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DNA Methylation in Prostate Cancer: Clinical Implications and Potential Applications.
No full textInternational audienceABSTRACT Background Prostate cancer is a common cancer with a variable prognosis. Its management is currently guided by histological and biological markers such as the Gleason score and PSA. Developments in molecular biology are now making it possible to identify new targets for better classification of prostate cancer. Among emerging biomarker, DNA methylation, an epigenetic process, is increasingly being studied in carcinogenesis. Techniques for analyzing DNA methylation are constantly improving, and digital PCR now allows absolute methylation quantification with high sensitivity. These techniques can be performed on circulating tumor DNA. Materials & Methods We conducted a literature review of scientific articles addressing the topic of DNA methylation in prostate cancer. Results & discussion This review summarizes the different genes whose methylation is involved in carcinogenesis and their clinical implications, both diagnostic and prognostic. Methylation monitoring could also be useful for the prediction of treatment response. However, most studies are retrospective, and prospective studies are needed to validate these data
Multimodal integration of data characterizing the evolution of the gutbrain axis during the prodromal phase of Parkinson's disease in a rat model
No full textManuscrit initialement soumis à la conférence IEEE International Symposium on Biomedical Imaging (ISBI) 2026.International audienceThis study explores the relationship between gut microbiota and brain connectivity in a rat model of Parkinson's disease (PD) through a multimodal integration approach. Longitudinal microbiota samples and resting-state functional MRI (rs-fMRI) data were collected following α-synuclein injection. Unsupervised clustering and supervised classification were applied to each modality to identify features that discriminated PD from control conditions. These top discriminative features were then integrated using Partial Least Squares (PLS) regression to link microbial composition with brain connectivity patterns relevant to PD. The resulting multimodal analysis revealed coordinated alterations across microbial and neural networks
From patient stoold to mechanistic insights : modeling IBS-D microbiota in the M-ARCOL.
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Outcomes After Kidney Transplantation in Antineutrophil Cytoplasmic Autoantibody–Associated Renal Vasculitis
No full textInternational audienceIntroduction: Antineutrophil cytoplasmic autoantibody (ANCA)-associated renal vasculitis (AAV) glomerulonephritis (GN) (AAV-GN) frequently leads to end-stage kidney disease (ESKD). Optimal management for patients with AAV-GN receiving a kidney transplantation (KT) remains poorly characterized. We compared posttransplant outcomes between patients with AAV-GN and controls in the modern era of immunosuppressive therapy.Methods: This multicenter retrospective study included 206 adult patients with AAV-GN and 412 matched controls who underwent KT between 2005 and 2023 in 12 French transplant centers. We compared the incidence of delayed graft function (DGF), graft failure, AAV relapses, acute rejection, and mortality between groups; and analyzed risk factors using multivariable models.Results: DGF incidence and kidney function up to 5 years after KT were similar between groups. Patients with AAV-GN showed a trend toward poorer graft survival (hazard ratio [HR] = 1.55, P = 0.077) and significantly lower overall survival (HR = 1.48, P = 0.034). AAV relapses occurred in 15 patients with AAV-GN (7.3%), significantly impacting graft survival (P = 0.008). ANCA positivity at KT tended to be associated with higher relapse risk (HR = 4.17, P = 0.065) and was associated with lower rejection risk (HR = 0.31, P = 0.016). Acute rejection incidence was comparable between groups. Azathioprine (AZA) maintenance therapy was associated with increased rejection (HR = 3.733, P = 0.012) and graft failure (HR = 3.73, P = 0.007 < 0.001). Although patients with AAV-GN were waitlisted later than controls, no specific transplant timing was associated with improved outcomes.Conclusion: Although KT offers patients with AAV-GN short-term outcomes similar to controls, they face higher long-term risk of graft failure and mortality. ANCA status at transplantation may help predict immunological events, emphasizing the need for careful evaluation and monitoring, but without delaying the process. As for other nephropathies, AZA should be avoided as maintenance therapy in patients with AAV-GN. These findings highlight the need for tailored posttransplant management in patients with AAV-GN
The addition of a tyrosine kinase inhibitor to intensive chemotherapy significantly improves outcome in de novo BCR::ABL1+ acute myeloid leukemia treated with intensive chemotherapy
No full textInternational audienceIntroduction: De novo BCR::ABL1+ acute myeloid leukemia (AML) is a distinct and rare entity (0.1%-3% of AML), classified as adverse-risk in the ELN 2022 classification (Döhner H et al., Blood 2022). However, we recently published the favorable outcome of 18 de novo BCR::ABL1+ AML from the French DATAML registry treated with imatinib + intensive chemotherapy (IC) (Gondran C et al., Blood Cancer Journal 2024): CR/CRi, 94.4%; 3-year OS, 77%; that compared favorably to intermediate- and adverse-risk AML. To confirm these results, we performed a multicentric European retrospective data collection of de novo BCR::ABL1+ AML characteristics, treatment data and outcome. Methods: Inclusion criteria for this retrospective study were: adult AML with ≥ 20% bone marrow blasts, BCR::ABL1+or t(9;22)(q34.1;q11.2), with no history of previous chronic myeloid leukemia (even if < 6 months) and no prior exposition to BCR::ABL1 tyrosine kinase inhibitor (TKI), who were treated with IC +/- TKI. Acute leukemia of ambiguous lineage were excluded. Results: We collected the data of 250 patients with de novo BCR::ABL1+ AML diagnosed from March 1999 to December 2024. 212 patients were treated with IC: 89 with IC alone and 123 with IC + TKI. Median age was 54 years and 67 patients (32%) were older than 60. Forty-three patients (28.5%) presented with splenomegaly. The median WBC was 45.109/L (29 in the IC arm vs. 53 in the IC + TKI arm). One hundred and fifteen patients (60%) had additional chromosomal abnormalities, 28 (15%) had a monosomal karyotype and 62 (32%) had complex abnormalities. BCR::ABL1 isotype was p210 in 80% and p190 in 20%. Molecular data were available for the most recent patients: the co-occurring mutations present in more than 10% of cases were: RUNX1 (N=32/100: 32%), BCOR (N=11/82: 13%), ASXL1 (N=10/79: 13%), WT1 (N=9/72: 13%), DNMT3A (N=8/73: 11%), and NPM1 (N=15/147: 10%); a TP53 mutation was found in 7% (N=5/77). IC was a 7+3 including daunorubicin+cytarabine in 107 patients (59%), idarubicin+cytarabine in 59 patients (36%) or another scheme in 14 (8%). In the IC + TKI arm, imatinib was added in 66 patients (54%; 400-800 mg/day), dasatinib in 40 patients (33%; 100-140 mg/day), ponatinib in 11 patients (9%; 15-45 mg/day), and nilotinib in 6 patients (5%; 600-800 mg/day). Response assessment was available in 78 patients in IC arm and 122 patients in IC + TKI arm. Composite complete remission (CR/CRi) was achieved in 52 patients (66.7%) in the IC arm, and 110 patients (90.2%) in the IC + TKI arm (P<0.0001). 28.2% and 9.0% of patients had primary refractory disease in the IC and IC + TKI arm, respectively (p<0.001). 97 patients (59.9%) were transplanted in CR1 (26 patients [50%] in IC arm and 71 patients [64.5%] in IC + TKI arm, P=0.077). The relapse rate was 28% in the IC arm and 18% in the IC + TKI arm (P=0.159). With a median follow-up of 66.7 months, the 3-year and 5-year OS were 42.1% and 38.5% in the IC arm and 70.9% and 62.9% in the IC + TKI arm (P<0.0001). The median OS was 20.5 months in the IC arm and not reached in the IC + TKI arm. The 3-year and 5-year RFS were 52.1% and 49.3% in the IC arm and 73.0% and 67.1% in the IC + TKI arm (P=0.0095). The 3-year and 5-year EFS were 32.1% and 30.4% in the IC arm and 66.7% and 61.4% in the IC + TKI arm (P<0.0001). Of note, in the IC + TKI arm, 26 out of 39 patients (67%) who were not transplanted did not relapse and had a median OS of 65.8 months. In multivariate analyses, the addition of TKI to IC was significantly and independently associated with an improvement in CR/CRi rate (OR: 4.74 [2.17-10.35]; P<0.001), in OS (HR: 0.40 [0.27-0.62]; P<0.001), in EFS (HR 0.37 [0.25-0.55]; P<0.001) and RFS (HR: 0.42 [0.23-0.75]; P=0.004) adjusted for confounding factors including allo-HSCT as time-dependent variable. The other independent poor predictive factors were: age older than 60 years for OS and EFS; and WBC over 50.109/L, IC regimen different than 7+3 and absence of alloSCT for RFS. Conclusions: The addition of a TKI significantly improves the outcome of de novo BCR::ABL1+ AML treated with intensive chemotherapy, and should be a standard of care for this entity. This study should lead to the revision of the current ELN AML genetic risk classification, as this entity no longer deserves to be classified as adverse
Outcome after relapse in older patients with Philadelphia Chromosome–Negative B-cell ALL treated with inotuzumab ozogamicin and low-dose chemotherapy in first-line therapy: A graall study
No full textInternational audienceBackground: With the advent of immunotherapy, the prognosis of older patients with Philadelphia-negative (Ph-neg) B-cell acute lymphoblastic leukemia (B-ALL) has significantly improved these recent years. Overall survival (OS) is now around 50% at 2 years, with the consequence that is it now possible to consider the outcome of relapsing patients (pts) after a first-line therapy. Here we studied the outcome of pts who relapsed after receiving a frontline immuno-chemotherapy with inotuzumab ozogamicin (InO), an anti-CD22 antibody conjugated to calicheamicin, as part of the EWALL-INO study (NCT03249870, JCO 2024). Methods The RELAPSINO study aimed to retrospectively describe post-relapse outcome in pts included in the single arm phase 2 prospective multicenterEWALL-INO study. In this former study, InO was associated with low dose chemotherapy for 2 induction cycles. In case of complete response (CR), pts then received 6 consolidation cycles and an 18-month (m) POMP maintenance or an allogeneic stem cell transplantation (allo-SCT). At diagnosis, all pts were aged ≥ 55 years and had a newly diagnosed CD22+ Ph-neg B-ALL. A total of 131 pts were included between December, 2017, and March, 2022, and 49 relapses (incidence 38% at 2 years) were documented at last follow-up in May, 2023, including 45 in France, 2 in Finland and 2 in Czech Republic. The RELAPSINO study was approved by the Groupe Nantais d'Ethique dans le domaine de la Santé (GNEDS, reference 24-79-07-100, July 2024). For administrative reason, only French pts were included in this new study. Data regarding pts were updated until May, 2025, and analyses were performed in June, 2025. Results Since the last follow-up, 6 additional relapses have been documented among French pts. Among the 45 previous relapsed French pts, we excluded 3 pts who presented concomitant therapy-related myelodysplastic syndrome. In total, 48 French relapsed pts (male n=25, female n=23) were included in this updated analysis, of whom 60% had a high-risk cytogenetics at diagnosis. None had received an allo-SCT in CR1. At relapse, median age was 70 years (IQR, 67-74; range, 55-86) and median duration of CR1 was 15.2m (IQR 5.3-22.9). Site of relapse was bone marrow (BM) in 38 (79%) pts, extra-medullary in 4 pts (CNS n=2, testis n=1, vertebra bone n=1) and combined in 3 pts (BM + skin n=1, BM + ocular n=1, BM + CNS n=1) (missing n=3). Although none of the patients received the CD19-CD3 bi-specific T-cell engager blinatumomab before relapse, CD19 and CD22 expressions were negative at relapse in 5/41 (12%) and 9/40 (23%) of evaluable pts, respectively. A large majority of pts were re-treated (n=41, 85%) and 29/41 (71%) received blinatumomab as salvage regimen, either alone (n=14) or after low-dose (n=9) or intensive (n=6) chemotherapy. Twelve pts received chemotherapy only (low dose n=3, intensive n=9). No patient was re-treated with InO or received CAR-T cells as salvage regimen. Half of the pts (n=20/41, 49%) achieved CR2. One was consolidated with CAR-T cells and 4 with an allo-SCT. By multivariate analysis (MA), a CR1 duration > 12m (but not >15m or 18m) was the only significant factor associated with CR2 achievement (p=0.04). With a median follow-up from relapse of 30.3 months (95%CI, 25.0–NA), median event-free survival (EFS) and OS were 3.2m (95%CI 2.3-5.7) and 4.5m (95%CI 3.8-11.0), respectively. Two-year EFS and OS were respectively 15% and 19%. By MA, salvage regimen with intensive chemotherapy (p=0.01), CR1 duration >18m (but not >12m or 15m) (p=0.04), and CR2 (p<0.001) were significantly associated with better OS. Intensive chemotherapy (p=0.008) and CR1 duration >18m (but not >12m or >15m) (p=0.01) were also associated with significant better EFS. The 2-year cumulative incidence of relapse after CR2 was 53%. No predictive factor for second relapse was identified. Median LFS and OS after CR2 were 13m and 24m, respectively, with 2-year LFS and OS of 36% and 46%. In pts who did not achieve CR2, median OS was 3.8m only. Overall, 38 pts (79%) died, the main cause of death being relapse or progression (n=36, 95%). Two pts died in CR2 of unknown cause.Conclusion: Half of older Ph-neg B-ALL patients relapsing after a front-line Ino-based therapy can achieve a new remission and good survival. These encouraging results support the risk of re-treating patients, especially those with late relapse, even with intensive chemotherapy, which appears the best salvage regimen in this series
Career Trajectories After Palliative Care Training: A National E-Survey of Medical Interns in France
No full textInternational audiencePalliative care has become a crucial component of healthcare, with an increasing need for specialized training. In France, a new one-year palliative care diploma was introduced in 2019 to disseminate palliative care knowledge across various medical specialties. Offered in the final year of medical residency, the program includes 2 six-month internships in palliative care settings and four national seminars covering topics such as symptom management, ethics, and communication. However, the impact of this training on physicians' career paths remains underexplored.AimThis study aimed to assess the current practices of physicians trained in palliative care, and how the training influenced their career choices.MethodsA national e-survey was conducted, aimed at all physicians who completed the palliative care training course between 2019 and 2023. Data were collected through a 36-question survey covering training completion and current practices.ResultsWe contacted 179 physicians. After excluding 40 responses from those who had not completed their diploma, the eligible sample consisted of 139 respondents. Of these, 81 complete responses were obtained, yielding a 58% response rate (81/139). Of these, 52 were currently practicing in specialized palliative care settings. Interestingly, 88.5% of those not practicing directly in palliative care still integrated a palliative dimension into their daily work. The proportion of physicians intending to work exclusively in palliative care tripled after the training course compared to before.ConclusionThis study highlights the significant role of the palliative care training in shaping physicians' career paths and disseminating palliative care practices across medical specialties
L’amélioration de la qualité de vie des aidants grâce aux interventions ergothérapiques à domicile
No full textContext: as Alzheimer's disease progresses, it leads to dependency, requiring daily assistance provided mainly by family carers. The 2008-2012 Alzheimer's plan will give occupational therapists the opportunity to work in the home, thanks to the creation of Alzheimer's Specialised Teams (ESA). The aim of this research is to analyse what occupational therapists do for carers to improve their quality of life. Method: a study was carried out using semi-directive interviews with occupational therapists practising in ESAs throughout France.Results: 9 occupational therapists agreed to take part in the study. In most cases, there appeared to be a correlation between the actions implemented by occupational therapists and an improvement in the quality of life of carers. The occupational therapist's role is to provide advice, information and guidance. Conclusion: occupational therapy support for carers is essential if people are to remain at home. However, support for the carer remains an area for improvement in occupational therapy practice in the home, through the introduction of long-term follow-up.Contexte : la maladie d’Alzheimer, en évoluant, engendre une dépendance qui nécessite une aide quotidienne majoritairement dispensée par les aidants familiaux. Le plan Alzheimer 2008-2012 offrira à l’ergothérapeute l’opportunité d’intervenir à domicile grâce à la création d’Équipe Spécialisée Alzheimer (ESA). L’objectif de cette recherche est d’analyser quelles actions les ergothérapeutes réalisent auprès des aidants pour améliorer leur qualité de vie. Méthode : une étude a été réalisée par le biais d’entretien semi-directif auprès d’ergothérapeute exerçant en ESA partout en France. Résultats : 9 ergothérapeutes ont accepté de participer à l’étude. Il apparait le plus souvent une corrélation entre les actions mis en œuvre par les ergothérapeutes et l’amélioration de la qualité de vie des aidants. Les missions de conseil, d’information et d’orientation sont alors privilégiées. Conclusion : l’accompagnement ergothérapique auprès des aidés/aidants est essentiel pour garantir le maintien à domicile de la personne. Cependant, l’accompagnement de l’aidant reste un axe d’amélioration dans la pratique en ergothérapie à domicile par un la mise en place d’un suivi à long terme
Surgical Management of Gastric Cancer in Elderly Patients: Results of a Multicenter Cohort of the French Surgical Association
No full textInternational audienceIntroduction: Gastric cancer primarily affects the elderly, but surgical management varies with age. This multicenter, retrospective cohort study assessed treatment approaches and outcomes in gastric cancer patients based on age. Methods: Between 2007 and 2017, 2,131 patients treated in French Surgical Association centers were identified. Patients with metastatic disease, those who did not undergo gastrectomy, those who underwent emergency surgery, those who underwent hyperthermic intraperitoneal chemotherapy and those with unspecified birth dates were excluded. The final cohort of 1,426 patients was divided into three age groups: <70 years (group 1, 60%), 70–79 years (group 2, 27%), and ≥80 years (group 3, 13%). Results: Elderly patients were more often female and received less neoadjuvant chemotherapy (58% vs. 43% vs. 17%, p<0.001). Despite similar tumor locations, they underwent fewer total gastrectomies (68% vs. 55% vs. 43%, p<0.001) and D2 dissections (22% vs. 22% vs. 12%, p=0.007). Medical complications increased with age, while surgical complications were not significantly higher in group 3. Advanced age was not an independent risk factor for severe postoperative complications (Dindo ≥III). Pathologic results were comparable, but elderly patients received less postoperative treatment (67% vs. 45% vs. 16%, p<0.001). Five-year overall survival decreased with age (64% vs. 52% vs. 37%, p<0.001), while cancer-specific survival remained stable (69% vs. 67% vs. 63%, p=0.56). Conclusion: Advanced age does not independently increase the risk of postoperative morbidity and should not justify less aggressive surgery. Despite receiving less perioperative treatment, selected elderly patients maintain a comparable cancer prognosis to younger individuals