Faculty Bibliography

Older people living with HIV (OPLWH) have higher rates of substance use (tobacco, alcohol, and other drugs) than their HIV-negative peers. Addressing health care needs of OPLWH who use substances is more challenging than for those who do not: they are highly impacted by comorbid conditions, substance use can interact with other medications (including antiretroviral therapy-ART) and reduce their effectiveness, and substance use has been associated with reduced adherence to ART and increased risky behaviors (including sexual risks). People who use substances also suffer disparities along the HIV continuum of care, resulting in lower viral suppression rates and poorer health outcomes. They are especially impacted by stigma and stress, which have implications for HIV treatment and care. Recommendations for health care providers working with OPLWH who use substances include: (1) the need to screen and refer for multiple associated conditions, and (2) training/continuing education to enhance care management and maximize health outcomes.

Background Somatic genetic alterations have been associated with differential disposition of the intratumoral immune milieu. In contrast, the role of germline genetics remains largely unknown. The Cancer Genome Atlas (TCGA) Pan-Cancer Immune Response Working Group recently analyzed associations between immunological features of tumor microenvironment, prognosis, and tumor-intrinsic properties (including somatic mutations and copy number aberrations). The study generated a comprehensive set of per-sample immune response signatures, and identified distinct tumor immunological subtypes shared across multiple cancer types [1]. Here, we examined the germline genetic contribution to >100 such immune response signatures, considered as potential traits, in >9,000 study participants across 30 different cancer types in the TCGA. Methods We used SNP data from Affymetrix 6.0 arrays typed on normal tissue and blood. After stringent quality control, we imputed missing SNPs using the Haplotype Reference Consortium dataset and included SNPs with minor allele frequency >0.005 and imputation quality R2>0.5. We inferred genetic ancestry using principal components analysis. We estimated genome-wide heritability of the immune signatures using the genomic-relatedness-based restricted maximumlikelihood (GREML) approach implemented in genome-wide complex trait analysis (GCTA). We performed genome-wide association studies (GWAS) using linear regression models. All analyses were adjusted for cancer type, age at diagnosis, gender, and genetic ancestry using principal components 1-7. Linear regression was also applied to germline exome sequence data [2] to evaluate rare variant associations. Results Across different tumor types, we found significant heritability (FDR< 0.05) for estimates of innate and adaptive immune cell enrichment including natural killer cells, activated dendritic cells, eosinophils and neutrophils, and T-cell subsets (CD8 Cytotoxic, T-helper, T-follicular helper, T-effector memory, T-central memory, Th1 and Th17 cells) respectively, as well as for antigen-presenting machinery and interferon-related signatures. Furthermore, we found significant interactions between germline modifiers and distinct immune subtypes (FDR<0.05). Through GWAS analysis, we identified several polymorphisms associated with both immune cells and immunomodulatory signaling passing the genome-wide significance threshold (p<5E-8). Two SNPs previously associated with the risk of several auto-immune diseases [3], rs2111485 and rs1990760 mapping to Interferon Induced Helicase C Domain 1 (IFIH1) locus, were significantly correlated with interferon signaling in tumors (Figure 1). Moreover, suggestive associations between rare variants and immune response traits were found. Conclusions We demonstrated that intratumoral immune disposition is partially under germline control through systematic pan-cancer analysis. Germline variants associated with differential immune response might be used to stratify patients based on likelihood of treatment response and to prioritize targets for development of novel therapies. (Figure Preseted)

Background: Patients with advanced kidney disease have an elevated symptom burden, increased mortality, and poor quality of life. While palliative care can address these issues, nephrology patients infrequently receive such care. To address this, we implemented an ambulatory kidney palliative care program. We describe our initial outcomes.
Method(s): Utilizing chart abstractions, we characterized the clinic population and symptom burden for patients seen from May 6, 2016-July 6, 2018.
Result(s): Ninety-four patients were referred; 74 (78.7%) patients seen. Forty (54.1%) had follow-up appointments (range 2-13). Mean patient age was 72.7 +/-16 years with 32 (43.2%) on dialysis. The mean symptom burden (n=65) was 12 (+/- 4.9) symptoms (out of 17) with mean severity of 2 (range 0-4), representing moderate severity. The most common physical symptoms were nausea (78%), dyspnea (72%), pain (68%) and itch (66%). Eighty-seven percent reported anxiety and 73% reported depression. There was no difference in symptom burden between patients on dialysis and those on conservative management (n=22). Patients on conservative management were significantly older and had more comorbidities. By visit two, there was a significant reduction in global symptom score (21.9 vs 19.0, p=0.01) in addition to a reduction in anxiety (2.1 vs 1.7, p=0.03), vomiting (0.8 vs 0.2, p=0.04), and restless legs syndrome (1.3 vs 0.8, p = 0.02).
Conclusion(s): Patients with serious kidney disease treated in a kidney palliative care clinic have a high symptom burden regardless of treatment choice. The decision to pursue conservative management is more prevalent in older patients with more comorbidities. Follow up visits to the clinic demonstrated a decrease in symptom burden, suggesting that a dedicated kidney-palliative care clinic may be successful in managing symptoms and addressing unmet need

Demographic and income disparities may impact food accessibility. Research has not yet well documented the precise location of healthy and unhealthy food resources around children's homes and schools. The objective of this study was to examine the food environment around homes and schools for all public school children, stratified by race/ethnicity and poverty status. This cross-sectional study linked data on the exact home and school addresses of a population-based sample of public school children in New York City from 2013 to all corner stores, supermarkets, fast-food restaurants, and wait-service restaurants. Two measures were created around these addresses for all children: 1) distance to the nearest outlet, and 2) count of outlets within 0.25 miles. The total analytic sample included 789,520 K-12 graders. The average age was 11.78 years (SD ± 4.0 years). Black, Hispanic, and Asian students live and attend schools closer to nearly all food outlet types than White students, regardless of poverty status. Among not low-income students, Black, Hispanic, and Asian students were closer from home and school to corner stores and supermarkets, and had more supermarkets around school than White students. The context in which children live matters, and more nuanced data is important for development of appropriate solutions for childhood obesity. Future research should examine disparities in the food environment in other geographies and by other demographic characteristics, and then link these differences to health outcomes like body mass index. These findings can be used to better understand disparities in food access and to help design policies intended to promote healthy eating among children.