Pre-hospital thrombolysis for ST-segment elevation myocardial infarction in regional Australia: long-term follow up.

BACKGROUND: Delivering reperfusion therapy to patients with ST-segment elevation myocardial infarction (STEMI) in regional areas without access to tertiary cardiology care remains challenging. The systems of care in Hunter New England Health, New South Wales, Australia (area covered = 130 000 km2 ) to provide reperfusion to patients with STEMI involve a 12-lead electrocardiogram in the ambulance, discussion between cardiologist and paramedic, followed by pre-hospital thrombolysis (PHT) delivered in ambulance to appropriate patients >60 min from the cardiac catheterisation laboratories. Patients who can access the cardiac catheterisation laboratories within 60 min are treated with primary percutaneous coronary intervention (PCI). AIMS: We have previously reported excellent 12-month outcomes for patients receiving PHT and the aim of the current analysis is to look at the long term outcomes. METHODS: We assessed long-term all-cause mortality and major adverse cardiovascular events of STEMI patients undergoing PHT in our health district from August 2008 to August 2013 and compared with the primary PCI group. RESULTS: One hundred and fifty (mean age: 62 ± 13 years, males: 76%, n = 114) patients were administered PHT and 334 patients (mean age: 65 ± 13 years, males: 75%, n = 251) underwent primary PCI during the study period. During a median follow up of 6.2 years (interquartile range: 4.8-7.4 years) all-cause mortality was 16% and 19% in the PHT and primary PCI groups respectively (P = 0.4). CONCLUSION: Our real-world experience shows that PHT followed by early transfer to a primary PCI-capable centre is an effective reperfusion strategy, with comparable results to primary PCI, and mortality benefits are sustained to more than 6 years.

MicroRNA-7 as a tumor suppressor and novel therapeutic for adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) has a poor prognosis with significant unmet clinical need due to late diagnosis, high rates of recurrence/metastasis and poor response to conventional treatment. Replacing tumor suppressor microRNAs (miRNAs) offer a novel therapy, however systemic delivery remains challenging. A number of miRNAs have been described to be under-expressed in ACC however it is not known if they form a part of ACC pathogenesis. Here we report that microRNA-7-5p (miR-7) reduces cell proliferation in vitro and induces G1 cell cycle arrest. Systemic miR-7 administration in a targeted, clinically safe delivery vesicle (EGFREDVTM nanocells) reduces ACC xenograft growth originating from both ACC cell lines and primary ACC cells. Mechanistically, miR-7 targets Raf-1 proto-oncogene serine/threonine kinase (RAF1) and mechanistic target of rapamycin (MTOR). Additionally, miR-7 therapy in vivo leads to inhibition of cyclin dependent kinase 1 (CDK1). In patient ACC samples, CDK1 is overexpressed and miR-7 expression inversely related. In summary, miR-7 inhibits multiple oncogenic pathways and reduces ACC growth when systemically delivered using EDVTM nanoparticles. This data is the first study in ACC investigating the possibility of miRNAs replacement as a novel therapy.