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

Therapeutic Hypothermia in Organ Donors: Follow-up and Safety Analysis Background: In a recent trial, targeted mild hypothermia in brain dead organ donors significantly reduced the incidence of delayed graft function (DGF) after kidney transplantation. This trial was stopped early for efficacy. Here, we report long-term graft survival for all organs along with donor critical care endpoints. Methods: We assessed graft survival through one year of all solid organ transplanted from 370 donors who had been randomly assigned to hypothermia (34-35°C) or normothermia (36.5-37.5°C) prior to donation. Additionally, changes in standardized critical care endpoints were compared between donors in each group. Results: Mild hypothermia was associated with a nonsignificant improvement in one-year kidney transplant survival (95% vs. 92%, hazards ratio [HR] 0.61 [0.31-1.20], p=0.15). Mild hypothermia was associated with higher one-year graft survival in the subgroup of standard criteria donors (97% vs. 93%, HR 0.39 [0.15 -1.00], p=0.05). There were no significant differences in graft survival of extra-renal organs. There were no differences in critical care endpoints between groups. Conclusions: Mild hypothermia in the donor safely reduced the rate of DGF in kidney transplant recipients without adversely affecting donor physiology or extra-renal graft survival. Kidneys from standard criteria donors who received targeted mild hypothermia had improved one-year graft survival. * Drs. Malinoski and Niemann contributed equally to the study. Conflict of Interest Statement: The authors of this manuscript have no conflicts of interest to disclose. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT01680744 Financial Disclosure: This publication was supported by Grant No. R38OT22183(to Claus U. Niemann, MD) from the Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services. The contents of this publication are solely the responsibility of the author(s) and do not necessarily represent the views of HRSA. Corresponding Author: Claus U. Niemann, M.D. University of California at San Francisco, Department of Anesthesia and Perioperative Care & Department of Surgery, Division of Transplantation, 521 Parnassus Avenue, C 450, San Francisco, CA 94143-0648, Phone: 415 502 2162, FAX: 415 502-2016, e-mail: Claus.Niemann@ucsf.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Video Intervention to Increase Organ Donor Registration at the Department of Motorized Vehicles Background. The goal of this study was to increase organ donor registrations at the Department of Motorized Vehicles (DMV) via utilization of a sustainable, low-cost, African American-centric organ donation educational video. Results from previous studies provided a framework to generate a 10-minute video that featured registered organ donors, deceased donor families, and transplant recipients. Methods. The video was presented via an interrupted time series design (repeating on 2 months, off 2 months) on TVs placed in 6 regional DMVs. 162,387 patrons visited the DMVs during the 12-month study. Results. Increases in organ donor registration were consistently observed in each DMV while the video was on compared to off [mean = +2.3% (range +1.98% to +3.35%); P < 0.0001]. Multivariable analysis demonstrated that females (OR 1.29; 95% CI 1.26 - 1.31) younger age (OR 0.982/year; 95% CI 0.982-0.983), and the video intervention (OR 1.09; 95% CI 1.07-1.12) were significantly associated with increased registration; while compared with Caucasian race, African American race was not, (OR 0.22; 95% CI 0.22-0.23). There was no video-dependent effect on registration between Caucasians and African Americans (P = 0.62). Exit interviews demonstrated only 16% of patrons could identify the key message in the video (becoming a registered organ donor). Conclusions. An educational video promoting organ donation resulted in increased organ donor registration at the DMV. The intervention was equally effective in African Americans and Caucasians. Future efforts should focus upon target-specific messaging and patron consumption of the educational video. Corresponding Author: Derek A. DuBay, MD, Department of Surgery, Division of Transplant Surgery, 96 Jonathan Lucas Street, MSC613/CSB409, Charleston, SC 29425 Email: dubay@musc.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Sequential deceased donor intestine transplantation followed by living donor liver transplantation, also known as “hybrid intestine-liver transplantation” No abstract available

Eculizumab as Primary Therapy for Active Antibody-Mediated Rejection of Renal Allografts: A Matter of Timing, Severity, and Donor-Specific Antibodies No abstract available

Aerosolization of second-generation triazoles: In vitro evaluation and application in therapy of invasive airway aspergillosis Background: A lung transplant patient with Invasive aspergillosis (IA) manifested symptoms of voriconazole induced transaminitis with systemic voriconazole and progression of IA after switching to oral posaconazole. With limited options for standard triazole therapy, aerosolized delivery with one of second generation triazoles was considered. Methods: Feasibility for aerosolized delivery was evaluated using cascade impactor and analysis of physicochemical characteristics of voriconazole (10 mg/mL) and posaconazole (6, 12 mg/mL) solutions. Results: Both triazoles showed favorable characteristics for aerosol delivery with mass median aerodynamic diameter, geometric standard deviation, respirable fraction (< 5.4 µm) of (2.8 µm, 2.0, 86%), (3.4 µm, 2.4, 78%) and (3.0 µm, 2.3, 79%) for voriconazole and 6, 12 mg/mL of posaconazole, respectively. The fumigatus isolate from patient was more susceptible to voriconazole, hence, aerosolized voriconazole was introduced around the 3rd month post transplant at 40 mg thrice daily for 1 week, 40 mg twice daily for 1 week, followed by 40 mg daily, thereafter, along with intravenous caspofungin (50 mg/day) and liposomal amphotericin B (300 mg/day). The aerosol regimen was well tolerated by patient with undetectable trough plasma levels of voriconazole. Bronchoscopy at 4th month, revealed improvement in anastomotic plaques with reduction in BAL galactomannan values (7.48 to 2.15 ng/mL). This consolidated aerosolized and intravenous regimen was maintained until 2.97 years post transplant. Conclusions: The intravenous solutions of both second generation triazoles showed characteristics that were suitable for aerosol delivery. Our report further adds to the therapeutic experience with use of aerosolized voriconazole for IA in a lung transplant patient. Disclosure:The authors declare no conflicts of interest. Funding:The authors declare no funding for this work. Corresponding author: Raman Venkataramanan, Professor of Pharmaceutical Sciences, Room 4103, University of Pittsburgh, 700 Technology drive, Pittsburgh Technology Center, Pittsburgh, PA 15219, Phone:412-648-8547, Fax:412-648-7671, Email: rv@pitt.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.