473 results on '"Hôpital St-Antoine"'
Search Results
2. ADA3-containing complexes associate with estrogen receptor alpha.
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Benecke, Arndt, Gaudon, Claudine, Garnier, Jean-Marie, vom Baur, Elmar, ChambonTo whom correspondence should be addressed. Tel: +33 3 88 65 32 13; Fax: +33 3 88 65 32 03; Email: chambon@igbmc.u-strasbg.fr Present address:Arndt Benecke, INSERM U417, Hôpital St Antoine, 75571 Paris Cedex 12, France, Pierre, and Losson, Régine
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- 2002
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3. Echinocandins Susceptibility Patterns of 2,787 Yeast Isolates: Importance of the Thresholds for the Detection of FKS Mutations
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Desnos-Ollivier, Marie, Bretagne, Stéphane, Lortholary, Olivier, Dromer, Françoise, French Mycoses Study Group, The, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This work was supported by Santé Publique France and Institut Pasteur., Members of the French Mycoses Study Group who contributed to the data are, in alphabetical order of the cities, all the French microbiologists and mycologists who sent isolates for characterization of unusual antifungal susceptibility profiles or to contribute to the ongoing surveillance program on the epidemiology of invasive fungal infections in France (YEASTS and RESSIF programs): N. Brieu (CH Aix), T. Chouaki, C. Damiani, A. Totet (CHU Amiens), J. P. Bouchara, D. Chabasse, M. Pihet (CHU Angers), S. Bland (CH Annecy), V. Blanc (CH Antibes), S. Branger (CH Avignon), A. P. Bellanger, L. Millon (CHU Besançon), C. Plassart (CH Beauvais), I. Poilane (Hôpital Jean Verdier, Bondy), I. Accoceberry, L. Delhaes, B. Couprie, F. Gabriel (CH Bordeaux), J. Dunand, A. L. Roux, V. Sivadon-Tardy (Hôpital Ambroise Paré, Boulogne Billancourt), F. Laurent (CH, Bourg en Bresse), S. Legal, E. Moalic, G. Nevez, D. Quinio (CHU Brest), M. Cariou (CH Bretagne Sud), J. Bonhomme, C. Duhamel (CHU, Caen), B. Podac (CH, Chalon sur Saône), S. Lechatch (CH, Charleville-Mézières), C. Soler (Hopital d’Instruction des armées, Clamart), M. Cambon, C. Nourrisson, P. Poirier, D. Pons (CHU, Clermont Ferrand), O. Augereau, I. Grawey (CH, Colmar), N. Fauchet (CHIC, Créteil), A. Bonnin, F. Dalle (CHU, Dijon), P. Cahen, P. Honderlick (CMC, Foch), N. Desbois, C. Miossec (CHU, Fort de France), J. L. Hermann (Hôpital Raymond Poincaré, Garches), M. Cornet, R. Grillot, B. Lebeau, D. Maubon, H. Pelloux (CHU, Grenoble), M. Nicolas (CHU, Guadeloupe), C. Aznar, D. Blanchet, J. F. Carod, M. Demar, (CHU, Guyane), A. Angoulvant (Hôpital Bicêtre, le Kremlin Bicêtre), C. Ciupek (CH, Le Mans), A. Gigandon (Hôpital Marie Lannelongue, Le Plessis Robinson), B. Bouteille (CH Limoges), E. Frealle, D. Poulain, B. Sendid (CHU Lille), D. Dupont, J. Menotti, F. Persat, M.-A. Piens, M. Wallon (CHU, Lyon), C. Cassagne, S. Ranque (CHU, Marseille), T. Benoit-Cattin, L. Collet (CH Mayotte), A. Fiacre (CH Meaux), N. Bourgeois, L. Lachaud, P. Rispail, Y. Sterkers (CHU, Montpellier), M. Machouart (CHU, Nancy), F. Gay-Andrieu, P. Lepape, F. Morio (CHU, Nantes), O. Moquet (CH, Nevers), S. Lefrançois (Hôpital Américain, Neuilly), M. Sasso (CHU, Nimes), F. Reibel (GH, Nord-Essone), M. Gari-Toussaint, L. Hasseine (CHU Nice), L. Bret, D. Poisson (CHR Orléans), S. Brun (Hôpital Avicenne, Paris), C. Bonnal, C. Chochillon, S. Houzé (Hôpital Bichat, Paris), A. Paugam (Hôpital Cochin, Paris), N. Ait-Ammar, F. Botterel, R. Chouk (CHU Henri Mondor, Paris), M. E. Bougnoux, E. Sitterle (Hôpital Necker, Paris), A. Fekkar, R. Piarroux (Hôpital Pitié Salpêtrière, Paris), J. Guitard, C. Hennequin, J.-L. Poirot (Hôpital St Antoine, Paris), M. Gits-Muselli, S. Hamane, C. Lacroix (Hôpital Saint Louis, Paris), S. Bonacorsi, P. Mariani (Hôpital Robert Debré, Paris), D. Moissenet (Hôpital Trousseau, Paris), C. Kauffmann-Lacroix, A. Minoza, E. Perraud, M. H. Rodier (CHU Poitiers), G. Colonna (CH, Porto Vecchio), A. Huguenin, D. Toubas (CHU Reims), S. Chevrier, J. P. Gangneux, F. Robert-Gangneux, C. Guigen (CHU Rennes), O. Belmonte, G. Hoarau, M. C. Jaffar Bandjee, J. Jaubert, S. Picot, N. Traversier (CHU Réunion), L. Favennec, G. Gargala (CHU, Rouen), N. Godineau, C. Tournus (CH, St Denis), C. Mahinc, H. Raberin (CHU, St Etienne), V. Letscher Bru (CHU, Strasbourg), S. Cassaing (CHU, Toulouse), P. Patoz (CH Tourcoing), E. Bailly, J. Chandenier, G. Desoubeaux (CHU Tours), F. Moreau (CH Troyes), P. Munier (CH Valence), E. Mazars (CH Valenciennes), O. Eloy (CH Versailles), E. Chachaty (Institut Gustave Roussy, Villejuif), and and members of the NRCMA (Institut Pasteur, Paris): A. Bertho, C. Blanc, A. Boullié, C. Gautier, V. Geolier, D. Hoinard, and D. Raoux-Barbot for technical help, and K. Boukris-Sitbon, F. Lanternier, A. Alanio, and D. Garcia-Hermoso for their expertise and contribution to the surveillance programs.
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Pharmacology ,Antifungal Agents ,[SDV]Life Sciences [q-bio] ,yeasts ,Microbial Sensitivity Tests ,antifungal resistance ,Anidulafungin ,bacterial infections and mycoses ,rare yeast ,common yeast ,Echinocandins ,Lipopeptides ,Infectious Diseases ,Susceptibility ,Caspofungin ,Drug Resistance, Fungal ,Mutation ,Micafungin ,polycyclic compounds ,FKS mutation ,Humans ,Candidiasis, Invasive ,Pharmacology (medical) ,MIC distribution - Abstract
International audience; Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.
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- 2022
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4. Azoles susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species
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Olivier Lortholary, Françoise Dromer, Stéphane Bretagne, Marie Desnos-Ollivier, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Cité (UPCité), Institut Pasteur and Santé Publique France., Members of the French Mycoses Study group who contributed to the data are in alphabetical order of the cities, all the French microbiologists and mycologists who sent isolates for characterization of unusual antifungal susceptibility profiles or to contribute to the ongoing surveillance program on the epidemiology of invasive fungal infections in France (YEASTS and RESSIF programs): N. Brieu (CH Aix), T. Chouaki, C. Damiani, A. Totet (CHU Amiens, J. P. Bouchara, M. Pihet (CHU Angers), S. Bland (CH Annecy), V. Blanc (CH Antibes), S. Branger (CH Avignon), A. P. Bellanger, L. Million (CHU Besançon), C. Plassart (CH Beauvais), I. Poilane (hôpital Jean Verdier, Bondy), I. Accoceberry, L. Delhaes, F. Gabriel (CH Bordeaux), A. L. Roux, V. Sivadon-Tardy (hôpital Ambroise Paré, Boulogne Billancourt), F. Laurent (CH, Bourg en Bresse), S. Legal, E. Moalic, G. Nevez, D. Quinio (CHU Brest), M. Cariou (CH Bretagne Sud), J. Bonhomme (CHU, Caen), B. Podac (CH, Chalon sur Saône), S. Lechatch (CH, Charleville-Mézières), C. Soler (hopital d’Instruction des armées, Clamart), P. Poirier, C. Nourrisson (CHU, Clermont Ferrand), O. Augereau (CH, Colmar), N. Fauchet (CHIC, Créteil), F. Dalles (CHU, Dijon), P. Cahen (CMC, Foch), N. Desbois, C. Miossec (CHU, Fort de France), J. L. Hermann (hôpital Raymond Poincaré, Garches), M. Cornet, D. Maubon, H. Pelloux (CHU, Grenoble), M. Nicolas (CHU,Guadeloupe), C. Aznar, D. Blanchet, J. F. Carod, M. Demar, (CHU, Guyane), A. Angoulvant (hôpital Bicêtre, le Kremlin Bicêtre), C. Ciupek (CH, Le Mans), A. Gigandon (hôpital Marie Lannelongue, Le Plessis Robinson), B. Bouteille (CH Limoges), E. Frealle, B. Sendid (CHU Lille), D. Dupont, J. Menotti, F. Persat, M. Wallon (CHU, Lyon), C. Cassagne, S. Ranque (CHU, Marseille), T. Benoit-Cattin, L. Collet (CH Mayotte), A. Fiacre (CH Meaux), N. Bourgeois, L. Lachaud (CHU, Montpellier), M. Machouart (CHU, Nancy), P. Lepape, F. Morio (CHU, Nantes), O. Moquet (CH, Nevers), S. Lefrançois (hôpital Américain, Neuilly), M. Sasso (CHU, Nimes), F. Reibel (GH, Nord-Essone), M. Gari-Toussaint, L. Hasseine (CHU Nice), L. Bret, D. Poisson (CHR Orléans), S. Brun (hôpital Avicenne, Paris), C. Bonnal, S. Houze (hôpital Bichat, Paris), A. Paugam (hôpital Cochin, Paris), E. Dannaoui (HEGP, Paris), N. Ait-Ammar, F. Botterel, R. Chouk (CHU Henri Mondor, Paris), M. E. Bougnoux, E. Sitterle (hôpital Necker, Paris), A. Fekkar, R. Piarroux (hôpital Pitié Salpêtrière, Paris), J. Guitard, C. Hennequin (hôpital St Antoine, Paris), M. Gits-Muselli, S. Hamane (hôpital Saint Louis, Paris), S. Bonacorsi, P. Mariani (hôpital Robert Debré, Paris), D. Moissenet (hôpital Trousseau, Paris), A. Minoza, E. Perraud, M. H. Rodier (CHU Poitiers), G. Colonna (CH, Porto Vecchio), D. Toubas (CHU Reims), J. P. Gangneux, F. Robert-Gangneux (CHU Rennes), O. Belmonte, G. Hoarau, M. C. Jaffar Bandjee, J. Jaubert, S. Picot, N. Traversier (CHU Réunion), L. Favennec, G. Gargala (CHU, Rouen), C. Tournus (CH, St Denis), H. Raberin (CHU, St Etienne), V. Letscher Bru (CHU, Strasbourg), S. Cassaing (CHU, Toulouse), P. Patoz (CH Tourcoing), E. Bailly, G. Desoubeaux (CHU Tours), F. Moreau (CH Troyes), P. Munier (CH Valence), E. Mazars (CH Valenciennes), O. Eloy (CH Versailles), E. Chachaty (Institut Gustave Roussy, Villejuif), and members of the NRCMA (Institut Pasteur, Paris): A. Boullié, C. Gautier, V. Geolier, C. Blanc, D. Hoinard and D. Raoux-Barbot for technical help, and K. Boukris-Sitbon, F. Lanternier, A. Alanio, D. Garcia-Hermoso for their expertise and contribution to the surveillance programs., Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Université de Paris (UP)
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Serotype ,Azoles ,Antifungal Agents ,Microbial Sensitivity Tests ,Candida parapsilosis ,Rhodotorula mucilaginosa ,Pichia ,Microbiology ,Candida tropicalis ,03 medical and health sciences ,0302 clinical medicine ,Drug Resistance, Fungal ,Pharmacology (medical) ,030212 general & internal medicine ,Candida albicans ,[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology ,Pharmacology ,chemistry.chemical_classification ,0303 health sciences ,biology ,Candida glabrata ,030306 microbiology ,Broth microdilution ,Rhodotorula ,biology.organism_classification ,3. Good health ,Infectious Diseases ,chemistry ,Susceptibility ,Saccharomycetales ,Azole ,France - Abstract
Invasive yeast infections represent a major global public health issue, and only few antifungal agents are available. Azoles are one of the classes of antifungals used for treatment of invasive candidiasis. The determination of antifungal susceptibility profiles using standardized methods is important to identify resistant isolates and to uncover the potential emergence of intrinsically resistant species. Here, we report data on 9,319 clinical isolates belonging to 40 pathogenic yeast species recovered in France over 17 years. The antifungal susceptibility profiles were all determined at the National Reference Center for Invasive Mycoses and Antifungals based on the EUCAST broth microdilution method. The centralized collection and analysis allowed us to describe the trends of azole susceptibility of isolates belonging to common species, confirming the high susceptibility for Candida albicans (n = 3,295), Candida tropicalis (n = 641), and Candida parapsilosis (n = 820) and decreased susceptibility for Candida glabrata (n = 1,274) and Pichia kudriavzevii (n = 343). These profiles also provide interesting data concerning azole susceptibility of Cryptococcus neoformans species complex, showing comparable MIC distributions for the three species but lower MIC(50)s and MIC(90)s for serotype D (n = 208) compared to serotype A (n = 949) and AD hybrids (n = 177). Finally, these data provide useful information for rare and/or emerging species, such as Clavispora lusitaniae (n = 221), Saprochaete clavata (n = 184), Meyerozyma guilliermondii complex (n = 150), Candida haemulonii complex (n = 87), Rhodotorula mucilaginosa (n = 55), and Wickerhamomyces anomalus (n = 36).
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- 2021
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5. Molecular determinants of SR-B1-dependent Plasmodium sporozoite entry into hepatocytes
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Langlois, Anne-Claire, Manzoni, Giulia, Vincensini, Laetitia, Coppée, Romain, Marinach, Carine, Guérin, Maryse, Huby, Thierry, Carrière, Véronique, François-Loïc, Cosset, Dreux, Marlène, Rubinstein, Eric, Silvie, Olivier, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche sur les maladies cardiovasculaires et métaboliques, UMR S 1166, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital St Antoine, Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virus, mmunité innée et trafic vésiculaire - Vesicular trafficking, innate response and viruses (VIV), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), ANR-16-CE15-0004,MALINV,Identification des facteurs de virulence de Plasmodium impliqués dans l'invasion des hépatocytes(2016), and Gestionnaire, Hal Sorbonne Université
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CD36 Antigens ,Models, Molecular ,Plasmodium ,[SDV]Life Sciences [q-bio] ,lcsh:R ,lcsh:Medicine ,Article ,Tetraspanin 28 ,Malaria ,Parasite biology ,Mice ,Protein Domains ,Sporozoites ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,parasitic diseases ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Hepatocytes ,Animals ,Humans ,lcsh:Q ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Amino Acid Sequence ,lcsh:Science ,[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology - Abstract
International audience; Sporozoite forms of the Plasmodium parasite, the causative agent of malaria, are transmitted by mosquitoes and first infect the liver for an initial round of replication before parasite proliferation in the blood. The molecular mechanisms involved during sporozoite invasion of hepatocytes remain poorly understood. Two receptors of the Hepatitis C virus (HCV), the tetraspanin CD81 and the scavenger receptor class B type 1 (SR-B1), play an important role during the entry of Plasmodium sporozoites into hepatocytes. In contrast to HCV entry, which requires both CD81 and SR-B1 together with additional host factors, CD81 and SR-B1 operate independently during malaria liver infection. Sporozoites from human-infecting P. falciparum and P. vivax rely respectively on CD81 or SR-B1. Rodent-infecting P. berghei can use SR-B1 to infect host cells as an alternative pathway to CD81, providing a tractable model to investigate the role of SR-B1 during Plasmodium liver infection. Here we show that mouse SR-B1 is less functional as compared to human SR-B1 during P. berghei infection. We took advantage of this functional difference to investigate the structural determinants of SR-B1 required for infection. Using a structure-guided strategy and chimeric mouse/human SR-B1 constructs, we could map the functional region of human SR-B1 within apical loops, suggesting that this region of the protein may play a crucial role for interaction of sporozoite ligands with host cells and thus the very first step of Plasmodium infection.
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- 2020
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6. Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome
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Wallid Deb, Bertrand Cariou, Arnaud Wiedemann, Julien Thevenon, Rhonda E. Schnur, Vincent Ramaekers, Alexandre N. Datta, Richard Redon, Solène Conrad, Natacha Sloboda, Benjamin Cogné, François Feillet, Geneviève Baujat, Bertrand Isidor, Pierre Vabres, Tawfeg Ben-Omran, Marie Vincent, Flora Breheret, Dorothea Wand, Aline Delignières, Laurence Faivre, Betty Gardie, Xavier Balguerie, Anne-Claire Bursztejn, Marion Lenglet, Lionel Van Maldergem, Sébastien Küry, Antonin Lamaziere, Virginie Carmignac, Eva Trochu, Sébastien Barbarot, Marie-Cécile Nassogne, Erin Torti, Yue Si, Paul Kuentz, Thomas Besnard, Jean-Louis Guéant, Alice Goldenberg, Stéphane Bézieau, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie pédiatrique, Service de Génétique Médicale, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Rouen, Hamad medical corporation, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), University of Basel (Unibas), Hôpital Bretagne Atlantique, Partenaires INRAE, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Liège (CHU-Liège), Gene Dx, Centre de Génétique, and Hôpital St-Antoine
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Male ,Developmental Disabilities ,Intellectual disability ,cholesterol pathway ,Whole Exome Sequencing ,chemistry.chemical_compound ,Missense mutation ,Age of Onset ,Child ,Intramolecular Transferases ,Genetics (clinical) ,Exome sequencing ,Genetics ,Sanger sequencing ,0303 health sciences ,biology ,Lanosterol ,030305 genetics & heredity ,LSS ,3. Good health ,Pedigree ,Cholesterol ,Phenotype ,intellectual disability ,Child, Preschool ,Allelic Imbalance ,Congenital cataracts ,symbols ,Female ,Squalene ,early-onset epileptic encephalopathy ,03 medical and health sciences ,symbols.namesake ,Cholesterol pathway ,Exome Sequencing ,medicine ,Humans ,030304 developmental biology ,Epilepsy ,Infant ,Alopecia ,alopecia ,medicine.disease ,Early-onset epileptic encephalopathy ,chemistry ,Mutation ,biology.protein ,Hypotrichosis ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology ,Lanosterol synthase - Abstract
International audience; Purpose Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with early-onset epilepsy and other dermatological features. Methods Through a multicenter international collaborative study, we identified LSS pathogenic variants in APMR individuals either by exome sequencing or LSS Sanger sequencing. Splicing defects were assessed by transcript analysis and minigene assay. Results We reported ten APMR individuals from six unrelated families with biallelic variants in LSS. We additionally identified one affected individual with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. Conclusion In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome.
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- 2019
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7. Safety and efficacy of the combination simeprevir-sofosbuvir in HCV genotype 1- and 4-mono-infected patients from the French ANRS CO22 hepather cohort
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Anne Laurain, Sophie Metivier, Georges Haour, Dominique Larrey, Céline Dorival, Christophe Hezode, Fabien Zoulim, Patrick Marcellin, Marc Bourliere, Jean-Pierre Zarski, Dominique Thabut, Laurent Alric, Nathalie Ganne-Carrie, Paul Cales, Jean-Pierre Bronowicki, Ghassan Riachi, Claire Geist, Xavier Causse, Armand Abergel, Olivier Chazouilleres, Philippe Mathurin, Dominique Guyader, Didier Samuel, Albert Tran, Véronique Loustaud-Ratti, Ventzislava Petrov-Sanchez, Alpha Diallo, Clovis Luzivika-Nzinga, Hélène Fontaine, Fabrice Carrat, Stanislas Pol, on behalf of the ANRS/AFEF HEPATHER study group, Département d'hépatologie [CHU Cochin], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Rouen, Normandie Université (NU), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional d'Orléans (CHRO), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS)-Clermont Université, Service d'hépatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, ANRS (France Recherche Nord&sud Sida-vih Hepatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé) and MSD, Janssen, Gilead, Abbvie, BMS, Roche.The biobank of the cohort is stored by Cell&Co Biorepository, Pont du Château, France and has been managed temporarily by Centre de Ressources Biologiques-HUEP, Hôpital St Antoine, Paris, France., Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Jonchère, Laurent, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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Adult ,Liver Cirrhosis ,Male ,Genotype ,Aucun ,Hepacivirus ,Sciences du Vivant [q-bio]/Médecine humaine et pathologie ,Antiviral Agents ,Drug Administration Schedule ,Direct acting antivirals ,lcsh:Infectious and parasitic diseases ,Cohort Studies ,Simeprevir ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Humans ,lcsh:RC109-216 ,Prospective Studies ,Aged ,Real life cohort ,Hepatitis C virus ,Hepatitis C, Chronic ,Middle Aged ,Treatment Outcome ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Drug Therapy, Combination ,Female ,Sofosbuvir ,Research Article - Abstract
BACKGROUND: Although real-life results of sofosbuvir/simeprevir have been extensively reported from the United States, data from other geographical areas are limited. In the French observational cohort, ANRS CO22 HEPATHER, 9432 patients were given the new oral antivirals from December 2013 to June 30, 2018. We report the results of sofosbuvir/simeprevir in genotypes 1- and 4-infected patients. METHODS: Demographics and history of liver disease were collected at entry in the cohort. Clinical, adverse events, and virological data were collected throughout treatment and post-treatment follow-up. The choice of treatment duration or addition of ribavirin was left up to the physician. RESULTS: Five hundred ninety-nine HCV (467 genotype 1 and 132 genotype 4) mono-infected, naive for all oral-DAAs regimen patients were given sofosbuvir/simeprevir with (n = 63) or without ribavirin (n = 536) for 12 or 24 weeks; 56% had cirrhosis (4% decompensated) and 71% had prior treatment failure to interferon-based regimen. 7 patients (1.16%) were lost to follow-up. The overall SVR12 rate was 92.6%. The SVR12 was 90% in GT1a, 94.2% in GT1b and 91.6% in GT4 with no significant difference for genotype, treatment duration or ribavirin addition. Severity of liver disease was not associated with a lower SVR12 rate on multivariate analysis but was associated with a higher rate of severe side effects. Early treatment discontinuations were rare; no new safety signals were reported. CONCLUSION: In this real life, observational, prospective cohort study, the 12-week sofosbuvir/simeprevir+/-ribavirin combination appears to be efficient and safe. TRIAL REGISTRATION: Trial registration with ClinicalTrials.gov NCT01953458 . Anrs Afef Hepather study group PMC6446259
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- 2019
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8. Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab
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Laharie, D, Bourreille, A, Branche, J, Allez, M, Bouhnik, Y, Filippi, J, Zerbib, F, Savoye, G, Vuitton, L, Moreau, J, Amiot, A, Cosnes, J, Ricart, E, Dewit, Olivier, Lopez-Sanroman, A, Fumery, M, Carbonnel, F, Bommelaer, G, Coffin, B, Roblin, X, van Assche, G, Esteve, M, Farkkila, M, Gisbert, J P, Marteau, P, Nahon, S, de Vos, M, Lambert, J, Mary, J Y, Louis, E, Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives, Department of Gastroenterology, Centre Hospitalier Général Cannes, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire Électronique Ondes et Signaux pour les Transports (IFSTTAR/COSYS/LEOST), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-PRES Université Lille Nord de France, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Amiens-Picardie, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Service de Gastroentérologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Ghent University Hospital, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Science et Ingénierie des Matériaux et Procédés (SIMaP), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de Rangueil, CHU Toulouse [Toulouse], Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Gastroentérologie et nutrition [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), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Cliniques Universitaires Saint-Luc [Bruxelles], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Clermont-Ferrand, Hôpital Louis Mourier - AP-HP [Colombes], Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), University Hospitals Leuven [Leuven], Hospital Universitario Mutua de Terrassa, University of Helsinki, Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain., Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Liège (CHU-Liège), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Recherche Agronomique (INRA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière, Science et Ingénierie des Matériaux et Procédés (SIMaP ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hépato-gastroentérologie [CHU Nantes], Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hépato-gastro-entérologie [Hôpital Saint-Louis, APHP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Beaujon, AP HP, Departement de Gastroenterologie et d'assistance Nutritive, Université Paris Diderot - Paris 7 (UPD7), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [Rouen], Institute for Research and Innovation in Biomedicine (IRIB), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Cliniques Universitaires Saint-Luc, UCL, 1200 Bruxelles, Belgique, parent, Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hépato-Gastroentérologie [CHRU Clermont-Ferrand], Centre Hospitalier Universitaire de Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hopital Louis Mourier - AP-HP [Colombes], Department of Gastroenterology, Hospital Universitari Mútua de Terrassa, University of Barcelona, Terrassa. CIBEREHD, Catalonia, Spain., Helsinki University, and Helsinki University Central Hospital, Clinic of Gastroenterology, HUS, Finland., Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) y Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain., Hôpital St-Antoine, service de Gastroentérologie, Paris, France., Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Ghent University Hospital, Gent, Belgium., Department of Gastroenterology, University Hospital CHU of Liège, Liège, Belgium., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [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), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,IBD ,Drug Resistance ,Azathioprine ,Disease-Free Survival ,03 medical and health sciences ,COLORECTAL SURGERY ,0302 clinical medicine ,Refractory ,Gastrointestinal Agents ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Colectomy ,ComputingMilieux_MISCELLANEOUS ,business.industry ,Gastroenterology ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Middle Aged ,medicine.disease ,Ciclosporin ,Ulcerative colitis ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Colorectal surgery ,Infliximab ,3. Good health ,Surgery ,Treatment Outcome ,ULCERATIVE COLITIS ,030220 oncology & carcinogenesis ,Cohort ,Cyclosporine ,030211 gastroenterology & hepatology ,Colitis, Ulcerative ,Female ,Steroids ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
ObjectiveCiclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab.DesignBetween 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test.ResultsAfter a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment.ConclusionsIn this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other.Trial registration numberEudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.
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- 2018
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9. No evidence of hepatitis B virus reactivation among liver transplant recipients treated with interferon- free regimens for hepatitis C virus recurrence (ANRS CO23 CUPILT Cohort)
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Mouna, Lina, Rossignol, Emilie, Tateo, Mariagrazia, Duclos-Vallee, Jean-Charles, Duvoux, Christophe, Durand, Francois, Tran, Albert, Radenne, Sylvie, Canva-Delcambre, Valerie, Houssel-Debry, Pauline, Dumortier, Jérôme, Conti, Filomena, De Ledinghen, Victor, Leroy, Vincent, Kamar, Nassim, Di Martino, Vincent, Moreno, Christophe, Fridlund, Danielle M. Botta, D'Alteroche, Louis, Lebray, Pascal, perre, philippe, Besch, Camille, Silvain, Christine, Habersetzer, François, Debette-Gratien, Maryline, Abergel, Armando, Diallo, Alpha, Roque-Afonso, Anne Marie, Pageaux, Georges-Philippe, Jonchère, Laurent, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), DHU Hepatinov, Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hépatogastroentérologie [Hôpital de la Croix-Rousse, Hospices Civils de Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Service d'hépatogastroentérologie [Hôpital Edouard Herriot, Hospices Civils de Lyon], Hôpital Edouard Herriot [CHU - HCL], Hôpital St Antoine, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hôpital Michallon, CHU Toulouse [Toulouse], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Marseille, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHD Vendee (La Roche Sur Yon), Service d’Hépatogastroentérologie, NHC, CHU de Strasbourg, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, CHU Clermont-Ferrand, ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Lapeyronie [Montpellier] (CHU), Novartis, Astellas, Roche, MSD, GSK, Gilead, Supersonic Imagine, Janssen, Abbvie, Schering-Plough, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11)
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2017
10. Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis†
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Béranger Lueza, Lesley Seymour, C. Le Pechoux, Minoru Takada, Allan Price, S. Spiro, M. Pijls-Johannesma, M. O'Brien, Anne-Sophie Veillard, N. Murray, Nevin Murray, M. Takada, Taro Shibata, James Lovato, H. Choy, David H. Johnson, W. Blackstock, Jeffrey Crawford, Cécile Le Péchoux, Donald H. Johnson, J.P. Pignon, D.V. Skarlos, Jean-Pierre Pignon, William Blackstock, Mary O’Brien, Anne Sophie Veillard, Dirk Karel Maria De Ruysscher, Hak Choy, Baktiar Hasan, X. Wang, Bernard Lebeau, Urania Dafni, E. Paris, Suzanne E. Dahlberg, B. Lebeau, Madelon Pijls-Johannesma, Sylvie Chevret, Xiaofei Wang, Dirk De Ruysscher, L. Seymour, R. Arriagada, Emmanuelle Paris, Dimosthenis Skarlos, Allan Hackshaw, P. Baas, A. Price, Stephen G. Spiro, Rodrigo Arriagada, Paul Baas, Maastricht Radiation Oncology Clinic (MAASTRO), Maastricht University [Maastricht], Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Plateforme Ligue nationale contre le cancer de méta-analyse en oncologie [Villejuif], Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Département de radiothérapie [Gustave Roussy], Université Paris-Sud - Paris 11 (UP11), UT Southwestern University School of Medicine, EORTC Data Center, British Columbia Cancer Agency, University College London Hospitals (UCLH), Alliance Data and Statistical Center, Duke University [Durham], Osaka Prefectural Habikino Hospital, Hôpital St Antoine, Wake Forest University, Second Department of Medical Oncology, Metropolitan Hospital N. Faliro, The Netherlands Cancer Institute, Department of Radiation Oncology, University of Texas Southwestern Medical Center [Dallas], Cancer Research UK Edinburgh Centre [Edinburgh, UK], University of Edinburgh-MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council-Medical Research Council, NCIC Clinical Trials Group [Kingston, Canada], Université Queen's [Canada], The meta-analysis was funded by the French National Cancer Institute (Programme Hospitalier de Recherche Clinique), the Ligue Nationale Contre le Cancer, and partly by Sanofi-Aventis (unrestricted grants). The investigators meeting was also funded by Gustave Roussy, Lilly and Astra-Zeneca (unrestricted grants). No grant number is applicable., RTT-SCLC Collaborative Group : De Ruysscher D, Le Pechoux C, Lueza B, Paris E, Pignon JP, Pijls-Johannesma M, Veillard AS, Arriagada R, Baas P, Blackstock W, Chevret S, Choy H, Crawford J, Dafni U, Dahlberg S, De Ruysscher D, Hackshaw A, Hasan B, Johnson DH, Le Pechoux C, Lebeau B, Lovato J, Lueza B, Murray N, O'Brien M, Paris E, Pignon JP, Pijls-Johannesma M, Price A, Spiro S, Seymour L, Shibata T, Skarlos D, Spiro S, Takada M, Veillard AS, Wang X., Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Lueza, Béranger
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Thoracic radiotherapy ,Reviews ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Drug Therapy ,radiotherapy timing ,small-cell lung cancer ,medicine ,Humans ,030212 general & internal medicine ,Lung cancer ,Proportional Hazards Models ,Randomized Controlled Trials as Topic ,randomised clinical trials ,Chemotherapy ,business.industry ,Incidence (epidemiology) ,Standard treatment ,Hazard ratio ,Hematology ,medicine.disease ,individual participant data meta-analysis ,Combined Modality Therapy ,Small Cell Lung Carcinoma ,3. Good health ,Surgery ,Radiation therapy ,Oncology ,chemotherapy compliance ,030220 oncology & carcinogenesis ,Meta-analysis ,Female ,Cisplatin ,business ,thoracic radiotherapy - Abstract
International audience; BackgroundChemotherapy combined with radiotherapy is the standard treatment of “limited-stage” small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and chemotherapy.Material and methodsWe performed a meta-analysis of individual patient data in randomised trials comparing earlier versus later radiotherapy, or shorter vs. longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival.ResultsTwelve trials with 2,668 patients were eligible. Data from nine trials comprising 2,305 patients were available for analysis. The median follow-up was 10 years. When all trials were analysed together, “earlier or shorter” vs. “later or longer” thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of “earlier or shorter” radiotherapy among trials with a similar proportion of patients who were compliant with chemotherapy (defined as having received 100% or more of the planned chemotherapy cycles) in both arms (HR 0.79, 95% CI 0.69–0.91) and in favour of “later or longer” radiotherapy among trials with different chemotherapy compliance (HR 1.19, 1.05–1.34, interaction test p
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- 2016
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11. How to unveil self-quenched fluorophores and subsequently map the subcellular distribution of exogenous peptides
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Fabienne Burlina, Jean-Marie Swiecicki, Gérard Chassaing, Christelle Mansuy, Margherita Di Pisa, Julien Tailhades, Germain Trugnan, Frédéric Thiebaut, Solange Lavielle, Simon Gourdin-Bertin, Serge Chwetz Off, Swiecicki, Jean-Marie, HAL UPMC, Gestionnaire, Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC), PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), INSERM-ERL 1157, CHU St Antoine, Hôpital St Antoine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence Nationale de la Recherche [J12R139], PSL Research University (PSL), Centre National de la Recherche Scientifique (CNRS)-ESPCI ParisTech-Université Pierre et Marie Curie - Paris 6 (UPMC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Cell Membrane Permeability ,Chemical biology ,Cell-Penetrating Peptides ,Biology ,010402 general chemistry ,01 natural sciences ,Article ,03 medical and health sciences ,Confocal laser scanning microscopy ,medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,Fluorescent Dyes ,Multidisciplinary ,Microscopy, Confocal ,Ionophores ,Colocalization ,Fluorescence ,0104 chemical sciences ,Subcellular distribution ,030104 developmental biology ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Biophysics ,Intracellular ,Macromolecule ,Biophysical chemistry ,HeLa Cells - Abstract
Confocal laser scanning microscopy (CLSM) is the most popular technique for mapping the subcellular distribution of a fluorescent molecule and is widely used to investigate the penetration properties of exogenous macromolecules, such as cell-penetrating peptides (CPPs), within cells. Despite the membrane-association propensity of all these CPPs, the signal of the fluorescently labeled CPPs did not colocalize with the plasma membrane. We studied the origin of this fluorescence extinction and the overall consequence on the interpretation of intracellular localizations from CLSM pictures. We demonstrated that this discrepancy originated from fluorescence self-quenching. The fluorescence was unveiled by a “dilution” protocol, i.e. by varying the ratio fluorescent/non-fluorescent CPP. This strategy allowed us to rank with confidence the subcellular distribution of several CPPs, contributing to the elucidation of the penetration mechanism. More generally, this study proposes a broadly applicable and reliable method to study the subcellular distribution of any fluorescently labeled molecules.
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- 2015
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12. Quickly progressive amyotrophy of the thigh: An unusual cause of rapid chondrolysis of the knee
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Anne Miquel, Maeva Ferrari, Anthony Behin, Jérémie Sellam, Karine Louati, Olivier Benveniste, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiologie, Hôpital St Antoine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Administateur, HAL Sorbonne Université, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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myalgia ,Cartilage, Articular ,musculoskeletal diseases ,medicine.medical_specialty ,Myopathy ,Osteoarthritis ,Thigh ,Polymyositis ,Patellofemoral Joint ,Atrophy ,Rheumatology ,Muscular Diseases ,medicine ,Humans ,Muscle Strength ,Muscle, Skeletal ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,Amyotrophy ,Femoro-patellar osteoarthritis ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,Arthralgia ,Magnetic Resonance Imaging ,3. Good health ,Surgery ,Knee pain ,medicine.anatomical_structure ,Rapidly destructive osteoarthritis ,Female ,Risk factor ,medicine.symptom ,business ,Cartilage Diseases ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; While rapidly destructive OA is more recognized in hip, we report the case of a 50-year-old woman who presented a rapid chondrolysis in the patellofemoral joint in a context of rapid loss of muscular strength. She had arthralgia, myalgia and proximal muscular deficit of the limbs. Creatine phospho kinase level was elevated and electromyogram exam showed a myogenic syndrome. Neither immune nor visceral disease was highlighted. As we suspected a polymyositis, we started corticosteroids and physiotherapy, then methotrexate and intravenous immunoglobulin. Concomitantly to the worsening of the muscular deficit and atrophy of hamstrings, she developed a persistent and disabling knee pain. Initial radiographs and magnetic resonance imaging (MRI) showed only a patellofemoral dysplasia and tiny cartilage damages. Because of aggravation of myalgia, we treated by mycophenolate mofetyl then rituximab. One year later, the knee remained painful and swollen. MRI showed signs of advanced osteoarthritis including an important loss of cartilage with an atrophy of hamstrings. Several articular corticosteroids injections were done. In the same time, the evolution of the muscular disease was unusual. Another histological analysis of muscle has highlighted a genetic myopathy due to mutation of calpain. Immunosuppressive treatments were stopped and a total joint replacement was performed. We show for the first time a case of rapid chondrolysis of patellofemoral joint related to a severe genetic myopathy.
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- 2015
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13. Quels sont les patients atteints d'un cancer du sein dont la décision de prise en charge thérapeutique bénéficie de l'utilisation d'un système d'aide à la décision ? Un exemple utilisant la fouille de données et OncoDoc2
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Jacques Bouaud, Arnaud Soulet, Jean-Philippe Spano, Jean-Pierre Lefranc, Isabelle Cojean-Zelek, Brigitte Blaszka-Jaulerry, Laurent Zelek, Axel Durieux, Christophe Tournigand, Nizar Messai, Alexandra Rousseau, BRIGITTE SEROUSSI, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Fondamentale et Appliquée de Tours (LIFAT), Université de Tours-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Pôle oncologie médicale, Hôpital des Diaconesses, Service de radiothérapie-oncologie, CH Lagny Marne la Vallée, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Paris 13 (UP13), Institut de Cancérologie des Peupliers, Clinique des Peupliers, Service d'oncologie médicale, Hôpital St-Antoine, Service de pharmacologie - Dosage de médicaments [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), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris 13 (UP13), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Catherine Faron-Zucker, Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nivault, Estelle, Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Informatique de l'Université de Tours ( LI ), Université de Tours-Polytech'Tours, Service d'oncologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance Publique - Hôpitaux de Paris, Assistance publique - Hôpitaux de Paris (AP-HP), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), UFR Santé, Médecine et Biologie Humaine ( UFR SMBH ), Université Paris 13 ( UP13 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé ( LIMICS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris 13 ( UP13 ), and CHU Tenon [APHP]
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[INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI] ,Recommandations de pratique clinique ,conformité aux référentiels ,cancer du sein ,évaluation de la qualité des soins ,[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie ,[INFO.INFO-LG] Computer Science [cs]/Machine Learning [cs.LG] ,[ INFO.INFO-LG ] Computer Science [cs]/Machine Learning [cs.LG] ,fouille de données ,[INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI] ,[INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG] ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,système d'aide à la décision ,[ INFO.INFO-AI ] Computer Science [cs]/Artificial Intelligence [cs.AI] - Abstract
Session 2 : Utilisateurs et usages; National audience; OncoDoc2 est un système d'aide à la décision (SAD) s'appuyant sur des recommandations de pratique clinique (RPC) pour la prise en charge des cancers du sein. Il a été utilisé comme intervention dans un essai randomisé contrôlé dont l'objectif principal était d'évaluer son impact sur la conformité des décisions des réunions de concertation pluridisciplinaire aux RPC. Nous avons utilisé un algorithme de fouille de données pour découvrir les régularités des profils patients, ou " motifs émergents " (ME), associées à la conformité et à la non-conformité des décisions selon que le système OncoDoc2 était ou non utilisé, afin d'évaluer quels profils patients pouvaient bénéficier de l'utilisation du système. Les ME associés à la non conformité des décisions prises sans le système sont associées à la conformité quand le système est utilisé sauf dans certaines situations cliniques pour lesquelles la force de la recommandation est faible.
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- 2014
14. Long-term outcome in early survivors of cardiogenic shock at the acute stage of myocardial infarction: a landmark analysis from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) Registry
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Laurence Berard, Etienne Puymirat, Didier Blanchard, Nadia Aissaoui, Eric Durand, Eric Bonnefoy-Cudraz, Francois Schiele, Benamer H, Tabassome Simon, Denis Angoulvant, Fabrice Prunier, Nicolas Danchin, Philippe Quandalle, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Dpt Cardiologie [CHU Georges Pompidou], 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), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital St Antoine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Hospitalier J. Cartier, Hôpital Privé Jacques Cartier [Massy], Hôpital Victor Provo, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Rouen, Normandie Université (NU), Clinique St Gatien et Groupe Athérome Cardiologie Interventionnelle/SF, Clinique St Gatien, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Recherche Clinique des Hôpitaux Universitaires Est Parisien ( GH06-SAT-TNN-TRS-RTH ), AP-HP-CHU Saint-Antoine [APHP], Laboratoire de Recherche Vasculaire Translationnelle ( LVTS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Soins Intensifs et Urgences Cardiologiques, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-CHU Angers-UFR de Médecine Lyon-Sud, Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours, Soins Intensifs Cardiologiques, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Universitaire Jean Minjoz, Cardiologie, Cabinet de Cardiologie, Service de Cardiologie, CHU Angers-PRES Université Nantes Angers Le Mans ( UNAM ), Laboratoire de Protection et Remodelage du Myocarde ( PMRM ), Université d'Angers ( UA ) -Université d'Angers ( UA ), Service de cardiologie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Pôle Cardiologie Interventionnelle / Coro-scanner / IRM Cardiaque, Clinique Saint Gatien, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Université de Tours (UT), Service d'anesthésie et soins intensifs [CHRU Besançon], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de Protection et Remodelage du Myocarde (PMRM), Université d'Angers (UA)-Université d'Angers (UA), Service de cardiologie [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, HAL UPMC, Gestionnaire, Dupuis, Christine, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP), Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), CHRU Tours, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), and PRES Université Nantes Angers Le Mans ( UNAM )
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Male ,medicine.medical_specialty ,Time Factors ,Myocardial Infarction ,Shock, Cardiogenic ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology ,Internal medicine ,medicine ,Humans ,Registries ,030212 general & internal medicine ,Myocardial infarction ,Survival rate ,Aged ,Aged, 80 and over ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,Research ,ST elevation ,Cardiogenic shock ,Hazard ratio ,Middle Aged ,[ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,medicine.disease ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,3. Good health ,Survival Rate ,Treatment Outcome ,Shock (circulatory) ,Concomitant ,Cardiology ,Female ,France ,Myocardial infarction diagnosis ,medicine.symptom ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Follow-Up Studies - Abstract
Introduction There are little data about patients with cardiogenic shock (CS) who survive the early phase of acute myocardial infarction (AMI). The aim of this study was to assess long-term (5-year) mortality among early survivors of AMI, according to the presence of CS at the acute stage. Methods We analyzed 5-year follow-up data from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2005 registry, a nationwide French survey including consecutive patients admitted for ST or non-ST-elevation AMI at the end of 2005 in 223 institutions. Results Of 3670 patients enrolled, shock occurred in 224 (6.1%), and 3411 survived beyond 30 days or hospital discharge, including 99 (2.9%) with shock. Early survivors with CS had a more severe clinical profile, more frequent concomitant in-hospital complications, and were less often managed invasively than those without CS. Five-year survival was 59% in patients with, versus 76% in those without shock (adjusted hazard ratio (HR) = 1.72 [1.24-2.38], P = 0.001). The excess of death associated with CS, however, was observed only during the first year (one-year survival: 77% vs 93%, adjusted HR: 2.87 [1.85 to 4.46] P
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- 2014
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15. Cost-utility analysis of maintenance therapy with gemcitabine or erlotinib vs observation with predefined second-line treatment after cisplatin-gemcitabine induction chemotherapy for advanced NSCLC: IFCT-GFPC 0502-Eco phase III study
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Maurice Pérol, Sylvie Chabaud, David Pérol, Fabien Vaylet, Michel Poudenx, Lionel Falchero, Virginie Westeel, Gérard Zalcman, Armelle Lavolé, Pascal Do, Jacky Crequit, Laurent Greillier, Hervé Lena, Isabelle Borget, Hervé Le Caer, Pierre Fournel, Isabelle Monnet, Christos Chouaid, Alain Vergnenegre, HAL UPMC, Gestionnaire, Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Hospices Civils de Lyon (HCL), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Creil, Centre Hospitalier Universitaire [Rennes], CHI Créteil, Centre Hospitalier de la Dracénie [Draguignan], Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Hôpital Villefranche sur Saône, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hôpital d'Instruction des Armées Percy, Service de Santé des Armées, CHU Limoges, Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital St Antoine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and CHU Saint-Antoine [AP-HP]
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Oncology ,Male ,Cancer Research ,Palliative care ,Lung Neoplasms ,Cost-Benefit Analysis ,Deoxycytidine ,0302 clinical medicine ,Maintenance therapy ,Carcinoma, Non-Small-Cell Lung ,030212 general & internal medicine ,Prospective Studies ,Erlotinib Hydrochloride ,health care economics and organizations ,Cost-utility ,Health Care Costs ,Induction Chemotherapy ,Middle Aged ,3. Good health ,Erlotinib ,030220 oncology & carcinogenesis ,Female ,Quality-Adjusted Life Years ,medicine.drug ,Research Article ,Adult ,medicine.medical_specialty ,[SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antineoplastic Agents ,Maintenance Chemotherapy ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,Internal medicine ,Genetics ,medicine ,Humans ,Lung cancer ,Aged ,business.industry ,Induction chemotherapy ,medicine.disease ,Survival Analysis ,Gemcitabine ,Quality-adjusted life year ,Surgery ,Quinazolines ,Cisplatin ,business ,Non-small-cell lung cancer - Abstract
on behalf of the IFCT-GFPC investigators; International audience; Background: The IFCT-GFPC 0502 phase III study reported prolongation of progression-free survival with gemcitabine or erlotinib maintenance vs. observation after cisplatin–gemcitabine induction chemotherapy for advanced non-small-cell lung cancer (NSCLC). This analysis was undertaken to assess the incremental cost-effectiveness ratio (ICER) of these strategies for the global population and pre-specified subgroups.Methods: A cost-utility analysis evaluated the ICER of gemcitabine or erlotinib maintenance therapy vs. observation, from randomization until the end of follow-up. Direct medical costs (including drugs, hospitalization, follow-up examinations, second-line treatments and palliative care) were prospectively collected per patient during the trial, until death, from the primary health-insurance provider's perspective. Utility data were extracted from literature. Sensitivity analyses were conducted.Results: The ICERs for gemcitabine or erlotinib maintenance therapy were respectively 76,625 and 184,733 euros per quality-adjusted life year (QALY). Gemcitabine continuation maintenance therapy had a favourable ICER in patients with PS = 0 (52,213 €/QALY), in responders to induction chemotherapy (64,296 €/QALY), regardless of histology (adenocarcinoma, 62,292 €/QALY, non adenocarcinoma, 83,291 €/QALY). Erlotinib maintenance showed a favourable ICER in patients with PS = 0 (94,908 €/QALY), in patients with adenocarcinoma (97,160 €/QALY) and in patient with objective response to induction (101,186 €/QALY), but it is not cost-effective in patients with PS =1, in patients with non-adenocarcinoma or with stable disease after induction chemotherapy.Conclusion: Gemcitabine-or erlotinib-maintenance therapy had ICERs that varied as a function of histology, PS and response to first-line chemotherapy.
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- 2013
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16. Thrombolysis in cervical artery dissection--data from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) database
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Engelter, S. T., Dallongeville, J., Kloss, M., Metso, T. M., Leys, D., Brandt, T., Samson, Yves, Caso, V., Pezzini, A., Sessa, M., Beretta, S., Debette, S., Grond-Ginsbach, C., Metso, A. J., Thijs, V., Lamy, C., Medeiros, E., Martin, J. J., Bersano, A., Tatlisumak, T., Touzé, E., Lyrer, P. A., Renseigné, Non, Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut cellule souche et cerveau (SBRI), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Engelter, S, Dallongeville, J, Kloss, M, Metso, T, Leys, D, Brandt, T, Samson, Y, Caso, V, Pezzini, A, Sessa, M, Beretta, S, Debette, S, Grond Ginsbach, C, Metso, A, Thijs, V, Lamy, C, Medeiros, E, Martin, J, Bersano, A, Tatlisumak, T, Touzé, E, Lyrer, P, Ferrarese, C, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service Parasitologie-Mycologie, Hôpital St. Antoine, and Institut cellule souche et cerveau (U846 Inserm - UCBL1)
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Adult ,Male ,Databases, Factual ,Thrombolysi ,Carotid Artery, Internal, Dissection ,Cervical artery dissection ,Brain Ischemia ,Retrospective Studie ,Odds Ratio ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,Humans ,Multicenter Studies as Topic ,Thrombolytic Therapy ,cardiovascular diseases ,Ischaemic stroke ,Retrospective Studies ,Outcome ,Intracranial Hemorrhage ,Vertebral Artery Dissection ,Middle Aged ,Stroke ,Treatment Outcome ,Neurology ,Female ,Neurology (clinical) ,Intracranial Hemorrhages ,Complication ,Human - Abstract
Objective: To examine whether thrombolysis for stroke attributable to cervical artery dissection (CeADStroke) affects outcome and major haemorrhage rates. Methods: We used a multicentre CeADStroke database to compare CeADStroke patients treated with and without thrombolysis. Main outcome measures were favourable 3-month outcome (modified Rankin Scale 0-2) and 'major haemorrhage' [any intracranial haemorrhage (ICH) and major extracranial haemorrhage]. Adjusted odds ratios [OR (95% confidence intervals)] were calculated on the whole database and on propensity-matched groups. Results: Among 616 CeADStroke patients, 68 (11.0%) received thrombolysis; which was used in 55 (81%) intravenously. Thrombolyzed patients had more severe strokes (median NIHSS score 16 vs. 3; P
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- 2012
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17. Comparative genomics of the Nakaseomyces clade: Candida glabrata and enew merging pathogens
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Fairhead, Cécile, Gabaldón, Toni, Martin, Tiphaine, Durrens, Pascal, Lespinet, Olivier, Hennequin, Christophe, Bolotin-Fukuhara, Monique, Wincker, Patrick, Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Models and Algorithms for the Genome ( MAGNOME), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Modèles et algorithmes pour la Bioinformatique et la Visualisation d'informations, (MABIOVIS), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Service Parasitologie-Mycologie, Hôpital St. Antoine, Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology - Abstract
All authors wish to acknowledge the work of colleagues and collaborators who are authors of the final paper in preparation; International audience; C. glabrata has become the second fungal pathogenic agent of human illness after C. albicans, and two new species, C. nivariensis and C. bracarensis, have been described as emerging pathogens from the clade of the Nakaseomyces. We have sequenced these genomes and that of the other three environmental yeasts from the clade. These species share with Saccharomyces the common ancestor which underwent a whole genome duplication. Nonetheless, chromosome number is highly variable in the clade with some low chromosome numbers. Centromeres show less conservation than expected, as do telomeric repeats. All species share genomic and physiological features that define their monophylogeny. These include genome size and gene number, the presence of insertions in non coding RNA genes, loss of genes from metabolic pathways such as GAL and BNA, and absence of active transposable elements. All contain homologs of genes involved in mating, although most species are described as asexual, and all contain a putative HO gene, enabling mating-type switching in Saccharomyces. Indeed, sexual species in the clade are homothallic and may share with S. cerevisiae the HO gene and three duplicated cassettes. Nonetheless, variations are observed in the chromosomal structure of the cassettes. Other features are common only to C. glabrata and closest species. These include duplicated genes encoding ribosomal proteins, for example. We will report on gene family expansions and contractions in species, on specific features of pathogens, and on specificities of C. glabrata, such as tandem amplification of genes involved in virulence.
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- 2011
18. Rapid Discrimination between Candida glabrata, Candida nivariensis, and Candida bracarensis by Use of a Singleplex PCR ▿
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Pascal Durrens, Cécile Fairhead, Juliette Guitard, Tiphaine Martin, Christophe Hennequin, Adela Enache-Angoulvant, Frédéric Grenouillet, Mucoviscidose: physiopathologie et phénogénomique [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Parasitologie - Mycologie [CHU Saint-Antoine], CHU Saint-Antoine [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), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Physique Théorique - UMR 6207 (CPT), Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Immunité et Infection, IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de Parasitologie-Mycologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Mycology-Parasitology Department, Université de Franche-Comté (UFC), Models and Algorithms for the Genome ( MAGNOME), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Modèles et algorithmes pour la Bioinformatique et la Visualisation d'informations, (MABIOVIS), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Guitard, Juliette, Institut de génétique et microbiologie [Orsay] ( IGM ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Service Parasitologie-Mycologie, Hôpital St. Antoine, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Université de Franche-Comté ( UFC ), Models and Algorithms for the Genome ( MAGNOME ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), ( MABIOVIS ), Laboratoire Bordelais de Recherche en Informatique ( LaBRI ), Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Inria Bordeaux - Sud-Ouest, and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)
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Microbiology (medical) ,Microbiological Techniques ,[SDV]Life Sciences [q-bio] ,Molecular Sequence Data ,Mycology ,Biology ,Polymerase Chain Reaction ,Microbiology ,03 medical and health sciences ,[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology ,DNA, Ribosomal Spacer ,Humans ,Base sequence ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,DNA, Fungal ,[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Candida bracarensis ,030304 developmental biology ,Candida ,DNA Primers ,0303 health sciences ,Candida glabrata ,Base Sequence ,030306 microbiology ,Fungal genetics ,Candidiasis ,Sequence Analysis, DNA ,Amplicon ,biology.organism_classification ,Candida nivariensis ,[SDV] Life Sciences [q-bio] ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Primer (molecular biology) ,Sequence Alignment ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
We report here a PCR-based assay using a single primer pair targeting the RPL31 gene that allows discrimination between Candida glabrata , Candida bracarensis , and Candida nivariensis according to the size of the generated amplicon.
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- 2011
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19. Pneumocystosis: a network survey in the Paris area 2003-2008
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P. Roux, Marie-Elisabeth Bougnoux, M. Cornet, C. Sarfati, Françoise Botterel, Claire Bouges-Michel, Patrice Bourée, Hélène Yera, G. Galeazzi, D. Magne, C. Chochillon, Adela Angoulvant, Eric Dannaoui, Arnaud Fekkar, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Pitié-Salpêtrière [AP-HP], Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Cochin [AP-HP], Hôpital St Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Hôpital Bichat-Claude Bernard, Hôpital Hôtel Dieu, Hôpital Européen Georges Pompidou, Hôpital St Antoine, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ), Parasitogie-Mycologie, CHU Saint-Antoine [APHP], CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), CHU Pitié-Salpêtrière [APHP], Hopital Louis Mourier - AP-HP [Colombes], CHU Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Thérapeutique Recombinante Expérimentale ( TIMC-IMAG-THEREX ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Information – Technologies – Analyse Environnementale – Procédés Agricoles ( UMR ITAP ), Institut national d’études supérieures agronomiques de Montpellier ( Montpellier SupAgro ) -Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture ( IRSTEA ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
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Male ,Antifungal Agents ,MESH: CD4 Lymphocyte Count ,MESH : Genotype ,DHPS ,HIV Infections ,MESH: Comorbidity ,Drug resistance ,Comorbidity ,Pneumocystis carinii ,MESH: Genotype ,0302 clinical medicine ,Adrenal Cortex Hormones ,Neoplasms ,Epidemiology ,Pneumocystosis ,MESH: Immunocompromised Host ,MESH : Female ,MESH: Neoplasms ,MESH : Sulfanilamides ,030212 general & internal medicine ,MESH: Dihydropteroate Synthase ,[ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology ,[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology ,MESH : Pneumocystis jirovecii ,0303 health sciences ,MESH: Middle Aged ,Mortality rate ,Pneumonia, Pneumocystis ,MESH: Paris ,MESH : Pneumonia, Pneumocystis ,MESH : Paris ,Life Sciences ,MESH : Immunocompromised Host ,General Medicine ,MESH: HIV Infections ,MESH: Transplantation ,Middle Aged ,MESH: Hospitals ,Hospitals ,3. Good health ,MESH : Hospitals ,MESH : Antineoplastic Agents ,Infectious Diseases ,MESH : Comorbidity ,Female ,MESH : Dihydropteroate Synthase ,Microbiology (medical) ,medicine.medical_specialty ,Paris ,Genotype ,MESH : Male ,MESH : Antifungal Agents ,Antineoplastic Agents ,MESH: Drug Resistance, Fungal ,MESH : Adrenal Cortex Hormones ,MESH: Adrenal Cortex Hormones ,03 medical and health sciences ,Immunocompromised Host ,MESH: Sulfanilamides ,MESH: Pneumocystis jirovecii ,Drug Resistance, Fungal ,Internal medicine ,Sulfanilamides ,MESH : CD4 Lymphocyte Count ,MESH : HIV Infections ,medicine ,Humans ,MESH : Middle Aged ,Mycosis ,Dihydropteroate Synthase ,Transplantation ,MESH: Humans ,030306 microbiology ,business.industry ,MESH : Humans ,MESH : Drug Resistance, Fungal ,medicine.disease ,MESH: Antifungal Agents ,MESH : Neoplasms ,MESH: Male ,Surgery ,CD4 Lymphocyte Count ,MESH : Transplantation ,MESH: Antineoplastic Agents ,business ,MESH: Female ,MESH: Pneumonia, Pneumocystis - Abstract
International audience; The aims of this network group were to collect epidemiological data of PcP cases in 14 hospitals in the Paris area and to determine the Di-Hydro Pteroate Synthase (DHPS) genotypes, genetic markers for possible sulfamide resistance. From January 1, 2003 to December 31, 2008, 993 (mean 166/year) PcP cases have been reported. Sixty-five percent of patients were HIV-positive. The median count of CD4 lymphocytes was 32/mm(3) (30 in HIV-positive patients, 152 in HIV-negative patients). In HIV-positive patients, PcP revealed the HIV infection in 39%. Among 304 PcP occurring in HIV known infected patients, no prophylaxis was prescribed for 64%; cotrimoxazole prophylaxis had been prescribed to 47 patients but only one of them had the right compliance. In HIV-negative patients (264), corticosteroids were prescribed in 59% and cytotoxic chemotherapies in 34%; 78% did not receive prophylaxis. One hundred sixty nine tumoral pathologies and 116 transplantations were notified. The mortality rate was 16% at day 14 (13% in HIV-positive patients, 26% in HIV-negative patients). Mutations in DHPS genes were detected in 18.5% of samples; 12.5% of patients were infected with several strains. The total annual number of cases has been stable for five years but the proportion of HIV-negative patients increased from 25% to 43%.
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- 2011
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20. Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis
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Jacques Dubin, Christine Francannet, Jacqueline Levilliers, Thierry Mom, Magali Niasme-Grare, J.-P. Hardelin, Françoise Denoyelle, Diana Zelenika, Valérie Drouin-Garraud, Didier Lacombe, Sandrine Marlin, Marc Delepine, Patrick Collignon, Alain Duvillard, Christel Thauvin, Sabine Sigaudy, Jacqueline Vigneron, Albert David, Anne Marie Frances, Christophe Vincent, Françoise Duriez, Dominique Weil, Catherine Calais, Marine Parodi, M'hamed Grati, Hélène Dollfus, Delphine Feldmann, Bruno Delobel, Laurence Jonard, Christine Petit, Marie Françoise Thuillier-Obstoy, Bettina Montaut-Verient, Crystel Bonnet, Jean Weissenbach, Aziz El-Amraoui, Georges Challe, Dominique Bonneau, Mark Lathrop, Marie Madeleine Eliot, José-Alain Sahel, Rémy Couderc, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Collège de France - Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), NIDCD, National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Génétique, Service ORL, Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'ORL et chirurgie cervico-faciale, Service d'oto-rhino-laryngologie (ORL), Hôtel-Dieu, Maternité Régionale Adolphe Pinard [Nancy], Maternité Régionale Adolphe-Pinard, Centre de Référence des Maladies Neurogénétiques, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service Oto-Rhino-Laryngologie [CHU de Dijon] (ORL [CHU de Dijon]), Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'ORL, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'ophtalmologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service ORL Pédiatrique, Normandie Université (NU)-Normandie Université (NU), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale, Hôpital intercommunal de Font-Pré, CHU Pitié-Salpêtrière [AP-HP], Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), M.G. was supported by European Commission FP6 Integrated project, EuroHear (LSHG-CT-2004-512063) and C.B. by the French Foundation 'Voir et Entendre'. This work was supported by Fondation R & G Strittmatter (under the aegis of Fondation de France), FAUN Stiftung (Suchert Foundation), ECFP7 TREATRUSH (HEALTH-F2-2010-242013), Foundation Fighting Blindness, LHW-Stiftung, Fondation Orange, The Conny-Maeva Charitable Foundation, Genoscope-CNRG project AP2005, and S'entendre Foundation., Service de génétique et embryologie médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chaire Génétique et physiologie cellulaire, Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], Hôpital St-Antoine, Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Normandie Université (NU)-Hôpital Charles-Nicolle, Hôpital Charles-Nicolle, Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'ORL pédiatrique et Chirurgie Cervico-faciale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and BMC, Ed.
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Usher syndrome ,lcsh:Medicine ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,MESH: Amino Acid Sequence ,medicine.disease_cause ,MESH: Genotype ,Exon ,0302 clinical medicine ,Genotype ,Genetics(clinical) ,Pharmacology (medical) ,Genetics (clinical) ,Exome sequencing ,Medicine(all) ,Genetics ,0303 health sciences ,Mutation ,Splice site mutation ,MESH: Genomics ,Exons ,Genomics ,General Medicine ,MESH: Case-Control Studies ,Pedigree ,3. Good health ,France ,Usher Syndromes ,MESH: Mutation ,MESH: Pedigree ,Molecular Sequence Data ,Biology ,03 medical and health sciences ,medicine ,otorhinolaryngologic diseases ,Humans ,Amino Acid Sequence ,MESH: Usher Syndromes ,Gene ,Genotyping ,MESH: Genome, Human ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,MESH: Molecular Sequence Data ,Genome, Human ,Research ,lcsh:R ,medicine.disease ,MESH: France ,Case-Control Studies ,MESH: Exons ,030217 neurology & neurosurgery - Abstract
Background Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. Methods We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Results Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Conclusions Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.
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- 2011
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21. MALDI-TOF MS-based drug susceptibility testing of pathogens: the example of Candida albicans and fluconazole
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Dominique Sanglard, Arnaud Fekkar, Annick Datry, Jean-Louis Golmard, Georges Snounou, Christophe Hennequin, Alexandre Alanio, Martine Palous, Dominique Mazier, Jean-Yves Brossas, Stéphanie Kwasek, Carine Marinach, Sophie Brun, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Muséum national d'Histoire naturelle (MNHN), CHU Saint-Antoine [AP-HP], Université de Lausanne = University of Lausanne (UNIL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], Service Parasitologie-Mycologie, Hôpital St. Antoine, University of Lausanne and University Hospital Centre, Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de parasitologie - mycologie [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 Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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Drug ,Antifungal Agents ,media_common.quotation_subject ,[SDV]Life Sciences [q-bio] ,Drug resistance ,Microbial Sensitivity Tests ,Proteomics ,Biochemistry ,Microbiology ,03 medical and health sciences ,Candida albicans ,medicine ,Matrix-Assisted Laser Desorption-Ionization ,Molecular Biology ,Fluconazole ,030304 developmental biology ,media_common ,0303 health sciences ,biology ,030306 microbiology ,Spectrometry ,Fungi imperfecti ,Mass ,biology.organism_classification ,Yeast ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Proteome ,medicine.drug - Abstract
International audience; MALDI-TOF MS can be used for the identification of microorganism species. We have extended its application to a novel assay of Candida albicans susceptibility to fluconazole, based on monitoring modifications of the proteome of yeast cells grown in the presence of varying drug concentrations. The method was accurate, and reliable, and showed full agreement with the Clinical Laboratory Standards Institute's reference method. This proof-of-concept demonstration highlights the potential for this approach to test other pathogens.
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- 2009
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22. Characteristics and clinical course of primary sclerosing cholangitis in France: a prospective cohort study
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Armand Garioud, Yves Chretien, Philippe Seksik, Christophe Corphechot, Raoul Poupon, Olivier Chazouillères, Renée E. Poupon, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'hépatologie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital St Antoine
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Male ,medicine.medical_treatment ,Liver transplantation ,Gastroenterology ,Cholangiocarcinoma ,Cohort Studies ,Liver disease ,0302 clinical medicine ,Prospective Studies ,10. No inequality ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Incidence ,Liver Neoplasms ,Ursodeoxycholic Acid ,Middle Aged ,Prognosis ,3. Good health ,medicine.anatomical_structure ,Treatment Outcome ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Female ,Gallbladder Neoplasms ,France ,Colorectal Neoplasms ,Adult ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Adolescent ,Cholangitis, Sclerosing ,Primary sclerosing cholangitis ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Carcinoma ,Humans ,Aged ,Hepatology ,business.industry ,Gallbladder ,Cancer ,medicine.disease ,digestive system diseases ,Liver Transplantation ,Transplantation ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,business ,Liver Failure - Abstract
International audience; BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is a rare disease, and large-scale report of PSC in France is lacking. We initiated a prospective multisite observational study. METHODS: One hundred and fifty PSC patients (90 with associated inflammatory bowel disease) were included. At entry, 11 patients had a diagnosis of hepatobiliary or colon malignancy (cholangiocarcinoma: n = 5, hepatocellular carcinoma: n = 2, gallbladder carcinoma: n = 1 and colorectal cancer: n = 4). One hundred and forty-one patients (94%) were treated with ursodeoxycholic acid (UDCA) (median dose: 13.1 mg/kg/day), including 118 with UDCA started before inclusion. RESULTS: During follow-up [3.9 (0.1-7.2) years], colorectal cancer was diagnosed in four patients and biliary carcinoma in two (incidences: 0.76 and 0.38 for 100 patient-years, respectively). Kaplan-Meier transplant-free survival at 4 years was 79%. Main causes of death (n = 10) were cancer (n = 5, including three colorectal cancers and two cholangiocarcinoma) or liver failure (n = 4). Indications for transplantation (n = 25) were end-stage liver disease (n = 16), biliary cancer (known or suspected) (n = 5), recurrent acute cholangitis (n = 3) or pruritus (n = 1). Independent predictive factors of death or transplantation were alkaline phosphatase at least 3 upper limit of normal values, platelets less than or equal to 150000/mm3 and bilirubin at least 23 micromol/l. Observed and predicted survivals were similar. CONCLUSION: PSC in France shares common features with other series and is almost universally treated with UDCA. Under standard-dose UDCA, PSC remains a rather severe disease. However, the low incidence of cholangiocarcinoma is compatible with a potential chemoprotective effect of UDCA against biliary neoplasia development.
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- 2009
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23. Outbreaks of nosocomial candidiasis in France 1996-2006
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C. Hennequin, T. Ancelle, French biologists, S. Beretta, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Service de Parasitologie-Mycologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service Parasitologie-Mycologie, Hôpital St. Antoine, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
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Microbiology (medical) ,medicine.medical_specialty ,Disease Outbreaks ,03 medical and health sciences ,MESH: Infection Control ,0302 clinical medicine ,Surveys and Questionnaires ,Medicine ,Humans ,MESH: Hygiene ,030212 general & internal medicine ,MESH: Incidence ,MESH: Disease Outbreaks ,Intensive care medicine ,ComputingMilieux_MISCELLANEOUS ,Retrospective Studies ,MESH: Academic Medical Centers ,0303 health sciences ,Academic Medical Centers ,Cross Infection ,Infection Control ,MESH: Humans ,030306 microbiology ,business.industry ,Incidence ,MESH: Questionnaires ,Candidiasis ,Outbreak ,MESH: Cross Infection ,Hygiene ,MESH: Retrospective Studies ,General Medicine ,MESH: Candidiasis ,MESH: France ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,France ,business - Abstract
International audience
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- 2008
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24. Viral rebound on antiretroviral therapy in France according to region of origin, sex, and HIV acquisition group. Results from the French Hospital Database on HIV (ANRS CO4-FHDH).
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Abgrall S, Selinger-Leneman H, Lanoy E, Becker A, Matheron S, de Truchis P, Pavie J, Canestri A, Khuong MA, Rey D, Caby F, Tattevin P, Palich R, and Grabar S
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- Humans, Male, Female, France epidemiology, Adult, Middle Aged, Transients and Migrants statistics & numerical data, Viral Load, Sex Factors, Africa South of the Sahara epidemiology, Databases, Factual, West Indies epidemiology, Anti-HIV Agents therapeutic use, Anti-Retroviral Agents therapeutic use, Risk Factors, HIV Infections drug therapy, HIV Infections epidemiology
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Background: Assessing the potential increased risk of viral rebound (VR) in migrants requires adequate control for sex and acquisition risk groups., Methods: People living with HIV1, enrolled in the ANRS CO4-French Hospital Database on HIV, who achieved virological suppression with antiretroviral therapy (ART) initiated between 2006 and 2016 were included. We first compared the risk of VR, with loss to follow-up and death considered as competing events, across origin among the HIV acquisition groups, then across acquisition groups among the different origins, and finally across modality of a variable combining sex, acquisition group, and origin. Models were adjusted for clinical and biological confounding factors., Results: We included 21 571 French natives (FRA), 10 148 migrants from sub-Saharan Africa (SSA), 1137 migrants from the non-French West Indies (NFWI), and 4205 other migrants (OTHER). The 5-year probability of VR was 19% (95% confidence interval [CI] 19-20) overall, 15% in FRA, 21% in OTHER, 26% in SSA, and 34% in NFWI (p < 0.0001). It was 14% in men who have sex with men (MSM), 23% in heterosexual men, and 23% in women (p < 0.0001). After adjustment, all acquisition groups had a higher risk of VR than MSM from FRA, with men and women from NFWI having the highest risk (adjusted hazard ratio [aHR] 2.46; 95% CI 2.12-2.86 and aHR 2.59; 95% CI 2.20-3.04, respectively). Within each acquisition group, all groups of origin had a higher risk of VR than FRA. Within each region of origin, except the NFWI, heterosexual men had a higher risk of VR than MSM., Conclusions: After accounting for sex and acquisition group, migration, especially from NFWI, remains prognostic of VR., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)
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- 2025
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25. Final Results of the GRECCAR-6 Trial on Waiting Period Following Neoadjuvant Radiochemotherapy for Locally Advanced Rectal Cancer: 5 Years of Follow-up.
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Collard MK, Mineur L, Nekrouf C, Denost Q, Rouanet P, de Chaisemartin C, Merdrignac A, Jafari M, Cotte E, Desrame J, Manceau G, Benoist S, Buscail E, Karoui M, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Duchalais E, Lupinacci RM, Goasguen N, Simon T, Parc Y, and Lefevre JH
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- Humans, Male, Female, Middle Aged, Aged, Follow-Up Studies, Disease-Free Survival, Chemoradiotherapy methods, Proctectomy, Prognosis, Adult, Survival Rate, Chemoradiotherapy, Adjuvant methods, Rectal Neoplasms therapy, Rectal Neoplasms pathology, Rectal Neoplasms mortality, Neoadjuvant Therapy methods, Adenocarcinoma therapy, Adenocarcinoma pathology, Adenocarcinoma mortality, Fluorouracil therapeutic use, Fluorouracil administration & dosage, Capecitabine administration & dosage, Capecitabine therapeutic use, Neoplasm Staging
- Abstract
Background: The potential oncological benefit of extending the waiting period between neoadjuvant radiochemotherapy and surgical resection for rectal cancer is debated., Objective: To evaluate the impact of prolonging this waiting period on the 5-year oncological prognosis and 2-year functional result of locally advanced rectal adenocarcinoma., Design: Phase III, multicenter, randomized, open-label, parallel-group, controlled trial., Settings: Patients were enrolled from 24 colorectal centers., Patients: Patients with nonmetastatic mid or lower cT3/T4Nx or cTxN+ rectal adenocarcinoma who had received radiochemotherapy (45-50 Gy radiation dose with fluorouracil or capecitabine)., Intervention: Patients were randomly assigned to undergo total mesorectal excision either 7 weeks or 11 weeks after radiochemotherapy., Main Outcomes Measures: Overall survival and disease-free survival at 5-year follow-up and low anterior resection syndrome score assessed after 2 years of follow-up., Results: Among 265 patients enrolled, 133 were randomized in the 7-week group and 132 in the 11-week group. Twelve patients were excluded because they did not undergo resection. Among 253 patients analyzed, 5-year overall survival was not different between the 2 groups (81.6% in the 7-week group vs 82.6% in the 11-week group, p = 0.827), and neither was the 5-year disease-free survival (70.4% in the 7-week group vs 69.5% in the 11-week group, p = 0.856). No difference was observed between the 2 groups for distant recurrence (27.4% in the 7-week group vs 25.7% in the 11-week group, p = 0.777) or local recurrence (8.4% in the 7-week group vs 10.2% in the 11-week group, p = 0.543). The low anterior resection syndrome score was similar between the 7-week (25.0; interquartile range, 15.0-34.0) and 11-week groups (23.0; interquartile range, 14.2-32.0; p = 0.743)., Limitations: The response rate to the low anterior resection syndrome questionnaire was only 52%., Conclusions: Extending the waiting period between radiochemotherapy and resection from 7 to 11 weeks does not change the 5-year oncological prognosis in rectal cancer or the 2-year low anterior resection occurrence. See Video Abstract., Resultados Finales Del Ensayo Greccar Sobre El Perodo De Espera Tras La Radioquimioterapia Neoadyuvante Para El Cncer De Recto Localmente Avanzado Aos De Seguimiento: ANTECEDENTES:Se debate el posible beneficio oncológico de prolongar el periodo de espera entre la radioquimioterapia neoadyuvante y la resección quirúrgica del cáncer de recto.OBJETIVO:Evaluar el impacto de la prolongación de este periodo de espera sobre el pronóstico oncológico a 5 años y el resultado funcional a 2 años del adenocarcinoma rectal localmente avanzado.DISEÑO:Ensayo controlado de fase III, multicéntrico, aleatorizado, abierto, de grupos paralelos.LUGAR:Se reclutaron pacientes de 24 centros colorrectales.PACIENTES:Pacientes con adenocarcinoma rectal de tercio medio o inferior, no metastásico cT3-4 o TxN+ que habían recibido radioquimioterapia (45 a 50 Gy con fluorouracilo o capecitabina).INTERVENCIÓN:Se asignaron aleatoriamente a los pacientes para ser sometidos a una escisión mesorrectal total 7 semanas (W7) u 11 semanas (W11) después de la radioquimioterapia.MEDIDAS DE RESULTADOS PRINCIPALES:Supervivencia global y supervivencia libre de enfermedad a los 5 años de seguimiento y puntuación del síndrome de resección anterior baja evaluada a los 2 años de seguimiento.RESULTADOS:De los 265 pacientes reclutados, 133 fueron asignados aleatoriamente al grupo de 7 semanas y 132 al grupo de 11 semanas. Doce pacientes fueron excluidos porque no fueron sometidos a resección. Entre los 253 pacientes analizados, la supervivencia global a 5 años no fue diferente entre los dos grupos (81,6% en el grupo de 7 semanas frente a 82,6% en el grupo de 11 semanas, p = 0,827), así como para la supervivencia libre de enfermedad a 5 años (70,4% en el grupo de 7 semanas frente a 69,5% en el grupo de 11 semanas, p = 0,856). No se observaron diferencias entre los dos grupos en cuanto a la recidiva a distancia (27,4% en el grupo de 7 semanas frente a 25,7% en el grupo de 11 semanas, p = 0,777) o la recidiva local (8,4% en el grupo de 7 semanas frente a 10,2% en el grupo de 11 semanas, p = 0,543). La puntuación del síndrome de resección anterior baja fue similar entre los grupos de 7 semanas (25,0 IQR [15,0-34,0]) y 11 semanas (23,0 IQR [14,2-32,0], p = 0,743).LIMITACIONES:La tasa de respuesta al cuestionario LARS fue sólo del 52%.CONCLUSIONES:Ampliar el periodo de espera entre radioquimioterapia y resección de 7 a 11 semanas no modifica el pronóstico oncológico a 5 años en cáncer de recto ni la baja incidencia de resección anterior a 2 años. (Traducción-Dr Osvaldo Gauto )., (Copyright © The ASCRS 2024.)
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- 2025
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26. Beta-variant recombinant SARS CoV-2 vaccine induces durable cross-reactive antibodies against Omicron BA variants.
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Launay O, Gupta R, Machabert T, Konate E, Rousseau A, Vigne C, Beckers F, Devlin L, Botelho-Nevers E, Cachanado M, Chidiac C, Deplanque D, Dussol B, Ben Ghezala I, Lachatre M, Lacombe K, Laine F, Luong Nguyen LB, Pavese P, Schmidt-Mutter C, Tavolacci MP, Chicz RM, Coudsy B, Sridhar S, Touati A, Tartour E, and Simon T
- Abstract
Background: We previously reported the safety and immunogenicity data from a randomized trial comparing the booster responses of vaccinees who received monovalent (MV) recombinant protein Beta-variant (MVB.1.351) and MV ancestral protein (MVD614) vaccines with AS03 adjuvant (Sanofi/GSK) to booster response of vaccinees who received mRNA MV ancestral strain BNT162b2 vaccine (Pfizer-BioNTech)., Methods: First booster of the vaccines was administered in adult participants previously primed with 2 doses of MV ancestral strain BNT162b2. A subset of these participants with available blood samples collected at Day 0 (D0), at 28 days (D28), and 3 months (M3) post-booster were contacted for additional testing (195/208 participants). The persistence of cross-neutralizing antibodies, including against Omicron BA.1 and BA.4/5, up to 3 months after boosting was evaluated using a validated pseudovirus neutralization assay., Results: Across the whole population, MVB.1.351 vaccine induces highest NAbs titers against Omicron BA.1 and BA.4/5 variants at D28 and M3 post-booster. In participants with SARS-CoV-2 infection between D28 and M3, both MVB.1.351 and BNT162b2 vaccine groups show an increase in GMTs against Omicron BA.1 and Omicron BA.4/5 following infection. Among uninfected participants, the ratio of M3 to D28 GMTs was higher for the MVB.1.351 group than the BNT162b2 group against Omicron BA.1 (0.64 [0.53;0.77] versus 0.43 [0.35;0.53]), Omicron BA.4/5 (0.61 [0.50; 0.75] versus 0.44 [0.34; 0.56]), and D614 (0.68 [0.58,0.81] versus 0.46 [0.39,0.55])., Conclusions: The MVB.1.351 vaccine induces higher and durable cross-neutralizing antibodies against Omicron subvariants up to 3 months after boosting compared to an MV ancestral and mRNA BNT162b2 booster vaccine., Competing Interests: Competing interests: The authors declare the following competing interests: R.G., T.M., C.V., F.B., L.D., R.M.C., B.C. and S.S. are Sanofi employees and may hold stocks/shares in the company. O.L. reports grant from French Ministry of Health and grants or contracts from Pfizer, Sanofi-Pasteur, GSK, MSD, MD, AstraZeneca, and Johnson & Johnson. T.S. reports grant from AstraZeneca, Novartis, Sanofi, Bayer and personal fees for board membership and consulting. K.L. reports personal fees and fees for development of educational presentations from Gilead, MSD, Janssen, ViiV, Spikimm, Janssen, Sobi, and Chiesi. EBN has received grant pending from Sanofi Pasteur and fees for board membership from Pfizer, and Janssen. L.B.L.N. received personal fees for advisory experts and participation to conference from Pfizer. All other authors have no competing interests to declare., (© 2025. The Author(s).)
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- 2025
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27. HIV prevention and missed opportunities among people with recently acquired HIV infection: Α protocol for a systematic review.
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Karakosta A, Ruiz-Burga E, Tariq S, Touloumi G, Jay Nicholls E, Pantazis N, Jarrin I, Van der Valk M, Sabin C, Mussini C, Meyer L, Volny Anne A, Carlander C, Grabar S, Wittkop L, Spire B, Gill J, Porter K, and Burns F
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- Humans, HIV Infections prevention & control, HIV Infections epidemiology, Systematic Reviews as Topic
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Background: Individuals who have recently acquired HIV represent a unique population because the time frame since HIV acquisition is relatively short and identification of missed HIV prevention opportunities is, therefore, closer to real time and less subject to recall bias. Identifying prevention measures used and missed opportunities for using them, can help stop further HIV transmission., Objectives: This systematic review aims to synthesise current global evidence on uptake of HIV prevention methods among people with recently acquired HIV from 2007, the year that the concept of ART as a prevention method was first introduced., Methods and Analysis: MEDLINE/PubMed, EMBASE, PsycINFO, Cochrane and Web of Science databases, will be searched for articles published January 2007-December 2023. Eligible studies will be those that reported on HIV prevention methods among people with recently acquired HIV. Quality assessment of the studies selected will be undertaken, and reporting of the systematic review will be informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: The systematic review is expected to provide comprehensive insights into the uptake, use and adherence to HIV prevention methods among individuals with recently acquired HIV. Analysis anticipates identifying gaps in prevention coverage, missed opportunities for intervention, and variations in access to and use of prevention strategies. Sociodemographic, personal, and behavioural factors influencing prevention uptake and adherence will also be synthesised., Conclusions: The findings will be of key relevance to researchers, healthcare providers including third sector organisations/ community groups and policymakers, as they will offer insight into better understanding of missed or failed HIV prevention efforts and will help ensure future efforts meet the needs of those in need of them., Competing Interests: Conflicts of interest The funders did not participate in the study design and will not intervene in its process, analysis or publication of the findings. ST has received speaker honoraria and consultancy fees from Gilead Sciences. CC has received speaker/moderator honoraria and advisory board fees from Gilead Sciences, GSK/ViiV and MSD as well as an unrestricted Gilead Sciences Nordic Fellowship Research Grant. CS has received funding from Gilead Sciences, ViiV Healthcare and Janssen-Cilag for participation in Advisory Boards, speaker panels and for preparation of educational materials. MVdV has received consultancies fees for participation in advisory boards and research grants from Gilead, MSD and ViiV all paid to his institution. FB has received funding from Gilead Sciences Ltd for preparation and delivery of educational materials. IJ has received teaching fees from ViiV Healthcare and advisory fees from Gilead Sciences. GT has received research grants and advisory board fees from Gilead, all paid to her institution, and MJG has received honoraria for ad hoc participation in national Advisory boards of Gilead Merck and ViiV., (Copyright: © 2024 Karakosta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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28. Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease.
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Sissoko A, Cissé A, Duverdier C, Marin M, Dumas L, Manceau S, Maître B, Eckly A, Fricot-Monsinjon A, Roussel C, Ndour PA, Dussiot M, Dokmak S, Aussilhou B, Dembinski J, Sauvanet A, Paye F, Lesurtel M, Cros J, Wendum D, Tichit M, Hardy D, Capito C, Allali S, and Buffet P
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- Humans, Child, Adolescent, Male, Female, Adult, Hypersplenism etiology, Erythrocytes, Young Adult, Child, Preschool, Anemia, Sickle Cell blood, Anemia, Sickle Cell complications, Spleen pathology, Splenectomy, Erythrocytes, Abnormal pathology, Erythrocytes, Abnormal ultrastructure
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In children with sickle cell disease (SCD), splenectomy is immediately beneficial for acute sequestration crises and hypersplenism (ASSC/HyS) but portends a long-term risk of asplenia-related complications. We retrieved peripheral and splenic red blood cells (RBCs) from 17 SCD children/teenagers undergoing partial splenectomy for ASSC/HyS, 12 adult subjects without RBC-related disease undergoing splenectomy (controls), five human spleens perfused ex vivo with Hb
SS - and HbAA -RBC, and quantified abnormal RBC by microscopy, spleen-mimetic RBC filtration, and adhesion assays. Spleens were analyzed by immunohistochemistry and transmission electron microscopy (TEM). In circulating blood of SCD and control subjects, dysmorphic (elongated/spherocytic) RBCs were <2%, while proportions of pocked-RBC were 4.3-fold higher in SCD children than in controls. Compared to controls, splenic RBCs were more frequently dysmorphic (29.3% vs. 0.4%), stiffer (42.2% vs. 12.4%), and adherent (206 vs. 22 adherent RBC/area) in SCD subjects. By TEM, both polymer-containing and homogenous RBC contributed to spleen congestion, resulting in 3.8-fold higher RBC population density in SCD spleens than in control spleens, predominantly in the cords. Perfused spleens with normal function displayed similar congestion and retention of dysmorphic RBC as SCD spleens. The population density of active macrophages was similar in SCD and control spleens, with a relative deficit in phagocytosis of polymer-containing RBC. Despite the existence of hyposplenism, splenectomy in SCD children removes an organ that still efficiently filters out potentially pathogenic altered RBC. Innovative treatments allowing fine-tuned reduction of RBC retention would alleviate spleen congestion, the major pathogenic process in ASSC/HyS, while preserving spleen protective functions for the future., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)- Published
- 2024
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29. Multiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli.
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Fransson J, Bachelin C, Ichou F, Guillot-Noël L, Ponnaiah M, Gloaguen A, Maillart E, Stankoff B, Tenenhaus A, Fontaine B, Mochel F, Louapre C, and Zujovic V
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- Humans, Adult, Male, Female, Middle Aged, Macrophage Activation physiology, Phagocytosis, Oligodendroglia metabolism, Myelin Sheath metabolism, Monocytes metabolism, Monocytes immunology, Macrophages metabolism, Macrophages immunology, Multiple Sclerosis metabolism, Multiple Sclerosis immunology
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Background and Objectives: In multiple sclerosis (MS), immune cells invade the CNS and destroy myelin. Macrophages contribute to demyelination and myelin repair, and their role in each process depends on their ability to acquire specific phenotypes in response to external signals. In this article, we assess whether defects in MS patient macrophage responses may lead to increased inflammation or lack of neuroregenerative effects., Methods: CD14
+ CD16- monocytes from patients with MS and healthy controls (HCs) were activated in vitro to obtain homeostatic-like, proinflammatory, and proregenerative macrophages. Macrophage activation profiles were assessed through RNA sequencing and metabolomics. Surface molecule expression of CD14, CD16, and HLA-DR and myelin phagocytic capacity were evaluated with flow cytometry. Macrophage supernatant capacity to influence oligodendrocyte precursor cell differentiation toward an astrocytic or oligodendroglia fate was also tested., Results: We observed that MS patient monocytes ex vivo recapitulate their preferential activation toward the CD16+ phenotype, a subset of proinflammatory cells overrepresented in MS lesions. Functionally, MS patient macrophages display a decreased capacity to phagocytose human myelin and a deficit of processing myelin after ingestion. In addition, MS patient macrophage supernatant favors astrocytes over oligodendrocyte differentiation when compared with HC macrophage supernatant. Furthermore, even when exposed to homeostatic or proregenerative stimuli, MS patient macrophages uphold a proinflammatory transcriptomic profile with higher levels of cytokine/chemokine. Of interest, MS patient macrophages exhibit a distinct metabolic signature with a mitochondrial energy metabolism blockage. Transcriptomic data are further substantiated by metabolomics studies that reveal perturbations in the corresponding metabolic pathways., Discussion: Our results show an intrinsic defect of MS patient macrophages, reminiscent of innate immune cell memory in MS, lifting macrophage importance in the disease and as potential therapeutic targets.- Published
- 2024
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30. Changes in bodyweight after initiating antiretroviral therapy close to HIV-1 seroconversion: an international cohort collaboration.
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Pantazis N, Sabin CA, Grabar S, Van der Valk M, Jarrin I, van Sighem A, Meyer L, Carlander C, Gill J, Volny Anne A, Spire B, Tariq S, Burns F, Costagliola D, Ruiz-Burga E, Touloumi G, and Porter K
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- Humans, Male, Female, Adult, Retrospective Studies, Anti-HIV Agents therapeutic use, Middle Aged, HIV Seropositivity drug therapy, HIV Seropositivity immunology, Canada epidemiology, Young Adult, Seroconversion, Cohort Studies, United Kingdom epidemiology, HIV Infections drug therapy, HIV Infections immunology, HIV-1 drug effects, Body Weight
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Background: Understanding the reasons for and consequences of bodyweight change in people living with HIV initiating antiretroviral therapy (ART) is crucial to optimising long-term health and wellbeing. We aimed to examine bodyweight trends and associated factors among individuals with well estimated dates of HIV-1 seroconversion., Methods: In this cohort study, we pooled retrospective data from clinical records of participants in CASCADE aged 16 years and older recruited from clinics in France, Greece, the Netherlands, Spain, Sweden, the UK, and Canada. All participants had well estimated dates of HIV-1 seroconversion, seroconverted between Jan 1, 2007, and Dec 31, 2022 (HIV-1 positive antibody test within 12 months of an HIV-1 negative antibody test, or other laboratory evidence of seroconversion), initiated ART within 1 year of seroconversion, and were previously ART-naive. Participants were followed up to the time of data pooling (May 31, 2023). We modelled bodyweight changes after ART initiation by ART class, BMI categories, and other demographic characteristics using linear mixed models., Findings: Of 15 755 potentially eligible participants, 5698 met inclusion criteria. Of those, 5148 (90·3%) were assigned male at birth, 517 (9·1%) were assigned female at birth, and 33 (0·6%) had sex not known. 2778 (48·8%) participants initiated integrase strand transfer inhibitor (INSTI)-based ART regimens, 1809 (31·7%) initiated protease inhibitor-based regimens, and 1111 (19·5%) initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. The majority of participants were men who have sex with men (MSM; 4519 [79·3%]). Median age at seroconversion was 33·7 years (IQR 26·9-43·2). Bodyweight changes differed significantly by ART class within all baseline BMI categories (BMI <18·5 kg/m
2 p=0·026, BMI 18·5-24·9 kg/m2 p<0·0001, BMI 25·0-29·9 kg/m2 p=0·0021, and BMI ≥30·0 kg/m2 p=0·0033; ART class and BMI interaction p=0·011). Participants with BMI less than 30 kg/m2 on regimens including both INSTI and tenofovir alafenamide gained 4·76 kg (95% CI 4·05-5·46) or more at 3 years. Of those with baseline BMI 18·5-24·9 kg/m2 , 31·3% (95% CI 29·5-33·1) on INSTI-based regimens, 25·3% (23·0-27·7) on protease inhibitor-based regimens, 20·4% (18·8-22·9) on NNRTI-based regimens, 37·4% (33·9-40·9) on tenofovir alafenamide-based regimens, and 38·4% (34·6-42·1) on tenofovir alafenamide and INSTI-based regimens had gained more than 10% of their baseline bodyweight at 3 years. The greatest 3-year bodyweight gains by individuals on INSTI-based regimens and with BMI 18·5-24·9 kg/m2 were in women (5·63 kg [95% CI 4·92-6·35]), and people originating from sub-Saharan African (5·76 kg [5·06-6·46]), compared with MSM (3·82 kg [3·50-4·13])., Interpretation: Our findings suggest a direct effect of INSTIs and tenofovir alafenamide on bodyweight gain, rather than a return to health effect. Given the known risk for cardiometabolic disease, bodyweight management needs to be part of the overall care of individuals prescribed these drugs., Funding: ViiV Healthcare UK, Janssen Pharmaceutica, and Merck Sharp & Dohme., Competing Interests: Declaration of interests DC reports personal fees from Pfizer (2022) for a lecture outside the submitted work. JG reports advisory board fees from Merck, Gilead, and ViiV. NP has received grants unrelated to this study and paid to his institution from Gilead Sciences Hellas and European Centre for Disease Prevention and Control. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)- Published
- 2024
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31. Restrictive vs Liberal Blood Transfusions for Patients With Acute Myocardial Infarction and Anemia by Heart Failure Status: An RCT Subgroup Analysis.
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Ducrocq G, Cachanado M, Simon T, Puymirat E, Lemesle G, Lattuca B, Ariza-Solé A, Silvain J, Ferrari E, Gonzalez-Juanatey JR, Martínez-Sellés M, Lermusier T, Coste P, Vanzetto G, Cottin Y, Dillinger JG, Calvo G, and Steg PG
- Subjects
- Humans, Female, Male, Aged, Middle Aged, Blood Transfusion statistics & numerical data, Blood Transfusion methods, Cause of Death trends, Erythrocyte Transfusion methods, Erythrocyte Transfusion statistics & numerical data, Heart Failure therapy, Heart Failure complications, Anemia therapy, Anemia complications, Myocardial Infarction complications, Myocardial Infarction therapy
- Abstract
Background: Red blood cell transfusion can cause fluid overload. We evaluated the interaction between heart failure (HF) at baseline and transfusion strategy on outcomes in acute myocardial infarction (AMI)., Methods: We used data from the randomized REALITY trial. HF was defined as history of HF or Killip class > 1 at randomization. Primary outcome was major adverse cardiovascular events (MACE): composite of all-cause death, nonrecurrent AMI, stroke, or emergency revascularization prompted by ischemia at 30 days., Results: Among 658 randomized patients, 311 (47.3%) had HF. Patients with HF had higher rates of MACE at 30 days and 1 year and higher rates of nonfatal new-onset HF. There was no interaction between HF and effect of randomized assignment on the primary outcome or nonfatal new-onset HF. A liberal transfusion strategy was associated with increased all-cause death at 30 days and at 1 year in patients with HF (P
interaction = 0.009 and P = 0.049, respectively). The main numerical difference in cause of death between restrictive and liberal strategies was death by HF at 30 days (4 vs 11)., Conclusions: HF is frequent in patients with AMI and anemia and is associated with higher risk of MACE (including all-cause death) and nonfatal new-onset HF. Although there was no interaction of HF with effect of transfusion strategy on MACE, a liberal transfusion strategy was associated with higher all-cause death that appears driven by a higher risk of early death caused by HF., Clinical Trial Registration: NCT02648113., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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32. Recommendations of the French Society of Rheumatology for the management in current practice of patients with polymyalgia rheumatica.
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Wendling D, Al Tabaa O, Chevet B, Fakih O, Ghossan R, Hecquet S, Dernis E, Maheu E, Saraux A, Besson FL, Alegria GC, Cortet B, Fautrel B, Felten R, Morel J, Ottaviani S, Querellou-Lefranc S, Ramon A, Ruyssen-Witrand A, Seror R, Tournadre A, Foulquier N, Verlhac B, Verhoeven F, and Devauchelle-Pensec V
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- Humans, Adrenal Cortex Hormones therapeutic use, Glucocorticoids therapeutic use, Rheumatology standards, Polymyalgia Rheumatica diagnosis, Polymyalgia Rheumatica therapy, Polymyalgia Rheumatica drug therapy
- Abstract
Objective: To develop recommendations for the routine management of patients with polymyalgia rheumatica (PMR)., Methods: Following standard procedures, a systematic review of the literature by five supervised junior rheumatologists, based on the questions selected by the steering committee (5 senior rheumatologists), was used as the basis for working meetings, followed by a one-day plenary meeting with the working group (15 members), leading to the development of the wording and determination of the strength of the recommendations and the level of agreement of the experts., Results: Five general principles and 19 recommendations were drawn up. Three recommendations relate to diagnosis and the use of imaging, and five to the assessment of the disease, its activity and comorbidities. Non-pharmacological therapies are the subject of one recommendation. Three recommendations concern initial treatment based on general corticosteroid therapy, five concern the reduction of corticosteroid therapy and follow-up, and two concern corticosteroid dependence and steroid-sparing treatments (anti-IL-6)., Conclusion: These recommendations take account of current data on PMR, with the aim of reducing exposure to corticosteroid therapy and its side effects in a fragile population. They are intended to be practical, to help practitioners in the day-to-day management of patients with PMR., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
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33. Feasibility, safety, efficacy and potential scaling-up of sofosbuvir-based HCV treatment in Central and West Africa: (TAC ANRS 12311 trial).
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Lacombe K, Moh R, Chazallon C, Lemoine M, Sylla B, Fadiga F, Le Carrou J, Marcellin F, Kouanfack C, Ciaffi L, Sartre MT, Sida MB, Diallo A, Gozlan J, Seydi M, Cissé V, Danel C, Girard PM, Toni TD, Minga A, Boyer S, Carrieri P, and Attia A
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Africa, Central, Africa, Western, Aminoisobutyric Acids, Benzimidazoles therapeutic use, Benzimidazoles adverse effects, Benzopyrans, Carbamates therapeutic use, Cyclopropanes therapeutic use, Cyclopropanes adverse effects, Drug Therapy, Combination, Feasibility Studies, Fluorenes therapeutic use, Fluorenes adverse effects, Genotype, Hepatitis C drug therapy, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic virology, Heterocyclic Compounds, 4 or More Rings therapeutic use, Heterocyclic Compounds, 4 or More Rings adverse effects, Lactams, Macrocyclic, Leucine analogs & derivatives, Proline analogs & derivatives, Proline therapeutic use, Quinoxalines, Ribavirin therapeutic use, Ribavirin adverse effects, Sulfonamides therapeutic use, Sulfonamides adverse effects, Sustained Virologic Response, Treatment Outcome, Antiviral Agents therapeutic use, Antiviral Agents adverse effects, Hepacivirus genetics, Hepacivirus drug effects, Sofosbuvir therapeutic use, Sofosbuvir adverse effects
- Abstract
Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa., (© 2024. The Author(s).)
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- 2024
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34. Association of Use and Dose of Lipid-Lowering Therapy Post Acute Myocardial Infarction With 5-Year Survival in Older Adults.
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Fayol A, Schiele F, Ferrières J, Puymirat E, Bataille V, Tea V, Chamandi C, Albert F, Lemesle G, Cayla G, Weizman O, Simon T, and Danchin N
- Subjects
- Humans, Female, Male, Time Factors, France epidemiology, Aged, 80 and over, Treatment Outcome, Age Factors, Risk Factors, Risk Assessment, Dyslipidemias drug therapy, Dyslipidemias mortality, Dyslipidemias diagnosis, Dyslipidemias blood, Atorvastatin administration & dosage, Atorvastatin adverse effects, Drug Therapy, Combination, Percutaneous Coronary Intervention mortality, Percutaneous Coronary Intervention adverse effects, Lipids blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Registries, ST Elevation Myocardial Infarction mortality, ST Elevation Myocardial Infarction therapy, ST Elevation Myocardial Infarction diagnosis, Non-ST Elevated Myocardial Infarction mortality, Non-ST Elevated Myocardial Infarction diagnosis, Non-ST Elevated Myocardial Infarction therapy, Ezetimibe therapeutic use, Ezetimibe adverse effects, Ezetimibe administration & dosage
- Abstract
Background: Older people are underrepresented in randomized trials. The association between lipid-lowering therapy (LLT) and its intensity after acute myocardial infarction and long-term mortality in this population deserves to be assessed., Methods: The FAST-MI (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) program consists of nationwide French surveys including all patients admitted for acute myocardial infarction ≤48 hours from onset over a 1- to 2-month period in 2005, 2010, and 2015, with long-term follow-up. Numerous data were collected and a centralized 10-year follow-up was organized. The present analysis focused on the association between prescription of LLT (atorvastatin ≥40 mg or equivalent, or any combination of statin and ezetimibe) and 5-year mortality in patients aged ≥80 years discharged alive. Cox multivariable analysis and propensity score matching were used to adjust for baseline differences., Results: Among the 2258 patients aged ≥80 years (mean age, 85±4 years; 51% women; 39% ST-segment elevation myocardial infarction; 58% with percutaneous coronary intervention), 415 were discharged without LLT (18%), 866 with conventional doses (38%), and 977 with high-dose LLT (43%). Five-year survival was 36%, 47.5%, and 58%, respectively. Compared with patients without LLT, high-dose LLT was significantly associated with lower 5-year mortality (adjusted hazard ratio, 0.78 [95% CI, 0.66-0.92]), whereas conventional-intensity LLT was not (adjusted hazard ratio, 0.93 [95% CI, 0.80-1.09]). In propensity score-matched cohorts (n=278 receiving high-intensity LLT and n=278 receiving no statins), 5-year survival was 52% with high-intensity LLT at discharge and 42% without statins (hazard ratio, 0.78 [95% CI, 0.62-0.98])., Conclusions: In these observational cohorts, high-intensity LLT at discharge after acute myocardial infarction was associated with reduced all-cause mortality at 5 years in an older adult population. These results suggest that high-intensity LLT should not be denied to patients on the basis of old age., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00673036, NCT01237418, and NCT02566200., Competing Interests: Disclosures Dr Schiele reports research grants/lecture fees from Amgen, Bayer, Bouchara-Recordati, Sanofi-Aventis, Servier, Novo Nordisk, Lilly, Organon, Bouchara-Recordati, Boehringer Ingelheim, Lilly, Novartis, and Amarin. Dr Ferrières reports speaking fees for Amgen, Sanofi, Servier, and Merck, Sharp & Dohme. Dr Puymirat has received research grants/lecture fees from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Bouchara-Recordati, Biotronik, Bristol-Myers Squibb, Boehringer Ingelheim, Bracco, Cordis, Daiichi-Sankyo, Lilly, Merck, Sharp & Dohme, Novartis, Novo Nordisk, Organon, Pfizer, Sanofi, Servier, Sunpharm, and Vifor Pharma. Dr Lemesle reports having received fees for consulting and travel support from Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Merck, Sharp & Dohme, Novartis, Novo Nordisk, Organon, Pfizer, Recordati, Sanofi Aventis, and Servier. Dr Cayla has received research grants/lecture fees from Abbott, Amgen, AstraZeneca, Bristol Myers Squibb, Edwards, Microport Cardiac Rhythm Management, Medtronic, and Pfizer. Dr Simon reports having received grants or lecture fees or participation in scientific boards from Ablative Solutions,Air Liquide, AstraZeneca, Bayer, Boehringer, Daiichi-Sankyo, Eli-Lilly, Glaxo-Smith-Kline, Novartis, Servier, and 4Living Biotech Sanofi. Dr Danchin has received personal fees and nonfinancial support from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Sanofi, personal fees from Boehringer Ingelheim, Intercept, Merck, Sharp & Dohme, Novo Nordisk, Pfizer, Servier, Union Chimique Belge Pharmaceuticals, and Vifor, all outside the submitted work. The other authors report no conflicts.
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- 2024
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35. Albumin versus saline infusion for sepsis-related peripheral tissue hypoperfusion: a proof-of-concept prospective study.
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Gabarre P, Desnos C, Morin A, Missri L, Urbina T, Bonny V, Turpin M, Baudel JL, Berard L, Montil M, Guidet B, Voiriot G, Joffre J, Maury E, and Ait-Oufella H
- Subjects
- Humans, Male, Aged, Prospective Studies, Resuscitation, Saline Solution, Albumins therapeutic use, Ischemia, Sepsis complications, Sepsis therapy, Shock, Septic complications, Shock, Septic drug therapy
- Abstract
Background: Albumin has potential endothelial protective effects through antioxidant and anti-inflammatory properties. However, the effect of albumin on peripheral tissue perfusion in human sepsis remains poorly known., Methods: Bi-centric prospective study included patients with sepsis with or without shock and prolonged CRT > 3 s despite initial resuscitation. Clinicians in charge of the patients were free to infuse either saline 500 mL or human serum albumin 20% 100 mL over 15 min. Global hemodynamic parameters as well as peripheral tissue perfusion were analyzed after 1 (H1) and 4 h (H4). The primary endpoint was CRT normalization (< 3 s) at H1., Results: 62 patients were screened, and 50 patients (13 sepsis and 37 septic shock) were included, 21 in the saline group and 29 in the albumin group. SOFA score was 8 [5-11], and SAPS II was 53 [45-70]. Median age was 68 [60-76] years with a higher proportion of men (74%). The primary sources of infection were respiratory (54%) and abdominal (24%). At baseline, comorbidities, clinical and biological characteristics were similar between groups. At H1, CRT normalization (< 3 s) was more frequent in patients receiving albumin as compared to patients treated by saline (63 vs 29%, P = 0.02). The decrease in fingertip CRT was more important in the albumin group when compared to saline group (- 1.0 [- 0.3; - 1.5] vs - 0.2 [- 0.1; - 1.1] seconds, P = 0.04) as well as decrease in mottling score. At H4, beneficial effects of albumin on peripheral tissue perfusion were maintained and urinary output trended to be higher in the albumin group (1.1 [0.5-1.8] vs 0.7 [0.5-0.9] ml/kg/h, P = 0.08). Finally, arterial lactate level did not significantly change between H0 and H4 in the saline group but significantly decreased in the albumin group (P = 0.03)., Conclusion: In patients with resuscitated sepsis, albumin infusion might lead to greater improvement of tissue hypoperfusion compared to saline., Clinicaltrials: gov Identifier: NCT05094856., (© 2024. The Author(s).)
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- 2024
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36. [Allogeneic hematopoietic stem cell transplantation and treatment with CAR-T cells - identification of psycho-social vulnerability factors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].
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Polomeni A, Ainaoui M, Berr A, de Bentzman N, Denis M, Friser V, Magro L, and Yakoub-Agha I
- Subjects
- Humans, Social Vulnerability, Neoplasm Recurrence, Local, Societies, Medical, T-Lymphocytes, Bone Marrow Transplantation, Hematopoietic Stem Cell Transplantation
- Abstract
Allogeneic hematopoietic stem cell transplantation (HCT) and CAR-T cells therapy are treatments with curative aim for certain hematological malignancies, refractory or relapse. Nevertheless, they carry the risk of morbidity and mortality and may have a significant psychosocial impact, particularly for HCT. It is therefore necessary to identify psychological difficulties and social problems, as well as the patient's resources, and those of his entourage, in order to improve his overall management. The objective of this evaluation is not to pose contraindications to treatments, but to adapt the personalized care project. This identification must be carried out early on in the pre-HCT assessment journey to enable the implementation of appropriate actions by the various care providers. Based on a review of the literature, we designed a psychosocial data collection grid that can be initiated in pre-transplant and updated by accompanying the patient at each stage of follow-up (discharge from hospital, day-hospital follow-up, D100 evaluation). This grid is divided into 3 axes: socio-family context, psychological and somatic aspects. This tool allows the traceability of the interventions of different professionals and is a support for multidisciplinary exchanges., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
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- 2024
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37. Comité de surveillance indépendant dans les essais cliniques : de la justification scientifique à l’organisation.
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Locher C, Laporte S, Derambure P, Chassany O, Girault C, Avakiantz A, Bahans C, Deplanque D, Fustier P, Germe AF, Kassaï B, Lacoste L, Petitpain N, Roustit M, Simon T, Train C, and Cucherat M
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- 2024
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38. Generation of transgene-free hematopoietic stem cells from human induced pluripotent stem cells.
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Piau O, Brunet-Manquat M, L'Homme B, Petit L, Birebent B, Linard C, Moeckes L, Zuliani T, Lapillonne H, Benderitter M, Douay L, Chapel A, Guyonneau-Harmand L, and Jaffredo T
- Subjects
- Humans, Mice, Animals, Cell Differentiation, Hematopoietic Stem Cells, Bone Marrow, Induced Pluripotent Stem Cells, Pluripotent Stem Cells, Hematopoietic Stem Cell Transplantation
- Abstract
Hematopoietic stem cells (HSCs) are the rare cells responsible for the lifelong curative effects of hematopoietic cell (HC) transplantation. The demand for clinical-grade HSCs has increased significantly in recent decades, leading to major difficulties in treating patients. A promising but not yet achieved goal is the generation of HSCs from pluripotent stem cells. Here, we have obtained vector- and stroma-free transplantable HSCs by differentiating human induced pluripotent stem cells (hiPSCs) using an original one-step culture system. After injection into immunocompromised mice, cells derived from hiPSCs settle in the bone marrow and form a robust multilineage hematopoietic population that can be serially transplanted. Single-cell RNA sequencing shows that this repopulating activity is due to a hematopoietic population that is transcriptionally similar to human embryonic aorta-derived HSCs. Overall, our results demonstrate the generation of HSCs from hiPSCs and will help identify key regulators of HSC production during human ontogeny., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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39. Intensified screening for SARS-CoV-2 in 18 emergency departments in the Paris metropolitan area, France (DEPIST-COVID): A cluster-randomized, two-period, crossover trial.
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Leblanc J, Dusserre-Telmon L, Chauvin A, Simon T, Sabbatini CE, Hemming K, Colizza V, Bérard L, Convert J, Lazazga S, Jegou C, Taibi N, Dautheville S, Zaghia D, Gerlier C, Domergue M, Larrouturou F, Bonnet F, Fontanet A, Salhi S, LeGoff J, and Crémieux AC
- Subjects
- Adult, Female, Humans, Middle Aged, Cross-Over Studies, Emergency Service, Hospital, France epidemiology, Paris epidemiology, Surveys and Questionnaires, Male, COVID-19 diagnosis, COVID-19 epidemiology, SARS-CoV-2
- Abstract
Background: Asymptomatic and paucisymptomatic infections account for a substantial portion of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions. The value of intensified screening strategies, especially in emergency departments (EDs), in reaching asymptomatic and paucisymptomatic patients and helping to improve detection and reduce transmission has not been documented. The objective of this study was to evaluate in EDs whether an intensified SARS-CoV-2 screening strategy combining nurse-driven screening for asymptomatic/paucisymptomatic patients with routine practice (intervention) could contribute to higher detection of SARS-CoV-2 infections compared to routine practice alone, including screening for symptomatic or hospitalized patients (control)., Methods and Findings: We conducted a cluster-randomized, two-period, crossover trial from February 2021 to May 2021 in 18 EDs in the Paris metropolitan area, France. All adults visiting the EDs were eligible. At the start of the first period, 18 EDs were randomized to the intervention or control strategy by balanced block randomization with stratification, with the alternative condition being applied in the second period. During the control period, routine screening for SARS-CoV-2 included screening for symptomatic or hospitalized patients. During the intervention period, in addition to routine screening practice, a questionnaire about risk exposure and symptoms and a SARS-CoV-2 screening test were offered by nurses to all remaining asymptomatic/paucisymptomatic patients. The primary outcome was the proportion of newly diagnosed SARS-CoV-2-positive patients among all adults visiting the 18 EDs. Primary analysis was by intention-to-treat. The primary outcome was analyzed using a generalized linear mixed model (Poisson distribution) with the center and center by period as random effects and the strategy (intervention versus control) and period (modeled as a weekly categorical variable) as fixed effects with additional adjustment for community incidence. During the intervention and control periods, 69,248 patients and 69,104 patients, respectively, were included for a total of 138,352 patients. Patients had a median age of 45.0 years [31.0, 63.0], and women represented 45.7% of the patients. During the intervention period, 6,332 asymptomatic/paucisymptomatic patients completed the questionnaire; 4,283 were screened for SARS-CoV-2 by nurses, leading to 224 new SARS-CoV-2 diagnoses. A total of 1,859 patients versus 2,084 patients were newly diagnosed during the intervention and control periods, respectively (adjusted analysis: 26.7/1,000 versus 26.2/1,000, adjusted relative risk: 1.02 (95% confidence interval (CI) [0.94, 1.11]; p = 0.634)). The main limitation of this study is that it was conducted in a rapidly evolving epidemiological context., Conclusions: The results of this study showed that intensified screening for SARS-CoV-2 in EDs was unlikely to identify a higher proportion of newly diagnosed patients., Trial Registration: Trial registration number: ClinicalTrials.gov NCT04756609., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JLG reports personal fees for symposia presentations organized by Abbott Rapid Diagnosis SAS in 2021 and Qiagen Inc in 2022. TS reports grants or contracts from AstraZeneca, Bayer, Boehringer, Daiichi-Sankyo, Eli-Lilly, GSK, Novartis, Sanofi, payment or honoraria for lectures from Servier, Novartis, participation on a Data Safety Monitoring Board or Advisory Board from Ablative Solutions, Air Liquide, AstraZeneca, Sanofi, Novartis, 4Living Biotech., (Copyright: © 2023 Leblanc et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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40. Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI).
- Author
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Nze Ossima A, Ngaleu Siaha BF, Mimouni M, Mezaour N, Darlington M, Berard L, Cachanado M, Simon T, Freund Y, and Durand-Zaleski I
- Subjects
- Humans, Cost-Benefit Analysis, Emergency Service, Hospital, France, Venous Thromboembolism diagnosis, Venous Thromboembolism epidemiology, Pulmonary Embolism diagnosis
- Abstract
Background: The aim of this trial-based economic evaluation was to assess the incremental costs and cost-effectiveness of the modified diagnostic strategy combining the YEARS rule and age-adjusted D-dimer threshold compared with the control (which used the age-adjusted D-dimer threshold only) for the diagnosis of pulmonary embolism (PE) in the Emergency Department (ED)., Methods: Economic evaluation from a healthcare system perspective alongside a non-inferiority, crossover, and cluster-randomized trial conducted in 16 EDs in France and two in Spain with three months of follow-up. The primary endpoint was the additional cost of a patient without failure of the diagnostic strategy, defined as venous thromboembolism (VTE) diagnosis at 3months after exclusion of PE during the initial ED visit. Mean differences in 3-month failure and costs were estimated using separate generalized linear-regression mixed models, adjusted for strategy type, period, and the interaction between strategy and period as fixed effects and the hospital as a random effect. The incremental cost-effectiveness ratio (ICER) was obtained by dividing the incremental costs by the incremental frequency of VTE., Results: Of the 1,414 included patients, 1,217 (86%) were analyzed in the per-protocol analysis (648 in the intervention group and 623 in the control group). At three months, there were no statistically significant differences in total costs (€-46; 95% CI: €-93 to €0.2), and the failure rate was non inferior in the intervention group (-0.64%, one-sided 97.5% CI: -∞ to 0.21%, non-inferiority margin 1.5%) between groups. The point estimate of the incremental cost-effectiveness ratio (ICER) indicating that each undetected VTE averted in the intervention group is associated with cost savings of €7,142 in comparison with the control group. There was a 93% probability that the intervention was dominant. Similar results were found in the as randomized population., Conclusions: Given the observed cost decrease of borderline significance, and according to the 95% confidence ellipses, the intervention strategy has a potential to lead to cost savings as a result of a reduction in the use of chest imaging and of the number of undetected VTE averted. Policy-makers should investigate how these monetary benefits can be distributed across stakeholders., Clinicaltrials: Trial registration number ClinicalTrials.gov Identifier: NCT04032769; July 25, 2019., (© 2023. The Author(s).)
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- 2023
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41. ß-D-Glucan Assay in the Cerebrospinal Fluid for the Diagnosis of Non-cryptococcal Fungal Infection of the Central Nervous System: A Retrospective Multicentric Analysis and a Comprehensive Review of the Literature.
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Bigot J, Leroy J, Chouaki T, Cholley L, Bigé N, Tabone MD, Brissot E, Thorez S, Maizel J, Dupont H, Sendid B, Hennequin C, and Guitard J
- Subjects
- Humans, Glucans, Retrospective Studies, Sensitivity and Specificity, Central Nervous System, Multicenter Studies as Topic, beta-Glucans, Cryptococcosis diagnosis
- Abstract
Background: Except for cryptococcosis, fungal infection of the central nervous system (FI-CNS) is a rare but severe complication. Clinical and radiological signs are non-specific, and the value of conventional mycological diagnosis is very low. This study aimed to assess the value of β1,3-D-glucan (BDG) detection in the cerebrospinal fluid (CSF) of non-neonatal non-cryptococcosis patients., Methods: Cases associated with BDG assay in the CSF performed in 3 French University Hospitals over 5 years were included. Clinical, radiological, and mycological results were used to classify the episodes as proven/highly probable, probable, excluded, and unclassified FI-CNS. Sensitivity and specificity were compared to that calculated from an exhaustive review of the literature., Results: In total, 228 episodes consisting of 4, 7, 177, and 40 proven/highly probable, probable, excluded, and unclassified FI-CNS, respectively, were analysed. The sensitivity of BDG assay in CSF to diagnose proven/highly probable/probable FI-CNS ranged from 72.7% [95% confidence interval {CI}: 43.4%‒90.2%] to 100% [95% CI: 51%‒100%] in our study and was 82% in the literature. For the first time, specificity could be calculated over a large panel of pertinent controls and was found at 81.8% [95% CI: 75.3%‒86.8%]. Bacterial neurologic infections were associated with several false positive results., Conclusions: Despite its sub-optimal performance, BDG assay in the CSF should be added to the diagnostic armamentarium for FI-CNS., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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42. Allogeneic hematopoietic stem cell transplantation for NK/T-cell lymphoma: an international collaborative analysis.
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Berning P, Schmitz N, Ngoya M, Finel H, Boumendil A, Wang F, Huang XJ, Hermine O, Philippe L, Couronné L, Jaccard A, Liu D, Wu D, Reinhardt HC, Chalandon Y, Wagner-Drouet E, Kwon M, Zhang X, Carpenter B, Yakoub-Agha I, Wulf G, López-Jiménez J, Sanz J, Labussière-Wallet H, Shimoni A, Dreger P, Sureda A, Kim WS, and Glass B
- Subjects
- Humans, Male, Adult, Female, Retrospective Studies, Neoplasm Recurrence, Local therapy, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Lymphoma, T-Cell, Peripheral
- Abstract
Natural killer/T-cell lymphomas (NKTCL) represent rare and aggressive lymphoid malignancies. Patients (pts) with relapsed/refractory disease after Asparaginase (ASPA)-based chemotherapy have a dismal prognosis. To better define the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), we conducted a retrospective analysis of data shared with the European Society for Blood and Marrow Transplantation (EBMT) and cooperating Asian centers. We identified 135 pts who received allo-HSCT between 2010 and 2020. Median age was 43.4 years at allo-HSCT, 68.1% were male. Ninety-seven pts (71.9 %) were European, 38 pts (28.1%) Asian. High Prognostic Index for NKTCL (PINK) scores were reported for 44.4%; 76.3% had >1 treatment, 20.7% previous auto-HSCT, and 74.1% ASPA-containing regimens prior to allo-HSCT. Most (79.3%) pts were transplanted in CR/PR. With a median follow-up of 4.8 years, 3-year progression-free(PFS) and overall survival were 48.6% (95%-CI:39.5-57%) and 55.6% (95%-CI:46.5-63.8%). Non-relapse mortality at 1 year was 14.8% (95%-CI:9.3-21.5%) and 1-year relapse incidence 29.6% (95%-CI:21.9-37.6%). In multivariate analyses, shorter time interval (0-12 months) between diagnosis and allo-HSCT [HR = 2.12 (95%-CI:1.03-4.34); P = 0.04] and transplantation not in CR/PR [HR = 2.20 (95%-CI:0.98-4.95); P = 0.056] reduced PFS. Programmed cell death protein 1(PD-1/PD-L1) treatment before HSCT neither increased GVHD nor impacted survival. We demonstrate that allo-HSCT can achieve long-term survival in approximately half of pts allografted for NKTCL., (© 2023. The Author(s).)
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- 2023
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43. Respiratory multiplex PCR and procalcitonin to reduce antibiotic exposure in severe SARS-CoV-2 pneumonia: a multicentre randomized controlled trial.
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Fartoukh M, Nseir S, Mégarbane B, Cohen Y, Lafarge A, Contou D, Thille AW, Galerneau LM, Reizine F, Cour M, Klouche K, Navellou JC, Bitker L, Rousseau A, Tuffet S, Simon T, and Voiriot G
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- Adult, Humans, SARS-CoV-2 genetics, Procalcitonin therapeutic use, Anti-Bacterial Agents therapeutic use, Multiplex Polymerase Chain Reaction, Treatment Outcome, COVID-19 Testing, COVID-19 diagnosis, Respiratory Tract Infections diagnosis, Respiratory Tract Infections drug therapy, Bacterial Infections drug therapy
- Abstract
Objectives: We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia., Methods: This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28., Results: Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups., Discussion: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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44. A community-based strategy to eliminate hepatitis C among people who inject drugs in Vietnam.
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Nagot N, Binh NT, Hong TT, Vinh VH, Quillet C, Vallo R, Huong DT, Hai Oanh KT, Thanh NTT, Rapoud D, Quynh BTN, Nguyen DQ, Feelemyer J, Michel L, Vickerman P, Fraser H, Weiss L, Lemoine M, Lacombe K, Des Jarlais D, Khue PM, Moles JP, and Laureillard D
- Abstract
Background: Towards hepatitis C elimination among people who inject drugs (PWID), we assessed the effectiveness of a strategy consisting of a community-based respondent-driven sampling (RDS) as wide screening, a simplified and integrated hospital-based care, and prevention of reinfection supported by community-based organisations (CBO), in Hai Phong, Vietnam., Methods: Adults who injected heroin were enrolled in a RDS survey implemented in two CBO premises. Rapid HIV and HCV tests were done on site, and blood was taken for HCV RNA testing. Those with detectable HCV RNA were referred with CBO support to three public hospitals for 12-week sofosbuvir/daclatasvir, plus ribavirin for patients with cirrhosis. Participants were followed-up 12 weeks post-treatment (SVR12) and 48 weeks after enrolment. The primary endpoint was the rate of undetectable HCV RNA participants at 48 weeks., Findings: Among the 1444 RDS survey participants, 875 had hepatitis C. Their median age was 41 years (IQR 36-47), 96% were males, 36% were HIV-coinfected. Overall, 686 (78.4%) started sofosbuvir/daclatasvirs, and 629 of the 647 (97.2%) patients tested at SVR12 were cured. At week 48 (581/608) 95.6% had undetectable HCV RNA, representing 66.4% of all PWID identified with hepatitis C. The reinfection rate after SVR12 was 4/100 person-years (95% CI: 2-7)., Interpretation: Our strategy, involving CBO and addressing all steps from wide HCV screening to prevention of reinfection, stands as a promising approach to eliminate HCV among PWID in low and middle-income countries., Funding: France ANRS|MIE (#ANRS12380). The RDS survey was implemented with grants from the NIDA (#R01DA041978) and ANRS|MIE (#ANRS12353)., Competing Interests: ML received fees from Cepheid and Gilead US, as well as consultancy fees from Gilead US, outside the submitted work. KL received grants or contracts from MSD, honoraria from Janssen and Gilead, and travel support from Gilead, outside the submitted work. DDJ received grants and contracts from U.S. Centers for Disease Control, outside the submitted work. PV grants and contracts from Gilead medical Sciences outside the submitted work. Other authors declare no competing interest., (© 2023 The Author(s).)
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- 2023
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45. CASCADE protocol: exploring current viral and host characteristics, measuring clinical and patient-reported outcomes, and understanding the lived experiences and needs of individuals with recently acquired HIV infection through a multicentre mixed-methods observational study in Europe and Canada.
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Ruiz-Burga E, Tariq S, Touloumi G, Gill J, Nicholls EJ, Sabin C, Mussini C, Meyer L, Volny Anne A, Carlander C, Grabar S, Jarrin I, Van der Valk M, Wittkop L, Spire B, Pantazis N, Burns FM, and Porter K
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- Humans, Canada, Europe, Patient Reported Outcome Measures, Observational Studies as Topic, Multicenter Studies as Topic, HIV Infections epidemiology, Acquired Immunodeficiency Syndrome prevention & control, Pre-Exposure Prophylaxis methods
- Abstract
Introduction: Despite the availability of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), 21 793 people were newly diagnosed with HIV in Europe in 2019. The Concerted action on seroconversion to AIDS and death in Europe study aims to understand current drivers of the HIV epidemic; factors associated with access to, and uptake of prevention methods and ART initiation; and the experiences, needs and outcomes of people with recently acquired HIV., Methods and Analysis: This longitudinal observational study is recruiting participants aged ≥16 years with documented laboratory evidence of HIV seroconversion from clinics in Canada and six European countries. We will analyse data from medical records, self-administered questionnaires, semistructured interviews and participatory photography. We will assess temporal trends in transmitted drug resistance and viral subtype and examine outcomes following early ART initiation. We will investigate patient-reported outcomes, well-being, and experiences of, knowledge of, and attitudes to HIV preventions, including PrEP. We will analyse qualitative data thematically and triangulate quantitative and qualitative findings. As patient public involvement is central to this work, we have convened a community advisory board (CAB) comprising people living with HIV., Ethics and Dissemination: All respective research ethics committees have approval for data to contribute to international collaborations. Written informed consent is required to take part. A dissemination strategy will be developed in collaboration with CAB and the scientific committee. It will include peer-reviewed publications, conference presentations and accessible summaries of findings on the study's website, social media and via community organisations., Competing Interests: Competing interests: The funders did not participate in the study design and will not intervene in its process, analysis or publication of the findings. ST has received speaker honoraria and consultancy fees from Gilead Sciences. CC has received speaker/moderator honoraria and advisory board fees from Gilead Sciences, GSK/ViiV and MSD as well as an unrestricted Gilead Sciences Nordic Fellowship Research Grant. CS has received funding from Gilead Sciences, ViiV Healthcare and Janssen-Cilag for participation in Advisory Boards, speaker panels and for preparation of educational materials. MVdV has received consultancies fees for participation in advisory boards and research grants from Gilead, MSD and ViiV all paid to his institution. FMB has received funding from Gilead Sciences Ltd for preparation and delivery of educational materials. IJ has received teaching fees from ViiV Healthcare and advisory fees from Gilead Sciences. GT has received research grants and advisory board fees from Gilead, all paid to her institution, and MJG has received honoraria for ad hoc participation in national Advisory boards of Gilead Merck and ViiV., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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46. Real-world use of defibrotide for veno-occlusive disease/sinusoidal obstruction syndrome: the DEFIFrance Registry Study.
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Mohty M, Blaise D, Peffault de Latour R, Labopin M, Bourhis JH, Bruno B, Ceballos P, Detrait M, Gandemer V, Huynh A, Izadifar-Legrand F, Jubert C, Labussière-Wallet H, Lebon D, Maury S, Paillard C, Pochon C, Renard C, Rialland F, Schneider P, Sirvent A, Asubonteng K, Guindeuil G, Yakoub-Agha I, and Dalle JH
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- Humans, Prospective Studies, Retrospective Studies, Registries, Hepatic Veno-Occlusive Disease drug therapy, Hepatic Veno-Occlusive Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
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Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT) conditioning. The DEFIFrance post-marketing registry study evaluated effectiveness and safety in patients who received defibrotide. It collected retrospective/prospective patient data from 53 French HCT centres from July 2014 to March 2020. Primary endpoints were survival and complete response (CR; total serum bilirubin <2 mg/dL, multiorgan failure resolution) at Day 100 post-HCT among patients with severe/very severe VOD/SOS. A secondary endpoint was evaluation of treatment-emergent serious adverse events (TESAEs) of interest. Of 798 patients analysed, 251 and 81 received defibrotide treatment for severe/very severe VOD/SOS and mild/moderate VOD/SOS post-HCT, respectively; 381 received defibrotide for VOD/SOS prophylaxis. In patients with severe/very severe VOD/SOS post-HCT, Kaplan-Meier-estimated CR at Day 100 was 74% (95% confidence interval [CI]: 66%, 81%). At Day 100, 137/251 (55%) were alive and in CR. Kaplan-Meier-estimated Day 100 post-HCT survival was 61% (95% CI: 55%, 67%) in patients with severe/very severe VOD/SOS. TESAEs of interest occurred in 29% of these patients; VOD/SOS-related mortality at 12 months was 15%. DEFIFrance represents the largest collection of real-world data on post-registration defibrotide use, supporting the real-world utility of defibrotide for patients with severe/very severe VOD/SOS post-HCT., (© 2022. The Author(s).)
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- 2023
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47. Evaluating interventions to reduce behaviour associated with HCV reinfection in men who have sex with men: study protocol for a non-blinded, phase 2, randomised trial.
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Hage K, Boyd A, Davidovich U, Zantkuijl P, Hoornenborg E, Matser A, Generaal E, Schinkel J, Todesco E, van der Valk M, Rougier H, Lacombe K, and Prins M
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- Male, Humans, Hepacivirus, Homosexuality, Male, Reinfection complications, Sexual Behavior, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Clinical Trials, Phase II as Topic, HIV Infections prevention & control, Sexual and Gender Minorities, Hepatitis C diagnosis, Hepatitis C epidemiology, Hepatitis C prevention & control
- Abstract
Background: As highly effective therapy against hepatitis C virus (HCV) infection is available with rapid uptake, there is newfound optimism for HCV elimination. Nevertheless, certain key populations have a high risk of HCV reinfection, in particular men who have sex with men (MSM) in Western European countries. Modelling data indicate that HCV elimination will not be feasible without reduction in risk behaviour, thus supporting the need for effective interventions aimed at reducing risk behaviour and preventing reinfections in MSM., Methods: The ICECREAM study is an international, multi-centred, phase 2, 3-arm randomised trial comparing run-in and intervention periods enrolling MSM with a history of a cured or spontaneously cleared HCV infection. Individuals are followed in routine care for 6 months (i.e. run-in period) and then randomly allocated (1:1:1) to one of the following: a tailored, interactive online risk-reduction behavioural intervention, a validated home-based HCV-RNA self-sampling test service using dried blood spots, or a combination of both. After randomisation, individuals are followed every 6 months until 18 months (i.e. intervention period). Interventions are delivered in addition to standard of care. Online questionnaire measuring risk behaviour over the past 6 months is administered at every visit. The primary outcome is the proportion at risk of HCV infection during run-in versus intervention periods assessed by using the HCV-MOSAIC risk score. The risk score consists of six self-reported HCV-related risk behaviours. Secondary outcomes include incidence of HCV reinfection, changes in the individual risk behaviour items and changes in sexual well-being since changes in sexual behaviour may have an impact on sexual experience. Two hundred forty-six MSM aged 18 years or older will be invited to participate., Discussion: The ICECREAM study is a trial aimed at establishing interventions that could effectively decrease the incidence of HCV re-infection in MSM with a previous HCV infection. By offering an online behavioural risk-reduction intervention and HCV-RNA self-sampling, both of which are aimed to influence risk behaviour, we are able to provide products to at-risk MSM that could further reduce population-level HCV incidence and ultimately help reach HCV micro-elimination., Trial Registration: ClinicalTrials.gov NCT04156945. Registered on November 8, 2019., (© 2023. The Author(s).)
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- 2023
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48. Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology.
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Stym-Popper G, Matta K, Chaigneau T, Rupra R, Demetriou A, Fouquet S, Dansokho C, Toly-Ndour C, and Dorothée G
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- Mice, Animals, Amyloid beta-Protein Precursor genetics, Astrocytes metabolism, T-Lymphocytes, Regulatory, Mice, Transgenic, Plaque, Amyloid pathology, Amyloid beta-Peptides metabolism, Alzheimer Disease pathology
- Abstract
Background: Increasing evidence supports a key role for peripheral immune processes in the pathophysiology of Alzheimer's disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate and adaptive peripheral immune effectors. We previously showed that regulatory T cells (Tregs) have a beneficial impact on disease progression in AD-like pathology, notably by modulating the microglial response associated with Aβ deposits in a mouse model of amyloid pathology. Besides microglia, reactive astrocytes also play a critical role in neuroinflammatory processes associated with AD. Different phenotypes of reactive astrocytes have previously been characterized, including A1-like neurotoxic and A2-like neuroprotective subtypes. However, the precise impact of Tregs on astrocyte reactivity and phenotypes in AD still remains poorly defined., Methods: We assessed the impact of Treg immunomodulation on astrocyte reactivity in a mouse model of AD-like amyloid pathology. Using 3D imaging, we carried out extensive morphological analyses of astrocytes following either depletion or amplification of Tregs. We further assessed the expression of several A1- and A2-like markers by immunofluorescence and RT-qPCR., Results: Modulation of Tregs did not significantly impact the magnitude of global astrocyte reactivity in the brain nor in the close vicinity of cortical amyloid deposits. We did not observe changes in the number, morphology, or branching complexity of astrocytes according to immunomodulation of Tregs. However, early transient depletion of Tregs modulated the balance of reactive astrocyte subtypes, resulting in increased C3-positive A1-like phenotypes associated with amyloid deposits. Conversely, early depletion of Tregs decreased markers of A2-like phenotypes of reactive astrocytes associated with larger amyloid deposits. Intriguingly, modulation of Tregs also impacted the cerebral expression of several markers of A1-like subsets in healthy mice., Conclusions: Our study suggests that Tregs contribute to modulate and fine-tune the balance of reactive astrocyte subtypes in AD-like amyloid pathology, by dampening C3-positive astrocytes in favor of A2-like phenotypes. This effect of Tregs may partly relate to their capacity at modulating steady state astrocyte reactivity and homeostasis. Our data further highlight the need for refined markers of astrocytes subsets and strategy of analysis for better deciphering the complexity of astrocyte reactivity in neurodegeneration., (© 2023. The Author(s).)
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- 2023
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49. Striking differences in weight gain after cART initiation depending on early or advanced presentation: results from the ANRS CO4 FHDH cohort.
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Grabar S, Potard V, Piroth L, Abgrall S, Bernard L, Allavena C, Caby F, de Truchis P, Duvivier C, Enel P, Katlama C, Khuong MA, Launay O, Matheron S, Melica G, Melliez H, Meynard JL, Pavie J, Slama L, Bregigeon S, Tattevin P, Capeau J, and Costagliola D
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- Humans, Tenofovir therapeutic use, Weight Gain, Obesity complications, HIV Infections drug therapy, Acquired Immunodeficiency Syndrome, Anti-HIV Agents therapeutic use
- Abstract
Background: Many studies have reported weight gain in ART-naive people living with HIV (PWH) initiating an integrase strand-transfer inhibitor-based regimen. We studied the impact of early or advanced presentation and that of individual drugs in PWH initiating combined ART (cART) between 2012 and 2018., Methods: From the French Hospital Database HIV cohort, we assessed factors associated with a weight gain ≥10%, weight change after cART initiation or BMI increase ≥5 kg/m2 up to 30 months. The analyses were conducted overall, and among PWH with early (primary infection or CD4 >350/mm3 and viral load <100 000 copies/mL, without AIDS) and advanced presentation (AIDS or CD4 <200/mm3, not during primary infection)., Results: At 30 months, 34.5% (95% CI: 33.5-35.6) of the 12 773 PWH had a weight gain ≥10%, with 20.9% (95% CI: 19.6-22.2) among the 5794 with early presentation and 63.1% (95% CI: 60.9-65.3) among the 3106 with advanced presentation. Weight gain was 2.8 kg (95% CI: 2.0-3.7) for those with early presentation and 9.7 kg (95% CI: 8.4-11.1) for those with advanced presentation. Most weight gain occurred in the first 12 months. Underweight and obese PWH were at significantly higher risk of a BMI increase ≥5 kg/m2 than normal-weight PWH. Results differed within classes and by outcome. Raltegravir and dolutegravir were consistently associated with greater weight gain than the other third agents. Tenofovir alafenamide was also associated with higher weight gain than tenofovir disoproxil or abacavir., Conclusions: After initiating cART, PWH with early presentation exhibited a small weight gain, whereas it was large among those with advanced presentation. The choice of ART should account for the risk of weight gain, especially for PWH who present with advanced disease and/or are obese., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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50. Pleuropulmonary Manifestations of Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome.
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Borie R, Debray MP, Guedon AF, Mekinian A, Terriou L, Lacombe V, Lazaro E, Meyer A, Mathian A, Ardois S, Vial G, Moulinet T, Terrier B, Jamilloux Y, Heiblig M, Bouaziz JD, Zakine E, Outh R, Groslerons S, Bigot A, Flamarion E, Kostine M, Henneton P, Humbert S, Constantin A, Samson M, Bertrand NM, Biscay P, Dieval C, Lobbes H, Jeannel J, Servettaz A, Adelaide L, Graveleau J, de Sainte-Marie B, Galland J, Guillotin V, Duroyon E, Templé M, Bourguiba R, Georgin Lavialle S, Kosmider O, and Audemard-Verger A
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- Male, Humans, Aged, Female, Prednisone, Lung diagnostic imaging, Lung pathology, Syndrome, Mutation, Vacuoles, Pulmonary Fibrosis pathology
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Background: The vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a newly identified autoinflammatory disorder related to somatic UBA1 mutations. Up to 72% of patients may show lung involvement., Research Question: What are the pleuropulmonary manifestations in VEXAS syndrome?, Study Design and Methods: One hundred fourteen patients were included in the French cohort of VEXAS syndrome between November 2020 and May 2021. Each patient included in the study who had an available chest CT scan was discussed in an adjudication multidisciplinary team and classified as showing potentially pleuropulmonary-specific involvement of VEXAS syndrome or others., Results: Fifty-one patients had a CT scan available for review and 45 patients (39%) showed pleuropulmonary abnormalities on chest CT scan that were considered related to VEXAS syndrome after adjudication. Most patients were men (95%) with a median age 67.0 years at the onset of symptoms. Among these 45 patients, 44% reported dyspnea and 40% reported cough. All 45 patients showed lung opacities on chest CT scan (including ground-glass opacities [87%], consolidations [49%], reticulation [38%], and septal lines [51%]) and 53% of patients showed pleural effusion. Most patients showed improvement with prednisone, but usually required > 20 mg/d. The main clinical and biological features as well the median survival did not differ between the 45 patients with pleuropulmonary involvement and the rest of the cohort, suggesting that the prevalence of pleuropulmonary involvement might have been underdiagnosed in the rest of the cohort., Interpretation: Pulmonary manifestations are frequent in VEXAS syndrome, but rarely are at the forefront. The initial outcome is favorable with prednisone and does not seem to lead to pulmonary fibrosis., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
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- 2023
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