Citations

Abstract In adult-type diffuse gliomas CDKN2A and/or CDKN2B (CDKN2A/B) deletions often co-occur with deletion of MTAP, suggesting that MTAP immunohistochemistry (IHC) may be a surrogate marker of CDKN2A/B status. However, the association between CDKN2A/B and MTAP deletion at the genomic level remains unknown. We assessed CDKN2A/B and MTAP deletions by chromosomal microarray in 333 adult-type diffuse gliomas and performed MTAP IHC on a subset (n = 63). CDKN2A/B and MTAP deletions were detected in 216 and 215 cases, respectively, and were concurrent in 99.5% (215/216). While most tumors with CDKN2A/B homozygous deletion (n = 148) showed concurrent MTAP homozygous deletion (108/148; 73.0%), a subset harbored MTAP heterozygous deletion (39/148; 26.4%). By analyzing the size of the chromosomal alterations, we demonstrate that initial large chromosomal 9p losses result in concurrent heterozygous deletion of CDKN2A/B and MTAP whereas smaller “second hit” deletions leading to homozygous CDKN2A/B deletion do not always encompass the MTAP locus. Discordant CDKN2A/B and MTAP tumors affect the association between MTAP IHC and copy number status of MTAP and CDKN2A/B. These findings suggest that adult-type diffuse gliomas, regardless of IDH status, follow a stereotypic pathway involving concurrent CDKN2A/B and MTAP heterozygous deletion but may diverge for CDKN2A/B and MTAP homozygous deletion.

BACKGROUND There is a paucity of literature investigating the use of liposomal bupivacaine (LB) in a dermatologic surgery setting. OBJECTIVE To identify the treatment characteristics and adverse events, including Local Anesthetic System Toxicity (LAST), in patients receiving perioperative LB. MATERIALS AND METHODS A retrospective chart review was performed at a single institution using an institutional database and key words “Exparel” or “liposomal bupivacaine.” Patients ≥18 years old who received perioperative LB to the surgical site and surrounding skin were included. RESULTS A total of 140 LB administrations and 129 patients were included. Liposomal bupivacaine was used most often in the setting of excisions ( n = 88, 62.9%) and Mohs micrographic surgery ( n = 49, 35%), with hidradenitis suppurativa ( n = 77, 55%) and cutaneous neoplasms ( n = 56, 40%) the most frequent diagnoses. The median postoperative area and length were 23.6 cm 2 and 15.4 cm, respectively. The median LB dosage was 20 mL (range 1.5–20). There were no adverse events in 134 out of 136 patients of LB administration (98.5%). There were 2 reports (1.5%) of nausea on POD1 while these patients were taking opioids. CONCLUSION Liposomal bupivacaine should be considered for postoperative analgesia in patients undergoing dermatologic surgery because it is well tolerated and efficacious. The authors observed no cases of LAST.

Importance Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive and potentially life-threatening infection that predominantly affects immunocompromised patients. Recent advances in diagnostic imaging, antifungal therapy, and surgical techniques may have altered its incidence, morbidity, and mortality. Objective To evaluate temporal trends in the pooled proportion, morbidity, and mortality of AIFRS in immunocompromised patients and assess the association of diagnostic and therapeutic advances. Data Sources Systematic searches of Ovid MEDLINE, Ovid Embase, PubMed, Scopus, Web of Science, Cochrane, and Google Scholar from 1977 through October 20, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study Selection Prospective, retrospective, and cross-sectional studies and case series reporting pooled proportion, morbidity, or mortality of AIFRS in immunocompromised patients were included. Non-English articles, reviews, editorials, and studies with fewer than 10 patients were excluded. Data Extraction and Synthesis Two independent reviewers extracted data using standardized templates; disagreements were resolved by consensus. Risk of bias was assessed using the Newcastle-Ottawa Scale and Murad tool for case series. Random-effects meta-analysis generated pooled proportion, morbidity, and mortality rates with 95% CIs. Heterogeneity was quantified using I 2 statistics. Meta-regression and sensitivity analyses evaluated temporal trends and study-level effects. Main Outcomes and Measures Pooled proportion, morbidity, and mortality rates of AIFRS stratified by publication period (1983-2012 vs 2013-2025). Results A total of 205 studies comprising 48 437 immunocompromised patients (median [range] age, 49.4 [5.2-68.8] years), including 10 311 (21.3%) with AIFRS, were analyzed. The pooled proportion was 11.8% (95% CI, 7.9%-17.2%), rising to 16.6% (95% CI, 8.7%-29.2%) in studies from 2013 to 2025. Overall mortality was 31.2% (95% CI, 28.3%-34.3%), declining from 41.9% (95% CI, 35.0%-49.1%) before 2013 to 28.2% (95% CI, 25.1%-31.4%) after 2013. Morbidity was 37.0% (95% CI, 32.9%-41.4%), with similar rates across periods (39.3% before 2013 vs 36.4% after 2013). The most common complications were vision loss, exophthalmos/proptosis, and orbital exenteration. Conclusions and Relevance This systematic review and meta-analysis suggests that the pooled proportion of AIFRS among immunocompromised patients has increased while mortality has declined, reflecting advances in diagnostic and therapeutic approaches. Early detection and aggressive management remain critical to improving outcomes.

Background: Venous air embolism (VAE) is a potentially catastrophic complication during neurosurgical procedures, particularly in the sitting position. As practices vary widely, we conducted a survey to describe the global practice patterns for intraoperative detection and management of VAE. Methods: Following institutional review board (IRB) approval, we conducted a cross-sectional study using a 48-question online survey that was distributed via a snowball sampling approach, initially to the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) community and subsequently to international collaborators. Descriptive statistics summarized responses, and proportional comparisons between high-income and low- and middle-income country respondents were assessed using a χ 2 or the Fisher exact tests, as appropriate. Results: Of 307 responses, 297 were analyzed, representing 40 countries. Survey response rate was 25% among SNACC members. End-tidal carbon dioxide (EtCO 2 ) monitoring was the most frequently reported VAE monitoring modality, particularly for sitting craniotomies. Common barriers to implementing advanced monitoring included limited equipment availability and a lack of a transesophageal echocardiography (TEE) specialist. Decision-making for cases at VAE risk relied on team consensus (62%), review articles and primary literature (48%), and institutional protocols (42%). Among respondents, 89% expressed interest in consensus guidelines for VAE management. Conclusions: There is substantial global variability in both the preparation for and management of VAE during neurosurgical procedures. EtCO 2 is the preferred monitoring approach in routine practice, as resource limitations prevent the broader adoption of more sensitive techniques, such as TEE. The high interest in consensus guidelines underscores an opportunity for professional societies to standardize approaches and improve patient safety.

Background/Objectives: Postoperative opioid exposure after lumbar fusion remains a key clinical concern. Understanding which perioperative factors are associated with lower postoperative opioid use may help optimize recovery after minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF). This study aimed to determine if patients undergoing MIS-TLIF under spinal anesthesia (SA) showed lower postoperative opioid use compared to those undergoing MIS-TLIF under general anesthesia (GA). Methods: We retrospectively studied all adult patients (>18 years) undergoing 1- and contiguous 2-level MIS-TLIFs performed by a single surgeon. Patients undergoing the procedure under GA were compared to those undergoing the procedure under SA. Postoperative oral opioid use, up to 3 months post discharge, was collected. A 1:1 propensity score matching (PSM) protocol was implemented. Each outcome variable was initially assessed using univariate regression. Predictor variables with a p-value < 0.2 were included in the multivariate regression model. This was a retrospective, non-randomized study, and residual confounding cannot be excluded despite PSM. Results: The matched groups (n = 50 in each group) did not differ significantly depending on demographics or levels fused. Before regression, mean number of postoperative opioid prescriptions (p = 0.03), mean total operating room (OR) time in minutes (p < 0.01), and median length of stay (LOS) in days (p = 0.03) were significantly different. Multivariate regression showed that the GA group received 216.5 more total morphine milligram equivalents than the SA group (95% CI = 0.7–432.2, p = 0.049). The days of opioid use were higher in the GA group by 3.8 days (95% CI = 0.5 to 7.1, p = 0.025). On multivariate regression, LOS in hours was greater in the GA group by 14.1 h (p = 0.042). Conclusions: SA is an effective anesthetic modality for spinal surgery with the advantages of reduced postoperative opioid use, reduced OR time, and shorter LOS compared to GA.

Background: Large language models (LLMs) are increasingly integrated into clinical documentation, decision support, and patient-facing applications across healthcare, including plastic and reconstructive surgery. Yet, their evaluation remains bottlenecked by costly, time-consuming human review. This has given rise to LLM-as-a-judge, in which LLMs are used to evaluate the outputs of other AI systems. Methods: This review examines LLM-as-a-judge in healthcare with particular attention to judging architectures, validation strategies, and emerging applications. A narrative review of the literature was conducted, synthesizing LLM judge methodologies as well as judging paradigms, including those applied to clinical documentation, medical question-answering systems, and clinical conversation assessment. Results: Across tasks, LLM judges align most closely with clinicians on objective criteria (e.g., factuality, grammaticality, internal consistency), benefit from structured evaluation and chain-of-thought prompting, and can approach or exceed inter-clinician agreement, but remain limited for subjective or affective judgments and by dataset quality and task specificity. Conclusions: The literature indicates that LLM judges can enable efficient, standardized evaluation in controlled settings; however, their appropriate role remains supportive rather than substitutive, and their performance may not generalize to complex plastic surgery environments. Their safe use depends on rigorous human oversight and explicit governance structures.

Abstract Radiation therapy (RT) has long been included in the treatment of glioblastoma (GBM). However, radioresistance in cancer cells as well as toxicity in normal tissues are major obstacles to clinical efficacy. Improved understanding of the mechanisms of tumor microenvironment-induced radioresistance during and after radiation therapy can provide fundamental insights to improve clinical outcomes in GBM. Here, using three-dimensional engineered hydrogel models in vitro, we report the influence of extracellular matrix, hypoxia, and adjacent neuronal cells in radiotherapeutic sensitivity. We find that mechanical cues and oxygen availability regulate cellular response to radiation, with softer matrices allowing for more DNA damage. Hyaluronan fragments from the extracellular matrix also modulate rapid metabolic response to radiation, especially in hypoxic environments. We show that neuronal networks influence tumor metabolic activity and the inflammatory response. Overall, we demonstrate here that alternative radiation strategies, such as low dose rate radiation therapy and microenvironmental regulation, have the potential to be more effective in a specific subset of radiosensitive GBM tumors.

Sharing research code in an open access version-controlled repository offers significant benefits for both science as a whole and for individual researchers. In this article, we focus on this practice, which is fully aligned with the NIH’s Gold Standard Science (GSS) program as well as FAIR (findable, accessible, interoperable, reusable) and TRUST (transparency, responsibility, user focus, sustainability, technology) principles. Gold Standard Science supports open science by emphasizing transparency, reproducibility, and the use of best practices that enable others to verify and extend research. Pairing a research article’s cited data snapshot with a versioned, environment-specific code release, deposited in a companion code repository, ensures that, upon submission to a medical journal, readers and reviewers can directly verify results. An executable and updatable companion code repository complements, rather than replaces, established research data repositories. When code underlying medical research results is made openly available, then other scientists can inspect, run, and validate analyses. These activities enhance reproducibility, which is a core aim of GSS. Shared code also facilitates collaborative innovation by allowing researchers to extend the utility of the code to new datasets and applications. For researchers, code sharing can increase visibility, credibility, and citation impact. Demonstrating transparency through shared executable and updatable code builds trust with journal readers, peer reviewers, funders, and peers. Shared code in an open access repository signals adherence to high standards of scientific integrity and attracts opportunities for collaboration. A researcher who shares code receives recognition as a leader in reproducible, trustworthy research consistent with NIH’s GSS principles.

Abstract Background Amyloid related imaging abnormality edema (ARIA‐E) occurs in about 19% of individuals with autosomal dominant Alzheimer disease (ADAD) treated with an anti‐amyloid‐b monoclonal antibody (Salloway et al., 2021). In a previously reported case, ARIA‐E appeared to colocalize with decreases in PiB‐PET uptake (Joseph‐Mathurin, Llibre‐Guerra, et al, 2022), suggesting an association between amyloid‐b (Aβ) removal and ARIA‐E. Here, we compare longitudinal neuroimaging and corresponding neuropathology in an ADAD individual treated with gantenerumab, who experienced multiple ARIA‐E episodes as sulcal effusions that resolved by the end of the four‐year trial. Methods PiB‐PET and MRI were collected pre‐ and post‐randomization (2 and 4 years). The participant consented to brain donation, which was received a year after trial completion. Four tissue samples were taken from the location of the ARIA‐E in the parieto‐occipital left hemibrain as identified by MRI (one block contained the sulcus affected by ARIA‐E; the rest of the coronal section was captured in the remaining three blocks). Area fractions (AFs) of Aβ (10D5 immunohistochemistry (IHC)), tauopathy (PHF1), microglia (Iba1), and astrocytes (GFAP) in one sulcal region of interest (ROI) from each block and PiB‐PET SUVRs of corresponding ROIs were extracted ( n = 4, Figure 1). Additionally, we included PiB‐PET SUVRs corresponding to ARIA‐E findings observed in the right hemisphere at baseline, two‐year, and four‐year visits ( n = 6). Results Overall PiB‐PET uptake increased during the first two years (before ARIA‐E) and decreased during the last two years (including ARIA‐E episodes) (0.03±0.05 vs. ‐0.04±0.04 SUVR/year, p ‐value=0.01, Figure 2). The decrease seemed more pronounced in ARIA‐E ROIs versus normal‐appearing sulcus ROIs (‐0.05±0.04 vs. ‐0.02±0.03 SUVR/year). Lower PiB uptake at last visit appeared associated with lower Aβ AF (estimates=0.03±0.01, p ‐value=0.07). The ARIA‐E ROI had an Aβ AF of 0.009 while normal‐appearing sulcus ROIs had a mean of 0.02+0.003 (Figure 3). AFs for tauopathy, microglia, and astrocytes were within the range of those of normal‐appearing sulcus ROIs, suggesting an Aβ‐specific effect, although unexamined markers may play a role. Conclusions Our preliminary findings indicated that ARIA‐E is associated with longitudinal PiB‐PET decrease and Aβ AF, supporting the link between ARIA‐E, changes in PiB‐PET, and local Aβ removal observed at autopsy. Funding : K01AG080123; U01AG042791; R01AG046179; R01AG053267

Abstract Waldenström macroglobulinemia (WM) is characterized by recurrent MYD88 and CXCR4 mutations, whose prognostic value in patients treated with chemoimmunotherapy remains unclear. Moreover, the typically prolonged progression-free survival (PFS) correlates inconsistently with overall survival (OS), underscoring the importance of examining other surrogates. Progression of disease within 24 months (POD24), an established early end point, delineates functionally high-risk patients in other indolent lymphomas. This international study evaluated 253 patients receiving frontline fixed-duration bendamustine-rituximab (BR), a common chemoimmunotherapy for WM. At a median follow-up of 5.9 years, 5-year PFS and OS were 65% and 87%, respectively; 5-year PFS was similar between MYD88L265P (90%) and MYD88wild-type (WT) subcohorts (64% each; P = .4). Among 89 patients with known CXCR4 status, the subcohort with CXCR4mutation (28%) had shorter PFS (median 3.3 vs 8.8 years; hazard ratio [HR], 2.8; P = .0036) and OS (HR, 2.6; P = .036) compared with CXCR4WT. POD24 occurred in 11.5% of patients who demonstrated inferior subsequent OS (5-year OS, 71% vs 86%; HR, 3.1; P = .005) and higher mortality (standardized mortality ratio [SMR], 3.7), unlike the non-POD24 group, whose mortality was comparable to the matched general population (SMR, 1.1). In conclusion, BR is effective irrespective of the MYD88 status, but CXCR4 mutations and POD24 portend worse outcomes. Patients without POD24 represent a cohort with distinctly favorable outcome.