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Multi-patient Inverse Estimation of Effective Membrane Diffusion Coefficients in Calcium-Citrate Hemodialysis
No full textWe propose a multi-patient inverse modeling framework for identifying effective calcium and citrate diffusion coefficients in hollow-fiber hemodialysis devices. The approach relies on a coupled forward model combining axisymmetric fluid dynamics with multi-species convection-reaction-diffusion, together with a derivative-free optimization strategy to estimate membrane transport parameters from outlet concentration measurements. To account for inter-patient variability, physiological input parameters are first generated from clinical data and complemented by a patient-specific hydraulic calibration step, ensuring physical consistency across the synthetic cohort. The inverse problem is formulated as a global least-squares minimization aggregating residuals over multiple patients. Numerical experiments on synthetic data demonstrate multi-patient identifiability of the diffusion coefficients in the exact-data setting. Robustness with respect to measurement noise is subsequently assessed by perturbing observable outputs at various noise levels, and sensitivity analyses are performed to quantify the influence of membrane transport parameters on model predictions. The methodology is then applied to real clinical data obtained from an AK200 Gambro/Nikkiso DBB07 dialysis system. The results indicate that aggregating information from several patients substantially improves parameter identifiability and stability compared to single-patient inversions. Overall, this work provides a physically consistent and computationally tractable framework for multi-patient parameter estimation in dialysis models, Although the present contribution builds upon the framework introduced in the works of the present authors
Evaluation of induction practices for general anesthesia in patients with obesity: A French nationwide online survey
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P1071 Comparison of effectiveness between Vedolizumab and Filgotinib in patients with ulcerative colitis previously exposed to at least one anti-TNF agent: Results from the real-world evidence multicenter VEDOFIL study
No full textInternational audienceBackground We aimed to compare the effectiveness of vedolizumab and filgotinib in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent. Methods This was a multicenter real-world evidence retrospective study that consecutively included all UC patients aged ≥18 years with symptomatic UC (partial Mayo score > 2) who initiated vedolizumab (VDZ) or filgotinib (FLG) after prior exposure to at least one anti-TNF. VDZ was administered intravenously with induction at 300 mg at weeks 0, 2, and 6, and subsequent IV infusions every 4 or 8 weeks according to the investigator’s choice. FLG was prescribed at a unique dose of 200 mg orally once daily. The primary endpoint was symptomatic remission (partial Mayo score ≤2) without corticosteroids (CFREM) at week 16 (W16). Secondary endpoints were clinical remission per modified Mayo score, and histological and endoscopic improvement (HEMI). Comparisons were made using propensity-score analyses (IPTW) adjusted the usual potential confounders. Results Overall, 230 patients were included (151 in the VDZ group and 79 in the FLG group. The two groups were comparable except for higher proportion of patients with prior exposure to at least 2 biologics (36.1% vs 92.1%; p < 0.001) in FLG group and concomitant corticosteroids (31.1% vs 19.0%) or an associated immunosuppressant (20.5% vs 0%) in VDZ group. After propensity adjustment, CFREM at W16 was achieved in 38.1% and 31.1% of patients in VDZ and FLG groups, respectively (p = 0.51). Subgroup analyses (after IPTW) showed that VDZ was more effective than FLG after failure of a single biologic (p < 0.001), with no difference after two prior failures (OR = 2.05 [0.36–11.71], p = 0.41), whereas FLG was more effective after failure of at least three prior biologics (OR = 10.4 [1.1–102.4], p = 0.045). No predictor of FLG effectiveness was identified. Factors associated with absence of CFREM at W16 on VDZ were UC severity (p = 0.035), failure of ≥ 3 biologics (p = 0.013), and primary failure to at least one biologic (p = 0.013). No difference was observed between the two treatments regarding clinical remission and HEMI at W16 (p = 0.47 and 0.18, respectively). With a median follow-up of over 12 months, no significant differences were noted between the two treatments in time to treatment discontinuation, UC-related hospitalization, or colectomy. Conclusion In this real-world evidence study, VDZ appeared to be a more effective option than FLG as a second-line biologic (after anti-TNF failure), whereas FLG became a better option in third- or fourth-line of advanced therapies. These data may help physicians managing patients with UC to guide therapeutic decision-making. Conflict of interest: Prof. Dr. Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda Bouguen, Guillaume: Grant: Abbvie, Ferisinus Personal Fees: Abbvie, Takeda, Fresinus, Amgen, Biogène, Arena, Ferring, Gilead, Janssen, MSD, Pfizer, Sandoz, Takeda, Tillots, Vifor pharma Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Domas, Quentin: No conflict of interest Serrero, Melanie: No conflict of interest Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Caillo, Ludovic: Abbvie, Amgen, Celltrion, Ferring, Fresenius, Lilly, Jonhson&Jonhson, MSD, Pfizer, Takeda, Sandoz Hupé, Marianne: No conflict of interest Gilletta de Saint Joseph, Cyrielle: Speaker/ consultant fees from Abbvie, AlfaSigma, Amgen, Celltrion, Ferring, Fresenius, Janssen, Lilly, Pfizer, Takeda and Tillots Treton, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, johnson&Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Pereira, Bruno: No conflict of interes
P0869 Comparison of effectiveness between subcutaneous infliximab as monotherapy or combined with an immunosuppressant in patients with Crohn’s disease: interim results from the REMONO-CD study.
No full textInternational audienceBackground We aimed to demonstrate the non-inferiority of subcutaneous infliximab monotherapy (SC IFX mono) compared with combination therapy (SC IFX + IS) in patients with Crohn’s disease (CD). Methods In this multicenter (22 centers) retrospective study, we consecutively included all patients ≥18 years-old with symptomatic CD according to PRO-2 (abdominal pain subscore >1 or stool frequency >3) who started SC infliximab 120 mg every 2 weeks, from week 6 or W10 after an IV induction regimen (2 or 3 IV infusions at 5 mg/kg at week 0, W2 ± W6). The primary endpoint was clinical remission (abdominal pain subscore ≤1 and stool frequency ≤3) without steroid (CFREM) and is expressed as % of months (4-week periods) spent in CFREM (month being the statistical unit). The non-inferiority margin was predefined at -10% according to IOIBD recommendations. A priori sample-size calculation (considering hypothesis of 55% of months spent in CFREM in reference group, 90% power, one-sided 95% confidence interval due to non-inferiority design, and imbalance between groups), indicated that 2,160 months were required, i.e 210 patients. We present here the results of an interim analysis while data from half of participating centers have been collected. Secondary endpoints considered the patient as the statistical unit. All comparisons were performed using propensity-score adjustment (IPTW) Results To date, 196 patients (1,954 months) have been included (SC IFX mono = 62 and SC IFX +IS = 134 patients). The two groups were comparable except for higher complicated phenotypes and shorter disease duration in SC IFX+IS group (Table 1), which has been taken into account in propensity score analyses. Analysis on primary endpoint including 1,954 months, showed that 73.6% and 61.5% of months were spent in CFREM in SC IFX and SC IFX + IS groups, respectively, giving an absolute difference of + 12.1% [lower bound = +8.4%, upper bound = +15.6%], confirming the non-inferiority of SC IFX mono. After IPTW (N = 196 patients), no difference of CFREM at W12 (67.1% vs 59.8%;p=0.32), W24 (71.5% vs 64.2%;p=0.28), and W52 (65.4% vs 61.9%;p=0.66) was seen between SC IFX mono and SC IFX + IS, respectively, (Table 2) with no difference in subgroups such as bio-exposed, B2/B3 phenotypes, and prior exposure to IS. SC IFX mono was not associated with a higher risk of SC IFX dose optimization (HR = 0.81 [0.41–1.60], p = 0.55), IFX discontinuation (HR = 1.87 [0.96-3.65], progression of bowel damage (HR = 0.66[0.15–2.96]), bowel resection (HR = 0.15[0.02–1.15]), or hospitalization (HR = 0.80[0.30–2.10]) (median follow-up=19.4 months). Conclusion In this real-world multicenter study, SC infliximab monotherapy appeared non-inferior to combination therapy in CD at both short and mid-terms. Conflict of interest: Prof. Dr. Buisson, Anthony: Consulting fees from : Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda Caron, Bénédicte: No conflict of interest Le Berre, Catherine: Abbvie, Amgen, Celltrion, Ferring, Fresenius Kabi, Galapagos, Gielad, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda. Le Cosquer, Guillaume: consultant/lecture, transport fees from AbbVie, Amgen, Johnson & Johnson, Lilly, Takeda, Fresenius Kabi, Celltrion, and Pfizer. Serrero, Melanie: fees from Pfizer, Abbvie, Takeda, Janssen, MSD, Amgen, Ferring, Tillotts, Celltrion Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Boschetti, Gilles: No conflict of interest Vuitton, Lucine: No conflict of interest Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, johnson & Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Peyrin-Biroulet, Laurent: CONSULTING Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Gilletta de Saint Joseph, Cyrielle: Speaker/ consultant fees from Abbvie, AlfaSigma, Amgen, Celltrion, Ferring, Fresenius, Janssen, Lilly, Pfizer, Takeda and Tillots Guillo, Lucas: No conflict of interest Nancey, Stéphane: board membership and lecturing fees from Abbvie, Takeda, Celltrion Healthcare, Pfizer, Galapagos, Johnson & Jonshon, Lilly, Fresenius, Amgen, Medac, MSD. Domas, Quentin: No conflict of interest Pereira, Bruno: No conflict of interes
Prognostic Impact of Recreational Drug Use on 1-Year Outcomes in NSTEMI and STEMI Patients
No full textInternational audienceBackground: Recreational drug use is increasingly associated with adverse outcomes in acute coronary syndrome (ACS) patients, but differences in long-term outcomes between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction are not well defined.Objective: The authors evaluated the association between recreational drug use and major adverse cardiovascular events (MACE) 1 year after intensive cardiac care unit (ICCU) admission in ACS patients.Methods: The Addiction in Intensive Cardiac Care Units study systematically screened all patients admitted to ICCUs across 39 French centers (April 7-22, 2021) via prospective urinary testing. The primary outcome was MACE, defined as cardiovascular death, nonfatal myocardial infarction, or stroke. One-year follow-up was collected through clinical visits or direct contact between patients and cardiologists, concluding in June 2022. Outcomes were adjudicated by an independent cardiology committee. The prognostic impact of recreational drug use on MACE was assessed using multivariable Cox proportional hazards models, validated by propensity matching.Results: Of 712 ACS patients, 13.5% had recreational drug detection. At 1 year, MACE occurred in 7.0%, with higher rates among drug-positive vs drug-negative patients (12.5% vs 6.2%). Recreational drug use was associated with increased MACE (HR: 2.70; 95% CI: 1.30-5.57; P = 0.013). This association was significant in STEMI (HR: 4.11; 95% CI: 1.60-10.5; P = 0.005) but not in non-ST-elevation myocardial infarction patients. Propensity matching confirmed this in STEMI patients (HR: 3.39; 95% CI: 1.19-9.62; P = 0.022).Conclusions: Recreational drug use was associated with increased 1-year MACE risk in ACS patients, particularly STEMI, supporting routine drug screening
Protocole national de diagnostic et de soins– Péricardites récidivantes
No full textInternational audienceRecurrent pericarditis is characterised by repeated episodes of pericardial inflammation separated by an asymptomatic interval of at least 4 to 6 weeks. Diagnosis relies on typical clinical features (chest pain, pericardial friction rub), imaging-primarily echocardiography, with MRI when needed-and inflammatory markers, particularly C-reactive protein (CRP). The initial assessment aims to identify an underlying cause, which is most often idiopathic (frequently presumed post-viral) but may be autoimmune, autoinflammatory, or infectious. Management requires close coordination between specialists and reference centres, with the primary goal of preventing recurrence. Colchicine is the cornerstone of therapy and should be prescribed for 3 to 6 months, and often longer. During acute flares, NSAIDs or aspirin are recommended in combination with colchicine. Corticosteroids are no longer indicated, except in highly specific situations. In severe or refractory forms, early use of interleukin-1 inhibitors-particularly anakinra or rilonacept-should be considered. Long-term follow-up includes clinical and laboratory monitoring to ensure symptom resolution and normalisation of CRP levels, as well as regular assessment of quality of life. Treatment withdrawal must be very gradual, over several months or even years, and supported by therapeutic patient education to help patients recognise early warning signs. Coordinated follow-up within structured care networks is essential to ensure optimal access to treatment and advanced therapies. This French Protocol for Diagnosis and Management aims to provide clinicians with clear, harmonised, and up-to-date guidance to improve the diagnosis, treatment, and long-term care of patients with recurrent pericarditis.La péricardite récidivante se caractérise par des épisodes répétés d’inflammation péricardique séparés par un intervalle asymptomatique d’au moins 4 à 6 semaines. Le diagnostic repose sur des éléments cliniques typiques (douleur thoracique, frottement péricardique), l’imagerie — en premier lieu l’échocardiographie, complétée par l’IRM si nécessaire — et les marqueurs inflammatoires, en particulier la protéine C-réactive (CRP). L’évaluation initiale vise à identifier une cause, le plus souvent idiopathique (souvent présumée post-virale), mais parfois auto-immune, auto-inflammatoire ou infectieuse. La prise en charge nécessite une coordination étroite entre spécialistes et centres experts, avec pour objectif principal de prévenir les récidives. La colchicine constitue le traitement de base et doit être prescrite pendant 3 à 6 mois, souvent plus longtemps. Lors des poussées aiguës, les AINS ou l’aspirine sont recommandés en association avec la colchicine. Les corticoïdes ne sont plus indiqués, sauf dans des situations très spécifiques. Dans les formes sévères ou réfractaires, une inhibition précoce de l’interleukine-1 — notamment par anakinra ou rilonacept — doit être envisagée. Le suivi au long cours repose sur une surveillance clinique et biologique visant à confirmer la résolution des symptômes et la normalisation de la CRP, ainsi qu’une évaluation régulière de la qualité de vie. L’arrêt des traitements doit être très progressif, sur plusieurs mois voire années, et soutenu par une éducation thérapeutique permettant au patient de reconnaître les signes de récidive. Un suivi régulier au sein de réseaux de soins coordonnés est essentiel pour garantir une prise en charge optimale et l’accès aux thérapeutiques avancées. Ce Protocole National de Diagnostic et de Soins a pour objectif de fournir aux cliniciens des recommandations claires, harmonisées et actualisées afin d’améliorer le diagnostic, le traitement et le suivi des patients atteints de péricardite récidivante
DOP135 Bowel damage and disability in Crohn’s disease in the first year after diagnosis - results from the CROCO study.
No full textDigital oral presentationInternational audienceBackground Crohn’s disease (CD) progression can result in bowel damage (BD) and disability. BD is often believed to occur as a consequence of long-term progression. However, there is limited data about the early occurrence of BD within the first year of disease. Methods The Crohn’s Disease Cohort (CROCO) is a multicentre European study enrolling newly diagnosed CD patients (<12 months since diagnosis) and prospectively following them for 5 years to characterise BD progression and disability. BD is assessed using the Lémann Index (LI) (0 – no damage to 115 – maximal damage) at years 1 (Y1), 3, and 5 after diagnosis. The presence of any degree of BD was defined as a LI > 0, and the presence of significant BD as a LI > 2.1 Disability is evaluated every six months using the IBD-Disability Index (IBD-DI). Here, we report BD at Y1 and its associations with key disease features and with the IBD-DI. Results 539 patients were enrolled across 19 centres, with a median interval between diagnosis and inclusion of 3.7 months (IQR 1.5–7.3). Of these, 415 completed the Y1 visit, and 243 (58%) the LI evaluation [57% male; median age at diagnosis 35yo (IQR 25–50)]. At inclusion, 89% had ileal or ileocolonic disease, 73% had inflammatory phenotype, and 8% had perianal disease. During the first year, 10% underwent surgery (18 intestinal, 5 perianal) and 21% required hospitalisation. During the first year after diagnosis, 18% received 5-ASA, 30% systemic corticosteroids, 36% immunosuppressants, and 61% advanced therapy. The median time from diagnosis to advanced therapy was 3.5 months (IQR 1.4–5.7), with 48% initiating it within six months. Overall, 64% of patients showed some degree of BD at Y1, although the median LI remained low [0.6 (IQR 0–1)]; 41 patients (17%) had significant BD. In multivariate logistic regression analysis, B2/B3 behaviour (p < 0.001) and perianal disease (p = 0.008) were independently associated with BD at Y1 (Table 1). In a sensitivity analysis restricted to B1 patients without prior surgery, isolated colonic disease (L2) was associated with a decreased likelihood of BD (OR 0.34, 95% CI 0.12–1.00, p = 0.039). Among patients with LI data, 227 completed the IBD-DI at Y1. The median IBD-DI was 16 (IQR 10–29), with 18% showing moderate-to-severe disability (IBD-DI>35). No association was observed between any BD and moderate-to-severe disability (OR 1.06, 95% CI 0.52–2.15, p = 0.88). Conclusion In this cohort of newly diagnosed CD patients, two-thirds showed some degree of BD after one year, which was mostly minimal, with only 17% developing significant BD and 18% experiencing moderate-to-severe disability. No association was observed between BD and disability. These findings support early disease as an important period for disease modification. Reference: 1. Gilletta C, Lewin M, Bourrier A, Nion-Larmurier I, Rajca S, Beaugerie L, Sokol H, Pariente B, Seksik P, Cosnes J. Changes in the Lémann Index Values During the First Years of Crohn’s Disease. Clin Gastroenterol Hepatol. 2015 Sep;13(9):1633-40.e3. Conflict of interest: Revés, Joana: Has received consulting fees from Janssen and Pfizer. Arebi, Naila: Personal Fees: Janssen,Lilly, Pfizer and Takeda Non-financial Support: Janssen (J & J), Novonesis Fadra, Adam: None to declare Madsen, Gorm Roager: None Burisch, Johan: Grant: Johnson & Johnson, MSD, Takeda, Tillots Pharma, BMS, Novo Nordisk Personal Fees: Celgene, MSD, Pfizer, AbbVie, Takeda, Tillots Pharma, Samsung Bioepis, BMS, Pharmacosmos, Galapagos, Zealand Pharma, Orion Pharma, Ferring, Johnson & Johnson Cravo, Marilia: None Bonnet-Dodel, Marie: None Kaimakliotis, John: None Vieujean, Sophie: Speaker fees from Abbvie, Takeda and Janssen. Van Kemseke, Catherine: No conflicts Ellul, Pierre: No Conflicts Conti, Kelly: None. Duricova, Dana: Personal Fees: Lecture fee from Janssen, Takeda, Pfizer, Eli Lilly, AbbVie, Ferring. Horutova, Jana: None. Rodríguez-Lago, Iago: Financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma. Research support from AbbVie. Supported by a research grant from Gobierno Vasco-Eusko Jaurlaritza (Grant No 2020111061 and 2023222006). Elorza, Ainara: None. Ordás Jiménez, Ingrid: None. Fernandez Clotet, Agnes: None Sebastian, Shaji: Grant: Takeda, Tillots pharma, Biogen, Pfizer, Abbvie, Johnson & Johnson, Olympus -Odin Vision Personal Fees: Tillots, Johnson & Johnson, Olympus Odin Vision, AbbVie, Takeda, Merck, Pharmacosmos, Amgen, Eli Lilly, BMS, Odin Vision Non-financial Support: Tillots, Takeda, AbbVie, Celltrion, Johnson & Johnson, Eli Lilly, Alphasigma, Ferring Pharma Thut, Jessica: None. Mocanu, Irina: None. Hernández Ramirez, Vicente: Vicent Hernandez has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, FAES Farma, Galapagos, Lilly and Casen-Recordati Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Pedersen, Natalia: No any Rajão Saraiva, Margarida: None. Goldiș, Adrian Eugen: None. Guedes, Ana: None. Ribeiro, Ana Raquel: None. Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Bigot, Noemie: None. Mary, Jean-Yves: none Lambert, Jérome: none Colombel, Jean-Frédéric: Grant: AbbVie, Janssen Pharmaceuticals, Takeda, Prometheus and Bristol Myers Squibb Lectures from: AbbVie, Roche and Takeda Other: AbbVie, Amgen, AnaptysBio, Allergan, Apini, Arena Pharmaceuticals, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, candidrx Celgene, Celltrion, Clearview Curogen, Eli Lilly, Envision Pharma Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Roche, Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Iterative Scopes, Landos, Microba Life Science, Merck, Mirador, Novartis, Otsuka Pharmaceutical, Owkin, Pfizer, Protagonist Therapeutics, Sanofi, Sun Pharma, Takeda, Teva, TiGenix, and is holding stock options in Intestinal Biotech Development Buisson, Anthony: Grant: Abbvie, Celltrion, Pfizer and Takeda Personal Fees: Abbvie, Amgen, Arena, Biogen, Celltrion, Ferring, Janssen, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor Pharma, Tinoco da Silva Torres, Joana: Grant: Abbvie, Janssen Personal Fees: Pfizer, Janssen, Abbvie, Sandoz, Lilly, Sanofi, Takeda Non-financial Support: Janssen, Abbvi
Towards robust probabilistic maps in Deep Brain Stimulation: exploring the impact of patient number, stimulation counts, and statistical approaches
No full textInternational audienceIntroduction Probabilistic Stimulation Maps (PSMs) are increasingly employed to identify brain regions associated with optimal therapeutic outcomes in Deep Brain Stimulation (DBS). However, their reliability and generalizability are challenged by the limited size of most patient cohorts and the inherent variability introduced by different statistical methods and input data configurations. This study aimed to investigate the geometrical variability of Probabilistic Sweet Spots (PSS) as a function of both the number of patients (nPat) and the number of stimulations per patient (nStim), and to model a stability boundary defining the minimum data requirements for obtaining geometrically stable PSS. Methods Three statistical approaches–Bayesian t -test, Wilcoxon test with False Discovery Rate (FDR) correction, and Wilcoxon test with nonparametric permutation correction–were applied to two patient cohorts: a primary cohort of 36 patients undergoing DBS for Parkinson’s Disease (PD), and a secondary cohort of 61 patients treated for Essential Tremor (ET), used to assess generalizability. Stimulation test data was collected intra-operatively for the first cohort and post-operatively for the second one. Geometric stability was evaluated based on variability in PSS volume extent and centroid location. Results The analysis revealed a non-linear trade-off between nPat and nStim to yield stable PSS. A stability boundary was defined, representing the minimum combinations of nPat–nStim required for anatomically robust PSS. Among the tested methods, the Bayesian t -test achieved stability with smaller sample sizes (∼15 patients) and demonstrated a consistent performance across both cohorts. In contrast, the Wilcoxon-based methods showed variable behavior between cohorts, which differed in symptom type and testing phase (intra-operative testing vs. post-operative screening). Discussion The proposed PSS stability boundary provides a practical reference for designing DBS studies and stimulation screening protocols aimed at probabilistic mapping. The Bayesian t -test emerged as a reliable method across both cohorts, supporting its potential in studies with limited sample sizes and scenarios where the method needs to be readily generalized to varying symptoms. These findings underscore the importance of considering both cohort size and stimulation count in probabilistic DBS mapping and call for further investigation into method-specific sensitivities to clinical and procedural factors
Ethosuximide and Irritable Bowel Syndrome–Related Abdominal Pain
No full textInternational audienceImportance T-type calcium channels, particularly the Cav3.2 subtype, are involved in pain transduction. Experimental studies and human data suggested that increased T-type channels activity or expression contributes to visceral hypersensitivity in irritable bowel syndrome (IBS), and that their inhibition alleviates pain. Objective To evaluate the therapeutic potential of ethosuximide, a T-type calcium channel blocker, for IBS-related abdominal pain. Design, Setting, and Participants This proof-of-concept, multicenter, double-blinded, placebo-controlled randomized clinical trial started in February 2018 and completed in February 2022, with analyses performed between October 2023 and December 2024. Participants were adults meeting Rome IV criteria for IBS, treated in 10 gastroenterology departments in French university hospitals, with abdominal pain intensity rated at least 4 out of 10 during a 7-day run-in period. Interventions Patients were randomized to receive ethosuximide or placebo daily for 12 weeks. Main Outcomes and Measures The primary end point was the responder rate, defined as at least 30% reduction in mean abdominal pain intensity associated with a Subject Global Assessment of relief score at least 4 (ie, considerably or completely relieved). Secondary outcomes included safety, IBS symptom severity, and quality of life. Results Of 161 enrolled patients, 124 were randomized (64 ethosuximide; 60 placebo). The mean (SD) age was 43.7 (14.9) years, 72 (58.1%) were women, the median (IQR) IBS duration was 5.0 (1.4-10.6) years, and the mean (SD) abdominal pain intensity was 6.0 (1.0). In the intent-to-treat analysis, responder rates did not differ significantly between groups (17 of 64 patients [26.6%] for ethosuximide vs 14 of 60 patients [23.3%] for placebo; relative risk, 1.14; 95% CI, 0.61-2.11). Ethosuximide was less well tolerated, with higher discontinuation rates (30 patients [46.9%] vs 13 patients [21.7%]; P = .003) and more adverse events (261 of 463 adverse events reported overall [56.4%] were determined to be caused by ethosuximide; P &lt; .001), most commonly headaches, sleep disturbances, and nausea, compared with placebo. Conclusions and Relevance In this randomized clinical trial, ethosuximide did not demonstrate efficacy over placebo for the treatment of IBS-related abdominal pain, and was associated with reduced tolerability. These findings do not support the use of ethosuximide for IBS pain management but highlight the need for development of more selective and better-tolerated T-type calcium channel modulators. Trial Registration ClinicalTrials.gov Identifier: NCT0297354
Phenotypic description of a large French series of individuals with Potocki-Lupski syndrome
No full textInternational audienceBackground: Potocki-Lupski syndrome (PTLS) is a rare genetic disorder, with an estimated prevalence of 1:25 000. Detection of a duplication at position 17p11.2 comprising the RAI1 gene establishes the diagnosis. Deletion of this same region is responsible for Smith-Magenis syndrome (SMS). Hitherto, the non-specific clinical features included psychomotor and growth retardation and multiple congenital anomalies. Our aim was to further delineate the clinical spectrum of PLTS.Methods: We gathered a series of 56 individuals carrying a 17p11.2 duplication, one of the largest reported to date. We collected detailed phenotypic data and established a phenotypic comparison with individuals already described in the literature.Results: We corroborated the main clinical signs associated with PTLS and highlighted additional features present in a significant proportion in our series, such as intrauterine growth retardation or low birth weight, musculoskeletal and ophthalmological anomalies, and abnormalities of the skin appendages. In line with previous reports, behavioural disorders were frequently identified (23%). Yet unexpectedly, self-aggressive and hetero-aggressive behaviours, characteristic features of SMS, were found in a small number of individuals. Forty-six individuals harboured the recurrent duplication (85%), five had larger duplications (9%) and three had smaller duplications (6%). We did not identify inherited duplications when parental information was available (n=43).Conclusion: Our study refined the clinical features of PTLS and their relative frequencies. Our findings therefore contribute to improving management of people with PTLS. These open up new pathophysiological hypotheses involving RAI1 gene dosage of the genesis and control of behaviour, as well as new, more complex regulatory pathways