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A French consensus proposal: Analytical performance targets for total and allergen-specific IgE and total tryptase
No full textInternational audiencePrecision medicine allows thorough characterization of patients endotype in allergy and anaphylaxis, thanks to progress in diagnostic tests and biomarkers. Allergy tests must therefore offer reliable, robust, and proficient quantitative results in each patient. These requirements have led to the development of quality assurance programs for allergy laboratory assays and their implementation in virtually all clinical laboratories performing in vitro allergy diagnosis and follow-up. However, consensus analytical performance targets for allergy assays have not yet been established. Here, the multicentric French network of public clinical laboratories and the Working Group on in vitro allergy diagnosis of the French Society of Allergy define performance criteria for specific and total IgE and tryptase tests
French Guidelines of the AchroPuce Network for the Interpretation and Reporting of Constitutional Copy Number Variants
No full textInternational audienceABSTRACT Over the past 15 years, molecular methods for human genome analysis have evolved significantly, becoming integral to routine genetic diagnostics. Among various genomic alterations, copy‐number variations (CNVs) are particularly important as sources of both benign and pathogenic variants. Accurate assessment of these variants' clinical implications is critical, especially for rare, non‐recurrent CNVs and for susceptibility loci linked to neurodevelopmental disorders (NDDs). To address these challenges, the French AchroPuce CNV Interpretation Working Group proposes a novel classification termed “PIEV,” referring to CNVs associated with NDDs characterized by incomplete penetrance and variable expressivity. This category complements the existing five‐tier ACMG classification system, supporting genetic professionals in harmonizing practice through standardized French national guidelines, thereby enhancing genetic counseling and clinical interpretation precision. Distinguishing clearly pathogenic variants from those with incomplete penetrance is crucial, and the consistent classification of these CNVs independently of the clinical context is essential. Clinical significance assessments should entail collaboration between biologists and multidisciplinary clinical teams, especially in prenatal diagnostics. The working group maintains an annually reviewed curated list of recurrent neurodevelopmental CNVs with reduced penetrance and provides consensus recommendations with a customized interpretation tool to enhance national consistency in CNVs reporting
Real-life safety of peanut oral immunotherapy: Results from a French multicenter observational study
No full textInternational audienceBackground: Peanut oral immunotherapy (POIT) has been widely used in France for more than 10 years. However, the overall ''real-life'' safety of POIT has not been evaluated to date. Objective: We sought to describe the number, severity, and circumstances of allergic reactions (ARs) in patients undergoing POIT. Methods: We performed a retrospective multicenter study from November 2019 to July 2021 in 12 French centers, including patients with peanut allergy who were older than 3 years and treated by POIT for 6 months or more. Data collected from the patients' charts about ARs occurring during the previous year included the number, severity (using the Astier score grades 1-5), and circumstances of all immediate allergic reactions (IARs) and non-IARs. Results: Among the 295 patients included, 46 (15.6%) experienced an IAR, accounting for a total of 75 IARs. The IARs were mainly grade 1; however, 22 (29.3%) were defined as a serious systemic reaction (ie, Astier score grade > _ 3) and 8 (10.6%) were managed by epinephrine injection at home. Proven cofactors were involved in 38 of 73 IARs (52.1%): exercise in 65.8%, fatigue in 18.4%, stress in 13.2%, irregular peanut intake in 5.3%, and pollen exposure in 5.3%. The use of epinephrine was more frequent when a cofactor was involved (0% vs 18.4%; P = .01). Among the 279 patients with available data, 32 (11.5%) experienced non-IARs, mainly chronic abdominal pain (20 [62.5%]). Conclusions: Although POIT is safe for most patients, some severe IARs influenced by cofactors may occur several months after the beginning of the process. These results highlight the overriding importance of maintaining therapeutic education, especially about risk cofactors, throughout oral immunotherapy programs.
Contribution of Addictovigilance data to assess adverse‐events linked to psychoactive substances in children and adolescents
No full textInternational audienceAims: We sought to characterize adverse events and deaths associated with the use of psychoactive substances in children and adolescents.Methods: Two French Addictovigilance databases were analysed: spontaneous reports and deaths over the period 2016–2021, in subjects aged 10–<18 years. An unsupervised classification was implemented on consumption data (medications or nondrug substances [NDS]) to identify subject clusters.Results: A total of 1544 spontaneous reports were analysed, comprising mainly boys (65.6%), aged on average 16 ± 1 years. Four clusters were identified: The cannabinoids users cluster (n = 597) was typified by the use of cannabis or/and synthetic cannabinoids (95.1%), with psychiatric (67.7%) and digestive disorders (16.7%). The medications/solvents/cannabidiol users cluster (n = 699) was distinguished by the use of medications or NDS including nitrous oxide/cannabidiol, with mainly neurological disorders (46.5%). The polydrug users cluster (n = 177) includes polyusers (98.3%) of NDS and medications. These users mainly have substance use disorders (63.8%). The psychotropic medications users cluster (n = 71) was characterized by the use of psychotropic medications. This cluster appeared to be correlated with psychiatric and organic disorders. The death database recorded 44 deaths, mainly in boys (61.4%) aged over 15 years. The main substances involved in the deaths were NDS (70.5%) and methadone. In 68.2% of cases, a single substance was responsible for the death.Conclusion: The adverse events related to the abuse of psychoactive substances identified in children and adolescents and the emerging signals show the need for increased surveillance and the implementation of prevention campaigns adapted to each group of consumers
Female Exercise Metabolism: Quality Assessment of Existing Knowledge Base and Key Challenges in Study Design
No full textInternational audienceA better understanding of the practical and methodological challenges inherent in accurately tracking female hormonal status would enhance the clarity of research findings in exercise metabolism. The purpose of this study was to conduct an objective assessment of the quality of existing literature in this area and to provide a general overview of the practical conditions and issues encountered in studies investigating substrate metabolism during exercise in women, both in those using (HC+) or not using (HC−) hormonal contraceptives. Forty-four articles were identified through systematic reviews, meta-analyses, and searches on PubMed/MEDLINE. A quality assessment framework was developed and applied using a double-blind scoring approach. The loss/exclusion of data between baseline and final analyses per study was quantified, and the main challenges were highlighted. A higher mean global score was observed in studies conducted among HC+ women (81%) than those among HC− women (46%). Although the dropout rates were rarely mentioned in HC+ women articles, the mean rate of participant/data loss in HC− groups was 22.1%. The rate of HC− participant loss was positively correlated with the global score ( r = .504, p = .02). High-quality research may be easier to achieve in studies involving HC+ women compared with those involving HC− women. Studies on HC− women seem to face more practical challenges, such as tracking the menstrual cycle and targeting specific (sub)phases of the menstrual cycle, along with technical and feasibility limitations. Thus, although the framework for designing such studies exists, the quality assessment of the available literature emphasizes its challenge in terms of research implementation
Targeted therapies overcome the poor prognosis of stereotyped Subset#2 chronic lymphocytic leukemia : a real-world multicentric study
No full textInternational audienceTO THE EDITOR:The outcome of patients with chronic lymphocytic leukemia (CLL) is known to be influenced by the mutational status of the immunoglobulin heavy-chain variable (IGHV) region [1]. In the past decade, it has been shown that a large part of CLL share B-cell receptor (BCR) sequence homologies, defining subsets of patients with similar clinical outcome [2]. The CLL Subset#2 (S#2), defined by the presence of the stereotyped IGHV3-21-derived rearrangement, with a short third complementarity-determining region (CDR3), has been linked to unfavorable prognosis. This translates in shorter time to first treatment, independently of other prognostic factors such as IGHV mutational status or genetic alterations [3, 4]. Despite S#2 being the most prevalent subset, few studies have investigated treatment responses and progression-free survival (PFS) in this context. Chemoimmunotherapy (CIT) is unsatisfactory in this group of patients [5, 6], but responses to targeted therapies (TT) have not been investigated. The aim of this study was to evaluate the outcome of patients with S#2 compared to patients with other IGHV3-21 subsets in the era of TT.A retrospective multicentric study was conducted across 31 French Innovative Leukemia Organization (FILO-CLL) affiliated centers in France, including patients diagnosed between 1998 and 2023. The study was declared to the Health data Hub according to French legislation. Patients identified with a productive IGHV3-21 rearrangement, available clinical and survival data, and no opposition to the study, were included. S#2, not-Subset#2 (nS#2) and IGHV mutational status were categorized according to the recommendations of the European Research Initiative on CLL (ERIC) [7]. Treatment strategies were CIT, Bruton Tyrosine Kinase inhibitors (BTKi), and B-Cell Lymphoma 2 inhibitors (BCL2i). Survival analysis, according to ERIC recommendations [7], considered borderline IGHV status as mutated. Time to first treatment (TTFT) and subsequent PFS analysis were performed using Kaplan-Meier estimation and log-rank test (R software, CRAN). Potential confounders, including age, sex, mutated (mIGHV) and unmutated (uIGHV) status, complex karyotype (CK) (≥3 abnormalities), high-CK (HCK) (≥5 abnormalities) and TP53</div
The CROCO (CROhn’s Disease COhort Study) – study design and protocol
No full textInternational audienceBackground: Crohn’s disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease that can be associated with significant bowel damage and disability. The Lémann Index (LI) is a validated tool for measuring cumulative bowel damage in CD patients through a comprehensive assessment of stricturing, penetrating and surgical lesions. However, prospective studies evaluating bowel damage progression in recently diagnosed CD patients remain limited. Objectives: To characterise the absolute and longitudinal variations in bowel damage progression, as measured by the LI, in a cohort of recently diagnosed CD patients, and to assess its association with relevant disease features, including disease phenotype, treatment strategies, biomarkers and disability. Design: Study protocol for the Crohn’s Disease Cohort Study (CROCO Study), a multicentre, European, prospective cohort study. Methods and analysis: Patients with recently diagnosed CD (within the previous 12 months) will be enrolled and followed up for 5 years. Patients will receive standard-of-care treatment determined by the practising gastroenterologist. Morphological assessments to measure the LI and to evaluate bowel damage progression will be performed at years 1, 3 and 5 after the diagnosis. Disability will be assessed annually using the Inflammatory Bowel Disease – Disability Index (IBD-DI). The primary outcome will be the absolute LI at year 3 following diagnosis. Predictors of bowel damage progression and the association between bowel damage and disability will be analysed. Discussion: The CROCO study represents a unique multicentre cohort of recently diagnosed CD patients, designed to advance the understanding of CD’s natural history and evolution. It will facilitate the development of composite scores for predicting bowel damage progression and provide valuable tools for designing future disease-modification trials. Trial registration: NCT05420233
Système endocannabinoïde et santé musculaire : focus sur le potentiel du cannabididiol
No full textInternational audienceThe endocannabinoid (EC) system is a complex network comprising endogenous ligands, enzymes responsible for their synthesis and degradation, and various receptors (including CB1 and CB2). EC system plays a central role in regulating energy homeostasis. Present in many peripheral tissues, including skeletal muscle, it is now recognized to influence key physiological processes such as insulin sensitivity, mitochondrial metabolism, protein homeostasis and muscle development. Alterations in this system are associated with a variety of pathologies, including obesity, type 2 diabetes, sarcopenia, cachexia and muscle dystrophies. In this context, cannabidiol (CBD), a phytocannabinoid devoid of psychoactive properties, is attracting growing interest as a potential therapeutic agent. This article provides an analysis of the mechanisms by which the EC system, and more specifically the CB1 receptor, influences skeletal muscle development and function, while exploring emerging data on the potential benefits of CBD in various pathological conditions affecting skeletal muscle.RESUMELe système endocannabinoïde (EC) est un réseau complexe composé de ligands endogènes, d'enzymes impliquées dans leur synthèse et leur dégradation, ainsi que de divers récepteurs (notamment CB1 et CB2). Il joue un rôle central dans la régulation de l'homéostasie énergétique. Présent dans de nombreux tissus périphériques, dont le muscle squelettique, il est aujourd'hui reconnu pour influencer des processus physiologiques clés, tels que la sensibilité à l'insuline, le métabolisme mitochondrial, l'homéostasie protéique et le développement musculaire. Des altérations du système EC sont associées à diverses pathologies, notamment l'obésité, le diabète de type 2, la sarcopénie, la cachexie et certaines dystrophies musculaires.Dans ce contexte, le cannabidiol (CBD), un phytocannabinoïde dépourvu de propriétés psychoactives, suscite un intérêt grandissant en tant qu'agent thérapeutique potentiel. Cet article propose une analyse approfondie des mécanismes par lesquels le système EC, et plus particulièrement le récepteur CB1, influence le développement et la fonction musculaires squelettiques, tout en explorant les données émergentes sur les bénéfices potentiels du CBD dans diverses conditions pathologiques affectant le muscle squelettique.</div
Toxicités hématologiques après CAR-T cells, recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)
No full textInternational audienc
Effectiveness of Switching From Intravenous to Subcutaneous Infliximab in Patients With Inflammatory Bowel Disease
No full textInternational audienceGoals: We assessed clinical outcomes over 6 months in an integrated analysis of inflammatory bowel disease (IBD) patients switching from intravenous (IV) to subcutaneous (SC) infliximab (IFX). Background: Real-world data from large multinational IBD patient populations treated with SC IFX are lacking. Study: This individual participant data meta-analysis combined anonymized data from 3 real-world cohorts and evaluated clinical remission [Crohn’s disease (CD): Harvey-Bradshaw Index (HBI)/modified HBI (mHBI) <5; ulcerative colitis (UC): Simple Clinical Colitis Activity Index (SCCAI)/partial Mayo score (PMS) <3], disease activity (HBI/mHBI/SCCAI/PMS), treatment persistence, pharmacokinetics, immunogenicity, biomarkers [fecal calprotectin (FCP); C-reactive protein (CRP)], and reasons for discontinuation. Subgroup analyses determined the effect of clinical parameters on outcomes. Results: Of 428 patients (CD, n=302; UC, n=126), 85.4% were in clinical remission at baseline, which was maintained at 6 months (84.7%), and was higher in patients with CD versus UC (89.8% vs. 71.9%; P <0.001); disease activity scores remained low. High treatment persistence was observed (94.5%) at 6 months. Median serum IFX levels increased from 5.6 μg/mL at baseline to 16.0 μg/mL at 6 months. Most patients (96.1%) maintained negative antidrug antibody status and low levels of FCP and CRP up to 6 months. Drug discontinuation rate was low (5.8%). Intensified preswitch IV IFX was the only factor negatively associated with CD remission at 6 months [intensified vs. standard estimated marginal mean probability difference −0.107 (95% CI: −0.191, −0.024); P =0.012]. Conclusions: Switching from IV to SC IFX maintains clinical effectiveness in patients with IBD regardless of various patient factors