Research Archives - Page 16 of 28

Immobilisation of a fibrillin-1 fragment enhances the biocompatibility of PTFE

January 3, 2015April 21, 2014 by Hajian H, Wise SG, Bax DV, Kondyurin A, Waterhouse A, Dunn LL, Kielty CM, Yu Y, Weiss AS, Bilek MM, Bannon PG, Ng MK

Hajian H, Wise SG, Bax DV, Kondyurin A, Waterhouse A, Dunn LL, Kielty CM, Yu Y, Weiss AS, Bilek MM, Bannon PG, Ng MK

Colloids Surf B Biointerfaces 2014 Apr;116:544-52

PMID: 24572497

Abstract

Current vascular biomaterials exhibit poor biocompatibility characterised by failure to promote endothelialisation, predisposition to neoinitmal hyperplasia and excessive thrombogenicity. Fibrillin-1, a major constituent of microfibrils is associated with elastic fibres in the arterial wall. Fibrillin-1 binds to endothelial cells through an RGD cell adhesion motif in the fourth TB module. The RGD motif is present in PF8, a recombinant fibrillin-1 fragment. We investigated the potential of PF8 to improve the biocompatibility of PTFE. PF8 enhanced endothelial cell attachment and cell proliferation to a greater extent than fibronectin (p<0.01). PF8 immobilised on PTFE using plasma immersion ion implantation (PIII), retained these favourable cell interactive properties, again promoting endothelial cell attachment and proliferation. The thrombogenicity of covalently bound PF8 on PTFE was assessed in both static and dynamic conditions. In static conditions, uncoated PIII treated PTFE was more thrombogenic than untreated PTFE, while PF8 coating reduced thrombogenicity. Under flow, there was no difference in the thrombogenicity of PF8 coated PTFE and untreated PTFE. Immobilised PF8 shows a striking ability to promote attachment and growth of endothelial cells on PTFE, while providing a non-thrombogenic surface. These features make PF8 a promising candidate to improve the biocompatibility of current synthetic vascular grafts.

Standardizing clinical end points in aortic arch surgery: a consensus statement from the International Aortic Arch Surgery Study Group

January 3, 2015April 15, 2014 by Yan TD, Tian DH, Lemaire SA, Hughes GC, Chen EP, Misfeld M, Griepp RB, Kazui T, Bannon PG, Coselli JS, Elefteriades JA, Kouchoukos NT, Underwood MJ, Mathew JP, Mohr FW, Oo A, Sundt TM, Bavaria JE, Di Bartolomeo R, Di Eusanio M, Trimarchi S,

Yan TD, Tian DH, Lemaire SA, Hughes GC, Chen EP, Misfeld M, Griepp RB, Kazui T, Bannon PG, Coselli JS, Elefteriades JA, Kouchoukos NT, Underwood MJ, Mathew JP, Mohr FW, Oo A, Sundt TM, Bavaria JE, Di Bartolomeo R, Di Eusanio M, Trimarchi S,

Circulation 2014 Apr;129(15):1610-6

PMID: 24733540

Abstract

Detection of serious complications by MR imaging in asymptomatic young adults with repaired coarctation of the aorta

January 3, 2015March 31, 2014 by Padang R, Dennis M, Semsarian C, Bannon PG, Tanous DJ, Celermajer DS, Puranik R

Padang R, Dennis M, Semsarian C, Bannon PG, Tanous DJ, Celermajer DS, Puranik R

Heart Lung Circ 2014 Apr;23(4):332-8

PMID: 24210077

Abstract

BACKGROUND: Despite early repair, patients with aortic coarctation (CoA) continue to have a reduced life expectancy due to the development of late complications. We sought to define the rate of aortic abnormalities in patients with previous CoA repair, referred for surveillance magnetic resonance (MR) imaging.

METHODS: We evaluated 59 asymptomatic adults consecutively for repaired CoA with MR imaging between 2008 and 2012.

RESULTS: Patients were aged 29 ± 8 (16-49) years; 34 males (58%) and 34 with bicuspid aortic valve (58%). Median age at the time of initial repair was two years. Surveillance MR imaging was performed 23 ± 8 years post-procedure. The three most common interventions performed were subclavian-flap repair (25%), end-to-end repair (33%) and patch aortoplasty (33%). Re-intervention with balloon angioplasty or repeat surgery had been performed in 22% of subjects. There were 28 cases of recoarctation (48%), of which seven were at least moderate in severity. Repair site and ascending aortic aneurysm occurred in eight (14%) and four (7%) subjects, respectively. Freedom from any degree of recoarctation and other aortic complications was observed in eight subjects (14%).

CONCLUSION: MR imaging detected a high rate of aortic abnormalities in asymptomatic adults after CoA repair, including 27% with clinically significant recoarctation and/or local aneurysm formation.

Outcomes of aortic arch replacement surgery after previous cardiac surgery

January 3, 2015February 5, 2014 by Davies RA, Black D, Bannon PG, Bayfield MS, Hendel PN, Hughes CF, Wilson MK, Vallely MP

Davies RA, Black D, Bannon PG, Bayfield MS, Hendel PN, Hughes CF, Wilson MK, Vallely MP

ANZ J Surg 2013 Nov;83(11):827-32

PMID: 23782742

Abstract

BACKGROUND: Aortic arch replacement is a potentially high-risk operation and in the re-operative setting has been found to be a risk factor for poor outcome, yet there is a dearth of published data specifically on this topic. The aim of the study was to review our unit’s outcomes in this re-operative setting.

METHOD: Data were collated for all patients who underwent aortic arch replacement surgery after previous cardiac surgery from January 1988 to November 2011. The patients were divided based primarily on elective versus non-elective and also early (≤2005) and late (≥2006) series.

RESULTS: Twenty-seven eligible patients (22 male; median age: 53.0 years; elective: 14, non-elective: 13) were identified. There was a mean period of 14.5 years between the first operation and the subsequent aortic arch replacement. The overall 30-day mortality rate was 22.2% – 0% elective and 46.2% non-elective (P = 0.004). Overall permanent neurological dysfunction was 21.7% – 28.6% elective and 11.1% non-elective (P = 0.463). There were 11 early-series patients and 16 late-series patients. For early-series patients, 90.9% were non-elective versus 18.8% in the late-series patients. The 30-day mortality rate was 54.5% early series versus 0% late series.

CONCLUSION: Aortic arch replacement is high risk in the re-operative setting. These risks are even greater for non-elective procedures. This highlights the need for aggressive first-time surgery to reduce re-operative procedures and good long-term follow-up programmes to allow elective procedures if required.

A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma

January 3, 2015January 27, 2014 by Cao C, Tian D, Park J, Allan J, Pataky KA, Yan TD

Cao C, Tian D, Park J, Allan J, Pataky KA, Yan TD

Lung Cancer 2014 Feb;83(2):240-5

PMID: 24360321

Abstract

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive disease of the pleural lining with a dismal prognosis. Surgical treatments of MPM with a curative intent include extrapleural pneumonectomy and extended pleurectomy/decortication (P/D). This meta-analysis aimed to compare the perioperative and long-term outcomes of EPP and extended P/D for selected surgical candidates.

METHODS: A systematic review of the literature was performed on six electronic databases to identify all relevant data on comparative outcomes of extended P/D and EPP in a multimodality setting. Endpoints included perioperative mortality and morbidity, as well as long-term overall survival.

RESULTS: Seven relevant studies with comparative data on EPP (n=632) versus extended P/D (n=513) were identified from the current literature. Comparison of these two groups demonstrated significantly lower perioperative mortality (2.9% vs. 6.8%, p=0.02) and morbidity (27.9% vs. 62.0%, p<0.0001) for patients who underwent extended P/D compared to EPP. Median overall survival ranged between 13-29 months for extended P/D and 12-22 months for EPP, with a trend favouring extended P/D.

CONCLUSIONS: Although it must be emphasized that patient selection and treatment strategies differ between EPP and extended P/D, a number of comparative studies have recently been conducted to compare these two surgical techniques for patients with resectable MPM. The present study indicated that selected patients who underwent extended P/D had lower perioperative morbidity and mortality with similar, if not superior, long-term survival compared to EPP, in the context of multi-modality therapy. This may represent an important paradigm shift in the surgical management of MPM.

ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma

January 3, 2015January 24, 2014 by Cheng YY, Kirschner MB, Cheng NC, Gattani S, Klebe S, Edelman JJ, Vallely MP, McCaughan BC, Jin HC, van Zandwijk N, Reid G

Cheng YY, Kirschner MB, Cheng NC, Gattani S, Klebe S, Edelman JJ, Vallely MP, McCaughan BC, Jin HC, van Zandwijk N, Reid G

J Thorac Oncol 2013 Oct;8(10):1317-28

PMID: 24457242

Abstract

INTRODUCTION: Epigenetic inactivation of tumor suppressor genes is involved in the development of malignant pleural mesothelioma (MPM). ZIC1, a potential tumor suppressor gene involved in regulating cell growth and apoptosis, was investigated in MPM cell lines and tumors.

METHODS: ZIC1 expression and promoter methylation were evaluated in MPM cell lines and tumor samples by quantitative polymerase chain reaction (PCR), Combined Bisulfite Restriction Analysis, and methylation-specific PCR. ZIC1 was reexpressed in cell lines and functional effects were assessed. miRNA expression was quantified by microarray and reverse transcription quantitative PCR. ZIC1 knockdown and miRNA inhibitors were used to study the relationship between ZIC1 and miRNA expression and confirmed by chromatin immunoprecipitation PCR.

RESULTS: ZIC1 expression was low in MPM cells, and was correlated with ZIC1 promoter methylation and reversed upon decitabine treatment. ZIC1 reexpression inhibited proliferation and invasion in MPM cells whereas knockdown enhanced the growth of MeT-5A. In MPM tumor samples ZIC1 expression was either low or undetectable, with promoter methylation observed in 16 of 24 cases. The overexpression of miR-23a and miR-27a was reduced by ZIC1 reexpression, with inhibitors of miR-23a or miR-27a reducing colony formation. miR-23a overexpression was also associated with shorter survival of MPM patients.

CONCLUSION: ZIC1 is down-regulated in MPM through promoter methylation and acts as a tumor suppressor through down-regulation of its direct targets miR-23a and miR-27a.

An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma

January 3, 2015January 22, 2014 by Linton A, Cheng YY, Griggs K, Kirschner MB, Gattani S, Srikaran S, Chuan-Hao Kao S, McCaughan BC, Klebe S, van Zandwijk N, Reid G

Linton A, Cheng YY, Griggs K, Kirschner MB, Gattani S, Srikaran S, Chuan-Hao Kao S, McCaughan BC, Klebe S, van Zandwijk N, Reid G

Br. J. Cancer 2014 Jan;110(2):510-9

PMID: 24327015

Abstract

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed.

METHODS: Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients.

RESULTS: Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis.

CONCLUSION: These results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.

Custodiol for myocardial protection and preservation: a systematic review

January 3, 2015December 18, 2013 by Edelman JJ, Seco M, Dunne B, Matzelle SJ, Murphy M, Joshi P, Yan TD, Wilson MK, Bannon PG, Vallely MP, Passage J

Edelman JJ, Seco M, Dunne B, Matzelle SJ, Murphy M, Joshi P, Yan TD, Wilson MK, Bannon PG, Vallely MP, Passage J

Ann Cardiothorac Surg 2013 Nov;2(6):717-28

PMID: 24349972

Abstract

INTRODUCTION: Custodiol cardioplegia is attractive for minimally invasive cardiac surgery, as a single dose provides a long period of myocardial protection. Despite widespread use in Europe, there is little data confirming its efficacy compared with conventional (blood or crystalloid) cardioplegia. There is similar enthusiasm for its use in organ preservation for transplant, but also a lack of data. This systematic review aimed to assess the evidence for the efficacy of Custodiol in myocardial protection and as a preservation solution in heart transplant.

METHODS: Electronic searches were performed of six databases from inception to October 2013. Reviewers independently identified studies that compared Custodiol with conventional cardioplegia (blood or extracellular crystalloid) in adult patients for meta-analysis; large case series that reported results using Custodiol were analyzed. Next, we identified studies that compared Custodiol with other organ preservation solutions for organ preservation in heart transplant.

RESULTS: Fourteen studies compared Custodiol with conventional cardioplegia for myocardial protection in adult cardiac surgery. No difference was identified in mortality; there was a trend for increased incidence of ventricular fibrillation in the Custodiol group that did not reach statistical significance. No difference was identified in studies that compared Custodiol with other solutions for heart transplant.

CONCLUSIONS: Despite widespread clinical use, the evidence supporting the superiority of Custodiol over other solutions for myocardial protection or organ preservation is limited. Large randomised trials are required.

Systematic review of robotic minimally invasive mitral valve surgery

January 3, 2015December 18, 2013 by Seco M, Cao C, Modi P, Bannon PG, Wilson MK, Vallely MP, Phan K, Misfeld M, Mohr F, Yan TD

Seco M, Cao C, Modi P, Bannon PG, Wilson MK, Vallely MP, Phan K, Misfeld M, Mohr F, Yan TD

Ann Cardiothorac Surg 2013 Nov;2(6):704-16

PMID: 24349971

Abstract

BACKGROUND: Robotic telemanipulators have evolved to assist the challenges of minimally invasive mitral valve surgery (MVS). A systematic review was performed to provide a synopsis of the literature, focusing on clinical outcomes and cost-effectiveness.

METHOD: Structured searches of MEDLINE, Embase, and Cochrane databases were performed in August 2013. All original studies except case-reports were included in qualitative review. Studies with ≥50 patients were presented quantitatively.

RESULTS: After applying inclusion and exclusion criteria to the search results, 27 studies were included in qualitative review, 16 of which had ≥50 patients. All studies were observational in nature, and thus the quality of evidence was rated low to medium. Patients generally had good left ventricular performance, were relatively asymptomatic, and mean patient age ranged from 52.6-58.4 years. Rates of intraoperative outcomes ranged from: 0.0-9.1% for conversion to non-robotic surgery, 106±22 to 188.5±53.8 min for cardiopulmonary bypass (CPB) time and 79±16 to 140±40 min for cross-clamp (XC) time. Rates of short-term postoperative outcomes ranged from: 0.0-3.0% for mortality, 0.0-3.2% for myocardial infarction (MI), 0.0-3.0% for permanent stroke, 1.6-15% for pleural effusion, 0.0-5.0% for reoperations for bleeding, 0.0-0.3% for infection, and 1.1-6% for prolonged ventilation (>48 hours), 1.5-5.4% for early repair failure, 12.3±6.7 to 36.6±24.7 hours for intensive care length of stay, 3.1±0.3 to 6.3±3.9 days for hospital length of stay (HLOS) and 81.7-97.6% had no or trivial mitral regurgitation (MR) before discharge.

CONCLUSIONS: All subtypes of mitral valve prolapse are repairable with robotic techniques. CPB and XC times are long, and novel techniques such as the Cor-Knot, Nitinol clips or running sutures may reduce the time required. The overall rates of early postoperative mortality and morbidity are low. Improvements in postoperative quality of life (QoL) and expeditious return to work offset the increase in equipment and intraoperative cost. Evidence for long-term outcomes is as yet limited.

A meta-analysis of MitraClip system versus surgery for treatment of severe mitral regurgitation

January 3, 2015December 18, 2013 by Wan B, Rahnavardi M, Tian DH, Phan K, Munkholm-Larsen S, Bannon PG, Yan TD

Wan B, Rahnavardi M, Tian DH, Phan K, Munkholm-Larsen S, Bannon PG, Yan TD

Ann Cardiothorac Surg 2013 Nov;2(6):683-92

PMID: 24349969

Abstract

BACKGROUND: Mitral regurgitation (MR) is the second most common valvular heart disease after aortic stenosis. Without intervention, prognosis is poor in patients with severe symptomatic MR. While surgical repair is recommended for many patients with severe degenerative MR (DMR), as many as 49% of patients do not qualify as they are at high surgical risk. Furthermore, surgical correction for functional MR (FMR) is controversial with suboptimal outcomes and significant perioperative mortality. The percutaneous MitraClip implantation can be seen as a viable option in high surgical risk patients. The purpose of this meta-analysis is to compare the safety, clinical efficacy, and survival outcomes of MitraClip implantation with surgical correction of severe MR.

METHODS: Six electronic databases were searched for original published studies from January 2000 to August 2013. Two reviewers independently appraised studies, using a standard form, and extracted data on methodology, quality criteria, and outcome measures. All data were extracted and tabulated from the relevant articles’ texts, tables, and figures and checked by another reviewer.

RESULTS: Overall 435 publications were identified. After applying selection criteria and removing serial publications with accumulating number of patients or increased length of follow-up, four publications with the most complete dataset were included for quality appraisal and data extraction. There was one randomized controlled trial (RCT) and three prospective observational studies. At baseline, patients in the MitraClip group were significantly older (P=0.01), had significantly lower LVEF (P=0.03) and significantly higher EuroSCORE (P2 was significantly higher in the MitraClip group compared to the surgical group (17.2% vs. 0.4%; P<0.0001). 30-day mortality was not statistically significant (1.7% vs. 3.5%; P=0.54), nor were neurological events (0.85% vs. 1.74%; P=0.43), reoperations for failed MV procedures (2% vs. 1%; P=0.56), NYHA Class III/IV (5.7% vs. 11.3; P=0.42) and mortality at 12 months (7.4% vs. 7.3%; P=0.66).

CONCLUSIONS: Despite a higher risk profile in the MitraClip patients compared to surgical intervention, the clinical outcomes were similar although surgery was more effective in reducing MR in the early post procedure period. We conclude the non-inferiority of the MitraClip as a treatment option for severe, symptomatic MR in comparison to conventional valvular surgery.

Immobilisation of a fibrillin-1 fragment enhances the biocompatibility of PTFE

Abstract

Standardizing clinical end points in aortic arch surgery: a consensus statement from the International Aortic Arch Surgery Study Group

Abstract

Detection of serious complications by MR imaging in asymptomatic young adults with repaired coarctation of the aorta

Abstract

Outcomes of aortic arch replacement surgery after previous cardiac surgery

Abstract

A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma

Abstract

ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma

Abstract

An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma

Abstract

Custodiol for myocardial protection and preservation: a systematic review

Abstract

Systematic review of robotic minimally invasive mitral valve surgery

Abstract

A meta-analysis of MitraClip system versus surgery for treatment of severe mitral regurgitation

Abstract

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