Bronchial-arterial-circulation-sparing lung preservation: A new organ protection approach for lung transplantation Background: Compromised microvasculature resulting from disrupted bronchial arterial circulation appears to trigger chronic lung allograft dysfunction (CLAD). Maintaining the microvasculature throughout the transplant process could improve the long-term health of transplanted lungs. We recently developed a bronchial-arterial-circulation-sparing (BACS) lung preservation approach and tested whether this approach would decrease microvascular damage and improve allograft function. Material and Methods: The lungs of Lewis rats were procured using either the BACS approach, where the bronchial and pulmonary arteries were synchronously perfused; a conventional approach, where only the pulmonary artery was perfused; or a conventional approach with a prostaglandin flush. After 4 hours of cold ischemia, physiologic function and vascular tone of the grafts were evaluated during ex vivo lung perfusion (EVLP), and microvasculature damage was assessed using two-photon microscopy analysis. Lung function was compared after transplant among the groups. Results: After 4 hours of cold ischemia, the BACS group exhibited significantly higher adenosine triphosphate levels and lower expression of phosphorylated myosin light chain (p-MLC), which is essential for vascular smooth muscle contraction. On EVLP, the BACS and prostaglandin groups showed lower pulmonary vascular resistance and less arterial stiffness. BACS attenuated microvasculature damage in the lung grafts as compared with conventional preservation. After transplantation, the lungs preserved with the BACS approach exhibited significantly better graft function and lower expression of p-MLC. Conclusion: Our data suggest that BACS lung preservation protects the dual circulation inherent to the lungs, facilitating robust microvasculature in lung grafts after transplantation, leading to better posttransplant outcomes. Disclosure: The authors declare no conflicts of interest. Funding: The authors declare no funding was received for this study. Competing interests: All authors declare no conflict of interests. Address for Correspondence: Norihisa Shigemura, MD, PhD. Surgical Director of Lung Transplantation and Lung Failure, Division of Cardiovascular Surgery, Temple University Health System and Lewis Katz School of Medicine, Philadelphia, PA, USA. E-mail address: Norihisa.Shigemura@tuhs.temple.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Utilizing a Hospital Based Setting to Increase Organ Donor Registrations Background: Shortages of organs for transplantation is a concern for many countries. In Australia’s “opt-in” system, people register their donation decision on the Australian Organ Donor Register (AODR) in their own time, yet less than 30% of the population have done so. Consent registrations are honored by the next-of-kin in 90% of cases, so increasing registrations will increase donated organs for transplantation. This study investigated the efficacy of offering an immediate registration opportunity in 2 hospitals, and the role that beliefs about organ donation play in registration behavior. Methods: An immediate registration opportunity was offered at a public and private hospital in NSW, Australia. Participants (N = 168) categorized as medical/healthcare (e.g. doctor, nurse) and nonhealthcare (e.g. teacher, chef) completed a measure of beliefs about organ donation, were encouraged to discuss their fears and concerns about organ donation, and given an immediate opportunity to register on the AODR. Results: 81.5% of medical/ healthcare participants who were eligible registered, and 71.5% of all eligible participants registered on the spot. Beliefs about the negative consequences of donation and concerns over the medical care given to potential donors predicted (non) registration. Medical/healthcare participants reported lower levels of fears and concerns than nonhealthcare participants. Although both groups reported strong positive beliefs about donation, these did not predict registration. Conclusions: Offering an immediate registration opportunity in 2 hospitals notably increased the number of registrations on the Australian Organ Donor Register, suggesting this is a strategy that could potentially increase registrations in opt-in donation systems. Disclosure: The authors declare no conflicts of interest. Funding: This research was funded by NSW Organ and Tissue Donation Service Correspondence information: Dr Gail Moloney, School of Health and Human Sciences, Southern Cross University, Hogbin Drive, Coffs Harbour, NSW 2450. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Association of Clinical Rejection vs. Rejection on Protocol Biopsy with Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients Background: Two or more early rejections (<1 year) or any late acute rejection (>1 year) have been associated with coronary artery vasculopathy (CAV) in pediatric heart transplant (HT) recipients. We hypothesized that clinical rejection, defined by concurrent new-onset heart failure or left ventricular systolic dysfunction is more strongly associated with future CAV than rejection diagnosed on protocol biopsy. Methods: We identified all subjects <21 years old who received first HT at Boston Children’s Hospital during 1986-2015 with at least one post-HT coronary angiogram. CAV was diagnosed using 2010 ISHLT guidelines. Time to CAV diagnosis was assessed using a Cox model with occurrence of clinical rejection analyzed as a time-varying covariate. Results: Of 228 study subjects, 106 remained rejection-free, 77 had rejection diagnosed only on protocol biopsy (≥ 2R cellular or antibody-mediated) and 45 had a clinical rejection. Subjects with rejection diagnosed only on protocol biopsy were not at higher risk of CAV (HR 1.09, 95% CI 0.54, 2.09). In contrast, clinical rejection was significantly associated with risk of CAV (HR 4.84, 95% CI 2.99, 7.83). Late rejection was associated with a higher risk of CAV (HR 4.27, 95% CI 2.42, 7.51) if it was clinical rejection but not if it was diagnosed on protocol biopsy (HR 0.83, 95% CI 0.51, 1.37). Conclusion: Clinical rejection poses a far greater risk for future CAV than rejection on protocol biopsy in pediatric HT recipients. Preventing CAV should therefore become the focus of medical management after initial treatment and resolution of clinical rejection. * EPA and JCG contributed equally to this work Disclosure: The authors declare no conflict of interest. Funding: The study was supported by Heart Transplant Research and Education Fund, Boston Children’s Hospital, MA. J.C.G. was funded by the John S. LaDue Memorial Fellowship in Cardiology from Harvard Medical School. Address for Correspondence:Tajinder P. Singh, MD, MSc, Department of Cardiology, Children’s Hospital Boston, Tel: 617-355-0558; FAX: 617-734-9930, Email: TP.Singh@cardio.chboston.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Oral and Inhaled Ribavirin Treatment for Respiratory Syncytial Virus Infection in Lung Transplant Recipients Background: Respiratory syncytial virus (RSV) infection in lung transplant recipients (LTRs) causes mortality rates of 10-20% despite antiviral therapy. Ribavirin (RBV) has been used to treated RSV infected LTRs with limited data. Methods: A retrospective study including all LTRs at Duke Hospital during January 2013-May 2017 with positive RSV PCR respiratory specimens was performed. Results: Fifty six of 70 patients in the oral RBV group and 29 of 32 in the inhaled RBV group had symptomatic RSV infection. One patient receiving oral RBV had to prematurely stop drug due to significant nausea and vomiting. While unadjusted all-cause one-year mortality was significantly higher in the inhaled RBV group [24.1% vs 7.1% (oral RBV), p 0.03], adjusted hazard ratio (HR) for death and oral RBV use (compared to inhaled RBV), accounting for oxygen requirement and need for mechanical ventilation, showed the HR for death and oral RBV use was 0.38 ([0.10, 1.46], p 0.38). The HR for death in patients with supplemental oxygen > 2 L/min at diagnosis was 6.18 ([1.33, 26.83], p 0.02). Kaplan-Meier curves showed patients with FEV1 decline ≥ 5% and ≥ 10% at 90 days post-RSV infection had a higher 1-year mortality (p 0.004 and p 0.001, respectively). Conclusions: Oral and inhaled RBV appear to be well tolerated in LTRs and our data supports the use of oral RBV as a safe alternative to inhaled ribavirin in LTRs. Oxygen requirement > 2 L/min at diagnosis and FEV1 decline ≥ 5% post infection may be markers for increased mortality. Disclosure: N.P. served as a consultant for Alcimed. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Funding: No funding sources to be disclosed for the study. Corresponding author: Nitipong Permpalung, Address: 601 N Wolfe Street, Carnegie Building room 340, Baltimore, MD, 21231, USA. Business telephone: 443-287-6217; fax: 410-955-0788, Email: npermpa1@jhmi.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Comparing glycaemic benefits of active versus passive lifestyle intervention in kidney allograft recipients (CAVIAR): a randomised controlled trial Background. New-onset diabetes is common after kidney transplantation but the benefit of lifestyle intervention to improve glucose metabolism post transplantation is unproven. Methods. We conducted a single-center, randomised controlled trial involving 130 nondiabetic kidney transplant recipients with stable function between 3-24 months post transplantation. Participants were randomly assigned in a 1:1 ratio to receive active intervention (lifestyle advice delivered by renal dietitians using behaviour change techniques) versus passive intervention (leaflet advice alone). Primary outcome was six-month change in insulin secretion, insulin sensitivity and disposition index. Secondary outcomes included patient-reported outcomes, cardio-metabolic parameters, clinical outcomes and safety endpoints. Results. Between August 17th 2015 and December 18th 2017, 130 individuals were recruited of whom 103 completed the study (drop-out rate 20.8%). Active versus passive intervention was not associated with any change in glucose metabolism; insulin secretion (mean difference -446 [95% CI -3184 to 2292], p=0.748), insulin sensitivity (mean difference -0.45 [95% CI -1.34 to 0.44], p=0.319) or disposition index (mean difference -940 [95% CI -5655 to 3775], p=0.693). Clinically, active versus passive lifestyle intervention resulted in reduced incidence of post transplantation diabetes (7.6% versus 15.6% respectively, p=0.123), reduction in fat mass (mean difference -1.537kg [-2.947 to -0.127], p=0.033) and improvement in weight (mean difference -2.47kg [-4.01 to -0.92], p=0.002). No serious adverse events were noted. Conclusions. Active lifestyle intervention led by renal dietitians did not improve surrogate markers of glucose metabolism. Further investigation is warranted to determine if clinical outcomes can be improved using this methodology. Trial Registration Registered with clinicaltrials.org registry (identifier; NCT02233491). Disclosure: The authors have no relevant disclosures to declare. Funding: This study was supported by grants from the European Foundation for the Study of Diabetes and the British Renal Society/Kidney Care UK. Corresponding author contact information. Dr. Adnan Sharif, Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2GW, United Kingdom. Phone: (0121 371 5861), Fax: (0121 472 4942), Email: adnan.sharif@uhb.nhs.uk. Orchid ID: 0000-0002-7586-9136 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Multiple listings: Good for a few, but no solution for the organ shortage No abstract available

Optimizing allocation of older donors in liver transplantation: the objectives of allocation policies also matter No abstract available

Multiple regional listing increases liver transplant rates for those with MELD score less than 15 TPA-2019-0259R2 Clean Copy Background: Multiple listing (ML) at more than one transplant center is one mechanism to combat the geographic disparities in liver transplantation (LT) rates. The objective of our study was to determine the impact of multiple listing on LT rates. Patients & Methods: We examined the UNOS database from 2002 to 2016 after excluding those listed for multiple-organs, hepatocellular carcinoma or living donor LT. The waitlist mortality and LT rates for the ML groups and the single listed (SL) group were compared after stratifying patients by the MELD with a cut-off at 15 (<15 and ≤15). Results: Of the 83,935 listed during the study period, 80,351 were listed in a single center (SL group), and 3,584 were listed in more than one center (ML group). Of the ML groups, 2,028 (2.4%) were listed at multiple donor service areas but within the same region (ML-SR) and 1,556 (1.9%) listed in different regions (ML-DR). The median MELD at LT was 20, 21 and 24 for ML-DR, ML-SR and SL groups respectively (p=0.001). Although the probability of receiving LT was significantly higher for the ML groups relative to the SL group for both MELD groups (<15 and ≥15), the impact was highest for ML-DR group. At MELD score < 15, the probability of LT was 72% for ML-DR, 38% for ML-SR and 32% for SL groups. At MELD score ≥15, the probability of LT was 79% for ML-DR, 67% for ML-SR and 61% for SL groups. Conclusion: Multiple listing appeared to considerably improve a patient's chance of receiving LT and survival with the highest benefit for those with low MELD scores (<15) listed at multiple regions. Contribution of authors: SB contributed to the study concept. PT and SB drafted the manuscript study design, analysis and interpretation of data. YS did the statistical analysis. RB and JL contributed to the critical revision of manuscript Funding: None Conflict of Interests: None Corresponding author: Paul J. Thuluvath, MD., FAASLD, FRCP., Institute of DigestivS2264e Health & Liver Diseases, Mercy Medical Center, Baltimore MD 21202 , Tel: 410 332 9308, Email: thuluvath@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Differential Influence of Donor Age Depending on the Indication for Liver Transplantation – A Collaborative Transplant Study Report Background. Despite steadily increasing donor age, there are no general guidelines for the use of organs from elderly donors in liver transplantation. This study focuses on identifying the recipients who are less affected from an old-donor organ graft and conversely in whom a rather unfavorable outcome is expected due to high donor age. Methods. 48,261 adult liver transplantations, performed between 2000 and 2017 and reported to the Collaborative Transplant Study, were analyzed. Results. The proportion of ≥ 65-year-old donors has risen to more than 33% in recent years. The donor age has an approximately linear influence on graft survival. On average, each year’s rise in the donor age was associated with a 0.9% increase in the risk of graft loss, hazard ratio (HR) 1.009, P < 0.001. The impact of donor age was “strong” in patients with hepatitis C-related cirrhosis (HR 1.013, P < 0.001), “substantial” in patients with alcoholic cirrhosis (HR 1.007, P < 0.001), and “rather weak” in patients with hepatocellular carcinoma (HCC) (HR 1.003, P = 0.038). The increase in the risk of graft loss per year rise in donor age was 1.4% for 18- to 49-year-olds, 1.0% for middle-aged, and only 0.4% for ≥ 60-year-old recipients (all P < 0.001). Conclusions. Consequently, older recipients and especially patients with HCC seem to be less affected by an increased donor age, whereas the donor age is an important factor in all other patient groups. Disclosure: The authors of this manuscript have no conflicts of interest to disclose. Funding: The study received no external funding. Corresponding author Philipp Houben, MD, Department of General, Visceral, and Transplant Surgery, Heidelberg University Hospital Im Neuenheimer Feld 11069120 Heidelberg, Germany. Telephone:+49 6221 56-6111, Fax:+49 6221 64215, Email:philipp.houben@med.uni-heidelberg.de Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Too Much, Too Little, or Just Right? The Importance of Allograft Portal Flow in Deceased Donor Liver Transplantation Background. While portal flow (PF) plays an important role in determining graft outcomes in living donor liver transplantation, its impact in deceased donor whole liver transplantation (DDLT) is unclear. The aim of this study was to investigate the correlations between graft PF and graft outcomes in DDLT. Methods. We retrospectively investigated 1,001 patients who underwent DDLT between January 2007 and June 2017 at our institution. The patients were divided into three groups according to hazard ratio for one-year graft loss at each PF value, which was standardized with graft weight. Graft and recipient outcomes were compared between the groups. Results. The low-PF group (PF < 65 mL/min/100g, n = 210, P = 0.011) and the high-PF group (PF > 155 mL/min/100g, n = 159, P = 0.018) showed significantly poorer one-year graft survival compared with the intermediate-PF group (PF > 65 mL/min/100g and < 155 mL/min/100g, n = 632). The patients in the low-PF group had severe reperfusion injury and were more frequently complicated with primary nonfunction (P = 0.013) and early allograft dysfunction (P < 0.001) compared with the other groups. In contrast, the patients in the high-PF group had milder reperfusion injury, but had lower intraoperative hepatic artery flow with higher incidence of hepatic artery thrombosis (P = 0.043) and biliary complication (P = 0.041) compared with the other groups. Conclusions. These results suggest that intraoperative PF plays an important role in determining early graft outcomes after DDLT. Disclosure: The authors declare no conflicts of interest. Study findings were presented in 2019 at the Rising Star Plenary Session of the ILTS 25th Annual Congress, Toronto, Canada, and in 2019 at the American Transplant Congress, Boston, MA Reprints and Corresponding to: Koji Hashimoto, M.D., Ph.D. Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, 9500 Euclid Ave, A100, Cleveland, OH, 44195 , Telephone: 216-445-0753, Fax: 216-444-9357, E-mail: hashimk@ccf.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.