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Higher levels of host-cell DNA methylation markers ZNF582 and ASCL1 on anal smears are predictive for progression to anal cancer in patients with previous high-grade lesions
No full textInternational audienceBackground: French and International anal cancer screening recommendations for at-risk populations, published in 2024, are based on cytology and/or high-risk human papillomavirus (HPV) detection on anal smears. Biological markers to triage the patients most at-risk for anal cancer are crucial in prioritising patients needing high-resolution anoscopy consultations, which are frequently overwhelmed.Methods: The AIN3 cohort is a French national multicenter study including patients with a history of high-grade anal lesions (AIN3). Patients were followed-up for at least 3 years, with anal smears and clinical examinations performed yearly. Levels of ZNF582 and ASCL1 gene methylation were quantified using real-time PCR on anal smears collected at the time of inclusion.Findings: Overall, 514 anal smears were contributive for host-cell DNA methylation analysis. Patients' mean age was 50.8 years and 40% were women. Among the 41% who were living with HIV, 91% were men. Median follow-up duration was 48 months, and 22 patients (4%) developed anal cancer during follow-up. Higher methylation levels of ZNF582 and ASCL1 were significantly associated with high-grade squamous cell intraepithelial lesion (HSIL) cytology, p16-Ki67 dual-staining positivity, and high-risk HPV and HPV16 positivity on the same anal smear. Both methylation markers showed an AUC of 0.72 for discrimination between HSIL and non-HSIL cytology on the same anal smear. Higher methylation levels of both markers were significantly associated with evolution to anal cancer in univariate and multivariable analyses adjusted for age and HIV status (p < 0.001). When assessing the AUC over 1 and 3 years of follow-up, methylation markers demonstrated superior predictive value for anal cancer compared to other markers.Interpretation: We have demonstrated the predictive value of host-cell DNA methylation marker levels in anal smears with regard to evolution to anal cancer in a very high-risk population
Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts
No full textInternational audienceAbstract Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leukocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls. Therefore, we hypothesized the presence of additional genetic predispositions. In this genome-wide association study and meta-analysis, we studied a discovery cohort of 131 French LGI1-Ab-E and a validation cohort of 126 American, British and Irish LGI1-Ab-E patients, ancestry-matched to 2613 and 2538 European controls, respectively. Outside the known major HLA signal, we found two single nucleotide polymorphisms at genome-wide significance (P < 5 × 10−8), implicating PTPRD, a protein tyrosine phosphatase, and LINC00670, a non-protein coding RNA gene. Meta-analysis defined four additional non-HLA loci, including the protein coding COBL gene. Polygenic risk scores with and without HLA variants proposed a contribution of non-HLA loci. In silico network analyses suggested LGI1 and PTPRD-mediated interactions via the established receptors of LGI1, ADAM22 and ADAM23. Our results identify new genetic loci in LGI1-Ab-E. These findings present opportunities for mechanistic studies and offer potential markers of susceptibility, prognostics and therapeutic responses
Persistent organic pollutants in food systems: A comparative study across four contrasting socio-ecosystems: Portugal, Senegal, French Guiana, and Guadeloupe
No full textInternational audienceThis study quantifies persistent organic pollutants (POPs) in food across four territories undergoing dietary transitions: French Guiana, Guadeloupe, Senegal, and Portugal. A total of 200 local and imported food samplesfrom 12 categories were analyzed for polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). Concentrations varied by food matrix, region, and origin. The highest PCDDlevels were found in butter from Senegal (16.64 pg/g), and the highest PCDFs in leafy vegetables from Portugal (2.4 pg/g). Fish category showed the highest levels of dioxin-like PCBs (600.7 pg/g) and non-dioxin-like PCBs (3.6 ng/g). All values complied with EU Regulation 2023/915. To estimate dietary exposure, the maximum allowable daily intake (g of food/day) was calculated using Toxic Equivalents (TEQ), EFSA’s tolerable weekly intake (TWI: 2 pg TEQ/kg bw/week), and compared to national food consumption data. In Portugal, exposure from fish exceeded the TWI, highlighting the influence of regional contamination sources and dietary habits
Cardiac autonomic responses to cortical electrical stimulation: a SEEG study
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WONOEP XVII appraisal: Targeting network excitability beyond the synapse ‐Neurotransmitter, ionic, and electro ‐diffusions
No full textInternational audienceAbstract Epilepsy affects approximately 1% of the population worldwide, and although medications are effective in the majority of cases, seizures persist in approximately 30% of patients. Despite the effort to develop new antiseizure drugs, the rate of pharmacoresistance in patients has not diminished over the past 3 decades. There is thus a real unmet need, and new approaches and therapeutic targets should be pursued. Seizures are caused by a change in neuronal excitability resulting in hyperexcitation and hypersynchronization of neurons, and modulating either intrinsic neuronal properties or synaptic transmission has been and still is the best way to reduce excitation and synchronization of the neuronal network. However, network excitability and synchronicity are also influenced by many extrasynaptic regulators. Extracellular diffusion of glutamate and γ‐aminobutyric acid (GABA) and activation of their extrasynaptic receptors also participate in the generation of a hyperexcitable environment. Interestingly, even without synaptic transmission, neuronal activity can synchronize and propagate throughout the network via gap junctions, extracellular potassium ionic diffusion, and electric fields. In this review, we will discuss the recent advances in our understanding of how different extrasynaptic signaling mechanisms influence neuronal excitability and whether they could be candidate therapeutic targets to treat refractory epilepsy. This review emanated from the XVII Workshop on Neurobiology of Epilepsy meeting (Kilkea, Ireland) organized in 2023 by the Neurobiology Commission of the International League Against Epilepsy
Mass medical evacuations to decrease the intensive care burden: results from the TRANSCOV cohort study.
No full textInternational audienceBackground: In a context of overwhelming demand, mass transfers between intensive care units (ICU) were organized in France during the first COVID-19 epidemic wave (spring 2020). According to early reports, transferred patients experienced a 3-to-4-fold lower ICU case fatality. It is not known whether this difference stems only from the selection of healthier patients for transfer.Research question: Is the 28-day ICU case fatality of transferred patients different from that of matched control (not transferred) patients?Study design and methods: Multicenter retrospective cohort study that included 285 transferred patients, and 667 control (not transferred) patients admitted simultaneously (± 2 days) to the same "origin" ICU and alive five days after the transfer date. The 28-day ICU case fatality and clinical events during ICU stay were compared in transferred and control patients.Results: At ICU admission, age, COVID-19 severity, comorbidities and Simplified Acute Physiology Score II (SAPS II) were similar, but transferred patients were lighter (81 versus 89 kg, p<0.0001) and more autonomous than the matched control patients (64.5 versus 55.0%, p=0.01). Case fatality was approximately 7-fold lower in transferred patients (adjusted incidence rate ratio = 0.14 [95% CI: 0.10-0.19]). ICU stay was longer and delirium, psychiatric disorders and neuromuscular blockade exposure were more frequent in transferred patients than controls. Conversely, acute kidney injury was more frequent in controls (51.5 versus 37.7%, p<0.0001).Interpretation: Although the selection of healthier patients likely contributed to better survival, removal from an overcrowded care environment probably also explains the large survival benefit associated with transfer. By reducing workload, mass transfers might have also benefited patients who remained in origin ICUs. Organizing mass transfers as early as possible may be an appropriate strategy for mitigating the impact of an overwhelming intensive care demand
Image‐based robotics enhance precision and efficiency in lateral UKA: A comparative study of 135 UKAs
No full textInternational audiencePurpose : Robotic‐assisted lateral unicompartmental knee arthroplasty (UKA) remains technically demanding due to the complex biomechanics of the lateral compartment. Image‐based (IBRA) and imageless (ILRA) robotic systems have both demonstrated superior accuracy compared to conventional mechanical instrumentation, but have not yet been directly compared in lateral UKA. This study aimed to evaluate their respective accuracy and surgical efficiency. Methods This retrospective study included 135 patients who underwent lateral UKA using either IBRA or ILRA systems. Post‐operative radiographic outcomes included hip–knee–ankle (HKA) alignment, posterior tibial slope (PTS) and joint line (JL) restoration. Surgical time was assessed as a secondary outcome. Target zones were HKA 180°–185°, PTS 2°–8° and JL ± 2 mm. Results IBRA showed higher rates of HKA inliers (94.9% vs. 78.9%, p = 0.011) and JL restoration (76.2% vs. 31.6%, p < 0.001) compared to ILRA. PTS accuracy was similar between groups ( p = 0.30). Operative time was significantly shorter with IBRA (61.6 ± 13.5 vs. 81.9 ± 26.1 min, p < 0.001). Conclusion IBRA outperformed ILRA in terms of alignment accuracy and surgical duration. These findings support the added value of IBRA systems in lateral UKA. Level of Evidence Level IV, retrospective case series study
Adaptive radiotherapy, promises and pitfalls
No full textInternational audienceAdaptive radiotherapy is a technique that adapts the radiotherapy to the changes of the patient's anatomy and tumour volume by using repeated images acquired during the treatment course. Adaptive radiotherapy aims to optimize the dose distribution, ensure that the tumour remains in the treatment volume and spare the organs at risk. Adaptive radiotherapy can be applied at three timescales: between fractions (offline), immediately before a fraction (online) or real-time (online, during a fraction). Over the last decade, manufacturers have developed linear accelerators dedicated to online adaptive radiotherapy, based on either computed tomography or magnetic resonance imaging. These systems allow for treatment plan adaptation according to deformable, registration-based segmentation and physicistdriven plan optimization. This has led to a rapid rise of this technique on a larger scale, although robust data on its benefits remains scarce. Adaptive radiotherapy has demonstrated dosimetric benefits, such as improved lesion coverage and sparing of organs at risk, in various tumour sites. However, the clinical benefit, in terms of toxicity reduction or improved tumour control, remains to be demonstrated in many disease sites. Furthermore, the implementation of adaptive radiotherapy requires careful planning, increased time, logistics and security, which represents an extra burden and impacts the cost-efficiency of the approach.</div
Intrascleral Tunnel Clamping of Fluocinolone Acetonide Implant: A Novel Scleral Fixation Technique
No full textDecision-making algorithm for difficult intermittent self-catheterization: construction and validation using the Delphi method
No full textInternational audiencePurpose: Intermittent Self Catheterization (ISC) is the gold standard for chronic neurogenic and non neurogenic urinary retention. However, difficulties encountered may lead to poor adherence and discontinuation. This study aimed to develop and validate a decision-making algorithm to guide first and second line management of the more common difficulties reported by patients performing ISC.Methods: A survey conducted amongst patients, nurses and physicians identified the most frequent difficulties encountered with ISC. Based on a literature review and expert experience, a steering committee, composed of 14 urologists and physical medicine and rehabilitation practitioners, developed a preliminary algorithm outlining management strategies for each identified issues. The algorithm was then validated by a panel of experts through a Delphi process.Results: Six difficulties were identified: pain, infections, bleeding, blockage, technical issues and neuro-psychological barriers. Twenty experts participated in the voting group. Of the 68 initial items, 61 were validated and included in the final algorithm (30 with a strong agreement, 31 with a relative agreement).Conclusions: This multidisciplinary collaborative work resulted in a validated decision-making algorithm designed to complement to existing guidelines. It supports healthcare professionals from different backgrounds in managing patients who report difficulties with ISC