Evaluation of metabolism of adenosine triphosphate as a novel biomarker of tissue ischaemia in vivo.

Introduction Ischaemia is often a medical emergency, clinical signs and symptoms vary dependant on organ or organ system affected. Timely restoration of oxygen delivery to affected tissues is paramount to preventing morbidity and mortality. Current diagnostic aids are non-specific and often late markers of ischaemia where there has been irreversible tissue damage. Metabolism of adenosine triphosphate (ATP) is altered during periods of ischaemia and intermediate nucleosides such as adenosine, inosine and hypoxanthine are released into the systemic circulation in demonstrable quantities. Development of an amperometric biosensor sensitive to these purine nucleosides, produced early in ischaemia prior to cell death, gives potential for purine nucleosides to be a clinically relevant biomarker. Methods A series of prospective observational cohort studies have been designed to provide pilot data on purine nucleoside changes, measured in real-time in vivo in populations of both surgical and non-surgical patients where a simple test for early identification of ischaemia would be clinically useful expedite diagnosis and prevent patient harm. Results There was no significant variation from baseline readings in purine nucleosides in systemically obtained samples intra-operatively in patients who are anaesthetised with general anaesthetic. There were significant increases in nucleosides in blood samples obtained locally within acutely ischaemic tissue. Elevated purine nucleosides were also identified in patients with critical limb ischaemia and following some types of brain injury. Conclusions Reliable determination of purine nucleosides in vivo remains challenging; multiple factors may interfere with quantification in vivo. Results here have identified purine nucleosides may have a role in acute and chronic limb ischaemia as well as traumatic brain injury. This requires further validation in populations of patients in clinical practice. Expansion to further areas of ischaemia may also be of clinical value

Intended Consequences Statement in Conservation Science and Practice

As the biodiversity crisis accelerates, the stakes are higher for threatened plants and animals. Rebuilding the health of our planet will require addressing underlying threats at many scales, including habitat loss and climate change. Conservation interventions such as habitat protection, management, restoration, predator control, trans location, genetic rescue, and biological control have the potential to help threatened or endangered species avert extinction. These existing, well-tested methods can be complemented and augmented by more frequent and faster adoption of new technologies, such as powerful new genetic tools. In addition, synthetic biology might offer solutions to currently intractable conservation problems. We believe that conservation needs to be bold and clear-eyed in this moment of great urgency

Editor's Choice – Acute Kidney Injury (AKI) in aortic intervention: Findings from the Midlands Aortic Renal Injury (MARI) cohort study

Objectives: The incidence of acute kidney injury (AKI) after open (OAR) or endovascular (EVAR) aortic repair is unknown. This research assessed the proportion of patients who develop AKI after aortic intervention using validated criteria, and explored AKI risk factors. Methods: This was a multicentre national prospective cohort study. Eleven centres recruited patients undergoing EVAR or OAR (September 2017–December 2018). Serum creatinine (SCr) and urine outputs were measured over a minimum of 48 h or throughout the index inpatient stay to define post-operative AKI using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Renal decline at 30 days was calculated using estimated glomerular filtration rate (eGFR) and the Major Adverse Kidney Events (MAKE) 30 day composite endpoint (consisting of: death, new dialysis, > 25% eGFR decline). Results: 300 patients (mean age: 71 years, standard deviation [SD] 4 years; 9% females) were included, who underwent: infrarenal endovascular aneurysm repair (EVAR) 139 patients, fenestrated EVAR (fEVAR) 30, branched EVAR (bEVAR) seven, infrarenal open aneurysm repair (OAR) 98, juxtarenal OAR 26. Overall, 24% of patients developed stage 1 AKI (defined at 48 h as per KDIGO), 2.7% stage 2 AKI and 1% needed renal replacement therapy before discharge. AKI proportions per intervention were: infrarenal EVAR 18%; fEVAR 27%; bEVAR 71%; infrarenal OAR 41%; juxtarenal OAR 63%. Older age (odds ratio [OR] 1.44 for EVAR, 1.58 for OAR), lower baseline eGFR (OR 0.88 EVAR, 0.74 OAR), and ischaemic heart disease (OR 4.42 EVAR, 5.80 OAR) were the main predictors of AKI for infrarenal EVAR and OAR. Overall, 24% developed the MAKE30 endpoint. All patients who died (0.6%) or developed a major cardiac event (5.6%) at one year had developed AKI. Conclusion: AKI and short term renal decline after aortic intervention are common. Age, renal function, and cardiovascular disease are the main risk factors. Research should now focus on AKI prevention in this high risk group

Acute Kidney Injury (AKI) in Aortic Intervention: Findings From the Midlands Aortic Renal Injury (MARI) Cohort Study

OBJECTIVES:The incidence of acute kidney injury (AKI) after open (OAR) or endovascular (EVAR) aortic repair is unknown. This research assessed the proportion of patients who develop AKI after aortic intervention using validated criteria, and explored AKI risk factors. METHODS: This was a multicentre national prospective cohort study. Eleven centres recruited patients undergoing EVAR or OAR (September 2017-December 2018). Serum creatinine (SCr) and urine outputs were measured over a minimum of 48 h or throughout the index inpatient stay to define post-operative AKI using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Renal decline at 30 days was calculated using estimated glomerular filtration rate (eGFR) and the Major Adverse Kidney Events (MAKE) 30 day composite endpoint (consisting of: death, new dialysis, > 25% eGFR decline). RESULTS: 300 patients (mean age: 71 years, standard deviation [SD] 4 years; 9% females) were included, who underwent: infrarenal endovascular aneurysm repair (EVAR) 139 patients, fenestrated EVAR (fEVAR) 30, branched EVAR (bEVAR) seven, infrarenal open aneurysm repair (OAR) 98, juxtarenal OAR 26. Overall, 24% of patients developed stage 1 AKI (defined at 48 h as per KDIGO), 2.7% stage 2 AKI and 1% needed renal replacement therapy before discharge. AKI proportions per intervention were: infrarenal EVAR 18%; fEVAR 27%; bEVAR 71%; infrarenal OAR 41%; juxtarenal OAR 63%. Older age (odds ratio [OR] 1.44 for EVAR, 1.58 for OAR), lower baseline eGFR (OR 0.88 EVAR, 0.74 OAR), and ischaemic heart disease (OR 4.42 EVAR, 5.80 OAR) were the main predictors of AKI for infrarenal EVAR and OAR. Overall, 24% developed the MAKE30 endpoint. All patients who died (0.6%) or developed a major cardiac event (5.6%) at one year had developed AKI. CONCLUSION: AKI and short term renal decline after aortic intervention are common. Age, renal function, and cardiovascular disease are the main risk factors. Research should now focus on AKI prevention in this high risk group.</div