Higher baseline BMI and lower estimated median income is associated with increasing BMI after endometrial cancer diagnosis.

Introduction: Endometrial cancer is often directly related to obesity and interventions for weight loss have mixed results. Risk factors for continued weight gain after diagnosis are not clearly defined in the literature. The objective of this study is to describe risk factors associated with increased body mass index (BMI) trajectory among endometrial cancer patients. Methods: Patients who were surgically treated for endometrial cancer at a single institution between 2010 and 2015 were identified. Demographics including age, race/ethnicity and estimated median income at diagnosis were obtained. BMI at five time points after diagnosis were calculated. BMI trajectories were estimated by latent class growth modeling using the PROC TRAJ procedure in SAS. Chi-squared tests and ANOVA were used to assess differences between trajectory groups. Statistical significance was set to a p-value < 0.05. Results: Of 695 patients included in the study, the average age at diagnosis was 62 years and over 70% of patients were obese at baseline. Patients experienced increasing, stable, or decreasing BMI over 2 years following diagnosis. Patients with younger age and lower estimated median income were most likely to be in the increasing BMI group. Among obese patients, those with Class I obesity (BMI 30 to 34.9 kg/m2) were most likely to experience decreasing BMI and those with Class III obesity (BMI > 40 kg/m2) were most likely to experience increasing BMI, p < 0.0001. Conclusion: A third of endometrial cancer survivors experience increasing BMI. Severity of obesity at diagnosis matters, patients with severe obesity (Class III) were most likely to experience weight gain.

Higher baseline BMI and lower estimated median income associated with increasing BMI after endometrial cancer diagnosis.

Introduction: Endometrial cancer is often directly related to obesity and interventions for weight loss have mixed results. Risk factors for continued weight gain after diagnosis are not clearly defined in the literature. The objective of this study is to describe risk factors associated with increased body mass index (BMI) trajectory among endometrial cancer patients. Methods: Patients who were surgically treated for endometrial cancer at a single institution between 2010 and 2015 were identified. Demographics including age, race/ethnicity and estimated median income at diagnosis were obtained. BMI at five time points after diagnosis were calculated. BMI trajectories were estimated by latent class growth modeling using the PROC TRAJ procedure in SAS. Chi-squared tests and ANOVA were used to assess differences between trajectory groups. Statistical significance was set to a p-value < 0.05. Results: Of 695 patients included in the study, the average age at diagnosis was 62 years and over 70% of patients were obese at baseline. Patients experienced increasing, stable, or decreasing BMI over 2 years following diagnosis. Patients with younger age and lower estimated median income were most likely to be in the increasing BMI group. Among obese patients, those with Class I obesity (BMI 30 to 34.9 kg/m2) were most likely to experience decreasing BMI and those with Class III obesity (BMI > 40 kg/m2) were most likely to experience increasing BMI, p < 0.0001. Conclusion: A third of endometrial cancer survivors experience increasing BMI. Severity of obesity at diagnosis matters, patients with severe obesity (Class III) were most likely to experience weight gain.

Brief Report: Adiponectin Levels Linked to Subclinical Myocardial Fibrosis in HIV.

BACKGROUND: Persons living with HIV (PLWH) are at an increased risk of myocardial dysfunction and metabolic disturbances represent one of several potential contributing factors. Adiponectin is an adipokine that enhances insulin sensitivity with potential cardioprotective effects. We therefore investigated the relationship between myocardial fibrosis, adiponectin, and related metabolic parameters to better understand the pathophysiologic mechanisms of myocardial injury in PLWH. METHODS: This is a prospective, cross-sectional study of PLWH without known cardiovascular disease (n = 87) and 28 healthy matched controls. Diffuse myocardial fibrosis and epicardial adipose tissue (EAT) were evaluated using cardiac magnetic resonance imaging and cardiac computed tomography. RESULTS: Myocardial fibrosis was increased in PLWH and was correlated with adiponectin (r = 0.26, P = 0.004) and EAT (r = -0.42, P < 0.0001). Myocardial fibrosis was not associated with smoking pack years or CD4/CD8 ratio. In multivariate analysis that included body mass index, HIV status (P = 0.04), female sex (P < 0.0001), higher adiponectin (P = 0.046) and lower EAT (P = 0.01) were independently associated with myocardial fibrosis. CONCLUSION: We describe a novel association between serum adiponectin and subclinical intramyocardial fibrosis, as well as a significant inverse relationship between intramyocardial fibrosis and EAT. Adiponectin may represent a target for preventing myocardial injury in the future; however, our findings reflect the complexity of the metabolic interactions of adiponectin and epicardial adipose as factors associated with the myocardial architecture.

Long-term changes in hepatic fibrosis following hepatitis C viral clearance in patients with and without HIV.

BACKGROUND: While acute changes in hepatic fibrosis are recognized shortly after achieving sustained virological response (SVR) using direct-acting antiviral therapies, long-term outcomes for the growing population of successfully treated patients with HCV remain uncertain. The aim of this study is to characterize long-term changes in fibrosis following SVR in patients with and without HIV and to identify potential factors associated with progression or regression of fibrosis. METHODS: We completed a prospective longitudinal study of 162 subjects with HCV (34% HIV-coinfected) with pre-treatment fibrosis stage determined by liver biopsy and post-SVR transient elastography. Progression of fibrosis was defined as a two-stage or greater increase in fibrosis, while regression was defined as a two-stage or greater decrease at last follow-up. The median duration of follow-up was 4.1 years. RESULTS: Fibrosis progression occurred in 4% of subjects while regression occurred in 7% and 89% were stable and did not differ by HIV coinfection. Fibrosis progression was associated with increased body mass index (BMI), hepatic steatosis and smoking pack-years. In a multivariable logistic regression, HIV coinfection (P=0.009), lower steatosis score (P<0.05) and lower smoking pack-years (P=0.0007) were associated with a lower fibrosis score at last follow-up. CONCLUSIONS: We identify potentially important relationships between BMI, hepatic steatosis and smoking, and changes in hepatic fibrosis post-SVR in patients with and without HIV coinfection. Attention to modifiable risk factors such as body weight and smoking may reduce the risk of liver disease progression in the growing population of successfully treated chronic HCV patients.

Increased Prevalence of Hepatic Steatosis in Young Adults With Lifelong HIV.

Little is known about the effects of lifelong human immunodeficiency virus (HIV) or antiretroviral therapy on hepatic steatosis and fibrosis. Using transient elastography, we evaluated 46 young adults with lifelong HIV and 20 matched HIV-negative controls. Steatosis was present in 33% of persons with HIV and only 10% of controls (P = .04). Hepatic fibrosis scores were not elevated and did not differ between groups. Metabolic parameters, particularly increased waist circumference, and not HIV-specific factors, were significantly associated with steatosis. While this finding should be examined in larger cohorts, modifiable metabolic disturbances may be important targets to optimize liver health in this population.

RNA binding protein RBM3 increases ß-catenin signaling to increase stem cell characteristics in colorectal cancer cells.

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. It arises from loss of intestinal epithelial homeostasis and hyperproliferation of the crypt epithelium. In order to further understand the pathogenesis of CRC it is important to further understand the factors regulating intestinal epithelial proliferation and more specifically, regulation of the intestinal epithelial stem cell compartment. Here, we investigated the role of the RNA binding protein RBM3 in stem cell homeostasis in colorectal cancers. Using a doxycycline (Dox) inducible RBM3 overexpressing cell lines HCT 116 and DLD-1, we measured changes in side population (SP) cells that have high xenobiotic efflux capacity and increased capacity for self-renewal. In both cell lines, RBM3 induction showed significant increases in the percentage of side population cells. Additionally, we observed increases in spheroid formation and in cells expressing DCLK1, LGR5 and CD44Hi . As the Wnt/ß-catenin signaling pathway is important for both physiologic and cancer stem cells, we next investigated the effects of RBM3 overexpression on ß-catenin activity. RBM3 overexpression increased levels of nuclear ß-catenin as well as TCF/LEF transcriptional activity. In addition, there was inactivation of GSK3ß leading to decreased ß-catenin phosphorylation. Pharmacologic inhibition of GSK3ß using (2'Z,3'E)-6-Bromoindirubin-3'-oxime (BIO) also recapitulates the RBM3 induced ß-catenin activity. In conclusion, we see that RNA binding protein RBM3 induces stemness in colorectal cancer cells through a mechanism involving suppression of GSK3ß activity thereby enhancing ß-catenin signaling. © 2015 Wiley Periodicals, Inc.