performed, including consecutive myeloma patients admitted to one medical ICU between 1 January 2007 and 1 September 2015 and treated with RRT. Patients were evaluated 60 days after initiation of RRT and divided into three groups: alive without dialysis, alive and dialysis-dependent or deceased. A univariate analysis was performed to identify factors associated with renal recovery (alive without dialysis 60 days after initiation of RRT). Results Fifty patients were included in the study. Mean age was 63 (interquartile range: 58-70) years and 32 (64%) were male. Patients were admitted to the ICU 4 (1-7) years after the diagnosis of myeloma. Twenty-one (42%) had already been treated with high-dose therapy combined with autologous stem cell transplantation. Baseline renal function evaluated by estimated glomerular filtration rate (GFR) before ICU admission was 63 (44-90) mL/min/1.73 m2. The mean SOFA score at Day 1 was 7 (4-8). The three main reasons for ICU admission were AKI (n = 31, 62%), acute pulmonary oedema (n = 17, 32%) and sepsis (n = 10, 20%). During ICU stay, RRT was implemented in all patients, 16 (32%) patients required invasive mechanical ventilation and 12 (24%) received vasopressors. The mean ICU and hospital length of stay were 6 (1-7) and 28 (13-34) days, respectively. At Day 60, 23 (46%) patients were alive without dialysis, 17 (32%) had died and 10 (20%) were still undergoing dialysis. Among the 23 patients who recovered, the mean duration of dialysis was 6 (2-18) days and renal function was not significantly different from baseline [estimated GFR at baseline = 65 (25-74) mL/min/1.73 m2 versus 63 (56-70) mL/min/1.73 m2 at Day 60, P = 0.70]. By univariate analysis, two factors were associated with nonrecovery of renal function at Day 60: a history of high-dose therapy combined with autologous stem cell transplantation [odds ratio (OR) = 6.1, 95% confidence interval (CI) 1.7-21.6; P = 0.008] and a proteinuria at ICU admission >370 mg/mmol creatinine (OR = 4.2, 95% CI 1.1-17; P = 0.02). None of the other variables related to the haematological malignancy or to the ICU stay was associated with renal recovery at Day 60. Conclusions AKI Stage 3 in critically ill myeloma patients was associated with a lower than expected hospital mortality. Patients with a high level of proteinuria and a history of high-dose therapy combined with autologous stem cell transplantation were less likely to recover their renal function at Day 60. Key words dialysis, intensive care, multiple myeloma, prognosis, proteinuria.
Published: 2017
Full Text: View/download PDF

50. Syndrome de Fanconi lié au Tenofovir et récupération à l’arrêt du traitement : considérations physiologiques à propos d’un cas

Author: Martin Flamant, Adrien Joseph, Emmanuelle Vidal-Petiot, and Yazdan Yazdanpanah
Subjects: 0301 basic medicine, Gynecology, medicine.medical_specialty, Withholding Treatment, Tenofovir, business.industry, Fanconi syndrome, General Medicine, medicine.disease, 03 medical and health sciences, Remission induction, 030104 developmental biology, 0302 clinical medicine, medicine, 030212 general & internal medicine, business, medicine.drug
Abstract: La Presse Medicale - In Press.Proof corrected by the author Available online since mercredi 4 janvier 2017
Published: 2017
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

126 results on '"Adrien Joseph"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources