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The purpose was to describe first and subsequent relapses in patients from the OS2006/Sarcome-09 trial, to help future trial design. We prospectively collected and analysed relapse data of all French patients included in the OS2006/Sarcome-09 trial, who had achieved a first complete remission. 157 patients experienced a first relapse. The median interval from diagnosis to relapse was 1.7 year (range 0.5–7.6). The first relapse was metastatic in 83% of patients, and disease was not measurable according to RECIST 1.1 criteria in 23%. Treatment consisted in systemic therapy (74%) and surgical resection (68%). A quarter of the patients were accrued in a phase-II clinical trial. A second complete remission was obtained for 79 patients. Most of them had undergone surgery (76/79). The 3-year progression-free and overall survival rates were 21% and 37%, respectively. In patients who achieved CR2, the 3y-PFS and OS rates were 39% and 62% respectively. Individual correlation between subsequent PFS durations was poor. For osteosarcoma relapses, we recommend randomised phase-II trials, open to patients from all age categories (children, adolescents, adults), not limited to patients with measurable disease (but stratified according to disease status), with PFS as primary endpoint, response rate and surgical CR as secondary endpoints.

Background. Morbidity and mortality are higher among human immunodeficiency virus (HIV) exposed but uninfected (HEU) infants than unexposed infants, particularly if the mother had a low CD4 count. We investigated the possible association between maternal immune depression during pregnancy and the risk of infection in HEU infants in the national French Perinatal Cohort (EPF). Methods. All neonates, born alive, to HIV-1–infected women enrolled in the EPF between 2002 and 2010 were included. The primary outcome was the first serious (hospitalization or death) infection during the first year of life. The main exposure variable was maternal CD4 cell count near delivery. The Kaplan–Meier method and multivariate Cox models were applied, with the different types of infections managed as competing events. Results. Among 7638 HEU neonates, 699 had at least 1 serious infection (of which 159 were bacterial) with a Kaplan–Meier probability of 9.3% (95% confidence interval, 8.7–10.0) at 1 year. The risk of serious bacterial infection during the first year of life significantly increased with lower maternal CD4 cell count, before and after adjustment for maternal CD4 cell count <350 and 350–499 CD4/mm 3 (adjusted hazard ratio = 1.7 [1.2–2.6] and 1.2 [0.8–1.9], respectively; P = .03). This association mainly concerned infections involving encapsulated bacteria (P = .03). The risk of serious viral infection was, by contrast, independent of the mother's CD4 cell count. Conclusions. Maternal CD4 count is significantly and specifically associated with the risk of serious infections with encapsulated bacteria in HEU infants.

Temperature‐sensitive Transient Receptor Potential (TRP) channels contribute to modulating skin vascular tone. Their role in Raynaud's Phenomenon (RP) remains unknown. We aimed to investigate TRPs expression in the skin, along with microvascular reactivity to cooling in patients with primary and secondary RP, compared with healthy subjects. Skin blood flow was measured in 10 regions of interest on the dorsum of the hand before, during, and after a 30‐min cooling at 8°C. Skin biopsies were performed from a subset of participants at the distal phalanx before and after cooling. RNAs were extracted, sequenced, and TRPs mRNA expression quantified. TRPs mRNA were successfully quantified, but no significant differences in their expression were observed between groups, or in response to cooling. There was a decreased perfusion at the distal phalanx over time, in secondary RP compared with primary RP (adjusted p = 0.03) or healthy subjects (adjusted p = 0.042). Gene expression profiles were more similar between primary RP and healthy subjects than with secondary RP. This study shows an impairment of microvascular reactivity to cold in secondary, but not in primary RP. Transcriptomic data suggest involvement of the NO pathway in secondary RP, while TRP channel expression appears unchanged; however, their function could be impaired, which should be further investigated.

The late effects of treatments for childhood cancers may lead to severe and multiple health conditions requiring hospitalisation. We aimed to estimate the hospitalisation rate among childhood cancer survivors (CCS) in France, to compare them with the general population and to investigate the associated factors. We matched total of 5439 5-year solid CCS diagnosed before the age of 21 between 1945 and 2000 by sex, birth year and region of residence to 386,073 individuals of the French general population. After linkage with the national hospital discharge database, we estimated the relative hospitalisation rate (RHR), the absolute excess risks (AERs) and the relative bed-day ratio (RBDR) during 2006–2018. We used generalised linear models to estimate associations between hospitalisation and survivor characteristics. Overall, the RHR was 2.49 (95% confidence interval [CI] 2.46–2.52) and the RBDR was 3.49 (95% CI 3.46–3.51). We found that neoplasm-related hospitalisations had the highest AER (105.8 per 1000 person-years), followed by genitourinary system diseases (34.4 per 1000 person-years) and cardiovascular diseases (19.2 per 1000 person-years). In adjusted analysis, CCS treated with chemotherapy (risk ratio [RR] 1.62, 95% CI 1.53–1.70), radiotherapy (RR 2.11, 95% CI 1.99–2.24) or both (RR 2.59, 95% CI 2.46–2.73) had a higher risk of hospitalisation than the ones who had not received any of these treatments. CCS treated during the past decades by chemotherapy and/or radiotherapy now had a higher hospitalisation risk for all main categories of diagnosis than the general population. Prevention strategies and medical surveillance programmes may promote a long-term decrease in the hospitalisation rate among CSS.

BackgroundWe aimed to study adherence to cardiac screening in long-term childhood cancer survivors (CCS) at high risk of cardiomyopathy.MethodsThis study involved 976 5-year CCS at high risk for cardiomyopathy from the French Childhood Cancer Survivor Study. Determinants of adherence to recommended surveillance were studied using multivariable logistic regression models. Association of attendance to a long-term follow-up (LTFU) visit with completion of an echocardiogram was estimated using a Cox regression model.ResultsAmong participants, 32% had an echocardiogram within the 5 previous years. Males (adjusted RR [aRR] 0.71, 95% CI 0.58–0.86), survivors aged 36–49 (aRR 0.79, 95% CI 0.64–0.98), Neuroblastoma (aRR 0.53, 95% CI 0.30–0.91) and CNS tumour survivors (aRR 0.43, 95% CI 0.21–0.89) were less likely to adhere to recommended surveillance. Attendance to an LTFU visit was associated with completion of an echocardiogram in patients who were not previously adherent to recommendations (HR 8.20, 95% CI 5.64–11.93).ConclusionsThe majority of long-term survivors at high risk of cardiomyopathy did not adhere to the recommended surveillance. Attendance to an LTFU visit greatly enhanced the completion of echocardiograms, but further interventions need to be developed to reach more survivors.

This study aimed to define the potential role of circulating tumor DNA (ctDNA) in children, adolescents, and young adults (CAYA) with classical Hodgkin lymphoma (cHL). This prospective trial was conducted in France between 2019 and 2023 and recruited CAYA patients (≤25 years old) with a new diagnosis of cHL. Patients were treated according to the EuroNet‐PHL‐C2 trial (EudraCT: 2012‐004053‐88), and plasma ctDNA evaluations were performed at diagnosis, after two cycles of chemotherapy, and in case of relapse. Two hundred and seventy‐five patients were included. Median age at diagnosis was 15 years (range 2–22), and 47% of the patients were treated as advanced stages (treatment level 3 [TL‐3]). Using an 18‐gene amplicon‐based next‐generation sequencing (NGS) targeted panel encompassing the most frequently mutated genes in cHL, at least one mutation was detected in 236/275 patients (86%). B‐symptoms, erythrocyte sedimentation rate, and advanced stages were significantly associated with the level of ctDNA at diagnosis. TP53 mutations (19/275, 7%) were strongly associated with inadequate response at early response assessment. XPO1 and IGLL5 mutations were associated with a higher risk of relapse. The presence of detectable ctDNA after two cycles of chemotherapy (10%) was a strong and independent prognostic marker of relapse.

Cette recherche soulève la problématique de la perception par les auditeurs légaux et les vérificateurs sociétaux, des mutations - en cours et souhaitables - de leurs missions, de leurs compétences et de leurs méthodes, destinées à préserver ou à renforcer leur statut de tiers de confiance au service de l'entreprise. Elle mobilise une méthodologie qualitative à la fois exploratoire et originale, basée sur un sondage et sur des entretiens semi-directifs. Elle révèle la diversité des facteurs qui viennent modifier les conditions d'exercice des métiers du chiffre. Ces facteurs sont de nature institutionnelle (le foisonnement réglementaire et normatif, le relèvement des seuils d'audit obligatoire), technologique (l'émergence de l'IA et de la blockchain) et organisationnelle (la multiplication des contrôles, audits et vérifications internes et externes à l'entreprise).