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.

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).

Background: The modified HEART score has been validated to accurately risk stratify patients presenting to the Emergency Department (ED) with chest pain, however, its ability to predict outcomes has not been evaluated against standard clinical assessment. Objective: This study compared standard care by clinical assessment alone to modified HEART score to evaluate which method was superior in predicting cardiovascular events in patients presenting with acute chest pain. Methodology: A retrospective cohort study of all chest pain presentations was performed over three months. Patients were excluded if they had ST elevation infarct or an alternative cause of chest pain. Major adverse cardiovascular events (MACE) outcomes assessed included acute coronary syndrome (ACS), unplanned revascularisation, readmission for heart failure and cardiovascular death. These were assessed at 12 months, and statistical significance determined by Chisquared test. Results: A total of 199 patients were included. Of those, 12 (6%) had ACS at index admission, 16 (8%) at six weeks and 23 (12%) at twelve months. At twelve months, the modified HEART score demonstrated higher sensitivity for predicting MACE compared with standard care alone (96% vs 74%; p = 0.03), however, specificity was higher with standard care compared to modified HEART score (74% vs 53%; p < 0.0001). Conclusions: Modified HEART score provided higher sensitivity but lower specificity than clinical assessment alone in predicting cardiovascular events in patients presenting to ED with chest pain. The modified HEART score is of potential use to more accurately exclude ACS in the emergency department compared to standard clinical assessment alone.

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