The 4th Annual Research Days in Central Texas successfully came together on May 4–5, 2016. This multi- and cross-disciplinary event showcases the breadth of research at Baylor Scott & White Health. Medical residents and fellows, postdoctoral research fellows, medical students, nurses, research staff, and faculty represented the diverse group of investigators presenting research. This year, 86 abstracts were accepted from varying aspects of research, including basic/translational science, clinical effectiveness/delivery, case studies, and quality improvement. Abstract peer review resulted in the selection of 10 podium presentations and 76 posters. Departmentally nominated podium presentations were given by Di Ai, MD, Chad Hall, MD, and Matthew McMillin, PhD, and research podium presentations were given by Laura Hargrove, MS, Matthew Gestaut, MD, Connie Barker, PhD, Gurkarminder Sandhu, MD, Emily Wu, MD, Eric Sparks, MD, and David Olek, MD. Poster presentation winners included Bella Mogaka, PharmD, Christopher Johnson, MD, PhD, Ryang Hwa Lee, PhD, and Zachary Burke, BS. Selected abstracts are presented below.
Activation of the apelin–apelin receptor axis promotes cholangiocarcinoma growth and angiogenesis
Chad Hall, MD,∗ Laurent Ehrlich, BA, Tori Sheppard, April O'Brien, BS, Terry C. Lairmore, MD, Gianfranco Alpini, PhD, and Shannon Glaser, PhD(∗e-mail: chad.hall@BSWHealth.org)
The apelin receptor (APLNR), a G-protein coupled receptor, is involved in benign and malignant pathologies, including diabetes, obesity, and colon, prostate, and breast cancer. Cholangiocarcinoma (CCA) is an often fatal malignancy of intra- and extrahepatic cholangiocytes. We tested the hypothesis that the apelin–APLNR axis regulates CCA growth by autocrine/paracrine mechanisms. CCA cell lines (CCLP, HuH-28, HuCCT-1, SG231, TFK, and Mz-ChA-1) and nonmalignant cholangiocytes (H69) were used to measure the expression of APLNR via immunoblots. Immunohistochemistry was also used to measure APLNR expression in human CCA tissue arrays. Apelin secretion from CCA and H69 cell lines was measured by enzyme-linked immunosorbent assay (ELISA). CCA cell lines were treated with apelin in the presence and absence of APLNR antagonist over various timepoints. Changes in proliferation were measured through quantitative polymerase chain reaction (qPCR) for Ki-67 and proliferating cell nuclear antigen. Angiogenesis markers, including vascular endothelial growth factor-A and -C, were measured by qPCR. The Muse MAPK Dual Detection kit was used to measure phosphorylation of ERK1/2, a known pathway for cholangiocyte proliferation. Results showed that APLNR was upregulated in CCA cell lines and human CCA tissue arrays compared with nonmalignant controls. By ELISA, there was enhanced secretion of apelin in CCA lines compared with H69. Treatment of CCA cells with apelin increased CCA growth, whereas the APLNR antagonist significantly decreased basal proliferation and expression of angiogenesis markers. Treatment of CCA cells with apelin increased ERK1/2 phosphorylation compared with untreated cells. In conclusion, apelin and APLNR are up-regulated in CCA compared with normal controls. Apelin promotes CCA proliferation through activation of the ERK1/2 pathway. Inhibition of APLNR decreases basal proliferation, suggesting an autocrine mechanism of CCA growth. Modulation of the apelin–APLNR axis may serve as a novel therapeutic strategy to inhibit CCA tumorigenesis.
Ursodeoxycholic acid treatment reverses biliary proliferation and hepatic fibrosis in Mdr2−/− mice and human primary sclerosing cholangitis by decreasing mast cell infiltration and histamine release
Laura Hargrove, MS, Lindsey Kennedy, BS, Jennifer Demieville, AAS, Victoria Huynh, BS, Fanyin Meng, MD, PhD, Christopher Johnson, DO, Sharon DeMorrow, PhD, Francesca Bernuzzi, MD, Pietro Invernizzi, MD, Gianfranco Alpini, PhD, and Heather Francis, PhD∗ (∗e-mail: heather.francis@BSWHealth.org)
Ursodeoxycholic acid (UDCA) is used to treat biliary disorders. Bile acids alter histamine release from mast cells (MCs), which infiltrate the liver in the Mdr2−/− mouse model of primary sclerosing cholangitis (PSC). This study aimed to determine the effects of UDCA treatment on MC infiltration and liver pathology in PSC. Wild-type and Mdr2−/− mice were fed a control diet or UDCA. Human samples were collected from control and PSC patients treated with placebo or UDCA. MC infiltration was measured by immunofluorescence for FC∊R1 and quantitative polymerase chain reaction (qPCR) for c-kit, chymase, and tryptase. Intrahepatic bile duct mass was evaluated by CK-19. Fibrosis was detected by qPCR for α-SMA, fibronectin, and collagen-type 1a. In vitro, MCs were treated with UDCA prior to measuring histamine secretion and co-culturing with cholangiocytes. Biliary proliferation was measured in co-cultured cells. In PSC, the MC number increased and MCs were found close to bile ducts. UDCA treatment decreased MC number, marker expression, intrahepatic bile duct mass, and fibrosis. In vitro, UDCA decreased MC histamine release and proliferation in cholangiocytes co-cultured with UDCA-treated MCs. In conclusion, during PSC, MCs infiltrate the liver, inducing fibrosis. UDCA reduces MC histamine, thereby decreasing fibrosis. Inhibition of MCs' migration/infiltration may be a therapeutic option for PSC.
Behavior of prostate cancer in patients with very low risk disease but an isolated high risk prostate-specific antigen level
Matthew Gestaut, MD,∗ Jessica E. Pruszynski, PhD, and Gregory Swanson, MD (∗e-mail: matthew.gestaut@BSWHealth.org)
Rarely, a subset of patients with prostate cancer presents with biochemically divergent risk stratification. Other than markedly elevated prostate-specific antigen (PSA) scores (>20 ng/mL), these patients meet very low-risk criteria for Gleason scores (GS), stage, and number/percent cores involved with cancer. Oncologists debate whether malignancies in these patients behave more comparably to low-risk or high-risk disease. From 2000 to 2013, a retrospective chart review was completed of very low-risk disease: T1a–T2a, GS ≤6, ≤3 cores positive, ≤50% involvement of any core, and PSA <10. The divergent-risk group met low-risk criteria except for PSA scores of 20 to 80 ng/mL. The high-risk, low-volume group had T1c–T2a, PSA <20, GS of 4+4 only, and <4 cores positive. Failure was defined as PSA nadir +2 ng/mL. Eighteen, 60, and 19 patients were in the divergent, low-risk, and high-risk groups, respectively. The mean PSA follow-up was 56 months (divergent), 74 months (low-risk), and 63.6 months (high-risk), and 61%, 2%, and 73% of patients in the divergent, low-, and high-risk groups received androgen deprivation therapy. Respective biochemical failure rates were 22.2%, 11.7%, and 30% for divergent, low-, and high-risk patients. The biochemical failure rate differed significantly between the divergent group and the low-risk group (P = 0.021) and between the low-risk group and the high-risk group (P = 0.025), but not between the divergent group and the high-risk group (P = 0.53). Biochemical progression-free survival at 5 years was 71.3% for the divergent group, 68.8% for the high-risk group, and 98.3% for the low-risk group. Thus, divergent disease did not appear to behave differently from low-volume, high-risk disease. These findings are relevant when counseling patients with low-risk/low-volume but divergent PSA disease. Both oncologists and patients should be aware that outcomes for divergent patients are poor, similar to those for their low-volume, classically high-risk counterparts.
Variation in use of prophylactic antibiotics in gynecologic procedures before and after an education intervention
Emily Wu, MD,∗ Jessica Langsjoen, MD, Jessica Pruszynski, PhD, Thomas Kuehl, PhD, and Wilma Larsen, MD (∗e-mail: Emily.Wu@bswhealth.org)
Guidelines for prophylactic antibiotic use in gynecology procedures are put forth by the American College of Obstetricians and Gynecologists. Despite clear guidelines, there is a high rate of use of nonindicated prophylactic antibiotics. The objective was to examine variations in use of prophylactic antibiotics in patients undergoing gynecology surgery at Scott and White Memorial Hospital. A secondary aim was to determine if an educational intervention to gynecology physicians was associated with a significant decrease in nonindicated prophylactic antibiotics. A retrospective chart review was performed for women undergoing gynecology surgery over a 1-year period. An educational intervention regarding prophylactic antibiotic use was held for the obstetrics and gynecology physicians in the middle of this time period. Subjects were included if they had CPT codes corresponding with a procedure that did not require prophylactic antibiotics. Subjects were excluded if they had concurrent procedures for which antibiotics were recommended. A total of 500 subjects were included, 243 before the educational intervention and 257 after. A significant decrease (P < 0.0001) in nonindicated prophylactic antibiotic use was demonstrated, from 45.7% (111/243) before the intervention to 24.9% (64/257) after the intervention. A simple educational intervention was associated with a significant decrease in use of nonindicated prophylactic antibiotics in gynecology procedures.
Medication reconciliation in the emergency department performed by pharmacy personnel: a prospective cohort comparison study
Bella Mogaka, PharmD,∗ Darren Clary, PharmD, Chau Le Bao Hong, PharmD, Charlotte Farris, PharmD, and Sebastian Perez, PharmD (∗e-mail: bella.mogaka@BSWHealth.org)
Admission to an emergency department (ED) is a key moment when patients are at risk of medication discrepancies. Medication histories are an effective way of ensuring that fewer errors are made. The objective of this study was to determine the role of pharmacy personnel in obtaining best possible medication histories and performing reconciliation at the admission interface of care from the ED to the inpatient setting, therefore maximizing transition of care opportunities. The intervention group consisted of pharmacists conducting medication histories and reconciliations on patients 18 years or older admitted through the Scott & White Memorial Hospital ED to general medicine floors from February 15 to March 13, 2016. The control group consisted of a retrospective chart review between November 23 and December 20, 2015, of reconciliations done by ED providers (physicians, physician assistants, nurse practitioners, nurses, and medical students). Both groups then received a second standardized reconciliation by trained pharmacy personnel, and all discrepancies were recorded. The primary outcome of this study was to compare the number of discrepancies identified in each group. No medication discrepancies were noted after pharmacist-led medication reconciliations, compared with 561 discrepancies reported with the admitting personnel reconciliations. The most frequent discrepancies included unnecessary drug therapy, medication omission, and wrong frequency. In conclusion, medication histories and reconciliations performed in the ED by pharmacy personnel led to fewer discrepancies during admission.
The epithelioid granuloma as a biomarker of severity in Crohn's disease
Chris Johnson, MD, PhD (e-mail: Christopher.Johnson@BSWHealth.org)
The epithelioid granuloma is considered a histologic hallmark of Crohn's disease. However, controversy remains regarding the significance of this finding with relation to disease severity and behavior. In this retrospective analysis of 1466 patients followed over a 5-year period from 2009 to 2014 at a tertiary inflammatory bowel disease referral center, we examined the relationship of the epithelioid granuloma with various markers of disease severity as well as the effect of treatment with biologic therapies targeting TNF-alpha. Data were collected on various parameters measuring disease activity and behavior, quality of life, medication use, and health care utilization. The entire cohort and the subset of patients undergoing surgical resection were analyzed with regard to granuloma rates. Both univariate and multivariate analyses were conducted. The overall rate of epithelioid granulomas in our cohort was 12.8% (187/1466). In the subset of surgical patients, the rate was 21.0% (126/600). The presence of granuloma was associated with elevated inflammatory markers (C-reactive protein odds ratio = 2.9 [2.078–4.208], P < 0.0001), younger age at diagnosis (23.6 ± 11.3 years vs 27.9 ± 13.3 years, P = 0.0005), higher rates of steroid and narcotic use, higher rates of stricturing/penetrating disease phenotype, and higher health care utilization. Among the surgical cohort, the presence of granulomas was associated with need for repeat surgery (odds ratio = 2.5 [1.54–4.02], P = 0.0002). Patients using infliximab had a significantly lower granuloma rate compared with biologically naïve patients (odds ratio = 0.22 [0.05–0.97], P = 0.03), but this trend was not observed for either adalimumab or certolizumab pegol. In conclusion, epithelioid granulomas are detected in a minority of Crohn's disease patients and are associated with a more aggressive disease phenotype. Infliximab use is associated with lower granuloma rates, suggesting that this drug may work to destroy granulomas or prevent their formation in Crohn's disease.
Adapting cognitive work analysis for creating usable standardized work procedures: the case of a telemetry unit
Zachary Scott Burke, BS (e-mail: zachb89@gmail.com)
Every set of standardized work procedures in health care is a model of the processes through which a given unit contributes to the overall goal of patient care. However, to be useful, standardized work procedures need to strike a delicate balance between minimizing unnecessary process variability while still allowing flexibility to adapt to unexpected events inherent in a system as complex as a hospital unit. Unfortunately, little progress has been made towards developing a design methodology capable of striking this balance in a system often marked by seemingly conflicting priorities. To fill this gap, a cognitive work analysis was adapted to structure the design of an effective set of standardized work procedures. It was tested by creating a set of standardized work procedures for a small telemetry monitoring unit responsible for monitoring patients located across several floors of a hospital. The cognitive work analysis was able to be completed by a single experienced member of the telemetry unit, at which point it was validated and expanded upon through unstructured interviews with the unit's four other members. The result was the completion of the background design work needed to create a set of procedures that is both accurate and appropriately specific. It is believed that, with further development, this framework will be valuable in creating an evidence-based practice framework that also accounts for the unique structure of an individual hospital unit.