Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial.

Background: The state of prediabetes comprises atherosclerotic changes leading to decreased vascular function in humans. This study examined the effects on incretin mimetics on vascular physiology in the prediabetic postprandial state. Methods: Fifteen obese adults with prediabetes participated in a randomized, crossover, double-blinded trial comparing the postprandial effects of exenatide, saxagliptin, and placebo on peripheral vasodilation. All studies utilized a standardized high-fat meal. Resting and peak forearm blood flow (FBF) were measured via strain gauge venous occlusion plethysmography, and makers of vascular dysfunction were measured in plasma. Results: Exenatide attenuated resting FBF at 3 hr (P = 0.003) and 6 hr (P = 0.056) postmeal, compared to placebo. Nonsignificant reductions in resting FBF were observed between saxagliptin and placebo at the same time points. No group differences were observed for peak FBF, plasma nitrotyrosine, and plasma 8-iso-prostaglandin F2alpha. A transient increase in plasma triglyceride was abated in the exenatide group, when compared to saxagliptin and placebo groups. Only exenatide group showed no significant upsurge in plasma insulin. Plasma-free fatty acids significantly declined in all three groups, although less markedly for exenatide. Postmeal glucose increased at 2 hr with placebo and saxagliptin, but simultaneously decreased with exenatide. Conclusions: Acute treatment with exenatide blunted the postprandial vasodilatory effect of a high-fat meal in prediabetes. Exenatide's acute effects derived primarily from multiple endothelium-independent processes. Trial Registration Number: NCT02104739.

Large database utilization in health outcomes research in pancreatic cancer: an update.

We sought to review published aggregate dataset studies on pancreatic cancer in the national and international settings, discuss the advantages and disadvantages these datasets possess, and possible future directions. A combination of Google Scholar, PubMed, and MEDLINE were used with search terms "pancreatic cancer" + "resectable" + "national cancer database", "pancreatic cancer" + "unresectable" + "national cancer database" and more broadly "borderline resectable pancreatic cancer", "locally advanced pancreatic cancer", "unresectable pancreatic cancer", and "resectable pancreatic cancer". Original articles and abstracts from this search were included, including data from the Surveillance, Epidemiology, and End Results (SEER) database, National Cancer Database (NCDB), and SEER-Medicare within the United States (US), as well as international database studies. Multiple database studies have been published regarding the role for radiotherapy in resected pancreatic cancer (n=6), the timing of additional therapy in resectable pancreatic cancer (n=4), and the role for radiotherapy and resection in locally advanced pancreatic cancer (LAPC) (n=4). Studies from both SEER and NCDB found a survival benefit to post-operative radiotherapy. In resectable pancreatic cancer, neoadjuvant treatment was found to be superior to adjuvant (NCDB). Chemoradiotherapy was found to be more beneficial than chemotherapy alone in LAPC, and patients who received highly-conformal or stereotactic body radiotherapy (SBRT) had improved survival compared to either conformal radiotherapy or chemotherapy alone. These studies also found that up to 10% of patients underwent resection, with a 90% margin-negative rate, and either one-half to one-third the risk of death of non-surgical patients. Criticism of large datasets includes lack of granularity of performance status, diagnosis, treatment, and outcomes-related data compared to properly administered prospective trials, as well as cross-over between treatment arms that cannot be accounted for, and concerns over quality of data represented. The US has witnessed a growing number of comparative effectiveness studies in pancreatic cancer. When taken together, certain themes emerge that are consistent with both single-institution data and clinical trials. These studies have also provided insight into questions not readily answerable by clinical trials. However, they require caution in interpretation.

Patient reported dry mouth: Instrument comparison and model performance for correlation with quality of life in head and neck cancer survivors.

PURPOSE: To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). METHODS: Head and neck cancer survivors who had received radiation therapy (RT) completed the MDASI-HN, the University of Michigan Hospital Xerostomia Questionnaire (XQ), and the health visual analog scale (VAS) of the EuroQol Five Dimension Questionnaire (EQ-5D). The Bayesian information criteria (BIC) were used to test the prediction power of each tool for EQ-5D VAS. The modified Breiman recursive partitioning analysis (RPA) was used to identify a cut point of the MDASI-HN dry mouth score (MDASI-HN-DM) with EQ-5D VAS, using a ROC-based approach; regression analysis was used to confirm the threshold effect size. RESULTS: Two-hundred seven respondents formed the cohort. Median follow-up from the end of RT to questionnaire completion was 88 months. The single item MDASI-HN-DM score showed a linear relationship with the XQ composite score (ρ = 0.80, p < 0.001). The MDASI-HN-DM displayed improved model performance for association with EQ-5D VAS as compared to XQ (BIC of 1803.7 vs. 2016.9, respectively). RPA showed that an MDASI-HN-DM score of ≥6 correlated with EQ-5D VAS decline (LogWorth 5.5). CONCLUSION: The single item MDASI-HN-DM correlated with the multi-item XQ and performed favorably in the prediction of QOL. A MDASI-HN-DM cut point of ≥6 correlated with decline in QOL.