Transplantation

The utility of ECMO, not just after but also during Liver Transplantation No abstract available

Impact of a Mobile Health Intervention on Long-Term Nonadherence After Lung Transplantation: Follow-up After a Randomized Controlled Trial Background: In a randomized controlled trial (RCT), lung transplant recipients (LTRs) using a mobile health intervention, Pocket Personal Assistant for Tracking Health (Pocket PATH), showed better adherence to the medical regimen than LTRs receiving usual care during the first year posttransplant. We examined whether these effects were maintained beyond the trial’s end, and evaluated other potential risk factors for long-term nonadherence. Methods: Adherence in eight areas was evaluated at follow-up in separate LTR and family caregiver (collateral) assessments. Pocket PATH and usual care groups’ nonadherence rates were compared; multivariable regression analyses then examined and controlled for other patient characteristics’ associations with nonadherence. Results: 105 LTRs (75% of survivors) were assessed (M=3.9 years posttransplant, SD=0.8). Nonadherence rates in the past month were 23%-81% for self-care and lifestyle requirements (diet, exercise, blood pressure monitoring, spirometry), 13%-23% for immunosuppressants and other medications, and 4% for tobacco use, with 31% clinic appointment nonadherence in the past year. In multivariable analysis, the Pocket PATH group showed lower risk of nonadherence to lifestyle requirements (diet/exercise) than the usual care group (p<.05). Younger age and factors during the first year posttransplant (acute graft rejection, chronically elevated anxiety, less time rehospitalized, nonadherence at the final RCT assessment) were each associated with nonadherence in at least one area at follow-up (p’s<.05). Conclusion: Pocket PATH did not have sustained impact on most areas of the regimen, although we identified other risk factors for long-term nonadherence. Future work should explore strategies to facilitate sustained effects of mobile health interventions. Funding: Preparation of this article was supported in part by Grant TL1TR000145 from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH), Rockville, MD, and Grant R01NR010711 from the National Institute of Nursing Research of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Disclosure: The authors declare no conflicts of interest. Address for Correspondence: Mary Amanda Dew, PhD, University of Pittsburgh School of Medicine and Medical Center, 3811 O’Hara Street, Pittsburgh, PA 15213. 412-624-3373, fax: 412-586-9255, email: dewma@upmc.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Plasmacytoid dendritic cell driven induction of Tregs is strain-specific and correlates with spontaneous acceptance of kidney allografts Background: DBA/2J kidney allografts, but not heart allografts, are spontaneously accepted indefinitely in C57BL/6 (B6) mice, through regulatory tolerance mechanism dependent on Foxp3+ cells. In contrast, B6 kidneys are rejected within a week in DBA/2J recipients. We hypothesized that the tolerogenic difference of the kidneys might be due to differences in number or function of plasmacytoid dendritic cells (pDCs), since these cells are potent inducers of Foxp3+ cells. Methods: pDCs from murine bone marrow, native kidneys, and spontaneously accepted kidney allografts were analyzed using flow cytometry and immunohistochemical staining. Naïve T cells were co-cultured with pDCs in specific strain combinations and analyzed for FoxP3 induction and functionality. MEK/ERK and NFB inhibitors were used to assess the Treg induction pathways. pDCs and T cell cultures were adoptively transferred prior to heterotopic heart transplantation to assess allograft survival. Results: DBA/2J pDCs were more potent in inducing Foxp3+ in B6 T cells than the reverse combination, correlating with survival of the kidney allografts. Foxp3 induction by pDCs in vitro was dependent on pDC viability, immaturity, and class II MHC mismatch, and blocked by MEK/ERK and NFκB inhibition. pDC-induced Foxp3+ T cells suppressed proliferation of B6 T cells in vitro, and adoptive transfer into B6 recipients two weeks prior to heterotopic DBA/2J heart transplantation resulted in prolonged allograft survival. Conclusions: These data suggest that pDC-induced Tregs are dependent on down-stream signaling effects and strain-dependent, MHC class II disparity with naïve T cells, which may explain organ and strain specific differences in spontaneous tolerance. * N.O., T.O., and D.K.N. contributed equally to this work Conflict of Interest Statement: Manuscript Title: Plasmacytoid dendritic cell driven induction of Tregs is strain-specific and correlates with spontaneous acceptance of kidney allografts Disclosure Statement of Financial Interest: Manuscript Title: Plasmacytoid dendritic cell driven induction of Tregs is strain-specific and correlates with spontaneous acceptance of kidney allografts Address correspondence to Alessandro Alessandrini, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, Phone: 617-643-4820; Fax: 617-724-3901; E-mail: aalessandrini@partners.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Is it time to make renal transplantation referral mandatory? No abstract available

First European Case of Simultaneous Liver and Pancreas Transplantation as Treatment of Wolcott-Rallison Syndrome in a Small Child Background: The concept of organ transplantation as treatment for complex genetic conditions including Wolcott-Rallison syndrome (WRS) continues to show promise. Liver transplantation is essential for survival of patients with WRS, and pancreas transplantation cures their type I diabetes mellitus. Methods: The recipient, a 3-year-old girl weighing 14 kg at the time of transplantation, suffered from major complications of WRS including repetitive liver failure episodes and poorly controlled diabetes. The patient underwent a non-acute, combined, simultaneous liver and pancreas transplantation from a paediatric donor without us the en bloc technique. Results: Well-preserved graft functions at 2-year follow-up with normal liver and pancreas function. Conclusions: This is the first case report of simultaneous liver and pancreas transplantation as treatment of WRS in a small child in Europe. Two-year follow-up demonstrates that organ transplantation can halt life-threating recurrent liver failure episodes and cure type 1 diabetes. Financial disclosure: All authors declare no financial disclosures for this work. Conflicts of interest: The authors declare no conflicts of interest. Ethics statement: This work was exempted from approval from an ethics’ board. Patient consent: Informed consent has been obtained from the parents. Corresponding Author: Johan Nordström, Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, and Department of Transplantation Surgery, Karolinska University Hospital, SE-14186 Stockholm, SwedenEmail: johan.nordstrom@sll.se Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Metformin attenuates cyclosporine A-induced renal fibrosis in rats Background: The aim of the present study was to investigate the therapeutic potential of metformin in preventing cyclosporine A-induced nephrotoxicity. Methods: Three groups of adult male Sprague-Dawley rats were treated with vehicle, cyclosporine A, and cyclosporine A + metformin for 4 weeks following one week on low sodium diet, respectively. At the end of treatment, all animals were sacrificed, and the samples of kidney, urine, and blood were collected for functional, morphological, and molecular biological evaluation. Results: Metformin effectively prevented cyclosporine A-induced renal dysfunction with increased creatinine clearance rate, reduced blood urea nitrogen and serum creatinine, as well as less proteinuria in comparison to the cyclosporine A group. Morphologically, metformin ameliorated cyclosporine A-induced renal fibrosis and tissue collapse in the areas of arteries, glomeruli and proximal tubules. We further demonstrated that the anti-fibrotic effects of metformin in kidneys treated with cyclosporine A were associated with decreased phosphorylation of ERK1/2. Conclusions: In conclusion, our study revealed new therapeutic potential of metformin to attenuate calcineurin inhibitor-induced renal fibrosis, which was closely related to the suppression of MEK/ERK1/2 pathway. * These authors contributed equally to the work and should be regarded as co-first author. # These authors should be considered as co-correspondence authors for their equal contribution in this work. Disclosure: The authors declare no conflict of interests. Funding: The work was supported by grants from National Natural Science Foundation of China (81370847 and 81702618). Correspondence information: Jun-Meng Zheng, Department of Cardiothoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Tel: 86-20-34070153. Fax: 86-20-34070402. Email: zhengjm27@mail.sysu.edu.cn Shan-Ying Liu, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China Tel: 86-20-81332601. Fax: 86-20-81332601. Email: liushany@mail.sysu.edu.cn Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ileostomy after intestinal transplantation: the first in depth report on techniques, complications, and outcomes Background: Temporary ileostomy during intestinal transplantation (ITx) is the standard technique for allograft monitoring. A detailed analysis of the ITx ileostomy has never been reported. Methods: A retrospective review of a single-center ITx database was performed. The analysis was divided into ileostomy formation and takedown episodes. Results: 135 grafts underwent ileostomy formation and 79 underwent ileostomy takedown. Median age at ITx was 7.7 yrs and weight was 23 kg. Allograft types were intestine (22%), liver/intestine (55%), multivisceral (16%), modified multivisceral (7%). 64% had 1-stage ITx whereas 36% required 2-staged ITx. Final ileostomy types were end (20%), loop (10%), distal blow-hole (59%) and proximal blow-hole (11%). Ileostomy formation: 31 grafts had complications (23%) including prolapse (26%), ischemia (16%), parastomal hernia (19%). 12 required surgical revision. There were no significant differences in graft type, ileostomy type, survival and ileostomy takedown rate between grafts with and without complications. Colon inclusive grafts had higher complication rates (p = 0.002). Ileostomy takedown: Ileostomy takedown occurred at a median of 422 days post-ITx. 25 complications occurred after 22 takedowns (28%) including SBO (27%) and abscess (18%). 15 grafts required surgical correction. Recipients with complications had longer hospital stay (17 vs. 9 days, p = 0.001) than those without complications. Graft type, ileostomy type and survival were not different. Conclusions: The first of its kind analysis of the surgical ileostomy after ITx reveals that most recipients can undergo successful ileostomy formation/takedown, complication rates are significant but within an acceptable range, and that complications do not affect survival. This study demonstrates that the routine use of transplant ostomies remains an acceptable practice after intestinal transplantation. However true analysis of risk and benefit will require a randomized, control trial. The authors declare no conflicts of interest. Corresponding author: Douglas G. Farmer, MD, 757 Westwood Blvd, Suite 8501E, Los Angeles, CA, 90095, 310-267-9612, dgfarmer@mednet.ucla.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Long-term seroprotection of varicella-zoster immunization in pediatric liver transplant recipients Background: Chickenpox is a highly contagious vaccine-preventable disease that can lead to severe complications, especially in immunocompromised patients. Varicella-zoster virus (VZV) vaccine appears to be safe and immunogenic in pediatric solid organ transplant recipients, but there are few data on the long-term vaccine-induced seroprotection. Methods: In this prospective interventional study we offered two doses of VZV vaccine to all eligible and nonseroprotected children seen 1 year after liver transplant. Vaccine responses were measured 1 month later and yearly thereafter. Vaccine safety was closely monitored. A supplementary dose was administered if protective levels were not reached/maintained. Results: Among 121 enrolled patients, 49 were vaccinated and followed during 5.5 years (IQR 3.7-8.0). Their seroconversion rate reached 100% (97.5% confidence interval [CI] 92.7-100). Low VZV-antibody concentration (≤400 UI/L) after the first 1-2 dose/s was associated with the need for a supplementary dose (odds ratio 15.0; 95% CI 3.4-67.0, p=0.001) and was given to 31% (15/47) of children at 1.1 year (IQR [interquartile range] 0.9-3.9). Although antibody concentrations declined during follow-up, 96% (95% CI 86.0-99.5) of patients maintained protective antibody concentrations at a median of 5.5 years post vaccination. One breakthrough disease was identified. Conclusion: VZV immunization of pediatric solid organ transplant recipients confers sustained seroprotection. Clinical Trial Notation: This study is registered in Clinical trials.gov: no. NCT00492739. Disclosure: The authors have no conflicts of interest to disclose. Funding: Research grants from Geneva University Hospitals and the Center for Vaccinology and Neonatal Immunology, University of Geneva. Corresponding author: Professor Klara Posfay-Barbe, MD, MS, Pediatric Infectious Diseases Unit, Children’s Hospital, Geneva University Hospitals, 6 Rue Willy-Donzé, 1211 Geneva 14, Switzerland. Phone: +41 22 372 5462, Fax: +41 22 372 5490, E-mail: Klara.PosfayBarbe@hcuge.ch Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Kidney after Liver Transplantation Matched-Pair Analysis: Are Kidneys Allocated to Appropriate Patients to Maximize Their Survival? Background: Kidney after liver transplantation (KALT) is the best therapeutic option for patients with end-stage renal disease after liver transplantation (OLT). New allocation policies prioritize kidneys to patients in renal failure within the first year following OLT. There is little data on how kidney quality, measured by kidney donor profile index (KDPI), impacts KALT survival outcomes. Methods: The UNOS database was queried for adult KALT recipients from 1988-2015 and compared to their paired kidney transplant alone (KTA) recipients. 745 pairs were stratified into three KDPI sub-groups and compared patient survival, graft survival and death-censored graft survival among matched-paired recipients. Results: Overall, KTA recipients had superior patient and graft survival compared to the KALT group. KTA patient survival was superior for all three KDPI sub-group analysis. KTA graft survival was superior compared to KALT recipients of KDPI 21-85% kidneys. Inferior graft half-life was observed in KALT vs KTA recipients with KDPI 21-85% and >85%. Conclusions: From a utilitarian perspective, it is important that kidneys are allocated to recipients that are able to maximize their benefit from the full life of the organ. In KTA recipients, graft quality correlates directly to graft survival. However, in KALT patients receiving the matched-pair kidneys of the KTA recipients, patient mortality, rather than kidney quality, dictates graft survival significantly. As allocation practices continue developing, utilization of expanded criteria kidneys that better match anticipated patient and graft survival should be strongly considered to maximize the benefits of limited resources for the greatest number of patients. Disclosures: The authors declare no conflicts of interest Corresponding Author: Luis A. Fernandez, MD, FACS, Professor, Department of Surgery, Division of Transplantation, 600 Highland Ave BX7375 Clinical Science CNTR-H4 Madison, WI 53792-3284, Phone: (608) 263-9903, E-mail: luisf@surgery.wisc.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The Authors’ Reply to Letter to the Editor, Re: Biliary Bicarbonate, pH and Glucose Are Suitable Biomarkers of Biliary Viability During Ex Situ Normothermic Machine Perfusion of Human Donor Livers No abstract available