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P1056 Effectiveness and Safety of Upadacitinib Induction Therapy in Real-World Setting for 234 Patients with Crohn’s Disease: A GETAID Multicentre Cohort Study
No full textInternational audienceBackgroundWhile upadacitinib has demonstrated its efficacy as an induction treatment for Crohn’s disease (CD) in two phase 3 randomized, placebo-controlled trials1, real-world data remain limited.MethodsFrom September 2022 to September 2024, all consecutive patients with refractory CD treated with once-daily upadacitinib 45 mg in 30 French and Belgian GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission (SFCR) at week 12, defined as a Harvey-Bradshaw Index (HBI) score of < 4. Secondary endpoints included clinical response (decrease of ≥ 3 points in the HBI score and/or an HBI score < 4), clinical remission, biological remission (calprotectin ≤ 250 µg/g, or CRP ≤ 5 if calprotectin was unavailable), endoscopic or radiological (IUS and/or MRI) response, and adverse events (AEs).Results234 patients were included, all of whom had been previously exposed to at least one biologic (median 4, IQR[3-4]), and 125 (53.9%) had undergone prior intestinal resection (Table 1). At week 12, SFCR was observed in 107 patients (n=107/197, 54%), clinical response in 120 (n=120/190, 63%) and clinical remission in 111 (n=111/197, 56%). Ninety-two (n=92/179, 51%) achieved biological remission and endoscopic or radiological response was observed in 19 (n=19/40, 48%) patients (Figure 1). Respectively 28 (n=28/37, 76%) and 20 (n=20/37, 54%) of patients with articular EIMs achieved clinical response and remission. For cutaneous EIM, clinical response was achieved in 10 patients (n=10/11, 91%), and clinical remission was achieved in nine patients (n=9/11, 82%). In multivariate analysis, body mass index < 18.5 kg/m2 (OR=0.09, 95%CI: 0.01-0.33, p=0.002) and HBI > 7 (OR=0.24, 95%CI: 0.12-0.47, p<0.0001) were associated with lower rates of SFCR at W12 while the number of prior biologics did not influence SFCR (OR = 0.72, 95% CI: 0.35-1.48; p = 0.36).At week 12, 35 (15%) patients discontinued upadacitinib (lack of effectiveness, n=31; AEs, n=2 and other, n=2). CD-related hospitalization was needed in 18 (7.7%) patients, and 4 (1.7%) underwent intestinal resection. Sixty-eight AEs occurred in 61 patients (26%), including 19 serious AEs, corresponding to 18 cases of CD exacerbation and one case of colonic EBV-associated lymphoproliferative disorder. Acne was observed in 25 (10.7%), justifying treatment discontinuation in one (0.4%).ConclusionIn this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response in about two-thirds of patients and SFCR in half of patients
Maintien du contrôle restreint du juge administratif sur la mesure de prolongation d'isolement
No full textInternational audienc
Engagement de la responsabilité de l'État en matière de non-recouvrement de l'impôt concernant un établissement public à caractère industriel et commercial
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Cytokine Hemoadsorption versus Standard Care in Cardiac Surgery Using the Oxiris® Membrane: the OXICARD single center randomized trial
No full textInternational audienceBackground: Cardiac surgery can lead to dysregulation with a pro-inflammatory state, resulting in adverse outcomes. Hemadsorption using the AN69 membrane (Oxiris membrane) has the properties to chelate inflammatory cytokines. We hypothesized that in patients at high risk of inflammation, the use of the Oxiris membrane could decrease inflammation, preserve endothelial function, and improve postoperative outcomes. Methods: We conducted a randomized single-center study at Amiens University Hospital. The study population consisted of adult patients admitted for scheduled cardiac surgery with an expected cardiopulmonary bypass (CPB) time over 90 minutes. The patients were allocated to either the standard group or the Oxiris group. The intervention consisted of using the Oxiris membrane on a Prismaflex device at a blood flow rate of 450 ml/min during CPB. The primary outcome was the assessment of microcirculation on day 1 after surgery by measuring sublingual microcirculation using the microvascular flow index (MFI). MFI reflects the microcirculation flow type and is graded from 0 to 3 as follows: 0: no flow; 1: intermittent flow; 2: sluggish flow; 3: continuous flow. The secondary outcome was a composite adverse outcome within 30 days after surgery. Cytokines and endothelial biomarkers were measured in all patients at different time points. An intention-to-treat analysis was performed. Results: From October 2019 to November 2022, we included 70 patients. Two patients were excluded from the Oxiris group: one patient did not undergo surgery and one procedure was performed under deep hypothermia. The MFI did not differ between groups on day 1 from baseline: difference Oxiris-standard at -0.17 [-0.44; 0.10]; P =0.2. The occurrence of a composite adverse outcome did not significantly differ between groups (14 [42%] for the Oxiris group vs 12 [35%] for the standard group; P=0.7). The overall variation in cytokines and angiopoietins did not significantly differ between groups. Conclusions: In patients scheduled for a cardiac surgery with prolonged CPB, we could not demonstrate the benefit on microcirculation and major cardiovascular events. Registration: URL: https://clinicaltrials.gov/study/NCT04201119. Identifier: NCT0420111
Digitally-assisted structure design of a large-size proton exchange membrane fuel cell
No full textInternational audienceA digitally-assisted method is proposed to accelerate the structure design of large-size proton exchange membrane fuel cells, including backward engineering and forward design
Semiclassical Estimates of Pressure-induced Line Widths for Infrared Absorption in Hot (Exo)planetary Atmospheres
No full textInternational audienceAbstract Because of elevated temperatures and high fluxes of stellar radiation irreproducible in laboratory conditions, molecules and molecular ions found or expected in exoplanetary atmospheres are generally poorly characterized from the viewpoint of their spectroscopic line-shape parameters; in many cases, there are no data at all. Advanced theoretical approaches (classical, semiclassical, and quantum mechanical), without mentioning their high computational cost, are also impracticable due to the lack of potential energy surfaces. To fill this gap of crucially missing line-broadening parameters, we provide estimated values issued from a simple rotationally independent semiclassical expression. Only the index related to the leading long-range interaction term, molecular masses and kinetic diameters, as well as temperature are used as input parameters. A wide range of absorbers and perturbation by He, Ar, H 2 , N 2 , O 2 , CO, NO, CO 2 , H 2 O, CH 4 , and NH 3 as well as self-perturbation are considered. The explicit temperature dependence T −0.5 allows calculations to be limited to the single reference temperature of 296 K; for other temperatures a simple scaling can be used. The full set of line-broadening coefficients obtained with various possible values of kinetic diameters is provided by the new Collisional Line-broadening Parameters database, which is specifically designed for this purpose. “Midvalue” (or more recent) kinetic diameters are retained to create one-value line-broadening data required to populate the ExoMol database. A way to generate rotationally dependent line widths is proposed
Cumul d'une fonction publique avec une profession libérale
No full textInternational audienceAucune formalité ne peut être exigée - Note sous Conseil d'Etat, 24 juillet 2024, no 475767 (sera mentionné aux tables du Lebon
L'histoire de l'adverbe à base adjectivale avec préposition depuis l'ancien français : confrontation de sources (Matériaux de projet)
No full textMatériaux de projetLes adverbes et les adverbiaux sont largement analysés dans la linguistique actuelle, que ce soit dans une perspective de délimitation ou de classification (récemment : Duplâtre/Modicom 2022) ou, comme ici, dans une perspective variationnelle (p. ex. Hummel 2017, 2019ab). Pourtant, l’adverbe formé d’une préposition et d’un adjectif est, lui, passé largement inaperçu, y compris dans la grammaticographie des langues romanes. Ce document de travail a été conçu dans un projet panroman qui retrace l’évolution depuis le latin d’adverbiaux comme à l’extrême, en grand, pour le sûr ou par exprès, construits selon le schéma ‘< PREP (+ PREP) (+ ADV) (+ DET) + ADJ >. Il constitue l'annexe à des articles à paraître dans les Romanische Forschungen et chez De Gruyter. Il présente une synthèse de la représentation de ces adverbes en français dans un corpus de sources essentiellement métalinguistiques. Il s’appuie sur les grandes grammaires et les dictionnaires historiques incontournables du français en ciblant l’histoire du français dans la francophonie du Nord, plus exactement en Europe ainsi qu’en Amérique du Nord
Clinically relevant cell culture model of inflammatory bowel diseases for identification of new therapeutic approaches
No full textInternational audienceInflammatory Bowel Diseases (IDB) are chronic disorders characterized by gut inflammation, mucosal damage, increased epithelial permeability and altered mucus layer. No accurate in vitro model exists to simulate these characteristics. In this context, drug development for IBD or intestinal inflammation requires in vivo evaluations to verify treatments efficacy. A new model with altered mucus layer composition; altered epithelial permeability and pro-inflammatory crosstalk between immune and epithelial cells will be developed to enhance in vitro models for studying IBD treatments. The effects of dextran sulfate sodium and/or lipopolysaccharides on intestinal permeability, cytokines synthesis (IL-6, IL-8, TNF-α and IL-1β), mucins (MUC2, MUC5AC) and tight junction proteins expression (Claudin-1, ZO-1 and Occludin) were investigated in a tri-coculture model combining differentiated Caco-2/HT29-MTX cells and THP-1 cells. Two anti-inflammatory agents were evaluated to assess the model’s therapeutic strategy applicability (corticoids and pro-resolving factors). Two in vitro models have been developed. The first model, characterized by increased permeability of the epithelial layer and subsequent secretion of inflammatory cytokines, can reproduce the different phases of inflammation, and enables the evaluation of preventive treatments. The second model simulates the acute phase of inflammation and allows for the assessment of curative treatments. Both models demonstrated reversibility when treated with betamethasone and pro-resolving factors. These in vitro models are valuable for selecting therapeutic agents prior to their application in in vivo models. They enable the assessment of agents’ anti-inflammatory effects and their ability to permeate the inflamed epithelial layer and interact with immune cells
Whole-cell aptamer-based techniques for rapid bacterial detection: Alternatives to traditional methods
No full textInternational audienceControlling the spread of bacterial infectious diseases is a major public health issue, particularly in view of the pandemic of bacterial resistance to antibiotics. In this context, the detection and identification of pathogenic bacteria is a prerequisite for the implementation of control measures. Current reference methods are mainly based on culture methods, which generate a delay in obtaining a result and requires equipment. Consequently, focusing on the detection of the whole bacterium represents a very attractive alternative, since no culture is required. Several techniques have already been deployed to identify whole-cell bacteria. In recent decades, growing interest in nucleic acid aptamers has emerged as a viable alternative to antibodies as recognition elements, offering preferable stability, cost-efficiency, good specificity and affinity. This review explores current alternative methods for the detection of whole-cell bacteria, with particular emphasis on aptamer-based assays. These assays have shown promising results in various transduction mechanisms, including optical, electrochemical, and mechanical approaches, enhancing their versatility in different diagnostic platforms. The integration of aptamers in these detection methods offers rapid, sensitive, versatile and portable solutions for pathogen identification, positioning them as valuable tools in the fight against bacterial infections