Citations

ABSTRACT Objectives To characterize practice patterns and outcomes in the management of low‐ and intermediate‐grade salivary gland carcinoma prior to the existence of treatment guidelines. Methods Analysis of a registry of patients who underwent parotid and submandibular gland resections for low‐and intermediate‐grade carcinomas between 2010 and 2019. Results Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial ( n = 384, 53%) or total ( n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was associated with a significant increase in transient facial weakness (72/177 (41%) vs. 82/311 (26%), RR 0.65, 95% CI 0.50–0.84, p < 0.05) and permanent facial nerve weakness (23/176 (13%) vs. 16/301 (5%), RR 0.41, 95% CI 0.22–0.75, p < 0.05) compared to superficial parotidectomy. Adjuvant radiation therapy ( RT ) was delivered to 285 (36%) patients. The proportion of patients receiving adjuvant RT declined significantly over the time period from 2015 to 2019 compared to 2010 to 2014 at 162/504 (32%) and 123/282 (44%), respectively ( RR 0.74, 95% CI 0.61–0.89, p < 0.05). When comparing the time periods from 2015 to 2019 and 2010 to 2014, there was no significant difference in local control rates ( RR 0.52, 95% CI 0.26–1.04, p = 0.06) or regional control rates ( RR 0.75, 95% CI 0.26–2.13, p = 0.58). Conclusions Management of low‐ and intermediate‐grade salivary cancer from 2010 to 2019 was variable, which is expected given the rarity and heterogeneity of the disease and the lack of treatment guidelines prior to 2021. Most patients with parotid malignancies underwent superficial or total parotidectomy. The extent of parotidectomy had an impact on facial nerve function outcomes. Delivery of adjuvant radiation trended down with time. The data presented here will support dissemination of the guidelines and provide data that could inform future trials. Level of Evidence 2b.

ABSTRACT Glioblastoma (GBM), the most aggressive primary brain tumour in adults, presents significant challenges due to its universal recurrence and limited survival rates. A key driver of GBM progression is the subpopulation of brain tumour‐initiating cells (BTICs), which contribute to therapy resistance and interact with the tumour microenvironment, particularly the cellular components in the subventricular zone (SVZ). Extracellular vesicles (EVs) are critical mediators of intercellular communication, carrying bioactive molecules, such as proteins and RNAs, that can modulate the behaviour of recipient cells. This study investigates the role of EVs in GBM's communication with non‐cancer cells. We utilised the proximity‐labelling system TurboID to achieve global and unbiased labelling of proteins within GBM‐derived EVs. By inducing TurboID expression in primary‐cultured human BTICs from GBM patients, we achieved efficient biotinylation of EV proteins without compromising vesicle integrity, and performed proteomic analysis of biotinylated proteins, which revealed a diverse cargo within BTIC‐EVs. Our method marks the first implementation of TurboID for unbiased global labelling of EV protein cargo in primary cells. This approach facilitates the investigation of EV‐mediated communication and potential therapeutic targets, contributing to the understanding of GBM's complex interactions with the brain's microenvironment and identification of biomarkers for improved diagnosis and treatment response.

In women with dense breasts, adding molecular breast imaging to digital breast tomosynthesis (DBT) increased both overall and invasive cancer detection rates, while modestly raising the recall rate compared with DBT alone.

Abstract Oxygen deprivation within large or poorly vascularized bone defects remains a key barrier to successful regeneration, especially during the early postimplantation period before vascular ingrowth. Here, the development of COSnPPOD (CaO 2 –Silica NP Platform for Osteogenic Development) is reported, a visible light digital light processing‐printed hydrogel scaffold that integrates oxygen‐releasing nanoparticles (NPs) within a Primitive‐type triply periodic minimal surface architecture. The scaffold combines a gelatin methacrylate‐poly(ethylene glycol) diacrylate matrix with calcium peroxide (CaO 2 )‐loaded hollow silica NPs, enabling localized, short‐term oxygen release while preserving structural fidelity. COSnPPOD scaffolds demonstrate favorable degradation kinetics, tunable stiffness, and increased protein adsorption in vitro. In a preosteoblast model, COSnPPOD maintains cell viability and supports osteogenic gene expression without cytotoxic effects. While overall gene expression is comparable to controls, a 16‐fold increased expression of phosphoprotein 1 (Spp1) suggests scaffold‐driven activation of matrix remodeling pathways. In vivo, COSnPPOD scaffolds enhance bone regeneration in a murine calvarial defect model, with significantly greater bone formation and collagen deposition than untreated defects and hydrogel controls. Additionally, vascular endothelial growth factor immunostaining is increased within the defect, consistent with a proangiogenic response, and no systemic toxicity is observed. These findings establish COSnPPOD as a promising scaffold system that combines sustained oxygenation with biomimetic geometry to support localized bone regeneration.

ABSTRACT Introduction A novel therapy for heavily pretreated triple‐class–exposed multiple myeloma (TCE MM) is B‐cell maturation antigen (BCMA)‐targeted immunotherapy. While the number of TCE+BCMA‐exposed patients is growing, real‐world data for this group are limited. Methods We present real‐world data from patients with TCE+BCMA‐exposed MM who initiated a subsequent line of therapy (LOT) using a US‐based claims database, Komodo's Healthcare Map. Results We identified 656 TCE+BCMA‐exposed patients; mean age was 66.5 years. Time from MM diagnosis to index was 5.4 years; mean number of prior LOTs was 5.9. The most prevalent prior therapy received within each drug class was daratumumab (98.5%), pomalidomide (86.0%), carfilzomib (85.8%) and belantamab mafodotin (74.5%). A total of 137 different subsequent treatment regimens were observed following TCE+BCMA exposure; the most common regimen was teclistamab (10.4%). The top three targeted agents within the subsequent regimen were carfilzomib (20.2%), pomalidomide (20.1%) and bortezomib (16.6%). Among this TCE+BCMA‐exposed population who received subsequent treatment, the median time to next treatment or death was 6.8 (95% CI, 6.1–7.5) months; time to treatment discontinuation or death was 3.5 (95% CI, 3.2–3.7) months. Conclusion This first real‐world analysis of patients with heavily pretreated TCE+BCMA‐exposed MM shows poor clinical outcomes, frequent therapy retreatment and no standard‐of‐care, highlighting the need for novel treatments. Clinical Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Spinal cord stimulation (SCS) is effective for some pain syndromes, but inappropriate referrals can frustrate patients and misuse resources. This retrospective study reviewed 370 patients referred to a Neuromodulation for Pain Program (NPP) from July 2022 to June 2024. Of these, 241 were deemed appropriate for SCS. The SCS-appropriate group had higher pain intensity, more neuropathic pain, and lower opioid use. Inappropriate referrals were often from family physicians. Key factors associated with inappropriateness included low pain intensity, lack of neuropathic features, and high opioid use. Enhancing referral quality through targeted education may improve care and system efficiency.

A three year old male neutered mixed breed dog presented with a mass on the right carpus and accompanying lameness. A Jamshidi bone biopsy was performed, and histopathology results were consistent with a sarcoma. The dog received oncolytic virotherapy (OV) with vesicular stomatitis virus (VSV) as part of a clinical trial in dogs with osteosarcoma (OSA). Ten days after VSV treatment, the affected limb was amputated, and histopathology was consistent with intramedullary HSA. Considering the new diagnosis, standard doxorubicin chemotherapy was prescribed. With this combination of therapies, the dog had an extended survival of more than seven years and remains alive at the time of writing. This is the first case report documenting OV given in conjunction with the standard of care for canine appendicular HSA.

Abstract BACKGROUND Tau‐derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid‐beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long‐term anti‐Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them. METHODS A post‐hoc analysis of the DIAN‐TU‐001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab ( n = 50), gantenerumab ( n = 52), or placebo ( n = 40). High‐resolution mass spectrometry quantified CSF tau species over four years. RESULTS Phosphorylated tau (p‐tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab‐mediated Aβ plaque reduction. Nearly a decade later, MTBR‐tau243 and p‐tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression. DISCUSSION Initially changing soluble p‐tau species track Aβ plaque reduction, while ptau205 and MTBR‐243 reflect tau tangle pathology, informing different pathways of therapeutic strategies. Highlights p‐tau217 and p‐tau231 correlate with Aβ‐PET and respond to Aβ‐plaque lowering therapies. Aβ immunotherapy trials support a direct link between p‐tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT‐related biomarkers. Blood‐based p‐tau217 assays may provide a non‐invasive tool to monitor Aβ therapies. MTBR‐tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT‐targeting therapies.

AbstractBackgroundVEXAS syndrome is an autoinflammatory disease caused by somatic UBA1 mutations on the X chromosome, predominantly affecting men.ObjectiveTo characterize VEXAS syndrome in women and to compare the features of VEXAS syndrome between sexes.MethodsWe conducted an international, multicenter study, including 12 women and 301 men with genetically confirmed VEXAS syndrome. Data were collected using a standardized case report form. Bone marrow analyses and molecular investigations were performed locally.ResultsClinical features, age at onset, UBA1 mutation type, variant allele frequency, and mortality were comparable between sexes. Acquired X monosomy was found in 6/8 tested women. Additional clonal mutations were present in 3/5 tested women. Three additional UBA1‐mutated women without typical inflammation are described separately.ConclusionVEXAS syndrome affects women with clinical features similar to men, supporting the need for UBA1 testing in women with compatible presentations. X monosomy is common but not universal, suggesting alternative pathogenic mechanisms.