Tom Smith

Effects of low cobalamin diet and chronic cyanide toxicity in baboons

The effects of a low cobalamin (Cbl) diet, together with chronic cyanide or thiocyanate administration in some animals have been investigated in baboons over a period of 42 months. All animals remained healthy throughout the study and gained weight at a similar rate. None became anaemic or showed major haematological changes and there were no major neurological changes. Plasma total Cbl in the animals on the low Cbl diet fell within 9 months to values below the lower limit in man and were lowest at 24 months in baboons not receiving cyanide or thiocyanate. A striking feature in all animals, however, was an apparently seasonal increase in the plasma total Cbl each autumn with a corresponding decrease the following spring. This fluctuation was detected by radioisotopic assay but not by Euglena. Methylmalonic (MMA) excretion after oral valine ranged from 0.1--8.4 mg/24 h and was greatest in animals on the low Cbl diet and not receiving cyanide or thiocyanate. The results suggested an inverse relationship between MMA excretion and plasma total Cbl. Plasma thiocyanate was consistently higher in animals receiving cyanide or thiocyanate and at the end of the study plasma cyanide was highest in animals on the low Cbl diet receiving cyanide. The results support the suggestions that cyanide affects bodily handling of Cbl and that hydroxo-cobalamin plays a part in detoxication of cyanide.

Metabolomic Perfusate Analysis during Kidney Machine Perfusion: The Pig Provides an Appropriate Model for Human Studies

Introduction Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs. Methods Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy. Results There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples. Conclusions Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies.

Evolution of renal transplant practice over the past decade: a U.K. center experience

OBJECTIVE As renal transplantation continues to evolve, there appears to be a change in both donor and recipient populations. Traditional markers of high-risk donor (e.g. donation after cardiac death [DCD]/expanded criteria donor [ECD]) and recipient (e.g. obese, highly sensitized) operations appear to be more common without any noticeable worsening of patient outcome. The present study aimed to compare outcome and define the change in donor and recipient populations for cadaveric transplants over a 10-year period at a large U.K. center. METHODS Single-center analysis of all adult patients undergoing cadaveric renal transplantation between January 2004 and January 2014 (n = 754). Transplants were divided into 3 groups (early, middle, and late) depending on the era, with donor, recipient and outcomes compared. RESULTS There were considerable changes in both donor and recipient factors between the 3 eras, with a greater proportion of high-risk operations performed, as reflected by significant increases in Donor Risk Index (median: 1.11-1.16, P = .022), and the proportions of ECD (22.2%-33.9%, P = .003) and DCD kidneys (10.8%-19.4% P = .011). However, 1-year graft survival was comparable between the eras, with a decrease in the average 1-year serum creatinine between the early and late cohort (median: 161 μmol/L vs 132 μmol/L, P < .001). There was no significant increase in body mass index (BMI) in either the donor or recipient population across the eras. CONCLUSION Improvement in transplant outcome continues despite a greater proportion of transplants previously considered as high risk being performed. This is likely to reflect a considerable improvement in pre- and postoperative management. BMI remains a major continuing block to transplantation.

S61 Risk factors and short-term outcomes of developing postoperative pulmonary complications after vats lobectomy

Introduction Postoperative pulmonary complications (PPC), such as pneumonia and atelectasis are associated with poor outcomes following thoracotomy and lung resection, with risk factors identified.1,2 Video-assisted thoracoscopic surgery (VATS) is increasingly performed, however, there are varying reports regarding the incidence of PPC with little is known about their effect on short-term outcomes or potential risk factors. Methods A prospective observational study of consecutive patients undergoing VATS lobectomy was performed in a regional centre (2012–2016). Exclusion criteria included re-do VATS/completion lobectomy. All patients received physiotherapy assessment/intervention as necessary from postoperative day 1 (POD1). The presence of PPC was determined daily using the Melbourne Group Scale. Outcomes included hospital length of stay (LOS), intensive therapy unit (ITU) admission and hospital mortality. Results 287 patients underwent VATS lobectomy, 2 patients undergoing completion lobectomy were excluded. Of 285 patients; 137 were male (48%), median (IQR) age of 69 years (13) and mean (±SD) FEV1 of 87% (±19). PPC developed in 21 patients (7.4%); the median day that PPC developed was postoperative day 3 (Figure 1). Patients who developed a PPC had a significantly longer hospital LOS (4 vs 3 days), higher rate of ITU admission (25% vs 0%) and higher hospital mortality (14% vs 0%) (p < 0.001). Current smoking and COPD diagnosis were significantly different on univariate analysis (p < 0.05), but on forward stepwise logistic regression, only current smoking was a significant independent risk factor for PPC (p = 0.015). Those with PPC required significantly more physiotherapy contacts/time, with more specific pulmonary therapy and emergency out-of-hours therapy. Abstract S61 Figure 1 Day PPC detected following surgery Conclusions Patients undergoing VATS remain at risk of developing a PPC associated with significantly worse short-term morbidity and mortality. Patients that develop a PPC following VATS required increased postoperative physiotherapy compared to non-PPC patients. Current smoking is an independent risk factor for PPC development following VATS, thus vigorous addressing of preoperative smoking cessation is urgently needed. References Agostini P, et al. Postoperative pulmonary complications following thoracic surgery: are there any modifiable risk factors? Thorax 2010;65(9):815–8. Lugg ST, et al. Long-term impact of developing a postoperative pulmonary complication after lung surgery. Thorax 2016;71(2):171–6.

Manipulating the HIF Pathway in Renal Transplantation, Current Progress and Future Developments

Renal transplantation is the gold standard treatment for end stage renal disease; however, there are currently not enough suitable organs to meet a growing demand. The Hypoxia Inducible Factor (HIF) pathway comprises a number of oxygen sensitive transcription factors which activate cellular protective functions. Allografts from cadaveric organs make up a large proportion of the organ pool. These organs are subjected to hypoxic and ischemic conditions during the harvesting and transplant process. Manipulation of the HIF pathway may reduce organ damage and improve outcomes. This review evaluates the current evidence for the use of the HIF pathway in renal transplantation and also adds new research conducted into the effect on organ metabolism.