Purpose: The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation, and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma. Experimental Design: Two hundred twenty-one extrahepatic cholangiocarcinoma patients with clinicopathologic data, including survival, were arrayed into tissue microarrays. Phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were studied with multiplex tissue immunoblotting assay. Results: Expressions of p-AKT and p-mTOR were significantly increased in extrahepatic cholangiocarcinoma cases compared with normal and dysplastic bile duct epithelium (P < 0.05 both). Decreased PTEN expression was observed in patients with increasing depth of invasion (P < 0.05), T classification (P < 0.05), and stage grouping (P < 0.05), and the presence of invasion of the pancreas (P < 0.05) and duodenum (P < 0.05). Decreased PTEN expression (P = 0.004) as well as decreased PTEN/p-AKT (P = 0.003) and PTEN/p-mTOR (P = 0.009) expression showed shorter survival by univariate but not by multivariate analysis. Conclusions: The AKT pathway is activated in a subset of extrahepatic cholangiocarcinoma. Elevated PTEN expression correlates with longer survival. Quantitative data obtained by multiplex tissue immunoblotting may provide additional information than assessment of immunohistochemistry alone. Quantitative analysis of PTEN, PTEN/p-AKT and PTEN/p-mTOR shows differences in survival by univariate analysis.

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.

Background: After a diagnosis of prostate, breast, or colorectal cancer, Latinos experience higher mortality rates and lower health‐related quality of life (HRQOL) in comparison with other ethnic/racial groups. Patient navigation (PN) and lay community health workers or promotores are effective in increasing cancer screening and early‐stage diagnosis among Latinos. However, little is known about the effect of PN on HRQOL among Latino cancer survivors.Methods: Latinos previously diagnosed with breast, prostate, or colorectal cancer (n = 288) were randomized to 1 of 2 conditions: 1) the Patient Navigator LIVESTRONG Cancer Navigation Services (PN‐LCNS) survivor care program or 2) PN only. HRQOL was measured with the Functional Assessment of Cancer Therapy–General, and cancer‐specific HRQOL was measured with the Functional Assessment of Cancer Therapy–Breast, the Functional Assessment of Cancer Therapy–Prostate, and the Functional Assessment of Cancer Therapy–Colorectal for breast, prostate, and colorectal cancer survivors, respectively, at the baseline and at 3 follow‐up time points. Generalized estimating equation analyses were conducted to estimate the effect of condition on HRQOL with adjustments for covariates and baseline HRQOL.Results: PN‐LCNS demonstrated a significant improvement in HRQOL in comparison with PN only for colorectal cancer survivors but not for breast and prostate cancer survivors.Conclusions: Enhanced PN improves HRQOL among Latino colorectal cancer survivors. Future research should identify the best strategies for engaging Latino survivors in PN programs. PN programs should also be adapted to address HRQOL concerns among Latina breast cancer survivors.

Background: Latinos living in rural South Texas have a higher prevalence of diabetes, but their access to diabetes self-management education and support (DSMES) is limited. Objective: We aimed to test the feasibility of a community health worker-led, mobile health (mHealth)-based DSMES intervention to reduce disparities in accessing DSMES in underserved rural Latino residents in South Texas. Methods: This 12-week, single-arm, pre-post trial was delivered by trained community health workers to 15 adults with type 2 diabetes. The intervention consisted of digital diabetes education, self-monitoring, a cloud-based connected platform, and community health worker support. Feasibility was evaluated as retention, actual intervention use, program satisfaction, and barriers to implementation. We also explored the intervention’s effect on weight loss and hemoglobin A1c (HbA1c). Results: All 15 participants were Latino (mean age 61.87 years, SD 10.67; 9/15 female, 60%). The retention rate at posttest was 14 of 15 (93%). On average, the participants completed 37 of 42 (88%) digital diabetes education lessons with 8 participants completing all lessons. Participants spent 81/91 days (89%) step tracking, 71/91 days (78%) food logging, 43/91 days (47%) blood glucose self-monitoring, and 74/91 days (81%) weight self-monitoring. The level of program satisfaction was high. On average, participants lost 3.5 (SD 3.2) kg of body weight (P=.001), while HbA1c level remained unchanged from baseline (6.91%, SD 1.28%) to posttest (7.04%, SD 1.66%; P=.668). Conclusions: A community health worker-led mHealth-based intervention was feasible and acceptable to improve access to DSMES services for Latino adults living in rural communities. Future randomized controlled trials are needed to test intervention efficacy on weight loss and glycemic control.