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BACKGROUND AND OBJECTIVES: En bloc spondylectomies are essential for controlling malignant spinal tumors, but existing classification systems are often complex and impractical. This study introduces the Column, Line-of-Sight, Margins, Ring (CLiMR) framework, a novel system simplifying and standardizing en bloc spondylectomy planning and classification. METHODS: A retrospective review of patients who underwent single- or multistage en bloc spinal tumor resections was conducted at a single academic center (October 2019-December 2024). The CLiMR framework assigns scores to 4 components: Column (osteotomies/diskectomies for tumor release), Line-of-Sight (approach for circumferential access), Margin (adjacent structures sacrificed), and Ring (size of the vertebral ring window for safe delivery of neural tissue). Scores were applied using operative notes and imaging. RESULTS: Column scores ranged from 0.5 to 4.5. Of the patients included, 40.9% underwent sagittal split osteotomies, 22.7% radical diskectomies, 18.2% horizontal osteotomies, and the remaining 18.2% combinations of previous osteotomies . A posterior-only approach (Line-of-Sight score = 1) was used in 45.4% of cases, whereas 45.4% required a multistage approach (score = 2). Margin scores reflected increasing morbidity: 31.8% (n = 7) involving chest wall/pleura resection (grade 3), 40.9% (n = 9) requiring eloquent nerve sacrifice (grade 6), and 9.1% (n = 2) necessitating limb sacrifice (grade 7). The majority (86.4%, n = 19) of ring scores were grade 1, requiring laminectomies/facetectomies. The mean CLiMR score was 9.36 ± 2.43, with higher scores correlating with longer hospital stays (R = 0.64, P = .0012), longer case durations (R = 0.61, P = .0023), and increased blood loss (R = 0.40, P = .067). Patients with local recurrence, positive margins, or complications trended toward greater CLiMR scores. CONCLUSION: The CLiMR framework provides a novel, user-friendly method for planning and communicating en bloc spondylectomies. By addressing technical complexities and morbidity, CLiMR enables standardized assessment, facilitates surgical decision-making, and supports future research. This study demonstrates feasibility and lays the foundation for future validation studies.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate are intended to serve as a resource for health care providers to identify individuals who may benefit from cancer risk assessment and genetic counseling and testing; help guide decisions related to genetic testing; and facilitate a multidisciplinary approach in the comprehensive care of individuals at increased risk for hereditary breast, ovarian, pancreatic, and prostate cancer. The current guidelines focus primarily on assessment of pathogenic and likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants associated with increased risk of these cancers. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding screening for prostate cancer and pancreas cancer, as well as testing criteria for nonepithelial ovarian cancer.

Background: A critical component of conducting systematic reviews or meta-analyses is assessing the methodological quality and bias of included studies. Several methodological quality assessment tools have been developed; however, these tools may not be relevant to observational sports medicine research, which carries numerous unique nuances and biases. Purpose: To develop the Sport Publication Observational Research Tool (SPORT), which evaluates and scores the methodological quality of observational sports medicine research. Study Design: Consensus statement. Methods: SPORT was developed through a modified Delphi approach involving members from the Herodicus Society and The FORUM. All active members were invited to participate in the process aimed at building consensus on SPORT content and scoring. After finalizing SPORT, a power analysis led to the independent selection of 55 observational clinical sports medicine studies, which were scored twice by 4 reviewers of varying training levels. Interrater and intrarater reliability for SPORT was assessed using intraclass correlation coefficients (ICCs). The distribution and percentiles for total SPORT score across the 55 studies were calculated. SPORT was also compared with the methodological index for non-randomized studies (MINORS), a commonly utilized quality assessment tool. Results: A total of 51 members participated and achieved 100%, 100%, 98.0%, and 98.0% completion rates for rounds 1 through 4, respectively. The final SPORT included 19 subscores related to methodological quality and bias and achieved 94% consensus approval. Mean SPORT completion time was 6 minutes and 19 seconds per study, which varied significantly by reviewer training level. The subscore "peer review" demonstrated unacceptable reliability and was removed. The remaining 18 subscores exhibited ICC ranges of 0.599 to 0.955 for interrater reliability and 0.530 to 0.936 for intrarater reliability. Total SPORT score demonstrated excellent agreement, for interrater (ICC, 0.967) and intrarater reliability (ICC, 0.966). Median SPORT score across the 55 studies was 20.0 and skewed toward lower scores. There was a moderate significant correlation between SPORT and MINORS ( r [53] = 0.575; P < .001). Conclusion: An objective tool to assess the methodologic quality of observational sports medicine research (SPORT) was successfully developed through a modified Delphi approach with numerous content experts in the field. This tool may be useful in assessing the methodological quality of primary observational sports medicine studies included in systematic reviews and meta-analyses.

Abstract Diffuse hemispheric glioma, H3 G34‐mutant (DHG‐H3 G34) has been primarily molecularly characterized by methylation profiling and sequencing studies. We describe an integrated histomolecular evaluation including high‐resolution copy number profiling of a series of 60 DHG‐H3 G34 to further our understanding of the spectrum of genetic changes associated with this tumor type. Cases were clinically tested using an 187‐gene mutation and fusion targeted neuro‐oncology next‐generation sequencing panel ( n = 60) and Oncoscan chromosomal microarray ( n = 26) by a single laboratory (2018–2022). A subset of cases had immunohistochemical results for OLIG2 ( n = 42), p53 ( n = 48), and ATRX ( n = 46), and methylation array data ( n = 8). Median age at testing was 21 years (range, 12–50). No significant difference was noted in clinical, histopathological, and mutational profile between pediatric and adult patients. H3‐3A G34 mutations included G34R ( n = 56; 94%), G34V ( n = 3), and a non‐canonical G34E ( n = 1). Concurrent mutations most often involved TP53 ( n = 55; 92%), ATRX ( n = 50; 83%), and PDGFRA ( n = 34; 57%). A reportedly primary tumor was confirmed to be hypermutant and had a PMS2 mutation. A single case also showed an FGFR3::FAM184B fusion. All cases with available chromosomal microarray data had unbalanced genomes, which were often complex (14/26; 54%). The most frequent recurrent copy number abnormalities were losses involving 3q, 4q, 10q, 13q, and 18q, and 17p copy‐neutral loss of heterozygosity (cnLOH) encompassing TP53 . This copy number profile was reminiscent of that seen in Grade 4 IDH‐mutant astrocytomas. Collectively, a TP53 abnormality at copy number (12/26, all cnLOH), sequence (55/60) and protein expression (46/48) level was detected in all 60 cases. In conclusion, integrated high‐resolution copy number and histomolecular analysis expanded the spectrum of genetic changes associated with DHG‐H3 G34, including the presence of universal TP53 abnormalities with frequent cnLOH—a copy number abnormality that has been largely unrecognized—for this new 2021 World Health Organization central nervous system tumor type.

ABSTRACT Objective To evaluate demographic and clinical factors influencing survival in patients with major salivary gland tumors (MSGTs) using the surveillance, epidemiology, and end results (SEER) database. Study Design A retrospective cohort study using SEER data from 2000 to 2021. Setting Data were collected from the SEER registry, a comprehensive database capturing cancer statistics across the United States. Methods Patients diagnosed with major salivary gland malignancies were analyzed for demographic factors, including age, sex, race, marital status, and income, as well as clinical variables, including tumor grade and site. Stratification by sex was done to assess sex‐specific outcomes. Results The cohort included 13,869 patients. Key findings include that older age and male sex were associated with worse survival outcomes. Single patients had better survival than married individuals, likely due to younger age at diagnosis. Additionally, higher income and Asian/Pacific Islander race conferred a survival advantage. There were disparate impacts between males and females in income, marital status, and race, with higher income and marriage providing a survival advantage for male patients but none for females. Additionally, Black females but not Black males, and widowed females but not widowed males, had slightly increased hazard ratios compared to White individuals. Conclusion Men and women experience disparate effects that impact survival and outcomes in major salivary gland tumors. These findings highlight the need for targeted interventions to address disparities in care and improve survival outcomes while emphasizing the importance of further research to understand the underlying mechanisms driving these disparities.

Abstract In a real-world analysis of brexucabtagene autoleucel recipients with relapsed/refractory B-cell acute lymphoblastic leukemia (N = 278), lack of response to prior blinatumomab correlates with significantly worse following chimeric antigen receptor T-cell therapy outcomes.

GGGGCC (G 4 C 2 ) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toxicity is thought to result from the accumulation of either repeat RNAs and/or dipeptide repeat proteins (DPRs) translated from repeat-containing transcripts through repeat-associated non-AUG (RAN) translation. To disentangle RNA from DPR toxicity, we mutated a CUG codon predominantly used to initiate DPR translation from all three reading frames. This mutation disrupted DPR synthesis while preserving the expression of repeat-containing RNAs. Despite the accumulation of RNA foci, behavioral deficits and pathological abnormalities, including p-TDP-43 inclusions, STING activation, motor neuron loss, neuroinflammation, and increased plasma neurofilament concentration, were alleviated in C9ORF72 mice. Base editing of the CUG codon also improved molecular phenotypes and survival in patient induced pluripotent stem cell–derived neurons, which highlights the potential of therapeutically targeting DPR production rather than repeat RNAs.

Abstract Background Alcohol consumption and its relationship with cardiovascular disease (CVD) remains controversial. Observational studies have reported J-shaped associations suggesting cardioprotective effects of moderate drinking, while other observational and Mendelian Randomization studies have found dose-response harm. Biases such as abstainer misclassification, sick quitter effects, and residual confounding may obscure true associations. This study aimed to reassess alcohol’s impact on CVD using novel methods to minimize bias. Purpose We evaluated the relationship between alcohol and subclinical (coronary artery calcium [CAC]) and clinical (myocardial infarction [MI], stroke, cardiovascular death, major adverse cardiovascular events [MACE], and heart failure) outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA). We compared conventional models with those using (1) occasional drinkers as the reference group instead of lifetime abstainers and (2) intention-to-treat (ITT) reallocation of former drinkers based on past drinking patterns. Methods MESA is a prospective cohort study of 6,814 participants aged 45-84 years without baseline CVD. Alcohol use was classified as lifetime abstainer, former drinker, or current drinker (occasional [≤1 drink/week], light [2-7 drinks/week], moderate [8-14 drinks/week], heavy [&gt;14 drinks/week]). We used multinomial logistic regression for CAC and Cox proportional hazards models for clinical outcomes across four models: (1) non-drinker reference, (2) lifetime abstainer reference, (3) occasional drinker reference, and (4) occasional drinker reference with ITT reallocation of former drinkers to their previous drinking levels. Results Increasing alcohol consumption correlated with a dose-response increase in CAC. Heavy drinking was consistently associated with severe CAC (&gt;300). In fully adjusted models, light (OR: 1.23, 95% CI: 1.02-1.48), moderate (OR: 1.27, 95% CI: 1.04-1.55), and heavy drinking (OR: 1.42, 95% CI: 1.12-1.78) were associated with higher CAC scores compared to occasional drinkers. Traditional models replicated protective effects of moderate drinking for MI and cardiovascular mortality. However, these associations attenuated in adjusted models. Moderate drinking showed an attenuated, non-significant benefit for MI (HR: 0.64, 95% CI: 0.38-1.06) and cardiovascular mortality (HR: 0.81, 95% CI: 0.53-1.25) in fully adjusted models. Light drinking shifted from null to increased risk for MI (HR: 1.46, 95% CI: 1.11-1.92), stroke (HR: 1.54, 95% CI: 1.17-2.03), MACE (HR: 1.33, 95% CI: 1.12-1.57), and heart failure (HR: 1.42, 95% CI: 1.10-1.84). Conclusion Adjusting for abstainer and sick quitter biases altered the observed relationship between alcohol and CVD, showing increased harm with light drinking, attenuated protective effects of moderate drinking, and a dose-response relationship for CAC in bias-adjusted models. These findings illustrate the importance of methodology in alcohol-CVD relationships.

Abstract Background Identification of the microorganisms causing infection in children with central nervous system infection is important. Conventional cerebrospinal fluid (CSF) tests may provide limited pathogen detection. CSF metagenomic next-generation sequencing (mNGS) may provide broader pathogen detection in a single assay. Methods Results of CSF mNGS testing performed at Mayo Clinic on patients and nonpatients between January 2024 and June 2025 were retrospectively analyzed. The subcohort of children treated at Mayo Clinic was analyzed to assess test performance as compared with conventional CSF diagnostics and potential clinical impact. Results In total 134 patients (138 CSF mNGS tests) from 22 US states and 2 international sites were included. Overall positivity was 16% with viruses representing most (59%) detections. In the Mayo Clinic subcohort (n = 15), test positivity was 27%: organisms included single detections of Streptococcus mitis group and HIV type 1, as well as 2 detections of Epstein-Barr virus, all confirmed by conventional tests. Positive results were associated with CSF pleocytosis (P = .026). Higher yield was observed in participants whose care was overseen by pediatric infectious diseases (PID) specialists (P = .026) and when a specimen hold strategy was applied (P = .033). Most results (87%) did not alter antimicrobial therapy, with 2 negative results contributing to antimicrobial de-escalation. Conclusions CSF mNGS demonstrated higher diagnostic yield in patients whose specimens showed CSF pleocytosis and in those who had PID consultation. Diagnostic stewardship strategies were applied, including specimen hold approaches and PID consultation.