Citations

Adenosine boasts promising preclinical and clinical data supporting a vital role in modulating vascular homeostasis. Its widespread use as a diagnostic and therapeutic agent have been limited by its short half‐life and complex biology, though adenosine‐modulators have shown promise in improving vascular healing. Moreover, circulating adenosine has shown promise in predicting cardiovascular (CV) events. We sought to delineate whether circulating plasma adenosine levels predict CV events in patients undergoing invasive assessment for coronary artery disease. Patients undergoing invasive angiography had clinical data prospectively recorded in the Cardiovascular and Percutaneous ClInical TriALs (CAPITAL) revascularization registry and blood samples collected in the CAPITAL Biobank from which adenosine levels were quantified. Tertile‐based analysis was used to assess prediction of major adverse cardiovascular events (MACE; composite of death, myocardial infarction, unplanned revascularization, and cerebrovascular accident). Secondary analyses included MACE subgroups, clinical subgroups and adenosine levels. There were 1,815 patients undergoing angiography who had blood collected with adenosine quantified in 1,323. Of those quantified, 51.0% were revascularized and 7.3% experienced MACE in 12 months of follow‐up. Tertile‐based analysis failed to demonstrate any stratification of MACE rates (log rank, P = 0.83), when comparing low‐to‐middle (hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.68–1.78, P = 0.70) or low‐to‐high adenosine tertiles (HR 0.95, 95% CI 0.56–1.57, P = 0.84). In adjusted analysis, adenosine similarly failed to predict MACE. Finally, adenosine did not predict outcomes in patients with acute coronary syndrome nor in those revascularized or treated medically. Plasma adenosine levels do not predict subsequent CV outcomes or aid in patient risk stratification.

Abstract Objective Persistent posttraumatic headache (PPTH), one of the most common symptoms following mild traumatic brain injury, is often associated with substantial functional disability. The objective of this study was to assess the contribution of demographics, headache characteristics, and psychological symptoms to disability associated with PPTH. Methods Participants completed the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), the Pain Catastrophizing Scale (PCS), and the Migraine Disability Assessment (MIDAS) questionnaire. Two linear regression models were formulated to interrogate the relationships between 1) demographics and headache characteristics with the MIDAS questionnaire and 2) demographics, headache characteristics, and psychological symptoms with the MIDAS questionnaire. A two-way stepwise regression using the Akaike information criterion was performed to find a parsimonious model describing the relationships between demographics, headache characteristics, and psychological measures with the MIDAS questionnaire. Results Participants included 58 patients with PPTH and 39 healthy controls (HCs). The median MIDAS score among those with PPTH was 48.0 (first quartile [1Q] = 20.0, third quartile [3Q] = 92.0), indicative of severe disability. Compared with the HCs, those with PPTH had higher scores on the BDI, STAI, and PCS. Older age predicted lower MIDAS scores (age: B=–0.11, P<0.01), whereas higher headache frequency, greater headache intensity, and higher trait anxiety scores predicted higher MIDAS scores in individuals with PPTH (headache frequency: B=0.07, P<0.001; headache intensity: B=0.51, P=0.04; trait anxiety score: B=1.11, P=0.01). Conclusions Individuals with PPTH had substantial psychological symptoms and headache-related disability. Disability was partially explained by age, headache frequency and intensity, and trait anxiety. Holistic management of patients with PPTH to address headaches and psychological symptoms might reduce headache-associated disability.

Background and Objective: Symptoms of persistent post-traumatic headache (PPTH) most often resemble those of migraine, including the presence of photo-, phono-, and cutaneous hypersensitivities. The severity of these hypersensitivity symptoms in those with PPTH compared to those with migraine has yet to be fully elucidated. The objective of this study was to compare symptoms of sensory hypersensitivities between PPTH, migraine, and healthy controls (HCs). Further defining characteristics of PPTH and its similarities to migraine might assist with developing future diagnostic criteria for PPTH and provide insights into PPTH mechanisms. Methods: This analysis included 56 individuals with PPTH attributed to mild traumatic brain injury, 30 with migraine, and 36 HCs. To assess sensory hypersensitivities, all subjects completed the Allodynia Symptom Checklist-12, the Photosensitivity Assessment Questionnaire, and the Hyperacusis Questionnaire. Differences among groups were assessed using Fisher’s exact test, Kruskal–Wallis, or Mann–Whitney U test. Results: PPTH and migraine groups had greater severity of cutaneous, photo-, and phono-hypersensitivity symptoms compared to HCs. There were no statistically significant differences between the PPTH and migraine groups for cutaneous allodynia (median [first quartile, third quartile]; PPTH: 4.0 [2.0, 7.0]; migraine: 5.0 [3.0, 8.0]; p = 0.54) or photosensitivity severity (PPTH: 5.0 [2.0, 7.0]; migraine: 5.0 [2.0, 6.0]; p = 0.53). Those with PPTH had higher hyperacusis scores compared to those with migraine (PPTH: 23.0 [17.0, 31.0]; migraine: 13.5 [9.0, 24.0]; p = 0.001). Conclusion: Sensory hypersensitivity symptoms among individuals with PPTH are at least as severe as those experienced by people with migraine. Results further confirm symptom similarities between PPTH and migraine and could suggest that PPTH and migraine have a partially shared underlying pathophysiology.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal malignancies with few known risk factors and biomarkers. Identification of disease biomarkers is critical for understanding the pathogenesis of this cancer and identifying high risk individuals for close surveillance. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers usually in small samples. To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, by using genetic instruments. Protein quantitative trait loci (pQTLs) for 1,226 plasma proteins identified in a large INTERVAL study of 3,301 healthy European descendants were used as instruments to evaluate associations between genetically predicted protein levels and PDAC. For proteins showing a significant association, we further conducted conditional analysis with adjustments for previously identified risk variants to assess whether the observed associations between genetically predicted protein concentrations and PDAC risk were independent of the risk variants identified in genome-wide association studies (GWAS). Furthermore, for the proteins that were associated with PDAC risk, we performed an enrichment analysis of the genes encoding these proteins to examine whether they are enriched in specific pathways, functions or networks. We observed associations between predicted concentrations of 38 proteins and PDAC risk at a false discovery rate of < 0.05, including those of 23 proteins that showed a significant association even after Bonferroni correction (4.08 × 10−5). These include Histo-blood group ABO system transferase encoded by ABO, which has been previously implicated as a potential target gene of PDAC risk variant identified in GWAS. Eight of the identified proteins (Beta-crystallin B2, Dedicator of cytokinesis protein 9, VIP36-like protein, Erythrocyte band 7 integral membrane protein, Tensin-2, Transmembrane protease serine 11D, Alcohol dehydrogenase 1B, and C-X-C motif chemokine 10) were associated with PDAC risk after conditioning on previously reported pancreatic cancer risk variants (odds ratios ranged from 0.79 to 1.52, P-values from 1.28 × 10−3 to 6.47 × 10−4). Pathway enrichment analysis showed that the encoding genes for the implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL-15 production. In conclusion, we identified 38 protein biomarker candidates for PDAC risk, which if validated by additional studies, may contribute to the etiological understanding of PDAC tumor development. Citation Format: Jingjing Zhu, Xiang Shu, Xingyi Guo, Duo Liu, Jiandong bao, Roger Milne, Graham G Giles, Chong Wu, Mengmeng Du, Emily White, Harvey A Risch, Nuria Malats, Eric J. Duell, Phyllis J. Goodman, Donghui Li, Paige Bracci, Verena Katzke, Rachel E Neale, Steven Gallinger, Stephen Van Den Eeden, Alan Arslan, Federico Canzian, Charles Kooperberg, Brian Wolpin, Laura Beane-Freeman, Ghislaine Scelo, Kala Visvanatha, Christopher A. Haiman, Loïc Le Marchand, Herbert Yu, Gloria M Petersen, Rachael Stolzenberg-Solomon, Alison P Klein, Laufey T Amundadottir, Qiuyin Cai, Jirong Long, Xiao-Ou Shu, Wei Zheng, Lang Wu. Associations between genetically predicted blood protein biomarkers and pancreatic ductal adenocarcinoma risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1200.

Abstract Background: Gastric cancer is one of the leading causes of cancer-related mortality worldwide, with a global burden of 5.7% new cases each year and 8.2% of cancer-related deaths. Area of residence has been found to affect survival in different cancers but their impact on gastric cancer remains largely unknown. The purpose of this study is to address the potential disparities between the rural and urban populations affected specifically by gastric adenocarcinoma. Methods: We conducted a retrospective study, analyzing different socio-economic factors associated with populations affected by gastric adenocarcinoma between 2004 and 2013. Data was obtained from the National Cancer Database (NCDB). Univariate and multivariable analyses were performed to evaluate overall survival (OS). Different socio-demographic factors, location of residence were included, urban area (UA) or rural area (RA), gender, race, insurance status and marital status were included in the analyses. Results: A total of 88,246 [RA, N=12,365; UA, N=75,881] patients were included in the study. Majority of the study population was white (N = 67,792, 77%) and male (N = 59,574, 68%). Univariate and multivariable analysis showed that RA had the worst OS (univariate - HR=1.08, p<0.001; multivariate HR=1.04; p<0.001) compared to UA. When comparing different racial backgrounds, univariate and multivariable analysis showed Native American and African American population had poor OS when compared to the white population, however, Asian patients tend to have better OS (univariate HR=0.66, multivariable HR=0.68, p<0.01). From quality of care standpoint, UA patients median days to undergo surgery (28 vs. 33; p<0.01) post diagnosis was significantly sooner, with significantly fewer positive margins (6.3% vs. 6.9%; p<0.01) when compared to RA patients. Though, there is no minimum number of lymph nodes examined during resection, but total of 15 or above is an accepted practice. When comparing the lymph node dissection, 19.6% UA patients underwent more than or equal to 15 lymph nodes dissection in comparison to 18.7% patients in RA (p=0.03). Discussion: This study identifies socio-demographic disparities in gastric adenocarcinoma. Access to healthcare, variations in patient care, environmental and lifestyle factors as well as genomic differences are all potential factors that affect the OS. This is consistent with the available literature in gastric cancer, including studies demonstrating survival differences in different populations undergoing surgical treatment in the United States. Based on the above data, it is imperative for future health policy initiatives to address these disparities in an effort to improve OS. Citation Format: Rohit Gosain, Navpreet Rana, Riccardo Lemini, Chong Wang, Sarbajit Mukherjee. Sociodemographic disparities in gastric adenocarcinoma: A population-based study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A054.

Background and Objectives The association between migraine, depression, and anxiety has been established, but the impact of these psychiatric comorbidities on functional impairment in people with migraine has been under‐investigated. The purpose of this cross‐sectional observational study was to investigate the relationship between anxiety and depression symptoms on migraine‐related disability, pain interference, work interference, and career success in a cohort of patients with migraine. Methods This analysis included 567 migraine patients who had been enrolled into the American Registry for Migraine Research (ARMR) between February 2016 and June 2019. Patients completed the Generalized Anxiety Disorder‐7 (GAD‐7) and Patient Health Questionnaire‐2 (PHQ‐2) to measure symptoms of anxiety and depression, respectively. Patients completed the Migraine Disability Assessment Scale (MIDAS), Pain Interference (PROMIS pain short) questionnaire, and Work Productivity and Activity Interference (WPAI) questionnaire to measure levels of functional impairment at work and in daily activities. In addition, patients answered questions designed for ARMR regarding education and career interference. Models were created to describe the relationship between severity of psychiatric symptoms (anxiety and depression), and each outcome of interest (WPAI, MIDAS, pain interference, reporting that migraine had interfered with career success). Each model was controlled for age, sex, headache frequency, years with migraine, and average headache intensity. Results Among the 567 patients with migraine, mean (SD) age was 47.1 (13.7), 87.3% were female, and average headache frequency was 19.1 (9.3) days/month. PHQ‐2 scores were positively associated with scores on MIDAS ( b = 0.06, SE = 0.01, P ≤ .001), pain interference ( b = 1.4, SE = 0.2, P < .001), and WPAI including absenteeism ( b = 0.16, SE = 0.04, P = .007), presenteeism ( b = 2.7, SE = 1.1, P = .012), overall work productivity impairment ( b = 3.7, SE = 1.2, P = .001), and activity impairment ( b = 3.0, SE = 1.2, P = .009). PHQ‐2 scores were also associated with reporting that migraine interfered with career success ( b = 0.34, SE = 0.08, P ≤ .001). GAD‐7 scores were not associated with MIDAS, pain interference, WPAI, or reduced career success. Conclusions Severity of depression symptoms in patients with migraine is associated with migraine‐related disability, work interference, pain interference, and reduced career success. Patients with more severe symptoms of depression are more likely to have greater functional impairment. A management approach that addresses depression in those with migraine may lead to improvements in patient functioning.

Background and Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans. Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts. Results: In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the HNF1A gene that reached genome-wide significance ( P =4.62×10 −8 ) and an additional 29 variants with suggestive evidence of association ( P <1×10 −6 ), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction P value of 2.08×10 −3 (0.05/24 unique loci), we were able to validate associations at the HNF1A locus in both SiGN ( P =8.18×10 −4 ) and METASTROKE ( P =1.72×10 −3 ) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the HNF1A gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the SFXN4 and TMEM108 genes represent potential novel ischemic stroke loci. Conclusions: These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.

e19047 Background: Colorectal cancer is one of the leading causes of cancer deaths in the US. Area of residence affects survival in many cancers, though largely unknown in colorectal cancer. The purpose of this study is to evaluate disparities between the metropolitan, urban and rural populations and the impact on survival in colorectal cancer. Methods: Data was obtained from the National Cancer Database (NCDB) colon, rectosigmoid, and rectal data sets. Patients (pts) were categorized by area of residence: metropolitan (MA), urban (UA), or rural (RA). Gender, race, insurance status, income, marital status, and tumor related data was collected. Univariate and multivariate analyses were performed to evaluate variables affecting overall survival (OS). Results: A total of 973,139 pts, spanning 2004-2013 were included in the study, 83% MA, 15% UA, 2% RA. RA and UA pts were more likely to be white than MA pts (92.7 v 91.4% v 83%). RA and UA were more likely to have lower income, with slightly lesser amounts of women and pts with no comorbidities. Uninsured rates were similar (3.3%). On univariate analysis, OS was worse for RA (HR 1.10) and UA (1.06) pts, as compared with MA. On multivariate analysis, small differences persisted with worse OS for RA (HR 1.02, p = .043) and UA (HR 1.01, p = .003). Black (HR 1.14) and native American (HR 1.17) pts had worse outcomes, while Asian (HR 0.8) pts had improved OS. Women (HR 0.88) and pts with higher incomes ( > 46K or 63K) had improved OS (HR 0.88). Conclusions: This study identifies socio-demographic disparities in colorectal cancer outcomes. Pts from rural and urban areas had worse OS, even though the proportion of minority pts with poor outcomes was lower. The difference in OS for RA and UA remained statistically significant in multivariate analysis, though it was largely corrected when adjusting for influencing variables. Part of this difference may be due to economic disparities, as lower income was linked to worse OS. This can independently limit access to care, especially for geographically isolated individuals. Additional research efforts are needed in order for us to better understand the key issues facing and the optimal means to improve outcomes in at risk populations.