Exploring the Paradoxical Relationship of a Creb 3 Regulatory Factor Missense Variant With Body Mass Index and Diabetes Among Samoans: Protocol for the Soifua Manuia (Good Health) Observational Cohort Study.

BACKGROUND: The prevalence of obesity and diabetes in Samoa, like many other Pacific Island nations, has reached epidemic proportions. Although the etiology of these conditions can be largely attributed to the rapidly changing economic and nutritional environment, a recently identified genetic variant, rs373863828 (CREB 3 regulatory factor, CREBRF: c.1370G>A p.[R457Q]) is associated with increased odds of obesity, but paradoxically, decreased odds of diabetes. OBJECTIVE: The overarching goal of the Soifua Manuia (Good Health) study was to precisely characterize the association of the CREBRF variant with metabolic (body composition and glucose homeostasis) and behavioral traits (dietary intake, physical activity, sleep, and weight control behaviors) that influence energy homeostasis in 500 adults. METHODS: A cohort of adult Samoans who participated in a genome-wide association study of adiposity in Samoa in 2010 was followed up, based on the presence or absence of the CREBRF variant, between August 2017 and March 2019. Over a period of 7-10 days, each participant completed the main study protocol, which consisted of anthropometric measurements (weight, height, circumferences, and skinfolds), body composition assessment (bioelectrical impedance and dual-energy x-ray absorptiometry), point-of-care glycated hemoglobin measurement, a fasting blood draw and oral glucose tolerance test, urine collection, blood pressure measurement, hand grip strength measurement, objective physical activity and sleep apnea monitoring, and questionnaire measures (eg, health interview, cigarette and alcohol use, food frequency questionnaire, socioeconomic position, stress, social support, food and water insecurity, sleep, body image, and dietary preferences). In January 2019, a subsample of the study participants (n=118) completed a buttock fat biopsy procedure to collect subcutaneous adipose tissue samples. RESULTS: Enrollment of 519 participants was completed in March 2019. Data analyses are ongoing, with results expected in 2020 and 2021. CONCLUSIONS: While the genetic variant rs373863828, in CREBRF, has the largest known effect size of any identified common obesity gene, very little is currently understood about the mechanisms by which it confers increased odds of obesity but paradoxically lowered odds of type 2 diabetes. The results of this study will provide insights into how the gene functions on a whole-body level, which could provide novel targets to prevent or treat obesity, diabetes, and associated metabolic disorders. This study represents the human arm of a comprehensive and integrated approach involving humans as well as preclinical models that will provide novel insights into metabolic disease. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/17329.

Esophagectomy for cancer in octogenarians: should we do it?

PURPOSE: Inconsistent data exists regarding esophagectomy outcomes in octogenarians undergoing transhiatal esophagectomy for esophageal cancer. METHODS: A retrospective review was performed for esophagectomy cancer patients between 2000 and 2012 at our tertiary referral center. Outcome data for octogenarians was compared to younger patients aged 20 to 79 years. A case-matched group of patients younger than 80 years old (n = 33) was included based on the Charlson comorbidity index with the octogenarian group (n = 33). Endpoints included operative morbidity and mortality as well as short- and long-term survival. RESULTS: Thirty-three octogenarians met inclusion criteria. The median age was 82 years, and 79% were male; 76% had adenocarcinoma, 87% had distal esophageal, and 52% had poorly differentiated tumors. Stages 0 through III were observed in 6, 18, 27, and 48% of octogenarians, respectively. Neoadjuvant therapy was administered to 70% of patients, with 48% experiencing downstaging. Transhiatal esophagectomy was performed in 82% of patients, with R0 resection in 94%. The mean hospital stay was 18 days, with morbidity and mortality rates 56 and 9%, respectively, not significantly different from 13-day hospital stay, 45% morbidity, and 9% mortality in younger patients. Cardiac, pulmonary, and surgical site complications occurred in 24, 27, and 6% of octogenarians, respectively. Anastomotic leak occurred in 18% and reoperations in 3%. The median, 3-year survival, and 5-year survival were 21 months, 55.9%, and 37.1%, respectively. Overall survival was worse for octogenarians (p < 0.001). CONCLUSIONS: Postoperative mortality, morbidity, and length of stay in octogenarians are comparable to younger patients, while the overall survival is worse. With appropriate patient selection, good outcomes can be accomplished in octogenarians undergoing esophagectomy for cancer.

A new algorithm to allow early prediction of mortality in elderly burn patients.

INTRODUCTION: The elderly are the fastest growing population segment, and particularly susceptible to burns. Predicting outcomes for these patients remains difficult. Our objective was to identify early predictors of mortality in elderly burn patients. METHODS: Our Burn Center's prospective database was reviewed for burn patients 60+ treated in the past 10 years. Predictor variables were identified by correlative analysis and subsequently entered into a multivariate logistic regression analysis examining survival to discharge. RESULTS: 203 patients of 1343 (15%) were eligible for analysis. The average age was 72 ± 10 (range 60-102) and the average total body surface area (TBSA) burned was 23 ± 18% (range 1-95). Age, TBSA, base deficit, pO(2), respiratory rate, Glasgow Coma Score (GCS), and Revised Trauma Score (RTS, based on systolic blood pressure, respiratory rate, and GCS) all correlated with mortality (p ≤0 .05). Using multiple logistic regression analysis, a model with age, TBSA and RTS was calculated, demonstrating: In this model, ß(0) is a constant that equals -8.32. CONCLUSIONS: Predicting outcomes in elderly burn patients is difficult. A model using age, TBSA, and RTS can, immediately upon patient arrival, help identify patients with decreased chances of survival, further guiding end-of-life decisions.

Modified use of the Hemodialysis Reliable Outflow (HeRO) graft for salvage of threatened dialysis access.

The Hemodialysis Reliable Outflow (HeRO) graft (Hemosphere Inc, Eden Prairie, Minn) offers a new option to provide upper extremity arteriovenous (AV) dialysis access in patients with central venous occlusive disease. Creative use of this device can allow for salvage of failing or threatened AV fistulas and grafts. We present two patients who underwent a modified implantation of the HeRO device for immediate salvage of a malfunctioning AV access. Ipsilateral central venous occlusions were successfully overcome by anastomosing a HeRO device to the existing AV access and tunneled across the chest to the contralateral internal jugular vein.