Faculty Bibliography

Antithrombotic therapy for stroke prevention in patients with atrial fibrillation (AF) has dramatically shifted from warfarin, a vitamin K antagonist, to the direct oral anticoagulants (DOACs) such as dabigatran, apixaban, and rivaroxaban. In patients with contraindications to oral anticoagulation, left atrial appendage occlusion (LAAO) devices, such as the Watchmanâ„¢ device, may be considered; however, temporary postimplantation antithrombotic therapy is still a recommended practice. We present a case of complex antithrombotic management, post LAAO device implantation, designed to avoid drug interactions with concomitant rifampin use and remained necessary secondary to subsequent device leak. This case highlights the challenges of antithrombotic therapy post LAAO device placement in a complex, but representative, patient.

Background: Identifying genetic risk factors for AKI could provide insights into pathophysiology and help identify novel pathways for therapeutic development.
Method(s): We conducted a genome-wide association study in a multi-ethnic population of 1,370 prospectively enrolled subjects in the ASSESS-AKI Study. Genotyping was completed using the Illumina MEGA chip and the Haplotype Reference Consortium was used for genome-wide multiple imputation. Genetic association testing for AKI was conditioned on: age, sex, diabetes, center and first three principal components of ancestry. Threshold for significance included single-nucleotide polymorphisms (SNPs) with a p < 5 X 10^-6.
Result(s): Among 637 AKI and 733 non-AKI participants, 5,645,675 SNPs were tested for the association with AKI. Among AKI participants, 72% had Stage 1 AKI and 7% required new dialysis during hospitalization. We found that 56 SNPs in six novel loci were associated with the development of AKI (Figure 1). The SNP with the strongest association with AKI was rs17538288>A. The minor allele of rs17538288 was associated with an increased risk for AKI (adjusted odds ratio 1.53, 95% confidence interval 1.30-1.79, p=2.08 x 10^-7). Utilizing integrated functional epigenomic analyses, we found that top-performing SNPs localized to regulatory DNA elements in primary human glomerular and cortex cell culture. We also investigated 22 SNPs identified in two prior AKI GWAS studies and found that none of the SNPs replicated in ASSESS-AKI (p<0.05).
Conclusion(s): We identified six novel genetic loci that were associated with prevalent AKI. Functional annotation in kidney cells/tissue provides insights into the mechanism of kidney injury. Future work will require replication in well-phenotyped AKI cohorts and mechanistic studies to understand the relationship of genetic variation and AKI development. (Figure Presented)

Introduction Pancreatic cancer is one of the leading causes of death in both males and females in the United States. Nearly 85% of pancreatic cancer is adenocarcinoma. Given the silent disease progression of pancreatic cancer, identifying at-risk populations will help diagnose these fatal cancers as early as possible. Methods The United States Cancer Statistics (USCS) registry was used to obtain data for pancreatic adenocarcinoma from 2001 to 2015. The incidence analysis was stratified based on sex, race, stage, and US regional location. Results The overall incidence of pancreatic adenocarcinoma from 2001 to 2015 was 5.2 per 100,000 people per year. The overall incidence rates were the greatest for each stratification in males, blacks, distant disease, and in the Northeast. The incidence in blacks continued to rise with an annual percent change (APC) of 2.28 between 2001 and 2015. Between 2001 and 2006, the incidence of distant disease increased at a rapid rate (APC 5.34). However, after 2006, the incidence continued to increase but no longer at the previously rapid rate (APC 1.91). For incidence based on US regional location, the overall incidence was greatest in the Northeast and Midwest. The incidence in the South was increasing at an expeditious rate (APC 2.70). Conclusion In our study, we analyzed the incidence of pancreatic adenocarcinoma using data from all 50 states in the US. Our findings showed that there was a worsening incidence in blacks, those with a distant stage at diagnosis, and those in the North and Midwest. Ultimately our findings help identify at-risk populations and can contribute to improving surveillance of this deadly disease.

Solid-state nanopores are an emerging biosensor for nucleic acid and protein characterization. For use in a clinical setting, solid-state nanopore sensing requires sample preparation and purification, fluid handling, a heating element, electrical noise insulators, and an electrical readout detector, all of which hamper its translation to a point-of-care diagnostic device. A stand-alone microfluidic-based nanopore device is described that combines a bioassay reaction/purification chamber with a solid-state nanopore sensor. The microfluidic device is composed of the high-temperature/solvent resistance Zeonex plastic, formed via micro-machining and heat bonding, enabling the use of both a heat regulator and a magnetic controller. Fluid control through the microfluidic channels and chambers is controlled via fluid port selector valves and allows up-to eight different solutions. Electrical noise measurements and DNA translocation experiments demonstrate the integrity of the device, with performance comparable to a conventional stand-alone nanopore setup. However, the microfluidic-nanopore setup is superior in terms of ease of use. To showcase the utility of the device, single molecule detection of a DNA PCR product, after magnetic bead DNA separation, is accomplished on chip.

Introduction Esophageal cancer is one of the leading causes of death in males in the United States (US). Previous studies have analyzed incidence rates of esophageal cancer in the US using the data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. However, given its limited patient population, certain groups and regions in the US are underrepresented. Our study utilizes the United States Cancer Statistics (USCS) database, which combines the SEER database with the Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) to cover all 50 states to examine the incidence of esophageal cancer. Methods The USCS registry was used to obtain data for esophageal cancer from 2001 to 2015. Incidence analysis was stratified based on sex, race, stage, histology, and US regional location/histology. Results The overall incidence of esophageal cancer from 2001-2015 was 4.7 per 100,000 people per year. Overall incidence rates were greatest for each stratification in males, blacks, distant disease, adenocarcinoma, and those in the Midwest with adenocarcinoma. Blacks, compared to other races, had the greatest statistically significant decrease in incidence between 2001-2015 (annual percent change (APC) -4.55). The incidence rate is also increasing the most rapidly in those with adenocarcinoma in the Northeast from 2011 to 2015 (APC 2.16). Conclusion In our study, we were able to determine the incidence of esophageal cancer using data from all 50 states in the US. Our findings of decreasing incidence in blacks and increasing incidence of adenocarcinoma in the Midwest and Northeast help elucidate the at-risk populations. Moreover, our findings help bring to light risk factors that may be contributing to the development of esophageal cancer and how diagnosis and surveillance can be improved based on these risk factors.