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Disease Progression in Multiple System Atrophy: The ASPIRE Multi-Modal Biomarker Study
No full textInternational audienceOBJECTIVE: The objective of this study was to characterize changes in candidate biomarkers in early multiple system atrophy (MSA) and identify baseline predictors of faster progression. METHODS: This 1-year, multicenter, prospective study assessed clinical, neuroimaging (3T-magnetic resonance imaging [MRI], dopamine transporter single-photon emission computed tomography [DaT-SPECT]), and neurofilament light chain (NfL) changes in patients with early MSA (\textless 5 years from symptom onset) and healthy controls (HCs). Clinical and biomarker changes from baseline to 6 months (M6) and 12 months (M12) were analyzed. Survival status was collected at 24 months. Mixed linear regression analyzed repeated measures, whereas univariate regression identified biomarkers linked to progression. Sample size simulations were conducted for future trials. RESULTS: Forty-one patients with MSA and 20 HCs were included in this study. The Unified Multiple System Atrophy Rating Scale (UMSARS)-I + II scores worsened (mean percent change from baseline was 19.8% at M6; 95% confidence interval [CI] = 13.3 to 26.4% and 31.1% 95% CI = 24.9 to 37.2% at M12). Patients with MSA showed increased cerebellar white matter and pons atrophy (M6 = -5.9 to -2.8% and M12 = -9 to -4.9%) and decreased striatal specific binding ratio (SBR; M6 = -15.8 to -7.9% and M12 = -24 to -10.4%). Patients with multiple system atrophy parkinsonian (MSA-P) exhibited greater striatal SBR reduction, whereas patients with multiple system atrophy cerebellar (MSA-C) had greater cerebellar and pons atrophy, evident at M6. Baseline brainstem and pons volume predicted clinical worsening at M6, whereas SBR predicted worsening at M12. Higher plasma NfL levels correlated with early dropout (14% at M12), worse UMSARS scores, lower SBR, and increased mortality risk within 24 months. INTERPRETATION: Neuroimaging changes occur within 6 months in early MSA. High plasma NfL levels are linked to increased mortality and dropout risk. Longitudinal biomarker assessments provide valuable insights into disease progression. ANN NEUROL 2025
Évaluation de l'impact de la thérapie manuelle dans la prise en charge des lombalgies : revue exploratoire des résultats utilisés dans les essais cliniques
No full textInternational audienceBackground: Low Back Pain (LBP) is the leading cause of disability worldwide, 90% of which is nonspecific. Manual therapy is one of the recommended treatment modalities. However, reported outcomes may be variable. This review aims to identify their scope in the context of the development of a Core Outcome Set (COS), which is defined as « an agreed standardised set of outcomes that should be measured and reported, as a minimum, in all clinical trials in specific areas of health or health care ».Methods: A scoping review with risk of bias assessment of randomised controlled trials (RCTs) of manual therapy for nonspecific LBP was conducted using MEDLINE, CENTRAL, PEDro, WebOfScience and ClinicalTrials.gov, from 2010 up to August 2024. Manual therapy was considered the use, alone or in combination, of manipulations (high velocity, low amplitude), mobilisations (low-grade velocity, small-to-large amplitude) or soft tissue relaxation (especially massage, trigger points, muscle contractions).Results: Out of 3929 articles, 147 RCTs and 74 protocols were included. Two main outcomes emerged: pain intensity (assessed by numerical rating scale or visual analogue scale) and disability (mostly assessed by Rolland-Morris Disability Questionnaire or Oswestry Disability Index). Range of motion is the most frequent clinical outcome assessed. Psychological factors such as fear-avoidance beliefs, kinesiophobia and catastrophising, and healthcare consumption, particularly medication, are also frequent. Most of the outcomes were patient-reported outcomes.Conclusion: Consistent with a previous COS on nonspecific low back pain, manual therapy appears to address the same outcomes. Clinical trials in manual therapy should focus on using the existing COS by measuring pain intensity using a numerical rating scale, disability using the ODI 2.1a or the 24-item RMDQ, health-related quality of life using the SF-12 or the 10-item PROMIS. Additionally, due to the gap between clinical research and pain experience, trials should consider conducting subgroup analyses to identify effects on outcomes related to gender or age, paying particular attention to health inequalities by carrying out analyses based on socioeconomic status, as these factors are well known to significantly impact pain experience and access to care.Review protocol: PROSPERO registration CRD42024576475, COMET Database registration 322
Complications following curative brain arteriovenous embolization: a 12-year single-center cohort study with MRI-monitored adverse events
No full textInternational audienceOBJECTIVE Advancements in endovascular devices and techniques have improved cure rates for selected brain arteriovenous malformations (AVMs). However, data on angiographic and treatment-related complications remain limited. This study presents a 12-year single-center experience with curative endovascular treatment (EVT), along with comparative insights from previously published cohorts. METHODS Data from all brain AVMs treated with curative intent EVT between 2010 and 2022 were reviewed for baseline demographic characteristics, angioarchitectural features, treatment techniques (single arterial, double arterial, venous, arterial and venous, and transvenous embolization with selective temporary flow arrest [TFATVE]), complications, and clinical and angiographic outcomes. Hemorrhagic and ischemic complications were assessed with postprocedural MRI. Ischemic volumes were semiautomatically calculated on apparent diffusion coefficient maps using regions of interest segmentation by two independent readers. Univariate and multivariate analyses were performed to identify predictors of cure and complications. RESULTS A total of 193 patients (54% male, mean ± SD age 38.7 ± 15.9 years) with 193 AVMs (60.6% ruptured) were included. The following techniques were included: single arterial (37.8%), double arterial (26.4%), arterial and venous (19.7%), TFATVE (8.3%), and single venous (7.8%). Intraprocedural complications occurred in 10.4% of cases. Both hemorrhagic and symptomatic ischemic complications occurred in 15.5% of patients. Mean ischemic volume was 9.4 ± 15.1 cm 3 and was significantly higher in symptomatic cases. Overall minor and major complications rates were 14% and 3.1%, respectively. The mortality rate was 4.7% and was lower in unruptured AVMs though these had a higher complication rate. The overall angiographic cure rate was 80.3%, increasing to 93%–100% in cases treated with advanced approaches. On multivariate analysis, AVM in an eloquent brain location was associated with lower cure rates (OR 0.3, p = 0.023), while advanced techniques involving TVE were associated with higher cure rates (OR 7.9, p < 0.001). CONCLUSIONS This large, single-center experience adds to the growing evidence that curative EVT can be a valuable option, especially when advanced techniques are used for low-grade and ruptured deep AVMs. At the same time, higher complication rates in unruptured or higher grade (Spetzler-Martin [SM] grade IV–V) lesions highlight the importance of cautious patient selection. Larger, multicenter prospective studies in high-volume centers are needed to better define the role of curative EVT
Motor and Non-motor Complications Following Different Early Therapies in Parkinson’s Disease: Longitudinal Analysis of Real-Life Clinical and Therapeutic Data from the French NS-PARK Cohort
No full textInternational audienceBackground: Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.Methods: NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity.Results: We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness.Conclusions: In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy.Gov identifier: NCT04888364. Registered June 2021
Facilitators and barriers to orthosis prescription for people with knee osteoarthritis: a qualitative study
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Adolescent pregnancy in French Guiana: double trouble for young mothers and small vulnerable newborns
No full textInternational audienceObjectives: Adolescent pregnancies (AP), defined as pregnancies in girls aged 10-19 years, are associated with adverse maternal and neonatal outcomes. They are frequently reported among those with low economic status. French Guiana (FG) is a French overseas territory with important social inequalities in South America, marked by inequalities. Our study aimed to describe the sociodemographic characteristics and use of the healthcare system for AP in FG. Study design: Population based historical cohort. Methods: This study included all births in FG between 2013 and 2021. Data from each mother-newborn pair ≥22 weeks of gestation and/or weighing ≥500 g were analysed. AP were compared to non-AP. Results: 67,962 newborns were included. AP accounted for 8810 pregnancies (13.0 %), which was 10 times more than in France. Newborns from AP were more frequently transferred to neonatal care units when compared to those from non-AP (10.6 % vs 9.5 %, p < 10 -3 ). St-Laurent-du-Maroni hospital (western part of FG) was the main place of delivery for AP with 50.7 % of all AP delivering there. Two countries of origin of the mothers accounted for the majority of AP: FG (65.9 %) and Suriname (17.3 %) (p<10 -3 ). AP were more frequently associated with preterm birth (aOR = 1.09 [1.01-1.18]), small for gestational age newborns (aOR = 1.66 [1.55-1.78]) and lack of health insurance coverage at delivery (aOR = 1. 34[1.19-1.49]). Conclusions: AP in FG is a public health concern. Comprehensive prevention and care approaches are needed given the double burden faced by young mothers and their children.</div
Induction chemotherapy with a single anthracycline-containing cycle in younger adults with newly diagnosed AML – the french backbone intergroup (BIG)-1 study on behalf of the filo, ALFA, and SFGM-TC study groups
No full textInternational audienceIntroduction The BIG-1 multicenter study was a prospective trial designed for younger AML patients with multiple randomizations at each stage of treatment, including induction, post-induction and hematopoietic stem-cell transplantation. Results of the post-induction randomization (intermediate vs high dose cytarabine) have been already reported (Hunault M et al, NEJM Evid 2025). Here, we report the results of the first randomization that compared high dose idarubicin (IDA, 45 mg/m2 total dose) to high dose daunorubicin (DNR, 270 mg/m2 total dose) during the first and unique induction cycle containing anthracyclines. Methods Patients (pts) aged 18-60 years with newly diagnosed AML, untreated post-MDS AML, or t-AML were eligible if they had an ECOG performance status ≤3, normal cardiac, liver and renal functions, no active infection or neoplasia. Pts with APL, Ph+ AML, CBF AML, or post-MPN AML were not eligible. Pts were randomly assigned to receive either daunorubicin (90 mg/m², d1-3) or idarubicin (9 mg/m², d1-5), combined with cytarabine 200 mg/m² (d1-7). The protocol planned for a single cycle of anthracycline. All patients alive after this first cycle, including those not achieving CR/CRi, underwent a second randomization to compare post-induction IDAC vs HDAC. The primary endpoint was overall survival (OS). Evaluations of treatment effects were adjusted on ELN-2022 risk, post-induction IDAC vs HDAC randomization, and time-dependent HSCT in first CR/CRi. According to French's regulation, no racial or ethnic data were collected. Results 1,159 pts were included from 01/2015 to 05/2018, 578 in the DNR arm and 581 in the IDA arm. Baseline characteristics were well balanced between the two arms. Median age was 50y, 563 pts were female. According to ELN-2022, 308 (27%), 330 (28%), 464 (40%) and favorable, intermediate or adverse risk; 57 pts (5%) were non-classified. With a median follow-up of 5.6y, 5-year OS was 51.8% (95% CI, 47.5-55.9) in the DNR arm vs 50.3% (95% CI, 46.0-54.5) in the IDA arm (adjusted HR, 1.03 [95% CI, 0.87-1.22], p= 0.75). When evaluated in patient subgroups including ELN-2022 risk groups, post-induction IDAC vs HDAC, and allo-HSCT in first remission, no significant interactions with the DNR vs IDA treatment effect were observed for OS. 5y-estimates of EFS (38 vs 38%), RFS (41 vs 44%), and cumulative incidence of relapse (43 vs 41%) did not differ between the two arms. Following induction, there was no difference in remission rate (CR+ CRi, 72.0 vs 73.7%) or early death (2.8 vs 2.8%) in the DNR and IDA arms, respectively. After salvage chemotherapy, the rates of CR/CRi, persistent AML, and early death were 85.6 vs 81.6%, 10.6 vs 13.9%, and 3.8 vs 4.5% in the DNR and IDA arms, respectively. Post-induction CR/CRi (DNR vs IDA) by ELN-2022 groups were: 96 vs 95%, 73 vs 78%, 55 vs 56% in favorable, intermediate and adverse groups respectively, whereas post-salvage CR/CRi were 97 vs 98%, 87 vs 84% and 76 vs 68%. 5y-OS by ELN-2022 groups was 73 vs 74%, 60 vs 58% and 38 vs 38% in favorable, intermediate and adverse groups, respectively. The severity of chemotherapy-induced myelosuppression and the incidences of adverse events were lower after DNR with shorter durations of thrombocytopenia and neutropenia, lower needs for RBC transfusions, number of days on antibiotics, and frequency of fungal infections. The rate of allo-HSCT in first CR/CRi was 43% in the DNR arm and 42% and the IDA arm. The BIG-1 trial enrolled more pts in further phase 2 studies planned in the protocol. Since there was no difference in efficacy and treatment-related mortality between DNR and IDA, we pooled the two arms to build a cohort of 2023 pts included between 01/2015 and 06/2021. To determine the crude contribution of first-line chemotherapy to OS in selected subgroups, we computed the salvage-free, transplantation-free survival (STFS) as the time between the date of inclusion until treatment failure, salvage treatment, morphological or molecular relapse, allo-HSCT or death. 5y-STFS was 52%, 31%, 15%, 11% and 2% in pts with CEBPA-bZIP, NPM1, IDH2, IDH1 mutations or KMT2A rearrangement (except KMT2A-MLLT3), respectively. Conclusions The first two randomizations of the BIG-1 study allowed us to establish a simplified treatment regimen consisting of a single cycle of daunorubicin 90 for induction and IDAC for consolidation. We now consider this regimen as a standard backbone on which new molecules can be added to improve results
Balancing Cohort Size and Variability in Iterative Deep Brain Template Creation
No full textInternational audienceThis study investigates the effect of cohort size on the creation of cohort-specific deep brain anatomical templates for movement disorder populations. Preoperative MRI data from 70 patients implanted with deep brain stimulation (DBS) systems were used to generate anatomical templates with varying cohort sizes (5 to 67 subjects). An iterative non-linear normalization pipeline was employed to optimize template generation. Template variability was assessed using Dice overlap of anatomical structures. The templates created with 44 subjects achieved optimal balance between variability and accuracy. Tukey’s HSD test confirmed significant differences across iterations and cohort sizes. This study underscores the importance of cohort size and iterative registration methods in creating high-quality anatomical templates
Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma
No full textInternational audienceBackground Efficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in the randomized PRODIGE 59-FFCD 1707-DURIGAST trial. Methods ctDNA was evaluated before treatment (baseline) and at 4 weeks (before the third cycle of treatment, C3) using droplet-digital PCR assays based on the detection of CpG methylation.Results Progression-free survival (PFS) and overall survival (OS) were shorter in patients with a high (>1.1 ng/mL) versus low (<1.1 ng/mL) ctDNA concentration at baseline (2.3 vs. 5.8 months; HR = 2.19; 95% CI, 1.09-4.41; p = 0.03 and 4.5 vs. 12.9 months; HR = 2.73; 95% CI, 1.29-5.75; p < 0.01), respectively, after adjustment for identified prognostic variables. Patients with a ctDNA decrease ≤75% between baseline and C3 versus a ctDNA decrease >75% had a worse objective response rate (p = 0.007), shorter PFS (2.2 vs. 7.4 months, HR = 1.90; 95% CI, 1.03-3.51; p = 0.04) and OS (6.6 vs 16.0 months; HR = 2.18; 95% CI, 1.09-4.37; p = 0.03). Conclusions An early decrease in ctDNA concentration is a strong predictor of the therapeutic efficacy of ICI plus chemotherapy in advanced gastric/GEJ adenocarcinoma. Clinical Trial Information NCT03959293 (DURIGAST).The prognosis of advanced gastric and gastro-esophageal junction (GEJ) adenocarcinoma remains poor, with overall survival (OS) ranging from 10% to 15% at 5 years 1 . In Human Epidermal Growth Factor Receptor-2 (HER2) negative unresectable advanced/metastatic tumors, the most frequently used first-line palliative chemotherapy is a doublet of fluoropyrimidine (5fluorouracil (5FU) or capecitabine) plus a platinum salt (cisplatin or oxaliplatin) 2,3 . Recently, the addition of docetaxel (TFOX regimen), immune checkpoint inhibitors (ICI, in PD-L1 positive tumors) and anti-claudin 18.</div
Formation des ergothérapeutes aux transidentités
No full textIntroduction: transgender care does not seem to interest French occupational therapists. This study aims at evaluating to which extent French occupational therapy (OT) training enables transgender care, in regard to gender identity, PEO model, occupational transition, occupational justice and social occupational therapy.Methods: a questionnaire was sent to the 28 French OT training institutes (IFE) staff to identify which above-mentioned notions were taught and the methods used. A teaching profile was then created for each IFE to compare results and identify teaching trends.Results: 20 profiles were created based on 29 complete responses. 6 IFE included all concepts in their curriculum, with gender identity being the less taught topic (10 IFE). New conceptual models were also identified.Conclusion: the trainings analysed were therefore insufficient to provide appropriate support for this population, especially due to the lack of consideration given to the impact of gender identity on occupations.Introduction : la situation des personnes transgenres semble susciter peu d’intérêt chez les ergothérapeutes français. Cette étude vise à évaluer dans quelle mesure les formations françaises en ergothérapie préparent à l’accompagnement des personnes trans, à travers les notions d’identité de genre, de modèle PEO, de transition occupationnelle, de justice occupationnelle et d’ergothérapie sociale.Méthode : un questionnaire a été envoyé aux équipes des 28 Instituts de Formations en Ergothérapie (IFE) pour recenser l’enseignement des notions précitées et leurs modalités. Un profil pédagogique a ensuite été créé pour chaque IFE afin de comparer les résultats et identifier des tendances pédagogiques.Résultats : 20 profils ont été créés sur la base de 29 réponses complètes. 6 IFE incluaient tous les concepts identifiés dans leur cursus, avec la notion d’identité de genre la moins enseignée (10 IFE). De nouveaux modèles conceptuels ont aussi été recensés.Conclusion : les formations des IFE analysées étaient donc insuffisantes pour accompagner cette population de manière adaptée, notamment à cause de la faible prise en compte de l’impact de l’identité de genre sur les occupations