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Facteurs prédictifs d’une résection hystéroscopique des fibromes sous-muqueux en deux temps. Étude rétrospective unicentrique
No full textInternational audienceBackground: While thrombectomy benefits patients with large infarcts, it is unclear whether this benefit persists across different levels of reperfusion. Aims: This study investigates how the degree of reperfusion influences the effectiveness of endovascular thrombectomy (EVT) combined with best medical treatment (BMT), compared to BMT alone, in patients with large infarcts. Methods: This post hoc analysis of the TENSION trial, a randomized controlled study, assessed EVT versus BMT in patients with extensive infarction (Alberta Stroke Program Early CT Score (ASPECTS) 3–5). Primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included infarct volume at 24 h, mortality, and symptomatic hemorrhage. Outcomes were stratified by final reperfusion level, measured with the modified thrombolysis in cerebral infarction (mTICI) scale. Confounder-adjusted common odds ratios (cORs) and average treatment effects (ATEs) were estimated using inverse probability weighting with regression adjustment. Results: A total of 246 patients (median age, 74 years (interquartile range (IQR), 65–80); median baseline ASPECTS, 4 (IQR, 3–5)) were included. Compared to BMT alone, unsuccessful EVT (mTICI ⩽ 2a) was not associated with worse functional outcomes (cOR:1.2, 95% CI, 0.95 to 1.52; p = 0.131), higher mortality (ATE: –11.6%; 95% CI, –28.82 to 5.61; p = 0.187), or larger infarct volumes on follow-up (ATE:0.99 mL; 95% CI, –45.30 to 45.32; p = 0.965). First-pass complete reperfusion (mTICI 3) showed the greatest treatment benefit, significantly improving all endpoints, with a cOR of 4.85 (95% CI, 3.74–6.31; p < 0.001) for improved mRS scores and a 29% absolute reduction in mortality. Conclusion: In this post hoc analysis of the TENSION trial, unsuccessful EVT did not worsen outcomes compared to BMT alone. The highest benefit of EVT occurred with first-pass complete reperfusion, emphasizing the importance of achieving optimal reperfusion in this vulnerable stroke subgroup. These findings do not justify general treatment recommendations
Totum‐448 Improves MASLD and Modulates Microbiota in Hamsters: Dose–Response Study and Effects of Supplementation Cessation
No full textInternational audienceABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a global condition linked to obesity. Totum‐448, a polyphenol‐rich blend of five plant extracts and choline, was developed to target MASLD progression. This study evaluated the dose‐dependent effects of Totum‐448 and their sustainability after supplementation cessation on MASLD features and cecal microbiota. Male hamsters were fed a normal diet, a Western diet (WD), or WD supplemented with Totum‐448 (3.5% or 5% w/w) for 12 weeks (dose–response study). A parallel 18‐week on/off study included 12 weeks of Totum‐448 (5% w/w) followed by a 6‐week cessation period. Totum‐448 dose‐dependently reduced hepatic and circulating triglycerides, total cholesterol, and free fatty acids, independently of any changes in body composition. Gene markers of liver inflammation ( Tgfb1 , Il1b, Ccl2 , Il6 ) and fibrosis ( Col3a1, Vcam ) were downregulated with the highest dose of Totum‐448 only. Supplementation cessation led to a gradual rebound in serum and liver lipid levels and in relative expression of gene markers of hepatic inflammation and fibrosis, resulting in the loss of the majority of the benefits conferred by Totum‐448, although partial effects on hepatic steatosis and hepatocyte ballooning were maintained. Cecal microbiota analysis revealed modulation of the relative abundance of Acetatifactor , Alloprevotella , Lactobacillus , and Lawsonibacter , with identified correlations with certain metabolic outcomes. In conclusion, Totum‐448 demonstrated dose‐dependent improvements in key MASLD features in WD‐fed hamsters which gradually diminished after supplementation stopped. These findings underscore its therapeutic potential in MASLD management. The correlations with microbiota changes suggest a possible gut–liver axis role in its effects
What enhancement could β-titanium bring to oral implantology?
No full textInternational audienceObjectives: Titanium and its alloys are widely used in medicine, particularly in dentistry, due to their excellent biocompatibility and mechanical properties. However, limitations associated with commercially pure Titanium (cp-Ti) grade IV and conventional alloys such as Ti-6Al-4V require the development of alternative materials. This short review aims to highlight the potential of β-phase Titanium alloys as next-generation materials for oral implantology. Methods: This review is based on ISO standards and clinical requirements related to dental biomaterials, with a particular focus regarding mechanical properties and biocompatibility. Literature research, was conducted targeting studies on both the mechanical and biological performance of Titanium-based materials, with emphasis on β-phase Titanium alloys. Results: Cp-Ti grade IV remains the most commonly used Titanium for dental implants due to its long-standing clinical use, however, it exhibits some limitations, including a high elastic modulus and limited wear resistance. Ti-6Al-4V provides enhanced mechanical strength but raises biocompatibility concerns due to potential Aluminium and Vanadium ion release. β-phase Titanium alloys, with their body-centered cubic structure, demonstrate reduced elastic modulus closer to that of bone, enhanced mechanical strength and improved corrosion resistance, making them promising candidates for dental implants applications. Conclusion: β-phase Titanium alloys present significant potential to overcome the limitations of current Titanium materials used in oral implantology. Their favorable biomechanical behavior and the absence of released toxic elements, suggest improved implant performance and longevity. Nonetheless, rigorous in vitro and in vivo investigations are essential to confirm their safety, biocompatibility, and long-term clinical outcome before widespread clinical adoption
Long-term evolution of retinal atrophy after focal laser photocoagulation of telangiectatic capillaries: LyoMAC3 study
No full textInternational audienceObjective To assess the evolution of retinal atrophy secondary to focal laser photocoagulation (FLP) for telangiectatic capillaries (TelCaps) in patients with diabetic macular oedema (DMO) or macular oedema secondary to retinal vein occlusion (MERVO).Methods A multicentre retrospective study was conducted in DMO or MERVO patients who underwent at least one FLP session for TelCaps followed for 36 months after FLP. The post-FLP horizontal diameter and surface area of atrophic scars were measured by Optical Coherence Tomography (OCT) and on the OCT infrared image, respectively. The degree of atrophy was quantified on the OCT B-scan.ResultsSixty-nine eyes of 61 patients were included, corresponding to 86 laser scars analysed. The mean scar diameter increased from 315 ± 162 µm at month 1 (M1) to 350 ± 167 µm at M36 (mean increase: 35 µm, p < 0.001). The mean scar area increased from 0.10 ± 0.09 mm2 at M1 to 0.13 ± 0.10 mm2 at M36 (mean increase: 0.03 mm2, p < 0.01) At M1, 2 (2.6%), 74 (96%) and 1 (1.3%) scars were respectively considered “complete Outer Retinal Atrophy” (c-ORA), “incomplete Retinal pigment epithelium and Outer Retinal Atrophy” (i-RORA) and “complete Retinal pigment epithelium and Outer Retinal Atrophy” (c-RORA). At M36, 1 (1.8%), 40 (72.7%) and 14 (25.4%) scars were respectively considered c-ORA, i-RORA and c-RORA.Conclusion The size of retinal atrophy secondary to FLP for TelCaps increases significantly over time. Moreover, retinal atrophy undergoes phenotypic changes. Therefore, it seems imperative to respect a laser impact-free perifoveolar safety zone
Multidimensional tumor-blood profiling uncovers systemic lymphocyte-monocyte imbalance in pituitary neuroendocrine tumors
No full textInternational audienceAbstract Pituitary neuroendocrine tumors (PitNETs) are pathologically characterized by dysregulation of neuroendocrine function and systemic disruption of hormonal homeostasis, yet their regulatory effects on peripheral immune networks remain poorly characterized. Here, we systematically analyzed bulk RNA sequencing (RNA‑seq) from 883 PitNET tumors, 108 PitNET‑associated peripheral blood mononuclear cells (PBMC) samples, and 175 healthy PBMC controls, combined with 69 single‑cell RNA sequencing (scRNA-seq) samples covering tumors, normal pituitaries, as well as tumor‑derived and normal PBMCs. We identified a systemic immune disequilibrium in PitNET patients, characterized by increased circulating lymphocyte proportions, accompanied by upregulated cytokine-receptor interaction signatures. Notably, tumor resection reversed this imbalance, as supported by the normalization of monocyte and neutrophil counts, validated by flow cytometry and routine blood data from 600 samples (200 healthy controls and 200 PitNET patients with paired pre- and post-surgery follow‑up). Trajectory analysis identified terminally differentiated, secretory-specialized cell populations with lineage-specific hormone and cytokine hypersecretion. Ligand-receptor inference suggested these tumor-derived factors potentially engage circulating immune cell receptors. A random‑forest classifier based on PBMC transcriptomes distinguished PitNET subtypes, underscoring the diagnostic potential of peripheral immune signatures. Furthermore, in an estrogen-induced rat model, elevated PRL level coincided with the same peripheral immune skewing. Overall, our work provides a valuable resource and demonstrates PitNETs can be systemic immune modulators, where intrinsic hormone secretory activity and monocyte-lymphocyte imbalance collectively drive peripheral immune dysfunction
ASSOCIATION BETWEEN TYPE AND LOCATION OF GERMLINE BRCA1/2 PATHOGENIC OR LIKELY PATHOGENIC VARIANTS WITH PHENOTYPE AND PROGNOSIS IN YOUNG PATIENTS WITH BREAST CANCER: RESULTS FROM AN INTERNATIONAL COHORT STUDY
No full textInternational audienceBackground: Clinical implications of specific pathogenic and likely pathogenic variant (LP/PV) types and locations in the BRCA1 or BRCA2 tumor-suppressor genes remain to be elucidated.Patients and methods: The BRCA BCY Collaboration (NCT03673306) is an international, multicenter, hospital-based, retrospective cohort study that included BRCA mutation carriers diagnosed with invasive breast cancer at the age of ≤40 years between January 2000 and December 2020. In this analysis, only patients with detailed available information on LP/PVs in the BRCA genes were included. Clinicopathologic features and survival outcomes (disease-free survival [DFS] and overall survival [OS]) were investigated according to LP/PV type (insertion-deletion mutations [INDEL] vs single nucleotide variants [SNV] vs copy number variations [CNV]; truncating vs non-truncating LP/PVs; frameshift vs nonsense vs splicing vs missense LP/PVs) and location (exon involved and protein domain).Results: Out of 5660 patients from 109 centers worldwide, 3294 were eligible for the present analysis (2080 BRCA1 and 1214 BRCA2). The distribution of LP/PV types showed no meaningful associations with baseline clinicopathologic features. BRCA1 protein truncating variants were associated with worse OS compared to non-truncating variants (HR 2.00 [1.17-3.41]). A similar, though non-significant, trend was observed for BRCA2. Missense variants were linked to better OS for both BRCA1 (HR 0.48 [0.28-0.84]) and BRCA2 mutation carriers (HR 0.17 [0.03-0.96]). Regarding variant location, BRCA1 LP/PVs outside exons 2, 10, and 19 were associated with improved OS. In BRCA2, LP/PVs located in exons 15-26 and other regions were linked to worse DFS compared to those in exon 10, with no significant differences in OS.Conclusions: This study advances our understanding of the influence of specific types of BRCA LP/PVs on breast cancer characteristics and outcomes. A deeper understanding of these mutation-specific features will drive future research and support the development of tailored clinical strategies based on individual BRCA variant
Efficacy of erythroid‐stimulating agent and luspatercept in VEXAS syndrome: A multicenter retrospective study by the FRENVEX group
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Rapid-sequence clinical research before and during a pandemic: Lessons learned and the way forward
No full textInternational audienceIn the aftermath of the COVID-19 pandemic, the structuring of a nationwide research network for preparation and response to emerging infectious diseases (EID) with epidemic or pandemic potential has become increasingly essential. A nationwide EID operational research network (OPEN-ReMIE),is funded for five years through the France 2030 program and run by the French national research agency (ANR). Its primary missions are to accelerate hospital-based clinical research under epidemic or pandemic conditions with academic or industrial sponsors, and to pursue this effort in international research networks. OPEN-ReMIE governance is geared to steering this network and to guaranteeing its operability in inter- as well as crisis modes. It will be the point of entry for key international trial platforms, academic and private sponsors, regulatory agencies, associations of citizens and patients, and think tanks committed to promoting scientific integrity. OPEN-ReMIE encompasses six work packages: (i) regulatory affairs, sponsoring, fast-track procedures and contracts; (ii) clinical site network management; (iii) methodology and management centers to provide methodological expertise (generic master protocols, sets of core and extended variable catalogs, electronic case reports form templates, data management and interoperability, monitoring…); (iv) laboratory and biological resource center management; (v) drug supply and pharmacovigilance supervisory board; (vi) training programs and communication plans for various stakeholders: research teams, healthcare professionals, students, associations of citizens and patients and, increasingly, civil society actors. All in all, OPEN-ReMIE is a nationwide \"preparedness task force\" embedded in a large-scale European consortium for EID clinical research and working with other international EID clinical research platforms
High Expression of CCL2 Correlated With Dendritic Cell Recruitment in Neuroblastomas Associated With Opsoclonus-Myoclonus Syndrome
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Pleiotropy accelerates tooth phenotypic and genomic evolution - An in silico study under the lens of development
No full textPleiotropy, which can occur when a gene affects multiple traits, is a central property of living organisms, influencing their response to mutations and their evolutionary trajectories. Despite many studies and discussions, it remains very difficult to reconcile molecular, developmental and quantitative evolutionary genetics viewpoints on pleiotropy and appreciate how much it puts constraints on genetic evolution, phenotypic evolution and adaptation. Here, we revisit this question by simulating evolution in silico. Our model captures multiple levels of integration observed in complex organisms: from genes to development to phenotype to fitness, additionally allowing to remove pleiotropy to directly test its effect. We focus on the pleiotropic interactions between two organs, specifically teeth. Fitness is determined from the functional interaction between these two teeth, which are produced by an in silico model of tooth morphogenesis. The developmental parameters are produced by a genome consisting of pleiotropic genes which may be influenced by one tooth-specific transcriptional regulator per tooth. Our simulations with and without pleiotropy confirm several acknowledged consequences of pleiotropy. It reduced genetic and phenotypic exploration, and facilitated the rapid accumulation of adaptive mutations in the modular cis-regulatory regions of pleiotropic genes, which are specific to each tooth. Unexpectedly, pleiotropy promoted fitness improvements, morphological complexity, and the accumulation of genetic divergence. Mutations in pleiotropic genes contributed significantly to adaptation, and removing pleiotropy did not increase the proportion of adaptive mutations. Thus pleiotropy does not act as a conservative force, but a channeling force promoting genetic divergence