Shortage of organs for transplantation has led to the renewed interest in donation after circulatorydetermination of death (DCDD).We conducted a retrospective analysis (2001-2009) and a subsequent prospective validation (2010) of liver MaastrichtCategory-3-DCDD and donation-after-brain-death (DBD) offers to our program. Accepted and declined offers were compared. Accepted DCDD offers were divided into donors who went on to cardiac arrest and those who did not. Donors who arrested were divided into those producing grafts that were transplanted or remained unused. Descriptive comparisons and regression analyses were performed to assess predictor models of donor cardiac arrest and graft utilization. Variables from the multivariate analysis were prospectively validated. Of 1579 DCDD offers, 621 were accepted, and of these, 400 experienced cardiac arrest after withdrawal of support. Of these, 173 livers were transplanted. In the DCDD group, donor age < 40 years, use of inotropes and absence of gag/cough reflexes were predictors of cardiac arrest. Donor age >50 years, BMI >30, warm ischemia time >25 minutes, ITU stay >7 days and ALT ≥ 4× normal rates were risk factors for not using the graft. These variables had excellent sensitivity and specificity for the prediction of cardiac arrest (AUROC = 0.835) and graft use (AUROC = 0.748) in the 2010 prospective validation. These models can feasibly predict cardiac arrest in potential DCDDs and graft usability, helping to avoid unnecessary recoveries and healthcare expenditure.

The origin of cells replacing ageing b-cells in adult life is unknown. This study assessed the expression of classic stem cell markers: Oct4, Sox2 and CD34 in islet-enriched fractions versus exocrine cell-enriched fractions from 25 adult human pancreases following human islet isolation. Expression of Oct4, Sox2 and CD34 mRNAs was found in all cell samples, with no significant differences between endocrine and exocrine cell fractions. Immunohistochemical staining for Oct4, Sox2, CD133, CD34, CK19, insulin and nestin on human pancreas sections showed that the majority of Oct4Cve cells were found in the walls of small ducts. Similar localisations were observed for Sox2Cve cells. The majority of Sox2Cve cells were found to co-express Oct4 proteins, but not vice versa. Cells positive for Oct4 and Sox2 appeared to be a unique cell population in the adult human pancreases without co-expression for CK19, CD34, CD133, insulin and nestin proteins. The numbers of Oct4Cve and Sox2Cve cells varied among donors and were w1-200 and 1-30 per 100 000 pancreatic cells respectively.

Islets from brain-dead donors (BDDs) are being used in the treatment of Type 1 diabetes. However, both donor numbers and islet survival are limited. We explored the clinical potential for islets from non-heartbeating donors (NHBDs), who have lower circulating cytokines, by comparing islets from 10 NHBDs against 12 identically-isolated islets from BDDs over the same time period. The quantity and quality of islets from NHBDs was good. NHBD yielded ∼12.6% more islets than those of BDDs (505 000 ± 84 230 vs. 400 970 ± 172 430 islet equivalent number [IEQ]/pancreas, p = 0.01) with comparable viability. ATP and GTP contents were lower (6.026 ± 3.076 vs. 18.105 ± 7.8 nM/mg protein, p = 0.01 and 1.52 ± 0.87 vs. 3.378 ± 0.83 nM/mg protein, p = 0.04) and correlated negatively to warm ischemia time (R 2 = 0.8022 and R 2 = 0.7996, respectively). Islets from NHBDs took longer to control hyperglycemia in diabetic mice, but were equally able to sustain euglycemia. With a warm ischemia time (WIT) of ≤25 min, islets from NHBDs are at least as competent as islets from BDDs and should be suitable for clinical use.

Islet transplantation alone (ITA) is indicated for patients with type 1 diabetes (T1D) with disabling severe hypoglycaemia (SH) despite optimised medical therapy. We examined outcomes for patients referred to an islet transplant unit with recurrent SH. Retrospective case note audit of 45 patients with ≥1 SH per year who were referred to our ITA unit between 2009-2012; 36 patients attended follow-up appointments. The cohort was 52.8% male, mean (± SD) age 43.9 (± 11.4) years, and duration of diabetes 26.5 (± 12.9) years. Baseline HbA1c was 8.3% (± 1.7) (67.2 mmol/mol), median (IQR) frequency of SH was 6.0 (2.0-24.0) per/patient/year and 83.3% had impaired awareness of hypoglycaemia (IAH). 80.6% of patients were referred from other secondary diabetes services, 22.2% had completed structured education, and 30.6% were using continuous subcutaneous insulin infusion (CSII). Seventeen patients were optimised with conventional therapy; SH reduced from 2.0 (1.5-9.0) to 0.0 (0.0-0.5) episodes/patient/year; p<0.001, and there was concurrent improvement in HbA1c (8.1-7.7%; 65.0 vs. 60.7 mmol/mol; p=0.072). Ten patients were listed for transplantation as they were not optimised despite structured education, CSII, and continuous glucose monitoring (CGM). The remaining 9 had a reduction in SH [7.0 (4.8-40.5) to 4.0 (2.5-6.3) episodes/patient/year; p=0.058] and either left the service (n=5) or are still being optimised (n=4). In conclusion, 47.2% of patients presenting with problematic hypoglycaemia resolved with optimal medical therapy, with a further 25% achieving clinically relevant improvement, however 27.8% required transplantation despite access to all therapies. Provision of expertise in hypoglycaemia management is essential to focus limited transplant resources on those who need it most.