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Safety and efficacy of neoadjuvant immunotherapy with durvalumab (MEDI 4736) in combination with neoadjuvant chemotherapy (gemcitabine/cisplatin or carboplatin) in patients with operable high-risk upper tract urothelial carcinoma.
No full textInternational audienceBackground: Most patients following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) face a poor prognosis. Combination of chemotherapy and immunotherapy in neoadjuvant setting have demonstrated survival improvement in several tumors. Additional systemic therapy in a neoadjuvant setting may prolong survival for UTUC patients, especially those after RNU who are ineligible to receive nephrotoxic chemotherapy. Methods: Phase 2 clinical trial (NCT04617756) was conducted in 10 French centers. Eligible patients had non metastatic, high-grade disease on ureteroscopic tumor biopsy or on urine cytology and infiltrative aspect of renal pelvis/ureteral wall on CT imaging. Subjects received a combination of: Durvalumab/Gemcitabine/Cisplatin (cohort 1) or Carboplatin (cohort 2) every 3 weeks for a total of 4 cycles based on glomerular filtration rate, prior to RNU. The primary objective was to assess the pathological complete response (ypT0) rate (pCR) of each combination. Results: A total of 50 patients were enrolledbetween 2021 and 2023 (31 in cohort 1 and 19 in cohort 2). Median age was 66 years old (range 38-79), 58% were males. 90% of patients (44) received 4 cycles of treatment, 3 patients 3 cycles and 2 patients received 2 cycles. Five patients switched for carboplatin during chemotherapy. We observed in cohort 1 : 20/31 (65%) patients with non infiltrative residual tumor; In cohort 2 : 9/19 (42%) patients (table). Secondary endpoint was safety, no immunotherapy-mediated AE was observed, 2 patients had Grade 3 neutropenia, 1 grade 4, 1 patient had grade 3 thrombopenia and 1 grade 3 anemia. Conclusions: Combination of durvalumab with platin-based chemotherapy, especially cisplatin, showed promising activity in UTUC, with the occurrence of complete responses and a high rate of non-infiltrative residual tumor. Safety profile was secure without increasing surgical risk. A randomized Phase 3 controlled study comparing neoadjuvant chemotherapy with chemotherapy combined with immunotherapy in patients with high-risk localized UTUC (iNDUCT-3) will open soon to validate these encouraging results. Clinical trial information: NCT04617756. Pathological response rate. ypT0 ypTIS /ypTa ypT1 ypT2 ypT3 ypT4 Missing data Withdrawal surgery Total Cis-Gem Durva 4 (13%) 5 (16%) 11 (36%) 1 (3%) 6 (19%) 1 (3%) 1 2 31 Carbo-Gem Durva 1 (5%) 6 (32%) 1 (5%) 3 (16%) 5 (26%) 1 (5%) 1 1 1
Vers une oncologie plus « verte » à l’heure du réchauffement climatique ?
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Evaluation of the Atmospheric Circulation of CMIP6 Models for Extreme Temperature Events Using Latent Dirichlet Allocation
No full textInternational audienceFor climate models to continue improving, we need to uncover as many discrepancies they have with reality as possible. In particular, evaluating the representation of extreme events is important but challenging owing to their rarity. Here, we study how general circulation models reproduce large-scale atmospheric circulation associated with extreme temperature events. To this end, we apply latent Dirichlet allocation (LDA), a dimensionality reduction method, to a set of sea level pressure ERA5 maps over the North Atlantic region. LDA provides a basis of sparse latent modes called u201cmotifsu201d that consist of localized objects at the synoptic scale. Any pressure map can be approximated by a generally sparse combination of motifs, whose coefficients are called the weights, containing local information about large-scale circulation. Weight statistics can be used to locally characterize circulation patterns, in general and during extreme events, allowing for detailed comparison of datasets. For four CMIP6 models and reanalyses, we quantify local circulation errors and identify model-agnostic and model-specific biases. On average, large-scale circulation is well predicted by all models, but model errors are increased for heat waves and cold spells. Significant errors were found to be associated with Mediterranean motifs for all models in all cases. In addition, the combination of motif and temperature error can discriminate between models in the general and cold spell cases, while models perform similarly on heat waves. The sparse characterization provided by the LDA analysis is, therefore, well suited for the model preselection for the study of extreme events
Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk : A Mendelian Randomization Study
No full textInternational audienceBackground : Differentiated thyroid carcinoma (DTC) is occurring three times more frequently in females than in males. However, the underlying biological mechanisms driving this discrepancy remain poorly understood. To investigate the causal role of sex hormones and reproductive factors in the risk of DTC, we implemented a two-sample Mendelian randomization (MR) analysis. Methods : We utilized genome-wide association studies (GWAS) summary statistics to explore these associations. GWAS data on DTC were derived from a meta-analysis of six studies including 7705 cases and 963,612 controls of European ancestry. GWAS summary statistics on sex hormones, reproductive factors, and gynecological conditions were retrieved from publicly available sources. We used the inverse-variance weighted (IVW) method to estimate odds ratio (OR), with additional sensitivity analyses and conducted multivariable MR (MVMR) to account for potential confounding by body mass index (BMI) and thyrotropin (TSH). Results : We identified a positive association between sex hormone binding globulin (SHBG) and DTC (ORivw = 1.13, p = 0.046). After controlling for TSH and BMI in a MVMR analysis, the strength of this association remained similar but lost statistical significance. Bioavailable testosterone also showed a positive but marginally significant association with DTC after adjustment for BMI in the MVMR (ORivw = 1.13, p = 0.07). Putative causal association was observed with uterine fibroids in females under 50 years old (ORivw = 1.52, p = 0.017). Endometrial cancer was associated with DTC (ORivw = 1.15, p = 9.0 × 10−3); however, a genetic correlation of r2 = 13% suggested potential pleiotropy. No significant associations were observed for other investigated factors. Conclusions : Our study does not provide strong evidence for a causal role of reproductive and hormonal factors in DTC risk, despite the observed sex disparity in incidence rates. The associations observed with SHBG, bioavailable testosterone, uterine fibroids, and endometrial cancer indicate potential risk factors, but further investigation is required
Sexe et genre dans la destructivité adolescente: l'intérêt d'une approche écosystémique
No full textInternational audienceRecent data show a significant increase in suicidal behavior among adolescent since the end of 2020. Preventive measures are being sought, but identifying risk factors goes beyond the scope of mental disorders and requires a more comprehensive approach.This implies studies from distinct scientific registers, ranging from the individual to the societal, and is difficult to grasp as a whole. How can these different levels of analysis be integrated to understand, prevent, and treat this increase in adolescent self-destructiveness?The aim of this study is to propose an ecosystemic analysis of the environment of adolescents hospitalized in psychiatry. Method:This is a case-control study of 425 adolescents aged 15.5 on average, from the u201cFamily and Careu201d study. It compares a group of patients with suicidal behavior (n = 197) to control patients, based on the following variables: family interactions (according to the At Risk Family Interactions and Levers scale, or ARFIL, which includes 30 items, 2 scores, and 3 dimensions), abuse, neglect, medical diagnoses, and socio-professional categories. With regard to suicidal behaviour, a group of adolescents with heteroaggressive behavior was also identified (n = 87) and compared based on the same variables. Results:The group of adolescents who had made one or more suicide attempts consisted of a large majority of girls (81.2%) from all socioeconomic backgrounds. The impact of sexual violence (35% of cases), compounded by a lack of family affiliation and borderline personality disorder, all contribute to suicidal behaviors. In boys, socioeconomic status, the accumulation of abuse and neglect, as well as a lack of containment, affiliation, and individuation, contribute, along with neurodevelopmental disorders, to heteroaggressive behaviors. Conclusion:The comprehensive approach to suicidal behavior, and its counterpart, heteroaggressive behavior, shows that it is possible to identify specific profiles at three levels: individual (micro), family (meso), and societal (macro). Behind this analysis, the fundamental needs of these young people emerge, and it is possible to address them at these different levels.Des données récentes montrent une forte augmentation des comportements suicidaires chez les adolescents depuis fin 2020. Des mesures préventives sont recherchées, mais l'identification des facteurs de risque dépasse le champ des troubles mentaux et demande une approche plus globale. Cela implique des études provenant de registres scientifiques distincts, allant de l'individu au sociétal, et difficiles à appréhender ensemble. Comment intégrer ces différents niveaux du2019analyse pour comprendre, prévenir et traiter cette augmentation de l'autodestruction adolescente ? L'objectif de cette étude est de proposer une analyse écosystémique de l'environnement d'adolescents hospitalisés en psychiatrie. Méthode: Il s'agit d'une étude cas-témoin de 425 adolescents de 15,5 ans en moyenne, issus de l'étude « Family and Care», qui compare un groupe de patients avec comportement suicidaire (n = 197) aux patients contrôles, selon les variables suivantes: interactions familiales (selon l'échelle At Risk Family Interactions and Levers scale ou ARFIL, qui se décline selon 30 items, 2 scores et 3 dimensions), abus, négligences, diagnostics médicaux et catégories socio-professionnelles. En regard des comportements suicidaires, un groupe d'adolescents avec hétéroagressivité est également identifié (n = 87) et comparé selon les mêmes variables. Résultats: Le groupe des adolescents ayant réalisé une ou plusieurs tentatives de suicide est composé d'une très large majorité de jeunes filles (81,2 %) de tous niveaux socio-économiques. L'impact des violences sexuelles (35 % des cas) renforcé par un manque d'affiliation familiale et par un trouble borderline concourent ensemble aux comportements suicidaires. Chez les garçons, le niveau socio-économique, le cumul de violences et de négligences, ainsi qu'un manque de contenance, d'affiliation et d'individuation, contribuent avec le trouble neurodéveloppemental à des comportements de type hétéroagressifs. Conclusion: L'approche globale des comportements suicidaires, et de leurs pendants, les comportements hétéroagressifs, montre qu'il est possible de discerner des profils spécifiques sur les trois niveaux, individuel (micro), familial (méso) et sociétal (macro). Derrière cette analyse apparaissent finalement les besoins fondamentaux de ces jeunes auquel il est possible de répondre à ces différents niveaux
Early toxicity of moderately hypofractionated radiation therapy in breast cancer patients receiving locoregional irradiation: First results of the UNICANCER HypoG-01 phase III trial
No full textInternational audiencePurpose: To investigate early adverse events (AEs) in HypoG-01, a randomised, controlled, multicentre, non-inferiority phase 3 trial comparing toxicity and efficacy of adjuvant loco-regional moderately hypofractionated radiation therapy versus 2 Gy daily radiation therapy. Methods: Women ≥ 18 years with T1-3 N0-3 M0 breast cancer were randomised 1:1 after surgery +/- systemic therapy to receive either 40 Gy/15 fractions (3-week-RT) or 50 Gy/25 fractions (5-week-RT) +/-tumour-bed boost. AEs at baseline, end of treatment, and 6-month follow-up were graded using CTCAEV4.0, LENT/SOMA and Harris 4-point scales. Competing risk analysis for cumulative incidence of AEs, worst grade dermatitis according to risk factors, and cosmetic assessment were performed in the intention-to-treat (ITT) population. Results: From September 2016 to March 2020, 29 sites enrolled 1265 women. The ITT population included 1260 patients (3-week-RT: 631, 5-week-RT: 629). The proportion of patients with maximum grade ≥ 2 AEs were 284 (45 %) in 3-week-RT and 326 (51.8 %) in 5-week-RT. Overall, 88 (7 %) grade 3, one grade 4 and no grade 5 AEs were observed. Reported AEs were mostly dermatitis, fatigue, and pain, numerically lower in 3-week-RT than 5-week-RT. Grade ≥ 2 dermatitis was more frequent in patients receiving a tumour-bed boost or with BMI > 30 but numerically less frequent with 3-week-RT than 5-week-RT even in those subgroups. Of the 552 patients with breast-conserving surgery who completed cosmetic evaluation at M6, 88.4 % had excellent to good cosmetic results with no imbalance between groups. Conclusion: Early AEs were mild and do not raise safety concerns for 3-week-RT in women receiving nodal RT
Voice Quality as Digital Biomarker in Bipolar Disorder : A Systematic Review
No full textInternational audienceBackground: Voice analysis has emerged as a potential biomarker for mood state detection and monitoring in bipolar disorder (BD). The systematic review aimed to summarize the evidence for voice analysis applications in BD, examining (1) the predictive validity of voice quality outcomes for mood state detection, and (2) the correlation between voice parameters and clinical symptom scales. Methods: A PubMed, Scopus, and Cochrane Library search was carried out by two investigators for publications investigating voice quality in BD according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Studies were assessed using the modified methodological index for non-randomized studies (MINORS). Results: Of the 400 identified publications, 16 studies met the inclusion accounting for 575 BD patients. Machine learning approaches were implemented in 87.5% of studies, with classification accuracies ranging from 70.9% to 96.9%. Manic state detection showed the strongest predictive validity [area under the curve (AUC) up to 0.89], while depression detection demonstrated moderate performance (AUC: 0.66-0.78). Individual-specific models outperformed population-level approaches (correlation coefficients: 0.78 versus 0.44). Voice quality showed significant correlations with standardized clinical scales, particularly Young Mania Rating Scale and Hamilton Depression Rating Scale (normalized root mean square errors: 1.985 and 3.945, respectively). Prosodic features were examined in 81.25% of studies, with pitch consistently elevated during manic episodes. MINORS varied from 10 to 14, with notable limitations in sample size calculations and blinding procedures. Conclusions: Voice quality is a promising biomarker in BD, particularly for manic state detection and individualized monitoring. While controlled settings showed strong performance, naturalistic applications yielded more modest results. Future research should focus on standardizing protocols across different environments and conducting large-scale longitudinal studies with robust methodological controls
La coopération sans coopérative : la gestion des tensions au sein d’une organisation alternative d’inspiration anarchiste
No full textFNEGE 3International audienceThrough the study of self-managed grocery stores inspired by anarchist philosophy, we illustrate how tensions inherent to the alternative cooperative model manifest and are understood by the members of these organizations.To achieve this, we rely on a set of qualitative data. The results of the study highlight two specificities derived from anarchist philosophy—freedom and individual responsibility on the one hand, and autonomist leadership on the other—that enable actors to activate the three modes of tension resolution identified in the literature: acceptance, confrontation, and transcendence (Smith, 2011), in an original way. These results highlight ways to better manage tensions and avoid coalition dynamics that are present in most cooperatives.À travers l’étude d’épiceries autogérées s’inscrivant dans la philosophie anarchiste, nous montrons comment les tensions inhérentes au modèle alternatif des coopératives se manifestent et sont appréhendées par les membres de ces organisations. Pour y parvenir, nous nous appuyons sur un ensemble de données qualitatives. Nous constatons que deux spécificités émanant de la philosophie anarchiste – la liberté et responsabilité individuelle d’une part et le leadership autonomiste d’autre part – permettent aux acteurs d’actionner de manière originale les trois modes de gestion des tensions identifiées dans la littérature que sont : l’acceptation, la confrontation et la transcendance (Smith, 2011). Ces résultats mettent en lumière des pistes pour mieux gérer les tensions et éviter les logiques de coalitions qui se forment souvent au sein des coopératives
François Vidron (1916-1970) : la figure complexe et méconnue d'un expert forestier-cynégéticien et protecteur de la nature
No full textNational audienceHomme des trois républiques françaises et du régime de Vichy, François Vidron est à la fois forestier et chasseur, éleveur de faisan et protecteur de cerfs. Ingénieur des Eaux et Forêts (IGREF) de formation, il est plus largement un homme-carrefour dont le parcours renseigne sur un chapitre entier de l’histoire de l’environnement en France et plus encore sur une certaine gestion nationale et républicaine de la nature « à la française ». Né le 8 février 1899 à Fontainebleau et mort en 1985 en région parisienne, il commence sa formation dans l’Est de la France en pleine Première Guerre mondiale, puis rejoint l’Île-de-France où il a une carrière professionnelle importante que l’on peut expliquer par son passage et même sa « rencontre » avec Rambouillet. Cet article étudie le parcours complexe et méconnu de ce forestier dans les plus hautes fonctions de l'administration des Eaux et Forêts et de la chasse française
Artificial intelligence and infertility surgery
No full textInternational audienceRecent years have seen the growing integration of artificial intelligence (AI) into infertility surgery for both men and women. In andrology, AI optimises the selection of candidates for varicocele surgery, predicts the chances of success of testicular biopsies and automates sperm detection, improving accuracy and speed. In gynaecology, it personalises surgical indications (myomectomy, tubal surgery, endometriosis), assists robotic surgery through anatomical segmentation and image fusion, and promotes training through intelligent simulators. Benefits include better preoperative planning, real-time intraoperative guidance and postoperative analysis to anticipate complications and adapt follow-up care. Prospects are emerging for ‘learning’ and partially automated surgery, with personalised care thanks to predictive models and big data analysis. However, obstacles remain: data heterogeneity, high costs, the need for specialised training, and ethical and regulatory issues. AI appears to be a promising lever for more accurate, safer and more individualised reproductive medicine, provided that its adoption is regulated and well thought out