Browsing by Author "Wegermann, Kara"
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Item Open Access Branched chain amino acid transaminase 1 (BCAT1) is overexpressed and hypomethylated in patients with non-alcoholic fatty liver disease who experience adverse clinical events: A pilot study.(PloS one, 2018-01) Wegermann, Kara; Henao, Ricardo; Diehl, Anna Mae; Murphy, Susan K; Abdelmalek, Manal F; Moylan, Cynthia ABackground and objectives
Although the burden of non-alcoholic fatty liver disease (NAFLD) continues to increase worldwide, genetic factors predicting progression to cirrhosis and decompensation in NAFLD remain poorly understood. We sought to determine whether gene expression profiling was associated with clinical decompensation and death in patients with NAFLD, and to assess whether altered DNA methylation contributes to these changes in gene expression.Methods
We performed a retrospective analysis of 86 patients in the Duke NAFLD Clinical Database and Biorepository with biopsy-proven NAFLD whose liver tissue was previously evaluated for gene expression and DNA methylation using array based technologies. We assessed the prospective development of liver and cardiovascular disease related outcomes, including hepatic decompensation as identified by the development of ascites, hepatic encephalopathy, hepatocellular carcinoma, or variceal bleeding as well as stroke and myocardial infarction via medical chart review.Results
Of the 86 patients, 47 had F0-F1 fibrosis and 39 had F3-F4 fibrosis at index liver biopsy. Gene expression probe sets (n = 54,675) were analyzed; 42 genes showed significant differential expression (p<0.05) and a two-fold change in expression between patients with and without any outcome. Two expression probes of the branched chain amino-acid transaminase 1 (BCAT1) gene were upregulated (p = 0.02; fold change 2.1 and 2.2 respectively) in patients with a clinical outcome. Methylation of three of the 34 BCAT1 CpG methylation probes were significantly inversely correlated with BCAT1 expression specific to the probes predictive of clinical deterioration.Conclusion
We found differential gene expression, correlated to changes in DNA methylation, at multiple BCAT1 loci in patients with cardiovascular outcomes and/or hepatic decompensation. BCAT1 catalyzes the transformation of alpha-ketoglutarate to glutamate and has been linked to the presence and severity of NAFLD, possibly through derangements in the balance between glutamate and alpha-ketoglutarate. Given the potential for BCAT1 to identify patients at risk for poor outcomes, and the potential therapeutic implications, these results should be validated in larger prospective studies.Item Open Access Diagnosis of Capnocytophaga canimorsus Sepsis by Whole-Genome Next-Generation Sequencing.(Open Forum Infect Dis, 2016-09) Abril, Maria K; Barnett, Adam S; Wegermann, Kara; Fountain, Eric; Strand, Andrew; Heyman, Benjamin M; Blough, Britton A; Swaminathan, Aparna C; Sharma-Kuinkel, Batu; Ruffin, Felicia; Alexander, Barbara D; McCall, Chad M; Costa, Sylvia F; Arcasoy, Murat O; Hong, David K; Blauwkamp, Timothy A; Kertesz, Michael; Fowler, Vance G; Kraft, Bryan DWe report the case of a 60-year-old man with septic shock due to Capnocytophaga canimorsus that was diagnosed in 24 hours by a novel whole-genome next-generation sequencing assay. This technology shows great promise in identifying fastidious pathogens, and, if validated, it has profound implications for infectious disease diagnosis.Item Open Access Standardizing inpatient colonoscopy preparations improves quality and provider satisfaction.(International journal of health care quality assurance, 2020-03) Sullivan, Brian; Zhang, Cecelia; Wegermann, Kara; Lee, Tzu-Hao; Leiman, David APURPOSE:Inpatient colonoscopy bowel preparation quality is frequently suboptimal. This quality improvement (QI) intervention is focused on regimenting this process to impact important outcomes. DESIGN/METHODOLOGY/APPROACH:Define, Measure, Analyze, Improve and Control (DMAIC) methodology was employed, including generating a root-cause analysis to identify factors associated with inpatient bowel quality. These findings motivated the creation of a standardized electronic health record (EHR)-based order set with consistent instructions and anticipatory guidance for administering providers. FINDINGS:There were 264 inpatient colonoscopies evaluated, including 198 procedures pre-intervention and 66 post-intervention. The intervention significantly improved the adequacy of right colon bowel preparations (75.0 percent vs 86.9 percent, p = 0.04) but not overall preparation quality (73.7 percent vs 80.3 percent, p = 0.22). The intervention led to numerical improvement in the proportion of procedures in which the preparation quality interfered with making a diagnosis (10 percent-6 percent, p = 0.29) or resulted in an aborted procedure (3.5 percent-1.5 percent, p = 0.39). After the intervention, provider satisfaction with the ordering process significantly increased (23.3 percent vs 61.1 percent, p < 0.001). PRACTICAL IMPLICATIONS:The QI intervention significantly reduced the number of inpatient colonoscopies with inadequate preparation in the right colon, while also modestly improving the diagnostic yield and proportion of aborted procedures. Importantly, the standardized EHR order set substantially improved provider satisfaction, which should justify broader use of such tools. ORIGINALITY/VALUE:Novel clinical outcomes such as ability to answer diagnostic questions were improved using this intervention. The results align with strategic goals to enhance provider experience and continuously improve quality of patient care.