Faculty Bibliography

BACKGROUND:The role of maternal and fetal characteristics in determining kidney size in early childhood remains largely unexplored. This study aims to evaluate the association between birth weight and kidney size in children aged one to six years and explore other children and maternal determinants in a United States cohort. METHODS:We analyzed data from 892 mother-child pairs enrolled in the New York University Children's Health and Environment Study (CHES). Renal sonographic measurements were taken from one to six years of age. Kidney size outcomes included average kidney length, width, depth, total kidney volume (TKV), adjusted kidney length (kidney length/body length), and adjusted TKV (TKV/body surface area). Maternal determinants include age, demographic characteristics, pre-pregnancy BMI, lifestyle, pregnancy complications, and diet during pregnancy. Fetal determinants included sex, birth weight for gestational age z-score, and gestational age at delivery. Anthropometric z change and breastfeeding duration were also considered. Associations were examined using crude and covariate-adjusted linear mixed models. RESULTS:Birth weight z-score and anthropometric z change were observed positively associated with all measures except adjusted kidney length. Female children had smaller average kidney length and TKV, and breastfeeding duration was negatively associated with average kidney depth and TKV. Children of non-Hispanic Black mothers and parous mothers had smaller kidney measures. CONCLUSION/CONCLUSIONS:In NYU CHES, we found that early childhood kidney size measures were consistently influenced by birth weight z-scores and changes in postnatal weight gain z-scores. Additionally, we observed racial differences and the influence of breastfeeding duration on kidney size. TRIAL REGISTRATION/BACKGROUND:Not applicable.

OBJECTIVES/OBJECTIVE:Much research has documented disruptions to parent well-being and family functioning because of the COVID-19 pandemic in the United States, but little is known about how parents' provision of cognitive stimulation to young children has been affected. This question is of added importance for families with low incomes, who were disproportionately disadvantaged by the pandemic. The current study examined whether and how provision of cognitive stimulation at home, as measured by the parent-reported StimQ2, changed for parents with low incomes after onset of the COVID-19 pandemic. We examined scores on a total scale and subscales tapping multiple aspects of verbal responsivity and reading. DESIGN/METHODS:Data from 7 cohorts of families with low incomes across 3 US cities were de-identified and combined into a single analytic sample for secondary analysis. Cohorts ranged in timing relative to the onset of the pandemic (i.e., as early as 2015 and as late as April 2023). Each study contributed data from families assessed at multiple timepoints between birth and age 4 years. RESULTS:Total scores on the StimQ2 increased after the onset of the COVID-19 pandemic. Subscales reflecting reading stayed the same (quantity) or declined (quality), whereas subscales reflecting verbal responsivity increased. CONCLUSION/CONCLUSIONS:Relative to prepandemic levels, low-income parents' child-directed speech and responsivity increased postpandemic, but the quantity of parent-child reading was unchanged and its quality declined. Findings suggest the possibility of stability or improvement among parents with low incomes during the pandemic and opportunities for intervention.

Reliable structural brain measurements are essential for studying neurodegeneration and for designing adequately powered aging and Alzheimer's disease (AD) research. We evaluated the test-retest reliability of FreeSurfer 7.1 morphometric measures in 100 older adults (mean age 73.5 years) ranging from cognitively unimpaired to dementia. Each participant underwent two T1-weighted 3T MRI scans on the same scanner within a short interval (mean 5.5 weeks), minimizing biological change. Segmentation was performed in both standard cross-sectional and longitudinal FreeSurfer modes, focusing on AD-relevant volumes of entorhinal cortex, hippocampus, lateral ventricles, choroid plexus, and the AD cortical thickness signature. Reliability was quantified using absolute and root-mean-square test-retest differences, standard deviation of differences, and intraclass correlation coefficients. Longitudinal processing improved precision by 15-50% across most measures compared with cross-sectional processing, with the largest gain observed for entorhinal thickness. Larger, anatomically well-defined regions (e.g., hippocampus, AD signature) demonstrated higher reliability than small structures or those with complex geometry (e.g., entorhinal cortex, choroid plexus). Image quality, indexed by the Euler characteristic, was the only factor significantly associated with measurement variability; reliability was unrelated to age, sex, cognitive status, inter-scan interval, or amyloid/tau PET burden. Power analyses indicated that detecting a 1% within-individual change requires sample sizes ranging from 36 (AD signature) to >300 (entorhinal cortex). We observed low reliability of choroid plexus volumetry by FreeSurfer 7. These results provide practical benchmarks for expected FreeSurfer measurement variability in older adults. They highlight the advantages of longitudinal processing and rigorous quality control for research on brain aging and AD.

More than 6 million persons living with dementia (PLWD) in the United States rely on the emergency department (ED) for unscheduled care, with up to half discharged home after treatment. The ED-to-home transition poses significant challenges for PLWD and their care partners (referred to as "dyads"), contributing to high rates of ED revisits and adverse outcomes. The Community Paramedic-led Transitions Intervention (CPTI) was developed to address these challenges by adapting the validated Care Transitions Intervention for the ED setting. Delivered by trained community paramedics, CPTI is a short-term 30-day program that includes one home visit and up to three follow-up phone calls. Using a coaching model, paramedic coaches work with members of the dyad to strengthen their knowledge, skills, and confidence to manage their health and successfully navigate the health care system. CPTI is being implemented as part of Emergency Departments LEading the Transformation of Alzheimer's and Dementia Care (ED-LEAD), a cluster-randomized pragmatic trial testing 3 interventions designed to improve outcomes for PLWD discharged home from the ED across 14 health systems and 79 EDs nationwide. This paper describes the CPTI model as implemented within ED-LEAD, detailing its theoretical foundation, structure, training curriculum, workflow integration, and implementation monitoring. This framework can provide a model for health systems, provider groups, and emergency medical service agencies interested in adopting this innovative approach and implementing the CPTI. Insights from its implementation within ED-LEAD will guide future efforts to improve post-ED outcomes and continuity of care for PLWD and their care partners.

Individuals of African ancestry carrying APOL1 (apolipoprotein L1) high-risk genotypes face a markedly increased risk of kidney failure, yet tools to identify those individuals likely to progress to chronic kidney disease are lacking. Here we profiled plasma proteomes of 851 Penn Medicine BioBank participants of African ancestry (285 males and 566 females) with APOL1 high-risk genotypes and preserved estimated glomerular filtration rate (eGFR) (≥60 ml min^-1 1.73 m^-2). Using elastic net Cox regression adjusted for age, sex, eGFR and albuminuria, we derived a nine-protein APOL1 Proteomic Risk Score (APRS) that predicts a composite outcome of ≥40% eGFR decline, kidney failure or death. APRS achieved a time-dependent area under the receiver operating characteristic curve (tAUC) of 86.5%, outperforming the Kidney Failure Risk Equation (66.1%) and polygenic risk scores, with 10-year event rates of 62.5% versus 3.3% across risk quintiles. External validation in Atherosclerosis Risk in Communities and UK Biobank cohorts confirmed robust accuracy (tAUC 82-85%) and consistent performance across demographic and clinical subgroups. Plasma levels of APRS component proteins correlated with kidney tissue fibrosis and tubular injury pathways, indicating strong biological plausibility. By enabling early and accurate prediction of disease progression in APOL1 high-risk individuals, APRS bridges the gap between genetic susceptibility and clinical translation. This scalable and biologically informed approach provides a precision medicine framework for early intervention and may accelerate development of APOL1-targeted therapies to reduce kidney disease disparities.

BACKGROUND:The current generation of 1.3 billion adolescents (10-19-year-olds), most of whom live in low- and middle-income countries, face large and growing mental health problems. Collective action that could lead to significant improvement in adolescent mental health and well-being (AMH) remains limited. We analyse the factors shaping the global prioritization of AMH for funding and action and reflect on a way forward. METHODS:We triangulate data from interviews with key informants knowledgeable in AMH; focus group discussions with youth representatives who are mental health advocates, some with lived experience of mental ill-health; and document review. We collected the qualitative data from 2021 to 2023, followed by thematic analysis and stakeholder consultations. RESULTS:We identify four themes which shape the global prioritization of AMH. First, prevailing interpersonal and institutional stigma and discrimination directed against adolescents with mental health problems hamper attention to AMH. Second, limited data on the burden of mental health problems and evidence of what works have led to the perception among decision-makers that AMH is an intractable problem. Third, diverse ways of framing AMH are often viewed as a sign of weak alignment rather than as opportunities for coalition-building. Fourth, a wide variety and increasing number of stakeholders are involved in AMH, while the stakeholder landscape remains fragmented, inhibiting coalition-building for AMH. CONCLUSIONS:To overcome the barriers that currently impede the prioritization of AMH, we recommend that (1) stakeholders conduct an adolescent-led consultative process to develop an "umbrella framing", supported by common metrics, (2) advocates use existing global platforms to shape the political priority for AMH, (3) decision-makers, funders and research partners invest in meaningful engagement of adolescents (with lived experience), researchers and implementing partners (4) identify a leadership, governance and accountability structure for a global coalition that could transform AMH and (5) conduct context-specific analyses to inform coalition-building nationally.

PURPOSE/OBJECTIVE:To develop and evaluate a hybrid large language model (LLM)- and rule-based algorithm for tracking pancreatic cystic lesions (PCLs) across serial radiology reports and apply it to a single-center cohort to characterize cyst growth using first-to-last and consecutive comparisons. METHODS:This retrospective study included all abdominal imaging reports interpreted by abdominal radiologists between 2005 and 2024. A validated LLM identified reports describing PCLs. A hybrid algorithm combining LLM-extracted cyst features (size, location) with rule-based logic matched dominant cysts across serial reports. Two blinded radiologists independently annotated cyst matches in a subset of reports. Agreement between algorithm and radiologists was assessed using percent agreement and Cohen's κ. Discrepancies were adjudicated by a third radiologist for error analysis. Absolute size-based growth was assessed according to American College of Radiology (ACR) criteria, whereas cyst growth rate as a worrisome feature was assessed per Kyoto criterion, using both first-to-last and consecutive studies. Predictors of meeting the Kyoto cyst growth rate criterion were analyzed using multivariable Cox regression. RESULTS:In 58 patients with 418 longitudinal reports, agreement with the adjudicated reference standard was 96%. Cohen's κ was 0.81 (95% CI: 0.66-0.91). The overall cohort included 8,176 patients (61.8% female; mean age 67.6 ± 11.7 years) with 8,389 cysts across 28,489 reports over 40.6 ± 28.5 months (annual growth rate = 0.35 mm/year). ACR absolute growth criteria classified a higher proportion of cysts than the Kyoto cyst growth rate criterion using first-to-last examinations (16.3% vs. 7.4%, p < 0.001), whereas Kyoto cyst growth rate criterion identified a higher proportion using consecutive examinations (21.4% vs. 14%, p < 0.001). Larger baseline cyst size predicted meeting the Kyoto cyst growth rate criterion (HR 1.9-4.0; highest HR 4.0, 95% CI 3.08-5.21; p < 0.001). CONCLUSION/CONCLUSIONS:A hybrid LLM-rule-based algorithm enables reliable automated longitudinal tracking of PCLs across serial radiology reports. When applied at scale, cyst growth classification varied according to the guideline framework and interval comparison method used, and baseline cyst size was the strongest predictor of meeting Kyoto growth rate threshold.

An important goal of precision medicine is to personalize medical treatment by identifying individuals who are most likely to benefit from a specific treatment. The likely responder (LR) framework, which identifies a subpopulation where treatment response is expected to exceed a certain clinical threshold, plays a role in this effort. However, the LR framework, and more generally, data-driven subgroup analyses, often fail to account for uncertainty in the estimation of model-based data-driven subgrouping. We propose a simple two-stage approach that integrates subgroup identification with subsequent subgroup-specific inference on treatment effects. We incorporate model estimation uncertainty from the first stage into subgroup-specific treatment effect estimation in the second stage, by utilizing Bayesian posterior distributions from the first stage. We evaluate our method through simulations, demonstrating that the proposed Bayesian two-stage model produces better calibrated confidence intervals than naïve approaches. We apply our method to an international COVID-19 treatment trial, which shows substantial variation in treatment effects across data-driven subgroups.

PURPOSE/OBJECTIVE:Fertility preservation (FP) is essential for adolescents and young adults (AYAs) with cancer aged 15-39, yet gaps persist in guideline-concordant care. Despite American Society of Clinical Oncology (ASCO)'s 2018 recommendations, clinician and systemic barriers hinder timely FP counseling. Allied health care professionals (AHPs) play a critical role in supporting patient education and support. This study examined AHPs' conceptualizations of optimal FP care, assessed alignment with ASCO guidelines, and identified facilitators and barriers to implementation. METHODS:This study analyzed data from Cohort 4 (2020) of the Enriching Communication Skills for Health Professionals in Oncofertility (ECHO) program, an 8-week web-based training for AHPs on AYA reproductive health communication. A directed content analysis was used to qualitatively examine factors influencing FP care delivery. Multilevel themes were analyzed to identify potential mechanisms to facilitate optimal FP care, resources needed for implementation, and barriers to FP patient education. RESULTS:Among 130 AHPs (92% female, 72% White), most were social workers (29%) or oncology nurses (25%), working in academic cancer centers (49%). Alignment with ASCO guidelines was observed in fertility risk discussions (72%) and specialist referrals (56%). Key facilitators included patient education (46%), clinician training (48%), and interdisciplinary collaboration (47%). Primary barriers identified were systemic challenges (20%), including financial constraints, limited institutional resources, and time pressures. CONCLUSION/CONCLUSIONS:AHPs demonstrated strong commitment to advancing FP care for AYAs with some alignment to ASCO guidelines. Persistent gaps in psychosocial support and system-level resources highlight the need for expanded clinician education, stronger interdisciplinary networks, and institutional prioritization to ensure equitable, developmentally appropriate FP care.