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Guided-VCTE: An Enhanced FibroScan Examination With Improved Guidance and Applicability
No full textInternational audienceObjective: Although FibroScan (FS), based on Vibration-Controlled Transient Elastography (VCTE), is a widely used non-invasive device for assessing liver fibrosis and steatosis, its current standard-VCTE examination remains timely and difficult on patients with obesity. The Guided-VCTE examination uses continuous shear waves to locate the liver by providing a real-time predictive indicator for shear wave propagation and uses shear wave maps averaging to increase the signal-to-noise ratio in difficult to assess patients. We aimed to evaluate the effectiveness of the new indicator, as well as compare examination times and success rates with both standard-VCTE and Guided-VCTE examinations.Methods: We recruited 130 patients all with varying BMI in this multicenter study. Sensitivity, specificity, positive predictive values and negative predictive values assessed the new indicator effectiveness. Success rates were compared using Wilcoxon signed rank tests rates and time-to-event analyses were used to investigate examination times. Agreement and repeatability of both methods were assessed using Wilcoxon signed-rank test.Results: The new indicator was highly effective, with a 97% sensitivity for predicting valid liver stiffness measurements (LSM). LSM and controlled attenuation parameter results remained in good agreement between two examinations. The Guided-VCTE examination significantly increased the success rate of individual measurements and significantly reduced the time required for localization in the study cohort, especially in patients with grade 2 obesity (BMI ≥35 kg/m²). Additionally, the proportion of patients scanned in less than 4 minutes was significantly higher with the Guided-VCTE examination.Conclusion: Guided-VCTE is a new effective technique that simplifies further FS use, particularly for patients with obesity.Trial registration: ClinicalTrials.gov NCT05567328
Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas
No full textInternational audienceObjective Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values. Methods We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry ( NCT03275298 ) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival. Results BRCA -mutated (BRCA m) patients had higher standardized KELIM than BRCA -wild type ( BRCA wt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCA wt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either BRCA m and unfavorable KELIM, or BRCA wt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCA m and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001). Conclusions The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCA m or BRCA wt patients. Patients with both BRCA wt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies
Lecanemab for early Alzheimer's disease: Appropriate use recommendations from the French federation of memory clinics.
No full textInternational audienceLecanemab, a monoclonal antibody targeting β-amyloid protofibrils, has shown promising results in a Phase III clinical trial for the treatment of early stages of Alzheimer's disease (AD) and has been approved by the European Medicines Agency. An Early Market Authorization could be submitted to the French regulatory agencies, potentially allowing for the drug's use in clinical practice in France in 2025.To guide French clinicians in administering lecanemab in a standardized way, the French Federation of Memory Clinics has developed appropriate use recommendations for lecanemab that highlight relevant questions established to ensure an optimal risk-benefit ratio.The recommendations emphasize that lecanemab treatment requires a comprehensive individualized evaluation of the risk-benefit ratio, which should occur in multidisciplinary meetings. When approved, the guidelines support the use of blood biomarkers, proposing specific cutoffs for patients eligible for lecanemab under restricted conditions. In addition to the European Medicines Agency restrictions in patients on anticoagulants, and APOE4 homozygotes, the guidelines recommend against lecanemab treatment for patients with high amyloid-related hemorrhagic risk such as probable cerebral amyloid angiopathy (Boston criteria v1.5) until further data become available. Additionally, we recommend that MRI monitoring be started before the third infusion to account for early Amyloid Related Imaging Abnormalities (ARIA) occurring on lecanemab. It is recommended to establish a specific clinical care pathway with protocols for patients with ARIA, with trained physicians and radiologists with expertise in neurological emergency and intensive care. Finally, a discontinuation protocol based on dementia severity assessment after 18 months of lecanemab treatment is suggested.Access to lecanemab requires a personalized biological and genetic diagnosis of AD, which is currently not necessary in most cases. Therefore, the healthcare system must rapidly adjust to new diagnostic procedures and treatment delivery to ensure equal access for all individuals
METHOFRACT, a methotrexate osteopathy multicentre cohort study
No full textInternational audienceMethotrexate-induced osteopathy (MTX-IO) is a rare condition typically involving the lower limbs, especially tibia or foot fractures, among patients with well-controlled rheumatoid arthritis (RA) or psoriatic arthritis (PsA). This study aimed to identify the affected population, describe fracture characteristics and identify risk factors for poor clinical outcome. A multicentre retrospective study included patients with MTX-IO diagnosed by bone specialists or identified through French pharmacovigilance. The data collected included clinical presentation, imaging features, bone mineral density and biochemical markers. Between 2012 and 2024, 92 patients were included, predominantly postmenopausal women with seropositive RA. A history of major fractures was noted for 22% of the patients, and 56% presented osteoporosis at diagnosis. Fractures were most common in the tibial metaphysis (distal and proximal) (88%) and the foot bones (49%), with multiple fractures often present at diagnosis (76%), and frequently repeated fractures in the patients’ recent histories (63%). Diagnosis was conducted using MRI of the painful sites (84%), but bone scintigraphy was also used (41 patients, 45%). Management involved methotrexate discontinuation in 79% of the cases. Fracture healing and pain relief were achieved in 77% of the cases, with a significant difference in outcomes between those who discontinued methotrexate (91%) versus those who continued (29%) (p&amp;lt;0.001). MTX-IO is a rare but significant condition, especially among postmenopausal women with RA or PsA. Early diagnoses via MRI or bone scintigraphy and the discontinuation of methotrexate are critical, as stopping the drug significantly improves outcomes and prevents further fractures
DECORIN, a triceps‐derived myokine, protects sorted β‐cells and human islets against chronic inflammation associated with type 2 diabetes
No full textInternational audienceAim: Pancreatic βcells are susceptible to inflammation, leading to decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps-derived myokine, DECORIN, which plays a pivotal role in skeletal muscleto-pancreas interorgan communication. However, whether DECORIN can directly impact βcell function and susceptibility to inflammation remains unexplored. Methods:The effect of DECORIN was assessed in sorted human and rat βcell and human islets from healthy and type 2 diabetes (T2D) donors. We assessed glucose-stimulated insulin secretion (GSIS) and cytokine-mediated cell death.We then challenged sorted βcells and human islets with inflammatory cytokines commonly associated with diabetes, such as tumor necrosis factor-α (TNF-α) alone or in combination with interleukin1-β (IL1-β) and interferon-γ (cytomix).Results: DECORIN enhanced cell spreading and the localization of phosphorylated FAK at adhesions, promoting GSIS under basal conditions. It also increased insulin granule docking adhesion length and countered the inhibitory effects of TNF-α on adhesion and actin remodeling at the βcell surface, resulting in preserved GSIS. DECORIN protected from cell death in sorted βcells and islets challenged with TNF-α alone or TNF-α + cytomix. Interestingly, DECORIN increased both insulin content and secretion in human islets from T2D individuals. Additionally, DECORIN treatment reversed the impaired gene expression caused by T2D and enhanced the expression of genes essential for islet function and metabolism. Conclusion:Collectively, we have shown that DECORIN had a beneficial effect on human islets, protecting them from inflammation-induced cell death. In T2D islets, DECORIN restores islet function and reverses the expression of T2Dassociated genes. Based on our data, we propose that DECORIN is a promising therapeutic target for diabetes-associated inflammation and diabetes itself.</div
Overlapping upstream ORFs ending at c.125 lead to reduced Endoglin, contributing to Hereditary Hemorrhagic Telangiectasia
No full textInternational audienceAbstract Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular disease mainly caused by pathogenic mutations in ACVRL1 and ENG genes. Despite advances in HHT diagnosis, the molecular origin of some cases remains unclear. Recently, we observed a high prevalence of HHT-causing 5’UTR variants in ENG . These variants commonly introduce upstream AUG codons (uAUGs) at the origin of upstream open reading frames (upORFs) overlapping the coding sequence, all terminating at the same stop codon located at position c.125 (uAUG-c.125). Here, we analyzed all 5’UTR ENG single nucleotide variants that could alter upORFs in silico. Interestingly, we found that 85% of uAUG-c.125 variants alter the protein levels. Furthermore, we identified 2 variants creating uAUG-c.125 and uCUG-c.125 in HHT patients and experimentally demonstrated their association with reduced endoglin levels This study provides new elements for the interpretation of upORF-altering variants in the 5’UTR of ENG with new insights for the molecular diagnosis of HHT
Faisabilité et efficacité de l'entraînement physique sur les symptômes du sommeil et les comorbidités dans la narcolepsie de type 1 : une étude interventionnelle prospective
No full textInternational audienceCurrent treatments for narcolepsy type 1 (NT1) have little impact on psychiatric, cognitive and metabolic comorbidities. Here, we evaluated the feasibility, safety and efficacy of a prospective Exercise Training (ET) program on sleep-related symptoms and comorbidities in NT1. Sedentary adult with NT1 participated in a 6-week supervised ET program followed by a 18-week self-directed program. Outcomes included the Narcolepsy Severity Scale (NSS), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), cardiometabolic parameters (body mass index [BMI], glycemia, insulin, CRP, lipid panel with insulin resistance [IR] [TG/HDL-C] and cardiovascular risk [Total-C/HDL-C] markers), cardiorespiratory fitness, and attention (Bron/Lyon Attention Stability Test). Wilcoxon tests compared baseline, 6-week, and 6-month data. Among 30 participants (73.3% women, 39.8±13.9 years, BMI=31.0±5.1 kg/m2), 25 completed the 6-month program. Of the 379 supervised sessions (84.2% attendance), only 7 partial cataplexies occurred. At 6 weeks, significant improvements were observed in median[IQR] NSS (-2.0[-4.0;0], p=0.046), ISI (-1.0[-3.0;1.0], p=0.050), triglycerides (-0.21[-0.46;-0.09]g/L, p=0.015), IR (-0.19[-0.46;-0.04], p=0,003), cardiorespiratory fitness ((+15.0[5.0;20.0]watts, p<0.001), and in most attention scores (stability, intensity, reaction time: p<0.05). At 6 months, NSS and ISI changes were no longer significant but anxiety (-1.0[-3.0;1.0], p=0.041) and depression (-2.0[-4.0;0.0], p=0.004) decreased. Improvements in IR (-0.27[-0.44;-0.11], p=0.002), triglycerides (-0.2[-0.4;0.0]g/L, p=0.033), cardiovascular risk (-0.16[-0.41;-0.02], p=0,019), and attention scores (intensity, reaction time, number of errors p<0.05) were sustained. VO2max and BMI showed no significant changes. Physical activity is feasible and safe in NT1, enabling improvements in narcolepsy symptoms, anxiety/depression, cognition, and cardiometabolic markers. Larger randomized controlled trials are needed to confirm these findings.Les traitements actuels de la narcolepsie de type 1 (NT1) ont peu d'impact sur les comorbidités psychiatriques, cognitives et métaboliques. Nous avons évalué la faisabilité, la sécurité et l'efficacité d'un programme prospectif d'entraînement physique (EP) sur les symptômes liés au sommeil et les comorbidités dans la NT1. Des adultes sédentaires atteints de NT1 ont participé à un programme d'EP supervisé de 6 semaines, suivi d'un programme autodirigé de 18 semaines. Les résultats comprenaient l'échelle de gravité de la narcolepsie (NSS), l'échelle d'anxiété et de dépression en milieu hospitalier (HADS), l'indice de gravité de l'insomnie (ISI), les paramètres cardiométaboliques (indice de masse corporelle [IMC], glycémie, insuline, CRP, profil lipidique avec résistance à l'insuline [IR] [TG/HDL-C] et marqueurs de risque cardiovasculaire [Total-C/HDL-C]), la capacité cardiorespiratoire et l'attention (test de stabilité de l'attention de Bron/Lyon). Les tests de Wilcoxon ont comparé les données de référence, celles obtenues après 6 semaines et celles obtenues après 6 mois. Parmi les 30 participants (73,3 % de femmes, 39,8 ± 13,9 ans, IMC = 31,0 ± 5,1 kg/m2), 25 ont terminé le programme de 6 mois. Sur les 379 séances supervisées (taux de participation de 84,2 %), seules 7 cataplexies partielles ont été observées. À 6 semaines, des améliorations significatives ont été observées dans la médiane [IQR] NSS (-2,0[-4,0;0], p = 0,046), ISI (-1,0[-3,0;1,0], p = 0,050), triglycérides (-0,21[-0,46;-0,09]g/L, p = 0,015), l'IR (-0,19[-0,46;-0,04], p = 0,003), la capacité cardiorespiratoire ((+15,0[5,0;20,0]watts, p<0,001) et la plupart des scores d'attention (stabilité, intensité, temps de réaction : p<0,05). Au bout de 6 mois, les changements de NSS et de l'ISI n'étaient plus significatifs, mais l'anxiété (-1,0[-3,0;1,0], p=0,041) et la dépression (-2,0[-4,0;0,0], p=0,004) avaient diminué. Les améliorations de l'IR (-0,27[-0,44;-0,11], p=0,002), des triglycérides (-0,2[-0,4;0,0]g/L, p=0,033), du risque cardiovasculaire (-0,16[-0,41;-0,02], p=0,019) et des scores d'attention (intensité, temps de réaction, nombre d'erreurs p<0,05) ont été maintenues. La VO2max et l'IMC n'ont pas montré de changements significatifs. L'activité physique est réalisable et sans danger chez les patients atteints de NT1, permettant une amélioration des symptômes de la narcolepsie, de l'anxiété/dépression, des fonctions cognitives et des marqueurs cardiométaboliques. Des essais contrôlés randomisés à plus grande échelle sont nécessaires pour confirmer ces résultats
Application of the anti-IgLON5 disease composite score to assess severity, clinical course, and mortality in a French cohort
No full textInternational audienceAbstract Anti-IgLON5 disease presents with diverse symptoms, whose severity can be measured by the anti-IgLON5 disease composite score (ICS). This study applied the ICS to a retrospective anti-IgLON5 disease cohort ( n = 52; median age 72 years, 63% male) diagnosed in the French Reference Center on Autoimmune Encephalitis (2016–2024), aiming to describe severity and clinical course, and to assess its potential to predict mortality. At diagnosis, the ICS distribution (median 18) aligned with previous publications and correlated with the time to diagnosis (median 19 months); all patients had symptoms in ≥ 2 ICS domains: bulbar (88%), sleep (84%), movement disorders (90%), cognition (64%), and/or other (78%). Of 46 patients with follow-up data, 7 (16%) died shortly after diagnosis; for the others, changes in the ICS mirrored the clinical course: at last visit, it decreased in improving patients (16/46, 35%; median 12 vs 17; p = 0.004), increased in worsening patients (11/39, 24%; median 26 vs 21; p = 0.006) and did not change significantly in stable patients (12/46, 26%; median 16 vs 15; p = 0.222). In the ROC analyses, 2-year mortality was predicted by the total ICS at diagnosis (AUC 69.51, 95% CI [50.19; 88.83]; optimal cut-off > 20, sensitivity 59%, specificity 77%), and by the bulbar score at diagnosis (AUC 74.68, 95% CI [56.17, 93.19]; optimal cut-off > 3, sensitivity 83%, specificity 62%). The ICS is a reproducible tool for assessing anti-IgLON5 disease severity and clinical course. Higher total and bulbar ICS at diagnosis are associated with increased mortality risk, underscoring the need for early and intensive management of bulbar dysfunction
Impact of socioeconomic individual and ecological factors on extreme diagnosis-to-treatment interval in diffuse large B-Cell lymphoma in the French real-world cohort REALYSA
No full textInternational audienceIntroduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive though potentially curable lymphoid malignancy requiring timely treatment initiation. We investigated the impact of individual socioeconomic status and home area-level (ecological) factors on the diagnosis-to-treatment interval (DTI) in DLBCL patients, focusing on extreme delays in a French real-world cohort (REALYSA).Methods: We analyzed patients with newly diagnosed DLBCL in the multicentric prospective cohort. DTI was defined as a duration in days between diagnosis confirmation and first-line therapy. Short and long DTIs (10th percentiles) were compared to intermediate DTI using multinomial models to identify factors associated with extreme DTIs. Socio-demographic data (including sex, education, employment, marital status, social support (SSQ6-score)…) and ecological characteristics (French deprivation index, local accessibility to general practitioners) were considered.Results: Among 889 newly diagnosed DLBCL patients (median age 66 years, 49 % with aaIPI ≥1, 35 % with B-symptoms, 33 % with bulky disease), median DTI was 25 days (interquartile range: 15-39 days). The 10th- and 90th-percentile for extreme DTIs were < 8 and > 50 days respectively. In multivariable analysis, factors associated with short DTI included aaIPI (OR=3.03, CI95 %[1.44-6.41]), bulky disease (OR=3.06, CI95 %[1.68-5.58]), and B symptoms (OR=2.35, CI95 %[1.30-4.25]) - indicating expedited treatment for aggressive presentations. Conversely, factors associated with long DTI included older age (OR>80 y = 3.31, CI95 %[1.39-7.89]), being a blue-collar worker or farmer (OR=2.36, CI95 %[1.18-4.73]), or changing type of treatment facility between biopsy and initial treatment.Conclusion: In this large real-world cohort of newly diagnosed DLBCL patients, age, occupational status, and patients' pathway were linked to very long delays to treatment. Interventions to streamline DTIs, especially for older and/or blue-collar or farmer patients, and for those changing facility of treatment, are warranted to improve quality of care
Medical SAM for LGE-MRI cardiac segmentation: promise or hype ?
No full textInternational audienceLate gadolinium enhancement (LGE) cardiac magnetic resonance(MR) imaging is a key technique for assessing myocardial damagein various cardiovascular diseases. Precise identification of cardiac structuresis essential for computing clinical biomarkers used in diagnosisand prognosis. While many deep learning methods have been proposedfor automatic segmentation, their generalizability is hindered by limitedtraining data and domain adaptation issues, restricting clinical deployment.Foundation models have recently emerged as a promising solution,able to perform zero and few-shot segmentation across various imagingmodalities through large-scale pretraining. Among them, the SegmentAnything Model (SAM) has become a widely recognized reference, withadaptations for medical imaging, such as MedSAM and SAM-Med2D.In this study, we evaluate MedSAM and SamMed2D for segmenting theleft ventricle and myocardium in LGE MR images from a private datasetcomprising 135 patients. We first demonstrate that zero-shot performanceremains limited, due to the scarcity of LGE MR data in theirpretraining. Next, we show that fine-tuning the MedSAM decoder significantlyimproves segmentation quality, surpassing the nnU-Net baseline,though it requires precise bounding box initialization. We thus proposea modified MedSAM architecture that enables multi-class segmentationfrom a single bounding box. However, our experiments reveal that despitevarious improvements, MedSAM continues to produce mixed results.While our approach can segment multiple structures with one BB,it still requires accurate initialization, and its performance converges towardsthat achieved by nnU-Net