Citations

Summary The objective of this study was to critically review the empirical evidence from all relevant disciplines regarding obesity stigma in order to (i) determine the implications of obesity stigma for healthcare providers and their patients with obesity and (ii) identify strategies to improve care for patients with obesity. We conducted a search of M edline and PsychInfo for all peer‐reviewed papers presenting original empirical data relevant to stigma, bias, discrimination, prejudice and medical care. We then performed a narrative review of the existing empirical evidence regarding the impact of obesity stigma and weight bias for healthcare quality and outcomes. Many healthcare providers hold strong negative attitudes and stereotypes about people with obesity. There is considerable evidence that such attitudes influence person‐perceptions, judgment, interpersonal behaviour and decision‐making. These attitudes may impact the care they provide. Experiences of or expectations for poor treatment may cause stress and avoidance of care, mistrust of doctors and poor adherence among patients with obesity. Stigma can reduce the quality of care for patients with obesity despite the best intentions of healthcare providers to provide high‐quality care. There are several potential intervention strategies that may reduce the impact of obesity stigma on quality of care.

Abstract Purpose: Esophageal cancer is an aggressive malignancy and often resistant to therapy. Overexpression of EGFR has been associated with poor prognosis of patients with esophageal cancer. However, clinical trials using EGFR inhibitors have not provided benefit for patients with esophageal cancer. Failure of EGFR inhibition may be due to crosstalk with other oncogenic pathways. Experimental Design: In this study, expression of YAP1 and EGFR were examined in EAC-resistant tumor tissues versus sensitive tissues by IHC. Western blot analysis, immunofluorescence, real-time PCR, promoter analysis, site-directed mutagenesis, and in vitro and in vivo functional assays were performed to elucidate the YAP1-mediated EGFR expression and transcription and the relationship with chemoresistance in esophageal cancer. Results: We demonstrate that Hippo pathway coactivator YAP1 can induce EGFR expression and transcription in multiple cell systems. Both YAP1 and EGFR are overexpressed in resistant esophageal cancer tissues compared with sensitive esophageal cancer tissues. Furthermore, we found that YAP1 increases EGFR expression at the level of transcription requiring an intact TEAD-binding site in the EGFR promoter. Most importantly, exogenous induction of YAP1 induces resistance to 5-fluorouracil and docetaxcel, whereas knockdown of YAP1 sensitizes esophageal cancer cells to these cytotoxics. Verteporfin, a YAP1 inhibitor, effectively inhibits both YAP1 and EGFR expression and sensitizes cells to cytotoxics. Conclusions: Our data provide evidence that YAP1 upregulation of EGFR plays an important role in conferring therapy resistance in esophageal cancer cells. Targeting YAP1-EGFR axis may be more efficacious than targeting EGFR alone in esophageal cancer. Clin Cancer Res; 21(11); 2580–90. ©2015 AACR.

Study Design Retrospective case series. Objective To determine the effect of obesity on the resource utilization and cost in 3270 consecutive patients undergoing elective noninstrumented decompressive surgeries for degenerative spine disease at Mayo Clinic Rochester between 2005 and 2012. Methods Groups were assessed for baseline differences (age, gender, and American Society of Anesthesiologists [ASA] classification, procedure type, and number of operative levels). Outcome variables included the transfusion requirements during surgery, the total anesthesia and surgical times, intensive care unit (ICU) admissions, standardized costs, as well as the ICU and hospital length of stay (LOS). Regression analysis was used to evaluate for strength of association between obesity and outcome variables. Results Baseline differences between the groups (nonobese: n = 1,853; obese: n = 1,417) were found with respect to age, ASA class, gender, procedure type, and number of operative levels. After correcting for differences, we found significant associations between obesity and surgical ( p < 0.0001) and anesthesia times ( p < 0.0001) and hospital LOS ( p < 0.0001). Additionally, ICU admission rates ( p = 0.02) and requirement for postoperative ventilation ( p = 0.048) were significantly higher in obese patients. Finally, mean difference in total cost ($1,632, p < 0.0001) was significantly higher for the obese cohort. Conclusion Obesity is associated with increased resource utilization and cost in patients undergoing a noninstrumented decompressive surgery for degenerative spine disease.

SummaryBackgroundPrimary osteolysis syndromes represent a number of rare conditions characterized by destruction and resorption of bone that is unrelated to neoplasia, infection, or trauma.AimTo characterize the periprocedural course of patients with primary osteolysis syndrome undergoing procedures that require anesthesia care.MethodsThe medical records database from our institution was searched from 1976 to 2013 to identify patients with primary osteolysis syndromes who received anesthesia care. We reviewed demographic characteristics, comorbidities, and perioperative course of patients with different forms of primary osteolysis. A systematic review of the literature was performed to identify reports describing the anesthetic management of patients with these conditions.ResultsWe identified 11 patients with a primary osteolysis syndrome who received 111 anesthetics. The patients' ages at the time of surgery ranged from 3 to 62 years. Difficult airway management was a common finding. On preoperative examination, difficulty with endotracheal intubation was predicted in 8 of 11 patients. Three patients had preexisting tracheostomies. One patient required multiple awake fiberoptic intubations. Another two patients where successfully intubated early in life via direct laryngoscopy, but eventually required awake fiberoptic intubations as the disease process caused progressive distortion of airway structures. Intraoperative complications were absent. In the postoperative period, three patients required prolonged mechanical ventilation due to airway swelling, respiratory failure, and infection.ConclusionsAirway management may be challenging in patients with primary osteolysis syndromes. Because the osteolytic process advances with aging and craniofacial dysmorphism may progressively worsen, the airway should always be reassessed before surgery with an appropriate strategy for potentially difficult intubation. In all patients with primary osteolysis, a potential for pathologic fracture must be considered and careful intraoperative positioning is warranted.

Adipose tissue fatty acid storage varies according to sex, adipose tissue depot, and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We examined whether differences in adipose tissue glycerol-3-phosphate acyltransferase (GPAT) might play a role in these variations. We optimized an enzyme activity assay for total GPAT and GPAT1 activity in human adipose tissue and measured GPAT activity. Omental and subcutaneous adipose tissue was collected from obese and nonobese adults for measures of GPAT and GPAT1 activities, ex vivo palmitate storage, acyl-CoA synthetase (ACS) and diacylglycerol-acyltransferase (DGAT) activities, and CD36 protein. Total GPAT and GPAT1 activities decreased as a function of adipocyte size in both omental ( r = −0.71, P = 0.003) and subcutaneous ( r = −0.58, P = 0.04) fat. The relative contribution of GPAT1 to total GPAT activity increased as a function of adipocyte size, accounting for up to 60% of GPAT activity in those with the largest adipocytes. We found strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots ( r values 0.58–0.91) and between these storage factors and palmitate storage rates into TAG ( r values 0.55–0.90). We conclude that: 1) total GPAT activity decreases as a function of adipocyte size; 2) GPAT1 can account for over half of adipose GPAT activity in hypertrophic obesity; and 3) ACS, GPAT, and DGAT are coordinately regulated.