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Rear R.,University College London | Bell R.M.,University College London | Hausenloy D.J.,University College London | Hausenloy D.J.,National Heart Research Institute Singapore | Hausenloy D.J.,National University of Singapore
Heart | Year: 2016

CIN represents a significant clinical and health economic problem that may be under-recognised through limitations in the currently available biomarkers. Although often a transient injury, CIN may progress to significant persistent renal impairment, ESRF and adverse cardiovascular outcomes. There are a number of recognised risk factors, although the prediction of CIN, particularly prior to contrast administration, remains challenging. Current interventions are largely centred on the avoidance of dehydration, the withdrawal of nephrotoxic agents and minimisation of contrast load, which has limited efficacy in preventing CIN in vulnerable patients. The unmet clinical need in CIN therefore resides in accurate prediction, effective intervention and rapid detection to prevent adverse cardiorenal outcomes. Each of these areas, particularly predictive risk scoring systems, innovative pharmacological and mechanical interventions and novel biomarkers are currently the subject of intensive research and development that may lead to the future development effective strategies to mitigate the risk of CIN. Source

Serebruany V.L.,Johns Hopkins University | Cherepanov V.,Johns Hopkins University | Cabrera-Fuentes H.A.,Justus Liebig University | Cabrera-Fuentes H.A.,National University of Singapore | And 3 more authors.
Thrombosis and Haemostasis | Year: 2015

The role of anticoagulants and antiplatelet agents in tumour growth and prognosis is not new, and currently under intense investigation. Some randomised data strongly suggest that this association exists, but it is complex, and not necessarily pointed at the same direction. The potential mechanisms responsible for such harmful association include a direct hazard of novel antithrombotics on cancer, indirect promotion of tumour growth, easier metastatic dissemination due to instability of platelet-tumour cell aggregates, or/and inability to keep cancer cells locally in situ are considered. The latest randomised evidence ultimately rejected the drug-specific cancer risks, clearly indicating the class-effect. In lay terms “cancers follow bleeding”, which seems to be true for antithrombotic agents in general. Significant excess of solid cancers which was similar after prasugrel in TRITON, and with vorapaxar in TRACER trials was confirmed by the FDA reviews. Later, extra cancer deaths reported following clopidogrel and prasugrel in DAPT, and after ticagrelor in PEGASUS are also of concern. However, there are remaining controversies with regard to published cancer risks after ticagrelor (PLATO), or another vorapaxar trial (TRA2P), while full disclosure of separate clopidogrel and prasugrel cancer data in DAPT is still lacking. In short, if we apply moderate antiplatelet strategies for over two years, or aggressive regimens including triple therapy for much less than one year, the solid cancer risks emerge. Currently, more delicate platelet inhibition, and shorter exposure to dual oral antiplatelet agents should prevail. © Schattauer 2015. Source

Hausenloy D.J.,University College London | Hausenloy D.J.,National Health Research Institute | Hausenloy D.J.,National Heart Research Institute Singapore | Hausenloy D.J.,National University of Singapore | And 14 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND Whether remote ischemic preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. METHODS We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote ischemic preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. RESULTS We enrolled a total of 1612 patients (811 in the control group and 801 in the ischemic- preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with ischemic preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P = 0.58). Furthermore, there were no significant between- group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life. CONCLUSIONS Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery. Copyright © 2015 Massachusetts Medical Society. All rights reserved. Source

Rosa V.,National University of Singapore | Toh W.S.,National University of Singapore | Cao T.,National University of Singapore | Shim W.,National Heart Research Institute Singapore
Expert Opinion on Biological Therapy | Year: 2014

Introduction: The induced pluripotent stem cells (iPSCs) have characteristics similar to embryonic stem cells, including the capability of self-renewal and large-scale expansion and the ability to differentiate into all types of cells including germ cells, which defines pluripotency. Using iPSC avoids problems of immunological rejection and ethical controversy. The possible future uses of iPSC are diverse and go beyond the differentiation into somatic cells for regeneration of damaged tissues.Areas covered: A unique feature of iPSC is the potential to generate patient disease-specific tissues. Thus, cells from patients can be differentiated into relevant cells of interest for drug screening, characterization of drug effects and cytotoxic assays. This review presents key aspects related to iPSC, such as their generation, potential for disease modeling, treatment, drug development and future contributions to the craniofacial complex.Expert opinion: It is undisputable that the evolution in iPSC knowledge will improve the approaches for drug screening and development, help to understand and treat disease origins and mechanisms and provide new strategies to clinical treatment. However, it is necessary to fine-tune protocols to establish iPSCs that are cost-effective and safe for clinical use. © Informa UK, Ltd. Source

Bulluck H.,University College London | Yellon D.M.,University College London | Hausenloy D.J.,University College London | Hausenloy D.J.,National Heart Research Institute Singapore | Hausenloy D.J.,National University of Singapore
Heart | Year: 2016

Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is 'myocardial reperfusion injury', a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-ofconcept clinical studies-however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury. Source

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