Background & Aims Fibroblast growth factor 21 (FGF21) is a hepatic protein that plays a critical role in metabolism, stimulating fatty acid oxidation in liver and glucose uptake in fat. Systemic administration to obese rodents and diabetic monkeys leads to improved glucose homeostasis and weight loss. In rodents, FGF21 increases with fasting and consumption of a ketogenic diet (KD). In humans, FGF21 correlates with body mass index, but studies evaluating other parameters show inconsistent results. We examined FGF21 serum levels in lean and obese individuals and in response to dietary manipulation. We also evaluated FGF21 serum levels and liver mRNA expression in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Methods Serum FGF21 was measured after an overnight fast in individuals with BMI ranging from normal to obese. Volunteers fasted for 16 or 72 hours and then ate a standard meal. Another group consumed KD for 12 days. Serum FGF21 and hepatic mRNA expression were measured in obese individuals with NAFLD or NASH. Results There was a positive correlation between BMI and FGF21. There was no change in FGF21 in response to a short fast or KD. A non-statistically significant fall in FGF21 levels was seen after a 72 hour fast. Hepatic FGF21 mRNA expression was significantly elevated in NAFLD, which correlated with a substantial increase in serum FGF21. In NASH, serum FGF21 but not liver mRNA was increased. Conclusion FGF21 correlates with BMI and may be a novel biomarker for NAFLD but is not nutritionally regulated in humans.

OBJECTIVETo investigate the effect of treatment with the glucagon-like peptide 1 receptor agonist exenatide on weight loss and metabolic parameters in obese nondiabetic women.RESEARCH DESIGN AND METHODSForty-one obese women (aged 48 ± 11 years and BMI 33.1 ± 4.1 kg/m2) participated in a 35-week randomized, double-blind, placebo-controlled, crossover study, including two 16-week treatment periods separated by a 3-week washout period. There was no lifestyle intervention. The primary outcome was change in body weight.RESULTSSubjects treated with exenatide lost an average of 2.49 ± 0.66 kg compared with a 0.43 ± 0.63 kg weight gain during placebo treatment. Weight loss with exenatide treatment was noted at 2 weeks. The degree of weight loss could be stratified. A total of 30% of subjects were high responders who lost ≥5% body weight (−7.96 ± 0.52%), 39% were moderate responders who lost <5% body weight (−2.43 ± 0.45%), and 31% were nonresponders who gained weight (1.93 ± 0.53%). Waist circumference also decreased significantly with exenatide treatment. Subjects experienced more nausea during exenatide treatment compared with placebo, but the severity decreased over time and did not correlate with weight loss.CONCLUSIONSShort-term exenatide treatment was associated with modest weight loss and decreased waist circumference in a cohort of obese nondiabetic women. A subset of individuals demonstrated robust weight loss that was detected very early in the course of treatment.

Objective To investigate causes of failure of free flap reconstructions in patients undergoing reconstruction of head and neck defects. Study Design Case series with chart review. Setting Single tertiary care center. Subjects and Methods Patients underwent reconstruction between January 2007 and June 2017 (n = 892). Variables included were clinical characteristics, social history, defect site, donor tissue, ischemia time, and postoperative complications. Statistical methods used include univariable and multivariable analysis of failure. Results The overall failure rate was 4.8% (n = 43). Intraoperative ischemia time was associated with free flap failures (odds ratio [OR], 1.062; 95% confidence interval [CI], 1.019-1.107; P = .004) for each addition of 5 minutes. Free flaps that required pedicle revision at time of initial surgery were 9 times more likely to fail (OR, 9.953; 95% CI, 3.242-27.732; P < .001). Patients who experienced alcohol withdrawal after free flap placement were 3.7 times more likely to experience flap failure (OR, 3.690; 95% CI, 1.141-10.330; P = .031). Ischemia time remained an independent significant risk factor for failure in nonosteocutaneous free flaps (OR, 1.105; 95% CI, 1.031-1.185). Alcohol withdrawal was associated with free flap failure in osteocutaneous reconstructions (OR, 5.046; 95% CI 1.103-19.805) while hypertension was found to be protective (OR, 0.056; 95% CI, 0.000-0.445). Conclusion Prolonged ischemia time, pedicle revision, and alcohol withdrawal were associated with higher rates of flap failure. Employing strategies to minimize ischemic time may have potential to decrease failure rates. Flaps that require pedicle revision and patients with a history of significant alcohol use require closer monitoring.

Background: Understanding factors impacting successful salvage of a compromised free flap. Methods: Multi-institutional review of free flap reconstructions for head and neck defects (n = 1764). Results: Free flap compromise rate: 9% (n = 162); 46% salvaged (n = 74). Higher salvage rates in initial 48 hours (64%) vs after (30%; P < .001). Greater compromise (14%) and failure (8%) if inset challenging vs straightforward (6% compromise, 4% failure; P = .035). Greater compromise (23%) and failure (17%) following intraoperative anastomosis revision vs no revision (7% compromise, 4% failure; P < .0001). Success following arterial insufficiency was lower (60% failed, 40% salvaged) vs venous congestion (23% failed, 77% salvaged) (P < .0001). Greater flap salvage following thrombectomy (66%) vs no thrombectomy (34%; P < .0001). Greater flap salvage if operative duration ≤8 hours (57%), vs >8 hours (40%) (P = .04). Conclusions: There were higher rates of free flap salvage if the vascular compromise occurred within 48 hours, if due to venous congestion, if operative duration ≤8 hours, and if the anastomosis did not require intraoperative revision. K E Y W O R D S free flap, free flap salvage, head and neck reconstruction, outcomes, surgical complications 1 | INTRODUCTION Microvascular free flap reconstruction of head and neck defects was first introduced in the 1970s and has resulted in superior aesthetic and functional results and improved patient quality of life. 1-3 Free flap survival rates in recent years are consistently cited as greater than 95%, 4-10 with still a small percentage of free flaps experiencing vascular compromise. Salvage of a compromised free flap is often attempted as complete failure of a free flap results in significant morbidity for the patient, increased length of hospitalization, and increased health care cost. 7,11-15 The ability to salvage a compromised free flap has been cited as high as 60% to 80%. 9,16-19 Therefore, great efforts are undertaken to salvage a compromised free flap. Most academic centers, which perform high volume free tissue transfer, are prepared to rapidly intervene once a compromised free flap is identified. A timely recognition of a

While many traditional clinico-pathologic markers of aggressive disease in head and neck cancer also impact survival in surgically treated HPV-associated oropharyngeal cancer, extracapsular extension may be less important.