Institute Mutualiste Montsouris

Vedolizumab has become the preferred first-line advanced therapy in ulcerative colitis (UC). However, the optimal second-line treatment following vedolizumab failure remains unclear. We aimed to evaluate the effectiveness and safety of second-line therapies after first-line vedolizumab. We conducted a multicenter retrospective study including UC patients from 31 centers who received infliximab (IFX), subcutaneous (SC) anti-TNFs, or ustekinumab after vedolizumab failure. The primary endpoint was steroid-free clinical remission (SFCR) at week 14. Predictors of remission were identified using multivariate logistic regression. Among 196 patients, 99 received IFX, 27 anti-TNF SC, and 70 ustekinumab. At week 14, SFCR was achieved in 78 patients (39.8%): 38 (38.4%) with IFX, 8 (29.6%) with anti-TNF SC, and 32 (45.7%) with ustekinumab, with no significant difference between groups (p=0.32). Median treatment persistence ranged from 8 to 9.2months. Baseline corticosteroid use was associated with lower odds of SFCR (OR=0.37, 95% CI [0.18-0.73]). Adverse events occurred in 15.8% of patients, including 12.2% serious events. Overall adverse events were less frequent with ustekinumab than with IFX (10.0% vs. 24.2%, p=0.02), while serious events were comparable (5.7% vs. 16.1%, p=0.08). Discontinuation due to adverse events was more frequent with IFX (12.1%) and anti-TNF SC (14.8%) than with ustekinumab (2.9%, p=0.045 and 0.049). In UC patients failing vedolizumab, second-line IFX, anti-TNF SC, and ustekinumab showed similar effectiveness and persistence. Infliximab remains a robust option for rapid control in high inflammatory burden, whereas ustekinumab may be preferred for its superior safety profile in high-risk patients.

Thymomas are rare thymic epithelial tumors harboring a high but variable proportion of lymphocytes without obvious function. Autoimmunity is present in one third of patients at diagnosis. In this study, we performed a phenotypic, single-cell RNA sequencing and spatial analysis of both the T cells and tumoral cells. T cells at all stages of T-cell development-from immature to mature-were present in the tumor, suggesting active thymopoiesis in thymoma. However, data generated through multiple approaches suggested a maturation blockade at the double-negative to double-positive stage of T-cell development. In the mature T-cell compartment, the frequency of regulatory T cells was strongly decreased. The single-cell RNA sequencing analysis showed that the transcriptome of tumoral thymic epithelial cells (TEC) was most similar to that of nontumoral medullary TEC, but the expression of key molecules involved in positive and negative selection was defective. Multiplexed IHC consecutive staining revealed a loss of the cortex-medulla zoning in thymoma, which may be related to a decrease in the expression of T cell-targeted chemokines by tumoral TEC. Altogether, these results suggest that the thymopoiesis present in thymoma is abnormal and may be the cause of the prevalent autoimmunity observed in this disease.

Background:Biliary tract cancers (BTC) are often diagnosed after the age of 70, when comorbidities and compromised performance status (PS) are more prevalent.Objectives:This study compared clinical and disease characteristics and outcomes in BTC patients aged ⩽70 and >70 years.Design and methods:PRONOBIL-ACABI is a cohort study including 1256 BTC patients treated across 16 French centers from January 2003 to June 2021. We analyzed demographics, clinical characteristics, treatment modalities, molecular profiles, overall survival (OS) as the primary endpoint, and progression-free survival (PFS).Results:Among the 1256 BTC patients (53% male; median age: 64.5), 31% were aged >70. Patients >70 exhibited poorer PS (PS ⩾2, 17% vs 8%; p < 0.0001), a higher rate of comorbidities (⩾1, 89% vs 78%; p < 0.0001), and were less often proposed a molecular profile (43% vs 65%; p < 0.0001) than those ⩽70. Patients with unresectable BTC aged >70 had significantly shorter OS compared to younger patients (median OS: 14.6 vs 17.4 months, p < 0.0001), despite similar PFS (median PFS: 6.6 vs 5.8 months, p = 0.61). They were also less likely to receive first-line chemotherapy (87% vs 97%, p < 0.0001). In resected BTC, survival outcomes were comparable across age groups, with a median OS of 47.0 months in patients >70 vs 48.8 months in those ⩽70.Conclusion:Patients aged >70 years with unresectable BTC had a significantly shorter OS compared to those aged ⩽70, despite similar first-line PFS. In resected BTC, elderly patients achieved OS and PFS outcomes comparable to those aged ⩽70.

Comprehensive knowledge of the clinical presentation, contemporary management, and outcomes on "all-comer" patients referred for mitral valve surgery (MVS) are critical to evaluate current practice and adherence to guidelines, understand selection biases, and inform key stakeholders on quality improvement. MITRACURE is a large international retrospective registry of consecutive adult patients who underwent isolated or combined MVS for mitral regurgitation (MR) in France or Canada in 2019 with in-depth clinical and echocardiographic characterization. Patients operated on for isolated mitral stenosis or who had a prior mitral valve intervention were excluded. Data were obtained from detailed chart abstraction and were site reported. In 2019, 3522 patients underwent MVS (48% combined) across 40 centers (88±46 MVSs/center, median 80, interquartile [51-131]). Mean age was 65±12 years, and 35% were women. The most common MR etiology was myxomatous (61%), followed by functional (9%), infective endocarditis (9%), and rheumatic disease (7%). MR quantification was performed in only 43%. Advanced clinical presentation was common: 43% were in New York Heart Association class III/IV, 30% exhibited congestive heart failure, 47% were on diuretics, 22% had atrial fibrillation/flutter, 35% presented with reduced ejection fraction, and 22% had pulmonary hypertension (≥50 mm Hg). Most patients were symptomatic or presented with class I/IIa indication for intervention, and an early intervention was performed only in 3% of patients. The repair rate was 62% overall and 80% in myxomatous disease. In-hospital mortality was 4.5% overall but 2.3% in patients with myxomatous MR (1.8% isolated, 3.1% combined). MITRACURE provides a contemporary, multicenter, "real-world" picture of the clinical presentation, management, and in-hospital outcomes of MVS for MR in two Western countries. Patients were often referred late in the disease process, with few patients undergoing early intervention. The higher mortality and lower repair rates reported may be more reflective of an unselected MR patient population but have room for improvement. Our results underline the need to develop strategies to improve management and outcomes of patients with MR.

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized in cancer patients and survivors, yet it remains underdiagnosed and its epidemiology largely unknown. This statement underscores the imperative need to include HFpEF in the cardiotoxicities identified during or after anticancer treatments. It also highlights the prognostic value of pre‐existing HFpEF for periprocedural and cardiotoxicity risk and it discusses the challenges in the diagnosis and treatment of HFpEF in cancer patients. It also explores the aetiologic role of anticancer therapies (chemotherapy, targeted and hormonal therapies and radiotherapy) in the pathogenesis of HFpEF. Special emphasis is given on the importance of considering HFpEF from cancer diagnosis throughout treatment and survivorship and provides useful insights for cardiologists and oncologists in the monitoring and management of these patients. Finally, it highlights the key gaps in current knowledge that require further investigation through well‐designed research trials to enhance our understanding and improve clinical outcomes.