Faculty Bibliography

BACKGROUND/UNASSIGNED:Hydroxychloroquine (HCQ) is a cornerstone of systemic lupus erythematosus (SLE) management. However, the medication can accumulate within organs and cause toxicity including retinopathy. HCQ is usually discontinued once ocular toxicity is diagnosed, but this is not always sufficient to avoid further damage. Whether retinal injury progresses following HCQ cessation, and which patients are at risk, is of great interest. Prior studies examining progression after HCQ discontinuation are sparse and limited by small sample sizes, and none specifically examine patients with SLE. This study aimed to identify predictors of progression of HCQ-induced retinopathy in SLE patients after medication discontinuation. METHODS/UNASSIGNED:We queried the NYU Lupus Cohort to identify patients with documented HCQ-induced retinopathy who discontinued HCQ and had at least one optical coherence tomography (OCT) follow-up to assess for progression. Demographic information, cumulative HCQ dose, duration of therapy, presence of chronic kidney disease or tamoxifen use, SLE disease activity, and ophthalmologic follow-up intervals were collected. Two ophthalmologists independently reviewed OCT and Humphrey visual field data to confirm retinopathy, grade its severity, and determine progression following drug discontinuation. Statistical analysis was performed using Student's t-test or Wilcoxon rank-sum test for continuous variables and Chi-square or Fisher's exact test for categorical variables. RESULTS/UNASSIGNED:Twenty-one patients with confirmed HCQ retinopathy were included. The mean duration of HCQ therapy preceding diagnosis was 16.2 years and the mean cumulative exposure was 1884 g. Retinal toxicity progressed in 6 patients (28.6%) despite HCQ discontinuation. There appeared to be a trend towards a greater likelihood of progression with more severe retinal toxicity at the time of diagnosis. However, there were no differences between progressors and non-progressors with respect to age at diagnosis, duration or cumulative HCQ exposure, SLE disease activity, tamoxifen use, chronic kidney disease, or guideline-concordant care. CONCLUSIONS/UNASSIGNED:Nearly thirty percent of patients with SLE and HCQ retinopathy progressed despite drug discontinuation. No baseline clinical predictors were associated with progression, though there was a descriptive trend toward greater risk with more severe baseline retinopathy. These data emphasize the importance of continued ocular surveillance for progression of toxicity after discontinuation.

OBJECTIVE:Physical activity can reduce cardiovascular disease and depression risk and improve quality of life in patients with systemic lupus erythematosus (SLE). To facilitate physical activity and achieve health benefits in patients with SLE, it is critical to understand potential barriers to physical activity, including socioeconomic, social, demographic, quality-of-life, or clinical factors. METHODS:We conducted cross-sectional analyses of data from a large, diverse cohort of patients with SLE. All completed the International Physical Activity Questionnaire, recalling the past seven days of vigorous physical activity, moderate activity, or walking. Data included financial insecurity, Everyday Discrimination Scale, education, demographics, lupus-specific disease activity, immunosuppressive medication, Census Block Area Deprivation Index, and patient-reported pain, fatigue, and cognitive function. Multivariable models included logistic regression for dichotomous outcome of "any" moderate/vigorous physical activity and quasi-Poisson model for total combined days of moderate and vigorous activity. RESULTS:Of the 271 participants, 170 (63%) reported any moderate or vigorous activity in the past 7 days (mean = 2.6 days of moderate/vigorous activity). Only 4% reported zero days of physical activity. Logistic regression analysis indicated that active disease was associated with 47% lower odds of engaging in any moderate/vigorous physical activity (P = 0.04) and with a 35% reduction in the mean number of days of moderate to vigorous physical activity (P = 0.04). In contrast, individual- and area-level socioeconomic factors and patient-reported outcomes were not associated with physical activity. CONCLUSION/CONCLUSIONS:Moderate/vigorous physical activity was negatively associated only with disease activity. The current study reinforces the need primarily to control SLE disease activity to promote patients' ability to be physically active, which may improve symptoms.

Polygenic risk scores (PRS) compress genome-wide associations into a single predictor, but this aggregation obscures the distinct biological mechanisms through which genetic variation shapes complex traits. Here we introduce a framework that additively decomposes a trait's PRS, without loss of SNP heritability, into independent components defined by the tissue-specific and tissue-agnostic cis-regulatory elements (CREs) in which its variants act. Applied to blood pressure (BP) using ~0.5 million CREs across four BP-relevant tissues (adrenal gland, artery, heart, kidney), the framework reveals that regulatory effects are globally additive across tissues yet locally non-additive, and that the resulting partitioned scores carry pronounced, reproducible heterogeneity in their effects on BP and cardiovascular outcomes. We show this heterogeneity reflects gene-environment interactions, and trace one example to its mechanism: a kidney-CRE-partitioned score is protective against coronary artery disease and myocardial infarction through an interaction between ATP2B1 and antihypertensive medication. Explicitly modeling these interactions improves prediction and transferability, and tissue-focused partitioning increases power to resolve causal genes and reveals genes such as ADAMTS8 with antagonistic effects across BP components. Validated in an independent All of Us cohort, these findings recast the PRS from a blunt aggregate predictor into a mechanistic probe of context-dependent genetic architecture.

ObjectivesThis quality improvement project evaluated trends in guideline-concordant statin prescription rates during implementation of an email-based nudge intervention among healthcare providers at a large FQHC network.MethodsEligible encounters included patients meeting UDS guideline criteria but not receiving treatment. On the morning of each eligible visit, providers received an email nudge. Providers were categorized as early adopters or non-early adopters, with early adopters defined as opening >50% of emails during this period. Outcomes included provider-level prescribing rates, and encounter-level prescribing stratified by email engagement. This study was designed, conducted, and reported in accordance with SQUIRE 2.0 guidelines.ResultsSeventy-five providers who received ≥5 nudges within the first three months were included in the early adopter analysis, and a total of 124 providers with 1,236 unique patient encounters were analyzed over 12 months for encounter-level prescribing rates. Guideline-concordant statin prescribing was modestly higher over time in both groups (early adopters: 85.6% to 89.2%, p < 0.001; non-early adopters: 83.3% to 89.4%, p < 0.001), with no significant evidence of differences between groups over the 1-year period (p = 0.734). At the encounter level, while successful prescribing occurred in 21.8% of visits when the email was opened prior to the encounter compared with 19.5% when it was not opened, this difference was not statistically significant (p = 0.442).ConclusionGuideline-concordant statin prescribing was modestly higher over the study period, though no differential association by email engagement was observed. Given that email nudges are scalable and low-cost, they have the potential to serve as useful adjunctive tools, however further research is needed in settings lacking EHR-integrated alerts or with lower baseline adherence.

Artificial intelligence is increasingly embedded in colonoscopy to enhance detection, standardize optical diagnosis, and support quality metrics. Randomized trials show that computer-aided detection raises adenoma detection and lowers miss rates, while real-world gains are smaller and variable. Computer-aided diagnosis can facilitate resect-and-discard and diagnose-and-leave when performance meets American Society of Gastrointestinal Endoscopy (ASGE) Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds and is strongest as an adjunct to expert assessment. This article highlights the current evidence base, remaining limitations, and key considerations for clinical adoption.

INTRODUCTION/BACKGROUND:In eastern, central and southern Africa, HIV is a leading cause of mortality, and both HIV and depression contribute substantially to morbidity. Depression can impede effective HIV treatment and prevention, yet access to depression treatment remains limited. We estimated the impact and cost-effectiveness of scaling up depression screening and treatment to different population segments in western Kenya . METHODS:We adapted a previously validated HIV transmission model for western Kenya (EMOD-HIV) to include age- and sex-specific depression incidence, remission and recurrence. The model incorporated depression's effects on HIV risk; HIV testing and linkage to care; antiretroviral therapy (ART) adherence; and ART retention. We evaluated four depression screening and treatment scale-up strategies for adults aged 15+ years: (1) universal screening/treatment for all adults; (2) co-administering depression and HIV screening; (3) screening ART recipients; and (4) screening ART recipients with unsuppressed viral load. We assumed 62% depression treatment efficacy and calculated costs from the provider perspective, including US$3.35 for depression screening and US$20.32 per person for psychotherapy; future costs were discounted at 3%, and costs were varied in sensitivity analyses. We calculated incremental cost-effectiveness ratios as the cost (2024 USD) of depression screening and treatment per overall and HIV-related disability-adjusted life-year (DALY) averted. RESULTS:Without depression treatment, we projected 129,000 new HIV infections, 95,900 HIV-related deaths and 1.83 M depression episodes between 2025 and 2035. Universal screening had the highest impact, averting 29.3% (95% CI 29.2%-29.3%) of person-years lived with depression, 2.8% (95% CI 2.6%-3.1%) of HIV acquisitions and 1.4% (95% CI 1.3%-1.6%) of HIV deaths. The cost-effectiveness of universal screening and treatment was US$1291 per DALY averted (95% CI: $1288-1296). Screening ART clients was most cost-effective at $744 per DALY averted (95% CI: $730-760), followed by screening ART clients with unsuppressed viral load at $752 per DALY averted (95% CI: $710-799). Co-administering HIV and depression was dominated by other strategies. CONCLUSIONS:Integrating depression interventions into HIV care could substantially reduce both depression and HIV burden. Cost-effective scale-up could initially focus on individuals with unsuppressed viral load, then to all ART recipients, and finally expand to communities.

OBJECTIVES/UNASSIGNED:To develop and evaluate the Community Research Consulting Initiative (CRCI), a no-cost, student-led model designed to build bidirectional capacity between academic institutions and community-based organizations (CBOs) through research consulting and project-based assistance. STUDY DESIGN/UNASSIGNED:This formative program evaluation examined the feasibility, acceptability, and preliminary outcomes of CRCI, which includes virtual Office Hours for short-term research consultation and Project-Based Assistance (PBA) for longer-term collaborations. The goal was to support CBOs with technical research needs while providing academic trainees with real-world experience. METHODS/UNASSIGNED:Academic consultants (students, staff, faculty) were recruited through institutional listservs and outreach and completed an intake form outlining their expertise and learning goals. CBOs were engaged through Community Advisory Boards, faculty referrals, and existing networks. Consultants provided support via Zoom-based Office Hours and were matched with CBOs for PBA through a memorandum of understanding. Data collection included Zoom registration logs, post-session surveys, and follow-up communications. Quantitative data were analyzed descriptively, and qualitative feedback was reviewed thematically to inform implementation improvements. RESULTS/UNASSIGNED:Thirty-three consultants expressed interest; 21 participated in Office Hours or PBA projects, representing a range of NYU departments. Consultants sought practical experience applying academic skills in community settings. Fifty-one unique CBOs registered for 90 Office Hours slots, primarily serving racial/ethnic minority and at-risk populations in New York City. Grant writing and data analysis were the most frequently requested topics. Among 20 completed surveys, 95% of CBO respondents found sessions useful and relevant, citing take-home resources as especially beneficial. Six CBOs engaged in PBA projects involving survey design, data analysis, and program evaluation. Consultants appreciated the learning opportunity but highlighted challenges related to attendance, preparation time, and expectation setting. CONCLUSION/UNASSIGNED:CRCI demonstrates a feasible and replicable model for advancing equitable academic-community partnerships aligned with NIH priorities. The initiative supports community capacity building while fostering practical training for future leaders in community-engaged research. Broader implementation of CRCI-like models may enhance the sustainability and impact of academic-community collaborations.

BACKGROUND:Extensive-stage small cell lung cancer (ES-SCLC) is associated with a high symptom burden and impaired health-related quality of life (HRQoL). This prespecified analysis from the phase 3 DeLLphi-304 trial evaluated patient-reported outcomes (PROs) for tarlatamab versus standard-of-care (SoC) chemotherapy following first-line platinum-based therapy. METHODS:DeLLphi-304 is a multicenter, open-label, randomized phase 3 study in adults with ES-SCLC. PROs were assessed using validated instruments, including the EORTC QLQ-C30, EORTC QLQ-LC13, FACT-G GP5, BPI-SF, and the EQ-5D-5L visual analogue scale. Change from baseline, response rates, and time to deterioration in these PROs were analyzed. RESULTS:PRO data from all 509 patients enrolled were evaluated. Compliance with QLQ-C30 and QLQ-LC13 assessments remained above 69% through 19 weeks. A higher proportion of patients receiving tarlatamab achieved symptom or functional improvement at 19 weeks compared with SoC in chest pain (19% vs 10%), cough (35% vs 26%), dyspnea (22% vs 7%), physical functioning (13% vs 8%), and global health status (23% vs 15%), respectively. Tarlatamab also delayed deterioration in symptoms, physical functioning, and pain at worst relative to SoC. FACT-G GP5 results indicated that patients receiving tarlatamab were less bothered by treatment side effects over time. CONCLUSIONS:In addition to its previously reported antitumor activity, tarlatamab demonstrated clinically meaningful improvements in symptoms and HRQoL compared with SoC. These findings support a favorable benefit-risk profile of tarlatamab in patients previously treated for ES-SCLC.

Nickel is a transition metal that is widely distributed in the environment. Nickel compounds are classified as Group 1 carcinogens (human carcinogens) by the International Agency for Research on Cancer (IARC). Despite extensive studies, the molecular mechanisms underlying nickel-induced carcinogenesis remain incompletely understood. Maternally Expressed Gene 3 (MEG3) is the first long non-coding RNA (lncRNA) identified as a tumor suppressor. Previous studies have shown that downregulation of MEG3 increases HIF-1α expression in human bronchial epithelial BEAS-2B cells chronically exposed to nickel. In the present study, we observed that MEG3 expression is markedly reduced in nickel-transformed cells. Dysregulation of Runt-Related Transcription Factor 2 (RUNX2) has also been implicated in multiple cancer types. Previous studies have demonstrated that RUNX2 is upregulated in nickel-induced malignantly transformed BEAS-2B cells. Consistent with these findings, we observed that chronic exposure of BEAS-2B cells to low-dose nickel increases both RUNX2 mRNA and protein expression, accompanied by elevated expression of mesenchymal markers and enhanced migratory and invasive capacities. Overexpression of MEG3 in nickel-transformed cells reduces RUNX2 protein levels and reverses the alterations of epithelial-mesenchymal transition (EMT) markers, resulting in decreased cell migration and invasion in nickel-transformed cells. Similarly, silencing RUNX2 reverses the expression of EMT markers and suppresses the migratory and invasive capacities of nickel-transformed cells. Notably, shRNA-mediated RUNX2 knockdown increases MEG3 expression, indicating reciprocal regulation between MEG3 and RUNX2 in nickel-transformed cells. Collectively, our findings demonstrate that MEG3 and RUNX2 form a reciprocally regulated signaling axis that contributes to EMT, thereby promoting migration and invasion in nickel-transformed cells. These results identify MEG3 and RUNX2 as interconnected biomarkers and potential therapeutic targets for cancer prevention and treatment, warranting further mechanistic investigation.