No abstract

The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery.

No abstract

Type VI collagen (COL6) forms a microfibrillar network often associated with type I collagen and constitutes a major component of the desmoplastic reaction in pancreatic ductal adenocarcinoma (PDA). We have demonstrated recently that the α3 chain of COL6, COL6A3, is highly expressed in PDA tissue and undergoes tumor-specific alternative splicing. In this study, we investigated the diagnostic value and clinical significance of circulating COL6A3 protein and mRNA in PDA. COL6A3 levels in sera from patients with PDA (n = 44), benign lesions (n = 46) and age-matched healthy volunteers (n = 30) were analyzed by enzyme-linked immunosorbent assays (ELISA). Predictive abilities of COL6A3 were examined using receiver operating characteristic (ROC) curves from logistic regression models for PDA versus normal or benign serum levels. Expression levels were correlated with clinicopathological parameters. Real-time PCR was used to analyze the presence of COL6A3 mRNA containing alternative spliced exons E3, E4, and E6. Circulating COL6A3 protein levels were significantly elevated in PDA patients when compared to healthy sera (p = 0.0001) and benign lesions (p = 0.0035). The overall area under the ROC was 0.975. Log(COL6A3) alone provided good discrimination between PDA and benign lesions (area under the curve (AUC) = 0.817), but combined with CA19-9 provided excellent discrimination (AUC = 0.904). Interestingly, high COL6A3 serum levels were significantly associated with perineural invasion and cigarette smoking. Combined E3, E4, and E6 serum RNA values provided good sensitivity but low specificity. Our data demonstrate for the first time the potential clinical significance of circulating COL6A3 in the diagnosis of pancreatic malignancy.

We examined whether combining biomarkers measurements and brain images early after the return of spontaneous circulation improves prognostic performance compared with the use of either biomarkers or brain images for patients with cardiac arrest following target temperature management (TTM). This retrospective observational study involved comatose out-of-hospital cardiac arrest survivors. We analyzed neuron-specific enolase levels in serum (NSE) or cerebrospinal fluid (CSF), grey-to-white matter ratio by brain computed tomography, presence of high signal intensity (HSI) in diffusion-weighted imaging (DWI), and voxel-based apparent diffusion coefficient (ADC). Of the 58 patients, 33 (56.9%) had poor neurologic outcomes. CSF NSE levels showed better prognostic performance (area under the curve (AUC) 0.873, 95% confidence interval (CI) 0.749–0.950) than serum NSE levels (AUC 0.792, 95% CI 0.644–0.888). HSI in DWI showed the best prognostic performance (AUC 0.833, 95% CI 0.711–0.919). Combining CSF NSE levels and HSI in DWI had better prognostic performance (AUC 0.925, 95% CI 0.813–0.981) than each individual method, followed by the combination of serum NSE levels and HSI on DWI and that of CSF NSE levels and the percentage of voxels of ADC (AUC 0.901, 95% CI 0.792–0.965; AUC 0.849, 95% CI 0.717–0.935, respectively). Combining CSF/serum NSE levels and HSI in DWI before TTM improved the prognostic performance compared to either each individual method or other combinations.