Faculty Bibliography

The 2025 Leon Thal Summit convened an international panel of clinicians, neuroscientists, neuropathologists, and neuroimaging specialists to evaluate the current state of biomarker development for chronic traumatic encephalopathy (CTE) and to outline priorities for advancing translational research for this important area. Discussions integrated emerging findings from longitudinal cohorts, new molecular and neuroimaging approaches, expanding post mortem evidence, and evolving insights into exposure biology and genetic modifiers. Consensus themes emphasized the need for biomarkers that detect CTE-specific tau proteoforms, integration of existing imaging and fluid markers into traumatic encephalopathy syndrome research criteria, and refinement of multimodal magnetic resonance imaging and blood-based tools that capture early CTE pathology. The group underscored the importance of coordinated, longitudinal clinicopathological studies and collaborative research frameworks to validate candidate biomarkers and accelerate progress toward accurate diagnosis, disease monitoring, and therapeutic development for individuals at risk for or exhibiting signs of CTE.

Delayed chest closure is frequently required following heart and lung transplantation due to graft edema, bleeding, size mismatch, or hemodynamic instability, yet current open-chest management strategies rely largely on improvised spacers with recognized mechanical and physiologic limitations. We describe the design and initial clinical application of a modular open-chest management system intended to provide controlled sternal separation while minimizing mediastinal compression and direct cardiac interaction. The device incorporates interchangeable plates and crossbars constructed from a biocompatible-fiberglass-reinforced polymer selected for mechanical strength, low profile, partial radiopacity, and MRI compatibility. Observational clinical use in thoracic transplant recipients demonstrated reproducible deployment, stable chest wall mechanics, preserved ventricular filling, and compatibility with postoperative imaging without device-related complications. This approach may provide a more standardized and physiologically consistent alternative to improvised open-chest techniques in selected transplant patients requiring delayed closure.

The genomics era has yielded high-quality genome assemblies, comprehensive atlases of biochemical signatures of gene regulation, and genetic associations for thousands of common human diseases and traits. These dramatic advances in observational approaches have not been matched by perturbational genetic tools to facilitate direct and systematic hypothesis testing. Enabled by advances in DNA synthesis and assembly, genome engineering tools, and genomic readouts, synthetic regulatory genomics now promises access to a new scale of genomic manipulation to study the function of cohesive genomic units. Synthetic regulatory genomics is distinguished by the breadth of the genetic manipulations and their divergence from the reference sequence. These new tools enable an expanded focus to encompass sufficiency in addition to necessity and to enable a new era of perturbation analysis.

PURPOSE/OBJECTIVE:Prospective, multi-institutional surgical data collection in pediatric neuro-oncology remains limited despite substantial variation in operative and perioperative management across institutions. To address this, we are developing the NeuroPoint Alliance (NPA) Quality Outcomes Database (QOD) Pediatric Tumor Surgery Registry. Here, we used a modified Delphi process to define a core outcome set for the registry. METHODS:A modified Delphi study was conducted among pediatric neurosurgeons serving as site principal investigators for the proposed registry. Candidate data elements were rated on a 9-point Likert scale. Consensus for inclusion was predefined as ≥70% of respondents rating an item 7-9 and ≤15% rating it 1-3; consensus for exclusion was defined as the reverse. Items not reaching consensus in Round 1, along with new items derived from free-text responses, were re-evaluated in Round 2. Near-consensus items after Round 2 underwent discussion and re-rating in a final virtual round. RESULTS:In Round 1, 48 of 83 candidate items (57.8%) reached consensus for inclusion, while 35 advanced to Round 2. Fourteen additional candidate items were generated from free-text suggestions, resulting in 49 items evaluated in Round 2; 13 reached consensus for inclusion. Seventeen items were classified as near-consensus and advanced to the final round, in which 4 reached consensus for inclusion and 1 for exclusion. Across all three rounds, 66 items achieved consensus. CONCLUSIONS:This modified Delphi study established a consensus-based core outcome set for the NPA QOD Pediatric Tumor Surgery Registry, providing a practical foundation for standardized, prospective, multicenter pediatric neurosurgical oncology data collection.

Inflammatory myocardial and pericardial syndromes (IMPS), including myocarditis, pericarditis, and overlapping myopericardial syndromes, constitute a heterogeneous group of immune-mediated cardiac disorders with clinical trajectories ranging from complete recovery to progressive heart failure and sudden death. This state-of-the-art review synthesizes current insights into immunopathogenesis, emphasizing the interplay among genetic susceptibility, environmental factors, and systemic inflammatory drivers, including rheumatological diseases. A pragmatic diagnostic framework is presented; it integrates targeted serological evaluation, genetic testing, multimodality imaging, and selective endomyocardial biopsy to enable precise etiologic classification. Therapeutic strategies are examined across the spectrum of disease severity, including guideline-directed medical therapy for heart failure, immunosuppression for autoimmune and fulminant phenotypes, and cytokine-directed biologics for recurrent pericarditis. Prognostic determinants, indications for advanced heart failure therapies, and emerging directions in precision immunology, molecular profiling, and AI-enabled risk stratification are discussed to guide future clinical and translational advances.

School-based health centers (SBHCs) play a key role in connecting youth to health services, including primary care. Despite some literature exploring their mental health services, little is known about the role SBHCs play in screening for and treating eating disorders. In this study, we surveyed 56 SBHC providers, assessing their familiarity with providing care and screening for mental health concerns, including eating disorders. We also qualitatively explored areas to improve efforts around mental health care and screening. Results suggest that while the majority of participants indicated that they were familiar with mental health disorders, they were less familiar with eating disorders. Furthermore, despite rating screenings for eating disorders of great importance, the frequency of such screenings was comparably lower. Qualitative findings highlight two emerging themes focused on addressing gaps in mental health care: (a) training, continuing education, and addressing misconceptions around eating disorders; and (b) SBHC staffing and resource constraints.

Protease-activated receptor 2 (PAR₂) mediates oral cancer pain. Patients with metastatic (N + ) cancers report greater pain. PAR₂ is activated by N-terminal proteolytic cleavage. Here we show that proteases encoded by genes overexpressed in N+ cancers from patients with pain (matrix metallopeptidase 1, MMP1 and serine protease 23, PRSS23) elicit protease-specific receptor redistribution (trafficking) and signaling that differs from that promoted by proteases encoded by genes not differentially expressed (transmembrane serine protease matriptase, ST14 and cathepsin S, CTSS). Mixtures of the proteases prepared to model the oral cancer microenvironment revealed that ST14-mediated PAR₂ activation predominated at low protease concentrations. At high concentrations, MMP1 and PRSS23 prevailed over the greater potency of ST14. We propose that PAR₂ activation in oral N+ cancers from patients with pain is driven by high levels of MMP1 and PRSS23. Our study informs design of signaling and location-specific antagonists to provide more efficacious analgesia.

IMPORTANCE/UNASSIGNED:The physician-scientist workforce has been in decline for decades, and the shortage of physician-scientists from racial and ethnic groups that are underrepresented in medicine (URiM) is particularly acute. Medical school is a key developmental period during which research career intentions (RCI) may change, yet little is known about RCI evolution during this period. OBJECTIVE/UNASSIGNED:To evaluate factors associated with RCI among first-year medical students, overall and by URiM status. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This is a cross-sectional analysis of baseline data from the ongoing Longitudinal Evaluation of Research Career Intentions Among Medical Students Study. Participants were first-year medical students enrolled during the 2024 to 2025 academic year at US medical schools accredited by the Liaison Committee on Medical Education. MD-PhD students were excluded. EXPOSURES/UNASSIGNED:The baseline survey collected information on sociodemographic factors, pre-medical school and first-year research experiences (eg, research education, research participation, mentorship, and authorship), medical school learning environment, and psychosocial characteristics. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was RCI in year 1 of medical school, defined as intending to be significantly or exclusively involved in research during one's medical career. Characteristics associated with RCI were evaluated using stability selection. RESULTS/UNASSIGNED:Among 1136 first-year medical student respondents (mean [SD] age, 24.7 [2.7] years; 790 female [69.5%]) at 134 US medical schools, 26.9% (306 students) reported RCI, with a slightly higher prevalence among URiM students than non-URiM students (246 students [28.2%] vs 60 students [23.9%]; standardized mean difference, 0.097). Prematriculation factors associated with RCI among all students included research participation (odds ratio [OR], 1.51; 95% CI, 1.13-2.00), conference presentation (OR, 1.56; 95% CI, 1.16-2.09), and manuscript authorship (OR, 1.38; 95% CI, 1.03-1.86). Postmatriculation factors included research participation (OR, 1.74; 95% CI, 1.31-2.30) and having a physician-scientist role model (OR, 1.72; 95% CI, 1.31-2.30). Factors uniquely associated with RCI among URiM students included prematriculation research experiences (OR, 1.51; 95% CI, 1.14-2.01) and presentation of research (OR, 1.57; 95% CI, 1.17-2.11) and postmatriculation manuscript authorship (OR, 1.84; 95% CI, 1.04-3.25). Among non-URiM students, only postmatriculation factors were uniquely associated with RCI, including having a research mentor (OR, 1.76; 95% CI, 1.34-2.31) and receiving education about physician-scientist work-life balance (OR, 1.63; 95% CI, 1.24-2.15). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cross-sectional analysis of baseline data from an ongoing cohort study found that RCI was prevalent among first-year medical students and was associated with characteristics and experiences prior to matriculation and during year 1. Some factors associated with RCI differed between URiM and non-URiM medical students, suggesting distinct pipelines to research career development. These findings highlight opportunities to support physician-scientist training through tailored education, exposure, and mentorship.

BACKGROUND:Testosterone replacement therapy (TRT) may cause side effects after orthopedic procedures. With total hip arthroplasty (THA) rates increasing, this study evaluates the relationship between TRT and postoperative complications in THA patients. METHODS:A retrospective review in a large academic hospital was conducted of hypogonadal patients treated with TRT, who underwent primary, elective THA between 2012 and 2024. These were 1:2 propensity-matched based on age, body-mass index, and comorbidities to a "control" group that was not treated with TRT. Patient and TRT characteristics including serum testosterone levels, form of administration, 90-day emergency department visits (ED) and readmissions, reoperations and revisions were explored. RESULTS:Among 152 patients aged 61.3 years who underwent THA with a 2.7-year follow-up, TRT was mainly administered intramuscularly (51.3%) or via transdermal gel (46.1%), followed by pellets (2.0%), and oral tablets (1.6%). Overall rates of 90-day ED visits and readmissions did not differ significantly between TRT and control patients (7.9% vs. 5.3%, P = 0.270 and 7.9% vs. 5.6%, P = 0.225, respectively). TRT patients had a significantly lower rate of 90-day ED visits due to surgery-related causes (0.7% vs. 2.3%, P = 0.048) but a significantly higher rate due to non-surgery-related causes (7.2% vs. 3.0%, P = 0.034). The incidence of PJI did not differ significantly between the groups (2.0% vs. 1.0%, P = 0.319). Reoperations and revisions were not different between the groups (P = 0.650 and P = 0.057, respectively). TRT administration form was not associated with 90-day ED visits (P = 0.380), readmissions (P = 0.563), reoperations (P = 0.441) or revisions (P = 0.669). Testosterone levels demonstrated a weak, negative, yet significant correlation with 90-day ED visits (r = -0.35, P = 0.040), but not with reoperations or revisions (P = 0.348 and P = 0.431, respectively). CONCLUSIONS:TRT in THA patients was associated with a reduced rate of surgery-related 90-day ED visits but an increased rate of non-surgery-related 90-day ED visits. Incidence of PJI and overall 90-day ED visits and readmission rates did not significantly differ. Administration form had no significant impact, while higher testosterone levels were linked to fewer 90-day ED visits. Although limited by its retrospective design and patient exclusions, further investigation is warranted to guide perioperative management in these patients, particularly given the known immunomodulatory effects of exogenous TRT.