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Impact of lymph node staging on survival in presumed early-stage ovarian cancer: a multicentric retrospective study
No full textInternational audienceObjective:This study aimed to assess the impact of comprehensive staging on survival outcomes in this population.Methods:Patients who underwent surgery for epithelial ovarian cancer in one of the 14 Francogyn cancer centers between 2000 and 2020 were included in the study. The primary analysis evaluated the impact of lymphadenectomy on overall survival and recurrence-free survival. Lymph node count was analyzed as a continuous variable, and its association with survival, considered as a continuous outcome was assessed using linear regression (secondary analysis). Survival was compared using the log-rank test, and multivariate analysis was performed using a Cox model.Results:A total of 467 patients with presumed early-stage epithelial ovarian cancer were included, of which 198 underwent complete lymphadenectomy and 266 did not. No significant association was found between lymph node staging and survival in the primary analysis, possibly due to limited statistical power and a selection bias, as patients without lymphadenectomy had more favorable disease profiles (p=0.600 and p=0.700, respectively). Complete lymphadenectomy was associated with a significantly higher risk of complications (34.5% vs. 14%, p<0.001). In secondary analysis, the number of para-aortic lymph nodes harvested was identified as an independent predictor of both overall survival and recurrence-free survival (p=0.007 and p=0.002, respectively). Histological characteristics and adjuvant chemotherapy also showed a significant correlation with improved survival outcomes.Conclusion:Extensive para-aortic lymphadenectomy in early-stage epithelial ovarian cancer is associated with better overall and recurrence-free survival but comes with an increased risk of complications
Three- to 8-year old children do not favor male power when allocating resources
No full textInternational audienceAbstract From an early age, children perceive power imbalances between genders, but their attitudes toward gendered power remain largely unexplored. We studied this issue using a resource allocation task with 653 French children aged 3–8 (50.15% girls) recruited between 2022 and 2023. Participants were exposed to a dyadic power interaction and had to distribute more resources to either the dominant or the subordinate character. We tested three hypotheses: H1 predicted a male dominance bias; H2 predicted own-gender favoritism; and H3 predicted sensitivity to hierarchical status only. Contrary to H1, no pro-male bias was found. Results supported H3: younger children favored dominant characters, while older children favored subordinates. H2 was partially supported, showing own-gender bias, stronger in girls, without overriding sensitivity to status
Antidote administration in mice exposed to sarin resulted in brainwave stabilization without cognitive protection: Partial neuroprotective effects of antidote in mice exposed to sarin
No full textInternational audienceResurgence of sarin use in the Syrian conflict demonstrates that chemical weapons are a vivid threat. Like other organophosphate compounds, sarin inhibits acetylcholinesterase resulting in cholinergic crisis. The current antidote therapy includes atropine (a muscarinic cholinergic antagonist) + an oxime (e.g., pralidoxime) to reactivate the inhibited cholinesterases. Long-term sequelae reported in victims of the 1995 Tokyo subway sarin attack emphasize the need to improve neuroprotection and to delineate more precise biomarkers of intoxication severity. Previously, we proposed that brain oscillations could indicate exposure severity to a sublethal dose of a neurotoxic agent. In the present study, we evaluated the effects of atropine + pralidoxime in mice exposed to a sublethal dose of sarin (0.9 LD 50 ) on changes in short-term recovery, brainwaves and behavioral patterns. We demonstrated the benefits of the antidotes on alleviation of the sarin-induced encephalopathy, stabilization of brain oscillations, and attenuation of anhedonia behavior. Nevertheless, mice exhibited work memory impairments associated with the disruption of theta oscillations during the task, the disruption of sleep architecture and the anxiety-like behavior when exposed to the non-convulsive sarin dose. These outcomes were not mitigated by atropine + pralidoxime administration. Our findings suggest that the currently recommended antidote for sarin poisoning provides only partial neuroprotection. Despite stabilizing brain waves in resting state, current antidote is not effective in preventing long-term neurobehavioral complication
Impact of Cardiac Resynchronization Therapy in Patients With Left Ventricular Assist Devices: A Systematic Review and Meta-analysis
No full textInternational audienceBackground:Many patients with left ventricular assist devices (LVADs) have cardiac resynchronization therapy (CRT). However, the impact of CRT on their clinical and hemodynamic outcomes remains unclear.Methods:We conducted a systematic review and meta-analysis to evaluate CRT's impact on survival in LVAD patients. We searched PUBMED, EMBASE, and Cochrane databases from inception through April 30, 2025, for studies reporting outcomes in LVAD patients with CRT. The primary outcome was all-cause mortality in patients with versus without CRT. Secondary clinical outcomes included ventricular arrhythmias (VAs) and shocks delivered. Hemodynamic outcomes included heart rate, right atrial pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, thermodilution cardiac output, pulmonary artery saturation, right ventricular stroke work index, and left ventricular end-diastolic diameter.Results:13 studies including 3,665 patients were analyzed. CRT did not demonstrate any significant survival benefit, whether comparing CRT-D versus ICD (OR 1.12 [0.85–1.48]), CRT on versus CRT off (OR 1.48 [0.87–2.53]), CRT versus no device (OR 0.99 [0.61–1.59]), or CRT versus no device or ICD (OR 1.00 [0.16–6.31]). Similarly, none of the tested comparisons showed significant differences in VAs incidence or shock rates. Biventricular pacing demonstrated no advantage for any hemodynamic outcomes, whether compared to right ventricular pacing or intrinsic rhythm.Conclusion:In this meta-analysis, CRT was not associated with overall survival benefit in LVAD recipients, nor with hemodynamic improvement. Future randomized trials may be warranted to definitively establish CRT's value in this population and refine patient selection criteria for optimal outcomes
Characterization of soaked soft porous materials under cyclic compression for eX-Poro-HydroDynamic lubrication
No full textInternational audienceeX-Poro-HydroDynamic (XPHD) lubrication is an innovative method in which soaked soft porous materials are used to store and provide lubricant to moving surfaces. Storing the fluid in the pores of the porous media eliminates the need for an external source of lubricant, thus making this approach environmentally friendly and enabling the use of lubricants such as water or other environmentally friendly lubricants. This study aims to carry out experimental and numerical characterizations of the mechanism of dynamic re-imbibition of porous materials. An experimental device is developed to cyclically compress an open-pore foam soaked in water at different frequencies. The experimental results show a direct link between the variation in the normal force, the appearance of air inside the imbibed foam, and the frequency of stress. These parameters influence the ability of the foam to re-soak in the decompression phase, and hence control the maximum normal load that can be generated in the contact. A numerical model based on the Darcy model is also developed, which takes into account the phenomenon of film rupture. The use of a numerical model is made possible by the preceding experimental determination of the water permeability of the foam. Initial comparisons with experimental results show good similarity
Stiffness-sensitive gene regulation in human mesenchymal stem cells: Modelling mechanotransduction to predict mineralization and bone protein expression
No full textInternational audienceThe goal of our study was to establish how a specific part of the bone Gene Regulatory Network (GRN) controls mineralization in response to stiffness. We hypothesized that a system of differential equations model stiffness-sensitive gene regulation in human mesenchymal stem cells through the epistatic genetic interactions between stiffness (e.g. WNT-β catenin pathway) and five of the main transcription factors and bone proteins (e.g. RUNX2, BSP, OSX, OC, and OPN). To test this hypothesis, we (i) performed in-vitro experiments culturing bone cells on different stiffness, (i) adapted our previously published model from being continuously time-dependent to continuously stiffness-sensitive, and (iii) simulated protein production in function of stiffness and other protein production from the best estimate of parameters coming from the experimental work. Our experimental findings reveal a non-parametric relationship between stiffness and RUNX2 production, with no discernible linear trends for other proteins. Modeling results demonstrate that continuous variations in stiffness enable simulation of bone GRN gene expression, fitting our novel experimental dataset. Specifically, our computational results indicate that OPN production peaks at low stiffness (8 kPa), while RUNX2, OSX, and OC achieve maximum production at higher stiffness levels (64 kPa). This alignment underscores the model's capacity to replicate experimental data accurately. Additionally, our approach predicts that WNT-β-catenin activation serves as an enhancer for OPN and BSP production. The model also highlights a negative feedback-like interaction between OC and BSP production. Stiffness variations were shown to have a significant impact on OC and BSP production and a moderate effect on OPN production. By employing a stiffness-sensitive gene regulation model, we provide insights into one of the mineralization patterns through the prediction of bone protein expression dynamics
Dose- and genotype-dependent cardiac arrhythmia and sudden death in rats following microdystrophin gene therapy
No full textInternational audienceRecombinant adeno-associated virus (rAAV) vectors encoding microdystrophin (MD) are a promising treatment for Duchenne muscular dystrophy (DMD). GNT0004, an rAAV2/8 vector expressing MD1, is currently being tested in patients with DMD. Here, we explored supra-optimal intravenous doses of GNT0004 (2.1 × 1014 and 4.2 × 1014 vg/kg, up to 14 times the therapeutic dose) in wild-type (WT) and DMDmdx rats. In all cohorts, robust MD1 protein expression was observed. In DMD animals, creatine kinase levels were normalized, and skeletal muscle and heart histology and functions were improved. However, unexpected sudden deaths occurred at the highest dose. In WT animals, deaths were observed at both doses and were associated with increased arrhythmic events, which may promote structural and functional heart issues. Immunohistological analysis suggested that overexpression of MD1 may disrupt the dystrophin-associated protein complex, increasing the risk of arrhythmias and sudden death. In DMDmdx rats, the 2.1 × 1014 vg/kg dose was well tolerated, but some deaths occurred at 4.2 × 1014 vg/kg, for which a causal link to GNT0004 cannot be excluded. At this dose, increased arrhythmic risk and cardiac pathological remodeling were observed. These observations highlight the potential risk of MD overexpression in the heart and suggest a need for careful monitoring of patients with DMD treated with gene therapy
Restricted mean survival time in cluster randomized trials with a small number of clusters: Improving variance estimation of the intervention effect from the pseudo-values regression
No full textInternational audienceIn randomized clinical trials with a time-to-event outcome, the intervention effect could be quantified by a difference in restricted mean survival time (ΔRMST) between the intervention and control groups, defined as the expected survival duration gain due to the intervention over a fixed follow-up period. In cluster randomized trials (CRTs), social units are randomized to intervention or control groups; the correlation between survival times of the individuals within the same cluster must be taken into account in the statistical analysis. In a previous work, we proposed the use of pseudo-values regression, based on generalized estimating equations (GEEs), for estimating ΔRMST in CRTs. We showed that this method correctly estimated the ΔRMST and controlled the type I error rate in CRTs with at least 50 clusters. Here, we propose methods for CRTs with a small number of clusters (≤50). We evaluated the performance of four bias-corrections of the GEE sandwich variance estimator of the intervention effect. We also considered the use of a Student t distribution as an alternative to the normal distribution of the GEE Wald test statistic for testing the intervention effect and constructing the confidence interval. With a simulation study, assuming proportional or non-proportional hazards, we showed that the Student t distribution outperformed the normal distribution in terms of type I error rate, and the Fay and Graubard bias-corrected variance led to an appropriate type I error rate whatever the number of clusters. Therefore, we recommend the use of the Fay and Graubard variance estimator combined with a Student t distribution for the pseudo-values regression to correctly estimate the variance of the intervention effect. Finally, we provide an illustrative analysis of the DEMETER trial evaluating the use of a specific endotracheal tube for subglottic secretion drainage to prevent ventilator-associated pneumonia, by comparing each of the methods considered
Who are the healthcare professionals involved in interprofessional team meetings in French multidisciplinary primary care centres? A quantitative analysis of eight centres
No full textInternational audienceBACKGROUND: Interprofessional collaboration is crucial for providing high-quality care to patients with complex conditions in primary care. In France, multidisciplinary primary care centres (MPCC) receive funding if they organise at least 6 interprofessional team meetings (ITM) per year to discuss complex patient situations and collectively define care strategies. It remains unclear how ITM have been implemented in France. This study analyses healthcare professionals’ involvement in ITMs within MPCCs. METHOD: A multicenter retrospective quantitative study in 8 French MPCCs based on the analysis of ITM reports for the period from 2018 to 2019 was conducted. RESULTS: 1733 patients’situations (n = 1733 cases) discussed during ITMs were analysed. The 8 MPCCs were heterogeneous in terms of geographical location, creation date, and size (3 MPCCs with > 20,000 patients followed by more than 60 professionals and 3 MPCCs with < 20 professionals). On average, five healthcare professionals attended each ITM, with huge variations among MPCCs. The nurse-general practitioner (GP) pair was central. At least one GP was present at 89% (n = 1469) and nurses at 38.15% (n = 630) of ITMs. Participation of other professionals was less frequent and varied according to the MPCC. Physiotherapists were present at 7.8% of ITMs, and other healthcare professionals were present at < 6% of ITMs, including pharmacists (3% of ITMs). In some cases, healthcare professionals external to MPCC, particularly those related to mental health, were also involved in ITMs. CONCLUSIONS: Depending on the MPCC, the professionals involved in ITM vary widely, with the nurse-GP pair at the centre. The relative absence of certain professionals needs to be analysed in order to encourage interprofessional working. TRIAL REGISTRATION: Not applicable
Continuous Infusion of Aztreonam–Avibactam After High Loading Dose for an Infection Caused by an OXA-48- and NDM-1-Co-producing ST147 Klebsiella pneumoniae
No full textInternational audienceIntroduction: Infections caused by metallo-β-lactamase-producing Enterobacterales offer limited therapeutic options. Aztreonam-avibactam (ATM-AVI) provides a promising alternative, but its approved intermittent regimen is complex and can lead to substantial drug waste.Methods: We describe a case of mastoiditis with a retrotympanic abscess due to OXA-48- and NDM-1-producing Klebsiella pneumoniae, managed with continuous infusion (CI) of ATM-AVI after a full-vial loading dose, supported by therapeutic drug monitoring (TDM) and whole-genome sequencing (EPISEQ CS V2.0, bioMérieux).Results: A 35-year-old man previously treated abroad for meningitis and brain abscesses presented with residual deep-seated infection caused by OXA-48- and NDM-1-producing K. pneumoniae. After initial treatment with ceftazidime-avibactam plus aztreonam, therapy was switched to ATM-AVI using a full-vial loading dose followed by CI. TDM demonstrated sustained plasma levels of both drugs, and the patient improved without adverse events.Conclusion: CI of ATM-AVI following a high loading dose was feasible, safe, and allowed optimized pharmacokinetic/pharmacodynamic (PK/PD) exposure while preventing drug wastage. Larger studies are warranted to determine the clinical utility of CI ATM-AVI across different MIC ranges