Centre Hospitalier Universitaire Dijon Bourgogne

Shareable abstractWhile most relatives of TRG-variant carriers report exposure to inhaled toxics, few make behavioural changes within a year of genetic counsellinghttps://bit.ly/4iEGBBN

ObjectiveTo investigate whether oral ivermectin or topical 5% permethrin can clinically cure scabies in index cases and in members of their households.DesignMulticentre, assessor blinded, cluster randomised clinical trial.Setting28 French hospitals, 19 January 2016 to 16 December 2021.ParticipantsIndex cases; adults and children weighing >15 kg with scabies, confirmed by dermoscopy.InterventionsIndex cases were randomly assigned to the ivermectin group or permethrin group (1:1 ratio). Each member of the cluster, defined as the household of each index case, received the same treatment as the index case, except for children weighing <15 kg who were prescribed topical 5% permethrin. All participants received oral ivermectin 200 µg/kg or 5% permethrin cream on day 0 and day 10. Permethrin cream was applied to the whole body, from head to toe.Main outcome measuresThe primary outcome was clinical cure of the cluster on day 28 (ie, disappearance of clinical signs and symptoms of scabies for all cluster members). Secondary outcomes were index case and individual level analyses and safety. Dermatologists were used as assessors and were masked to the treatment.Results507 participants in 142 households (clusters) were treated with ivermectin and 568 participants in 147 households received permethrin. Cluster level cure rates were 71.8% versus 88.5% (–16.7 percentage point difference, 95% confidence interval (CI) –26.3 to –7.1) for ivermectin versus permethrin. Secondary outcome percentage point differences also showed the inferiority of ivermectin compared with 5% permethrin for index cases (76.6% v 91.5%; percentage point difference –14.9, 95% CI –23.6 to –6.2) and participants (85.3% v 94.2%; –9.2 percentage point difference, –14.9 to –3.5). Intraclass correlation coefficients were higher for permethrin than ivermectin for all clusters (0.68, 95% CI 0.61 to 0.75 v 0.46, 0.37 to 0.56) and for cluster size >1 (0.67, 0.60 to 0.74 v 0.47, 0.37 to 0.56). Cutaneous adverse events were found in 11.9% and 15.6% of participants treated with ivermectin and permethrin, respectively.ConclusionsThe results of this cluster randomised trial of classic scabies, confirmed by dermoscopy, did not show the non-inferiority of oral ivermectin compared with 5% permethrin cream, given on days 0 and 10, in achieving clinical cure of scabies on day 28 in index cases and their household members. Conversely, the trial showed the statistical superiority of 5% permethrin cream.Trial registrationNCT02407782.

Standard management with chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT) followed by total mesorectal excision (TME) reduces local recurrence but often is associated with significant long-term functional impairment. Organ preservation (OP) has become a key therapeutic goal in rectal cancer to reduce surgery-related morbidity without compromising oncological outcomes. Three main OP strategies have been developed: Watch and Wait (W&W) strategy, Local Excision (LE) and Contact X-ray Brachytherapy (CXB), both applicable in patients showing a favourable tumour response after neoadjuvant therapy. The current challenge is defining the optimal timing and modalities for response assessment to accurately identify complete clinical response while balancing oncological control, functional outcomes and patient preferences. This trial evaluates whether a structured tumour response surveillance program combined with shared decision-making (SDM) can safely increase OP rates. GRECCAR 20 is a multicentre, randomized, open-label, phase III trial enrolling patients with cT2-T3N0-1 rectal adenocarcinoma ≤ 8 cm from the anal verge and ≤ 4 cm in length, without involvement of the anal canal. Across the French GRECCAR and PRODIGE network, 270 patients will be recruited over 36 months. After neoadjuvant treatment (CRT or induction chemotherapy followed by CRT), participants are randomized to either a structured tumour response surveillance strategy with SDM over 8 to 24 weeks (experimental arm) or standard response assessment without SDM at 8 weeks (control arm). In the experimental arm (Arm A), reassessments at 2-, 4- and 6-month post-treatment will guide management decisions-W&W, LE, CXB or TME-through a collaborative process between patient and clinician. In the control arm (Arm B), treatment decisions at 2 months will be made solely by the clinician, between LE or TME, based on clinical, endoscopic and radiological assessment. The primary outcome is the OP rate at 2 years. Secondary endpoints include disease-free survival, TME-free survival, functional outcomes, quality of life (QoL) and patient-reported outcome measures (PROMs). GRECCAR 20 is the first randomized trial to assess a structured tumour response surveillance program incorporating SDM in rectal cancer. By prioritizing patient values and QoL, this trial aims to improve OP rates without compromising oncological safety, potentially establishing a new standard of personalized, patient-centred care.

Local muscle vibrations (LMV) acutely and chronically affect the sensorimotor system, but their effects vary depending on application conditions. The mechanisms behind repeated LMV exposure are still debated. This study investigated the chronic effects of LMV under illusion-inducing conditions on the upper limb. Nineteen healthy participants completed 9 LMV sessions (80 Hz, 20 min) over 11 days targeting the right wrist flexors. Illusions were assessed using subjective scales and EEG (alpha band desynchronization). Neurophysiological parameters (spinal, corticospinal excitabilities, and intracortical inhibition) and grip strength were evaluated before and after a control session (20-min rest) and an LMV session, as well as after 9 LMV sessions and 5 days post-protocol. Participants consistently experienced illusions throughout the protocol, with stronger perceptions during the first 15 min. However, subjective and objective measures were found to be independent. Acute LMV significantly reduced the H-reflex (-52.3% [-69.7 ; -21.0]) but did not affect strength or other neurophysiological measures. Additionally, repeated LMV exposure induced no chronic changes in strength or neural excitabilities and inhibition. While confirming acute LMV effects under illusion conditions, this study found no evidence of chronic adaptations. It also suggests that subjective and objective (EEG-based) illusion measures reflect distinct neurophysiological mechanisms.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-26915-z.

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Gastroparesis is predominantly caused by diabetes mellitus or vagal nerve injury post-surgery. About 30% of patients develop gastroparesis after esophagectomy with gastric pull-through. Standard treatments often fail, and endoscopic pyloromyotomy (G-POEM) has shown promising results. This study aimed to assess the efficacy and safety of G-POEM in patients with refractory gastroparesis after esophagectomy. A multicenter retrospective cohort study was conducted across 18 expert centers. Patients who underwent G-POEM for refractory gastroparesis following esophagectomy from August 2014 to December 2023 were included. Inclusion criteria were confirmed gastroparesis by scintigraphy, a mean Gastroparesis Cardinal Symptom Index (GCSI) of at least 1.0, and a minimum of 6 months of follow-up. The primary outcome was treatment success at 6 months, defined as a ≥50% decrease in the GCSI score. Of 113 G-POEM procedures, 108 patients (median age 65 years; 75% men) met the inclusion criteria. The primary indication for esophagectomy was adenocarcinoma (75.5%). At 6 months, 63.5% (95%CI 54.1%–72.0%) achieved clinical success, with the mean GCSI significantly decreased to 1.2 (95%CI 1.0–1.4) from 2.9 (95%CI 2.7–3.1) preprocedure. Minor adverse events occurred in 2.8% of cases. Long-term follow-up showed sustained efficacy with success rates of 54.9% and 66.1% at 12 and 24 months, respectively. G-POEM appears to be a safe and effective treatment for refractory gastroparesis in post-esophagectomy patients, achieving significant symptom relief in the majority of patients. Future prospective studies are necessary to further validate these findings and explore predictive factors for treatment success.

En 2024, le groupe de travail « Suivi thérapeutique pharmacologique et personnalisation des traitements de la Société française de pharmacologie et de thérapeutique » a élaboré un livre blanc dont l’objectif est de présenter l’état des lieux de la sous-discipline de la pharmacologie biologique, de décrire les compétences attendues pour exercer le métier de pharmacologue biologiste, de définir le périmètre de l’activité professionnelle, d’identifier les forces et les points d’amélioration actuels de la sous-discipline dans l’objectif final de proposer les évolutions du métier de pharmacologue biologiste. Ce document se compose de plusieurs parties : un préambule visant à rappeler le panorama de la pharmacologie biologique en France ; un état des lieux rappelant ce qu’est un pharmacologue biologiste, ses missions, les forces et faiblesses de la profession et les pré-requis en termes de formation ; un référentiel de compétences du pharmacologue biologiste et enfin les perspectives et nouvelles missions du pharmacologue biologiste. Ce document a pour vocation de servir de référentiel, d’aider à définir la profession de pharmacologue biologiste et de structurer la discipline afin de pouvoir la faire évoluer vers une profession d’interface entre biologie et clinique. In 2024, the therapeutic drug monitoring and treatment personalization working group of the Société française de pharmacologie et de thérapeutique (French Society of Pharmacology and Therapeutics) drew up a white paper, the aim of which is to present the current state of the biological pharmacology discipline, describe the skills required to exercise the profession, define the scope of professional activity, identify the discipline's current strengths and areas for improvement, with the ultimate aim of proposing changes to the profession of biological pharmacologist. This document is divided into several parts: a preamble outlining the panorama of biological pharmacology in France; a review of the current situation, outlining what a pharmacological biologist is, his or her missions, the strengths and weaknesses of the profession, and the prerequisites in terms of training; a reference framework of competencies for the pharmacological biologist; and, finally, the prospects and new missions of the pharmacological biologist. The purpose of this document is to serve as a term of reference, to help define the profession of pharmacological biologist, and to structure the discipline so that it can evolve into a profession at the interface between biology and the clinic.