Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation.

Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis and inflammation and, in some patients, progressive fibrosis leading to cirrhosis. An understanding of the pathogenesis of NASH is still evolving but current evidence suggests multiple metabolic factors critically disrupt homeostasis and induce an inflammatory cascade and ensuing fibrosis. The mechanisms underlying these changes and the complex inter-cellular interactions that mediate fibrogenesis are yet to be fully elucidated. Lipotoxicity, in the setting of excess free fatty acids, obesity, and insulin resistance, appears to be the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence contribute to activation of the inflammasome via a variety of intra- and inter-cellular signalling mechanisms leading to fibrosis. Current evidence suggests that periportal components, including the ductular reaction and expansion of the hepatic progenitor cell compartment, may be involved and that the Th17 response may mediate disease progression. This review aims to provide an overview of the pathogenesis of NASH and summarises the evidence pertaining to key mechanisms implicated in the transition from steatosis and inflammation to fibrosis. Currently there are limited treatments for NASH although an increasing understanding of its pathogenesis will likely improve the development and use of interventions in the future.

Transcatheter Balloon-Expandable Valve-in-Valve to Treat Severe Paravalvular Leak Secondary to ACURATE-neo Self-expanding Prosthesis-Annulus Mismatch.

A 75-year-old male with severe symptomatic aortic stenosis underwent transcatheter aortic valve implantation with a Large (27-mm) ACURATE-neo transcatheter aortic valve, complicated by severe paravalvular leak. He developed rapid and progressive worsening heart failure. Reanalysis of the computed tomography images suggested evidence of prosthesis-annulus mismatch. Therefore, a redo transcatheter aortic valve implantation utilizing a 29-mm SAPIEN 3 transcatheter aortic valve was performed. This case illustrates the importance of proper valve sizing to avoid paravalvular leak, and how to safely cross an ACURATE-neo valve to avoid catheter entangling.

Un homme de 75 ans présentant une sténose aortique symptomatique sévère a subi l'implantation d'une valve aortique par cathéter, dont une ACURATE neo de 27-mm compliquée par une fuite paravalvulaire sévère. Par la suite, le patient a présenté une insuffisance cardiaque sévère . Une nouvelle analyse de ses examens tomodensitométriques a indiqué des signes d'incompatibilité entre la prothèse et l'anneau mitral. Il a donc fallu réaliser une nouvelle implantation valvulaire aortique par cathéter avec une valve SAPIEN 3 de 29 mm. Ce cas illustre l'importance d'une bonne évaluation de l'anneau valvulaire pour éviter les fuites paravalvulaires, et décrit comment traverser une valve ACURATE neo pour éviter l'enchevêtrement du cathéter.

The Cone Flare Crush Modified-T (CFCT) stenting technique for coronary artery bifurcation lesions.

BACKGROUND: The present study is a prospective observational single arm clinical investigation, with parallel bench test interrogation, aimed at investigating the technical feasibility, safety and clinical outcomes with the cone flare crush modified-T (CFCT) bifurcation stenting technique. Bifurcation percutaneous coronary intervention (PCI) remains an area of ongoing procedural evolution. More widely applicable and reproducible techniques are required. METHODS: From April 2018 until March 2019, 20 consecutive patients underwent bifurcation PCI using the CFCT technique with a Pt-Cr everolimus drug-eluting stent with a bioresorbable polymer. Exercise stress echocardiography was performed at 12-month follow-up. The primary outcome was a composite of cardiac related mortality, myocardial infarction, target lesion/vessel revascularization and stroke. Safety secondary endpoints included bleeding, all-cause mortality and stent thrombosis. RESULTS: All patients underwent a successful CFCT bifurcation procedure with no complications to 30-day follow-up. One patient met the primary endpoint requiring target lesion revascularization at 9 months for stable angina. There were no other primary or secondary outcome events in the cohort. There were no strokes, deaths, stent thrombosis or myocardial infarction during the follow-up period. The mean CCS score improved from 2.25 to 0.25 (p < 0.0001). Optical coherence tomography (OCT) and bench test findings indicated optimal side branch ostial coverage and minimal redundant strut material crowding the neo-carina. CONCLUSIONS: The CFCT technique appears to be a safe, efficacious and feasible strategy for managing coronary artery bifurcation disease. Expanded and randomized datasets with longer term follow-up are required to further explore confirm this feasibility data. (ANZCTR ID: ACTRN12618001145291).