Objectives To determine the cumulative incidence and identify the factors associated with difficult-to-treat axial spondyloarthritis (D2T-axSpA) in French patients newly benefiting from the French ‘long-term illness’ (LTI) social security scheme for axial spondyloarthritis (axSpA). Methods This national cohort study was based on the French National Medico-Administrative Database, SNDS, which contains data on hospitalisation, LTI and outpatient care consumption. All French patients newly receiving LTI benefits for ankylosing spondylitis (AS) between 2010 and 2013 were included in the study. In France, LTI is required to access biological/targeted synthetic DMARDs (b/tsDMARDs). The follow-up period ended on 31 December 2018. So-called D2T-axSpA was defined as the failure of three b/tsDMARDs or of two b/tsDMARDs with different modes of action. Comorbidities and extra-musculoskeletal manifestations were identified using previously described algorithms. Characteristics were compared between patients with D2T-axSpA and patients with non-D2T-axSpA who had received at least one b/tsDMARD with bivariate and multivariate analysis using logistic regression. Incidence rates of major cardiovascular event (MACE) and death were compared using competitive risk analysis. Results 22 932 patients were included. 10 798 (47.08%) patients received at least one bDMARD. None received tsDMARD. During follow-up, 2115 patients were classified as having D2T-axSpA, representing 19.59% of patients who received at least one bDMARD. In multivariate analysis, D2T-axSpA was significantly associated with female gender, peripheral involvement, psoriasis, hypertension and depression (p<0.001 for each case). There was no difference in the incidence of MACE (p=0.92) or death (p=0.87). Conclusion D2T-axSpA affects one in five patients exposed to bDMARDs in this national cohort. D2T-axSpA is more common in women and patients with peripheral involvement and/or comorbidities.

Epidemiological studies have reported associations between prenatal exposure to outdoor air pollution and adverse pregnancy outcomes. However, most analyses assessed exposure over the entire pregnancy or by trimester, potentially missing specific critical windows of vulnerability that recent statistical methods can identify. The objective of this study was to summarise studies examining critical windows of exposure to outdoor air pollution in relation to adverse pregnancy outcomes. This systematic review (PROSPERO-CRD42024523345) followed PRISMA recommendations using PubMed, Embase and CENTRAL databases. The search was performed on April 2024 and udpated on February 2025. Eligible studies analysed critical windows of association between air pollutants (PM2.5, PM10, NO₂, O₃) and the following outcomes: prematurity, low birth weight, intrahepatic cholestasis of pregnancy, gestational diabetes, pre-eclampsia, eclampsia, gestational hypertension and stillbirth. Two independent reviewers screened titles, abstracts and full texts. Results were synthesised narratively. Out of 3631 articles, 20 studies were included. All were conducted in China or the United States and relied almost exclusively on distributed lag models (DLM or DLNM). Heterogeneity was observed across pathologies and between studies addressing the same outcome. The most consistent finding concerned preterm birth, for which the end of the second trimester (weeks 17-28) was often identified as a critical window. No studies addressed intrahepatic cholestasis of pregnancy or stillbirth. Conclusions. The variability in results reflects distinct pathophysiological mechanisms, differences in exposure levels, or individual characteristics. Precisely identifying critical windows of environmental exposure during pregnancy appears essential to improve perinatal environmental prevention and guide public health action.

Background and Method: The overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cancer is correlated with accelerated tumor progression and an unfavorable clinical outcome. Since the introduction of trastuzumab in 2002, the treatment of HER2-positive breast cancer has been revolutionized, leading to significant improvements in survival. This retrospective, multicenter study aimed to describe the characteristics of patients with HER2-positive metastatic breast cancer (MBC) who maintained disease control for a minimum of three years after first-line therapy with trastuzumab and/or pertuzumab combined with chemotherapy. Results: Among 280 eligible patients, 48 (17.5%) were classified as long-term responders. The study population primarily consisted of women with a median age of 56.7 years at diagnosis; de novo metastatic presentation was observed in approximately 70% of cases. An objective response rate of nearly 90% was observed, with a median duration of response of 5.8 years. Median progression-free survival was 11.0 years [95% CI: 6.6—not reached], and median overall survival was not reached [95% CI: 10.9—not reached]. Furthermore, about 15% of patients were able to discontinue systemic therapy without immediate disease progression. Discussion and Conclusions: These findings indicate the potential of achieving prolonged disease control in a subset of patients with HER2-positive MBC, raising questions about therapeutic intensification and potential treatment discontinuation strategies. This study underscores the need for future research to identify predictive factors of durable response and assess the feasibility of adaptive treatment strategies, including planned treatment discontinuation.

Background and Aims: One of today's challenges in terms of understanding the real impact of the environment on pregnancy and its complications is the ability to work with real‐life data that are correctly and extensively connected to data on the contamination of living environments and individualized exposures. We present a solution based on a data infrastructure that is directly usable for research. We describe (i) the methodological characteristics of the infrastructure, (ii) the geographical territory and environmental exposures covered by the infrastructure, and (iii) the initial description of the real‐life health data of the included population. Methods: The infrastructure is a relational database that integrates routine obstetric care data from CHUB with individual environmental exposure data linked via home addresses. The infrastructure includes all deliveries at Besançon University Hospital (CHUB) from January 1, 2010, to December 31, 2021. Results: Our infrastructure included information on 20,376 women, 28,344 pregnancies, and 29,190 births. The infrastructure described includes 20% of deliveries in an administrative region of more than 1.5 million inhabitants. The quality of the data is linked to highly contrasted exposure of living areas within this region and temporal coverage of more than 10 years of obstetrical events. This infrastructure is a research tool with the capacity to incorporate data in the future. Conclusion: This infrastructure can be used to address a wide range of questions aimed at describing the phenomena of environmental exposure during pregnancy, multiple exposures and their cumulative effects, particularly the phenomena of mediation, interaction, or confusion.