In France, disparities in the supply of and access to care can contribute to differences in population health status. These socio-territorial health inequalities (STHI) are both unfair and avoidable and therefore require better understanding in order to limit their occurrence and consequences. Social deprivation has been shown to be associated with an increased risk of chronic kidney disease, delayed referral to nephrologists, and reduced access to waitlisting and kidney transplantation. We hypothesize that limited access to primary care constitutes a barrier to access to nephrological care. This article proposes an updated overview of the terminology and tools used to define and measure STHI, as well as a review of studies examining the impact of geographical accessibility on the nephrological care pathway.
The use of immune checkpoint inhibitors (ICIs) after liver transplantation (LT) remains controversial due to rejection risk. This study aims to characterize patients receiving ICIs post-LT and identify the risk factors for rejection. This retrospective, multicenter study included patients who received at least one ICI (anti-programmed cell death 1, anti-programmed cell death ligand 1, or anti-cytotoxic T cell-associated protein 4) post-LT. Fifty-two patients were included (77% male), median age 66 (interquartile range [IQR], 57.5-69.7) years at ICI initiation. The median interval between LT and ICI was 4.5 (IQR, 2.6-9.9) years. ICIs were administered for hepatocellular carcinoma recurrence (62%) or de novo cancer (38%), with similar rejection and survival rates. Rejection occurred in 7 patients (13%) and was moderate/severe, developing at a median of 27 (IQR, 23-57) days post-ICI. The increase of immunosuppression and calcineurin inhibitor use at ICI initiation was associated with reduced rejection risk (P = .04 and P = .013, respectively). Rejection was associated with significantly lower survival (P = .0003). Overall survival following the introduction of ICI at 3, 6, and 12 months was 65%, 46.9%, and 38.9%, respectively. Rejection post-ICI occurs less frequently than previously reported, but early after therapy initiation, it is severe and linked to the absence of calcineurin inhibitors. Optimizing immunosuppression may enhance the safety of ICI use in transplant recipients.
Introduction:Earlier intervention in glaucoma has been suggested to slow disease progression and preserve visual function and quality of life. Consequently, minimally invasive glaucoma surgery (MIGS) is increasingly used in mild-to-moderate glaucoma. Although numerous techniques and devices are available, their comparative efficacy remains debated: most procedures lower intraocular pressure to the mid-teens in primary open-angle glaucoma, but without clear evidence of superiority. As these surgeries are now offered to younger, otherwise healthy patients, safety has therefore become a central criterion in technique selection. Methods:This PRISMA-based systematic review analyzed safety outcomes from peer-reviewed studies of the main MIGS procedures published between 2014 and 2024. Five databases were searched using current and historical device names. Non-clinical studies, case series, and nonstandard techniques were excluded from quantitative analysis but retained qualitatively to capture rare events. A total of 401 studies, representing 39,381 eyes and 68,917 eye-years of follow-up, were included. Highest reported and weighted mean complication rates were calculated by procedure type. Results:Safety profiles varied. Trabecular bypass implants and ab interno canaloplasty were associated with low rates of serious adverse events and minimal anatomical disruption. Suprachoroidal devices carried higher risks of hypotony, inflammation, and malposition. Across all categories, chronic changes to angle anatomy and occasionnal re-interventions highlighted the potential for long-term sequelae, with endothelial cell loss emerging as a key concern for certain procedures.However, heterogeneity in definitions and reporting limited comparability. Common events such as hyphema and IOP spikes were inconsistently documented, while late complications like endothelial cell loss or peripheral anterior synechiae were often overlooked. This underreporting risks conflicting conclusions and undermines comparisons. Conclusion:For patients with mild, stable disease or those undergoing opportunistic combined surgery, tissue-sparing procedures with the lowest observed complication rates may be preferable. Standardized definitions, long-term follow-up, and harmonized safety reporting are becoming essential.
BACKGROUND AND OBJECTIVES:Recent reports have suggested that levodopa exposure may contribute to freezing of gait (FOG), but this relationship remains controversial because of confounding by disease severity and duration. Our goal was to assess the relationship between levodopa use and FOG incidence and severity. METHODS:We studied 2 prospective, multicentric cohorts: NS-Park and Parkinson's Progression Markers Initiative (PPMI). Patients with ≥2 visits were selected. Three nested subcohorts were defined based on disease duration, baseline FOG, and levodopa exposure. FOG was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II 2.13. Analyses included mixed-effects ordered logistic regression to evaluate FOG severity and Kaplan-Meier and Cox proportional hazards models to assess incident FOG. Models adjusted for disease duration, Hoehn and Yahr (H&Y) stage, and MDS-UPDRS Part III scores. RESULTS:A total of 25,602 patients with Parkinson disease from the NS-Park (mean age 68.3 ± 29.1, 42% female) and 1,441 from the PPMI (mean age 62.9 ± 9.8, 37% female) cohorts were included. In unadjusted analyses with the NS-Park cohort, levodopa use was associated with higher FOG severity and incidence, but this association was no longer statistically significant in the PPMI cohort. In mixed-effects ordinal logistic regression models adjusting for disease duration/severity, levodopa status showed a nonsignificant effect size on FOG (NS-Park odds ratio [OR] 1.84, 95% CI 0.94-3.61, p = 0.074; PPMI OR 0.76, 95% CI 0.38-1.51, p = 0.430), while disease duration (NS-Park OR 4.4, 95% CI 3.01-6.29, p = 6.0e-15; PPMI OR 6.97, 95% CI 5.05-9.63, p = 4.7e-32), Hoehn & Yahr stage (NS-Park OR 6.8, 95% CI 3.52-13.08, p = 1.059e-08; PPMI OR 1.5, 95% CI 0.96-2.22, p = 0.073), and MDS-UPDRS-III score (NS-Park OR 1.85, 95% CI 1.38-2.49, p = 4.34e-05; PPMI OR 2.00, 95% CI 1.67-2.39, p = 2.4e-14) were independently associated with greater FOG severity. No statistically significant association was observed between future levodopa exposure and de novo FOG incidence. In turn, FOG incidence was driven by the H&Y (NS-Park: hazard ratio [HR] 1.94, 95% CI 1.68-2.23; PPMI: HR 1.78, 95% CI 1.47-2.17) and MDS-UPDRS III (NS-Park: HR 1.40, 95% CI 1.07-1.83; PPMI: HR 1.26, 95% CI 1.17-1.36). DISCUSSION:No significant or consistent association between levodopa exposure and FOG severity or incidence was observed after adjustment for disease duration and severity, with the effect estimates significantly attenuated despite residual uncertainty.
Glioblastoma is the most aggressive primary brain tumor in adults, characterized by rapid progression, resistance to therapy, and inevitable recurrence. Despite standard treatment—surgical resection, X-ray radiotherapy, and temozolomide chemotherapy—prognosis remains poor. Growing evidence indicates that glioma stem cells (GSCs) and hypoxia drive this resistance and recurrence.This review examines distinct GSC subtypes: mesenchymal GSCs, the most aggressive and invasive; proneural GSCs, which are more radiosensitive but highly proliferative and contribute to recurrence; and slow-cycling GSCs, which, though less well understood, are of growing interest due to their activation and deactivation during radiotherapy or through as-yet-unknown mechanisms. Hypoxia, a hallmark of the glioblastoma microenvironment, maintains these stem cells in a dedifferentiated state. As a key regulator, hypoxia orchestrates radioresistance mechanisms and promotes stem-like cell persistence through processes such as epithelial-mesenchymal transition-like (EMT-like), proneural-mesenchymal transition (PMT), or the reprogramming of differentiated cancer cells into GSCs.The review concludes by highlighting therapeutic strategies under development to overcome radioresistance, including targeting GSCs, hypoxia, or employing alternative irradiation modalities beyond X-ray radiotherapy.
