Faculty Bibliography

OBJECTIVE/UNASSIGNED:Surgical education guided by Halsted's, "see one, do one, teach one," model leans heavily on an apprenticeship structure since formalization of surgical education in the 1890s. While the sentiment holds true, surgical education must adapt with evolution of medicine, work hour restrictions, exponential increase in knowledge, and technological advances. DESIGN/UNASSIGNED:A longitudinal course grounded in adult learning theories was curated to cultivate knowledge in surgery residents on imaging-based liver anatomy and operative approaches, techniques, and decision making. PARTICIPANTS/UNASSIGNED:Junior surgical residents (PGY2-3) in dedicated research time at the Surgical Oncology and Immunotherapy Clinical Research Fellowship Programs of the NIH. RESULTS/UNASSIGNED:Nineteen participants demonstrated significant improvement in all metrics assessed. Overall pre-course knowledge scores (52.1%, 95%CI [48.2%, 56%]) significantly increased in post-course evaluations (87.7%, 95%CI [85.1%, 90%], p<0.0001), maintaining significance in individual course score comparisons. Confidence improved across all disciplines from 2.49 to 2.99 points (5-point Likert scale) (p<0.0001). Significance was maintained in subgroup analysis of individual skills (anatomic delineation (2.93 to 3.51), technical approach (2.39 to 2.83), and decision-making (2.17 to 2.65), (p<0.0001)). Participants reported positive feedback regarding content and course structure which guided real-time course augmentation. CONCLUSION/UNASSIGNED:This course represents a feasible educational model highlighting potential of a theory-based curriculum to enhance surgical education. Emphasizing adult learning theories can support deeper learning and advance critical thinking in trainees.

INTRODUCTION/BACKGROUND:Craniopharyngioma is histologically benign yet locally aggressive, with frequent recurrence. Long-term multicenter outcomes after stereotactic radiosurgery (SRS) remain incompletely defined. METHODS:We performed a retrospective multi-institutional cohort study through the International Radiosurgery Research Foundation including 296 patients from 13 centers. Median age at first SRS was 33.6 years. Median tumor volume was 1.32 cm³ and median margin dose was 12.0 Gy. The primary endpoint was local control (LC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier methods estimated outcomes, and Cox proportional hazards models evaluated predictors of LC. RESULTS:Actuarial 1-, 5-, and 10-year LC was 93.5%, 76.2%, and 70.1%. Actuarial 1-, 5-, and 10-year OS was 98.2%, 93.6%, and 85.2%, and PFS was 92.4%, 73.6%, and 64.8%. Mixed solid-cystic phenotype had worse LC than non-mixed tumors (log-rank p = 0.025); non-mixed phenotype remained independently associated with improved LC (HR 0.53, p = 0.026). Visual fields improved in 10%, were unchanged in 86%, and deteriorated in 4%; visual acuity improved in 6%, was unchanged in 91%, and worsened in 3%. Ten-year freedom from endocrine deterioration was 96.7%. Diabetes insipidus improved in 6.3%, worsened in 0.5% and other pituitary dysfunction was noted in 2.6%, CONCLUSION: In this international multi-institutional experience, SRS achieved durable long-term control with favorable survival and low incidence of visual and endocrinologic dysfunction. Mixed phenotype was an important determinant of LC. CLINICAL TRIAL NUMBER/BACKGROUND:Not applicable.

In response to declining public trust in healthcare institutions, the Institute for Healthcare Improvement (IHI) and the American Board of Internal Medicine Foundation (ABIMF) began a collaborative to identify changes that healthcare organizations could make to regain the trust of their care teams and communities. Using IHI and ABIMF's theory of change as a guide, six healthcare organizations tested this framework on-site and shared lessons learned, identifying the critical role of not just acknowledging past breaches but also demonstrating accountability as crucial steps to strengthening trust. The experiences of three healthcare organizations are summarized here.

Astrocyte loss occurs in various neurological conditions and can disrupt local tissue homeostasis. While astrocytes surrounding border-forming lesions adopt reactive states without restoring astrocyte networks, how astrocytes respond to spatially confined astrocyte loss remains poorly understood. Here we used longitudinal in vivo two-photon microscopy, combined with spatiotemporal transcriptional profiling, to examine astrocyte responses following focal aquaporin-4 antibody-mediated ablation in the somatosensory cortex of adult mouse brain, a model of astrocytopathy relevant to neuromyelitis optica spectrum disorder. Here we show that perilesional astrocytes undergo pronounced structural remodeling during lesion repopulation, characterized by cell proliferation, prolonged multinucleated astrocyte states, polarized process extension into the depleted area and gradual displacement of nuclei into previously unoccupied astrocyte territories. Spatial transcriptomics reveal an injury-associated molecular response that resolves as the astrocyte network is restored. Together, our findings delineate the spatiotemporal dynamics of astrocyte regeneration after astrocyte loss, extending current understanding of astroglial plasticity in the adult brain.

IMPORTANCE/UNASSIGNED:In a phase 2 randomized clinical trial, high-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared with standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC). OBJECTIVE/UNASSIGNED:To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Double-blind phase 3 randomized clinical trial enrolling 455 patients with previously untreated mCRC, conducted in the US through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024). INTERVENTIONS/UNASSIGNED:mFOLFOX6 (modified FOLFOX6 [5-fluorouracil, leucovorin, oxaliplatin]) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab every 2 weeks with either high-dose vitamin D3 (8000 IU daily × 14 days as loading dose followed by 4000 IU daily) or standard-dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end point was PFS assessed by the unstratified log-rank test. Secondary end points included objective response rate, overall survival, and toxicity. Prespecified subgroup analyses of PFS were performed according to known prognostic factors. RESULTS/UNASSIGNED:Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow-up 20 months, the median PFS for high-dose vitamin D3 (n = 228) was 11.8 months (95% CI, 10.3-13.3) vs 10.3 months (95% CI, 9.4-12.2) for standard-dose vitamin D3 (n = 227) (1-sided log-rank P = .25). There were no significant differences in objective response rate between high-dose and standard-dose vitamin D3 (51% [95% CI, 44%-58%] vs 44% [95% CI, 37%-50%], respectively; P = .12), or in overall survival (median, 25.6 vs 27.0 months; 1-sided log-rank P = .66). There were no clinically meaningful differences in the most common grade 3 or greater adverse events between the high- and standard-dose groups, including neutropenia (n = 67 [32%] vs n = 62 [30%]) and hypertension (n = 42 [20%] vs n = 49 [23%]) or in incidence of vitamin D-associated toxicities. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Among patients with previously untreated mCRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04094688.

In the phase 3 randomized controlled trial (RCT; NCT03355209) of fenfluramine in Lennox-Gastaut syndrome (LGS), patients in fenfluramine treatment groups (0.2 mg/kg/day, 0.7 mg/kg/day) experienced greater reduction from baseline in frequency of seizures associated with a fall versus placebo, which was sustained in the open-label extension (OLE) study (NCT03355209). In this post hoc analysis, trajectories of fenfluramine effectiveness and safety, along with dose changes over time, are described for patients with LGS randomized to placebo in RCT who switched to fenfluramine in OLE (PBO-FFA) and those who received fenfluramine in both RCT/OLE (FFA-FFA). Among patients who completed 12 months in OLE (N = 151), numerical improvements in effectiveness outcomes were seen in the PBO-FFA group (n = 59) after initiating fenfluramine and were similar to those in the FFA-FFA group (n = 92). Regression to the mean was not observed in the PBO-FFA group, suggesting that changes were due to fenfluramine. Incidence of the most commonly reported treatment-emergent adverse events increased in the PBO-FFA group after fenfluramine initiation but decreased in the FFA-FFA group in OLE. These data demonstrate rapid improvement in seizure frequency and global functioning in both groups with continued clinical improvement as the mean fenfluramine dose was increased. These results confirm that sustained fenfluramine treatment is effective and tolerable. PLAIN LANGUAGE SUMMARY: This study assessed the change over time in the number of seizures, overall improvement, and side effects in patients with LGS receiving placebo (no active medicine) or fenfluramine in a 14-week study; all patients later received fenfluramine in the extension study. Overall, the number of seizures (associated with a fall) decreased once patients initially receiving placebo changed to fenfluramine (optimal effect around Month 4 while receiving a higher dose), but as expected, common side effects were reported more frequently once patients began fenfluramine treatment. Patients, parents, and doctors should be aware of this time course to allow fenfluramine enough time to work.

Large language models (LLMs) have shown increasing promise in the mental health field. LLMs are especially well suited to play a role in the labor-intensive, costly process of clinical assessment, as they can interact with a patient or participant directly to conduct a mental health assessment. We conducted a preregistered scoping review to (a) describe the unique capabilities of LLMs for clinical assessment, (b) determine the current state of the field in applying LLMs to directly assess patient/participant mental health (including screening, diagnosis, and monitoring of symptoms), and (c) highlight future research to facilitate the application of LLMs. We included work published in both Chinese and English. Only 10 studies met criteria for direct LLM-based mental health assessment. The evidence base was recent and heterogeneous: Four studies focused primarily on diagnostic interviewing or classification, five on symptom or severity assessment, and one on task-based multimodal depression assessment. Studies varied across text, voice, and multimodal formats, and depression was the dominant target. Across studies, stronger performance tended to be reported in tools that used structured interviewing logic, domain-specific adaptation, and clinically anchored reference standards. However, the evidence base remains small, with many studies employing limited validation procedures, and heavily weighted toward early-stage or nonjournal publications. The limited pace of academic validation means that, at present, LLMs are best understood as emerging assessment-support tools rather than replacements for clinical evaluation. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

BACKGROUND:TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare, aggressive subtype that predominantly affects adolescents and young adults. Its marked morphologic heterogeneity can delay recognition and downstream confirmatory testing. METHODS:We assembled a two-center retrospective cohort of patients < 30 years with renal cell carcinoma (n = 228; 59 TFE3-rRCC), using fluorescence in situ hybridization (FISH) as the reference standard. Model development was performed in a development cohort (n = 129), followed by independent external validation (n = 99). We developed TFE3-DualNet, an ensemble of weakly supervised CLAM models trained on routine hematoxylin and eosin (H&E) whole-slide images (WSIs) using patch embeddings extracted from two pathology foundation models (UNI and CHIEF). We compared performance with three immunohistochemistry (IHC) scoring methods and a feature-fusion CLAM baseline using concatenated H&E-derived UNI and CHIEF features, and assessed interpretability by attention mapping. RESULTS:In the external validation cohort, TFE3-DualNet achieved an area under the receiver operating characteristic curve (AUROC) of 0.932, with accuracy 0.879, sensitivity 0.893, and specificity 0.873. The model outperformed IHC scoring methods (AUROC 0.793-0.819; all p < 0.05) and exceeded the feature-fusion baseline (AUROC 0.906). Attention hotspots localized to diagnostically relevant tumor regions and showed concordance with TFE3 IHC patterns. CONCLUSIONS:TFE3-DualNet showed encouraging performance as an interpretable H&E WSI-based screening model for TFE3-rRCC in young patients, supporting its potential use to prioritize confirmatory testing and pathologist review in routine diagnostic workflows.

BACKGROUND:Inflammatory proteins detectable in blood reflect pathoanatomic injury patterns after traumatic brain injury (TBI). Identifying biomarkers of secondary neurologic and systemic injury may improve detection of patients at risk for clinical decline and chronic disability. This study examined the utility of acute and subacute inflammatory biomarkers to differentiate TBI diagnosis and severity, and predict 6-month outcomes. METHODS:-unit increase in biomarker level were reported. RESULTS:Ten biomarkers (c-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-1ꞵ, IL-2, IL-4, IL-6, IL-10, IL-15, IL-17A, tumor necrosis factor (TNF)-α) differed significantly between GCS 3-12 vs. 13-15 TBI, CT-positive vs. CT-negative TBI, and GCS 3-12 TBI vs. OC, at both D1 and W2 (p < 0.001). IL-6, CRP, and SAA showed good discrimination of clinical TBI severity (D1/W2 area under-the-curve (AUC): 0.87/0.87, 0.82/0.88, 0.80/0.85, respectively), and moderate-to-good discrimination of radiographic TBI severity (D1/W2 AUC: 0.81/0.82, 0.78/0.83, 0.77/0.79, respectively). Five W2 biomarkers emerged as multivariable predictors of 6-month unfavorable outcomes (IL-15: AOR = 2.26 [1.14-4.49]; SAA: AOR = 1.91 [1.37-2.67]; IL-6: AOR = 1.80 [1.25-2.61]; IL-17A: AOR = 1.72 [1.24-2.39]; CRP: AOR = 1.40 [1.06-1.85]). CONCLUSIONS:Ten circulating inflammatory proteins were associated with TBI diagnosis and severity at D1 and W2. Of these, five biomarkers expressed subacute (W2) levels predictive of 6-month death/severe-disability, underscoring their potential for validation as a novel biomarker class and integration into TBI prognostic models. Distillation of pro- and anti-inflammatory biomarker cascades in TBI could facilitate precision medicine approaches for risk stratification and therapeutic modulation.