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Despite a stringent donor selection, human islet isolation remains frustratingly unpredictable. In this study, we measured acute insulin response to arginine (AIRarg), an in vivo surrogate measure of islet mass, in 29 human deceased donors before organ donation, and correlated values with the outcome of islet isolation. Thirteen isolations (45%) met the threshold for clinical islet transplantation. Among all measured donor characteristics, the only discriminating variable between successful or unsuccessful isolations was donor AIRarg (p < 0.01). Using a threshold of 55 lIU/mL (ROC curve AUC: 72%), isolation was successful in 12/19 donors with high AIRarg and in 1/10 donors with low AIRarg (p < 0.001). The negative and positive predictive values were 90 and 63%, respectively. If used to select donors in the entire cohort, AIRarg would have increased our success rate by 40% and avoided 56% of unsuccessful isolations while missing only 8% of successful preparations. Our results suggest that donor AIRarg is markedly superior to body mass index (BMI) and other criteria currently used to predict isolation outcome. If routinely performed in deceased donors, this simple test could significantly reduce the failure rate of human islet isolation.Key words: Donor evaluation, donor screening, donor selection, insulin secretion, islet isolation, islet transplantation Abbreviations: AIRarg, acute insulin response to arginine; IEQ, islet-equivalents; AUC, area under curve; BMI, body mass index.

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Organ procurement and transplantation have grown steadily, and the need for organs will only rise in the future. Increasing the number of potential donors is therefore paramount. However, transplant coordination teams face refusals that can be linked to the contexts of the deaths, especially when they involve legal issues. In France, deaths involving legal proceedings are not uncommon (7-10%). In these cases, the prosecutor is immediately contacted, and makes the decision of whether to remove the involved organs. Refusals of this type represent 4% (approximately 30 cases per year) of obstacles to organ removals, and are governed by specific legislation. Thus, the prosecutor must arrange contact with a forensic pathologist and with the organ transplant teams to assemble all of the necessary elements for him to take the decision. To assist prosecutors in their decision making and to ensure them scientific rigour, the French Society of Forensic Medicine sought to develop a national recommendation to harmonise practices; it emerged in early 2013. The guideline makes practical recommendations, including among others: nominating local referents; writing regional protocols between judicial authorities, forensic pathologists and transplant teams; establishing terms for the forensic pathologist's intervention on the donor's body before and after a procurement. This recommendation by the French Society of Forensic Medicine aimed to combine two interests: addressing the shortage of organs, and fulfilling the requisites of a criminal investigation by standardising practices and encouraging communication.

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The need for organs has increased in the recent years, and this shortage will only worsen. In addition to the organs procured from brain-dead donors, a procedure for non-heart-beating donors was therefore developed. When deaths involve legal proceedings, the medical examiner makes the decision of whether or not to remove organs. To assist medical examiner in their decision-making, a number of forensic scientific societies aimed to develop recommendations, and legal adjustments were adopted. Nevertheless, these do present certain limits in special cases of procurement: Maastricht class I and II non-heart-beating donors. The peculiarity of this procedure stems from the urgency of the process. Compliance with temporal criteria would require that the deceased subject be removed from the crime scene even before the arrival of the authorities. This is extremely problematic legally and technically because forensic teams must collect evidence at crime scenes. Developments will have to be made to further minimize the restrictions on donations in forensic deaths.

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