Citations

Background: Monitored anesthesia care (MAC) combined with regional anesthetic techniques is commonly used for open reduction and internal fixation (ORIF) of unstable ankle fractures. When compared to general anesthesia (GA), MAC with regional anesthesia has been associated with reduced systemic adverse effects and shorter recovery times, although regional anesthesia carries additional costs and potential complications of its own. A new technique involving the infiltration of high-volume, low-concentration (VL) local anesthetic was therefore developed. When used in conjunction with MAC, we refer to this technique as MAC-VL. This study evaluates outcomes and recovery metrics following outpatient ankle ORIF performed under GA vs MAC-VL without regional anesthesia. Methods: An IRB-approved retrospective cohort study was conducted including 159 adults who underwent outpatient ankle ORIF between February 1, 2023, and January 31, 2026. Patients were identified using standardized diagnostic and procedural codes and grouped according to anesthesia type. All patients received a standardized injection of local anesthetic around the proposed operative sites before the procedure; anesthesia type was MAC (n = 48) or GA (n = 111). The primary outcome was time to discharge, defined as the interval from incision closed to hospital discharge. Secondary outcomes were considered exploratory and included tourniquet, operative, anesthesia time, time in room, Post Anesthesia Care Unit length of stay, conversion from MAC to GA, reported postoperative nausea and vomiting, admissions, and postoperative emergency department visits. Results: Among 160 procedures for which no significant difference in case mix could be detected with the numbers available, MAC-VL was associated with a significantly shorter time to discharge—reducing discharge time by 55.2 minutes ( P < .001) following adjustment for demographic, clinical, and operative covariates—and shortened total anesthesia and operating room time compared with GA. With the numbers available, no significant difference was detected for the remaining secondary outcomes. Conclusion: The MAC-VL protocol was associated with shorter operating room and recovery times and may improve health care resource use. Level of Evidence: Level III, retrospective cohort study.

The chemotherapeutic 5‐fluorouracil (5‐FU) is commonly used to treat solid tumors, especially colorectal cancer. Deleterious variants in DPYD, which encodes dihydropyrimidine dehydrogenase (DPD), are strongly associated with severe and potentially lethal 5‐FU toxicity. Phenotypic assays for DPD function have been proposed as alternative or complementary approaches to identify DPD deficiencies with the rationale that they may capture unrecognized causes. These assays include the direct measurement of DPD activity in peripheral blood mononuclear cell (PBMC) lysates and measuring plasma metabolites uracil (U), dihydrouracil (UH 2 ), and the dihydrouracil/uracil (UH 2 :U) ratio. We evaluated correlations between PBMC DPD activity and plasma metabolite measures in matched samples from 203 patients with available DPYD exome sequencing data. We also compared the ability of phenotypic measures to identify carriers of deleterious DPYD variants. In addition to established high‐risk variants, we identified three rare DPYD variants predicted to be deleterious: c.274C>G, c.966C>A, and c.1435G>A. Collectively, these variants were associated with impaired DPD function with effect sizes comparable to well‐studied toxicity‐associated variants. At the population level and within carriers of specific genotypes, weak but significant correlations were observed between PBMC DPD activity and either UH 2 :U ratio or U level. These findings suggest that although phenotypic assays can detect severe DPD deficiency, high variability limits their utility as standalone diagnostic tools. Integration with genetic testing may provide a more robust pretreatment risk assessment strategy.

The bone marrow immune microenvironment (BMME) is a critical factor in multiple myeloma (MM) pathogenesis. Despite higher incidence of MM among self-identified African Americans, the relationship between African genetic similarity and the BMME remains unclear. We present the largest analysis to date assessing the impact of Ancestry on the BMME in myeloma (N=320, including 64 with ≥50% African genetic similarity, AFR-High) leveraging our recently generated Immune Atlas. AFR-High was associated with enrichment of late T-effector cells, driven by rare cytotoxic CD4⁺ T cells, suggesting a distinct adaptive BMME. AFR-High exhibited expansion of late-differentiated adaptive NK cells with high cytotoxic GNLY and GZMH expression. AFR-High depicted reduced CD14⁺ monocytes, increased CD16⁺ non-classical monocytes, and expansion of macrophage-like monocyte populations with enrichment of metabolic adaptation, efferocytosis and phagocytic clearance programs, and immunoregulatory pathways. These findings reveal a shift from an innate inflammatory immune landscape toward adaptive cytotoxic and immunoregulatory remodeling associated with African genetic similarity in MM.

Background: Operative decision-making in gastric gastrointestinal stromal tumor (GIST) surgery is strongly influenced by tumor anatomy. Although surgeons routinely consider anatomic features such as proximity to the gastroesophageal junction, posterior wall location, and endophytic growth during operative planning, their combined association with operative strategy has not been systematically evaluated. Methods: We evaluated whether commonly recognized anatomic features of gastric GISTs were associated with operative strategy in a contemporary minimally invasive surgical cohort. Tumors were characterized according to the presence of three predefined anatomic features: proximal location near the gastroesophageal junction, posterior wall involvement, and endophytic growth pattern. Cases were grouped as lower (0–1 features) or higher (2–3 features) complexity. The primary outcome was operative strategy, categorized as simple (wedge resection or enucleation) or complex (partial gastrectomy or transgastric resection). Associations between anatomic complexity and operative approach were evaluated. Results: A total of 83 patients were included, with 50 (60.2%) classified as lower complexity and 33 (39.8%) as higher complexity. Operative strategy varied significantly by complexity group. Tumors in the higher complexity group were more frequently managed with complex operative techniques, including partial gastrectomy and transgastric resection ( P = .002). This association remained significant after adjustment for tumor size (odds ratio 2.87, 95% CI: 1.12–7.65, P = .031). A graded relationship was observed, with increasing use of complex techniques as the number of anatomical features increased. The robotic platform was used more frequently in higher complexity cases ( P = .03). Perioperative outcomes were comparable between groups. Conclusions: Recognized anatomical features of gastric GISTs were associated with operative strategy and reflected real-world surgical decision-making. Systematically describing these features may facilitate preoperative assessment and improve consistency in reporting operative approaches.

Abstract Introduction Quantitative interpretation of pediatric brain [ 18 F]-FDG PET is limited by the lack of age-matched normative reference databases, despite substantial developmental variation in cerebral glucose metabolism. This study aimed to construct a large-scale normative pediatric [ 18 F]-FDG PET database and develop an age-specific z-score mapping framework for quantitative evaluation of pediatric epilepsy. Method Pediatric brain PET data were retrospectively derived from clinically acquired whole-body or dedicated [ 18 F]-FDG PET examinations in participants 0–19 years of age without neurologic disease or visible brain abnormalities. A total of 417 PET scans from 341 participants were stratified into five developmental age groups: infancy, early childhood, middle childhood/school age, adolescence, and late adolescence. SUVR maps were generated using whole-brain atlas and brainstem reference regions. Voxel-wise t-test analyses were performed to characterize age- and sex-related metabolic differences. Age-specific voxel-wise mean and standard deviation maps were generated from the normative cohort and used to calculate age-matched hypometabolic z-score maps in 14 pediatric patients with epilepsy. The resulting abnormalities were qualitatively evaluated for concordance with epileptogenic findings identified on clinical MRI and/or PET by expert image review. Results Voxel-wise analyses demonstrated prominent age-dependent SUVR differences, particularly between infancy and older age groups. With whole-brain atlas normalization, older children showed progressively higher relative SUVR in cortical and cerebellar gray matter regions, whereas infancy showed relatively higher SUVR in the occipital cortex, white matter, thalamus, and brainstem. Brainstem normalization produced distinct developmental patterns, emphasizing higher white matter SUVR in infancy and broader gray matter differences in older groups. Sex-related differences were limited and regionally specific. Whole-brain atlas normalization showed lower variability than brainstem normalization and was selected for z-score mapping. In representative epilepsy cases, age-matched z-score maps identified focal or regional hypometabolism corresponding to malformations of cortical development, focal cortical dysplasia, mesial temporal sclerosis, nonlesional MRI cases, remote insult, tumor-related abnormalities, and Sturge-Weber syndrome. Discussion A large-scale normative pediatric [18F]-FDG PET database can support developmentally appropriate quantitative interpretation of pediatric brain PET. Age-matched z-score mapping may complement visual assessment by highlighting abnormal cerebral glucose metabolism in pediatric epilepsy, although findings should be interpreted with MRI, EEG, seizure semiology, and other presurgical data.

This cohort study evaluates the association between measured lipoprotein(a) level and incident venous thromboembolism.

Abstract Purpose Large language models (LLMs) have proven performance for certain diagnostic tasks; however, limited studies have evaluated their consistency in recommending appropriate medication regimens for a given diagnosis. Medication management is a complex task that requires synthesis of drug formulation and complete order instructions for safe use. Here, the performance of GPT-4o, an LLM available with OpenAI’s ChatGPT, was tested on 3 medication management tasks. Methods GPT-4o performance was tested on 3 medication tasks: identifying available formulations for a given generic drug name, identifying drug-drug interactions (DDIs) for a given medication regimen, and preparing a medication order for a given generic drug name. For each experiment, the model’s raw text response was captured exactly as returned and evaluated using clinician evaluation in addition to standard LLM metrics, including Term Frequency-Inverse Document Frequency (TF-IDF) vectors, normalized Levenshtein similarity, and Recall-Oriented Understudy for Gisting Evaluation (ROUGE-1/ROUGE-L) F1 score between each response and its reference string. Results For the first task of drug-formulation matching, GPT-4o had 49% accuracy for generic medications being matched to all available formulations, with an average of 1.23 omissions per medication and 1.14 hallucinations per medication. For the second task of drug-drug interaction identification, the accuracy was 54.7% for identifying the DDI pair. For the third task, GPT-4o generated order sentences containing no medication or abbreviation errors in 65.8% of the cases. Conclusion Model performance for basic medication tasks was consistently poor. This evaluation highlights the need for domain-specific training through clinician-annotated datasets and a comprehensive evaluation framework for benchmarking performance.

Purpose To compare lower extremity soft tissue injury and revision surgery rates for patients with anorexia nervosa (AN) and bulimia nervosa (BN) compared with matched controls. Methods This retrospective cohort study used a deidentified claims database. Patients were included if they carried an International Classification of Diseases code for AN or BN. Respective matched cohorts for AN and BN were created using propensity score matching. Primary and revision surgeries for anterior cruciate ligament (ACL) reconstruction, posterior cruciate ligament reconstruction, knee collateral ligament reconstruction, meniscus repair or meniscectomy, and any ankle ligament reconstruction were identified by their CPT codes. Patients over the age of 40 and without a minimum 2‐year follow‐up after primary surgery were excluded. Differences in prevalence and revision rates were analyzed. Results A total of 56,146 patients with AN and 42,630 patients with BN were included in this study with equal numbers in respective matched cohorts. Patients with BN showed an increased risk of ACL injury (relative risk = 1.32, P = .019), medial collateral ligament injury (1.17, 0.04), calcaneofibular sprain (1.92, <0.001), deltoid sprain (1.41, 0.004), and unspecified ankle sprain (1.44, <0.001). Patients with AN showed an increased risk for calcaneofibular sprain (1.25, 0.007), deltoid sprain (1.28, 0.015), and unspecified ankle sprain (1.17, <0.001). Patients with BN were more likely to have revision ACL repair (1.89, 0.02), partial meniscus revision (3.44, <0.001) and any meniscus revision (4.74, <0.001) while patients with AN were more likely to have an ACL revision (2.81, <0.001), partial meniscus (4.37, <0.001), and any meniscus (4.52, <0.001). Conclusions In this study, patients with AN and BN had a significantly increased risk for various knee and ankle injuries and revision surgeries compared with matched controls. Additionally, patients with AN and BN who sustained these injuries were more likely to undergo a revision surgical procedure within the first 5 years of the primary procedure. Level of Evidence Level III, retrospective comparative study.