Faculty Bibliography

People with HIV are at increased risk of cardiovascular events; thus, care delivery strategies that increase access to comprehensive cardiovascular disease (CVD) risk management are a priority. We report the results of a multi-component telemedicine-based strategy to improve blood pressure control among people with HIV-Assess and Adapt to the Impact of COVID-19 on CVD Self-Management and Prevention Care in Adults Living with HIV (AAIM-High). The AAIM High strategy is a virtual adaptation of our previously published EXTRA-CVD strategy and consisted of hypertension education and six components: nurse-led care coordination (delivered by teleconference or telephone), home systolic blood pressure (SBP) monitoring, evidence-based treatment algorithms, electronic health records tools, technology coach, and communication preferences assessment. People with HIV (n = 74) with comorbid hypertension at three academic medical centers were enrolled in a single arm implementation study from January 2021 to December 2022. Over 12 months, the average patient-performed home SBP decreased by 7.7 mmHg (95% CI -11.5, -3.9). The percentage of patients at treatment goal, defined as average SBP <130 mmHg, increased from 46.0% to 72.5% at 12 months. By adapting to the growing use of telemedicine in healthcare delivery, our study effectively improved hypertension control in people with HIV through a virtual, nurse-led intervention.

Wildfires continue to increase in size, intensity, and duration. There is growing evidence that wildfire smoke adversely impacts clinical outcomes; however, few studies have assessed the impact of wildfires on household air quality and subclinical cardiovascular health indicators. We measured continuous indoor and outdoor fine particulate matter (PM_2.5) concentrations from July-October 2022 at 20 residences in the rural, mountainous state of Montana in the United States. We used a combination of satellite-derived smoke plume data from the National Oceanic and Atmospheric Administration's Hazard Mapping System and household-level daily mean PM_2.5 concentrations to classify wildfire-impacted days. One participant from each household self-reported in-home blood pressure (BP) on weekly electronic surveys. We used linear mixed-effects regression models to assess associations between air pollution exposures (PM_2.5 concentrations; number of wildfire-impacted days) and systolic BP (SBP) and diastolic BP (DBP). Models were adjusted for potential time-variant confounders including temperature, humidity, and self-reported exercise. Compared to survey periods with 0 wildfire days, SBP was 3.83 mmHg higher (95% Confidence Interval [95% CI]: 0.22, 7.44) and DBP was 2.36 mmHg higher (95% CI: -0.06, 4.78) during periods with 4+ wildfire days. Across the entire study period, a 10 µg m^-3 increase in indoor PM_2.5 was associated with 1.34 mmHg higher SBP (95%CI: 0.39, 2.29) and 0.71 mmHg higher DBP (95% CI: 0.07, 1.35). We observed that wildfire-impacted days and increasing household-level PM_2.5 concentrations are associated with higher in-home BP. Our results support growing literature which indicates that wildfires adversely impact subclinical cardiovascular health. Clinical and public health messaging should emphasize the cardiovascular health impacts of wildfire smoke and educate on exposure-reduction strategies such as indoor air filtration.

BACKGROUND:The prolonged turnaround time for next-generation sequencing (NGS) results may be a barrier to the timely selection of therapeutics in myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) with mutated TP53. Biomarker validation for early detection of TP53 mutation may have a significant impact on clinical decision-making. METHODS:In this study, p53 immunohistochemistry (IHC) (index test) and TP53 NGS (referent test) were performed on 145 bone marrow specimens from 82 unique patients with TP53-mutant MDS or AML to validate IHC as an early surrogate for NGS, and to assess the prognostic relevance of IHC. RESULTS:p53 IHC testing was able to correctly identify 95.5% of patients with TP53-mutant MDS and 100% of patients with TP53-mutant AML in this cohort. The mean p53 stain positivity was higher for AML compared to MDS (28% ± 3.67% vs. 8.8% ± 1.61%; p < .001), as well as for multihit TP53 compared to monoallelic TP53. Bootstrap analysis with 2000 iterations showed that a p53 IHC of 7% was the threshold best associated with multihit TP53. False-negative results were obtained with IHC in all TP53 sole nonsense or frameshift mutations. IHC positivity was inversely correlated with overall survival (OS), with the highest quintile of p53 positivity showing a median OS of just 2.53 months. CONCLUSIONS:IHC is a useful biomarker for the early detection of TP53-mutant MDS or AML and for prediction of TP53 allelic state. The results suggest a role for IHC across global markets, especially in geographic areas with inaccessibility to NGS testing.

INTRODUCTION/BACKGROUND:Secondhand exposure to e-cigarettes represents a potential population health risk given e-cigarette's prevalence and their unknown health effects, particularly among vulnerable populations such as pregnant people. OBJECTIVES/OBJECTIVE:To explore metabolomic differences between pregnant people exposed vs. not exposed to secondhand e-cigarette aeresols, to identify possible biomarkers of exposure and metabolic pathways perturbed by e-cigarettes. METHODS:Exposed participants (n = 19) from the NYU Children's Health and Environment Study were matched to unexposed participants (n = 57) at a 1:3 ratio on age, hospital of recruitment, and race/ethnicity. Early-pregnancy urine samples were analyzed via an untargeted metabolomics platform using reverse-phase liquid chromatography mass-spectrometry. Feature-exposure associations were estimated using conditional logistic regression to adjust for matching factors. A sensitivity analysis was conducted adjusting for secondhand tobacco exposure. RESULTS:Among features enriched in the exposed group were flavonoids and flavor-related compounds including homoeriodictyol and naringenin-7-O-beta-D-glucuronide, 3-acetomidocoumarin, and guaiacol pentosylglucoside; synthetic drugs such as the endocannabinoid AM1172 and the stimulant alpha-PVP; and metabolites associated with lipid metabolism, including 2,4-undecadiene-8,10-diynoic acid isobutylamide, palmitamide, glycerol trihexanoate, and tetradecyl phosphonate. Among features negatively associated with exposure were xanthines. CONCLUSION/CONCLUSIONS:This study is the first untargeted metabolomics study investigating metabolomic markers of e-cigarette exposure, including secondhand exposure, in a pregnant cohort. Despite this study's small size and exploratory nature, the results of this work suggest that flavoring components could be biomarkers for e-cigarette exposure, and that co-exposure to e-cigarettes and other drugs may be prevalent.

Variations in the airway microbiome are associated with inflammatory responses in the lung and pulmonary disease outcomes. Regional changes in microbiome composition could have spatial effects on the metabolic environment, contributing to differences in the host response. Here, we profiled the respiratory microbiome (metagenome/metatranscriptome) and metabolome of a patient cohort, uncovering topographical differences in microbial function, which were further delineated using isotope probing in mice. In humans, the functional activity of taxa varied across the respiratory tract and correlated with immunomodulatory metabolites such as glutamic acid/glutamate and methionine. Common oral commensals, such as Prevotella, Streptococcus, and Veillonella, were more functionally active in the lower airways. Inoculating mice with these commensals led to regional increases in several metabolites, notably methionine and tyrosine. Isotope labeling validated the contribution of Prevotella melaninogenica in generating specific metabolites. This functional characterization of microbial communities reveals topographical changes in the lung metabolome and potential impacts on host responses.

INTRODUCTION/BACKGROUND:Social media is the most prominent source of online food and beverage advertisements (ads) seen by adolescents. Companies target adolescent social media users with ads that feature calorie-dense, nutrient-poor products, and exposure to ads drives poor diet and risk for future diet-related diseases. Black, Hispanic and lower socio-economic status youth are exposed to significantly more ads than White peers. Several state-level policies in the USA have passed restricting youth from accessing social media without parental approval, and some policies have banned advertising to youth. This protocol paper describes a current study that aims to understand the impact of such policies in two states, Louisiana and Texas, as they were among the first to be implemented with racially/ethnically diverse populations. METHODS AND ANALYSIS/METHODS:This study employs a repeated cross-sectional difference-in-difference design in which 700 youth ages 13-17 years are being recruited each year for 5 years (Louisiana n=175, Texas n=175, matched comparisons from other states n=350). Youth screen record their mobile devices for 60 minutes while they browse social media platforms (eg, TikTok, Instagram) or use the internet. They also complete a brief survey about a variety of topics (eg, health behaviours, mental health). Adolescents are compensated for screen recording ($75) and the survey ($25). Study team members are coding recordings for several characteristics, including media platforms used, appearances of food or beverages, and food or beverage type. We will estimate the impact of policies on food and beverage ads seen per hour using Ordinary Least Squares regression models and heterogeneity-robust standard errors clustered at the state level (by year and cumulatively). We will run additional models with interaction terms with income and race/ethnicity, separately, to test the role of the policies on health disparities. ETHICS AND DISSEMINATION/BACKGROUND:Study procedures have been approved by the Institutional Review Board of the NYU Grossman School of Medicine. We will distribute findings in peer-reviewed journals and at local and national conferences. To complement traditional dissemination pathways, we will create infographics to share with relevant community stakeholders. We will also share findings with policymakers in states that have passed or considered similar policies.

BACKGROUND:Pulmonary vein (PV) isolation is the cornerstone of radiofrequency (RF) ablation for atrial fibrillation (AF) and PV reconnection is a common cause of recurrent AF. The relationship between PV ostial wall thickness (WT) and durable PV isolation is a matter of ongoing investigation. Additionally, the relationship between catheter impedance and WT is not well understood. We studied the relationship between PV ostial WT, ablation lesion metrics, and PV reconnection. METHODS:16 patients were identified who underwent an initial and redo AF ablation procedure and had a cardiac CTA analyzed using ADAS-3D imaging software performed prior to the initial ablation. Ablation lesion metrics from the initial ablation procedure were collected from the electroanatomic mapping software. Reconnected and isolated PV were identified based on electroanatomic mapping data collected at the redo AF ablation procedure. Patients with reconnected PV exhibited thicker left atrial walls (1.4 mm vs 1.2 mm, P < 0.05) and reconnected veins exhibited thicker ostial walls (1.7 mm, vs 1.5 mm, P < 0.05). LA volume, number of ablation lesions, and ablation lesion time were not significantly different between reconnected and isolated PV. Impedance drop during ablation was greater in patients with reconnected PV compared to patients with isolated PV (- 9.0 Ω vs - 6.6 Ω, P < 0.05). There was no correlation between PV ostial WT and ablation lesion impedance drop. CONCLUSION/CONCLUSIONS:PV reconnection was associated with thicker LA and PV ostial WT. Future studies will examine whether targeting thicker PV ostial tissue with more aggressive lesion metrics or different ablation technology can improve PV isolation and ablationoutcomes.

Vaccines have had a major impact on the control of infectious disease, most recently by helping to combat the COVID-19 pandemic. Prophylactic cancer vaccines have prevented several malignancies by protecting against cancer-causing pathogens. By contrast, therapeutic vaccines training the immune system to eliminate established tumours are now showing real promise in clinical settings. In the adjuvant setting, vaccines against melanoma and pancreatic cancer appear to be reducing minimal residual disease and relapse. In the macrometastatic setting, in-situ vaccines have induced systemic regressions in advanced-stage lung and breast cancers and lymphomas. More effective cancer vaccines are being developed through having a deeper understanding of crucial cellular factors in tumour immunology, the incorporation of newer vaccine components to effectively mobilise and activate cells, the use of omics and artificial intelligence in vaccine design, and addition of immune checkpoint blockade. In this Viewpoint, we analyse cancer vaccine trials, the strengths and limitations of different vaccine approaches, and we discuss how the next generation of cancer vaccines can help improve patient outcomes and quality of life.

OBJECTIVES/OBJECTIVE:Edentulism and diabetes mellitus (DM) are frequently seen among older adults. However, the joint effect of edentulism and DM on mortality was understudied. We aim to examine the joint effect of edentulism and DM on all-cause mortality and to what extent the joint effect varies by race/ethnicity. METHODS:Analysis of US Health and Retirement Study (HRS) data (2006-2018) included 11,813 non-Hispanic Whites, 2216 non-Hispanic Blacks, and 1337 Hispanics aged ≥ 50 years old. Mortality data came from the National Death Index or HRS surveys. Edentulism was self-reported and DM was determined by self-reported diagnosis, medication use, or glycosylated hemoglobin. Cox proportional-hazard models with inverse probability treatment weighting were applied. RESULTS:During mean follow-up of 9.6 years, 2874 Whites, 703 Blacks, and 441 Hispanics died. DM was associated with higher mortality across all groups (Whites: HR = 1.43, 95% CI = 1.25-1.64; Blacks: HR = 1.62, 95% CI = 1.28-2.04; Hispanics: HR = 1.46, 95% CI = 1.07-1.99). However, edentulism predicted higher mortality only in Whites (HR = 1.65, 95% CI = 1.51-1.80). Having both conditions showed highest mortality risk in all groups (Whites: HR = 2.31, 95% CI = 1.56-3.42; Blacks: HR = 1.94, 95% CI = 1.45-2.59; Hispanics: HR = 1.77, 95% CI = 1.16-2.70), with a significant additive interaction observed only in Whites (relative excess risk due to interaction = 0.22, p < 0.05). CONCLUSIONS:DM and edentulism pose an additive risk for mortality in Whites, and there are racial/ethnic differences in edentulism-related mortality.