Faculty Bibliography

Diets with high inflammatory potential are suspected to increase risk for pancreatic cancer (PC). Using pooled analyses, we examined whether this association applies to populations from different geographic regions and population subgroups with varying risks for PC, including variation in ABO blood type. Data from six case-control studies (cases, n=2,414; controls, n=4,528) in the Pancreatic Cancer Case-Control Consortium (PanC4) were analyzed, followed by replication in five nested case-control studies (cases, n=1,268; controls, n=4,215) from the Pancreatic Cancer Cohort Consortium (PanScan). Two polymorphisms in the ABO locus (rs505922 and rs8176746) were used to infer participants' blood types. Dietary questionnaire-derived nutrient/food intake was used to compute energy-adjusted dietary inflammatory index (DII®) scores to assess inflammatory potential of diet. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression. Higher E-DII scores, reflecting greater inflammatory potential of diet, were associated with increased PC risk in PanC4 (ORQ5 vs. Q1=2.20, 95% CI=1.85-2.61, Ptrend<0.0001; ORcontinuous=1.20, 95% CI=1.17-1.24), and PanScan (ORQ5 vs. Q1=1.23, 95% CI=0.92-1.66, Ptrend=0.008; ORcontinuous=1.09, 95% CI=1.02-1.15). As expected, genotype-derived non-O blood type was associated with increased PC risk in both the PanC4 and PanScan studies. Stratified analyses of associations between E-DII quintiles and PC by genotype-derived ABO blood type did not show interaction by blood type (Pinteraction=0.10 in PanC4 and Pinteraction=0.13 in PanScan). The results show that consuming a pro-inflammatory diet and carrying non-O blood type are each individually, but not interactively, associated with increased PC risk.

Cigarette smoking alters the oral microbiome; however, the effect of alternative tobacco products remains unclear. Middle Eastern tobacco products like dokha and shisha, are becoming globally widespread. We tested for the first time in a Middle Eastern population the hypothesis that different tobacco products impact the oral microbiome. The oral microbiome of 330 subjects from the United Arab Emirates Healthy Future Study was assessed by amplifying the bacterial 16S rRNA gene from mouthwash samples. Tobacco consumption was assessed using a structured questionnaire and further validated by urine cotinine levels. Oral microbiome overall structure and specific taxon abundances were compared, using PERMANOVA and DESeq analyses respectively. Our results show that overall microbial composition differs between smokers and nonsmokers (p = 0.0001). Use of cigarettes (p = 0.001) and dokha (p = 0.042) were associated with overall microbiome structure, while shisha use was not (p = 0.62). The abundance of multiple genera were significantly altered (enriched/depleted) in cigarette smokers; however, only Actinobacillus, Porphyromonas, Lautropia and Bifidobacterium abundances were significantly changed in dokha users whereas no genera were significantly altered in shisha smokers. For the first time, we show that smoking dokha is associated to oral microbiome dysbiosis, suggesting that it could have similar effects as smoking cigarettes on oral health.

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL=1.31, 95% CI=1.06-1.60; OR MZL=1.45, 95% CI=1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL=2.10, 95% CI=1.24-3.55; OR MZL= 2.10, 95% CI=0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (p-trend<0.0001, FDR=0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.

BACKGROUND:Hypertriglyceridemia is associated with increased remnant-like particle cholesterol (RLP-C) and triglycerides in low-density lipoprotein (LDL-TG). Recent studies have focused on atherogenicity of RLP-C, with few data on LDL-TG. OBJECTIVES:The aim of this study was to examine associations of RLP-C and LDL-TG with incident cardiovascular disease (CVD) events and genetic variants in the ARIC (Atherosclerosis Risk In Communities) study. METHODS:Fasting plasma RLP-C and LDL-TG levels were measured in 9,334 men and women without prevalent CVD. Participants were followed for incident CVD events (coronary heart disease and ischemic stroke) for up to 16 years. Associations between LDL-TG and RLP-C levels and genetic variants were assessed by whole-exome sequencing using single-variant analysis for common variants and gene-based burden tests for rare variants; both an unbiased and a candidate gene approach were explored. RESULTS:). CONCLUSIONS:RLP-C and LDL-TG levels were predictive of CVD and associated with APOE variants. LDL-TG may represent a marker of dysfunctional remnant lipoprotein metabolism associated with increased CVD risk. Further research is needed to determine whether LDL-TG plays a causal role in CVD and may be a target for therapy.

BACKGROUND:The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS2°P), a 0-to-9-point system based on the presence/absence of 9 clinical factors, was developed to classify the risk of major adverse cardiovascular events (MACE) (a composite of cardiovascular death, recurrent myocardial infarction, or ischemic stroke) among patients with a recent myocardial infarction. Its performance has not been examined internationally outside of a clinical trial setting. METHODS AND RESULTS:We evaluated the performance of TRS2°P for predicting MACE in 53 599 patients with recent myocardial infarction in 5 international cohorts from New Zealand, South Korea, Sweden, and the United States participating in the Chronic Kidney Disease Prognosis Consortium. Overall, there were 19 444 cases of MACE across 5 cohorts over a mean follow-up of 5 years, and the overall MACE rate ranged from 5.0 to 18.4 (per 100 person-years). The TRS2°P showed modest calibration (Brier score ranged from 0.144 to 0.173) and discrimination (C-statistics >0.61 in all studies except 1 from Korea with 0.55) across cohorts relative to its original Brier score of 0.098 and C-statistic of 0.67 in the derived data set. Although there was some heterogeneity across cohorts, the 9 predictors in the TRS2°P were generally associated with higher MACE risk, with strongest associations observed (meta-analyzed adjusted hazard ratio 1.6-1.7) for history of heart failure, age ≥75 years, and prior stroke, followed by peripheral artery disease, kidney dysfunction, diabetes mellitus, and hypertension (hazard ratio 1.3-1.4). Prior coronary bypass graft surgery and smoking did not reach statistical significance (hazard ratio ≈1.1). CONCLUSIONS:TRS2°P, a simple scoring system with 9 routine clinical factors, was modestly predictive of secondary events when applied in patients with recent myocardial infarction from diverse clinical and geographic settings.

Importance/UNASSIGNED:Health profiles and patterns of involvement in the criminal justice system among people with various levels of opioid use are poorly defined. Data are needed to inform a public health approach to the opioid epidemic. Objective/UNASSIGNED:To examine the association between various levels of opioid use in the past year and physical and mental health, co-occurring substance use, and involvement in the criminal justice system. Design, Setting, and Participants/UNASSIGNED:This retrospective, cross-sectional analysis used the 2015-2016 National Survey on Drug Use and Health to assess the independent association of intensity of opioid use with health, co-occurring substance use, and involvement in the criminal justice system among US adults aged 18 to 64 years using multivariable logistic regression. Exposures/UNASSIGNED:No opioid use vs prescription opioid use, misuse, or use disorder or heroin use. Main Outcomes and Measures/UNASSIGNED:Self-reported physical and mental health, disability, co-occurring substance use, and past year and lifetime involvement in the criminal justice system. Results/UNASSIGNED:The sample consisted of 78 976 respondents (42 495 women and 36 481 men), representative of 196 280 447 US adults. In the weighted sample, 124 026 842 adults reported no opioid use in the past year (63.2%; 95% CI, 62.6%-63.7%), 61 462 897 reported prescription opioid use in the past year (31.3%; 95% CI, 30.8%-31.8%), 8 439 889 reported prescription opioid misuse in the past year (4.3%; 95% CI, 4.1%-4.5%), 1 475 433 reported prescription opioid use disorder in the past year (0.8%; 95% CI, 0.7%-0.8%), and 875 386 reported heroin use in the past year (0.4%; 95% CI, 0.4%-0.5%). Individuals who reported any level of opioid use were significantly more likely than individuals who reported no opioid use to be white, have a low income, and report a chronic condition, disability, severe mental illness, or co-occurring drug use. History of involvement in the criminal justice system increased as intensity of opioid use increased (no use, 15.9% [19 562 158 of 123 319 911]; 95% CI, 15.4%-16.4%; prescription opioid use, 22.4% [13 712 162 of 61 204 541]; 95% CI, 21.7%-23.1%; prescription opioid misuse, 33.2% [2 793 391 of 8 410 638]; 95% CI, 30.9%-35.6%; prescription opioid use disorder, 51.7% [762 189 of 1 473 552]; 95% CI, 45.4%-58.0%; and heroin use, 76.8% [668 453 of 870 250]; 95% CI, 70.6%-82.1%). In adjusted models, any level of opioid use was associated with involvement in the criminal justice system in the past year compared with no opioid use. Conclusions and Relevance/UNASSIGNED:Individuals who use opioids have complicated health profiles and high levels of involvement in the criminal justice system. Combating the opioid epidemic will require public health interventions that involve criminal justice systems, as well as policies that reduce involvement in the criminal justice system among individuals with substance use disorders.

BACKGROUND AND OBJECTIVES:kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death. RESULTS:=0.02). CONCLUSIONS:kidney disease risk variants, independently of proteinuria and GFR.

OBJECTIVE:To assess changes in the practice patterns of urologists performing male infertility procedures (vasal reconstruction, sperm retrieval, varicocelectomy) from 2004 to 2015 in the United States. DESIGN/METHODS:Examination of self-reported procedural volumes from urologists undergoing certification and recertification using case log data provided by the American Board of Urology. The study period was stratified into early (2004-2007) and recent (2012-2015) time periods. SETTING/METHODS:Not applicable. PATIENT(S)/METHODS:None. INTERVENTION(S)/METHODS:None. MAIN OUTCOMES MEASURE(S)/METHODS:Temporal variations in male infertility practice patterns among different urologic subspecialties between the early and recent time periods. RESULT(S)/RESULTS:The overall proportion of total male infertility procedures performed by andrologists significantly increased between the early and recent groups (23% to 26%). This growth was driven by a significant increase in the proportion of varicocele repairs being performed by andrologists between the early and recent periods (19% to 25%). Most notably, an assessment of total number of male infertility procedures performed by newly certifying urologists showed that there was a significant increase in the overall proportion of all male infertility procedures being performed by recently trained andrologists (24% to 35%). This significant increase was seen individually among all three types of male infertility procedures. CONCLUSION(S)/CONCLUSIONS:With the increased trend in urologists obtaining fellowship training, male infertility surgical volume is beginning to shift from general urologists to subspecialized andrologists.