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Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study
La défaite électorale. Productions, appropriations, bifurcations
La défaite électorale est un phénomène structurant de la vie politique démocratique et cet ouvrage propose une plongée du côté des battus des élections. En réunissant des contributions empiriquement fondées sur des expériences variées de défaites électorales, dans différents contextes historiques, géographiques et politiques, il se donne pour objectif de mieux saisir les enjeux symboliques et matériels de la défaite aux niveaux individuel et collectif
Comparative analysis of human, rodent and snake deltavirus replication.
The recent discovery of Hepatitis D (HDV)-like viruses across a wide range of taxa led to the establishment of the Kolmioviridae family. Recent studies suggest that kolmiovirids can be satellites of viruses other than Hepatitis B virus (HBV), challenging the strict HBV/HDV-association dogma. Studying whether kolmiovirids are able to replicate in any animal cell they enter is essential to assess their zoonotic potential. Here, we compared replication of three kolmiovirids: HDV, rodent (RDeV) and snake (SDeV) deltavirus in vitro and in vivo. We show that SDeV has the narrowest and RDeV the broadest host cell range. High resolution imaging of cells persistently replicating these viruses revealed nuclear viral hubs with a peculiar RNA-protein organization. Finally, in vivo hydrodynamic delivery of viral replicons showed that both HDV and RDeV, but not SDeV, efficiently replicate in mouse liver, forming massive nuclear viral hubs. Our comparative analysis lays the foundation for the discovery of specific host factors controlling Kolmioviridae host-shifting.journal article2024 Mar2024 03 05importe
JAK1 promotes HDV replication and is a potential target for antiviral therapy.
Chronic co-infection with HBV and HDV leads to the most aggressive form of chronic viral hepatitis. To date, no treatment induces efficient viral clearance, and a better characterization of virus-host interactions is required to develop new therapeutic strategies.
Using loss-of-function strategies, we validated the unexpected proviral activity of Janus kinase 1 (JAK1) - a key player in innate immunity - in the HDV life cycle and determined its mechanism of action on HDV through various functional analyses including co-immunoprecipitation assays.
We confirmed the key role of JAK1 kinase activity in HDV infection. Moreover, our results suggest that JAK1 inhibition is associated with a modulation of ERK1/2 activation and S-HDAg phosphorylation, which is crucial for viral replication. Finally, we showed that FDA-approved JAK1-specific inhibitors are efficient antivirals in relevant in vitro models including primary human hepatocytes.
Taken together, we uncovered JAK1 as a key host factor for HDV replication and a potential target for new antiviral treatment.
Chronic hepatitis D is the most aggressive form of chronic viral hepatitis. As no curative treatment is currently available, new therapeutic strategies based on host-targeting agents are urgently needed. Here, using loss-of-function strategies, we uncover an unexpected interaction between JAK1, a major player in the innate antiviral response, and HDV infection. We demonstrated that JAK1 kinase activity is crucial for both the phosphorylation of the delta antigen and the replication of the virus. By demonstrating the antiviral potential of several FDA-approved JAK1 inhibitors, our results could pave the way for the development of innovative therapeutic strategies to tackle this global health threat.journal article2024 Feb2023 11 02importe
Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension
Persistent liver injury triggers a fibrogenic program that causes pathologic remodeling of the hepatic microenvironment (i.e., liver fibrosis) and portal hypertension. The dynamics of gene regulation during liver disease progression and early regression remain understudied. Here, we generated hepatic transcriptome profiles in two well-established liver disease models at peak fibrosis and during spontaneous regression after the removal of the inducing agents. We linked the dynamics of key disease readouts, such as portal pressure, collagen area, and transaminase levels, to differentially expressed genes, enabling the identification of transcriptomic signatures of progressive vs. regressive liver fibrosis and portal hypertension. These candidate biomarkers (e.g.,journal article2024 Mar 152024 02 20importe
Anastomotic biliary stricture after orthotopic liver transplantation: what can we propose after failure of classic ERCP technique to cannulate the stricture?
journal article2024 Dec2024 02 15importe
Curriculum for diagnostic endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.
The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in diagnostic endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in diagnostic EUS. This curriculum is set out in terms of the prerequisites prior to training; the recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should have achieved competence in upper gastrointestinal endoscopy before training in diagnostic EUS. 2: The development of diagnostic EUS skills by methods that do not involve patients is advisable, but not mandatory, prior to commencing formal training in diagnostic EUS. 3: A trainee's principal trainer should be performing adequate volumes of diagnostic EUSs to demonstrate maintenance of their own competence. 4: Training centers for diagnostic EUS should offer expertise, as well as a high volume of procedures per year, to ensure an optimal level of quality for training. Under these conditions, training centers should be able to provide trainees with a sufficient wealth of experience in diagnostic EUS for at least 12 months. 5: Trainees should engage in formal training and supplement this with a range of learning resources for diagnostic EUS, including EUS-guided fine-needle aspiration and biopsy (FNA/FNB). 6: EUS training should follow a structured syllabus to guide the learning program. 7: A minimum procedure volume should be offered to trainees during diagnostic EUS training to ensure that they have the opportunity to achieve competence in the technique. To evaluate competence in diagnostic EUS, trainees should have completed a minimum of 250 supervised EUS procedures: 80 for luminal tumors, 20 for subepithelial lesions, and 150 for pancreaticobiliary lesions. At least 75 EUS-FNA/FNBs should be performed, including mostly pancreaticobiliary lesions. 8: Competence assessment in diagnostic EUS should take into consideration not only technical skills, but also cognitive and integrative skills. A reliable valid assessment tool should be used regularly during diagnostic EUS training to track the acquisition of competence and to support trainee feedback. 9: A period of supervised practice should follow the start of independent activity. Supervision can be delivered either on site if other colleagues are already practicing EUS or by maintaining contacts with the training center and/or other EUS experts. 10: Key performance measures including the annual number of procedures, frequency of obtaining a diagnostic sample during EUS-FNA/FNB, and adverse events should be recorded within an electronic documentation system and evaluated.journal article2024 Mar2023 12 08importe
Impact of anti-HDV reflex testing at HBs antigen positive discovery in a single center France: Support for primary HDV screening in France.
Hepatitis Delta virus (HDV) infection is a major cause of liver-related morbidity and mortality in patients infected with HBV, with a global HDV prevalence uncertain. In France, 2 to 5 % of HBs antigen (HBsAg) carriers present anti-HDV antibodies (anti-HDV). The EASL recommends testing for anti-HDV in all HBsAg-positive patients. Since January 2022, we have systematically carried out anti-HDV serology when a positive HBsAg is discovered (new HBsAg carriers).
We evaluated the benefit of anti-HDV reflex testing after one year of practice by comparing anti-HDV and HBsAg serology data over the last six years, among the new HBsAg carriers and all the HBsAg carriers.
HBsAg and anti-HDV were screened using the Abbott Architect HBsAg quanti kit and the DIA.PRO HDVAb kit. Serological, demographic, virological, and clinical data were analyzed.
Implementing anti-HDV reflex testing leads to more than a 2-fold increase in diagnoses of HDV infection among all HBsAg carriers. If the anti-HDV positive rate remains stable among the new HBsAg carriers, a significant increase in the anti-HDV positive rate from 6.8 % to 10.3 % was observed considering all HBsAg carriers. Interestingly, the discovery of anti-HDV carriage increased from 3.9 % to 6.5 % in 2022, allowing earlier identification of HBV-HDV-infected patients and a fast referral to hepatologists for adequate clinical management and, in some cases, the introduction of bulevirtide-based therapy.
Our preliminary results at one year seem promising and evaluating the cost-effectiveness of reflex tests in real life with feedback would be helpful.journal article2024 Apr2024 02 03importe
Augmenter le temps d’enseignement de l’éducation physique et sportive à l’école primaire : sur quels facteurs peut-on agir ?
Réalisée auprès de 555 professeurs des écoles, cette étude avait pour objectif d’identifier des facteurs reliés au temps d’enseignement hebdomadaire de l’EPS, et de quantifier le poids respectif de onze facteurs liés au contexte d’enseignement, à la formation, et aux caractéristiques sociodémographiques et motivationnelles de l’enseignant. Les résultats montrent que plus de 55 % de l’échantillon rapportent un temps d’enseignement de l’EPS inférieur à 180 minutes. Ils soulignent la plus grande vulnérabilité des professeurs des écoles qui enseignent en cycle 2 et 3, de ceux qui ont le moins d’expérience, et des femmes. Ils font enfin ressortir que l’attitude envers l’activité physique et le sentiment d’auto-efficacité relatif à l’enseignement de l’EPS constituent des variables à cibler en priorité dans l’optique d’augmenter le temps d’enseignement hebdomadaire de cette discipline.
Carried out with 555 primary school teachers, this study aimed to identify factors relating to the weekly teaching time for physical education and to quantify the respective weight of eleven factors relating to the teaching context, training, and the socio-demographic and motivational characteristics of the teachers. The results show that more than 55% of the teachers report less than 180 minutes of teaching time per week. The results also highlight the greater vulnerability of teachers who teach 1st to 5th grades, those with the least experience, and women. Finally, results highlight that attitudes towards physical activity and self-efficacy for teaching physical education are priority variables to target in order to increase teaching time per week in this subject