ABSTRACT
BACKGROUND: The prognosis for patients with symptomatic, severe mitral regurgitation (MR) who have comorbidities precluding mitral valve surgery is poor. Treatment of MR using a percutaneous edge-to-edge technique may improve survival, quality of life and reduce hospitalisations. To date, there are few studies reporting outcomes after percutaneous mitral valve repair in high-risk patients and none reported from Australia. METHODS: The first 25 patients undergoing percutaneous mitral valve repair using the MitraClip in our Institution had follow-up to six months. These patients had severe, symptomatic MR and were deemed too high-risk for mitral valve surgery by a multidisciplinary heart team, including an interventional cardiologist and cardiothoracic surgeon. RESULTS: There were no peri-procedural deaths; the only peri-procedural morbidity was blood transfusion in three patients. Three patients had died at six months and there were six readmissions to hospital. There was a significant improvement in heart failure symptoms, 6-minute walk test and quality of life at six months. There was a significant improvement in the proportion of patients with MR ≤2+, but no significant change in other echocardiographic parameters. CONCLUSIONS: Percutaneous mitral valve repair is safe in patients at high-risk for surgery, and improves symptoms and quality of life.
Subject(s)
Cardiac Catheterization , Mitral Valve Insufficiency/mortality , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Aged , Aged, 80 and over , Australia/epidemiology , Female , Follow-Up Studies , Humans , Length of Stay , Male , Quality of Life , Risk FactorsABSTRACT
BACKGROUND: Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches to therapy are needed. Reduced expression of miR-15/16 in a range of cancer types has suggested a tumour suppressor function for these microRNAs, and re-expression has been shown to inhibit tumour cell proliferation. The miR-15/16 status in MPM is largely unknown. MATERIALS AND METHODS: MicroRNA expression was analysed by TaqMan-based RT-qPCR in MPM tumour specimens and cell lines. MicroRNA expression was restored in vitro using microRNA mimics, and effects on proliferation, drug sensitivity and target gene expression were assessed. Xenograft-bearing mice were treated with miR-16 mimic packaged in minicells targeted with epidermal growth factor receptor (EGFR)-specific antibodies. RESULTS: Expression of the miR-15 family was consistently downregulated in MPM tumour specimens and cell lines. A decrease of 4- to 22-fold was found when tumour specimens were compared with normal pleura. When MPM cell lines were compared with the normal mesothelial cell line MeT-5A, the downregulation of miR-15/16 was 2- to 10-fold. Using synthetic mimics to restore miR-15/16 expression led to growth inhibition in MPM cell lines but not in MeT-5A cells. Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine. In xenograft-bearing nude mice, intravenous administration of miR-16 mimics packaged in minicells led to consistent and dose-dependent inhibition of MPM tumour growth. CONCLUSIONS: The miR-15/16 family is downregulated and has tumour suppressor function in MPM. Restoring miR-16 expression represents a novel therapeutic approach for MPM.
Subject(s)
Lung Neoplasms/metabolism , Mesothelioma/metabolism , MicroRNAs/genetics , Pleural Neoplasms/metabolism , Animals , Cell Line, Tumor , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Glutamates/pharmacology , Guanine/analogs & derivatives , Guanine/pharmacology , Humans , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Mesothelioma/pathology , Mesothelioma/therapy , Mesothelioma, Malignant , Mice , Mice, Nude , MicroRNAs/metabolism , Neoplasm Transplantation , Pemetrexed , Pleural Neoplasms/pathology , Pleural Neoplasms/therapy , RNA Interference , Transfection , Tumor Burden , GemcitabineABSTRACT
Coronary artery bypass grafting (CABG) remains the standard of care for multi-vessel coronary disease. However, the increased rate of peri-operative stroke reported after surgery compared to percutaneous coronary intervention (PCI) remains of concern. Anaortic, total-arterial, off-pump coronary artery bypass (OPCAB) grafting is a technique that offers the main advantages of surgical revascularisation with a rate of stroke that is equivalent to that of PCI. Some recent trials comparing conventional on-pump CABG with OPCAB have questioned the efficacy of the off-pump technique - these are most often performed with manipulation of the ascending aorta. We review the potential benefits of the anaortic, total-arterial OPCAB technique to explain why it is being employed by an increasing number of surgeons.
