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Determinants of virological outcomes in kidney transplant recipients treated with maribavir for refractory cytomegalovirus infection
No full textInternational audienceMaribavir has demonstrated promising efficacy in treating refractory cytomegalovirus (CMV) infections among solid organ transplant recipients; however, factors influencing favorable outcomes remain uncertain. We conducted a retrospective cohort study that involved 88 kidney transplant recipients (KTRs) from 22 transplantation centers, all of whom had refractory CMV infections treated with maribavir (63 with and 25 without ganciclovir resistance mutations). CMV clearance at week 8 was achieved in 45 KTRs (51.1%). Among the 49 KTRs (55.7%) who achieved CMV clearance within 16 weeks, 37 (42%) did not develop CMV recurrence. Notably, CMV DNA levels <10 000 international unit/mL at the time of maribavir initiation (odds ratio, 3.21; 95% confidence interval, 1.29-9.54; P = .016) and asymptomatic CMV infection (odds ratio, 3.22; 95% confidence interval, 1.28-9.0; P = .017) were identified as independent factors associated with CMV clearance within 16 weeks without recurrence. Maribavir resistance mutations were identified in 18 KTRs (20.45%), predominantly among those who failed to achieve CMV clearance (35.9%) and those who experienced CMV recurrence (33.3%). In summary, refractory CMV infections characterized by high levels of CMV DNAemia or symptomatic presentations are more challenging to treat with maribavir. These findings may support the development of new strategies for patients at risk of poor outcomes
Evidence for the absence of a relationship between inflammation and cognition in a cohort of 1565 individuals with bipolar spectrum disorders: a Bayesian analysis of network
No full textInternational audiencePrevious studies have reported variable associations between peripheral inflammatory markers and cognitive functioning in individuals with bipolar spectrum disorders (BSD), with some identifying significant links and others finding no relationship. Such inconsistencies raise important questions about the role of inflammation in cognitive impairment among individuals with BSD. This study aims to investigate the relationship between peripheral inflammatory markers and cognitive function in a clinical sample of individuals with BSD using a Bayesian network analysis framework. We analyzed data from a large cohort (n = 1565) focusing on hsCRP and a subsample (n = 249) that included concurrent assessments of additional cytokines including Interleukin-6 and Tumor Necrosis Factor-alpha. A Bayesian approach was utilized to quantify uncertainty regarding the presence or absence of associations between inflammation and cognitive function. Our findings revealed no significant associations between inflammatory markers and cognitive performance in both samples. Strong evidence was found supporting the absence of association, with network analysis indicating distinct clusters for cognitive and inflammatory variables, suggesting they function as independent constructs with limited interactions. In our clinical sample of individuals with BSD, our findings do not support a direct association between some inflammatory markers and cognition, aligning with studies that found minimal or no associations. Our study emphasizes the importance of utilizing Bayesian methods to assess these relationships rigorously and suggests further exploration of individual differences and subgroup effects in future research
Understanding dopaminergic dose reduction following STN-DBS: mediation analysis
No full textInternational audienceBackground Levodopa equivalent dopaminergic dose (LEDD) reduction after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease varies widely. Identifying predictors may guide patient selection and programming. Our objectives were to identify predictors of LEDD reduction and to test whether motor improvement mediates this association. Methods Data from 144 patients treated by STN-DBS were analysed. Predictors of LEDD reduction were selected using the Boruta algorithm, a machine-learning method comparing variable importance to randomised features and then tested in a structural equation model for direct and motor-mediated effects. Results Mean LEDD reduction was 41.7% (±38.2%) and motor improvement was 48.6% (±26.7%) at 1 year. Among the four predictors identified by Boruta, lower baseline LEDD (β=0.39, p=0.001), greater axial impairment (β=−0.25, p=0.003) and higher total volume of tissue activated (β=−0.17, p=0.031) were directly associated with lower LEDD reduction, independent of motor improvement. Sensorimotor STN overlap was not directly linked to LEDD reduction but was positively associated with motor improvement (β=0.34, p=0.001), which showed a trend-level effect on LEDD reduction (β=0.16, p=0.065). The total effect of sensorimotor STN overlap on LEDD reduction was not significant. Discussion Dopaminergic dose reduction after STN-DBS is constrained by preoperative axial symptoms and stimulation spread, independently of motor improvement, while sensorimotor STN overlap improves motor symptoms but not dose reduction. Integrating motor phenotype with anatomical guidance may enhance medication management post DBS
Laminopathies: natural history and risk prediction of heart failure
No full textInternational audienceBackground and aims: Patients with LMNA gene variants are at high risk for dilated cardiomyopathy and heart failure (HF), but no prediction model for severe HF events exists. This study aimed to describe the incidence of severe HF events and develop a prediction model in a large cohort of patients with adult-onset laminopathies.Methods: From a population of 660 patients enrolled in the French LMNA nationwide registry, 470 adults were included in the derivation cohort. An independent international validation cohort included 245 additional patients. Baseline characteristics at genetic testing were assessed and the cumulative incidence of the primary endpoint HF-major adverse cardiac events (HF-MACE) was calculated, defined as HF hospitalization, HF-related death, mechanical circulatory support, or heart transplantation. Predictors of HF-MACE were studied after excluding patients with left ventricular ejection fraction (LVEF) <30% at baseline using a Fine-Gray competing risk model, adjusted hazard ratio (aHR) with 95% confidence interval (CI), and Harrell's concordance (C-) index. A secondary composite endpoint, without hospitalization, was also studied.Results: Among 470 patients of the derivation cohort, HF-MACE occurred in 65 over a median follow-up of 7.1 years (interquartile range: 3.4-12.1). Four independent predictors of HF-MACE were identified: male sex (aHR 1.86; 95% CI 1.060-3.290), LVEF <50% (aHR 2.18; 95% CI 1.080-4.400), missense variants in head and rod domains (aHR 2.91; 95% CI 1.110-7.630), and complete left bundle branch block (aHR 2.99; 95% CI 1.400-6.400). The C-index of the model was 0.750 (95% CI 0.720-0.780) in the derivation cohort and 0.758 (95% CI 0.720-0.800) in the validation cohort. The 5-year cumulative incidence of HF-MACE was 1.5% (95% CI 0.6-3.6), 5.0% (95% CI 1.8-8.2), and 22.0% (95% CI 15.6-28.4) among patients with 0, 1, and ≥2 risk factors, respectively. In patients with LVEF <30% at baseline, the 1-year incidence of HF-MACE was 50%, and those patients were excluded from the risk score.Conclusions: The first prediction model for severe HF events in adult laminopathies was developed, which may facilitate early and optimal preventive management.Clinical trial registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT03058185
Effects of deep brain stimulation on non motor fluctuations in Parkinson’s disease (assessed with the NMF severity scale)
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“Invented medicine”? Alliance building in first encounters between clinicians and adolescents with anorexia nervosa: a qualitative study
No full textInternational audienceCaring for adolescents with anorexia nervosa (AN) involves gaining patients’ and families’ trust in a condition fraught with ambivalence. While essential for subsequent care and the development of a therapeutic alliance, the first clinical encounter is also known to be emotionally challenging both for frontline professionals and for families. There are few studies investigating the experience of clinicians working in specialized care settings. Our study aims to explore the challenges experienced by specialized professionals during the initial encounter with patients presenting with AN and their families. Methods: A qualitative study was conducted at the Maison des Adolescents, Cochin Hospital, Paris, a facility specialized in holistic care for adolescents, based on semi-structured interviews using Interpretative Phenomenological Analysis (IPA). Results: Sixteen clinicians with various professional profiles were interviewed between March 15th 2024 and August 5th 2025. Verbatim analysis identified four superordinate themes: (1) The first encounter: a daunting experience. (2) Balancing two divergent clinical postures: empathy and suasion. (3) Strategies for building a therapeutic alliance in the face of reluctance. (4) Building professional legitimacy through experience. Conclusions: The emotional impact of these initial encounters can remain significant and complex, requiring introspective work and adaptability from professionals in order to promote therapeutic alliance. Developing of a formalized structure for initial interviews could be a possible avenue for improving these encounters
Health-related quality of life after second-line axi-cel in transplant-ineligible patients with large B-cell lymphoma
No full textInternational audienceThe phase 2 ALYCANTE trial aimed to evaluate the investigator-assessed complete metabolic response at 3 months from the axicabtagene ciloleucel (axi-cel) infusion as a primary end point in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation (ASCT). This study showed a significant improvement in complete metabolic response rate at 3 months based on historical controls. This study reports the health-related quality of life (HRQoL) results as a secondary end point. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) cancer-specific questionnaire, the Quality of Life Questionnaire high-grade non-Hodgkin lymphoma 29 (QLQ-NHL-HG29) , and the EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L) generic questionnaire at baseline and 1, 3, 6, and 12 months after axi-cel infusion. Among the 62 patients included, 60 (97%) completed a baseline and at least 1 postbaseline HRQoL assessment. At 1 month infusion, adjusted mean change in HRQoL scores from baseline showed a clinically significant deterioration (greater than the clinical threshold) in physical, role, social functioning, and fatigue. However, all HRQoL dimensions recovered by 3 months after infusion and remained stable or continued to improve by 12 months. In an exploratory analysis, adjusted mean change in HRQoL score from baseline in ALYCANTE was similar to or better than in ASCT-eligible patients who received axi-cel in the phase 3 ZUMA-7 trial. Finally, the global health status and fatigue scores of the ALYCANTE population improved to levels comparable to the general French population of similar age by 3 months after infusion. These findings indicate that axi-cel improves HRQoL regardless of transplant eligibility, supporting its use across a broad patient population. This trial was registered at www.clinicaltrials.gov as #NCT04531046
Increased intervals in enzyme replacement therapy for stable type 1 Gaucher disease: A non‐inferiority sequential trial emulation
No full textInternational audienceObjective To compare the efficacy and safety of extended interval (Q3–4W) enzyme replacement therapy (ERT) versus standard biweekly (Q2W) ERT in clinically stable type 1 Gaucher disease (GD) patients. Methods We emulated a target trial with a sequential trial design, using data from the French Gaucher Disease Registry. Eligible patients were treated for ≥2 years biweekly without clinical events. Every 3 months, switchers to Q3–4W were matched to Q2W patients by age, sex, referral center follow‐up, disease history (bone events, anemia, thrombocytopenia, splenectomy, and hepatosplenomegaly), and dose of ERT. The primary outcome was a composite of GD‐related events (bone events, anemia, and thrombocytopenia). A 10% non‐inferiority margin was prespecified. Secondary outcomes were biomarker changes and economic analyses. Results Among 280 eligible GD patients, 63 switched to Q3–4W and were matched to a total of 215 Q2W patients, followed for an average of 6.3 years. No significant difference in the risk of clinical events was observed between groups (hazard ratio: 0.98 [95% confidence intervals (CI): 0.54–1.51]). During follow‐up, absolute risk difference remained below the 10% non‐inferiority threshold at all timepoints. Biomarkers remained stable or slightly decreased in the Q3–4W group. The dosing interval extension led to an average reduction of 55 infusions per patient, corresponding to approximately €450,000 saved per patient over 6 years. Conclusion In stable GD1 patients, extending ERT administration to every 3–4 weeks was non‐inferior to the standard biweekly regimen, supporting personalized spacing strategies that may improve quality of life and reduce healthcare costs
OP03 Early kinetics of transmural healing in patients with Crohn’s Disease treated with risankizumab: Results of the multicenter prospective SKYNETICS study
No full textPrésentation oraleInternational audienceBackground We aimed to evaluate, in real-life practice, the kinetics of clinical, biochemical, and transmural efficacy of risankizumab in patients with Crohn’s disease (CD). Methods In this academic multicenter prospective study, adult patients (≥18 years) with CD who initiated risankizumab in routine practice for symptomatic CD according to PRO-2 with objective evidence of inflammation on ultrasound were included. Patients started risankizumab at a dose of 600 mg IV at weeks 0, 4, and 8, followed by 360 mg every 8 weeks (from W12) via an on-body injector. Ultrasound examinations were performed at W0, W4, and W12 to assess the kinetics of transmural response. Patients were subsequently followed long-term. The primary endpoint was transmural response, defined as a 25% decrease in IBUS-SAS at W4 and W12. Alternative definitions of transmural remission using the BUSS score or the us-C-score were also evaluated at W4 and W12. Secondary endpoints included clinical response and clinical remission according to PRO-2 (W4, W8, W12), biochemical response (change in fecal calprotectin), and transmural remission (normalization of ultrasound) (W4 and W12). Secondary long-term outcomes included treatment survival without discontinuation, hospitalization, progression of bowel damage, and surgery. Results A total of 101 patients were included, with a mean age of 42.9 ± 15.0 years, 58% women, and 45.9% active smokers. Montreal classification was as follows for disease location (L1 = 41% / L2 = 11% / L3 = 48%), phenotype (B1 = 28.9% / B2 = 42.1% / B3 = 28.9%), and prior perianal CD (37%). Among them, 44.9% had previously required intestinal resection. While 28% of patients had prior exposure to one biologic, 32% and 40% were exposed to two and ≥ 3 advanced therapies, respectively. Clinical response and clinical remission were observed in 57.7% and 33.9% at W4, 70.1% and 33.3% at W8, and 79.2% and 38.0% of patients at W12, respectively. Median fecal calprotectin levels were 269, 192, 200, and 135 µg/g at W0, W4, W8, and W12, respectively. Transmural response rates were 27.3% at W4 and 28.5% at W12 according to IBUS-SAS, 9.1% at W4 and 14.3% at W12 according to BUSS, and 52.3% at W4 and 54.3% at W12 according to the us-C-score. Transmural remission was achieved in 8.5% of patients at W12. Segmental transmural response did not differ between ileal and colorectal segments regardless of the scoring system used. Predictive factors of response and long-term outcomes will be available for the congress. Conclusion In this prospective multicenter study including unselected patients with Crohn’s disease previously exposed to at least one anti-TNF, risankizumab achieved early clinical, biochemical, and transmural effectiveness, supporting its use in this clinical situation. Conflict of interest: Domas, Quentin: No conflict of interest Serrero, Melanie: No conflict of interest Mathieu, Kelly: No conflict of interest M’Baye, Diari: No conflict of interest Huet, Julie: No conflict of interest Ferrari, Tessa: No conflict of interest Yzet, Clara: No conflict of interest Guillo, Lucas: No conflict of interest Hupé, Marianne: 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 Pereira, Bruno: No conflict of interest Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda</p