Donor insulin therapy in intensive care predicts early outcomes after pancreas transplantation.

AIMS/HYPOTHESIS: Approximately 50% of organ donors develop hyperglycaemia in intensive care, which is managed with insulin therapy. We aimed to determine the relationships between donor insulin use (DIU) and graft failure in pancreas transplantation. METHODS: UK Transplant Registry organ donor data were linked with national data from the UK solid pancreas transplant programme. All pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Logistic regression models determined associations between DIU and causes of graft failure within 3 months. Area under the receiver operating characteristic curve (aROC) and net reclassification improvement (NRI) assessed the added value of DIU as a predictor of graft failure. RESULTS: In 2168 pancreas transplant recipients, 1112 (51%) donors were insulin-treated. DIU was associated with a higher risk of graft loss from isolated islet failure: OR (95% CI), 1.79 (1.05, 3.07), p = 0.03, and this relationship was duration/dose dependent. DIU was also associated with a higher risk of graft loss from anastomotic leak (2.72 [1.07, 6.92], p = 0.04) and a lower risk of graft loss from thrombosis (0.62 [0.39, 0.96], p = 0.03), although duration/dose-dependent relationships were only identified in pancreas transplant alone/pancreas after kidney transplant recipients with grafts failing due to thrombosis (0.86 [0.74, 0.99], p = 0.03). The relationships between donor insulin characteristics and isolated islet failure remained significant after adjusting for potential confounders: DIU 1.75 (1.02, 2.99), p = 0.04; duration 1.08 (1.01, 1.16), p = 0.03. In multivariable analyses, donor insulin characteristics remained significant predictors of lower risk of graft thrombosis in pancreas transplant alone/pancreas after kidney transplant recipients: DIU, 0.34 (0.13, 0.90), p = 0.03; insulin duration/dose, 0.02 (0.001, 0.85), p = 0.04. When data on insulin were added to models predicting isolated islet failure, a significant improvement in discrimination and risk reclassification was observed in all models: no DIU aROC 0.56; DIU aROC 0.57, p = 0.86; NRI 0.28, p < 0.00001; insulin duration aROC 0.60, p = 0.47; NRI 0.35, p < 0.00001. CONCLUSIONS/INTERPRETATION: DIU predicts graft survival in pancreas transplant recipients. This assessment could help improve donor selection and thereby improve patient and graft outcomes.

Peri-transplant glycaemic control as a predictor of pancreas transplant survival.

AIMS: The relationship between peri-transplant glycaemic control and outcomes following pancreas transplantation is unknown. We aimed to relate peri-transplant glycaemic control to pancreas graft survival and to develop a framework for defining early graft dysfunction. METHODS: Peri-transplant glycaemic control profiles over the first 5 days postoperatively were determined by an area under the curve [AUC; average daily glucose level (mmol/L) × time (days)] and the coefficient of variation of mean daily glucose levels. Peri-transplant hyperglycaemia was defined as an AUC ≥35 mmol/day/L (daily mean blood glucose ≥7 mmol/L). Risks of graft failure associated with glycaemic control and variability and peri-transplant hyperglycaemia were determined using covariate-adjusted Cox regression. RESULTS: We collected 7606 glucose readings over 5 days postoperatively from 123 pancreas transplant recipients. Glucose AUC was a significant predictor of graft failure during 3.6 years of follow-up (unadjusted HR [95% confidence interval] 1.17 [1.06-1.30], P = .002). Death censored non-technical graft failure occurred in eight (10%) recipients with peri-transplant normoglycaemia, and eight (25%) recipients with peri-transplant hyperglycaemia such that hyperglycaemia predicted a 3-fold higher risk of graft failure [HR (95% confidence interval): 3.0 (1.1-8.0); P = .028]. CONCLUSION: Peri-transplant hyperglycaemia is strongly associated with graft loss and could be a valuable tool guiding individualized graft monitoring and treatment. The 5-day peri-transplant glucose AUC provides a robust and responsive framework for comparing graft function.

Donor insulin use predicts beta-cell function after islet transplantation.

Insulin is routinely used to manage hyperglycaemia in organ donors and during the peri-transplant period in islet transplant recipients. However, it is unknown whether donor insulin use (DIU) predicts beta-cell dysfunction after islet transplantation. We reviewed data from the UK Transplant Registry and the UK Islet Transplant Consortium; all first-time transplants during 2008-2016 were included. Linear regression models determined associations between DIU, median and coefficient of variation (CV) peri-transplant glucose levels and 3-month islet graft function. In 91 islet cell transplant recipients, DIU was associated with lower islet function assessed by BETA-2 scores (ß [SE] -3.5 [1.5], P = .02), higher 3-month post-transplant HbA1c levels (5.4 [2.6] mmol/mol, P = .04) and lower fasting C-peptide levels (-107.9 [46.1] pmol/l, P = .02). Glucose at 10 512 time points was recorded during the first 5 days peri-transplant: the median (IQR) daily glucose level was 7.9 (7.0-8.9) mmol/L and glucose CV was 28% (21%-35%). Neither median glucose levels nor glucose CV predicted outcomes post-transplantation. Data on DIU predicts beta-cell dysfunction 3 months after islet transplantation and could help improve donor selection and transplant outcomes.

Insulin therapy in organ donation and transplantation.

Hyperglycaemia is common in hospitalized individuals, and is often caused by physiological stress associated with critical illness or major surgery. Insulin therapy is an established treatment for hyperglycaemia and acute hyperkalaemia, and has also been used for myocardial dysfunction resistant to inotropic support. Insulin is commonly used in both organ donors and transplant recipients for hyperglycaemia, but the underlying knowledge base supporting its use remains limited. Insulin therapy plays an important yet poorly understood role in both organ donation and transplantation. Tight glycaemic control has been extensively studied in critical care over the past 15 years; however, this has not yet translated into the field of transplantation, where patients are more unwell and where improved outcomes remain an ongoing challenge. Insulin therapy and optimization of glycaemic control represent important areas for future hypothesis-driven research into organ donation and transplantation, such as amelioration of ischaemia-reperfusion injury, rejection and infection.

Major Adverse Cardiovascular Events Following Simultaneous Pancreas and Kidney Transplantation in the United Kingdom.

OBJECTIVE: People with type 1 diabetes and kidney failure have an increased risk for major adverse cardiovascular events (MACE). Simultaneous pancreas and kidney transplantation (SPKT) improves survival, but the long-term risk for MACE is uncertain. RESEARCH DESIGN AND METHODS: We assessed the frequency and risk factors for MACE (defined as fatal cardiovascular disease and nonfatal myocardial infarction or stroke) and related nonfatal MACE to allograft failure in SPKT recipients with type 1 diabetes who underwent transplantation between 2001 and 2015 in the U.K. In a subgroup, we related a pretransplant cardiovascular risk score to MACE. RESULTS: During 5 years of follow-up, 133 of 1,699 SPKT recipients (7.8%) experienced a MACE. In covariate-adjusted models, age (hazard ratio 1.04 per year [95% CI 1.01-1.07]), prior myocardial infarction (2.6 [1.3-5.0]), stroke (2.3 [1.2-4.7]), amputation (2.0 [1.02-3.7]), donor history of hypertension (1.8 [1.05-3.2]), and waiting time (1.02 per month [1.0-1.04]) were significant predictors. Nonfatal MACE predicted subsequent allograft failure (renal 1.6 [1.06-2.6]; pancreas 1.7 [1.09-2.6]). In the subgroup, the pretransplant cardiovascular risk score predicted MACE (1.04 per 1% increment [1.02-1.06]). CONCLUSIONS: We report a high rate of MACE in SPKT recipients. There are a number of variables that predict MACE, while nonfatal MACE increase the risk of subsequent allograft failure. It may be beneficial that organs from hypertensive donors are matched to recipients with lower cardiovascular risk. Pretransplant cardiovascular risk scoring may help to identify patients who would benefit from risk factor optimization or alternative transplant therapies and warrants validation nationally.

Interventional Radiology service provision and practice for the management of traumatic splenic injury across the Regional Trauma Networks of England.

INTRODUCTION: The management of blunt splenic injuries (BSI) has evolved toward strategies that avoid splenectomy. There is growing adoption of interventional radiology (IR) techniques in non-operative management of BSI, with evidence suggesting a corresponding reduction in emergency laparotomy requirements and increased splenic preservation rates. Currently there are no UK national guidelines for the management of blunt splenic injury. This may lead to variations in management, despite the reorganisation of trauma services in England in 2012. MATERIALS AND METHODS: A survey was distributed through the British Society of Interventional Radiologists to all UK members aiming to identify availability of IR services in England, radiologists' practice, and attitudes toward management of BSI. RESULTS: 116 responses from respondents working in 23 of the 26 Regional Trauma Networks in England were received. 79% provide a single dedicated IR service but over 50% cover more than one hospital within the network. All offer arterial embolisation for BSI. Only 25% follow guidelines. In haemodynamically stable patients, an increasing trend for embolisation was seen as grade of splenic injury increased from 1 to 4 (12.5%-82.14%, p<0.01). In unstable patients or those with radiological evidence of bleeding, significantly more respondents offer embolisation for grade 1-3 injuries (p<0.01), compared to stable patients. Significantly fewer respondents offer embolisation for grade 5 versus 4 injuries in unstable patients or with evidence of bleeding. CONCLUSION: Splenic embolisation is offered for a variety of injury grades, providing the patient remains stable. Variation in interventional radiology services remain despite the introduction of regional trauma networks.

Encapsulating peritoneal sclerosis: presentation without preceding symptoms.

Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis (PD), resulting in malnutrition and ultimately overt intestinal obstruction. We present the case of a 71-year-old man diagnosed with EPS incidentally at laparotomy for removal of PD catheter following an episode of PD peritonitis. He had been treated with continuous ambulatory PD for 18 months. He presented with anasarca and did not exhibit persistent symptoms of gastrointestinal dysfunction to suggest the EPS. Computed tomography scanning obtained 18 days prior to confirmation of the diagnosis did not demonstrate any features suggestive of EPS, highlighting a deficiency in the sensitivity of the diagnostic investigations. Management of the EPS is typically complicated by late diagnosis and concomitant malnutrition. This case highlights both the insidious nature of the EPS and a management problem to the surgeon faced with an unexpected abdominal cocoon. It further accentuates the necessity for increasingly sensitive diagnostic investigations to allow earlier diagnosis, thereby facilitating successful treatment.

Rectourethral fistula secondary to a bowel management system.

A 67-year-old Caucasian male was admitted under the vascular team with critical lower limb ischaemia. Bypass surgery was performed and he was admitted to the intensive care unit post-operatively. The patient experienced a turbulent post-operative recovery complicated by pneumonia, poor respiratory wean and faecal incontinence. A bowel management system was inserted but after 18 days it was reported faecal matter was bypassing his catheter. A CT scan demonstrated an area of necrosis where the bowel management system had been sited which formed a rectourethral fistula. Bowel management systems are frequently used in intensive care unit settings where a high proportion of patients suffer from faecal incontinence. If used correctly they can reduce skin contamination, infection and maintain patient hygiene. However, appropriate assessment and investigations should be addressed before inserting such devices. This case report highlights serious adverse effects of these devices and describes the first documented case of these devices causing a rectourethral fistula.