Effect of Remote Ischaemic Preconditioning on Liver Injury in Patients Undergoing Major Hepatectomy for Colorectal Liver Metastasis: A Pilot Randomised Controlled Feasibility Trial

BACKGROUND: Liver resection produces excellent long-term survival for patients with colorectal liver metastases but is associated with significant morbidity and mortality from ischaemia reperfusion injury (IRI). Remote ischaemic preconditioning (RIPC) can reduce the effect of IRI. This pilot randomised controlled trial evaluated RIPC in patients undergoing major hepatectomy at the Royal Free Hospital, London. METHODS: Sixteen patients were randomised to RIPC or sham control. RIPC was induced through three 10-min cycles of alternate ischaemia and reperfusion to the leg. At baseline and immediately post-resection, transaminases and indocyanine green (ICG) clearance were measured. FINDINGS: The RIPC group had lower ALT and AST levels immediately post-resection (ALT: 43% lower 497 ± 165 vs 889 ± 170 IU/L; p = 0.019 AST: 54% lower 408 ± 166 vs 836 ± 167 IU/L; p = 0.001) and at 24 h (ALT: 41% lower 412 ± 144 vs 698 ± 137 IU/L; p = 0.026 AST: 50% lower 316 ± 116 vs 668 ± 115 IU/L; p = 0.02). ICG clearance was reduced in controls versus RIPC immediately after resection (ICG-PDR: 11.1 ± 1.1 vs 16.5 ± 1.4%/min; p = 0.035). CONCLUSIONS: This pilot study shows that RIPC has potential to reduce liver injury following hepatectomy justifying a prospective RCT powered to demonstrate clinical benefits

Paving the way for culturally competent robots: a position paper

Cultural competence is a well known requirement for an effective healthcare, widely investigated in the nursing literature. We claim that personal assistive robots should likewise be culturally competent, aware of general cultural characteristics and of the different forms they take indifferent individuals, and sensitive to cultural differences while perceiving, reasoning, and acting. Drawing inspiration from existing guidelines for culturally competent healthcare and the state-of-the-art in culturally competent robotics, we identify the key robot capabilities which enable culturally competent behaviours and discuss methodologies for their development and evaluation

Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop

In 1993, Przyklenk and colleagues made the intriguing experimental observation that 'brief ischemia in one vascular bed also protects remote, virgin myocardium from subsequent sustained coronary artery occlusion' and that this effect '.... may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion'. This seminal study laid the foundation for the discovery of 'remote ischemic conditioning' (RIC), a phenomenon in which the heart is protected from the detrimental effects of acute ischemia/reperfusion injury (IRI), by applying cycles of brief ischemia and reperfusion to an organ or tissue remote from the heart. The concept of RIC quickly evolved to extend beyond the heart, encompassing inter-organ protection against acute IRI. The crucial discovery that the protective RIC stimulus could be applied non-invasively, by simply inflating and deflating a blood pressure cuff placed on the upper arm to induce cycles of brief ischemia and reperfusion, has facilitated the translation of RIC into the clinical setting. Despite intensive investigation over the last 20 years, the underlying mechanisms continue to elude researchers. In the 8th Biennial Hatter Cardiovascular Institute Workshop, recent developments in the field of RIC were discussed with a focus on new insights into the underlying mechanisms, the diversity of non-cardiac protection, new clinical applications, and large outcome studies. The scientific advances made in this field of research highlight the journey that RIC has made from being an intriguing experimental observation to a clinical application with patient benefit

The effects of remote ischemic pre-conditioning in reducing liver injury in a rabbit model and in patients

Ischemia reperfusion injury (IRI) following liver transplantation and major liver surgery results in a systemic inflammatory response syndrome (SIRS) with damage to the liver and remote organs. Physical methods of reducing liver IRI such as direct ischemic pre-conditioning (IPC) where a brief period of IRI is applied to the liver have been shown to reduce the adverse effects of liver IRI. However, direct liver IPC has been shown to impair liver regeneration in experimental models. Remote ischemic preconditioning (RIPC) is a novel strategy for reducing IRI through a brief period of IPC to a remote organ and this has been shown to reduce IRI to the heart and other organs. The purpose of the experiments described in this thesis is to investigate the effect and mechanism of RIPC in reducing liver IRI in an animal model and in patients. A rabbit model of total hepatic ischemia was established to study early warm liver IRI and in this model 25 minute of total portal inflow occlusion resulted in severe liver IRI at 2 hours of reperfusion. In the main experimental study rabbits were divided into four equal groups to study the effect of RIPC on early phase (2 hours) warm IRI following total portal inflow occlusion. RIPC before IRI reduced the adverse local and systemic effects of IRI, reduced acidosis and nitric oxide was shown to be an important mediator of protection. In a proof of concept study 16 patients undergoing major liver resection surgery were randomised into two groups, control and RIPC. In the RIPC group, post resection, there was a reduction in liver IRI