HAL Portal Chu Clermont-Ferrand
Not a member yet
7589 research outputs found
Sort by
Evaluating the applicability of ESGO quality indicators in the surgical management of endometrial cancer: Insights from a Francogyn cohort
No full textInternational audienceBackground: Endometrial cancer (EC) is a significant health concern in France, necessitating high-quality surgical care to improve patient outcomes. The European Society of Gynaecological Oncology (ESGO) established quality indicators (QIs) to standardize and improve management.Objective: This study evaluates the applicability of ESGO QIs in a real-world setting across 13 centers in France.Methods: This retrospective multicenter cohort study included 2789 patients surgically treated for EC from 2001 to 2020. Demographic data, surgical techniques, adherence to ESGO QIs and trends over time were analyzed. Key indicators analyzed included multidisciplinary team discussions, pre-operative imaging adequacy, surgical techniques employed, and molecular classifications.Results: All patients were discussed in multidisciplinary meetings. Adequate preoperative imaging was achieved in 80.63 % of cases. Minimally invasive surgery was performed in 66.12 % of early-stage patients, showing a significant year-on-year increase from 12 % in 2001 to 85 % in 2020. Among obese patients, 60.78 % underwent laparoscopic procedures, with a conversion rate to open surgery of 3.57 %. Molecular classification results highlighted 35 % of patients as low risk and 32 % as high risk.Conclusion: Our findings indicate that adherence to actual ESGO QIs has substantially improved the quality of surgical management for endometrial cancer in France, despite some areas requiring further enhancement. A coordinated political approach is essential to address existing barriers and ensure consistent implementation of these quality standards across all centers, ultimately aiming to elevate patient care and outcomes in the French healthcare system
Myostatin, activin-A and follistatin are produced by the tumor in head and neck cancer and likely contribute to sarcopenia: A case-control, cross-sectional exploratory study
No full textInternational audienceMyostatin (M), activin-A (A) and follistatin (F), three TGF-beta superfamily members, play a role in cancer sarcopenia. The aim of our study was to assess the association of MAF in head and neck cancer (HNC) skeletal muscle loss. Materials and methods: This prospective study involved 55 patients, 32 with HNC and 23 controls. The patients underwent a full nutritional assessment just before surgery. Tumor, muscle and plasma were harvested at the time of surgery. Plasma was harvested a second time 7 days after the procedure. Tumor explants were cultured and MAF were measured in the incubation medium. Results: A and F plasma levels were higher in cancer patients compared to control (320 vs. 203 pg/ml, p < 0.001, ES = 0.96 95 % CI [0.40; 1.52] and 3593 vs 2148 pg/ml, p < 0.001, ES = 1.10 95%CI [0.53; 1.66], respectively) and M plasma level lower (1542 vs. 2100 pg/ml, p = 0.01, ES = -0.70 95%CI [-1.24; -0.15]). M plasma level was correlated with the skeletal muscle index at the third lumbar vertebra (r = 0.44; p < 0.05) and negatively correlated with weight loss (r = -0.65; p < 0.05) and the C Reactive protein level (-0.44; p = 0.02). At the seventh postoperative day (D), A was increased (D7 vs D0) in the cancer group (379 vs 320 pg/ml; p < 0.001) while the concentrations of M and F were unchanged from the presurgical level. There was no difference between groups in the transcript levels of M and A in skeletal muscles. MAF were systematically detected in the tumor incubation medium with no correlation between tumor incubation medium level and plasma level at D0. Conclusion: The MAF secretory profile is modified in HNC. In particular, A seems to play a role in muscle loss while F protects against skeletal muscle mass loss
High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing
No full textInternational audienceThe prognostic heterogeneity of multiple myeloma is mainly driven by the genomic features of myeloma cells. The International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) recently proposed a high-risk (HR) genomic model to have a consensus definition of genomic risk. We performed next-generation sequencing in the form of a panel on samples from 6528 patients with newly diagnosed multiple myeloma (NDMM) and 1583 patients at first relapse between 2019 and 2024. We observed that 22.4% of patients at diagnosis and 36.7% of patients at first relapse were classified as high risk according to the Consensus Genomic Staging. Clinical data were available for 2695 patients at diagnosis. After a median follow-up of 35 months, the median progression-free survival (PFS) was 30 months for patients with HR NDMM and 51 months for standard-risk (SR) patients (P< .0001). The HR cytogenetic criteria from the Revised- International Staging System score were not able to differentiate between HR and SR patients based on the IMS/IMWG genomic subgroups. Looking at each criterion independently, we found that the presence of del(17p), TP53 mutation, biallelic del(1p32), or the combination of intermediate-risk cytogenetics (gain 1q, del(1p32), t(4;14), t(14;16), t(14;20)) significantly reduced the PFS when compared with SR patients. Moreover, patients with several cumulating criteria had an even worse prognosis. Among SR patients, classified according to the genomic definition with normal creatinine, the median PFS for those with high β2-microglobulin was not significantly different from that of patients with normal β2-microglobulin level. This study validated the IMS/IMWG genomic definition of HR myeloma in a large cohort of patients diagnosed from 2019 onwards
Dental Implants in Adults With Intellectual Disabilities: A Multicenter Retrospective Study. Part 1: Implant Outcomes
No full textInternational audienceABSTRACT Background Despite the potential benefits of implant‐supported rehabilitation, data on implant performance and peri‐implant health in adults with intellectual disabilities (ID) are limited. Objective To evaluate dental implant outcomes in adults with non‐syndromic ID and to identify variables associated with peri‐implant health, complications, and implant loss. Methods This multicenter retrospective cohort study included adults with non‐syndromic ID who received at least one dental implant and had a minimum follow‐up of 36 months. Dental implants placed in 137 patients across 7 specialised centers in Spain, France, Italy, and South Korea were analysed. Standardised data were collected on patient characteristics, oral health status, implant design, prosthetic variables, and follow‐up care. Clinical outcomes were categorised as peri‐implant health, mucositis, peri‐implantitis, or implant loss. Results Of the 453 implants placed, 418 (92.3%) remained functional at a mean follow‐up of 75.9 ± 42.7 months (range: 36–211 months). Among the 445 implants evaluated for clinical outcomes, 63.6% were classified as healthy, 23.4% as presenting with mucositis, 4.4% with peri‐implantitis, and 7.3% were lost during the follow‐up period. Tissue‐level implant type, cement‐retained fixed prostheses, and the use of general anaesthesia during the impression step were significantly associated with peri‐implant clinical outcomes. No variables were identified as statistically significant predictors of implant loss. Conclusions Dental implant therapy represents a viable long‐term treatment option for adults with non‐syndromic ID. Despite the clinical challenges of this population, high survival and success rates can be achieved, particularly when appropriate implant selection, prosthetic retention systems, and behavioural management techniques are implemented
Efficacy and mechanism of supervised adapted physical activity on quality of life for patients with fibromyalgia: single-center, prospective, randomised clinical and neuroimaging study
No full textInternational audienceFibromyalgia (FM) is a chronic overlapping pain condition that impairs quality of life (QOL). Adapted physical activity (APA) is recommended as a key non-pharmacological intervention, though its implementation and underlying mechanisms remain limited. Fibromyactiv, a prospective, randomised, single-blind clinical and neuroimaging study, evaluated the efficacy and mechanisms of a structured, supervised APA program in FM. Seventy-nine adults were assigned to supervised APA (n = 39) or standard care (n = 40) and followed for 12 months. The intervention consisted of diversified, lowintensity, fractionated sessions three times weekly for 6 months. Outcomes included the Fibromyalgia Impact Questionnaire (FIQ, primary endpoint at M6), clinical and psychological scales, functional tests, pedometer monitoring, and mechanistic measures (¹⁸F-FDG PET, blood/urine biomarkers). Supervised APA produced significantly greater FIQ improvement and broader benefits across PGIC, Widespread Pain Index, Symptom Severity Scale, tender points, mean pain, sleep quality, flexibility, and daily step counts. Immediate symptom relief occurred after each session. Brain PET revealed increased metabolism in the right cerebellum in the APA group, correlating positively with step-count improvement. This interdisciplinary trial demonstrates that a reproducible supervised APA program yields sustained improvements in QOL, symptoms, and functional activity in FM, potentially mediated by cerebellar modulation of motor and behavioural engagement. ClinicalTrials.</div
Relevance of Clinical High-Risk of Psychotic Transition Conceptto Avoid Misdiagnosis Risk in an Unaccompanied Minor Refugeewith Complex Trauma: A Case Report
No full textInternational audienceIntroduction: Unaccompanied refugee minors face a heightened risk of mental health disorders due to cumulative traumatic exposures and sociocultural displacement. Psychotic-like symptoms are common and frequently misdiagnosed as primary psychotic disorders, often overlooking trauma-related or culturally-influenced presentations. Case Presentation: We report the case of “Moussa”, a 15-year-old URM from Cameroon, who presented with transient psychotic symptoms during an acute stress episode. Following the CAARMS assessment, he was initially diagnosed with a Clinical High-Risk for psychosis state (CHRp), then later labeled as schizophreniform by another provider. However, his rapid remission and trauma history led to a revised diagnosis of complex PTSD. Conclusion: This case underscores the risks of early psychiatric labeling in traumatized migrant youth. Greater use of CHRp frameworks—if combined with cultural and ethical caution—may help delay premature diagnoses and favor tailored care. However, the CHRp construct itself remains debated, and its application should not obscure broader systemic biases. Main limitations include the single-case design and the absence of standardized trauma assessments. Therefore, longitudinal research is needed
P0663 Comparative Effectiveness of Advanced Therapies between Ulcerative Proctitis and More Extensive Forms of Ulcerative Colitis: Results from a Multicenter Real-World Study
No full textInternational audienceBackground Most pivotal trials for advanced therapies in ulcerative colitis (UC) exclude patients with isolated rectal disease. This study compares treatment effectiveness between E1 (rectal) and E2/E3 (left-sided or extensive) UC. Methods This analysis pooled individual-level data from several multicentre, retrospective, real-world comparative studies. All consecutive patients with active disease (partial Mayo score (PMS) > 2) who initiated an advanced therapy after failure of at least one biologic were included. The primary outcome was steroid-free symptomatic remission, defined as a PMS ≤ 2 at week 14 (W14). The comparison for the primary outcome was adjusted for potential confounders, including concomitant medications. The secondary outcome was discontinuation-free survival. A subgroup analysis of the primary outcome was performed within each therapeutic class. Results A total of 608 patients were included: 73 were E1 and 535 E2/E3. Among them, 48% were female, the median age was 39 years [interquartile range: 27–54], and the median disease duration was 6 years [3–10]. Overall, 38% of patients were initiating a second-line advanced therapy, 35% a third-line, 17% a fourth-line, and 4% a fifth-line treatment. The initiated drug was vedolizumab in 28% of cases, ustekinumab in 24%, and a JAK inhibitor (tofacitinib, filgotinib, or upadacitinib) in 48%. A concomitant treatment was prescribed in 256 patients (42%): 76 (13%) with 5-aminosalicylates, 55 (9%) an immunomodulator and 166 (27%) corticosteroids. E1 disease was not significantly associated with a different rate of symptomatic remission at week 14 in univariate analysis (OR = 1.50 [95% CI: 0.94–2.89], p = 0.09). In the multivariate analysis adjusted for age, disease duration, baseline PMS, elevated baseline CRP, concomitant therapy, and number of prior treatment lines, disease extent was not associated with remission (OR = 1.75 [0.87–3.70], p = 0.13). Conversely, an elevated PMS was independently associated with lower rates of remission (OR = 0.84 [0.75–0.95], p = 0.004). Survival analysis showed no difference between the two groups in time to treatment discontinuation for failure (HR = 0.78 [0.56–1.10], p = 0.20), Figure. Subgroup analyses by therapeutic class found no difference in efficacy according to disease extent, whether for vedolizumab (OR = 0.91 [0.30–2.84]), ustekinumab (OR = 1.81 [0.32–14.32]), or JAK inhibitors (OR = 2.63 [0.94–10.0]) (all non-significant). Conclusion In this large multicenter real-world cohort, advanced therapies demonstrated similar efficacy in patients with isolated rectal UC compared with those with more extensive disease, underscoring the need to adequately treat this disease location. Conflict of interest: Dr. Hupé, Marianne: Abbvie, Takeda, Celltrion Healthcare, Pfizer, Johnson & Johnson, Lilly, Amgen Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring 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 Domas, Quentin: No conflict of interest 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 Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, Johnson & Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Vuitton, Lucine: Abbvie, Amgen, Viatris, Celltrion, Janssen, Takeda, Lilly, Pfizer, Dr Falk Pharma, MSD, Ferring, Galapagos Caillo, Ludovic: Abbvie, Amgen, Celltrion, Ferring, Fresenius, Lilly, Jonhson & Jonhson, MSD, Pfizer, Takeda, Sandoz Gilletta de Saint Joseph, Cyrielle: Speaker/ consultant fees from Abbvie, AlfaSigma, Amgen, Celltrion, Ferring, Fresenius, Janssen, Lilly, Pfizer, Takeda and Tillots Pereira, Bruno: No conflict of interest 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
Rational and design of EACVI-MMVD study: an international registry on multimodality imaging for mixed and multiple valvular heart disease
No full textInternational audienceAims Multiple and mixed valvular heart disease (MMVD) are frequent situations in clinical practice. Despite a high prevalence, comprehensive insights into their clinical presentation, management strategies, impact of multimodality imaging, and outcomes are not well established, due to a lack of dedicated studies. Methods and results The ‘EACVI-MMVD Study’ will be a large prospective, multicentre, observational cohort study led by the Heart Imagers of Tomorrow of the European Association of Cardiovascular Imaging (EACVI). It will assess the proportion, management, and prognosis of MMVD over a 1-year period of follow-up. All consecutive patients diagnosed with MMVD using transthoracic echocardiography will be recruited over a 6-month recruitment period in 88 centres from 24 different countries. Baseline evaluation will be determined by physicians and encompass the whole spectrum of multimodality imaging including transthoracic and transoesophageal echocardiography, stress echocardiography, computed tomography, and cardiovascular magnetic resonance. Centres will have the opportunity to send cardiovascular imaging data for core laboratory analysis and to extend recruitment throughout a 5-year follow-up period. Conclusion The EACVI-MMVD study will be the largest international multicentre study evaluating the prevalence of MMVD in clinical routine and determining the impact of multimodality cardiovascular imaging in MMVD patients. Clinical Trial Registration: NCT06235385 URL: https://classic.clinicaltrials.gov/ct2/show/NCT0623538
Intracellular Membrane Repair Dysregulation and Accumulation of Mature Myostatin Protein are Novel Markers of Muscle Pathophysiology in Pompe Disease
No full textInternational audiencePompe disease is an autosomal recessive metabolic disorder caused by acid alphaglucosidase deficiency, characterized by progressive skeletal muscle weakness and respiratory insufficiency. Affected muscles exhibit glycogen-filled lysosomes, autophagic build-up, and mitochondrial abnormalities. Despite global myofibrillar disorganization, satellite cells (SCs) fail to activate, due to mechanisms that remain unclear. This study sought to comprehensively characterize the phenotypic features of affected muscles in Pompe disease, focusing in particular on membrane repair processes, as membrane damage is a primary trigger for SC activation. Longitudinal transcriptomic analysis of muscle from a Pompe disease mouse model, combined with immunohistochemical and biochemical analyses, showed early and sustained overexpression of dysferlin (DYSF), annexin A2 (ANXA2), and AHNAK2, proteins involved in membrane repair. Abnormal localization of these proteins was observed throughout the disease course, as evidenced by sarcoplasmic accumulation at lysosomes, autophagosomes, and T-tubules, respectively. These alterations suggest a compensatory mechanism to preserve the integrity of intracellular structures. Analysis of muscle biopsies from patients with lateonset Pompe disease (LOPD) suggested sarcoplasmic localization of DYSF, ANXA2 and AHNAK2 that correlated with the severity of the histological phenotype. Moreover, in the mouse model, we observed persistent post-transcriptional accumulation of mature myostatin, a key negative regulator of muscle growth, which may contribute to impaired SC activation and the absence of muscle regeneration despite extensive tissue damage. In conclusion, our findings identified differential expression of proteins associated with intracellular membrane repair and dysregulation of myostatin as key markers in the course of Pompe disease. These insights provide new perspectives on the underlying pathophysiology and point to novel therapeutic avenues for limiting disease-associated damage
