Heterogeneity of human pancreatic islet isolation around Europe: results of a survey study. Aim. Europe is currently the most active region in the field of pancreatic islet transplantation and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries. Methods. A web-based questionnaire about critical steps including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation and release criteria of the product was completed by isolation facilities participating at the 9th International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan. Results . Eleven islet isolation facilities completed the questionnaire. The facilities reported 445 and 53 islet isolations/year over last 3 years from deceased organ donors and pancreatectomized patients, respectively. This activity resulted in 120 and 40 infusions/year in allograft and autograft recipients, respectively. Differences among facilities emerged in donor selection (age, cold ischemia time, intensive care unit length, amylase concentration), pancreas procurement, isolation procedures (brand and concentration of collagenase, additive, maximum acceptable digestion time), quality evaluation and release criteria for transplantation (Glucose-Stimulated insulin Secretion tests, islet numbers and purity). Moreover, even when a high concordance about the relevance of one parameter was evident, thresholds for the acceptance were different among facilities. Conclusions /interpretation. The result highlighted the presence of a heterogeneity in the islet cell product process and product release criteria. * Authors equally contributed CONTRIBUTION STATEMENT: RN, JAK-C, HS, ME, MK, DB, BA, FB, BL, BK, FS, ZL, DLDP, PRVJ performed islet isolation, provided data and contributed to the discussion. RN, JAK-C, HS and LP developed the concept, analysed the data and wrote the manuscript. FP, TB, OK, EdK and LP promoted the study and researched data. All authors approved the version submitted for publication. LP is the guarantor of this work. DUALITY OF INTEREST: The authors declare that there is no duality of interest associated with this manuscript. FUNDING: The Juvenile Diabetes Research Foundation International supported this research (ECIT Islets for Research) DATA AVAILABILITY: The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request. Correspondence to: Lorenzo Piemonti, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan. Fax: 39 02 26432871. Tel: 39 02 26432706. E-mail: piemonti.lorenzo@hsr.it Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Developing Mobile Health (mHealth) Tools for Long-Term Medication Adherence in Transplant Patients—Invited Commentary No abstract available

Handling of Missing Data No abstract available

Bilirubin improves the quality and function of hypothermic preserved islets by its antioxidative and anti-inflammatory effect Background: Islet transplantation is a promising option for the treatment of type 1 diabetes. However, the current lack of practical techniques for the isolated islets preservation still hampers the advancement of life-saving islet transplantation. Islet suffers from internal or external stimuli induced oxidative stress and subsequent inflammation during preservation, which leads to disappointing outcomes regarding islet yield, survival and function. ROS overproduction is the primary cause of oxidative stress that induces islet loss and dysfunction. Thus, in this paper, we hypothesized that an endogenous antioxidant, bilirubin, that could efficiently scavenge ROS and inhibit inflammatory reactions could be beneficial for islet preservation. Methods: Herein, we studied the effect of bilirubin on the hypothermic preserved (4°C) islets, and evaluate the islets viability, insulin secretory function, oxidative stress levels, and in vivo transplantation performance. Results: Bilirubin could prevent cellular damages during short-term preservation, and maintain the co-cultured islets viability and function. The protective role of bilirubin is associated with its antioxidative ability, which dramatically increased the activities of antioxidant enzymes (SOD and GSH-Px), and decreased the levels of ROS and MDA. Diabetic mice transplanted with bilirubin preserved islets were normoglycemic for 28 days, even overmatched the diabetic mouse transplanted with fresh islets. Mice receiving bilirubin co-cultured islets required the least time to achieve normoglycemia among all groups and exhibited minimum inflammatory responses during the early transplantation stage. Conclusions: By utilizing bilirubin, we achieved highly viable and functional islets after hypothermic preservation to reverse diabetes in mice. † The first two authors contributed equally to this work Disclosure: The authors declare no conflicts of interest. Conflict of interest: The authors declare no conflict of interest. Funding: This research was supported by the Key Research and Development Program of Zhejiang Province (Grant No. 2018C03013), Zhejiang Province Natural Science Foundation (Grant No. LQ19H300001, LY19H180001, and LY17H180008), Zhejiang provincial program for the cultivation of high-level innovative health talents (Y.-Z.Z.), 151 talent project of Zhejiang province and 551 talent projects of Wenzhou (Y.-Z.Z.), and School Talent Start Fund of Wenzhou Medical University (Grant No. QTJ15020). * Corresponding author: Correspondence information: Dr. Ying-Zheng Zhao, Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China. Electronic address: zyzpharm@163.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Plasmacytoid Dendritic Cells and the Spontaneous Acceptance of Kidney Allografts No abstract available

Cytomegalovirus: The “Troll of Transplantation” is now the “Troll of Tolerance” No abstract available

Strategies to improve the oxygen supply to microencapsulated islets No abstract available

International Travel for Living Donor Kidney Donation: A Proposal for Focused Screening of Vulnerable Groups As the gap between organ donors and patients on the recipient waiting list grows, residents of the US who are in need of kidney transplantation occasionally contract with living donors from outside the US. Those donors then travel to the US to undergo living donor kidney donation at US transplant centers. This practice is not limited to the US and occurs with some regularity around the world. However, there is very little written about this practice from the perspective of the US transplant system, and there is little in the way of guidance (either legal or ethical) to assist centers that accommodate it in distinguishing between ethically permissible travel for transplant and what could potentially be human trafficking for organ removal. This paper will present an ethical analysis of travel for organ donation with particular attention to lessons that can be drawn from living donor donation in other countries. This inquiry is particularly germane because OPTN has promulgated guidelines with respect to obligations owed to living donors, but those guidelines appear to assume that the donor is a US resident. The critical question then, is whether and/or to what extent those guidelines are applicable to the instant scenario in which the living donor is a non-resident. In addition, this paper addresses several critical ethical concerns implicated by the often vulnerable populations from which donors are drawn. Finally, this paper proposes that focused inquiry by transplant centers is necessary when donors are non-residents. Corresponding Author: Jane A. Hartsock, JD, MA, Director, Department of Clinical Medical Ethics at IU Health, 1800 N. Capitol, Noyes Pavilion – Suite E644, Indianapolis, IN 46202, jhartsock@iuhealth.org, (317) 274-2906 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

DONOR PNPLA3 AND TM6SF2 VARIANT ALLELES CONFER ADDITIVE RISKS FOR GRAFT STEATOSIS AFTER LIVER TRANSPLANTATION Background: The rs58542926 polymorphism in TM6SF2 (transmembrane 6 superfamily member 2) is a genetic factor predisposing to nonalcoholic fatty liver disease. We aimed to explore the effect of recipient and donor TM6SF2 rs58542926 genotypes on liver graft fat content after liver transplantation. Methods: Steatosis was evaluated in liver biopsies from 268 adult recipients. The influence of recipient and donor TM6SF2 genotypes, PNPLA3 rs738409 genotypes and nongenetic factors on the steatosis grade assessed 6 - 30 months after transplantation was analyzed by ordinal logistic regression. Results: The presence of the TM6SF2 c.499A allele in the donor (p=0.014), the PNPLA3 c.444G allele in the donor (p<0.001), posttransplant BMI (p<0.001) and serum triglycerides (p=0.047) independently predicted increased liver fat content on multivariable analysis whereas noncirrhotic liver disease as an indication for liver transplantation was associated with lower risk of steatosis (p=0.003). The effects of the donor TM6SF2 A and PNPLA3 G alleles were additive, with an odds ratio (OR) of 4.90 (95%CI 2.01-13.00; p<0.001) when both minor alleles were present compared to an OR of 2.22 (95%CI 1.42-3.61; p=0.002) when only one of these alleles was present. Conclusions: The donor TM6SF2 c.499A allele is an independent risk factor of liver graft steatosis after liver transplantation that is additive to the effects of donor PNPLA3 c.444G allele. Disclosure: The authors declare that they have nothing to disclose regarding the funding or conflicts of interest with respect to this manuscript. Funding: This study was financially supported by the Ministry of Health of the Czech Republic, grant No. 15-26906A, and the project for development of research organization 00023001 (IKEM, Prague, Czech Republic) – Institutional support. All rights reserved. Corresponding author: Irena Míková, M.D., Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Prague, Czech Republic; email address: irena.mikova@ikem.cz Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Fine Balance: Using Letermovir For Salvage Antiviral Treatment While Preserving Efficacy No abstract available