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A prospective multicentre double-blind randomized controlled trial evaluating clinical, cognitive and neural effects of potentiation of electroconvulsive therapy by repetitive transcranial magnetic stimulation in patients with treatment-resistant depression (STIMAGNECT 2)
No full textInternational audienceMajor depressive disorder is a leading cause of disability worldwide, with treatment-resistant depression (TRD) affecting approximately one-third of patients and leading to increased morbidity and healthcare costs. Electroconvulsive therapy (ECT) remains a key treatment for TRD, but its efficacy is limited, and it is associated with cognitive side effects and delayed symptom relief. Repetitive transcranial magnetic stimulation (rTMS) shares action mechanisms with ECT and has shown potential in enhancing ECT efficacy in a previous trial. The STIMAGNECT 2 trial aims to evaluate whether an rTMS add-on protocol can improve ECT outcomes in TRD patients after 10 ECT sessions.Methods: Eighty patients with TRD will be enrolled in a prospective multicentric double-blind randomized controlled trial. All patients will receive a total of 10 ECT sessions. Patients will be randomly assigned to an active or sham rTMS arm. The rTMS protocol (either active or sham) consists of 5 rTMS sessions over 4 days before the beginning of the ECT protocol, with an additional rTMS session the day before each ECT session from the 6th ECT session onward. The main outcome is the response rate following 10 ECT sessions, defined as the proportion of patients achieving a ≥ 50% reduction in their Hamilton Depression Rating Scale (HAMD, 21 items). Secondary outcomes include changes in depression severity (HAMD and QIDS-SR-16) at baseline, during the protocol (Day 4, Day 19, Day 26) and at the end of the protocol, as well as assessment of side effects (adapted UKU), cognitive function (memory, attention, visuospatial abilities, subjective cognitive complaint), autobiographical memory (TEMPau), and ECT session parameters such as seizure characteristics and anesthetic doses. Additionally, potential changes in regional gray matter density, cortical thickness, brain connectivity, and GABA levels will be compared between groups using several magnetic resonance imaging (MRI) sequences (3D, resting-state functional MRI, magnetic resonance spectroscopy).Discussion: The aim of this trial is to optimize neurostimulation protocols using the synergistic effects of rTMS and ECT in order to improve the treatment of TRD
Subcutaneous infliximab in inflammatory bowel disease: bridging the gap between theory and practice.
No full textInternational audienceBackground: At the end of the past century, infliximab (IFX), the first-in-class biological therapy approved in inflammatory bowel disease (IBD), dramatically modified the therapeutic armamentarium. The recent development of subcutaneous (SC) formulations of IFX offers a promising alternative, with the potential to improve patient convenience, adherence, and overall outcomes. This review explores the clinical evidence supporting the initiation of SC IFX and the transition from intravenous (IV) to SC IFX.Methods: Comprehensive review using MEDLINE (source PUBMED).Results: Comparative studies have shown that SC IFX is associated with higher IFX serum concentration levels than IV, fewer neutralizing antibodies and similar levels of remission. Real-world studies have confirmed that switching from IV to SC IFX 120 mg is well accepted with a low risk of relapse. The ease of at-home administration has been associated with improved patient satisfaction and reduced healthcare burdens. The adoption of SC IFX could profoundly change the therapeutic landscape, offering a more patient-centered approach to long-term disease control but some questions remain, particularly about the place of IFX in certain populations.Conclusion: In this article, we reviewed the known and unknown data on SC IFX to provide a comprehensive summary and assist IBD physicians in integrating this knowledge into everyday clinical practice
Serum metabolomic signatures associated with frailty-related phenotypes in a cohort of older people
No full textInternational audienceFrailty is a geriatric syndrome characterized by reduced physiological reserves and increased vulnerability to stressors. Given its complex phenotypes and underlying biology, robust multidimensional biomarkers are needed to advance personalized care. We aimed to identify serum metabolomics signatures associated with frailty phenotypes and related features. We analyzed serum metabolomics data in 901 participants (47.5% males, mean age 68.3 +/- 3.5 years) from the Berlin Aging Study II, classified as non-frail, pre-frail, or frail using Fried's criteria at baseline (T0) and after 7 years (T1). Linear models assessed associations between metabolite levels, frailty, and related parameters. At T0, 1% were frail, increasing to 4.8% at T1. Over follow-up, 323 participants transitioned to a worse frailty category. Across 82 metabolites, no significant differences emerged for frailty status. However, in males, 27 and 30 circulating metabolites were negatively associated with handgrip strength at T0 and T1, respectively. Also in males, L-tyrosine was positively associated with fat mass, while 22 metabolites (carbohydrate-related, maltose, fructose, glucose, galactitol, mannose, lactate, acetylcarnitine; amino acid-related, valine, tyrosine, isoleucine, alpha-hydroxybutyrate) correlated with nutritional status at T0. In females, dimethylsulfone was positively associated with changes in handgrip strength over time, and glycerol with appendicular lean mass at T0. While serum metabolomics showed weak associations with frailty itself, clear links were observed with frailty-related features, notably muscle strength and nutritional status. These findings highlight insulin sensitivity as a central determinant, suggesting that early metabolic alterations may contribute to impaired muscle health in aging
Chlorhexidine vs Povidone-Iodine Alcohol Solutions for Cardiac Implantable Electronic Devices
No full textInternational audienceBACKGROUND Cardiac resynchronization therapy (CRT) improves heart failure outcomes and reduces morbidity and mortality but carries the highest infection risk among cardiac implantable electronic devices. Studies on surgical-site infections show conflicting results regarding the use of alcohol-based povidone-iodine vs chlorhexidine for skin antisepsis, especially as CRT implantation remains insufficiently studied. OBJECTIVES This study sought to compare the effectiveness of 2% alcohol-based chlorhexidine with that of 4-phase povidone-iodine-alcohol skin preparation in preventing local or systemic infections after cardiac resynchronization therapy device implantation, and to assess the impact on other major cardiovascular events and treatment-related adverse effects over 24 months. METHODS In this randomized, multicenter, open-label trial with blinded outcome adjudication, patients undergoing CRT (implantation, upgrade, or replacement) pacemaker, or defibrillator implantation were assigned 1:1 to receive skin antisepsis with either 2% alcoholic chlorhexidine or alcoholic povidone-iodine. Randomization was conducted centrally using an interactive web-response system, with stratification according to trial center. The primary outcome was local or systemic infection related to the device over a 24-month follow-up period. The secondary outcomes were major cardiovascular events and noninfectious side effects. RESULTS From April 2013 to December 2018, 2,272 patients were randomized to the chlorhexidine (n = 1,143) or the povidone-iodine group (n = 1,129). Median age was 72 years; 75.1% were men. Device-related infections occurred in 2.9% of the chlorhexidine group and 3.9% of the povidone-iodine group (adjusted subhazard ratio: 0.75; 95% CI: 0.48-1.20; P = 0.23). Major cardiovascular events occurred in 31.5% and 31.3% of patients, respectively (subhazard ratio: 1.01; 95% CI: 0.87-1.17). Noninfectious local side effects occurred in 12.9% vs 13.3%. CONCLUSIONS The study did not demonstrate a significant reduction in infection rates with alcoholic chlorhexidine compared with alcoholic povidone-iodine in patients undergoing cardiac resynchronization device implantation. Both antiseptics showed similar rates of major infectious and noninfectious events. Further research is needed to optimize infection prevention strategies in this population. (Comparison of Alcoholic Chlorhexidine 2% Versus Alcoholic Povidone Iodine for Infections Prevention With Cardiac Resynchronization Therapy Device Implantation [CHLOVIS]; NCT01841242) (JACC. 2026;87:200-211) (c) 2026 by the American College of Cardiology Foundation
Circulating tumour DNA in head and neck squamous-cell carcinomas: A literature review
No full textInternational audienceBackground: In 60 % of cases, head and neck cancers (HNCs) are diagnosed at an advanced stage and therefore have a poor prognosis with survival rates of only 49 months. Circulating tumour DNA (ctDNA) has emerged as a minimally invasive biomarker able to improve early detection, assess minimal residual disease, monitor systemic treatment response and identify therapeutic targets. This literature review aims to critically synthesise evidence from the past decade on the clinical use of ctDNA in both HPV-related and HPV-unrelated HNCs. Patients and methods: A literature review was performed using PubMed and Cochrane Library on March 11th 2024, updated on November 21st, 2025, using the keywords: "circulating tumour DNA", "head and neck cancer", "ctHPV-DNA associated with HNSCC", "liquid biopsy and HNSCC". Results: After evaluation of 363 articles identified, 92 were included. ctDNA has been investigated for screening, diagnosis, prognostic stratification, treatment-response assessment, relapse detection and identification of therapeutic targets. However, performance varies considerably across studies due to methodological and biological heterogeneity.Conclusion: ctDNA shows strong potential for response assessment and post-treatment monitoring, particularly in HPV-related disease. Nevertheless, its integration into clinical practice requires methodological standardisation and validation in larger prospective studies
Medium-term outcomes and prognostic factors after transcatheter paravalvular leak closure: an international prospective multicentre registry
No full textInternational audienceBackground: Medium- and long-term outcomes after transcatheter paravalvular leak (PVL) closure remain poorly documented, with limited prospective data on predictors of morbidity and mortality.Aims: This study aimed to assess medium-term outcomes and identify key predictive factors of mortality or surgical reintervention at 2 years after transcatheter PVL closure.Methods: The prospective Fermeture de Fuite ParaProthétique (FFPP) Registry included consecutive symptomatic patients undergoing transcatheter PVL closure across 24 European centres between 2017 and 2019. Predictive factors for mortality and surgical reintervention were analysed over a 2-year follow-up.Results: A total of 213 symptomatic patients underwent 237 procedures. The mean age was 68±11 years, with a median European System for Cardiac Operative Risk Evaluation (EuroSCORE) II of 6 (interquartile range [IQR] 4-10). PVL involved the mitral valve in 64.6% of cases and mechanical prostheses in 53.3%. Heart failure and haemolytic anaemia were present in 89.5% and 49.8% of patients, respectively. The transapical approach was used in 6.8% of cases. Technical success was achieved in 87.3% of procedures, and clinical success at 1 month was achieved in 70.5% of patients. The median follow-up was 24.4 months (IQR 23.2-26.4). The survival rate at 2 years without the need for surgical reintervention was 66.1% (95% confidence interval [CI]: 60.1-72.7). Multivariate analysis identified mitral PVL, mechanical valves, and haemolytic anaemia as independent risk factors for adverse outcomes during follow-up. The absence of clinical success at 1 month was the strongest predictor of adverse outcomes (hazard ratio 5.00, 95% CI: 2.70-9.09; p=0.001).Conclusions: Transcatheter PVL closure offers a durable therapeutic option for high-risk patients when early clinical success is achieved. Mitral valve involvement, mechanical prostheses, and haemolytic anaemia remain key predictors of poor outcomes over a 2-year follow-up
Characterizing suicidal intent among suicidal adolescents: a systematic review
No full textInternational audienceBackground :Suicidal intent contributes both to the assessment of suicide risk and to long-term prognosis in adults. Although suicidal intent is a key component in suicide risk assessment, its specific features and clinical implications in adolescents after a suicide attempt remain underexplored in the literature. However, it could represent an improvement in the assessment and prognosis of adolescent suicidal crisis. The aim of this study is to describe how suicidal intent manifests in adolescents after a suicide attempt, and how it relates to associated clinical and contextual characteristics.Method :We conducted a systematic review assessing suicidal intent in adolescents after a suicide attempt adhering to PRISMA guidelines. Five databases were searched up to September 2023. Seventeen studies met the inclusion criteria. We excluded studies focusing solely on suicidal ideation or on non-suicidal self-injury. Data were extracted and synthesized narratively. Study quality was assessed using standard tools.Results :Several studies suggest that suicidal intent may be more frequently reported in older adolescents, with a significant difference before and after the age of 16. High suicidal intent seems to be more frequently linked to internalized disorders. While suicidal intent does not appear directly linked to the lethality of the attempt, the highest level of suicidal intent reported across previous attempts may represent a prognostic marker for later suicide mortality.Conclusion :It seems essential to refine existing assessment tools or develop new ones specifically adapted to adolescents, in order to assess suicidal intent while taking into account the specificities of the adolescent population. This would help optimize interventions and support for both the patient and their family
Effet des antibiotiques sur la virulence et l'émergence des mécanismes de résistance chez les Enterobacterales
No full textI. Effet d'une antibiothérapie sur des souches d'Escherichia coli adhérentes et invasives isolées de patients atteints de la maladie de Crohn 37-47 A. Données bibliographiques 37-40 B. Projet 40-47 II. Évaluation de l'activité de l'amikacine sur des souches d'Enterobacterales productrices d'AAC(6')-Ib 48-53 A. Données bibliographiques 48-49 B. Projet 49-53 III. Emergence de résistance par efflux ou imperméabilité chez K. pneumoniae 54-57 A.</div
From non-specific biomarker to targeted action: transdiagnostic and sex-specific drivers of high-CRP status in severe mental illness across the FondaMental Advanced Centers of Expertise (FACE) cohorts
No full textInternational audienceBackground and objectives: Low-grade systemic inflammation contributes to the pathophysiology of severe mental illness (SMI) in a substantial subset of patients, who often experience greater disease burden and poorer treatment response. Elevated C-reactive protein (CRP), defined as CRP ≥ 3 mg/L, has been proposed to identify this group, but its non-specificity limits the biomarker's ability to guide targeted intervention. We aimed to determine the most consistent drivers of high CRP across bipolar disorder (BD), schizophrenia (SZ) and major depressive disorder (MDD), and to translate these into clinically actionable intervention targets using robust data-driven methods.Methods: We pooled and harmonised data from three large French national SMI cohorts (n = 7149: 4797 bipolar disorder, 1958 schizophrenia and 394 resistant major depression) and classified participants by CRP ≥ 3 mg/L, as well as an alternative cut-off of 5 mg/L. We applied penalised logistic regression (PLR), random forests (RF) and unsupervised clustering, using 28 biopsychosocial variables to identify robust drivers of high-CRP status. We then grouped these into actionable targets and assessed relative dominance.Results: In total, 30.16% of participants had CRP ≥ 3 mg/L. PLR identified female sex (OR [95% CI]: 1.60 [1.27, 1.93]), higher BMI (OR: 1.09 [1.07, 1.13]), current nicotine dependence (OR: 1.05 [1.02, 1.09]), lower HDL cholesterol (OR: 0.57 [0.44, 0.73]) and smoking (ex-smoker status OR: 0.84 [0.66, 0.98]) as consistent drivers. RF highlighted a similar set of key drivers, also including waist circumference, triglycerides and cardiovascular comorbidities. Clustering of the high-CRP group was almost entirely driven by smoking status and nicotine dependence. When grouped into actionable targets, the identified drivers accounted for 16% of variance in CRP status, with obesity emerging as most dominant contributor. This pattern was most pronounced in females; in males it was more diffuse, with a more prominent role for smoking.Conclusions: We propose a decision tree framework where CRP can serve as a first-line screening marker for inflammation in SMI, with subsequent steps focusing on the main contributing factors to guide targeted interventions. Priority should be given to targeting obesity and metabolic dysregulation. Among females, hyperuricemia represents the next most appropriate target, whereas in males, smoking warrants greater attention. This stepwise approach provides a route from a nonspecific biomarker to targeted treatment strategies and should be validated in prospective studies
