Citations

Gephyrin is a postsynaptic scaffold protein essential for inhibitory neurotransmission. Gephyrin‐immunoglobulin G (IgG) was reported, decades ago, in a single case of paraneoplastic stiff‐person‐like syndrome, but its broader clinical relevance remains unknown. While investigating unclassified synaptic IgGs mimicking amphiphysin‐IgG, we identified gephyrin‐IgG in 3 patients using human protein microarray. Gephyrin specificity was confirmed using confocal tissue‐based immunofluorescence assay, cell‐based assay, and Western blot. The 3 patients, all female, had: encephalitis (2) and myeloneuropathy and breast cancer (1). All had inflammatory cerebrospinal fluid and abnormal magnetic resonance imaging, and improved following immunotherapy. Gephyrin‐IgG is associated with a treatable autoimmune neurological disease, sometimes paraneoplastic. ANN NEUROL 2026

This case series describes multicenter experience with interleukin 6 (IL-6) receptor blockers used during attacks in aquaporin 4–immunoglobulin G–positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD).

Pharmacological plasminogen reduction enhanced liver regeneration experimentally and clinically. siRNA-induced plasminogen deficiency promoted hepatocyte proliferation after partial hepatectomy in mice, contrasting genetic deficiency models. In the HeLiX trial, tranexamic acid reduced post-hepatectomy liver failure odds, suggesting a novel therapeutic strategy.

Summary Functional ex vivo assays using live tumor tissues have demonstrated strong predictive accuracy for response to immune checkpoint inhibitors (ICIs) but are not scalable, requiring manual processing of large resections collected at academic centers. Here, an ex vivo live tumor fragment (LTF) platform was developed using standard-of-care biopsies from 228 patients with suspected malignancy collected across prospective, multicenter observational trials and biobanks. Hierarchical clustering of ICI-mediated changes in cytokine production identified two groups: responders and nonresponders. A binary classifier (elive index) using 8 cytokines achieved an AUC of 0.99 for cluster prediction. elive index correctly predicted clinical benefit in 93% (26/28) of patients ( P = 3.2x10 -5 ) and accurately identified 83% (10/12) of objective responders. Critically, elive responders were identified among biomarker-negative patients, highlighting the platform as a scalable approach that complements existing companion diagnostics and expands the population of patients identified to benefit from ICI therapy.