The comparable efficacy of lung donation after circulatory death and brain death: a systematic review and meta-analysis Background: Lung transplantations (LTx) have become an effective lifesaving treatment for patients with end-stage lung diseases. While the shortage of lung donor pool and severe posttransplantation complications exaggerate the obstacle of LTx. This meta-analysis aimed to evaluate the efficacy of donation after circulatory death (DCD) in LTx for patients with end-stage lung diseases. Methods: PubMed, EmBase and Web of Science were systematically searched for all relevant studies comparing the efficacy of DCD and conventional donation after brain death (DBD). The relative risk (RR) value as well as the weighted mean difference (WMD) with a 95% confidence interval (CI) were pooled for dichotomous and continuous outcomes, respectively. The heterogeneity across the included studies was also assessed carefully. Results: Overall, 17 studies with 995 DCD recipients and 38579 DBD recipients were included. The pooled analysis showed comparable 1-year overall survival (OS) between the 2 cohorts (RR 0.89, 95%CI [0.74, 1.07], p = 0.536, I2 = 0%). The airway anastomotic complications rate in DCD cohort was higher than that in DBD cohorts (RR 2.00, 95%CI [1.29, 3.11], p = 0.002, I2 = 0%). There was no significant difference between DCD and DBD regarding the occurrence of primary graft dysfunction grade 2/3, bronchiolitis obliterans syndrome, acute transplantation rejection, and length of stay. The stability of the included studies was strong. Conclusion: Evidence of this meta-analysis indicated that the use of lungs from DCD donors could effectively and safely expand the donor pool and therefore alleviate the crisis of organ shortage. * The first two author contributed equally to this work. Disclosure: None declared. Funding: This work was supported by Key Science and Technology Program of Sichuan Province, China (2016FZ0118) (to Dr. Lunxu Liu). Corresponding author: Lunxu Liu, Telephone: 86 28 85422494, Fax: 86 28 85422494, Address: No. 37, Guoxue Alley, Chengdu, Sichuan, 610041, China, E-mail: lunxu_liu@aliyun.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

HLA class II antibodies at the time of kidney transplantation and cardiovascular outcome: a retrospective cohort study Background. The negative role of HLA class II DSA on graft outcome is well-recognized. However, the potentially negative cardiovascular effects of preformed HLA class II antibodies and donor HLA in kidney transplant recipients (KTR) remain unestablished. Methods. We conducted a single-centre, retrospective cohort study including 1115 KTR (2003-2016) with up to 4449 person-years of follow-up after transplantation and a median follow-up time of 5.1 years (IQR: 2.7-7.6). We evaluated the unadjusted and multivariable-adjusted association between pretransplant HLA class I and II antibodies, as well as HLA-DR1 donor/recipient genotype and the primary (MACCE or all-cause mortality) and secondary (MACCE or cardiovascular mortality) outcome. Results. In a multivariate Cox proportional hazard model, HLA class II antibodies prior to transplantation were associated with increased adjusted hazard ratio (aHR) for MACCE or all-cause mortality (aHR 1.71 [1.13-2.60]; p=0.012) even after adjustment for time-varying covariates graft loss (aHR 1.68 [1.08-2.62]; p=0.022) and biopsy-proven acute rejection (aHR 1.71 [1.13-2.60]; p=0.012). HLA class II antibodies were also associated with increased aHR for the secondary outcome, MACCE or cardiovascular mortality (aHR 1.92 [1.12-3.30]; p=0.018). We investigated the effect of donor and recipient HLA-DR1 on these outcome parameters and demonstrated that KTR with HLA-DR1 positive donors had an increased aHR for MACCE with all-cause (aHR1.45 [1.09-1.94], p=0.012) and cardiovascular mortality (aHR1.49 [1.00-2.22], p=0.05). Conclusions. Prior sensitization against HLA class II antigens is associated with unfavourable long-term cardiovascular outcome in KTR independent of graft loss or rejection. Recipients of a HLA-DR1 donor also have an impaired cardiovascular outcome. Disclosure: The authors declare no conflicts of interest. Funding: The authors received no funding to conduct this study. Corresponding author: Email: thomas.malfait@azdelta.be, Address: AZ Delta, Wilgenstraat 2; 8800 Roeselare, Belgium. Phone:+3251237420, Fax:+3251237938 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Allograft and patient outcomes between Indigenous and non-Indigenous kidney transplant recipients Background: Kidney transplant outcomes of Indigenous Australians are poorer compared to non-Indigenous Australians, but it is unknown whether the type of acute rejection differs between these patient groups, or whether rejection mediates the effect between ethnicity, death-censored graft failure (DCGF) and death with a functioning graft (DWFG). Methods: Biopsy-proven acute rejection (BPAR) rates and types were compared between Indigenous and non-Indigenous recipients. The associations between ethnicity, BPAR, DCGF and DWFG were examined using adjusted competing risk analyses; and mediation analysis was conducted to determine whether BPAR mediated the adverse effects between ethnicity and outcomes. Results: Fifty-seven (9.3%) of 616 patients who have received kidney-only transplants between 2000-2010 in Western Australia were Indigenous. Compared to non-Indigenous recipients, BPAR rates were higher in Indigenous recipients (42 vs. 74 episodes/100 recipients, p<0.01), with an excess of antibody-mediated rejections. During a median follow-up of 8-years, Indigenous recipients were more likely to experience BPAR, DCGF and DWFG compared to non-Indigenous recipients, with adjusted subdistribution hazard ratio (HR) of 1.94 (1.39, 2.70), 1.53 (0.85, 2.76; p=0.159), and 2.14 (1.13,4.06; p=0.020), respectively. While 70% of the effect between ethnicity and DCGF was mediated by BPAR, no similar association was found for DWFG. Conclusions: Indigenous recipients experienced poorer allograft and patient outcomes compared to non-Indigenous recipients, with BPAR an important determinant for DCGF. Future research identifying other risk factors and mediators associated with patient survival in Indigenous recipients should be considered a priority. Declaration: No conflicts of interest. Funding source: None. Corresponding Author: Dr Prue Howson, Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia 6009, E-mail: prue.howson@health.wa.gov.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The Pathophysiology and Impact of Inflammation in Nonscarred Renal Interstitium: The Banff i Lesion Background. Interstitial inflammation (i-INT) is the driver of T cell rejection (TCMR). Its causes, pathophysiology, kinetics, and outcomes are poorly documented. Methods. The role of i-INT was evaluated in 2055 biopsies from 775 renal transplant recipients. Results. i-INT was present in 374 (18.2% prevalence) from acute and subclinical rejection (67.4%); IF/TA (14.4%); BK virus nephropathy (BKVAN) 9.9%; and acute tubular necrosis (ATN with i-INT) in 5.9% of cases. i-INT was predicted by prior TCMR and BKVAN, HLA mismatch, cyclosporine therapy, and indication biopsy for dysfunction. It correlated with tubulitis, arteritis, and antibody markers within concurrent histology (P<0.001). After treatment, renal functional recovery was best with histological ATN, milder i-INT, and early posttransplant biopsy times. The initial histological improvement of inflammation depended on baseline i-INT severity. Complete resolution to Banff i0 was predicted by early biopsy time, anti-lymphocyte therapy, recipient age, and medication compliance (all P<0.001). Clearance i-INT was followed by delayed resolution of tubulitis (P<0.001). i-INT was associated with histological ATN, renal dysfunction, and increased incident fibrosis on sequential pathology. Progressive fibrosis following related-rejection i-INT was dependent on tubulitis using multivariable analysis. In contrast, fibrogenesis after BKVAN or ATN was unrelated to inflammation. i-INT cases were followed by recurrent rejection in 35.3%, increased graft loss, and greater patient mortality. Multiple complementary outcome analyses determined the optimal lower diagnostic threshold for inflammation was Banff i1 score. Conclusion i-INT is a heterogeneous pathological phenotype that results in adverse functional and structural outcomes, for which active and robust therapy should be considered. Disclosures: The authors declare no conflicts of interest Funding: Nil. Correspondence: Dr Brian J Nankivell MD, BS, MSc, PhD, FRACP, Department of Renal Medicine, Westmead Hospital, WESTMEAD, 2145, NSW, AUSTRALIA. Telephone:61 2 8890 6962, Telefax: 61 2 9633 9351, Email: Brian.Nankivell@health.nsw.gov.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Trends, Determinants and Impact on Survival of Post-Lung Transplant Weight Changes: A single-Center Longitudinal Retrospective Study Background: Weight gain is commonly seen in lung transplant (LTx) recipients. While previous studies have focused on weight changes at fixed time periods and relatively early after transplant, trends over time and long-term weight evolution have not been described in this population. The study objectives were to document weight changes up to 15 years post-LTx and assess the predictors of post-LTx weight changes and their associations with mortality. Methods: Retrospective cohort study of LTx recipients between January 1st 2000 and November 30th 2016 (n=502). Absolute weight changes from transplant were calculated at fixed time periods (6 months, 1, 2, 5, 10 and 15 years) and continuous trends over time were generated. Predictors of weight changes and their association with mortality were assessed using linear and Cox regression analysis. Results: LTx recipients experienced a gradual increase in weight, resulting from the combination of multiple weight trajectories. Interstitial lung disease diagnosis negatively predicted post-LTx weight changes at all timepoints while transplant BMI categories were significant predictors at earlier timepoints. Patients with a weight gain >10% at 5 years had a better survival (HR 0.36 [0.20-0.66]) whereas a 10%-weight loss at earlier timepoints was associated with worse survival (1 years: HR 2.04 [1.22-3.41] and 2 years: HR 2.37 [1.22-4.58]). Conclusions: Post-LTx weight changes display various trajectories, are predicted to some extent by individual and LTx-related factors and have a negative or positive impact on survival depending on the time post-LTx. These results may lead to a better individualization of weight management after transplant. Disclosure: The authors declare no conflicts of interest. Funding: Alfonso Minicozzi and Family Chair in Thoracic Surgery and Lung Transplantation at the University of Montreal. GM is a scholar from FRQ-S (Fonds de Recherche du Québec en Santé). Corresponding Author: Valérie Jomphe, RD, MSc, CNSC, Lung Transplant Program, Centre Hospitalier de l’Université de Montréal, 900 Saint-Denis street (Pavillon R), Montreal, Quebec, Canada, H2X 0A9, Phone: (514) 890-8000 ext.: 20379 Fax: (514) 412-7714, valerie.jomphe.chum@ssss.gouv.qc.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

IL-17A contributes to lung fibrosis in a model of chronic pulmonary graft-versus-host disease Background: Chronic pulmonary graft-versus-host disease (cpGVHD) after hematopoietic cell transplant (HCT) manifests as progressive airway and parenchymal lung fibrosis. Based on our prior data, mice that undergo allogeneic HCT with Tbet-knockout donors (AlloTbet-/-) have increased lung Th17 cells and IL-17A and develop fibrosis resembling human cpGVHD. The role of IL-17A in posttransplant pulmonary fibrosis remains incompletely understood. We hypothesized that IL-17A is necessary for development of murine cpGVHD in this model. Methods: AlloTbet-/- mice received weekly intraperitoneal anti-IL-17A or IgG (200μg/mouse) starting 2 weeks post-HCT and were sacrificed after week 5. Histologic airway and parenchymal fibrosis was semi-quantitatively graded in a blinded fashion. Lung cells and proteins were measured by flow cytometry, ELISA, and multi-cytokine assays. Results: Anti-IL-17A modestly decreased airway and parenchymal lung fibrosis, along with a striking reduction in pulmonary neutrophilia, IL-6, MIP-1α, MIP-1β, CXCL1, and CXCL5 in AlloTbet-/- mice. Additionally, anti-IL-17A decreased CCL2, inflammatory monocytes and macrophages, and Th17 cells. Conclusions: In the setting of murine AlloHCT with Tbet-/- donors, IL-17A blockade decreases fibrotic features of cpGVHD. This may be mediated by the observed reduction in neutrophils and/or specific lung monocyte and macrophage populations, or alternatively via a direct effect on fibroblasts. Collectively, our results further suggest that anti-IL-17A strategies could prove useful in preventing alloimmune-driven fibrotic lung diseases. * First two authors contributed equally. Disclosure: The authors of this manuscript have no conflicts of interest to disclose. Funding: Funding was provided by NIH / NHLBI 1P50-HL084917-01 (SCCOR) (to SMP, TM, KG), NIH 1 K24 HL91140-01A2 (to SMP), Lung Transplant Foundation (to SMP), ISHLT Norman E. Shumway Career Development Award (to TM), and Steadman award (to WCM) Corresponding Author: Tereza Martinu, Address: 585 University Avenue, PMB 11-128, Toronto, ON Canada M5G 2N2, Email: tereza.martinu@uhn.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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.