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BackgroundAging, Western diet (WD) intake, and bile acid (BA) receptor farnesoid X receptor (FXR) inactivation are risk factors for metabolic disease development including nonalcoholic fatty liver disease (NAFLD) and chronic inflammation-related health issues such as dementia. The progression of the metabolic disease can be escalated when those risks are combined. Inactivation of FXR is cancer prone in both humans and mice. The current study used omics data generated within the gut-liver axis to classify those risks using bioinformatics and machine learning approaches.MethodsDifferent ages (5, 10, and 15 months) of wild-type (WT) and FXR knockout (KO) male mice were fed with either a healthy control diet (CD) or a WD since weaning. Hepatic transcripts, liver, serum, and urine metabolites, hepatic bile acids (BAs), as well as gut microbiota were used for risk prediction. A linear support vector machine withK-fold cross-validation was used for classification and feature selection.ResultsIncreased urine sucrose alone achieved 91% accuracy in predicting WD intake. Hepatic lithocholic acid (LCA) and serum pyruvate had 100% and 95% accuracy, respectively to classify age. Association analyses showed hepatic LCA was positively associated with serum concentrations of acetone, a ketone body, and 1,3-dihydroxyacetone (DHA), but negatively correlated with serum pyruvate. Urine metabolites (decreased creatinine and taurine as well as increased succinate) or gut microbiota (increasedDorea, Dehalobacterium, andOscillospira) could predict FXR functional status with greater than 90% accuracy. Integrated pathway analyses revealed that the predictors for diet and FXR expression were implicated in the central carbon metabolism in cancer. To assess the translational relevance, mouse hepatic transcripts were crosschecked with human NAFLD and hepatocellular carcinoma (HCC) datasets. WD-affected hepaticCyp39a1andGramd1bexpression were associated with human HCC and NAFLD, respectively. The metabolites and diseases interaction analyses uncovered that the identified features are implicated in human metabolic diseases, mental disorders, and cancer.ConclusionThe risk prediction using mouse models contributes to the identification of noninvasive biomarkers for early diagnosis of metabolic disease development.

One of the last frontiers facing interventionalists is the treatment of chronic total occlusions. Chronic total occlusions (CTO) are present in about one-third of all diagnostic coronary angiograms. Recanalizations of these CTOs have demonstrated a trend towards lower mortality. Unfortunately, use of standard angioplasty equipment has only resulted in a 50-60% success rate.5,6,7 Several recently developed guidewires have increased success rates to 79-90%. Further success in CTO revascularization has been improved by use of novel techniques such as crossing the lesion in a retrograde fashion from collateral vessels. Niche devices such as the Frontrunner CTO catheter (Lumend Inc., Johnson and Johnson, Picataway, NJ) have also facilitated in successful treatment of CTOs. Unfortunately, none of these developments address the issue of deliverability of angioplasty balloons and stents. A newly developed device, the Tornus catheter (Asahi Intech; Abbot Vascular, Redwood City, CA), plays a niche role in the recanalization of this lesion subset. The following contains two case reports which highlight successful revascularization of CTOs with utilization of this new catheter.

Thirty percent of diagnostic angiograms have at least 1 chronic total occlusion (CTO). The 10-year survival of patients with a CTO is improved if they have the CTO successfully recanalized. The success of recanalization with conventional wires is 50% and the impact of new technology on recanalization is unknown. This abstract reports a single center experience with one such new device, the Lumend Frontrunner catheter in revascularization of this difficult lesion subset. A consecutive series of 18 patients with CTO's of native coronary arteries were enrolled in this single center, single operator series. The mean age of the CTO was 5.3 years. The indication for attempt at recanalization was ischemia in the territory of the CTO on SPECT imaging. Success was defined as TIMI flow restoration and40% residual stenosis. Primary success (defined as TIMI 3 Flow restoration and40% residual stenosis) was achieved in 77% of patients. At 30 days and out to 6 months, clinical TVR was 11% (2/18) in this difficult lesion subset. Conventional predictors of failure to recanalize CTOs do not appear to hold true with the use of the Frontrunner catheter. In this small series, dual cusp injections and use of the Microglide catheter appears to correlate with favorable outcomes. Fluoroscopy times and contrast use are high when attempting recanalization of CTOs with this technology.