Faculty Bibliography

Renal papillary necrosis (RPN) is an uncommon but important cause of hematuria in patients with sickle cell trait. We report a 28-year-old female with sickle cell trait and beta thalassemia who developed recurrent, transfusion-dependent gross hematuria. Despite extensive imaging, endoscopic evaluation, and conservative management, bleeding persisted. Ureteroscopy demonstrated findings consistent with RPN. The patient required intensive multidisciplinary care and 21 units of packed red blood cells. Hematuria ultimately resolved following treatment with oral epsilon-aminocaproic acid. This case highlights the potential severity of RPN in sickle cell trait and supports consideration of antifibrinolytics as salvage therapy in refractory cases.

PURPOSE/UNASSIGNED:Orbital fractures are a major reason for ophthalmologic consultation in the emergency department. In this study, we studied ocular signs associated with intervention and compared 4 previously published protocols to identify which best identified higher risk patients in need of consultation. METHODS/UNASSIGNED:We performed a retrospective cross-sectional study of patients from the BALCITE (BALtimore Consultation, Inpatient, and Trauma of the Eye) database who received ophthalmologic consultation. Our primary outcomes were the ocular and orbital signs associated with receiving intervention. Our secondary outcome identified the most sensitive and specific screening algorithm for orbital fractures by comparing four existing protocols (HOPE+CT, STOP, MEE, and UTH) to our large independent cohort. RESULTS/UNASSIGNED: < 0.001). The STOP tool had the highest sensitivity of 96.3%, demonstrating a potential 29% reduction in hospital fracture consults, followed by MEE, with a sensitivity of 93.1%. The HOPE+CT tool had the highest specificity of 95.6%. CONCLUSION/UNASSIGNED:The presence of an APD and periorbital laceration are strong indicators of urgent ophthalmologic treatment in the setting of acute orbital fractures. Supportive implementation of the STOP and MEE algorithms can effectively screen orbital fracture patients to help triage in the acute setting, improve resource utilization, and reduce healthcare costs.

The neighborhood environment influences the amount of children's screen time, which in turn affects later development. Few studies have examined the potential for parent-child interventions to moderate such associations. This study examined the link between neighborhood disorder (observed and parent-reported) and infant screen time at 9 months, and whether the PlayReadVIP intervention attenuates this relation among Black/African-American and White families in Flint, MI. Three -hundred and ninety-nine families were included in analyses. Multigroup SEM path analyses indicated that observed neighborhood disorder predicted screen time for all participants (β=.19), but perceived neighborhood disorder was a significant -predictor of infant screen time only for the Control group (β=.11). Findings support the potential of early parent-child -programs to attenuate a range of risk factors for children's development.

BACKGROUND AND OBJECTIVES/OBJECTIVE: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 cm3. 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 cm3 (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/CONCLUSIONS: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 cm3 supports durable nidus control with acceptable toxicity. VS-SRS represents a key modality in multidisciplinary management of this historically difficult-to-treat population.

The inherently slow acquisition speed of MRI makes abdominal imaging highly sensitive to respiratory motion artifacts. Since the early days of MRI, the development of respiratory motion compensation techniques has been an active research topic, and this field has seen substantial progress. Despite these advances, the majority of these techniques are not used in daily clinical practice, and motion management methods used in clinical abdominal MRI today have changed little over the past decades. This observation points to a significant gap between technical innovation and clinical translation in this area. This review is motivated by this question: why have so many motion management techniques not been adopted into routine clinical workflows? Unlike conventional survey-style reviews that focus on summarizing emerging methods, this article takes a different, and perhaps opposite, perspective to investigate why those technologically sophisticated innovations are misaligned with practical clinical needs. Specifically, we discuss the barriers behind the gap between research advances and clinical practice, clarify the clinical requirements for effective respiratory motion management in abdominal MRI, and highlight research directions with stronger relevance to routine workflows. The review begins with an overview of the clinical impact of respiratory motion in abdominal MRI, followed by a discussion of standard abdominal MRI sequences and their motion sensitivity. We then summarize current clinical strategies and advanced approaches, along with the barriers that hinder their clinical adoption. The article concludes with future directions and broader lessons learned from this translational gap, with the goal of guiding future developments toward improved clinical integration.

Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45-74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45-74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen's d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen's d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

INTRODUCTION/UNASSIGNED:Few populations face more disadvantage than those with lifelong intellectual and developmental disabilities (IDD) and those with serious mental illness (SMI). People with IDD may face unique challenges in the manifestation and treatment of SMI; little is known about these challenges during the widespread expansion of telehealth mental health services during the COVID-19 pandemic which disrupted service availability. METHODS/UNASSIGNED:Using Medicaid claims from Kansas, Massachusetts, New York and South Carolina, mental health service utilization patterns for three cohorts of people ages 1-45 years were studied: those with IDD, those with SMI, and those with SMI and IDD. Utilization was examined before (2018-2019) and during (2020-2021) the emergence of telehealth services for each cohort. Meta-analysis was used to compare odds of mental health service utilization by demographic subgroups. RESULTS/UNASSIGNED:The prevalence of mental health service utilization was approximately 75% for the IDD/SMI cohort, 60% for the SMI cohort, and 30% of the IDD cohort in 2018. Teens 13-17 years and young adults tended to have the highest levels of service utilization. Service utilization was driven by different diagnoses for the groups. The SMI cohort utilized services significantly more for mood and anxiety disorders, and the IDD cohort utilized services significantly more for comorbid neurodevelopmental conditions, anxiety, and trauma-related disorders. The IDD/SMI cohort utilized services more bipolar and related disorders and had a younger median age of service utilizers for trauma- and stress-related disorders than the SMI cohort. DISCUSSION/UNASSIGNED:The IDD/SMI cohort had the highest mental health service utilization rates compared to the other two cohorts, with minimal urban-rural differences, suggesting mental health services may be reaching those at the highest levels of risk for adverse outcomes. People with IDD demonstrated substantially lower rates of telehealth utilization for mental health needs; however, people in the cohort with IDD and SMI demonstrated similar or higher rates (in adults) of telehealth utilization compared to people with SMI only. Even with expanded telehealth services, the COVID-19 pandemic appeared to partially disrupt utilization across all cohorts and age groups. Findings suggest that people with IDD and SMI experience trauma- and stressor-related disorders that require treatment at younger ages than people with SMI only.

BACKGROUND:Traumatic encephalopathy syndrome (TES) is a clinical research construct used to identify individuals at risk for chronic traumatic encephalopathy (CTE) following exposure to repetitive head impacts (RHI). Adjudication of TES relies on clinical features such as progressive cognitive impairment and neurobehavioral dysregulation. Blood-based biomarkers and structural neuroimaging abnormalities have been associated with TES but are not part of the criteria. This study evaluated whether TES identification was associated with the combined contribution of cognitive performance, blood biomarkers, and structural neuroimaging measures across two well-characterized cohorts. METHODS:Participants included 158 professional fighters from the Professional Athletes Brain Health Study and 149 former American football players from The DIAGNOSE CTE Research Project. Three indices were constructed representing complementary domains: a cognitive index reflecting cohort-specific cognitive features, a blood biomarker index including plasma neurofilament light chain, glial fibrillary acidic protein, total tau, tau phosphorylated at amino acid 231, and APOE-ε4 carrier status, and an imaging index comprising volumetric MRI measures of subcortical structures, ventricles, and corpus callosum subregions. Grouped weighted quantile sum regression models were estimated within each cohort to evaluate associations between these indices and TES while adjusting for age, race, competition status, and RHI exposure. RESULTS:Multidomain models demonstrated improved model performance compared with single-domain models in both cohorts (PABHS: AUC = 0.91, PPV = 0.80; DIAGNOSE CTE: AUC = 0.84, PPV = 0.85). Biomarker and imaging indices contributed additional information across cohorts, although imaging contributions were more prominent in fighters whereas blood biomarker associations were stronger in football players. CONCLUSION/CONCLUSIONS:TES in RHI-exposed athletes was associated with a convergent clinicobiological profile observed across two independent cohorts with distinct exposure patterns. These findings support multidomain analytic frameworks for evaluating correlated biological signals in RHI-exposed populations and may inform future studies of TES and CTE.

BACKGROUND:While previous literature has established a link between psychopathology symptom trajectories and psychosocial risk, most studies have not extended into adulthood or incorporated comprehensive risk measures. We aimed to identify symptom trajectories for externalizing and internalizing symptoms over a 25-year span and predict them using machine learning. METHODS:We used data from a longitudinal birth cohort study (N = 317, 171 females). Psychopathology symptoms were measured between age 8 and 33. Symptom trajectories were identified using growth mixture models. An extensive battery of risk and protective measures over the lifespan (e.g., polygenic scores, psychosocial risk factors, temperament) was used to train machine learning-based classification models. RESULTS:We identified three trajectories for both externalizing and internalizing symptoms (entropy > 0.8, likelihood ratio test p < .05): Low, increasing (late-adolescent emergence), and decreasing (childhood-limited) symptoms classes. Both genetic (e.g., polygenic scores for cognition and mental disorders) and environmental factors (e.g., adverse family characteristics, poor social functioning) predicted symptom trajectories. For externalizing symptoms trajectories, random forest achieved fair discriminatory power with a multiclass macro-average AUC of 0.77 and a multiclass micro-average of 0.88. For internalizing symptoms trajectories, logistic regression achieved modest discriminatory power with a multiclass macro-average AUC of 0.75 and a multiclass micro-average of 0.83. CONCLUSIONS:Psychopathology risk trajectories vary across development and are influenced by diverse risk factors. Understanding these risk factors can support early identification of at-risk individuals and inform targeted prevention and intervention efforts.