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Abstract Background/Purpose Diagnosing wrist ligament injuries is challenging; early detection and treatment are important to prevent osteoarthritis progression. Interosseous proximity maps, a proxy measure for joint space, can be generated from volumetric imaging data and may provide important information about wrist health. Artificial intelligence (AI) could enhance accuracy of noninvasive diagnosis based on imaging-derived metrics. This work demonstrates feasibility of AI training using synthetic proximity map data generated from finite element models (FEMs). Methods Personalized wrist FEMs for two asymptomatic participants were created from four-dimensional computed tomography-derived anatomic and kinematic data. Monte Carlo sampling varied 22 ligament material properties and simulated 7,500 unique injury scenarios generating 9,000,000 labeled red, green, and blue (RGB) images of interosseous proximity vector fields from FEM-derived motions. Images were associated with 17 descriptive metrics, including gross wrist angles and bone surface pairs, and used to develop mixed-input convolutional neural networks (CNNs). Model performance was evaluated for identifying specific ligament injuries. Results Average area under receiver operating characteristic curve (AUROC) for CNNs was 0.757 across all injury types and kinematics. In a subset with clinically-relevant functional angles, the average AUROC was 0.824. Best-performing individual ligament AUROCs ranged from 0.807 to 0.999. Sensitivities and specificities exceeded 0.99 for some ligament injury simulations under specific wrist angles and bone surface pairs. Conclusion This study demonstrates the feasibility of using synthetic data from FEMs to train AI models for classifying wrist ligament injuries. Proximity-based RGB images may be a relevant biomarker of ligamentous injury.

ABSTRACT Purpose Substantial endothelial cell loss (∼80%) occurs after keratoplasty. Corneal rigid and scleral lenses are frequently prescribed to manage irregular astigmatism and high refractive error, but lens wear may contribute to hypoxic stress. The relationship between various lens wear and corneal stress after penetrating keratoplasty remains unclear. This study characterizes cell density distribution in post‐keratoplasty corneas and evaluates its influence on swelling during lens wear. Methods Participants ≥5 years post‐surgery, with or without habitual lens wear, were enrolled. Specular microscopy measured endothelial cell density in central, superior, inferior, superotemporal, and superonasal corneal quadrants (@3 mm). Baseline corneal thickness maps (>2 h after waking without lens wear) were acquired using Scheimpflug imaging (Pentacam). Wearers applied habitual lenses and all participants returned 6–8 h later for imaging. Nonparametric tests assessed cell density variation by quadrant and lens designs. Linear mixed models evaluated associations between endothelial parameters and corneal swelling while accounting for within‐subject correlation, repeated measures, lens type, location, and interactions. Results Twenty‐five participants (31 eyes) from three centers were included; 90% had keratoconus preoperatively. Four wore large‐diameter scleral lenses (13%), nine wore small‐diameter scleral lenses (29%), 12 wore corneal rigid lenses (39%), and six did not wear lenses (19%). Cell density across quadrants averaged 780 ± 240 cells/mm 2 . Central thickness decreased slightly in non‐lens‐wearing eyes (−0.3%) but increased in lens‐wearing eyes (1.9% ± 3.1%). Central cell density showed a weak negative correlation with swelling ( r = −0.39, p = 0.03). Compared with non‐lens wearers, corneal rigid ( p = 0.02) and large diameter scleral lenses ( p = 0.05) generated greater swelling; smaller diameter scleral lenses did not. Conclusions Although all eyes fitted with various lens designs were clear, lower central cell density correlated with increased swelling during lens wear, except when smaller diameter scleral lenses were worn. Clinically, however, cell density does not seem to be a robust predictor of corneal swelling induced by lens wear post‐keratoplasty.

ABSTRACT Background Men with castration‐resistant prostate cancer (CRPC) who have a pre‐existing history of cardiovascular disease (CVD) or other comorbidities are often excluded from clinical trials involving oral androgen receptor pathway inhibitors (ARPi). In this study, we compared all‐cause and prostate cancer‐specific mortality among CRPC patients, with and without a pre‐existing history of CVD, receiving ARPi compared to chemotherapy. Methods Men with CRPC were identified using the Surveillance, Epidemiology, and End Results‐Medicare Linked Database from 2004 to 2015. Patients were grouped into two analytical cohorts by drug use. Inverse probability treatment weights (IPTW)‐adjusted Cox models and Fine‐Gray subdistribution hazards models were used to evaluate associations between ARPi and chemotherapy, and between ENZ and AA for all‐cause mortality and cancer‐specific mortality separately. Results The study cohort included 1438 men with CRPC. Nearly 54.4% of patients had a pre‐existing history of CVD. Patients with a pre‐existing history of CVD had a higher incidence of all‐cause and prostate cancer‐specific mortality compared to patients without a history of CVD (all‐cause mortality: 69.7% vs. 59.3%, prostate cancer‐specific mortality: 56.0% vs. 49.5%, respectively). In the pre‐existing history of CVD cohort, the IPTW‐adjusted Cox model showed a significantly lower all‐cause mortality in patients who received APRi, enzalutamide, and abiraterone, versus chemotherapy (IPTW‐adjusted hazard ratio [AHR], 0.56; 95% Confidence Interval [CI], 0.48–0.64; p ‐value < 0.001). Further, the IPTW‐adjusted competing risk model showed significantly lower prostate cancer‐specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW‐AHR, 0.48; 95% CI, 0.41 to 0.57; p ‐value < 0.001). In the without pre‐existing history of CVD cohort, the adjusted Cox model showed significantly lower all‐cause mortality in patients who received APRi than those who received chemotherapy (IPTW‐AHR, 0.49; 95% CI, 0.41–0.60; p ‐value < 0.001). Whereas the IPTW‐adjusted competing risk model showed significantly lower prostate cancer‐specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW‐AHR, 0.52; 95% CI, 0.42–0.64; p ‐value < 0.001). Conclusion In this population‐based cohort of older men with castration‐resistant prostate cancer, treatment with oral androgen receptor pathway inhibitors was associated with lower estimated risks of all‐cause and prostate cancer–specific mortality compared with chemotherapy in patients with and without pre‐existing CVD. These findings add real‐world comparative effectiveness evidence for patient populations not well represented in randomized clinical trials; however, given the observational design and limitations of administrative data, residual confounding and unmeasured clinical differences may have influenced the results.

Diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, arises from various pathogenic mechanisms including gene translocations and fusions. Detection of gene rearrangements using fluorescence in situ hybridization (FISH) is a standard practice for DLBCL diagnosis and guides treatment decisions. High-throughput chromosome conformation capture (Hi-C) DNA sequencing is a next-generation sequencing-based technology to identify genome-wide rearrangements using a single assay. In this study, Hi-C sequencing was performed using FFPE tissues from 159 patients with DLBCL, and identified 746 cancer genes at or proximal to the rearrangement breakpoints with a total of 1903 occurrences. Focusing on clinically important rearrangements, Hi-C detected 102 rearrangements of MYC, BCL2, and/or BCL6 in 92 patients and revealed the fusion partners, including 25 rearrangements missed by FISH. Causes of FISH negative results included FISH-cryptic breakpoints, complex or faint FISH signals, low percentage of FISH positivity, and issues related to tissue fixation. Moreover, in 20 patients (12.6%), Hi-C sequencing detected 22 rearrangements characteristic of other lymphoma types, including CCND1 rearrangements that could lead to reclassification as mantle cell lymphoma. Survival analysis for genome-wide rearrangements using machine learning models identified MYC, PD-L1, CCND1, BCL2, NTRK1/PRCC, RRAS, and FANCE rearrangements with significant prognostic effects in the DLBCL cohort. In conclusion, Hi-C sequencing detects gene rearrangements crucial for diagnosis in an unbiased and molecular manner and showed high sensitivity and specificity in our study. These advantages of Hi-C sequencing offer help to improve the workflow of clinical pathology laboratories, diagnostic precision, and treatment of large B-cell lymphoma.

Abstract INTRODUCTION Chronic traumatic encephalopathy (CTE) is a tauopathy linked to repetitive head impacts. Factors influencing brain regional susceptibility to tau deposition and spreading remain unclear. METHODS We used three datasets: [18F]flortaucipir positron emission tomography (PET) in 157 former professional American football players and 53 controls (DIAGNOSE CTE); cortical myelin water fractions (MWF) in 50 healthy individuals (Myelin Water Atlas); and white matter (WM) tract MWF and functional connectivity (FC) in 100 healthy individuals (Human Connectome Project). We tested associations between tau‐PET uptake and covariance in football players and typical cortical gray matter (GM) MWF, WM tract MWF, and FC. RESULTS Cortical regions with lower typical GM MWF showed higher tau‐PET uptake ( β = −0.399, p = 0.001). WM tracts with lower typical MWF were associated with higher tau‐PET covariance ( β = −0.238, p < 0.001). Higher typical FC was associated with higher tau‐PET covariance ( β = 0.447, p < 0.001). DISCUSSION In former football players at risk for CTE, regional susceptibility to tau deposition may be driven by low myelin and high FC.

BACKGROUND AND OBJECTIVES: Pediatric large-volume brain arteriovenous malformations (AVMs) carry a substantial lifelong hemorrhage risk, neurological symptoms, and treatment morbidity. Single-session stereotactic radiosurgery (SRS) is often unsuitable due to constraints on dose-volume toxicity. Volume-staged SRS (VS-SRS) enables sequential dosing of large nidus volumes, potentially enhancing safety while maintaining efficacy. Evidence in children remains limited. We aimed to evaluate outcomes of VS-SRS for large AVMs in pediatric patients. METHODS: A multicenter retrospective cohort was assembled from 21 centers, including patients aged younger than 21 years treated with VS-SRS for AVMs >10 cm 3 . Clinical and radiological end points included obliteration, hemorrhage, and permanent symptomatic radiation-induced changes (RIC). RESULTS: A total of 103 patients were included (median age 14 years; IQR, 12-17). The median nidus volume at first stage was 18.2 cm 3 (IQR, 12.3-25.6). Median prescription dose per stage was 17 Gy (IQR, 16-18). The median clinical follow-up from the first stage was 57.5 months (IQR, 25-138). Obliteration occurred in 42 of 103 patients (40.8%), with actuarial rates of 6.9% (95% CI: 2.8-14) at 3 years and 29% (95% CI: 20-39) at 5 years. Hemorrhage occurred in 17 of 103 patients (16.5%) during follow-up, and permanent RIC was observed in 9 of 103 patients (8.7%). CONCLUSION: VS-SRS is a reasonably safe, selected option for pediatric large-volume AVMs when microsurgical or endovascular cure is not feasible or prudent. Delivering ≥17 Gy per stage while limiting each treatment volume to <15 cm 3 supports durable nidus control with acceptable toxicity. VS-SRS represents a key modality in multidisciplinary management of this historically difficult-to-treat population.

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).

The NCCN Guidelines for Melanoma: Cutaneous provide strategies for the diagnosis, treatment, and follow-up of patients with cutaneous melanoma, which is among the most common cancers in the United States. The outcome of cutaneous melanoma is significantly influenced by stage at initial presentation. Generally, localized disease and smaller primary tumors have been associated with more favorable prognosis. Thus, the select content featured in this issue focuses on risk factors associated with cutaneous melanoma development and which should be considered during an initial assessment. These include (1) phenotypic predispositions, (2) personal medical history or comorbidities, (3) genetic predispositions, and (4) environmental factors.

Abstract Hematoxylin and eosin (H&E) slides are routinely available in cancer care, but molecular profiling often requires additional tissue processing and turnaround time. We introduce HistoMethyl, a DNA methylation-aware pathology foundation model that aligns whole-slide histopathology with matched genome-scale methylation beta-value profiles during pre-training while requiring only an H&E slide at inference. We evaluated HistoMethyl across four task groups: gene mutation prediction, morphology-associated classification, overall survival prediction, and direct DNA methylation beta-value recovery. Evaluation spanned TCGA cross-validation, a disease-held-out lower-grade glioma cohort, and external cohort validation in CPTAC glioblastoma and SurGen rectal adenocarcinoma, totaling 14 cancer cohorts and 81 gene mutation tasks. The best-performing configuration improved mean mutation AUROC by 5.03 percentage points. By converting DNA methylation supervision into an H&E-only representation, His-toMethyl could support an early molecular triage layer that helps prioritize cases for confirmatory sequencing, methylation profiling, immunohistochemistry, and molecular tumor board review. These image-only predictions are intended to accelerate downstream molecular testing and tissue allocation while leaving final diagnosis and treatment selection anchored in validated molecular assays.