Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 08/05/2025
• Auteurs : Pierre DanneelsAdrien LemaignenAurélien Lorleac’hJean-Philippe TalarminRodolphe BuzeléVincent Dubée
• Organismes : Centre Hospitalier Universitaire d'Angers Groupe d'Epidémiologie et Recherche en Infectiologie Clinique du Centre et de l'Ouest [Brest] Centre Hospitalier Régional Universitaire de Tours Groupe d'Epidémiologie et Recherche en Infectiologie Clinique du Centre et de l'Ouest [Brest] Groupe Hospitalier Bretagne Sud Groupe d'Epidémiologie et Recherche en Infectiologie Clinique du Centre et de l'Ouest [Brest] Centre Hospitalier Intercommunal de Cornouaille Quimper Concarneau [Quimper] Groupe d'Epidémiologie et Recherche en Infectiologie Clinique du Centre et de l'Ouest [Brest] Centre hospitalier Saint-Brieuc Paimpol Tréguier Groupe d'Epidémiologie et Recherche en Infectiologie Clinique du Centre et de l'Ouest [Brest] Centre Hospitalier Universitaire d'Angers Immunology and New Concepts in ImmunoTherapy Groupe d'Epidémiologie et Recherche en Infectiologie Clinique du Centre et de l'Ouest [Brest]
• Publié dans Journal of Antimicrobial Chemotherapy le 31/10/2020

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Résumé : No abstract available

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Fichiers liés : dkaf138.pdf

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• Type de publi. : Communication dans un congrès
• Date de publi. : 07/05/2025
• Auteurs : Adeline FauMina GhobrialPhilippe SeitierPierre LagarrigueMichel GalaupAlain DaidiéPatrick Gilles
• Organismes : Institut Clément Ader Institut Clément Ader Institut national universitaire Champollion Institut Clément Ader Institut national universitaire Champollion Institut Clément Ader Institut national universitaire Champollion Education, Formation, Travail, Savoirs Institut Clément Ader Institut Clément Ader

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Résumé : Modern production rates and the increasing complexity of mechanical systems require efficient and effective manufacturing and assembly processes. The transition to Industry 4.0, supported by the deployment of innovative tools such as Augmented Reality (AR), equips the industry to tackle future challenges. Among critical processes, the assembly and tightening of bolted joints stand out due to their significant safety and economic implications across various industrial sectors. This study proposes an innovative tightening method designed to enhance the reliability of bolted assembly tightening through the use of Augmented Reality and connected tools. A 6-Degrees-of-Freedom (6-DoF) tracked connected torque wrench assists the operator during tightening, ensuring each screw is tightened to the correct torque. The effectiveness of this method is compared with the conventional tightening method using paper instructions. Participants in the study carried out tightening sequences on two simple parts with multiple screws. The study evaluates the impact of the proposed method on task performance and its acceptability to operators. The tracked connected torque wrench provides considerable assistance to the operators, including wrench control and automatic generation of tightening reports. The results suggest that the AR-based method has the potential to ensure reliable torque tightening of bolted joints.

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Fichiers liés : version_deposee.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 06/05/2025
• Auteurs : Rémi-Vinh CoudertJean-Philippe CharrierFrédéric JauffritJean-Pierre FlandroisCeline Brochier-Armanet
• Organismes : Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 BIOMERIEUX [Lyon, France] Bioinformatique, phylogénie et génomique évolutive [LBBE] BIOMERIEUX [Lyon, France] Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
• Publié dans BMC Bioinformatics le 01/11/2020

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Résumé : Abstract Background Genome sequence databases are growing exponentially, but with high redundancy and uneven data quality. For these reasons, selecting representative subsets of genomes is an essential step for almost all studies. However, most current sampling approaches are biased and unable to process large datasets in a reasonable time. Methods Here we present MPS-Sampling (Multiple-Protein Similarity-based Sampling), a fast, scalable, and efficient method for selecting reliable and representative samples of genomes from very large datasets. Using families of homologous proteins as input, MPS-Sampling delineates homogeneous groups of genomes through two successive clustering steps. Representative genomes are then selected within these groups according to predefined or user-defined priority criteria. Results MPS-Sampling was applied to a dataset of 48 ribosomal protein families from 178,203 bacterial genomes to generate representative genome sets of various size, corresponding to a sampling of 32.17% down to 0.3% of the complete dataset. An in-depth analysis shows that the selected genomes are both taxonomically and phylogenetically representative of the complete dataset, demonstrating the relevance of the approach. Conclusion MPS-Sampling provides an efficient, fast and scalable way to sample large collections of genomes in an acceptable computational time. MPS-Sampling does not rely on taxonomic information and does not require the inference of phylogenetic trees, thus avoiding the biases inherent in these approaches. As such, MPS-Sampling meets the needs of a growing number of users.

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• Type de publi. : Article dans une revue
• Date de publi. : 06/05/2025
• Auteurs : Yves ChalandonRaynier DevillierAriane BoumendilStéphanie NguyenClaude-Eric BulaboisPatrice CeballosEolia BrissotMarie-Thérèse RubioHélène Labussière-WalletJohan MaertensPatrice ChevallierNatacha MaillardXavier PoiréCristina Castilla-LlorenteYves BeguinJérôme CornillonSébastien MauryTony MarchandEtienne DaguindauJacques-Olivier BayPascal TurlureMagalie JorisAnne-Lise MenardKarin BilgerGaelle GuillermSylvie FrançoisAli BazarbachiSylvain ChantepiePhilippe LewalleAmbroise MarçaisMichael LoschiMalek BenakliPaul ChauvetEdouard ForcadeAnne HuynhMarie RobinStavroula Masouridi-Levrat
• Organismes : Hôpitaux Universitaires de Genève = University Hospital of Geneva [Genève] Centre de Recherche en Cancérologie de Marseille Société Francophone de Greffe de Moëlle et de Thérapie Cellulaire = French-speaking Society for Bone Marrow Transplantation and Cell Therapy AP-HP - Hôpital de la Pitié Salpêtrière CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble Hôpital Saint Eloi [CHU Montpellier] Centre de Recherche Saint-Antoine Service d'Hématologie [CHRU Nancy] Centre Hospitalier Lyon Sud [CHU - HCL] Universitair Ziekenhuis Leuven = University Hospital of Leuven = Hopital universitaire de Louvain Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Cliniques universitaires St Luc [Bruxelles] Département d'hématologie [Gustave Roussy] Centre Hospitalier Universitaire de Liège Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne [CHU Saint-Etienne] AP-HP - Hôpital Henri-Mondor Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Microenvironment and B-cells: Immunopathology, Cell Differentiation, and Cancer Centre Hospitalier Régional Universitaire de Besançon Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) Service Hématologie Biologique [CHU Clermont-Ferrand] Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges] Centre Hospitalier Universitaire d'Amiens-Picardie Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen Laboratoire de Génétique Moléculaire [CHRU Strasbourg] Centre Hospitalier Régional Universitaire de Brest Centre Hospitalier Universitaire d'Angers American University of Beirut CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Hôpital Universitaire de Bruxelles M3C-Necker, Hôpital universitaire Necker-Enfants malades, Université de Paris, Paris, France Centre Hospitalier Universitaire de Nice Centre Pierre et Marie Curie [Alger, Algeria] Pole Cardio-vasculaire et pulmonaire [CHU Lille] Centre Hospitalier Universitaire de Bordeaux Service Hématologie - IUCT-Oncopole [CHU Toulouse] AP-HP - Hôpital Saint-Louis [Paris] Hôpitaux Universitaires de Genève = University Hospital of Geneva [Genève]
• Publié dans American Journal of Hematology le 26/10/2020

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Résumé : ABSTRACT There are very limited data regarding the outcomes of elderly patients with acute lymphoblastic leukemia (ALL) who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). A total of 316 ALL patients aged ≥ 60 years who underwent alloHSCT between 2010 to 2022 were identified in the SFGM‐TC registry. The primary objective was to evaluate progression‐free survival (PFS), non‐relapse mortality (NRM), relapse incidence (RI), and graft‐versus‐host disease (GvHD)‐free relapse‐free survival (GRFS), as well as their risk factors. The median age was 63.8 years (range 60–75.8), 49.8% of patients had Philadelphia‐positive B‐ALL (Ph + ALL), and 70.9% were in first complete remission (CR1) at transplantation. The donor was an unrelated donor in 52.1%, a matched related donor (MRD) in 26.3%, and a haplo‐identical donor in 17.7%. Reduced‐intensity conditioning (RIC) was administered to 64.6% of patients, while total body irradiation (TBI) was used in 35.8%. The 3‐year overall survival (OS) was 46% (95% CI 40%–53%). The 3‐year PFS, NRM, RI, and GRFS were 41% (95% CI 35%–48%), 23% (95% CI 18%–28%), 36% (95% CI 31%–42%), and 30% (95% CI 25%–37%), respectively. Multivariable analyses confirmed poorer OS and PFS in patients with advanced disease, with an HR of 1.79 (95% CI 1.22–2.64), p = 0.0032. Additionally, the ALL subtype significantly impacted outcomes, with an HR of 1.99 (95% CI 1.42–2.79) for non‐Ph + ALL. This study suggests that alloHSCT is a viable option for elderly ALL patients, as age itself did not impact outcomes. However, advanced disease and non‐Ph + ALL were associated with significantly worse survival.

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Fichiers liés : Chalandon - 2025 - Allogeneic Hematopoietic Stem Cell Transplantation for Elderly Acute Lymphoblastic Leukemia Patients _SFGM-TC elderly ALL alloHSCT paper revision 020325 unmarked version.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 06/05/2025
• Auteurs : Adrien VigneronLilian CloarecCéline Brochier-ArmanetJean Pierre FlandroisMarc TroussellierCécile BernardHélène AgoguéPhilippe OgerMylène Hugoni
• Organismes : Microbiologie, adaptation et pathogénie Microbiologie, adaptation et pathogénie Microbiologie des Environnements Extrêmes = Microbiology of Extreme Environments Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 MARine Biodiversity Exploitation and Conservation - MARBEC Molécules de Communication et Adaptation des Micro-organismes LIttoral ENvironnement et Sociétés Microbiologie des Environnements Extrêmes = Microbiology of Extreme Environments Microbiologie, adaptation et pathogénie Microbiologie, adaptation et pathogénie Institut universitaire de France Microbiologie des Environnements Extrêmes = Microbiology of Extreme Environments
• Publié dans Environmental Microbiome le 28/05/2020

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Résumé : Abstract Background Extreme environments are useful systems to investigate limits of life, microbial biogeography and ecology, and the adaptation and evolution of microbial lineages. Many novel microbial lineages have been discovered in extreme environments, especially from the Planctomycetota–Verrucomicrobiota–Chlamydiota (PVC) superphyla. However, their evolutionary history and roles in ecosystem functioning and microbiome assemblage are poorly understood. Results Applying a genome-centric approach on an 8-year metagenomic timeseries produced from the hypersaline and hyperalkaline waters of Lake Dziani Dzaha (Mayotte), we recovered 5 novel PVC extremophilic candidate lineages from the biosphere of the lake. Sibling to Elusimicrobia and Omnitrophota, these lineages represented novel halophilic clades, with global distributions bounded to soda lakes and hypersaline hydrosystems. Genome mining of these newly defined clades revealed contrasted, but ecologically relevant, catabolic capabilities involved in the carbon, hydrogen and iron/electron cycles of the Dziani Dzaha ecosystem. This also includes extracellular electron transfer for two of them, suggesting metal reduction or potential electron exchanges with other members of the lake community. By contrast, a putative extracellular giant protein with multiple carbohydrate binding domains and toxin-like structures, as observed in virulence factors, was identified in the genome of another of these clades, suggesting predatory capabilities. Conclusions Our results provided genomic evidences for original metabolism in novel extremophile lineages of the PVC superphyla, revealing unforeseen implications for members of this widespread and diverse bacterial radiation in aquatic saline ecosystems. Finally, monitoring the in-situ distribution of these lineages through the timeseries reveals the drastic effects of environmental perturbations on extreme ecosystem biodiversity.

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Fichiers liés : s40793-025-00699-1.pdf

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• Type de publi. : Communication dans un congrès
• Date de publi. : 05/05/2025
• Auteurs : Daniel ThirionJean-Marc DaveauV. EgloffDavid HelyVincent BeroullePhilippe Roche
• Organismes : STMicroelectronics [Crolles] Laboratoire de Conception et d'Intégration des Systèmes STMicroelectronics [Crolles] Laboratoire de Conception et d'Intégration des Systèmes Laboratoire de Conception et d'Intégration des Systèmes Conception et Test de SYStèmes embarqués Laboratoire de Conception et d'Intégration des Systèmes Conception et Test de SYStèmes embarqués STMicroelectronics [Crolles]

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Résumé : With the increase in cybersecurity requirements and the growing connectivity of critical systems like vehicles and satellites, implementing both functional safety and hardware security is crucial. Although safety and security methods are well studied, combined analysis at the RTL or Netlist level remains under-explored. This paper provides an initial analysis of multiple AES designs—one unprotected, one with a safety-oriented countermeasure (Lockstep), and one with security-oriented countermeasures (Parity-Predictor)—using both simulation and formal methods. We identify the challenges and opportunities for enhancing combined safety and security assessments. Additionally, we evaluate the AES designs against ISO 26262 safety metrics and analyze their resilience to laser attacks, offering insight into their security robustness.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2025
• Auteurs : Chloé GrolleauMaxime BattistellaEve ZakineThomas PoisotFlorence CordolianiThibault MahevasMarie JachietAdèle de MassonArsène MekinianBenjamin TerrierSophie Georgin LaviallePierre FenauxLionel AdèsLin-Pierre ZhaoKevin SerrorMatthieu DuchmannEmmanuelle ClappierRachel OnifarasoaniainaHelene Le BuanecPhilippe MogueletJean-David BouazizFrancois Chasset
• Organismes : Immunologie humaine, physiopathologie & immunothérapie Service de Dermatologie [AP-HP Hôpital Saint-Louis] Service de pathologie [Saint-Louis] Service de Dermatologie [AP-HP Hôpital Saint-Louis] Immunologie humaine, physiopathologie & immunothérapie Service de Dermatologie [AP-HP Hôpital Saint-Louis] Service de Dermatologie [AP-HP Hôpital Saint-Louis] Service de Dermatologie [AP-HP Hôpital Saint-Louis] Service de Dermatologie [AP-HP Hôpital Saint-Louis] AP-HP - Hôpital Saint-Antoine Université Paris Cité Centre national de référence pour les maladies auto-immunes systémiques rares [CHU Cochin] Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] Maladies génétiques d'expression pédiatrique AP-HP - Hôpital Tenon Service d'Hématologie Seniors - Hôpital Saint-Louis Service d'Hématologie Seniors - Hôpital Saint-Louis Service d'Hématologie Seniors - Hôpital Saint-Louis AP-HP - Hôpital Saint-Louis [Paris] Génomes, biologie cellulaire et thérapeutiques Service Hématologie Transplantation [Hôpital Saint Louis, AP-HP] Génomes, biologie cellulaire et thérapeutiques Service Hématologie Transplantation [Hôpital Saint Louis, AP-HP] Institut Cochin Immunologie humaine, physiopathologie & immunothérapie AP-HP - Hôpital Tenon Service de Dermatologie [AP-HP Hôpital Saint-Louis] Immunologie humaine, physiopathologie & immunothérapie AP-HP - Hôpital Tenon Centre d'Immunologie et des Maladies Infectieuses
• Publié dans JAMA Dermatology le 28/10/2020

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Résumé : Importance VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a monogenic disease caused by UBA1 somatic variants in hematopoietic progenitor cells, mostly involving adult men. It is associated with inflammatory-related symptoms, frequently involving the skin and hematological disorders. Recently described myelodysplasia cutis (MDS-cutis) is a cutaneous manifestation of myelodysplasia in which clonal myelodysplastic cells infiltrate the skin. In both cases, skin lesions are driven by the infiltration of clonal mutated myeloid cells and may clinically and histologically mimic Sweet syndrome (SS), a neutrophilic skin disease. Objective To decipher the underlying mechanisms driving these 3 myeloid-related skin diseases (ie, VEXAS, MDS-cutis, and SS) compared with leukemia cutis (LC), a neoplastic blastic myeloid-related skin condition, and healthy control skin samples. Design, Setting, and Participants This multicenter translational study on formaldehyde-fixed paraffin-embedded lesional skin samples of VEXAS syndrome, MDS-cutis, idiopathic SS, LC, and healthy controls using bulk RNA sequencing analyses was conducted in France. Patients included had cutaneous lesions of VEXAS syndrome, MDS-cutis, idiopathic SS, or LC. The data were analyzed from June 2023 to March 2024. Main Outcomes and Measures Differentially expressed genes between conditions were studied. These genes were used to characterize the enrichment in activated inflammatory pathways in each condition using Gene Set Enrichment Analysis and Ingenuity Pathway Analysis. Results Twenty patients with skin conditions (median [range] age, 67 [43-88] years; 10 [50%] men) were included. Six had cutaneous lesions of VEXAS syndrome, 4 had MDS-cutis, 5 had idiopathic SS, and 5 had LC. They were compared with 5 healthy control skin samples. Bulk RNA sequencing analysis reveals that MDS-cutis and VEXAS syndrome lesions display closely related transcriptomic profiles, highly imprinted by cytokine responses, interferon signatures, and activation of the apoptosis pathway. A shared inflammatory environment between MDS-cutis, VEXAS syndrome, and idiopathic SS was observed, mostly relying on a type 1 immune response led by type 1 and 2 interferons, along with the activation of tumor necrosis factor and interleukin (IL)–1β pathways. Conversely, LC showed an isolated transcriptomic profile mainly enriched in cell cycle pathways. Conclusions and Relevance The findings of this translational study highlight a common inflammatory pattern shared between VEXAS syndrome, MDS-cutis, and refractory idiopathic SS skin samples. This suggests the potential therapeutic targeting of interferon pathways in patients affected with refractory nonblastic myeloid-related skin diseases.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2025
• Auteurs : Chloé GrolleauMaxime BattistellaEve ZakineThomas PoisotFlorence CordolianiThibault MahevasMarie JachietAdèle de MassonArsène MekinianBenjamin TerrierSophie Georgin LaviallePierre FenauxLionel AdèsLin-Pierre ZhaoKevin SerrorMatthieu DuchmannEmmanuelle ClappierRachel OnifarasoaniainaHelene Le BuanecPhilippe MogueletJean-David BouazizFrancois Chasset
• Organismes : Service de Dermatologie [AP-HP Hôpital Saint-Louis] Immunologie humaine, physiopathologie & immunothérapie Service de pathologie [Saint-Louis] Service de Dermatologie [AP-HP Hôpital Saint-Louis] Immunologie humaine, physiopathologie & immunothérapie Service de Dermatologie [AP-HP Hôpital Saint-Louis] Service de Dermatologie [AP-HP Hôpital Saint-Louis] Service de Dermatologie [AP-HP Hôpital Saint-Louis] Service de Dermatologie [AP-HP Hôpital Saint-Louis] Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] AP-HP - Hôpital Cochin Université Paris Descartes - Paris 5 Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] Maladies génétiques d'expression pédiatrique Service d'Hématologie Seniors - Hôpital Saint-Louis Service d'Hématologie Seniors - Hôpital Saint-Louis Service d'Hématologie Seniors - Hôpital Saint-Louis AP-HP - Hôpital Saint-Louis [Paris] Service Hématologie Transplantation [Hôpital Saint Louis, AP-HP] Génomes, biologie cellulaire et thérapeutiques Service Hématologie Transplantation [Hôpital Saint Louis, AP-HP] Génomes, biologie cellulaire et thérapeutiques Institut Cochin Immunologie humaine, physiopathologie & immunothérapie AP-HP - Hôpital Tenon Service de Dermatologie [AP-HP Hôpital Saint-Louis] Immunologie humaine, physiopathologie & immunothérapie AP-HP - Hôpital Tenon Centre d'Immunologie et des Maladies Infectieuses
• Publié dans JAMA Dermatology le 28/10/2020

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Résumé : Importance VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a monogenic disease caused by UBA1 somatic variants in hematopoietic progenitor cells, mostly involving adult men. It is associated with inflammatory-related symptoms, frequently involving the skin and hematological disorders. Recently described myelodysplasia cutis (MDS-cutis) is a cutaneous manifestation of myelodysplasia in which clonal myelodysplastic cells infiltrate the skin. In both cases, skin lesions are driven by the infiltration of clonal mutated myeloid cells and may clinically and histologically mimic Sweet syndrome (SS), a neutrophilic skin disease. Objective To decipher the underlying mechanisms driving these 3 myeloid-related skin diseases (ie, VEXAS, MDS-cutis, and SS) compared with leukemia cutis (LC), a neoplastic blastic myeloid-related skin condition, and healthy control skin samples. Design, Setting, and Participants This multicenter translational study on formaldehyde-fixed paraffin-embedded lesional skin samples of VEXAS syndrome, MDS-cutis, idiopathic SS, LC, and healthy controls using bulk RNA sequencing analyses was conducted in France. Patients included had cutaneous lesions of VEXAS syndrome, MDS-cutis, idiopathic SS, or LC. The data were analyzed from June 2023 to March 2024. Main Outcomes and Measures Differentially expressed genes between conditions were studied. These genes were used to characterize the enrichment in activated inflammatory pathways in each condition using Gene Set Enrichment Analysis and Ingenuity Pathway Analysis. Results Twenty patients with skin conditions (median [range] age, 67 [43-88] years; 10 [50%] men) were included. Six had cutaneous lesions of VEXAS syndrome, 4 had MDS-cutis, 5 had idiopathic SS, and 5 had LC. They were compared with 5 healthy control skin samples. Bulk RNA sequencing analysis reveals that MDS-cutis and VEXAS syndrome lesions display closely related transcriptomic profiles, highly imprinted by cytokine responses, interferon signatures, and activation of the apoptosis pathway. A shared inflammatory environment between MDS-cutis, VEXAS syndrome, and idiopathic SS was observed, mostly relying on a type 1 immune response led by type 1 and 2 interferons, along with the activation of tumor necrosis factor and interleukin (IL)–1β pathways. Conversely, LC showed an isolated transcriptomic profile mainly enriched in cell cycle pathways. Conclusions and Relevance The findings of this translational study highlight a common inflammatory pattern shared between VEXAS syndrome, MDS-cutis, and refractory idiopathic SS skin samples. This suggests the potential therapeutic targeting of interferon pathways in patients affected with refractory nonblastic myeloid-related skin diseases.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2025
• Auteurs : Kien Vu TrungEinas Abou-AliAiste GullaKevin SoaresFabrice CaillolWoo PaikBertrand NapoleonAsif HalimiViliam MasarykMarco BrunoEnrique Pérez-Cuadrado-RoblesLouisa BolmSteffen SeyfriedMaria PetroneBengisu YilmazCharles VollmerArthur BergerLaura MagginoPeter SchemmerDörte WichmannElias KaramAna DugicLumir KunovskySara RegnerSébastien GaujouxMarcus HollenbachChristian HeiseFrancesco AuriemmaGalen LeungMark SchattnerWilliam JarnaginTiegong WangMarc GiovanniniJean Philippe RatoneAlessandro ZerbiGennaro NappoUrban ArneloErik HaraldssonAlexander WaldthalerUwe WillRita SaadehSophia van der WielPierre DeprezAlain SauvanetTobias KeckFrancois SoucheJean FabreNicolas MusquerGeorg KählerAlberto MarianiPiera ZaccariGiulio BelfioriMassimo FalconiStefano PartelliIhsan Ekin DemirGüralp CeyhanJean-Marc RégimbeauJohan GagniéreAlessandro RepiciAndrea AnderloniFabio CascianiMarco del ChiaroAtsushi ObaRichard SchulickRoberto SalviaAna LaranjoDiogo LibanioMadaline IlieJohanna LaukkarinenAlbrecht HoffmeisterJonas RosendahlBrigitte SchumacherLouise BarbierEphrem SalaméArnaud AlvèsNicolas RegenetSteffen MuehldorferStéphanie TruantKarel CacaMarcel TantauDavid BirnbaumJens WernerKestutis StrupasEdris WediKatrin SalzmannMatthieu BruzziRenato-Micelli LupinacciPatrice DavidLilian SchwarzArthur SchmidtTullio PiardiMartin BrunelJean-Christoph VaillantCharles de PonthaudCeline LejeuneRaffaele BrustiaRim CherifPaul-Noet DumontFrederic PratMatthias LöhrBenjamin MeierBogdan MiutescuRainer Christoph MikschYosuke InoueMario Dinis-RibeiroTobias KleemannVasile SandruReea AholaDavid AlbersTiago GonçalvesTobias WeismüllerDominik HelingThilo HackertStefano CrippaMoritz SchiemerSohei SatoiPatrick MichlSebastian Krug
• Organismes : Centre for Wireless Communications [University of Oulu] Vilnius University [Vilnius] Memorial Sloan Kettering Cancer Center Institut Paoli-Calmettes Hôpital privé Jean Mermoz [Lyon] Department of Gastroenterology and Hepatology AP-HP - Hôpital Européen Georges Pompidou Kaunas University of Technology Centre Hospitalier Universitaire d'Angers Heidelberg University Hospital [Heidelberg] Chirurgie digestive [CHU Amiens] Simplification des soins chez les patients complexes - UR UPJV 7518
• Publié dans Gastrointestinal Endoscopy le 25/10/2020

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Résumé : Background and study aims: Endoscopic papillectomy (EP) is the standard treatment for non-invasive ampullary lesions (AL), while advanced cases require surgery. Managing AL is challenging and may lead to over- or undertreatment. We developed a score to identify the best candidates for endoscopic or surgical treatment. Patients and methods: We analyzed 447 patients who underwent EP. The cohort was randomly split into a training (n=325) and validation set (n=122). Logistic regression identified predictors for incomplete resection (R1), which were incorporated into a four-item score. Performance was assessed using AUROC. Results: Independent predictors for R1 included size≥30mm(S), high-grade dysplasia/invasive cancer(D), laterally-spreading-lesion(L), and bile/pancreatic duct dilation(D). AL with 0-1 points had the highest R0 rates (training: 86.0%; validation: 88.5%), while ≥2 points significantly increased R1 rates (training: 52.0%; validation: 57.7%; p<0.001). AUROC was 0.792 (training) and 0.708 (validation). Conclusion: The SDLD score predicts incomplete resection in EP and aids treatment decisions.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2025
• Auteurs : Gilbert BensimonP Nigel LeighTimothy TreeAndrea MalaspinaChristine Am PayanHang Phuong PhamPieter KlaassenPamela ShawAhmad Al KhleifatMaria-Del-Mar AmadorShahram AttarianSimon BellStéphane BeltranEmilien BernardWilliam CamuPhilippe CorciaJean-Christophe CorvolPhilippe CouratierVéronique Brunaud-DanelRabab DebsClaude DesnuelleAikaterini DimitriouJohn EalingFlorence EsselinMarie-Céline FleuryGeorge GorrieAude-Marie GrapperonAdèle HestersRaul Juntas-MoralesIvan KolevGéraldine LautretteNadine Le ForestierChristopher McdermottNicolas PageotFrançois SalachasNikhil SharmaMarie-Hélène SorianiJemeen SreedharanJuliette SvahnNick VerberAnnie VerschuerenOzlem YildizCarey SuehsSafaa Saker-DelyeClaudie MullerChristophe MasseguinHana HajduchovaJanine KirbyCecilia GarlandaMassimo LocatiHenrik ZetterbergBernard AsselainAmmar Al-Chalabi
• Organismes : BESPIM AP-HP - Hôpital de la Pitié Salpêtrière Sorbonne Université Brighton and Sussex Medical School King‘s College London Blizard Institute Queen Mary University of London UCL Queen Square Institute of Neurology AP-HP - Hôpital de la Pitié Salpêtrière Hôpital Universitaire Carémeau [Nîmes] Parean biotechnologies The Institute of Neuroscience [Sheffield] University of Sheffield [Sheffield] King‘s College London AP-HP - Hôpital de la Pitié Salpêtrière Centre de Référence Maladies Rares SLA Ile de France [GHU Pitié-Salpêtrière] Hôpital de la Timone [CHU - APHM] ERN EURO-NMD – European Reference Network for Rare Neuromuscular Diseases University of Sheffield [Sheffield] NHS Foundation Trust [London] Centre Hospitalier Régional Universitaire de Tours Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL] Institut NeuroMyoGène - Appui à la recherche Institut des Neurosciences de Montpellier Hôpital Gui de Chauliac [CHU Montpellier] Centre Hospitalier Régional Universitaire de Tours Institut du Cerveau = Paris Brain Institute Sorbonne Université AP-HP - Hôpital de la Pitié Salpêtrière Centre Hospitalier Universitaire Dupuytren 1 et 2 Centre Hospitalier Régional Universitaire [CHU Lille] Centre de Référence Maladies Rares SLA Ile de France [GHU Pitié-Salpêtrière] Service de Neurologie [CHU Nice] King's College Hospital Institut des Neurosciences de Montpellier Département de Neurologie [Hôpital Gui de Chauliac - CHU Montpellier] Hôpital de Hautepierre [Strasbourg] Queen Elizabeth University Hospital (Glasgow) ERN EURO-NMD – European Reference Network for Rare Neuromuscular Diseases Hôpital de la Timone [CHU - APHM] AP-HP - Hôpital de la Pitié Salpêtrière Centre de Référence Maladies Rares SLA Ile de France [GHU Pitié-Salpêtrière] Vall d'Hebron University Hospital [Barcelona] Centre hospitalier de Saint-Brieuc [Hôpital Yves Le Foll] Centre Hospitalier Universitaire Dupuytren 1 et 2 Service de Neurologie [CHU Limoges] Institut du Cerveau = Paris Brain Institute University of Sheffield [Sheffield] Département de neurologie [Montpellier] AP-HP - Hôpital de la Pitié Salpêtrière Centre de Référence Maladies Rares SLA Ile de France [GHU Pitié-Salpêtrière] Malviya National Institute of Technology, J L N Marg, Jaipur, Rajasthan, India. Centre Hospitalier Universitaire de Nice Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL] Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM]
• Publié dans The Lancet le 02/11/2020

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Résumé : Background: Amyotrophic lateral sclerosis (ALS) is a life-threatening disease characterised by progressive loss of motor neurons with few therapeutic options. The MIROCALS study tested the hypothesis that low-dose interleukin-2 (IL-2LD) improves survival and function in ALS. Methods: In this randomised, double-blind, placebo-controlled trial, male and female riluzole-naive participants, with either a possible, laboratory-supported probable, probable, or definite ALS diagnosis (revised El Escorial criteria), aged 18-76 years, with symptom duration of 24 months or fewer, and slow vital capacity of 70% or more, underwent a riluzole-only 12-18 week run-in period before randomisation in a 1:1 ratio to either 2 million international units (MIU) IL-2LD or placebo by subcutaneous injection daily for 5 days every 28 days over 18 months. The primary endpoint was survival at 640 days (21 months). Secondary outcomes included safety, ALS Functional Rating Scale-Revised (ALSFRS-R) score, and biomarker measurements including regulatory T-cells (Tregs), cerebrospinal fluid (CSF)-phosphorylated-neurofilament heavy-chain (CSF-pNFH), and plasma and CSF-chemokine ligand 2 (CCL2). The primary endpoint analysis used unadjusted log-rank and Cox's model adjusted analyses using pre-defined prognostic covariates to control for the disease and treatment response heterogeneity. The study was 80% powered to detect a two-fold decrease in the risk of death by the log-rank test in the intention-to-treat (ITT) population, including all randomly allocated participants. MIROCALS is registered with ClinicalTrials.gov (NCT03039673) and is complete. Findings: From June 19, 2017, to Oct 16, 2019, 304 participants were screened, of whom 220 (72%) met all criteria for random allocation after the 12-to-18-week run-in period on riluzole. 136 (62%) of participants were male and 84 participants (38%) were female. 25 (11%) of the 220 randomly allocated participants were defined as having possible ALS under El Escorial criteria. At the cutoff date there was no loss to follow-up, and all 220 patients who were randomly allocated were documented as either deceased (90 [41%]) or alive (130 [59%]), so all participants were included in the ITT and safety populations. The primary endpoint unadjusted analysis showed a non-significant 19% decrease in risk of death with IL-2LD (hazard ratio 0·81 [95% CI 0·54-1·22], p=0·33), failing to demonstrate the expected two-fold decrease in risk of death. The analysis of the primary endpoint adjusted on prognostic covariates, all measured at time of random allocation, showed a significant decrease of the risk of death with IL-2LD (0·32 [0·14-0·73], p=0·007), with a significant treatment by CSF-pNFH interaction (1·0003 [1·0001-1·0005], p=0·001). IL-2LD was safe, and significantly increased Tregs and decreased plasma-CCL2 at all timepoints. Stratification on CSF-pNFH levels measured at random allocation showed that IL-2LD was associated with a significant 48% decrease in risk of death (0·52 [0·30-0·89], p=0·016) in the 70% of the population with low (750-3700 pg/mL) CSF-pNFH levels, while in the 21% with high levels (>3700 pg/mL), there was no significant difference (1·37 [0·68-2·75], p=0·38). Interpretation: With this treatment schedule, IL-2LD resulted in a non-significant reduction in mortality in the primary unadjusted analysis. However, the difference between the results of unadjusted and adjusted analyses of the primary endpoint emphasises the importance of controlling for disease heterogeneity in ALS randomised controlled trials. The decrease in risk of death achieved by IL-2LD therapy in the trial population with low CSF-pNFH levels requires further investigation of the potential benefit of this therapy in ALS.

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