Faculty Bibliography

Latinas are less likely to participate in genetic counseling (GC) and genetic testing (GT) than non-Hispanic Whites. A multisite, randomized pilot study tested a culturally targeted educational intervention to increase uptake of GC/GT among Latina breast cancer (BC) survivors (N = 52). Participants were recruited in Tampa, FL and Ponce, PR and randomized to: (a) fact sheet about BC survivorship (control) or (b) a culturally targeted educational booklet about GC/GT (intervention). Participants in the intervention condition were also offered no-cost telephone GC followed by free GT with mail-based saliva sample collection. Participants self-reported hereditary breast and ovarian cancer (HBOC) knowledge and emotional distress at baseline and 1- and 3-month follow-ups. We used logistic regression to examine differences in GC/GT uptake by study arm (primary outcome) and repeated measures ANOVA to examine the effects of study arm and time on HBOC knowledge and emotional distress (secondary outcomes). Compared to the control arm, intervention participants were more likely to complete GC (OR_Intervention  = 13.92, 95% CI = 3.06-63.25, p < .01) and GT (OR_Intervention  = 12.93, 95% CI = 2.82-59.20, p < .01). Study site did not predict uptake of GC (p = .08) but Ponce participants were more likely to complete GT (OR_Ponce  = 4.53, 95% CI = 1.04-19.72, p = .04). ANOVAs demonstrated an increase in HBOC knowledge over time across both groups (F(2,88) = 12.24, p < .01, η_p²  = 0.22). We also found a significant interaction of study arm and time, such that intervention participants demonstrated a greater and sustained (to the 3-month follow-up) increase in knowledge than control participants (F(2,88) = 3.66, p = .03, η_p²  = 0.08). No other main or interaction effects were significant (all p's> .15). Study findings demonstrate the potential of our culturally targeted print intervention. Lessons learned from this multisite pilot study for enhancing GC/GT in Latinas include the need to attend to both access to GC/GT and individual factors such as attitudes and knowledge.

There have been many publications detailing imaging features of malignant transformation of intraductal papillary mucinous neoplasms (IPMN), management and recommendations for imaging follow-up of diagnosed or presumed IPMN. However, there is no consensus on several practical aspects of imaging IPMN that could serve as a clinical guide for radiologists and enable future data mining for research. These aspects include how to measure IPMN, define reporting terminology, standardize reporting and unify guidelines for surveillance. The Society of Abdominal Radiology (SAR) created multiple Disease-Focused Panels (DFP) comprised multidisciplinary panel members who focus on a particular disease, with the goal to develop ways for radiologists to improve patient care, education, and research. DFP members met to identify the current controversies and limitations of imaging pancreatic IPMN. This paper aims to provide a practical review of the key imaging characteristics of IPMN for trainees and practicing radiologists, to guide uniformity of performance and interpretation of surveillance imaging studies, and to improve communication with clinicians by providing a lexicon and reporting template based on the experience of the SAR-DFP panel members.

Background Older adults with Alzheimer disease (AD) have high rates of emergency department (ED) visits, hospital admissions, and revisits to the ED, which are associated with poor clinical outcomes. ED providers are in a unique role to impact the care trajectories of older adults with AD since they are at the crossroads of inpatient and ambulatory care. Few studies have used administrative data to describe care trajectories of older adults with AD from the ED perspective. Our study aims to use Medicare claims data to 1) identify and characterize older adults with AD presenting to the ED, and 2) describe their post-ED visit outcomes including ED disposition, healthcare utilization and survival in the 12 months following an index ED visit. Methods We identified older adults aged 66+ years with AD who presented to 33 EDs across the United States between January 1, 2014 and June 30, 2019 using Medicare claims by selecting patients with two AD diagnoses, at least one of which is associated with an office visit, at least 7 days apart. Descriptive statistics were used to characterize demographics and post-ED visit outcomes. Results Of the 74,543 patients meeting inclusion criteria with an index ED visit during the study period, 62.6% were male, 75.7% were white, and the mean age was 83.2 years. The majority were admitted from home with (10.3%) or without (73.2%) home health, while 16.6% were admitted from a nursing facility. More than half of the patients were admitted to the hospital (54.6%), and few were discharged to a nursing home (2.9%), hospice (0.3%), or home health (1.4%). In the 12 months following the index ED visit, 42.7% of patients had at least one ED revisit, 44.6% were later admitted to the hospital, 12.7% were admitted to hospice, and 29.2% died. Conclusions This study highlights the utility of Medicare claims data to identify older adults with AD presenting to the ED and describe their care trajectories. It confirms older adults with AD who visit the ED have high rates of inpatient admissions, ED revisits, and subsequent hospital admissions despite high one-year mortality. This data is foundational for future interventions addressing the role of emergency providers in balancing the benefits and harms of hospitalization for older adults with AD and connecting these high-utilizers with appropriate outpatient services

OBJECTIVE:Familial Dysautonomia (FD) disease, lacks a useful biomarker for clinical monitoring. In this longitudinal study we characterized the structural changes in the macula, peripapillary and the optic nerve head (ONH) regions in subjects with FD. METHODS:Data was consecutively collected from subjects attending the FD clinic between 2012 and 2019. All subjects were imaged with spectral-domain Optical Coherence Tomography (OCT). Global and sectoral measurements of mean retinal nerve fiber layer (RNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness, and ONH parameters of rim area, average cup-to-disc (C:D) ratio, and cup volume were used for the analysis. The best fit models (linear, quadratic and broken stick linear model) were used to describe the longitudinal change in each of the parameters. RESULTS:91 subjects (149 eyes) with FD of ages 5-56 years were included in the analysis. The rate of change for average RNFL and average GCIPL thicknesses were significant before reaching a plateau at the age of 26.2 for RNFL and 24.8 for GCIPL (- 0.861 µm/year (95% CI - 1.026, - 0.693) and - 0.553 µm/year (95% CI - 0.645, - 0.461), respectively). Significant linear rate of progression was noted for all ONH parameters, except for a subset of subjects (24%), with no cupping that did not show progression in any of the ONH parameters. CONCLUSIONS:The rapidly declining RNFL and GCIPL can explain the progressive visual impairment previously reported in these subjects. Among all structural parameters, ONH parameters might be most suitable for longitudinal follow-up, in eyes with a measurable cup.

The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multi-ethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth type 2 diabetes cases (mean age 15.1±2.9 y) and 6,061 diabetes-free adult controls (mean age 54.2±12.4 y). After stratifying by principal component-clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified 7 genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P=3.2×10^-8, odds ratio [OR]=1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P=8.0×10^-20, OR 1.58), rs72982988 near MC4R (P=4.4×10^-14, OR=1.53), rs200893788 in CDC123 (P=1.1×10^-12, OR= 1.32), rs2237892 in KCNQ1 (P=4.8×10^-11, OR=1.59), rs937589119 in IGF2BP2 (P=3.1×10^-9, OR=1.34) and rs113748381 in SLC16A11 (P=4.1×10^-8, OR=1.04). Secondary analysis with 856 diabetes-free youth controls uncovered an additional locus in CPEB2 (P=3.2×10^-8, OR=2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome wide association study (GWAS) of youth-onset type 2 diabetes.

OBJECTIVE:One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS/METHODS:. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS:Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS:The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.

Maternal stress is associated with adverse child health. Breast milk microRNAs encapsulated in extracellular vesicles (EVs) are involved in mother-infant biochemical communication during early-life programming. We leverage the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort to investigate associations between maternal stress and breast milk EV-microRNAs. Lifetime stress and negative life events (NLEs) during pregnancy were assessed using the Life Stressor Checklist-Revised (LSCR) and the Crisis in Family Systems-Revised surveys, respectively. RNA was extracted from breast milk EVs (N = 80; collected 6.1 ± 5.9 weeks postnatally), and microRNAs were profiled using the TaqMan OpenArray Human miRNA panel. Associations between stress scores and detection (yes/no) of 173 microRNAs identified in 20-80% of samples were assessed using logistic regression; associations with expression levels of 205 EV-microRNAs identified in >50% of samples were assessed using linear regression. In adjusted models, detection of 60 and 44 EV-microRNAs was associated with higher LSCR and NLE scores, respectively (p < 0.05). Expression level of 8 and 17 EV-microRNAs was associated with LSCR and NLE scores, respectively, at our a priori criteria of p < 0.05 and |B

Breast cancer is the most commonly diagnosed cancer among women in the USA. Despite the availability of screening mammograms, significant disparities still exist in breast cancer outcomes of racial/ethnic and sexual/gender minorities. To address these disparities, the Mount Sinai Mobile Breast Health Program in New York City collaborated with local organizations to develop culturally and linguistically appropriate breast cancer education programs aimed at increasing screening mammogram utilization. Literature review of the barriers to mammography screening formed the basis to allow us to draft a narrative presentation for each targeted cultural group: African American, African-born, Chinese, Latina, and Muslim women, as well as LGBTQ individuals. The presentations were then tested with focus groups comprised of gatekeepers and members from local community and faith-based organizations which served the targeted populations. Feedback from focus groups and gatekeepers was incorporated into the presentations, and if necessary, the presentations were translated. Subsequently, the presentations were re-tested for appropriateness and reviewed for consistency in message, design, educational information, and slide sequencing. Our experience demonstrated the importance of collaborating with community organizations to provide educational content that is culturally and linguistically appropriate for minority groups facing barriers to uptake of screening mammography.

BACKGROUND:Prenatal development is a time when the brain is acutely vulnerable to insult and alteration by environmental factors (e.g., toxins, maternal health). One important risk factor is maternal obesity (Body Mass Index > 30). Recent research indicates that high maternal BMI during pregnancy is associated with increased risk for numerous physical health, cognitive, and mental health problems in offspring across the lifespan. It is possible that heightened maternal prenatal BMI influences the developing brain even before birth. METHODS:The present study examines this possibility at the level of macrocircuitry in the human fetal brain. Using a data-driven strategy for parcellating the brain into subnetworks, we test whether MRI functional connectivity within or between fetal neural subnetworks varies with maternal prenatal BMI in 109 fetuses between the ages of 26 and 39weeks. RESULTS:We discovered that strength of connectivity between two subnetworks, left anterior insula/inferior frontal gyrus (aIN/IFG) and bilateral prefrontal cortex (PFC), varied with maternal BMI. At the level of individual aIN/IFG-PFC connections, we observed both increased and decreased between-network connectivity with a tendency for increased within-hemisphere connectivity and reduced cross-hemisphere connectivity in higher BMI pregnancies. Maternal BMI was not associated with global differences in network topography based on network-based statistical analyses. CONCLUSIONS:Overall effects were localized in regions that will later support behavioral regulation and integrative processes, regions commonly associated with obesity-related deficits. By establishing onset in neural differences prior to birth, this study supports a model in which maternal BMI-related risk is associated with fetal connectome-level brain organization with implications for offspring long-term cognitive development and mental health.