Citations

Glioma-associated microglia/macrophages (GAMs) have traditionally been described as immunosuppressive. However, within their highly heterogeneous repertoire, pro-phagocytic and cytotoxic subsets with anti-tumoral properties exist. Although macrophages (MACs) can exhibit tumor-suppressive functions, their anti-glioma properties largely remain elusive. To identify anti-glioma myeloid cell effectors, we performed directionally concatenated ligand-receptor (L-R) interactome analyses from dendritic cells (DCs) and microglia (MG) to lymphoid (CD4 + T, Tregs, CD8 + T, NK, and NKT) cells identified by our recent single-cell transcriptomics interrogation of tumor-associated CD45 + leukocytes from tumor brains of eighteen isocitrate dehydrogenase (IDH)–stratified glioma patients. Within DC-specific and MG-specific interactomes, we identified LGALS9 , which encodes Galectin-9, as a key mediator of cell–cell interactions in IDH-wild type (IDH-wt) gliomas. Spectral cytometry, immunohistochemistry, and Western blotting analyses confirmed the abundant expression of Galectin-9 in glioma-associated MG, but not in tumor cells. Furthermore, differential gene enrichment analyses revealed transcripts associated with cellular adhesion (coronin 1A, integrin) and phagocytosis (FcγR, phospholipase D, Rab family proteins, etc.) pathways that were significantly upregulated in Galectin-9 + compared to Galectin-9 − MG and MACs. Using an ex-vivo primary human microglia (pMG) and patient-derived glioma stem cells (GSCs) co-culture system, we evaluated the functional role of Galectin-9. Confocal imaging analyses of co-cultured pMG with GSCs revealed that siRNA-mediated knockdown or antibody-based neutralization of Galectin-9 significantly impaired pMG–GSC adhesion. In addition to reduced adhesion, phagocytosis of GSCs was dramatically attenuated across all Galectin-9 silenced or neutralized pMG. Altogether, our study underscores the unappreciated non-canonical role of Galectin-9 in MG as a regulator of glioma cell adhesion and phagocytosis that can be harnessed for glioblastoma immunotherapy.

Summary Evidence for an association between insulin‐like growth factors (IGF) and multiple myeloma (MM) is inconsistent. We examined total IGF‐I concentrations and risk of MM by combining baseline serological data among UK Biobank participants ( n = 444 187; 732 incident MM) with a two‐sample Mendelian randomisation (MR) analysis using identified genetic variants associated with circulating total IGF‐I and IGF‐binding protein 3 (IGFBP‐3) in the InterLymph consortium (2434 MM and their 2567 controls). Finally, additional lymphoid neoplasm (LN) subtypes were included for comparison with the main hypothesis. Circulating IGF‐I level was positively associated with MM risk Hazard ratio‐HR‐per one standard deviation‐SD‐increase (HR 1‐SD = 1.11, 95% confidence interval [CI]: 1.01–1.22; p ‐value = 0.03), especially closer to diagnosis. Genetically inferred IGF‐I levels were associated with increased MM risk (odds ratio [OR] = 1.27, 95% CI: 1.05–1.54) but not with any other LNs. Genetically inferred IGFBP‐3 levels showed no associations with any LN evaluated. Corroborating previous findings, in a secondary analysis, IGF‐I levels were associated with the risk of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in males with higher body mass index (HR 1‐SD in obese male = 1.36, 95% CI: 1.14–1.61). Our serological and MR analyses suggest a contributing role of IGF‐I in the susceptibility of MM; the CLL/SLL findings warrant further investigation considering sex‐specific adiposity.

ABSTRACT Emergency physicians evaluate the full spectrum of traumatic brain injury (TBI) and generate the initial clinical descriptions that influence downstream care, follow‐up, and patient expectations. Despite advances in neuroimaging, biomarker science, and systems of care, acute TBI is still commonly summarized using categorical labels: mild, moderate, and severe, derived from the Glasgow Coma Scale (GCS). In 2025, the National Institutes of Health–National Institute of Neurological Disorders and Stroke (NIH–NINDS) Traumatic Brain Injury Classification and Nomenclature Initiative proposed a multidimensional framework for acute TBI characterization incorporating Clinical, Biomarker, Imaging, and Modifier elements (CBI‐M). The framework is intended to improve characterization and research rigor, and has generated broad interest and discussion across clinical disciplines. This special contribution introduced the CBI‐M framework to the emergency medicine community and provides an interpretive, clinically grounded commentary on its relevance to emergency practice. The rationale for the framework is described, its core components are summarized, and its relevance to emergency department (ED) practice is discussed. Areas where CBI‐M aligns with current emergency care, where important implementation questions remain, and how emergency physicians might engage with the framework as a shared language for describing injury rather than as a prescriptive management tool are highlighted. By situating CBI‐M within the realities of emergency care and existing ED decision frameworks, this article aims to inform, contextualize, and encourage discussion within the emergency medicine community as this new approach to TBI characterization continues to evolve.

Objective: To examine the benefit of cochlear implantation (CI) in pediatric patients with a history of temporal bone fracture resulting in single-sided deafness (SSD). Study design: Retrospective chart review. Setting: Two tertiary academic centers. Patients: Pediatric patients less than 18 years of age with SSD secondary to temporal bone fracture who underwent CI from 2012 to 2022. Intervention(s): CI. Main outcome measure(s): Postoperative audiometric testing. Results: Seven subjects were identified (median age: 10 years (y); Q1 to Q3: 5 to 16 y). Median time from temporal bone trauma to CI was 7 months (mo) (Q1 to Q3: 3 to 7 mo) and 85% had otic capsule involvement. Subjects were followed for a median length of 12 months (Q1 to Q3: 6 to 24 mo) after CI. All patients achieved full electrode insertion, though 2 required scala vestibuli insertion due to ossification of the scala tympani (one of whom had a history of meningitis after temporal bone fracture). Postoperative audiometric testing revealed variable speech perception outcomes with 4 of 7 obtaining open or closed set speech perception and 3 of 7 obtaining only sound awareness. No postoperative complications occurred. Conclusions: CI is a feasible intervention for SSD following pediatric temporal bone fractures, but outcomes are variable. Early evaluation and timely CI, ideally within 6 months of temporal bone fracture, may optimize outcomes. Cochlear ossification, either as a result of otic capsule fracture or subsequent meningitis, may lead to suboptimal outcomes.