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Publisher: John Wiley and Sons   (Total: 1592 journals)

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Showing 1 - 200 of 1592 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 13, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 66, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 54, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 175, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 6, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 37, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 5)
Addiction     Hybrid Journal   (Followers: 36, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 15, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 283, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 18, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 11)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 16, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 155, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 93, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 35, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 13, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 17, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 38, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 300, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 4, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 18, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 10, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 143, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 20)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 169)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 236, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 49, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 26, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 18, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 93, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 52, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 73, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 183, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 51, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 32, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 30, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 27, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 13, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 270, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 55, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 330, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (Followers: 1, SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 3, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 47, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 13, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 6, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 15, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 433, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 6, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 74, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 23, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 37, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 18, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 5, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 160, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 7, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 250, SJR: 2.083, h-index: 125)

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Journal Cover American Journal of Transplantation
  [SJR: 2.792]   [H-I: 140]   [18 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1600-6135 - ISSN (Online) 1600-6143
   Published by John Wiley and Sons Homepage  [1592 journals]
  • Transplant Recipients are Vulnerable Under the Medicare Part D Benefit
    • Authors: Lisa M. Potter; Angela Q. Maldonado, Krista L. Lentine, Mark A. Schnitzler, Zidong Zhang, Gregory P. Hess, Edward Garrity, Bertram L. Kasiske, David A. Axelrod
      Abstract: Transplant immunosuppressants are often used off-label due to insufficient randomized prospective trial data to achieve organ-specific US Food and Drug Administration (FDA) approval. Transplant recipients who rely on Medicare Part D for immunosuppressant drug coverage are vulnerable to coverage denial for off-label prescriptions, unless use is supported by Centers for Medicare & Medicaid Services (CMS)-approved compendia. An integrated data set including national transplant registry data and 3 years of dispensed pharmacy records was used to identify the prevalence of immunosuppression use that is both off-label and not supported by CMS-approved compendia. Numbers of potentially vulnerable transplant recipients were identified. Off-label and off-compendia immunosuppression regimens are frequently prescribed (3-year mean: lung 66.5%, intestine 34.2%, pancreas 33.4%, heart 21.8%, liver 16.5%, kidney 0%). The annual retail cost of these at-risk medications exceeds $30 million. This population-based study of transplant immunosuppressants vulnerable to claim denials under the Medicare Part D drug benefit demonstrates a substantial gap between clinical practice, current FDA approval processes, and policy mandates for pharmaceutical coverage. This coverage barrier reduces access to life-saving medications for patients without alternative resources and may increase the risk of graft loss and death from medication non-adherence.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-15T08:30:30.905811-05:
      DOI: 10.1111/ajt.14703
       
  • A Novel Technique for En Bloc Kidney Transplantation from Infant Donors
           with Extremely Low Body Weight by using the Distal Abdominal Aorta as an
           Outflow Tract
    • Authors: Helong Dai; Longkai Peng, Fenghua Peng, Gongbin Lan, Yu Wang, Jingjing Chen, Lei Liu, Chen Gao, Yong Guo, Chunhua Fang, Manhua Nie, Wang Long, Shaojie Yu
      Abstract: Pediatric kidney donors remain underutilized due to the high risk of postoperative thrombosis. To address this problem, we developed a novel en bloc kidney transplantation technique using donor thoracic aorta and the distal abdominal aorta as inflow and outflow tracts, respectively.Briefly, 8 kidneys from deceased infant donors under 5 months old and with low body weight (1.9-4.9 kg) were transplanted en bloc into 4 pediatric and 4 adult patients. The donor's common iliac artery or external iliac artery was anastomosed to the recipient's distal external iliac artery or inferior epigastric artery, respectively, as an outflow tract. Recipients received basiliximab or antithymocyte globulin as induction therapy followed by tacrolimus, mycophenolate mofetil, and prednisone but without prophylactic anticoagulation. Delayed graft function was observed in 1 patient but was reversed at 90 days post-transplant. Two patients had urine leakage, which was cured by conservative treatment. Two recipients developed lung infections that eventually cleared. No patients experienced post-transplant vascular thrombosis. After 1-1.5 years of follow up, all patients are well and have normal serum creatinine levels.In conclusion, this novel en bloc kidney transplantation technique using a modified arterial inflow and outflow tract can prevent vascular thrombosis and provide adequate graft function.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-15T04:11:04.63894-05:0
      DOI: 10.1111/ajt.14692
       
  • Study Rationale, Design and Pre-Transplant Alloantibody Status: A First
           Report of Clinical Trials in Organ Transplantation in Children-04
           (CTOTC-04) in Pediatric Heart Transplantation
    • Authors: Warren A. Zuckerman; Adriana Zeevi, Kristen L. Mason, Brian Feingold, Carol Bentlejewski, Linda J. Addonizio, Elizabeth D. Blume, Charles E. Canter, Anne I. Dipchand, Daphne T. Hsu, Robert E. Shaddy, William T. Mahle, Anthony J. Demetris, David M. Briscoe, Thalachallour Mohanakumar, Joseph M. Ahearn, David N. Iklé, Brian D. Armstrong, Yvonne Morrison, Helena Diop, Jonah Odim, Steven A. Webber
      Abstract: Anti-HLA donor-specific antibodies are associated with worse outcomes following organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor-specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase post-transplant morbidity and mortality. We address this clinical challenge in a prospective, multi-center, observational cohort study of children listed for heart transplantation (CTOTC-04). Outcomes were compared among sensitized recipients who underwent transplant with positive crossmatch, non-sensitized recipients, and sensitized recipients without positive crossmatch. Positive crossmatch recipients received antibody removal and augmented immunosuppression, while other recipients received standard immunosuppression with corticosteroid avoidance. This first CTOTC-04 report summarizes study rationale and design, and reports on pre-transplant sensitization status using solid phase technology. Risk factors for sensitization were explored. Of 317 screened patients, 290 were enrolled and 240 underwent transplantation. Core laboratory evaluation demonstrated that over half of patients were anti-HLA sensitized. Over 80% of sensitized patients had class I (with or without class II) HLA antibodies, and one third of sensitized patients had at least one HLA antibody with median fluorescence intensity (MFI) ≥8000. Logistic regression models demonstrated male sex, weight, congenital heart disease history, prior allograft and ventricular assist device are independent risk factors for sensitization.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-15T03:50:40.581043-05:
      DOI: 10.1111/ajt.14695
       
  • Effect of the iChoose Kidney Decision Aid in Improving Knowledge about
           Treatment Options among Transplant Candidates: a Randomized Controlled
           Trial
    • Authors: Rachel E. Patzer; Laura McPherson, Mohua Basu, Sumit Mohan, Michael Wolf, Mariana Chiles, Allison Russell, Jennifer C. Gander, John J. Friedewald, Daniela Ladner, Christian P. Larsen, Thomas Pearson, Stephen Pastan
      Abstract: We previously developed a mobile- and web-based decision aid (iChoose Kidney) that displays individualized risk estimates of survival and mortality, for the treatment modalities of dialysis versus kidney transplantation. We examined the effect of iChoose Kidney on change in transplant knowledge and access to transplant in a randomized controlled trial among patients presenting for evaluation in three transplant centers. A total of 470 patients were randomized to standard transplantation education (control) or standard education plus iChoose Kidney (intervention). Change in transplant knowledge (primary outcome) among intervention vs. control patients was assessed using 9-items in pre- and post-evaluation surveys. Access to transplant (secondary outcome) was defined as a composite of waitlisting, living donor inquiries, or transplantation. Among 443 patients (n=226 intervention; n=216 control), the mean knowledge scores were 5.1 ± 2.1 pre- and 5.8 ± 1.9 post-evaluation. Change in knowledge was greater among intervention (1.1 ± 2.0) vs. control (0.4 ± 1.8) patients (p
      PubDate: 2018-02-15T03:50:37.115387-05:
      DOI: 10.1111/ajt.14693
       
  • Impact of Ureteral Stricture and Treatment Choice on Long Term Graft
           Survival in Kidney Transplantation
    • Authors: E Arpali; T Al-Qaoud, E Martinez, R R Redfield, G E Leverson, D B Kaufman, J S Odorico, H W Sollinger
      Abstract: We aimed to evaluate the influence of urological complications occurring within the first year after kidney transplantation on long-term patient and graft outcomes, and sought to examine the impact of the management approach of ureteral strictures on long-term graft function. We collected data on urological complications occurring within the first-year post-transplant. Graft survivals, patient survival, and rejection rates were compared between recipients with and without urological complications. Male gender of the recipient, delayed graft function, donor age were found to be significant risk factors for urological complications after kidney transplantation (p
      PubDate: 2018-02-15T03:45:48.797278-05:
      DOI: 10.1111/ajt.14696
       
  • Reproductive Health in Women Following Abdominal Organ Transplant
    • Authors: Monika Sarkar; Kate Bramham, Michael Moritz, Lisa Coscia
      Abstract: Fertility is commonly impaired in women with end-stage kidney and liver disease although most women will have restoration of fertility within one year of transplant. Family planning is therefore critical to discuss with reproductive-aged transplant recipients in the early post-transplant period, in order to ensure timely initiation of contraception, and optimal timing for conception. For women seeking pregnancy the risks to the mother, graft, and baby should be discussed, including evaluation of immunosuppression safety and potential for adjusting medications prior to conception. With an increasing number of transplant patients now breastfeeding, immunosuppression safety in lactation continues to carry great importance.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-15T03:40:22.0099-05:00
      DOI: 10.1111/ajt.14697
       
  • Towards Donor Lung Recovery - Gene Expression Changes During Ex Vivo Lung
           Perfusion of Human Lungs
    • Authors: Jonathan C. Yeung; Ricardo Zamel, William Klement, Xiao-Hui Bai, Tiago N. Machuca, Thomas K. Waddell, Mingyao Liu, Marcelo Cypel, Shaf Keshavjee
      Abstract: We and others have demonstrated that acellular normothermic ex vivo lung perfusion of high-risk donor lungs can result in post-transplant outcomes equivalent to that of contemporaneous lung transplantation using standard donor lungs. However, the mechanism of this effect remains unclear. Given the restoration of cellular metabolic activity during normothermic perfusion, one possibility is that of lung healing via natural innate recovery mechanisms. We explored this by examining the gene expression changes occurring in human lungs during ex vivo lung perfusion. Human lungs clinically rejected for transplantation were perfused for 12h of EVLP with biopsies taken at the start, at 1h, at 3h, and then every 3h thereafter to 12h. Temporal changes were identified in 2585 genes using the Short Time-series Expression Miner and used for pathway analysis. Despite increases in endothelial markers of inflammation, circulating leukocyte cell-specific gene expression fell over 12h of EVLP, suggesting an interrupted inflammation response secondary to washout of circulating leukocytes. Analysis of these gene changes suggests lung recovery follows specific stages: cellular death, cellular preservation, cellular reorganization, and cellular invasion. Ex vivo lung perfusion may improve post-transplant lung function by washout of leukocytes and facilitating innate mechanisms of repair.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-15T03:30:30.156539-05:
      DOI: 10.1111/ajt.14700
       
  • VEGF mitigates histone induced pyroptosis in the remote liver injury
           associated with renal allograft ischemia-reperfusion injury in rats
    • Authors: Hailin Zhao; Han Huang, Azeem Alam, Qian Chen, Ka Chuen Suen, Jiang Cui, Qizhe Sun, Rele Ologunde, Wenwen Zhang, Qingquan Lian, Daqing Ma
      Abstract: Clinical evidence indicated a possible link between renal injury and remote liver injury. Herein, we investigated whether extracellular histone mediates remote hepatic damage following renal graft ischemia-reperfusion injury, whilst vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown-Norway renal graft was stored in 4°C preserving solution for 24 hours and then transplanted into Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery. Prolonged cold ischemia in renal grafts enhanced liver injury 24 hours after engraftment. Caspase-1, ASC, NLRP3 and AIM2 expression in hepatocyte, CD68+ infiltrating macrophages, tissue and serum IL-1β and IL-18 were greatly elevated, indicating that pyroptosis occurred in the liver and resulted in acute liver functional impairment. Blocking caspase-1 pathway decreased the number of necrotic hepatocytes. VEGF treatment suppressed the hepatocyte pyroptosis and liver function was partially restored. Our data suggested that renal allograft ischemia-reperfusion injury is likely associated with acute liver damage due to hepatocyte pyroptosis induced by histone and such injury may be protected by VEGF administration. VEGF, therefore, may serve as a new strategy against other remote organ injuries related to renal transplant.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-15T03:30:28.426721-05:
      DOI: 10.1111/ajt.14699
       
  • Response to Tumin's letter on Community social deprivation and solid organ
           transplant outcomes
    • Authors: Argiris Asderakis; Usman Khalid
      Abstract: We read with interest the letter of Tumin et al.1 referring to our paper on the association between socioeconomic deprivation and survival after pancreas transplantation in England2. Tumin et al. comment on the discrepancy in the results between the current study and those of our previous study on the role of social deprivation in pancreas outcomes in Wales3.We stressed that the Welsh index differs from the English one in its weighting of individual domains but importantly our study of the much smaller Welsh population was not powered to detect differences.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-14T13:50:21.36037-05:0
      DOI: 10.1111/ajt.14698
       
  • Incidence, Characterization and Impact of Newly Detected Donor Specific
           Anti-HLA Antibody in the First Year after Pediatric Heart Transplantation:
           A Report From the CTOTC-04 Study
    • Authors: A. I. Dipchand; S. Webber, K. Mason, B. Feingold, C. Bentlejewski, W. T. Mahle, R. Shaddy, C. Canter, E. D. Blume, J. Lamour, W. Zuckerman, H. Diop, Y. Morrison, B. Armstrong, D. Ikle, J. Odim, A. Zeevi,
      Abstract: Data on the clinical importance of newly detected donor specific antibodies (ndDSA) following pediatric heart transplantation is lacking despite mounting evidence of the detrimental effect of de novo DSA in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSA in the first year post-transplant in order to determine their incidence, pattern and clinical impact. One third of patients developed ndDSA; when present, these were mostly detected within the first 6 weeks after transplant suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of pre-existing DSA, patients with ndDSA had significantly more acute cellular rejection but not antibody-mediated rejection, and there was no impact on graft and patient survival in the first year post-transplant. Risk factors for ndDSA included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year following pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pre-transplant antibody screen. The impact on late graft and patient outcomes of first year ndDSA is being assessed in an extended cohort of patients.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-14T08:10:50.82803-05:0
      DOI: 10.1111/ajt.14691
       
  • A Liver for a kidney: Ethics of trans-organ paired exchange
    • Authors: Benjamin Samstein; Inmaculada de Melo-Martin, Sandip Kapur, Lloyd Ratner, Jean Emond
      Abstract: Living donation provides important access to organ transplantation, which is the optimal therapy for patients with end-stage liver or kidney failure. Paired exchanges have facilitated thousands of kidney transplants and enable transplantation when the donor and recipient are incompatible. However, frequently willing and otherwise healthy donors have contraindications to donation of the organ that their recipient needs. Trans-organ paired exchanges would enable a donor associated with a kidney recipient to donate a lobe of liver and a donor associated with a liver recipient to donate a kidney. This paper explores some of the ethical concerns that trans-organ exchange might encounter including unbalanced donor risks, the validity of informed consent, and effects on deceased organ donation.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-14T08:10:37.115088-05:
      DOI: 10.1111/ajt.14690
       
  • Kidney Exchange Match Rates in a Large Multicenter Clearinghouse
    • Authors: Courtenay M Holscher; Kyle Jackson, Eric KH Chow, Alvin G Thomas, Christine E Haugen, Sandra R DiBrito, Carlin Purcell, Matthew Ronin, Amy D Waterman, Jacqueline Garonzik Wang, Allan B Massie, Sommer E Gentry, Dorry L Segev
      Abstract: Kidney paired donation (KPD) can facilitate living donor transplantation for candidates with an incompatible donor, but requires waiting for a match while suffering the morbidity of dialysis. The balance between waiting for KPD versus desensitization or deceased donor transplantation relies on the ability to estimate KPD wait times. We studied donor/candidate pairs in the National Kidney Registry (NKR), a large multi-center KPD clearinghouse, between 10/2011-9/2015 using a competing risk framework. Among 1894 candidates, 52% were male, median age was 50 years, 66% were white, 59% had blood type O, 42% had PRA>80, and 50% obtained KPD through NKR. Median times to KPD ranged from 2 months for candidates with ABO-A and PRA 0, to over a year for candidates with ABO-O or PRA 98+. Candidates with PRA 80-97 and 98+ were 23% (95% CI: 6-37%) and 83% (78-87%) less likely to be matched than PRA 0 candidates. ABO-O candidates were 67% (61-73%) less likely to be matched than ABO-A candidates. Candidates with ABO-B or ABO-O donors were 31% (10-56%) and 118% (82-162%) more likely to match than those with ABO-A donors. Providers should counsel candidates about realistic, individualized expectations for KPD, especially in the context of their alternative treatment options.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-13T11:30:30.545365-05:
      DOI: 10.1111/ajt.14689
       
  • Observations on the ex situ perfusion of livers for transplantation
    • Authors: Christopher J. E. Watson; Vasilis Kosmoliaptsis, Caitlin Pley, Lucy Randle, Corinna Fear, Keziah Crick, Alexander E. Gimson, Michael Allison, Sara Upponi, Rebecca Brais, Ina Jochmans, Andrew J. Butler
      Abstract: Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with post-transplant peak transaminase levels. Lactate clearance occurred within 3 hours in 46 of 47 perfusions, and glucose rose initially during perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary non-function. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified 3 livers that developed cholangiopathy (peak pH7.5). In the 11 research livers where it could be studied, bile pH>7.5 discriminated between the 6 livers exhibiting>50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25-50% necrosis had a maximum pH 7.46. Liver viability during normothermic perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance and maintenance of acid-base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of post-transplant ischaemic cholangiopathy.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-08T10:52:11.445472-05:
      DOI: 10.1111/ajt.14687
       
  • Response to: Regarding “HIV protease inhibitors and mortality following
           kidney transplantation”
    • Authors: B A Shelton; D Sawinski, J E Locke
      Abstract: We thank Dr. Sullivan for his thoughtful commentary on our recent analysis of protease inhibitors (PI) and kidney transplant outcomes among HIV-infected kidney transplant recipients.(1, 2) He suggests that post-transplant PI use may be a marker of more advanced HIV infection, driven by genotypic evidence of HIV resistance to multiple classes of antiretroviral therapies. Thus, with a complicated HIV treatment history, the increased association of PIs with post-transplant mortality may actually be capturing the risk of death associated with antiretroviral resistance, rather than an impact of PIs themselves on outcomes.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-08T10:51:21.19814-05:0
      DOI: 10.1111/ajt.14688
       
  • The Pursuit of Happiness. The thin line between rights and duties
    • Authors: Davide Ghinolfi; Paolo De Simone
      Abstract: We read with some concern the paper by Halazun et al. on the use of elderly liver grafts in US (1). Even if more and more evidence is being accumulated about the favorable outcomes of liver transplantation from very old donors, (2) barriers to a wider use still exist and include both OPOs rules and skepticism from physicians. In 2015, 1673 patients (12.0%) died in US while waiting for a liver transplant, and 1227 (8.7%) were delisted due to increased severity of disease (2).This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-08T10:45:20.457194-05:
      DOI: 10.1111/ajt.14686
       
  • Antibody-mediated rejection in pediatric small bowel transplantation:
           Capillaritis is a major determinant of C4d positivity in intestinal
           transplant biopsies
    • Authors: Marion Rabant; Maud Racapé, Laetitia-Marie Petit, Jean Luc Taupin, Olivier Aubert, Julie Bruneau, Patrick Barbet, Olivier Goulet, Christophe Chardot, Caroline Suberbielle, Florence Lacaille, Danielle Canioni, Jean-Paul Duong Van Huyen
      Abstract: The diagnostic criteria for antibody-mediated rejection (ABMR) after small bowel transplantation (SBT) are not clearly defined, although the presence of Donor Specific Antibodies (DSA) has been reported to be deleterious for graft survival. We aimed to determine the incidence and prognostic value of DSA and C4d in pediatric SBT and to identify the histopathological features associated with C4d positivity. We studied all intestinal biopsies (IBx) obtained in the first year post-transplantation (n=345) in a prospective cohort of 23 children. DSAs and their capacity to fix C1q were identified using Luminex. Eighteen patients (78%) had DSA, and 9 had the capacity to fix C1q. Seventy-eight IBx (22.6%) were C4d positive. The independent determinants of C4d positivity were capillaritis grade 2 and 3 (OR 4.02, p=0.047 and OR 5.17, p=0.003 respectively), mucosal erosion/ulceration (OR 2.8, p=0.019), lamina propria inflammation grade 1 and 2/3 (OR 1.95, p=0.043 and OR 3.1, p=0.016, respectively) and chorion edema (OR 2.16, p=0.028). Complement-fixing DSA and repeated C4d positive IBx were associated with poor outcome (p=0.021 and p=0.001, respectively). Our results support that capillaritis should be considered as a feature of ABMR in SBT and identify C1q-fixing DSA and repeated C4d positivity as potential markers of poor outcome.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-03T14:30:22.405393-05:
      DOI: 10.1111/ajt.14685
       
  • Program-Specific Transplant Rate Ratios: Association with Allocation
           Priority at Listing and Posttransplant Outcomes
    • Authors: A Wey; S. K Gustafson, N Salkowski, J Pyke, B. L Kasiske, K Israni, J. J Snyder
      Abstract: SRTR is considering more prominent reporting of program-specific adjusted transplant rate ratios (TRRs). To enable more useful reporting of TRRs, SRTR updated the transplant rate models to explicitly adjust for components of allocation priority. We evaluated potential associations between TRRs and components of allocation priority that could indicate programs’ ability to manipulate TRRs by denying or delaying access to low-priority candidates. Despite a strong association with unadjusted TRRs, we found no candidate-level association between the components of allocation priority and adjusted TRRs. We found a strong program-level association between median laboratory model for end-stage liver disease score at listing and program-specific adjusted TRRs (r = 0.37; P < 0.001). The program-level association was likely confounded by regional differences in donor supply/demand and listing practices. In kidney transplantation, higher program-specific adjusted TRRs were weakly associated with better adjusted posttransplant outcomes (r = -0.14; P = 0.035) and lower adjusted waitlist mortality rate ratios (r = -0.15; P = 0.022), but these associations were absent in liver, lung, and heart transplantation. Program-specific adjusted TRRs were unlikely to be improved by listing candidates with high allocation priority and can provide useful information for transplant candidates and programs.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-03T14:25:22.60832-05:0
      DOI: 10.1111/ajt.14684
       
  • Recurrence of Eosinophilic Granulomatosis with Polyangitis after
           Orthotopic Heart Transplant
    • Authors: Ujjwal Rastogi; Ziad Sergie, Sean Pinney, Noah Moss
      Abstract: Eosinophilic granulomatosis with polyangitis (EGPA), previously referred to as Churg-Strauss syndrome, is a necrotizing small vessel vasculitis associated with eosinophilic infiltrates and extravascular granulomas. We report a case of a Caucasian woman successfully bridged to heart transplantation with a continuous flow left ventricular assist device (LVAD) who survived recurrence of EGPA in the allograft.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-02T04:00:37.935108-05:
      DOI: 10.1111/ajt.14679
       
  • Risk of ESRD in Prior Living Kidney Donors
    • Authors: Jennifer L. Wainright; Amanda M. Robinson, Amber R. Wilk, David K. Klassen, Wida S. Cherikh, Darren E. Stewart
      Abstract: We studied End Stage Renal Disease (ESRD) in living kidney donors (LKDs) who donated in the US between 1994 and 2016 (n=123,526), using Organ Procurement and Transplantation Network and Centers for Medicare and Medicaid Services data. 218 LKDs developed ESRD, with a median of 11.1 years between donation and ESRD. Absolute 20-year risk was low but not uniform, with risk associated with race, age, and sex and increasing exponentially over time. LKDs had increased risk of ESRD if they were male (adjusted Hazard Ratio(aHR): 1.75, 95% Confidence Interval (95%CI): 1.33-2.31), had higher BMI (aHR: 1.34 per 5 kg/m2, 95%CI: 1.10-1.64) or lower eGFR (aHR: 0.89 per 10 mL/min 95% CI: 0.80-0.99), were first degree relatives of the recipient (parent: (aHR: 2.01, 95% CI: 1.26-3.21); full sibling (aHR: 1.87, 95%CI: 1.23-2.84); identical twin (aHR: 19.79, 95%CI: 7.65-51.24)), or lived in lower SES neighborhoods at donation (aHR: 0.87 per $10k increase; 95%CI: 0.77-0.99). We found a significant interaction between donation age and race, with higher risk at older ages for white LKDs (aHR: 1.26 per decade, 95%CI: 1.04-1.54), but higher risk at younger ages for black LKDs (aHR: 0.75 per decade, 95%CI: 0.57-0.99). These findings further inform risk assessment of potential LKDs.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-02T04:00:36.495122-05:
      DOI: 10.1111/ajt.14678
       
  • Long- and short-term outcomes in renal allografts with deceased donors: A
           large recipient and donor genome-wide association study
    • Authors: Maria P. Hernandez-Fuentes; Christopher Franklin, Irene Rebollo-Mesa, Jennifer Mollon, Florence Delaney, Esperanza Perucha, Caragh Stapleton, Richard Borrows, Catherine Byrne, Gianpiero Cavalleri, Brendan Clarke, Menna Clatworthy, John Feehally, Susan Fuggle, Sarah A. Gagliano, Sian Griffin, Abdul Hammad, Robert Higgins, Alan Jardine, Mary Keogan, Timothy Leach, Iain MacPhee, Patrick B. Mark, James Marsh, Peter Maxwell, William McKane, Adam McLean, Charles Newstead, Titus Augustine, Paul Phelan, Steve Powis, Peter Rowe, Neil Sheerin, Ellen Solomon, Henry Stephens, Raj Thuraisingham, Richard Trembath, Peter Topham, Robert Vaughan, Steven H. Sacks, Peter Conlon, Gerhard Opelz, Nicole Soranzo, Michael E. Weale, Graham M. Lord,
      Abstract: Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.
      PubDate: 2018-02-01T20:00:02.651243-05:
      DOI: 10.1111/ajt.14594
       
  • American Journal of Transplantation: Volume 18, Number 2, January 2018
    • Abstract: On the cover this month: AJT presents the output from the 2017 Banff consortium for kidney allograft pathology (Haas et al, page 293), including revisions to the diagnostic criteria for T cell– and antibody-mediated kidney transplant rejection, specific criteria for chronic active T cell–mediated rejection, and prospects for integrative endpoints in clinical trials. Two Original Articles from Nankivell et al (page 364) and Lefaucheur et al (page 377) influence the new Banff recommendations regarding the relationship between T cell–mediated rejection and areas of interstitial scarring. We also present a new Banff classification for tissue engineering pathology in bioengineered organs and tissues for transplantation that will increasingly be used as prosthetic devices and tissue engineering become more common. Finally, be sure to read the “What's Hot, What’s New” feature from the 2017 American Transplant Congress! Cover image by Lauren Halligan, Duke University Department of Surgery.
      PubDate: 2018-01-30T10:27:36.896699-05:
      DOI: 10.1111/ajt.14646
       
  • Physical Frailty after Liver Transplantation
    • Authors: Jennifer C. Lai; Dorry L. Segev, Charles E. McCulloch, Kenneth E. Covinsky, Jennifer L. Dodge, Sandy Feng
      Abstract: Frailty is prevalent in liver transplant candidates, but little is known of what happens to frailty after liver transplantation. We analyzed data for 214 adult liver transplant recipients who had ≥1 frailty assessment using the Liver Frailty Index (LFI) at 3-(n=178), 6-(n=139), or 12-(n=107) months post-transplant [higher values=more frail]. “Frail” and “robust” were defined as LFI ≥4.5 and
      PubDate: 2018-01-30T03:26:54.224747-05:
      DOI: 10.1111/ajt.14675
       
  • DCD Donor Hemodynamics as Predictor of Outcome After Kidney
           Transplantation
    • Authors: H. Peters-Sengers; J.H.E. Houtzager, M.B.A. Heemskerk, M.M. Idu, R.C. Minnee, R.W. Klaasen, S.E. Joor, J.A.M. Hagenaars, P.M. Rebers, J.J. Homan van der Heide, J.I. Roodnat, F.J. Bemelman
      Abstract: Insufficient hemodynamics during agonal phase—i.e. the period between withdrawal of life-sustaining treatment and circulatory arrest—in Maastricht category III circulatory-death donors (DCD) potentially exacerbate ischemia/reperfusion injury. We included 409 Dutch adult recipients of DCD donor kidneys transplanted between 2006 and 2014. Peripheral oxygen saturation (SpO2–with pulse oximetry at the fingertip) and systolic blood pressure (SBP–with arterial catheter) were measured during agonal phase, and were dichotomized into minutes of SpO2>60% or SpO280 mmHg or SBP
      PubDate: 2018-01-30T02:16:17.338118-05:
      DOI: 10.1111/ajt.14676
       
  • Community social deprivation and solid organ transplant outcomes
    • Authors: Dmitry Tumin; Randi E. Foraker, Don Hayes, Joseph D. Tobias
      Abstract: We read with interest Asderakis and colleagues’ report on the association between greater socioeconomic deprivation scores and poorer patient and graft survival after pancreas transplantation in England. The English Index of Multiple Deprivation used in this study exemplifies the wealth of community-level data (7 domains, each comprising multiple indicators) which may be brought to bear on examining social disparities in transplant outcomes. With comparable data available in the US, Asderakis et al's use of community measures of social deprivation is clearly of international interest. Nevertheless, the lack of agreement between the present findings and this group's previous study of pancreas transplantation outcomes in Wales highlights some concerns about the utility of this approach. In the earlier study, the similar Welsh Index of Multiple Deprivation was not correlated with acute rejection or graft survival after pancreas transplantation.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-29T06:05:18.968642-05:
      DOI: 10.1111/ajt.14677
       
  • The Effects of Brain Death and Ischemia on Tolerance Induction are
           Organ-Specific
    • Authors: S G Michel; M L L Madariaga, G M I I LaMuraglia, V Villani, M Sekijima, E A Farkash, R B Colvin, D H Sachs, K Yamada, B R Rosengard, J S Allan, J C Madsen
      Abstract: We have previously shown that 12 days of high-dose calcineurin inhibition induced tolerance in MHC inbred miniature swine receiving MHC-mismatched lung, kidney, or co-transplanted heart/kidney allografts. However, if lung grafts were procured from brain dead donors, and transplanted alone, they were rejected within 19-45 days. Here, we investigated whether donor brain death with or without allograft ischemia would also prevent tolerance induction in kidney or heart/kidney recipients. Four kidney recipients treated with 12 days of calcineurin inhibition received organs from donors rendered brain dead for 4 hours. Six heart/kidney recipients also treated with calcineurin inhibition received organs from donors rendered brain dead for 4 hours, 8 hours or 4 hours with 4 additional hours of cold storage. In contrast to lung allograft recipients, all isolated kidney or heart/kidney recipients that received organs from brain dead donors achieved long term survival (> 100 days) without histologic evidence of rejection. Pro-inflammatory cytokine gene expression was upregulated in lungs and hearts, but not kidney allografts after brain death. These data suggest that the deleterious effects of brain death and ischemia on tolerance induction are organ-specific, which has implications in the application of tolerance to clinical transplantation.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-29T02:50:45.584516-05:
      DOI: 10.1111/ajt.14674
       
  • CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific
           T cells restricted by shared class I HLA molecules via presentation on
           donor cells
    • Authors: Philippe Gatault; Sally Al-Hajj, Johan Noble, Eloi Chevallier, Marie Piollet, Catherine Forconi, Catherine Gaudy-Graffin, Gilles Thibault, Elodie Miquelestorena-Standley, Jean Michel Halimi, Matthias Büchler, Roxane Lemoine, Christophe Baron
      Abstract: We aimed to determine the role of cytomegalovirus (CMV)-infected donor cells in the development of a CMV-specific immune response in kidney transplant recipients. We assessed the CMV pp65-specific immune response by using interferon-ɣ ELISPOT and dextramers in peripheral blood mononuclear cells from 115 recipients (D+R- 31, D+R+ 44, D-R+ 40) late after transplantation (mean 59±42 months). Receiving a kidney from a D+ donor resulted in a higher number of IFN-ɣ-producing anti-CMV T-cells (p=0.004). This effect disappeared with the absence of shared HLA class I specificities between donors and recipients (p=0.430). To confirm the role of donor cells in stimulating the expansion of newly developed CMV-specific CD8+ T cells after transplantation, we compared the number of HLA-A2–restricted CMV-specific CD8+ T cells in primo-infected recipients who received an HLA-A2 or non–HLA-A2 graft. The median of anti-CMV pp65 T cells restricted by HLA-A2 was very low for patients who received a non–HLA-A2 graft versus an HLA-A2 graft (300 [0-14638] vs 17972 [222-85594] anti-CMV pp65 CD8+ T cells/million CD8+ T cells, p=0.001). This adds new evidence that CMV-infected kidney donor cells present CMV peptides and drive an inflation of memory CMV-specific CD8+ T cells, likely because of frequent CMV replications within the graft.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-27T05:15:21.992057-05:
      DOI: 10.1111/ajt.14672
       
  • Causes and Timing of End-Stage Renal Disease after Living Kidney Donation
    • Authors: Arthur J. Matas; Danielle M. Berglund, David M. Vock, Hassan N. Ibrahim
      Abstract: End stage renal disease (ESRD) is a risk after kidney donation. We sought, in a large cohort of kidney donors to determine the causes of donor ESRD, the interval from donation to ESRD, the role of donor/recipient relationship, and the trajectory of the estimated GFR (eGFR) from donation to ESRD. Between 1/1/1963 thru 12/31/2015, 4030 patients underwent living donor nephrectomy at our center, and have had ascertainment of ESRD status. Of these, 39 have developed ESRD (mean age at ESRD, 62.4 ± 14.1 years; mean interval between donation and ESRD, 27.1 ± 9.8 years). Those developing ESRD were more likely to be males, smokers, younger at donation and to have donated to a first-degree relative. Of those with known cause of ESRD (n=25), 48% was due to diabetes and/or hypertension; only 2 had ESRD from a disease that would have affected 1 kidney (cancer). Of the 25 with ascertainable ESRD cause, 4 shared a similar etiology of ESRD with their recipient. Almost universally, eGFR change over time was stable, until new onset disease (kidney or systemic). Knowledge of factors contributing to ESRD after living kidney donation can improve donor selection and counseling, as well as long-term postdonation care.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-25T09:43:50.475615-05:
      DOI: 10.1111/ajt.14671
       
  • Biologic mechanisms and clinical consequences of pregnancy
           alloimmunization
    • Authors: Paige M. Porrett
      Abstract: Alloimmunization occurs during pregnancy when tissue antigens derived from the fetus and/or placenta prime maternal immune cells to divide and differentiate. For many women, the result of pregnancy alloimmunization is the formation of anti-HLA antibody that can endure for decades and preclude transplantation by limiting donor compatibility. Pregnancy alloimmunization may also generate memory B cells that can rapidly produce anti-HLA antibody after transplantation as well as pathogenic memory T cells which pose a threat to graft survival. However, emerging data suggest that pregnancy also programs the differentiation of anergic, dysfunctional, and regulatory T cell populations which may not mediate accelerated graft rejection. Hence, some of the immune mechanisms responsible for maternal immunologic tolerance of the fetus may persist into postpartum life and impact the response to an allograft. This review discusses these emerging data as well as the persistent knowledge gaps that impact women at multiple stages of their transplant care.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-25T09:25:26.519926-05:
      DOI: 10.1111/ajt.14673
       
  • Live nondirected uterus donors: Psychological characteristics and
           motivation for donation
    • Authors: A. M. Warren; G. Testa, T. Anthony, G.J. McKenna, G. B. Klintmalm, K. Wallis, E. C. Koon, R. T Gunby, L. Johannesson
      Abstract: Emerging research suggests that uterus transplantation is a viable option for women without a uterus who want to become pregnant and carry a child to term. Currently, no knowledge exists regarding nondirected uterus donors. This study (NCT 02656550) explored the baseline psychological characteristics of nondirected uterus donors at a single study site. Of the 62 potential donors who underwent initial screening, six nondirected donors were chosen and participated in uterus donation. Participants received a comprehensive evaluation, which included clinical history and psychological assessments. The mean age of the donors was 42 years; most (83%) were white/not Hispanic, and all had a college degree. Current depression was reported by two participants, past depression was reported in two participants, and past anxiety was reported in three participants. Based on several different psychological measures, donors had a higher general well-being than the normative sample, and none of the participants’ scores indicated psychological distress. All six women indicated that giving another woman an opportunity to carry her own child was a motivation for pursuing uterus donation. Further research on potential psychological motives and gains for the donor as well as long-term effects on donors is crucial for ethical practice.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-24T10:10:44.228844-05:
      DOI: 10.1111/ajt.14670
       
  • Ex vivo allotransplantation engineering: delivery of mesenchymal stem
           cells prolongs rejection-free allograft survival
    • Authors: Marc A Soares; Jonathan P Massie, William J Rifkin, Nakul Rao, April M Duckworth, Chin Park, Rohini L Kadle, Joshua A David, Piul S Rabbani, Daniel J Ceradini
      Abstract: Current pharmacologic regimens in transplantation prevent allograft rejection through systemic recipient immunosuppression, but are associated with severe morbidity and mortality. The ultimate goal of transplantation is prevention of allograft rejection while maintaining recipient immunocompetence. We hypothesized that allografts could be engineered ex vivo (after allotransplant procurement but prior to transplantation) using mesenchymal stem cell based therapy to generate localized immunomodulation without affecting systemic recipient immune competence. To this end, we evaluated the therapeutic efficacy of bone marrow derived mesenchymal stem cells in vitro and activated them towards an immunomodulatory fate by priming in inflammatory or hypoxic microenvironments. Using an established rat hind limb model for allotransplantation, we were able to significantly prolong rejection-free allograft survival with a single perioperative ex vivo infusion of bone marrow derived mesenchymal stem cells through the allograft vasculature, in the absence of long-term pharmacologic immunosuppression. Critically, transplanted rats rejected a second, non-engineered skin graft from the same donor species to the contralateral limb at a later date, demonstrating that recipient systemic immunocompetence remained intact. This study represents a novel approach in transplant immunology, and highlights the significant therapeutic opportunity of the ex vivo period in transplant engineering.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-23T02:18:18.619482-05:
      DOI: 10.1111/ajt.14668
       
  • Heterogeneity of memory B cells
    • Authors: Anita S Chong; M. Javeed Ansari
      Abstract: Potential solid-organ transplant recipients broadly sensitized to HLA have long wait times, low transplant rates and poor outcomes. The new kidney allocation system has improved access to the most highly sensitized recipients; however, their long-term outcomes are unknown. Emerging data suggest that memory B cell repertoire is broader than the plasma cell repertoire, therefore, despite refinements in anti-HLA antibody detection technology, donor-specific HLA- specific memory B cells may in fact be present in some, if not most, highly sensitized recipients with no detectable donor-specific antibodies. In addition, new findings have underscored the heterogeneity in memory B cell generation, and in the signals that determine memory versus plasma cell fate during primary antigen encounter, as well as memory B cell differentiation upon antigen reencounter into plasma cells or reentry into germinal centers to subsequently emerge as higher affinity and class-switched plasma cells. Thus, heterogeneity memory B cells generation may affect the efficacy of specific immunomodulation during the recall response. We propose that the ability to quantify donor-specific B cell in transplant recipients is urgently required to provide insights into the mechanisms of sensitization and recall, and for the early detection of acute and chronic AMR.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-23T02:06:13.941938-05:
      DOI: 10.1111/ajt.14669
       
  • Clostridium difficile Infection is Associated with Graft Loss in Solid
           Organ Transplant Recipients
    • Authors: A. Cusini; C. Béguelin, S. Stampf, K. Boggian, C. Garzoni, M. Koller, O. Manuel, P. Meylan, N. J. Mueller, H. Hirsch, M. Weisser, C. Berger, C. van Delden,
      Abstract: Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched two control subjects per case by age at transplantation, sex and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred and fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10′000 patient days was 0.47 (95% confidence interval (CI): [0.38, 0.58]), with the highest rate in lung (1.48, 95% CI: [0.93, 2.24]). In multivariable analysis, proven infections (hazard ratio (HR) 2.82, 95% CI: [1.29, 6.19]) and antibiotic treatments (HR=4.51, 95% CI: [2.03, 10.0]) during the preceding three months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI post-transplantation had an increased risk of graft loss (HR=2.24, 95% CI: [1.15, 4.37], p=0.02). These findings may help to improve the management of SOT recipients.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-19T01:01:00.040127-05:
      DOI: 10.1111/ajt.14640
       
  • Recognition of i-IF/TA as a component of the T cell-mediated rejection
           spectrum: Unselected population approach versus random case selection
    • Authors: Carmen Lefaucheur; Denis Viglietti, Alexandre Loupy
      Abstract: Whereas chronic active T cell-mediated rejection (TCMR) has long been acknowledged by the Banff classification, the spectrum of chronic active TCMR lesions was until now restricted to chronic allograft arteriopathy, without any consideration for chronic tubulo-interstitial injury following the acute infiltration of the interstitium and tubules by T cells and macrophages characterizing acute TCMR. To date, active TCMR has been defined only in the non-fibrotic areas of the allograft cortex and this artificial compartmentalization of the alloreactive response seems to have little biological relevance. The recognition of interstitial inflammation in fibrotic areas (i-IF/TA) and tubulitis in atrophic tubules (t-IF/TA) as components of chronic active TCMR represents a step forward in our understanding of the temporality and natural history of the TCMR process, consistent with the natural history of antibody-mediated rejection, which has been modified in the current era of more potent immunosuppression with the emergence of subclinical and chronic active forms.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-17T08:40:18.253842-05:
      DOI: 10.1111/ajt.14667
       
  • Establishment of practical recellularized liver graft for blood perfusion
           using primary rat hepatocytes and liver sinusoidal endothelial cells
    • Authors: H Kojima; K Yasuchika, K Fukumitsu, T Ishii, S Ogiso, Y Miyauchi, R Yamaoka, T Kawai, H Katayama, E.Y Yoshitoshi-Uebayashi, S Kita, K Yasuda, N Sasaki, J Komori, S Uemoto
      Abstract: Tissue decellularization produces a three-dimensional scaffold that can be potentially used to fabricate functional liver grafts following recellularization. An inappropriate cell distribution and clotting during blood perfusion hinder the practical use of recellularized livers. Here, we aimed to establish a seeding method for the optimal distribution of parenchymal and endothelial cells, and to evaluate the effect of liver sinusoidal endothelial cells (LSECs) in the decellularized liver. Primary rat hepatocytes and LSECs were seeded into decellularized whole-liver scaffolds via the biliary duct and portal vein, respectively. Biliary duct-seeding provided appropriate hepatocyte distribution into the parenchymal space, and portal vein-seeded LSECs simultaneously lined the portal lumen, maintaining function and morphology. Hepatocytes co-seeded with LSECs retained their function compared with those seeded alone. Platelet deposition was significantly decreased and hepatocyte viability was maintained in the co-seeded group after extracorporeal blood perfusion. In conclusion, our seeding method provided optimal cell distribution into the parenchyma and vasculature according to the three-dimensional structure of the decellularized liver. LSECs maintained hepatic function, and supported hepatocyte viability under blood perfusion in the engineered liver graft owing to their antithrombogenicity. This recellularization procedure could help produce practical liver grafts with blood perfusion.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-16T12:05:22.654192-05:
      DOI: 10.1111/ajt.14666
       
  • Prospective randomized study of conversion from tacrolimus to cyclosporine
           A to improve glucose metabolism in patients with posttransplant diabetes
           mellitus after renal transplantation
    • Authors: Karl M Wissing; Daniel Abramowicz, Laurent Weekers, Klemens Budde, Thomas Rath, Oliver Witzke, Nilufer Broeders, Mireille Kianda, Dirk RJ Kuypers
      Abstract: Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) as compared to cyclosporine A (CYC). The present 12-months, multi-center, investigator-driven, prospective, randomized study was designed to assess whether conversion from tacrolimus to cyclosporine A can reverse PTDM after renal transplantation. Predominantly Caucasian patients with PTDM according to the 2005 ADA criteria were randomized to either replacement of tacrolimus with cyclosporine or continuation of their tacrolimus-based regimen after stratification for type of glucose-lowering therapy, steroid therapy and hepatitis C status. At 12 months, 14 of 41 patients with complete data in the CYC arm (34%; 95%CI 19% to 49%) were free of diabetes whereas this was only the case in 4 of 39 patients (10%; 95%CI 3% to 20%) in the TAC arm (P=0.01). At 12 months, 39% of patients in the CYC arm were off glucose-lowering medication vs. 13% of patients in the tacrolimus arm (P=0.01). The CYC group decreased HbA1c over the 12-month follow up resulting in significantly lower levels as compared to the TAC group (6.0±0.9% vs. 7.1±1.7% at 12 months; P=0.002). In conclusion, replacement of tacrolimus with cyclosporine significantly improves glucose metabolism and has the potential to reverse diabetes during the first year after conversion. (EU Clinical Trials Register no. 2006-001765-42).This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-16T09:05:20.44982-05:0
      DOI: 10.1111/ajt.14665
       
  • Comments on Famulski and Halloran AJT i-IFTA letter
    • Authors: Michael Mengel; Mark Haas
      Abstract: Based on application of molecular diagnostics, including a molecular TCMR classifier, Famulski and Halloran [1] emphasize the lack of specificity of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) in renal allografts, and imply that adding a category of chronic active (CA) T cell-mediated rejection (TCMR) based on i-IFTA to the Banff classification is a potentially serious error. However, before this conclusion can be accepted, the basis for the consensus decision to add this CA TCMR category to the Banff 2017 classification [2] must be considered in its entirety.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-15T23:35:28.611713-05:
      DOI: 10.1111/ajt.14664
       
  • Decreasing Deceased Donor Transplant Rates among Children (≤ 6 years)
           under the New Kidney Allocation System
    • Authors: Brittany A. Shelton; Deirdre Sawinski, Christopher Ray, Rhiannon D. Reed, Paul A. MacLennan, Justin Blackburn, Carlton J. Young, Stephen Gray, Megan Yanik, Allan Massie, Dorry L. Segev, Jayme E. Locke
      Abstract: The Kidney Allocation System (KAS) was implemented in December 2014 with unknown impact on the pediatric waitlist. To understand the effect of KAS on pediatric registrants, deceased donor kidney transplant (DDKT) rate was assessed using interrupted time series analysis and time-to-event analysis. Two allocation eras were defined with an intermediary washout period: Era 1 (01/01/2013-09/01/2014), Era 2 (09/01/2014-03/01/2015), and Era 3(03/01/2015-03/01/2017). When using Cox proportional hazards, there was no significant association between allocation era and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97-1.18, p=0.17). However, this was not consistent across all subgroups. Specifically, while highly sensitized pediatric registrants were consistently less likely to be transplanted than their less sensitized counterparts, this disparity was attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01-0.14, p
      PubDate: 2018-01-15T03:35:28.150996-05:
      DOI: 10.1111/ajt.14663
       
  • Reply to letter to editor; re Famulski and Halloran
    • Authors: Brian J. Nankivell
      Abstract: Thank you for the opportunity to respond to an alternative perspective of i-IFTA presented by Drs Famulski and Halloran, which concentrates on a failed correlation with a singular molecular classifier in late indication-biopsies of mixed antibody-mediated rejection (1). Two recent cohort studies of i-IFTA started much earlier post-transplant, and both found strong correlations with TCMR that was independent of DSA (2, 3). Inferences and conclusions are not directly transferrable between these different populations.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-11T02:40:24.552613-05:
      DOI: 10.1111/ajt.14662
       
  • Immunosuppressive effect of the gut microbiome altered by high-dose
           tacrolimus in mice
    • Authors: Z. Zhang; L. Liu, H. Tang, W. Jiao, S. Zeng, Y. Xu, Q. Zhang, Z. Sun, A. Mukherjee, X. Zhang, X. Hu
      Abstract: The alterations induced in gut microbiota by tacrolimus may affect immune function and organ transplantation. Mice were treated with a high-dose of tacrolimus for 14 days. The fecal microbiota were analyzed by pyrosequencing the 16S rRNA genes, and the effect on metabolism was predicted using the sequence data. The subgroups of T cells in the serum, gut-associated lymphoid tissue and draining lymph nodes were determined by flow cytometry. Tacrolimus treatment significantly altered the relative abundance of Allobaculum, Bacteroides and Lactobacillus and CD4+CD25hiFoxP3+ regulatory T-cells in the colonic mucosa and the circulation. These were significantly increased after either tacrolimus treatment or treatment by fecal microbiota transfer, from tacrolimus-treated donors. Furthermore, treatment by low-dose tacrolimus plus fecal microbiota transfer from high-dose tacrolimus-altered mice increased skin allograft survival rate in a skin transplantation model. Thus, a high-dose of tacrolimus alters the compositions and taxa of the gut microbiota. Administration of these conditioned gut microbiota plus low-dose tacrolimus resulted in regulation of colonic and systemic immune responses and an increased allograft survival rate. This study demonstrated a new strategy for controlling allograft rejection by combining an immunosuppressive agent with gut microbiome transplant.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T11:14:04.405347-05:
      DOI: 10.1111/ajt.14661
       
  • Life of patients 10 years after a successful pediatric intestinal
           transplantation in Europe
    • Authors: Lorenzo Norsa; Girish Gupte, Esther Ramos Boluda, Francisca Joly, Olivier Corcos, Jacques Pirenne, Gustaf Herlenius, Florence Lacaille
      Abstract: A multicenter Europe-wide single point study in intestinal transplantation (ITx) centers was conducted to identify and describe patients surviving for more than 10 years after ITx in childhood. The health and nutritional status, care requirements and psychosocial status were recorded. Among 120 transplanted before 2005, 38 patients with a functioning graft were included. Thirty (79%) had an exclusive oral diet, 7 (18%) complimentary enteral nutrition for eating disorders, one a combination of parenteral and enteral nutrition. They daily received a median of 5 drugs, 5 had a stoma. We did not observe any catch-up growth during the 10 years of follow up. In the previous 5 years, 22 patients needed unplanned hospitalization with a median in-patient stay of 6 days. Eleven needed ongoing psychiatric, and 9 other specialist follow up. An increasing independency from parents was seen after the age of 18, with 3 having a stable employment and 31 in education. Despite a good graft function, growth may not catch up. The burden of medical care remains high on the long term. This has to be closely followed in a multidisciplinary setting to improve long term quality of life in these patients.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T11:05:41.825938-05:
      DOI: 10.1111/ajt.14654
       
  • Fatal outcome after reactivation of inherited chromosomally integrated
           HHV-6A (iciHHV-6A) transmitted through liver transplantation
    • Authors: P. Bonnafous; J. Marlet, D. Bouvet, E. Salamé, A-C. Tellier, S. Guyetant, A. Goudeau, H. Agut, A. Gautheret-Dejean, C. Gaudy-Graffin
      Abstract: HHV-6A and HHV-6B are found as inherited and chromosomally integrated forms (iciHHV-6A and -6B) into all germinal and somatic cells and vertically transmitted in a Mendelian manner in about 1% of the population. They were occasionally shown to be horizontally transmitted through hematopoietic stem cell transplantation. Here, we present a clinical case of horizontal transmission of iciHHV-6A from donor to recipient through liver transplantation. Molecular analysis performed on three viral genes (7.2 kb) in the recipient and donor samples supports transmission of iciHHV-6A from the graft. Transmission was followed by reactivation, with high viral loads in several compartments. The infection was uncontrollable, leading to severe disease and death, despite antiviral treatments and the absence of resistance mutations. This case highlights the fact that physicians should be aware of the possible horizontal transmission of iciHHV-6 and its consequences in case of reactivation in immunocompromised patients.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T11:05:40.638052-05:
      DOI: 10.1111/ajt.14657
       
  • Expanding Clarity or Confusion' Volatility of the Five-Tier Ratings
           Assessing Quality of Transplant Centers in the United States
    • Authors: Jesse D. Schold; Kenneth A. Andreoni, Anil K. Chandraker, Robert S. Gaston, Jayme E. Locke, Amit K. Mathur, Timothy Pruett, Abbas Rana, Lloyd E. Ratner, Laura D. Buccini
      Abstract: Outcomes of patients receiving solid organ transplants in the United States are systematically aggregated into bi-annual Program-Specific Reports (PSRs) detailing risk-adjusted survival by transplant center. Recently, the Scientific Registry of Transplant Recipients(SRTR) issued 5-tier ratings evaluating centers based on risk-adjusted one-year graft survival. Our primary aim was to examine the reliability of 5-tier ratings over time. Using ten consecutive PSRs for adult kidney transplant centers from June,2012 to December,2016(n=208) we applied 5-tier ratings to center outcomes and evaluated ratings over time. From the baseline period(June,2012), 47% of centers had at least a one-unit tier change within six months, 66% by one year, and 94% by three years. Similarly, 46% of centers had at least a 2-unit tier change by three years. In comparison, 15% of centers had a change in the traditional 3-tier rating at three years. 5-tier ratings at four years had minimal association with baseline rating(Kappa=0.07,95%C.I. -0.002,0.158). Centers had median 3 different 5-tier ratings over the period(q1=2,q3=4). Findings were consistent by center volume, transplant rate and baseline 5-tier rating. Cumulatively, results suggest that 5-tier ratings are highly volatile, limiting their utility for informing potential stakeholders, particularly transplant candidates given expected waiting times between wait listing and transplantation.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T11:05:36.047831-05:
      DOI: 10.1111/ajt.14659
       
  • MELD as a Metric for Survival Benefit of Liver Transplantation
    • Authors: Xun Luo; Joseph Leanza, Allan B. Massie, Jacqueline M. Garonzik-Wang, Christine E. Haugen, Sommer E. Gentry, Shane E. Ottmann, Dorry L. Segev
      Abstract: Currently, there is debate among the liver transplant community regarding the most appropriate mechanism for organ allocation: urgency-based (MELD) versus utility-based (survival benefit). We hypothesize that MELD and survival benefit are closely associated, and therefore, our current MELD-based allocation already reflects utility-based allocation. We used generalized gamma parametric models to quantify survival benefit of LT across MELD categories among 74,196 adult liver-only active candidates between 2006 and 2016 in the United States. We calculated time ratios (TR) of relative life expectancy with transplantation versus without and calculated expected life years gained after LT. LT extended life expectancy (TR>1) for patients with MELD>10. The highest MELD was associated with the longest relative life expectancy (TR=1.051.201.37 for MELD 11-15, 2.292.492.70 for MELD 16-20, 5.305.726.16 for MELD 21-25, 15.1216.3517.67 for MELD 26-30; 39.2643.2147.55 for MELD 31-34; 120.04128.25137.02 for MELD 35-40). As a result, candidates with the highest MELD gained the more life years after LT: 0.2, 1.5, 3.5, 5.8, 6.9, 7.2 years for MELD 11-15, 16-20, 21-25, 26-30, 31-34, 35-40, respectively. Therefore, prioritizing candidates by MELD remains a simple, effective strategy for prioritizing candidates with a higher transplant survival benefit over those with lower survival benefit.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T11:05:31.442625-05:
      DOI: 10.1111/ajt.14660
       
  • Pancreas transplant rejection episodes are not revealed by biopsies of the
           donor duodenum in a prospective study with paired biopsies
    • Authors: E Nordheim; R Horneland, E M Aandahl, K Grzyb, L Aabakken, V Paulsen, K Midtvedt, A Hartmann, T Jenssen
      Abstract: The surgical technique with duodeno- duodenal enteroanastomosis of pancreas transplants allows for representative endoscopic ultrasound guided needle biopsies of the donor duodenum and the pancreas graft. We assessed whether histological findings in transplanted donor duodenal biopsies can indicate rejection in the transplanted pancreas. From September 2012, a duodeno-duodenal enteroanastomosis has been default technique for pancreas transplantations at our center. In 67 recipients we prospectively examined 113 endoscopic ultrasound- guided procedures with representative biopsies from the duodenum- and the pancreas grafts (97 per protocol and 16 on indication). All graft biopsies were evaluated according to established rejection criteria. A total of 22 biopsy proven pancreas rejections were detected, with two matching duodenal biopsies showing rejection. This gives a sensitivity of 9% for detection of a pancreas rejection by duodenal biopsies. The other matching duodenal biopsies were either normal (n=13) or indeterminate (n=7). Rejection of the donor duodenum was found in only 6/113 biopsies, with two concurrent pancreas rejections. In conclusion, the donor duodenum is not a useful reporter organ for rejection in the pancreas graft.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T11:05:26.604902-05:
      DOI: 10.1111/ajt.14658
       
  • Exosomes Expressing the Self-Antigens Myosin and Vimentin Play an
           Important Role in Syngeneic Cardiac Transplant Rejection Induced by
           Antibodies to Cardiac Myosin
    • Authors: Monal Sharma; Wei Liu, Sudhir Perincheri, Muthukumar Gunasekaran, T. Mohanakumar
      Abstract: Long-term success of heart transplantation is hindered by humoral and cell-mediated immune responses. We studied preexisting antibodies to two cardiac self-antigens, myosin and vimentin, and exosomes induced by antibodies to self-antigens in eliciting immune responses to cardiac grafts. After syngeneic heterotopic murine heart transplantation, rabbit anti-myosin or normal rabbit immunoglobulin was administered at days 0 or 7. Sera were collected after heartbeat cessation and cellular infiltration was analyzed, and exosomes were isolated from sera. Histopathology of controls’ transplanted hearts demonstrated normal architecture, and their sera demonstrated neither antibodies to self-antigens nor exosomes expressing self-antigens. Administration of antibodies to cardiac myosin immediately post-transplant (day 0) but not day 7 triggered graft failure on day 7, and histopathology revealed marked cellular infiltration with neutrophils and lymphocytes. Rejected heart histopathology also demonstrated myocyte damage and sera had increased antibodies to myosin and vimentin, and development of exosomes expressing self-antigens. Administration of exosomes isolated from failed grafts containing self-antigens induced graft dysfunction; exosomes isolated from stable mice did not induce graft failure. Antibodies to self-antigens can induce exosomes containing self-antigens, initiating an immune response and causing graft failure after cardiac transplantation.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T09:31:38.035511-05:
      DOI: 10.1111/ajt.14650
       
  • Invited Letter in Response to: “Is the kidney donor profile index (KDPI)
           universal or UNOS-specific'
    • Authors: Piero Ruggenenti; Giuseppe Remuzzi
      Abstract: Graft survival in 37 recipients of one or two histologically evaluated kidneys from octogenarian donors with a KDPI of 96-100% was similar to that observed in 198 recipients of non-histologically evaluated single grafts from 60-year-old donors with cerebrovascular death and a KDPI of>85%. Thus, both studies, as well as previous reports in a similar context,3 converge to indicate that kidneys from>60-year-old donors with a KDPI of>85% can safely be used, provided their kidneys are selected and allocated on the basis of pre-transplant histological findings.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T09:30:55.203642-05:
      DOI: 10.1111/ajt.14652
       
  • Propensity score-based comparison of the graft failure risk between kidney
           transplant recipients of standard and expanded criteria donor grafts:
           towards increasing the pool of marginal donors
    • Authors: AH Querard; F Le Borgne, A Dion, M Giral, G Mourad, V Garrigue, L Rostaing, N Kamar, A Loupy, C Legendre, E Morelon, F Buron, Y Foucher, E Dantan
      Abstract: From a prospective and multicentric French cohort, we proposed an external validation study for the Expanded Criteria Donor (ECD), based on 4833 kidney recipients transplanted for the first time between 2000 and 2014. We estimated the subject-specific effect from a multivariable Cox model. We confirmed a 1.75-fold (95%CI from 1.53 to 2.00, p
      PubDate: 2018-01-09T09:30:44.401287-05:
      DOI: 10.1111/ajt.14651
       
  • Mobile ECMO team for controlled donation after circulatory death
    • Authors: Jose Miguel Pérez-Villares; Ramón Lara-Rosales, Alberto Fernández-Carmona, Patricia Fuentes-Garcia, Manuel Burgos-Fuentes, Blas Baquedano-Fernández
      Abstract: The scarcity of potential dead brain donors (DBD) and the persistent mismatch between supply and demand of organs for transplantation has led the transplant community to reconsider donation after circulatory death (DCD) as a strategy to increase the donor pool. Controlled donation after circulatory death (cDCD) has emerged as the most feasible way to expand the number of transplantations. In Spain, cDCD accounted for 18% of the total number of deceased donors in 2016. At present, a total of 68 hospitals in Spain have cDCD programs1. The experience accumulated in the last years has demonstrated that normothermic regional perfusion (nRP) by extracorporeal membrane oxygenation (ECMO) may be the most effective method for preserving abdominal organs in DCD, especially in liver transplantation.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T09:30:43.086134-05:
      DOI: 10.1111/ajt.14656
       
  • HIV protease inhibitors and mortality following kidney transplantation
    • Authors: Timothy Sullivan
      Abstract: In their recent study (1), Sawinski et al present compelling evidence of the potential harms of HIV protease inhibitors (PIs) following kidney transplantation. In this study, PI use was associated with an increased risk of both allograft loss and death. As the authors note, the link between graft failure and PI use can be attributed to the major interaction between PIs and calcineurin inhibitors (CNIs), which likely results in high rates of acute rejection and CNI toxicity.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T09:30:25.741333-05:
      DOI: 10.1111/ajt.14655
       
  • Letter to AJT editor re: Nankivell et al
    • Authors: Konrad S Famulski; Philip F Halloran
      Abstract: We read with interest the analysis of inflammation in areas of atrophy-scarring (i-IFTA) in renal transplant biopsies by Nankivell et al (1), concluding that this represents chronic active T cell-mediated rejection. This theme is also advocated by another recent publication (2) and by the forthcoming Banff report (3), contradicting the previous Banff consensus opinion that i-IFTA lesions are a reflection of injury and a risk for progression but not a sign of active TCMR. We write because molecular analyses do not support the conclusion that i-IFTA indicates chronic active TCMR.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T09:30:23.396684-05:
      DOI: 10.1111/ajt.14653
       
  • Single lung transplantation from a donor eight months after double lung
           transplantation
    • Authors: D. Bobylev; J. Salman, W. Sommer, F. Ius, T. Siemeni, M. Avsar, C. Kühn, A. Niehaus, J. Gottlieb, A. Haverich, I. Tudorache, G. Warnecke
      Abstract: Scarcity of donors leads transplant surgeons to consider extended-criteria lungs and occasionally to accept the unlikely. Here we report a case of successful single lung transplantation from a donor 8 months after double lung transplantation.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-04T11:40:14.431933-05:
      DOI: 10.1111/ajt.14644
       
  • Neutrophil derived CSF1 induces macrophage polarization and promotes
           transplantation tolerance
    • Authors: Mounia S. Braza; Patricia Conde, Mercedes Garcia, Isabel Cortegano, Manisha Brahmachary, Venu Pothula, Francois Fay, Peter Boros, Sherry A. Werner, Florent Ginhoux, Willem J.M. Mulder, Jordi Ochando
      Abstract: The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance. These results provide new mechanistic insights into the developmental requirements of tolerogenic macrophages and identify CSF1 producing neutrophils as critical regulators of the immunological response.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-04T10:05:37.451884-05:
      DOI: 10.1111/ajt.14645
       
  • Increased risk donors: A bird in the hand
    • Authors: Daniel R. Kaul
      Abstract: Unexpected donor-derived infections (DDI) are relatively uncommon events complicating less than 1% of solid organ transplants (1). Disease can be severe, however, with malignancies and agents that infect the central nervous system carrying a particularly high risk of adverse outcomes (2). In most cases, this risk is managed by a combination of clinical assessment and pre-procurement donor testing.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-04T08:55:27.874607-05:
      DOI: 10.1111/ajt.14643
       
  • Puerto Rico after Hurricane Maria
    • Authors: Lara C. Pullen
      Pages: 283 - 284
      Abstract: This month's installment of “The AJT Report” covers the recent hurricanes that devastated Puerto Rico and Houston, which necessitated prompt action and keen judgment by local hospitals on behalf of transplant patients, and shed a light on emergency response areas that require attention.
      PubDate: 2018-01-30T10:27:34.628568-05:
      DOI: 10.1111/ajt.14647
       
  • DC Metabolism Controls Lung T Cell Polarization
    • Authors: Maria-Luisa Alegre
      Pages: 285 - 285
      Abstract: Dendritic cells’ metabolism determines their adjustment to specific tissues and the type of adaptive immunity they instruct following inflammatory challenges.
      PubDate: 2018-01-30T10:27:33.483126-05:
      DOI: 10.1111/ajt.14648
       
  • CDC Grand Rounds: Improving medication adherence for chronic disease
           management — Innovations and opportunities
    • Authors: Andrea B. Neiman; Todd Ruppar, Michael Ho, Larry Garber, Paul J. Weidle, Yuling Hong, Mary G. George, Phoebe G. Thorpe
      Pages: 514 - 517
      Abstract: This article reviews interventions to improve adherence to medications in individuals with chronic medical issues, such as those seen in transplantation.
      PubDate: 2018-01-30T10:27:33.065498-05:
      DOI: 10.1111/ajt.14649
       
  • New-onset serositis in a kidney transplant patient
    • Authors: Sindhura Bobba; Hasan Fattah, Hugh Davis Massey, Gaurav Gupta
      Pages: 518 - 520
      PubDate: 2018-01-30T10:27:35.769657-05:
      DOI: 10.1111/ajt.14599
       
  • Meeting Report: FDA Public Meeting on Patient-Focused Drug Development and
           Medication Adherence in Solid Organ Transplant Patients
    • Authors: Robert Ettenger; Renata Albrecht, Rita Alloway, Ozlem Belen, Marc W Cavaillé-Coll, Marie. A. Chisholm-Burns, Mary Amanda Dew, William E Fitzsimmons, Peter Nickerson, Graham Thompson, Pujita Vaidya
      Abstract: The Food and Drug Administration (FDA) held a public meeting and scientific workshop in September 2016 to obtain perspectives from solid organ transplant recipients, family caregivers, and other patient representatives. The morning sessions focused on the impact- of organ transplantation on patients’ daily lives and the spectrum of activities undertaken to maintain grafts. Participants described the physical, emotional, and social impacts of their transplant on daily life. They also discussed their post-transplant treatment regimens, including the most burdensome side effects and their hopes for future treatment. The afternoon scientific session consisted of presentations on prevalence and risk factors for medication nonadherence after transplantation in adults and children, and interventions to manage it. As new modalities of Immunosuppressive Drug Therapy are being developed, the patient perceptions and input must play larger roles if organ transplantation is to be truly successful.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-30T12:35:25.857495-05:
      DOI: 10.1111/ajt.14635
       
  • Assessing Emergency Department Utilization in the Era of Population Health
    • Authors: Jesse D. Schold; Jayme E. Locke
      Abstract: Population health has been broadly defined as “health outcomes of a group of individuals, including the distribution of such outcomes within the group.” (1) Increasingly, population health has gained prominence and impact with emergence of Accountable Care Organizations that serve populations across transitions of care and different providers (often extended to communities). Population health has also been a focus of healthcare reform and development of policies and interventions aimed at simultaneously improving quality and reducing costs.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-30T12:35:23.525462-05:
      DOI: 10.1111/ajt.14641
       
  • Transplantation of Macro-encapsulated Human Islets within the
           Bioartificial Pancreas β Air to Patients with Type 1 Diabetes Mellitus
    • Authors: Per-Ola Carlsson; Daniel Espes, Amir Sedigh, Avi Rotem, Baruch Zimermann, Helena Grinberg, Tali Goldman, Uriel Barkai, Yuval Avni, Gunilla T. Westermark, Lina Carlbom, Håkan Ahlström, Olof Eriksson, Johan Olerud, Olle Korsgren
      Abstract: Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes. Four patients were transplanted with 1-2 βAir devices, each containing 155000-180000 IEQ (i.e. 1800–4600 IEQ per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T21:06:18.376629-05:
      DOI: 10.1111/ajt.14642
       
  • RNA expression profiling of non-human primate renal allograft rejection
           identifies tolerance
    • Authors: R.N. Smith; M. Matsunami, B.A. Adam, I.A. Rosales, T. Oura, A.B. Cosimi, T. Kawai, M. Mengel, R.B. Colvin
      Abstract: Tolerance induction to prevent allograft rejection is a long standing clinical goal. However, convincing and dependable tolerance identification remains elusive. Hypothesizing that intragraft RNA expression is informative in both rejection and tolerance, we profile intra-renal allograft RNA expression in a mixed chimerism renal allograft model of Cynomolgus monkeys and identify biologically significant tolerance. Analysis of 67 genes identified three dominant factors, each with a different pattern of gene expressions, relating to T cell mediated rejection (TCMR), chronic antibody mediated rejection (CAMR), or Tolerance. Clustering these three factors created nine groups. One of the nine clustered groups, the Tolerance cluster, showed the lowest probability of terminal rejection, the longest duration of allograft survival, and the lowest relative risk of terminal rejection. The Tolerance factor comprises a novel set of gene expressions including cytokine and immunoregulatory genes adding mechanistic insights into tolerance. The Tolerance factor could not be identified within current pathological diagnostic categories. The TCMR and CAMR factors are dominant to the Tolerance factor causing rejection even if the Tolerance factor is present. These three factors determine the probability of terminal rejection or tolerance. This novel a posteriori approach permits identification of pathways of rejection, including tolerance.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T21:05:43.402294-05:
      DOI: 10.1111/ajt.14637
       
  • Aggressive Infrainguinal Revascularization In Renal Transplant Patients Is
           Justifiable
    • Authors: Rebecca Craig-Schapiro; Besma Nejim, Isibor Arhuidese, Mahmoud B. Malas
      Abstract: While studies demonstrate poor outcomes of lower extremity revascularization in end-stage renal disease patients, little is known about results in renal transplant patients. We analyzed 2-year primary patency and limb salvage outcomes and associated risk factors of transplant (N=202) and non-transplant patients (N=25,274) in the Vascular Quality Initiative database undergoing infrainguinal bypass from 2003-2016. Multivariable Cox regression analysis and coarsened exact matching with many-to-one were employed. Transplant patients were more likely to have critical limb ischemia, revascularization of more distal arteries, and receive vein conduits. Primary patency was similar between transplant and nontransplant patients at 1-year (80.8% vs. 77.5%) and 2-years (67.9% vs. 63.7%, p=0.079). Amputation-free survival was higher for nontransplant patients (1-year: 82.4% vs. 75.3%, 2-years: 68.8% vs. 58.2%, p=0.0060), although overall survival was equivalent (2-years: 84.6% vs. 87.2%, 4-years: 75.9% vs. 79.6%, p=0.35). Risk factors for primary patency loss included female, critical limb ischemia, prior bypass, and distal bypass. Age, diabetes, prior contralateral amputation, critical limb ischemia, prosthetic conduit, and more distal bypass were associated with limb loss. This is the largest series of infrainguinal revascularization in transplant patients. Outcomes for transplant patients are not inferior, and aggressive approaches at limb salvage are justifiable in appropriately selected patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T21:05:36.889003-05:
      DOI: 10.1111/ajt.14636
       
  • RNA expression profiling of renal allografts in a non-human primate
           identifies variation in NK and endothelial gene expression
    • Authors: R. N. Smith; B. A. Adam, I. A. Rosales, M. Matsunami, T. Oura, A. B. Cosimi, T. Kawai, M. Mengel, R. B. Colvin
      Abstract: RNA transcript expression estimates are a promising method to study the mechanisms and classification of renal allograft rejections. Here we use the Nanostring platform to profile RNA expression in renal allografts in a non-human primate (NHP), the Cynomolgus monkey. We analyzed protocol and indication 278 archival renal allograft samples, both protocol and indication from 76 animals with diagnoses of chronic antibody (CAMR), acute cellular rejection (TCMR) and MIXED (both CAMR and TCMR), plus normals and samples with no pathological rejection using a Cynomolgus specific probe set of 67 genes. Analysis identified RNA expression heterogeneity of endothelial and NK genes within CAMR and TCMR, including the stages of CAMR. Three factors were partitioned into additional groups. One group with the longest allograft survival time is pure CAMR without NK or CD3. Three mixed groups show variation in NK and CD3. TCMR was split into two groups with variation in NK genes. Additional validation of the complete gene set correlated many of the genes with diagnoses of CAMR, MIXED, and TCMR rejections and with Banff histologic criteria defined in human subjects. These NHP data demonstrate the utility of RNA expression profiling to identify additional heterogeneity of endothelial and NK RNA gene expressions.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T08:40:28.280945-05:
      DOI: 10.1111/ajt.14639
       
  • Patterns of Kidney Injury in Pediatric Non-Kidney Solid Organ Transplant
           Recipients
    • Authors: C. Williams; K. Borges, T. Banh, J. Vasilevska-Ristovska, R. Chanchlani, V. L. Ng, A. I. Dipchand, M. Solomon, D. Hebert, S. J. Kim, B. C. Astor, R. S. Parekh
      Abstract: The incidence of acute kidney injury (AKI) and its impact on chronic kidney disease (CKD) following pediatric non-kidney solid organ transplantation is unknown. We aimed to determine the incidence of AKI and CKD and examine their relationship among children who received a heart, lung, liver or multi-organ transplant at the Hospital for Sick Children between 2002 and 2011. AKI was assessed in the first year post-transplant. Among 303 children, perioperative AKI (within the first week) occurred in 67% of children, and AKI after the first week occurred in 36%, with the highest incidence among lung and multi-organ recipients. Twenty-three children (8%) developed CKD after a median follow-up of 3.4 years. Less than 5 children developed end-stage renal disease, all within 65 days post-transplant. Those with 1 AKI episode by 3 months post-transplant had significantly greater risk for developing CKD after adjusting for age, sex, and eGFR at transplant (hazard ratio [HR]: 2.77, 95% CI: 1.13-6.80, p-trend= 0.008). AKI is common in the first year post-transplant and associated with significantly greater risk of developing CKD. Close monitoring for kidney disease may allow for earlier implementation of kidney-sparing strategies to decrease risk for progression to CKD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T08:40:23.847163-05:
      DOI: 10.1111/ajt.14638
       
  • The Influence of Socioeconomic Deprivation on Outcomes in Pancreas
           Transplantation in England; Registry Data Analysis
    • Authors: Argiris Asderakis; Usman Khalid, Susanna Madden, Colin Dayan
      Abstract: Socioeconomic deprivation is associated with poorer outcomes in chronic diseases. The aim of this study was to investigate the effect of socioeconomic deprivation on outcomes following pancreas transplantation among patients transplanted in England. We included all 1270 pancreas recipients transplanted between 2004 and 2012. We used the English Index of Multiple Deprivation (EIMD) score to assess the influence of socioeconomic deprivation on patient and pancreas graft survival. Higher scores mean higher deprivation status. Median EIMD score was 18.8, 17.7 and 18.1 in patients who received SPK, PAK and PTA respectively (p=0.56). Pancreas graft (censored for death) survival was dependent on the donor age (p=0.08), CIT (p=0.0001), the type of pancreas graft (SPK vs. PAK or PTA, p=0.0001), and EIMD score (p=0.02). The 5-year pancreas graft survival of the most deprived patient quartile was 62% compared to 75% among the least deprived (p=0.013), and it was especially evident in the SPK group. EIMD score also correlated with patient survival (p=0.05). Looking at the impact of individual domains of deprivation, ‘Environment’ (p=0.037) and ‘Health and Disability’ (p=0.035) domains had significant impact on pancreas graft survival. Socioeconomic deprivation, as expressed by the EIMD is an independent factor for pancreas graft and patient survival.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-23T22:15:27.292633-05:
      DOI: 10.1111/ajt.14633
       
  • Human Polyomavirus-7 associated eruption successfully treated with
           acitretin
    • Authors: T.N Canavan; J.W Baddley, P Pavlidakey, J.A Tallaj, B.E Elewski
      Abstract: Advances in molecular technologies have led to the discovery of several novel human polyomaviruses (HPyVs), including human polyomavirus-7 (HPyV-7). While low levels of HPyV-7 are shed from apparently normal skin, recent reports have described clinically significant cutaneous infection in immunocompromised patients that manifests as generalized pruritic plaques. The pruritus can be severe, and treatment options have not been described. Here we report HPyV-7 cutaneous infection in a heart transplant patient who experienced temporary improvement with IV cidofovir, and complete remission with acitretin. We report a case of HPyV-7 cutaneous infection demonstrating a good response to treatment.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-23T22:15:25.435655-05:
      DOI: 10.1111/ajt.14634
       
  • The TWEAK/Fn14 pathway is required for Calcineurin Inhibitor Toxicity of
           the Kidneys
    • Authors: Meike Claus; Rana Herro, Dennis Wolf, Konrad Buscher, Stefan Rudloff, Uyen Huynh-Do, Linda Burkly, Michael Croft, Daniel Sidler
      Abstract: Calcineurin inhibitor toxicity (CNT) is a frequent occurrence in transplanted renal grafts and autochthone kidneys from patients undergoing long-term treatment with Calcineurin inhibitors, notably Cyclosporin A (CsA) and Tacrolimus. Here, we show an indispensable role of the TNF superfamily molecule TWEAK (TNFSF12) in the pathogenesis of acute CNT lesions in mice. A deficiency in TWEAK resulted in limited tubulotoxicity after CsA exposure, which correlated with diminished expression of inflammatory cytokines and reduced intraparenchymal infiltration with immune cells. We further identified tubular epithelial cells of the kidney as major targets of CsA activity and found that Fn14 (TNFRSF12A), the receptor for TWEAK, is a highly CsA-inducible gene in these cells. Correlating with this, CsA pretreatment sensitized tubular epithelial cells specifically to the pro-inflammatory activities of recombinant TWEAK in vitro. Moreover, injection of rTWEAK alone into mice induced moderate disease similar to CsA, and rTWEAK combined with CsA resulted in synergistic nephrotoxicity. These findings support the importance of tubular epithelial cells as cellular targets of CsA toxicity and introduce TWEAK as a critical contributor to CNT pathogenesis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-21T09:45:25.039377-05:
      DOI: 10.1111/ajt.14632
       
  • Response to Invited letter to comment on “Impact of spontaneous donor
           hypothermia on graft outcomes after kidney transplantation”
    • Authors: Peter Schnuelle; Urs Benck, Bernhard K. Krämer
      Abstract: In response to Niemann et al, despite the limitations of the retrospective study design, our data share striking similarities with the intervention trial of therapeutic hypothermia (1). Both, baseline characteristics of the donors and the observed effect on a lessened incidence of delayed graft function (DGF) after transplantation were largely comparable. While the molecular mechanisms remain obscure, it may not be quite clear from the intervention trial to distinguish, whether the quantitative effect on DGF was due to the target cooling temperature or - according to the study protocol - inadvertently amplified by warming of the controls, including 12% of donors who were spontaneously hypothermic (2).This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-21T09:35:27.226765-05:
      DOI: 10.1111/ajt.14629
       
  • Geographic disparities in donor lung supply and lung transplant waitlist
           outcomes: A Cohort Study
    • Authors: Luke J. Benvenuto; David R. Anderson, Hanyoung P. Kim, Jaime L. Hook, Lori Shah, Hilary Y. Robbins, Frank D'Ovidio, Matthew Bacchetta, Joshua R. Sonett, Selim M. Arcasoy,
      Abstract: In spite of the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation with the majority of donor lungs being allocated locally to lower priority candidates. We conducted a retrospective cohort study of 19,622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (SHR: 1.84, 95% CI: 1.51-2.24, p
      PubDate: 2017-12-21T09:35:26.288053-05:
      DOI: 10.1111/ajt.14630
       
  • Inferior long-term allograft and patient outcomes among recipients of
           offspring living donor kidneys
    • Authors: J.B Cohen; L Owei, D.L Sawinski, P.M Porrett
      Abstract: While offspring-to-parent living donor kidney transplantations may represent an ideal donor-recipient combination to optimize long-term transplant outcomes, the gender-specific long-term success of these transplants remains unclear. We hypothesize that allograft and recipient survival in offspring-to-parent living donor kidney transplantation differs between men and women due to donor-specific alloimmunization during pregnancy. We retrospectively analyzed long-term allograft and patient survival among men and women who received an offspring living donor kidney compared to those who received other haplotype-matched living donor kidneys. By multivariable Cox proportional hazards modeling of Organ Procurement and Transplantation Network data from 2001 to 2015, we found that both men and women who received offspring living donor kidneys had significantly increased mortality compared to recipients who received non-offspring living donor kidneys. While male recipients of any living donor kidney had greater risk of mortality and allograft failure compared to females, there was no significant difference in all-cause allograft failure or mortality in male versus female recipients of offspring living donor kidney transplantations. Our analysis demonstrated no significant interaction between recipient gender and donor offspring status. We conclude that non-offspring living donors should be considered whenever feasible for both men and women with multiple donor options.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-21T09:35:24.343492-05:
      DOI: 10.1111/ajt.14631
       
  • What's Hot, What's New: Report from the American Transplant Congress 2017
    • Authors: Matthew Cooper; Xian C. Li, Andrew B Adams
      Abstract: Significant advances in clinical practice as well as basic and translational science were presented at the American Transplant Congress this year. Topics covered included innovative clinical trials to recent advances in our basic understanding of the scientific underpinnings of transplant immunology. Key areas of interest included: clinical trials utilizing HCV+ donors into HCV- recipients, the impact of the new allocation policies, normothermic perfusion, novel treatments for desensitization, attempts at precision medicine, advances in xenotransplantation, the role of mitochondria and exosomes in rejection, nanomedicine, and the impact of the microbiota on transplant outcomes. This review highlights some of the most interesting and noteworthy presentations from the meetingThis article is protected by copyright. All rights reserved.
      PubDate: 2017-12-19T02:10:25.059182-05:
      DOI: 10.1111/ajt.14628
       
  • Long-term outcome of liver transplantation in childhood: a study of
           20-year survivors
    • Authors: J. Martinelli; D. Habès, L. Majed, C. Guettier, E. Gonzalès, A. Linglart, C. Larue, V. Furlan, D. Pariente, C. Baujard, S. Branchereau, F. Gauthier, E. Jacquemin, O Bernard
      Abstract: We report the results of a study of survival, liver and kidney functions, and growth with a median follow-up of 24 years following liver transplantation in childhood. From 1988 to 1993, 128 children underwent deceased donor liver transplantation (median age: 2½ years). Twenty-year patient and graft survival rates were 79% and 64%, respectively. Raised serum aminotransferase and/or gamma-glutamyl transferase activities were present in 42% of survivors after a single transplantation. Graft histology (35 patients) showed signs of chronic rejection in 11 and biliary obstruction in 5. Mean total fibrosis scores were 4.5/9 and 3/9 in patients with abnormal and normal serum liver tests, respectively. Glomerular filtration rate was
      PubDate: 2017-12-15T21:15:34.192279-05:
      DOI: 10.1111/ajt.14626
       
  • Short-term Adverse Effects of Early Subclinical Allograft Inflammation in
           Kidney Transplant Recipients with a Rapid Steroid Withdrawal Protocol
    • Authors: Rajil Mehta; Sushma Bhusal, Parmjeet Randhawa, Puneet Sood, Aravind Cherukuri, Christine Wu, Chethan Puttarajappa, William Hoffman, Nirav Shah, Massimo Mangiola, Adriana Zeevi, Amit D Tevar, Sundaram Hariharan
      Abstract: The impact of Sub-Clinical Inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3-month biopsy.A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3-months post-transplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for rejection were identified. These were Group I: No Inflammation (NI, n=71) and Group II: Subclinical Inflammation (SCI, n=129). We evaluated differences in kidney function at 24-months and allograft histology score at 12-month biopsy.SCI patients had a higher serum creatinine (1.6+0.7 vs 1.38+0.45;p=0.02) at 24-months post-transplant, and at last follow up at a mean of 42.5 months (1.69±0.9 vs 1.46±0.5 mg/dl; p=0.027). The allograft chronicity score (ci+ct+cg+cv) at 12-months post-transplant was higher in the SCI group (2.4 +1.35 vs.1.9+1.2;p=0.02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (p=0.015). De novo DSA within 12 months was more prevalent in the SCI group (12/129 vs 1/71, p=0.03).SCI is likely not a benign finding and may have long-term implications for kidney allograft function.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-15T21:15:31.60067-05:0
      DOI: 10.1111/ajt.14627
       
  • The Banff 2017 Kidney Meeting Report: Revised Diagnostic Criteria for
           Chronic Active T Cell-Mediated Rejection, Antibody-Mediated Rejection, and
           Prospects for Integrative Endpoints for Next-Generation Clinical Trials
    • Authors: M Haas; A Loupy, C Lefaucheur, C Roufosse, D Glotz, D Seron, B J Nankivell, P F Halloran, R B Colvin, N Alachkar, S Bagnasco, Y Bouatou, J U Becker, L Cornell, J P Duong van Huyen, I Gibson, R Mannon, M Naesens, V Nickeleit, P Nickerson, D L Segev, H K Singh, M Stegall, P Randhawa, L Racusen, K Solez, M Mengel
      Abstract: The kidney sessions of the 2017 Banff Conference focused on two areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) and its relationship to T cell-mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody-mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by two groups that i-IFTA is associated with reduced graft survival. Furthermore, these groups presented that i-IFTA, particularly when involving>25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with under-immunosuppression. The classification was thus revised to include moderate i-IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor-specific antibodies (DSA), and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSA in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next generation clinical trials.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-15T04:33:50.696171-05:
      DOI: 10.1111/ajt.14625
       
  • Aquaporin 4 blockade improves survival of murine heart allografts
           subjected to prolonged cold ischemia
    • Authors: Katayoun Ayasoufi; Naoki Kohei, Michael Nicosia, Ran Fan, George W. Farr, Paul R. McGuirk, Marc F. Pelletier, Robert L. Fairchild, Anna Valujskikh
      Abstract: Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize IRI in transplanted organs, yet there is a need for novel approaches to improve outcomes of marginal allografts and expand the pool of donor organs suitable for transplantation. Aquaporins (AQPs) are a family of water channels that facilitate homeostasis, tissue injury and inflammation. We tested whether inhibition of AQP4 improves the survival of fully MHC-mismatched murine cardiac allografts subjected to 8 h CIS. Administration of a small molecule AQP4 inhibitor during donor heart collection and storage and for a short-time posttransplant improves the viability of donor graft cells, diminishes donor-reactive T cell responses and extends allograft survival in the absence of other immunosuppression. Furthermore, AQP4 inhibition is synergistic with CTLA4-Ig in prolonging survival of 8 h CIS heart allografts. AQP4 blockade markedly reduced T cell proliferation and cytokine production in vitro suggesting that the improved graft survival is at least in part mediated through direct effects on donor-reactive T cells. These results identify AQPs as a promising target for diminishing donor-specific alloreactivity and improving the survival of high-risk organ transplants.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-15T04:31:06.884377-05:
      DOI: 10.1111/ajt.14624
       
  • Efficacy and safety of everolimus with reduced tacrolimus in living-donor
           liver transplant recipients: 12-month results of a randomized multicenter
           study
    • Authors: Long-Bin Jeng; Sung Gyu Lee, Arvinder Singh Soin, Wei-Chen Lee, Kyung-Suk Suh, Dong Jin Joo, Shinji Uemoto, Jaewon Joh, Tomoharu Yoshizumi, Horng-Ren Yang, Gi-Won Song, Patricia Lopez, Jossy Kochuparampil, Carole Sips, Shuhei Kaneko, Gary Levy
      Abstract: In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30±5 days post-transplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months post-transplant: difference –0.7% [90%CI –5.2%, 3.7%]; p
      PubDate: 2017-12-13T18:14:36.507521-05:
      DOI: 10.1111/ajt.14623
       
  • Novel Techniques and Preliminary Results of Ex Vivo Liver Resection and
           Autotransplantation for End-Stage Hepatic Alveolar Echinococcosis: A
           Study of 31 Cases
    • Authors: Xianwei Yang; Yiwen Qiu, Bin Huang, Wentao Wang, Shu Shen, Xi Feng, Yonggang Wei, Jianyong Lei, Jichun Zhao, Bo Li, Tianfu Wen, Lunan Yan
      Abstract: Ex vivo liver resection combined with autotransplantation is a recently introduced approach to cure end-stage hepatic alveolar echinococcosis (HAE), which is considered unresectable by conventional radical resection due to echinococcal dissemination into the crucial intrahepatic conduits and adjacent structures. This manuscript aims discuss the manipulation details and propose reasonable indications for this promising technique. All patients successfully underwent liver autotransplantation with no intraoperative mortality. The median weight of the autografts was 636 g (360-1300 g), the median operation time was 12.5 h (9.4-19.5 h), and the median anhepatic phase was 309 min (180- 460 min). Intraoperative blood loss averaged 1800 mL (1200-6000 mL). Postoperative complications occurred in 13 patients during hospitalization; five patients experienced postoperative complications classified as Clavien-Dindo Grade III or higher, and two patients died of intra-abdominal bleeding and acute cerebral hemorrhage, respectively. Twenty-nine patients were followed for a median of 14.0 months (3-42 months), and no HAE recurrence was detected. The technique requires neither an organ donor nor any postoperative immunosuppressant, and the success of the treatment relies on meticulous preoperative assessments and precise surgical manipulation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-12T09:48:11.541284-05:
      DOI: 10.1111/ajt.14621
       
  • Geographic Disparity in Kidney Transplantation under KAS
    • Authors: Sheng Zhou; Allan B. Massie, Xun Luo, Jessica M. Ruck, Eric K.H. Chow, Mary G. Bowring, Sunjae Bae, Dorry L. Segev, Sommer E. Gentry
      Abstract: The Kidney Allocation System fundamentally altered kidney allocation, causing a substantial increase in regional and national sharing that we hypothesized might impact geographic disparities. We measured geographic disparity in deceased donor kidney transplant (DDKT) rate under KAS (6/1/2015-12/1/2016), and compared that with pre-KAS (6/1/2013-12/3/2014). We modeled DSA-level DDKT rates with multilevel Poisson regression, adjusting for allocation factors under KAS. Using the model we calculated a novel, improved metric of geographic disparity: the median incidence rate ratio (MIRR) of transplant rate, a measure of DSA-level variation that accounts for patient casemix and is robust to outlier values. Under KAS, MIRR was 1.751.811.86 for adults, meaning that similar candidates across different DSAs have a median 1.81-fold difference in DDKT rate. The impact of geography was greater than the impact of factors emphasized by KAS: having an EPTS score ≤20% was associated with a 1.40-fold increase (IRR=1.351.401.45, p
      PubDate: 2017-12-12T09:47:18.429865-05:
      DOI: 10.1111/ajt.14622
       
  • Campath, calcineurin inhibitor reduction and chronic allograft nephropathy
           (the 3C Study) – results of a randomized controlled clinical trial
    • Authors: Richard Haynes; Lisa Blackwell, Natalie Staplin, William G Herrington, Jonathan Emberson, Parminder K Judge, Benjamin C Storey, Martin J Landray, Paul N Harden, Colin Baigent, Peter Friend
      Abstract: Calcineurin inhibitors (CNI e.g. tacrolimus) reduce short-term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin pathway (mTOR e.g. sirolimus) might avoid long-term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial comprising sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6-months post-transplant. The primary outcome of this analysis was estimated glomerular filtration rate (eGFR) at 18 months after maintenance therapy randomization. 197 patients were assigned sirolimus-based and 197 to tacrolimus-based therapy. Allocation to sirolimus had no significant effect on eGFR at 18 months: baseline-adjusted mean (SE) eGFR 53.7 (0.9) mL/min/1.73m2 in the sirolimus group versus 54.6 (0.9) mL/min/1.73m2 in the tacrolimus group (p=0.50). Biopsy-proven acute rejection (29 [14.7%]) vs 6 [3.0%]; p
      PubDate: 2017-12-11T02:55:25.223351-05:
      DOI: 10.1111/ajt.14619
       
  • Comparative evaluation of simple indices using a single fasting blood
           sample to estimate beta cell function after islet transplantation
    • Authors: Justyna E. Gołębiewska; Julia Solomina, Celeste Thomas, Mark Kijek, Piotr Bachul, Lindsay Basto, Karolina Golab, Ling-jia Wang, Natalie Fillman, Martin Tibudan, Kamil Cieply, Luis Philipson, Alicja Dębska-Ślizień, J.Michael Millis, John Fung, Piotr Witkowski
      Abstract: Six single fasting blood sample based indices: Secretory Unit of Islet Transplant Objects (SUITO), Transplant Estimated Function (TEF), Homeostasis Model Assessment (HOMA)2-B%, C-peptide/glucose ratio (CP/G), C-peptide/glucose creatinine ratio (CP/GCr) and BETA-2 score, were compared against commonly used 90-min mixed meal tolerance test (MMTT) serum glucose and beta-score to assess which of them best recognizes the state of acceptable blood glucose control without insulin supplementation after islet allotransplantation (ITx). We also tested if the indices could identify the success of ITx based on the Igls classification of beta-cell graft function. We analyzed values from 47 MMTT tests in 4 patients with up to 140 months follow-up and from 54 MMTT tests in 13 patients with up to 42 months follow-up.SUITO, CP/G, HOMA2-B% and BETA-2 correlated well with the 90-min glucose of the MMTT and beta-score (r 0.54-0.76), whereas CP/GCr showed a modest performance (r 0.41-0.52) while TEF showed little correlation. BETA-2 and SUITO were the best identifiers and predictors of the need for insulin support, glucose intolerance and ITx success (p
      PubDate: 2017-12-08T03:20:30.815672-05:
      DOI: 10.1111/ajt.14620
       
  • Islet Damage during Isolation as Assessed by miRNAs and the Correlation of
           miRNA Levels with Posttransplant Outcome in Islet Autotransplantation
    • Authors: Prathab Balaji Saravanan; Mazhar A. Kanak, Charles A Chang, Carly Darden, Gumpei Yoshimatsu, Michael C. Lawrence, Bashoo Naziruddin
      Abstract: High-quality pancreatic islets are essential for better posttransplant endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet-enriched miRNAs -375 and -200c released during isolation to assess damage and correlated the data with posttransplant endocrine function. The absolute concentration of miR-375, miR-200c, and C-peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT. Posttransplant glycemic control was monitored through C-peptide, hemoglobin A1cs, insulin requirement, and SUITO index. The amount of miR-375 released was significantly higher during enzymatic digestion following by the islet bagging (P < 0.001). MiR-200c mirrored these changes, albeit at lower concentrations. In contrast, the C-peptide amount was significantly higher in the purification and bagging steps (P < 0.001). Lower amounts of miR-375 were associated with a lower 6-month insulin requirement (P = 0.03) and lower hemoglobin A1c (P = 0.04). Measurement of the absolute quantity of miRNAs 375 and 200c released during islet isolation is a useful tool to assess islet damage. The quantity of released miRNA is indicative of posttransplant endocrine function in TPIAT patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-06T02:15:23.335533-05:
      DOI: 10.1111/ajt.14615
       
  • Mood, Body Image, Fear of Kidney Failure, Life Satisfaction, and
           Decisional Stability Following Living Kidney Donation: Findings from the
           KDOC Study
    • Authors: J R Rodrigue; J D Schold, P Morrissey, J Whiting, J Vella, L K Kayler, D Katz, J Jones, B Kaplan, A Fleishman, M Pavlakis, D A Mandelbrot,
      Abstract: Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes pre-donation and at 1, 6, 12, and 24 months post-donation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes post-donation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes post-donation. Importantly, some LKDs showed improvement in psychosocial functioning from pre- to post-donation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory two-year follow-up period in the USA.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T10:50:21.603494-05:
      DOI: 10.1111/ajt.14618
       
  • Isolated v-lesion in kidney transplant recipients: Characteristics,
           association with DSA and histological follow-up
    • Authors: Marion Rabant; Fanny Boullenger, Viviane Gnemmi, Gaëlle Pellé, François Glowacki, Alexandre Hertig, Isabelle Brocheriou, Caroline Suberbielle, Jean-Luc Taupin, Dany Anglicheau, Christophe Legendre, Jean-Paul Duong Van Huyen, David Buob
      Abstract: Isolated v-lesion (IvL) represents a rare and challenging situation in renal allograft biopsies because it is unknown whether IvL truly represents rejection, antibody- or T cell-mediated, or not.This multicentric retrospective study describes the clinicopathological features of IvL with an emphasis on the Donor Specific Antibodies (DSA) status, histological follow-up, and graft survival. Inclusion criteria were the presence of v-lesion with minimal interstitial (i≤1) and microvascular inflammation (g+ptc≤1). C4d positive biopsies were excluded.We retrospectively found 33 IvL biopsies in 33 patients, mainly performed in the early post-transplant period (median time 27 days) and clinically indicated in 66.7%. A minority of recipients (5/33, 15.2%) had DSA at the time of biopsy. IvL was treated by anti-rejection therapy in 21 cases (63.6%), whereas 12 (36.4%) were untreated. 70% of untreated patients and 66% of treated patients showed favorable histological evolution on subsequent biopsy. Kidney graft survival in IvL was significantly higher than in a matched cohort of antibody-mediated rejection with arteritis.In conclusion, IvL is not primarily antibody-mediated and may show a favorable evolution. The heterogeneity of IvL pathophysiology on early biopsies should prompt DSA testing as well as close clinical and histological follow-up in all patients with IvL.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T10:45:40.429972-05:
      DOI: 10.1111/ajt.14617
       
  • Novel Approaches to Antifungal Therapy
    • Authors: George R. Thompson; Thomas F. Patterson
      Abstract: Invasive fungal infections remain a major cause of morbidity and mortality in the solid organ transplant population. Non-Aspergillus infections are of particular concern due to the reduced antifungal susceptibility of many of these fungi (Scedopsorium, Lomentospora, Fusarium etc), the difficulty in distinguishing these organisms from Aspergillus spp based on histopathology alone, and the higher associated mortality observed with these organisms. Current treatment options for these fungi are limited, and voriconazole is the most commonly recommended primary agent1, 2 with combination therapy (terbinafine or an echinocandin) also recommended by some experts.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T10:45:38.336819-05:
      DOI: 10.1111/ajt.14616
       
  • Multi-level factors are associated with immunosuppressant nonadherence in
           heart transplant recipients: the international bright study
    • Authors: Kris Denhaerynck; Lut Berben, Fabienne Dobbels, Cynthia L. Russell, Marisa G Crespo-Leiro, Alain Jean Poncelet, Sabina De Geest,
      Abstract: Factors at the level of family/healthcare worker-, organization- and system are neglected in medication nonadherence research in heart transplantation (HTx). The four-continent, eleven-country cross-sectional BRIGHT study used multi-staged sampling to examine 36 HTx centers, including 36 HTx directors, 100 clinicians, and 1397 patients. Nonadherence to immunosuppressants–defined as any deviation in taking or timing adherence and/or dose reduction–was assessed using the BAASIS® interview. Guided by the Integrative Model of Behavioral Prediction and Bronfenbrenner's ecological model, we analyzed factors at these multiple levels using sequential logistic regression analysis (6 blocks). The nonadherence prevalence was 34.1%. Six multi-level factors were associated independently (either positively or negatively) with nonadherence: patient level: barriers to taking immunosuppressants (OR: 11.48); smoking (OR:2.19); family/healthcare provider level: frequency of having someone to help patients read health-related materials (OR:0.85); organization level: clinicians reporting non-adherent patients were targeted with adherence interventions (OR: 0.66); pick-up of medications at physician's office (OR: 2.31); and policy level: monthly out-of-pocket costs for medication (OR: 1.16). Factors associated with nonadherence are evident at multiple levels. Improving medication nonadherence requires addressing not only the patient, but also family/healthcare provider, organization, and policy levels.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T02:00:57.519023-05:
      DOI: 10.1111/ajt.14611
       
  • Duodenal graft complications requiring duodenectomy after pancreas and
           pancreas-kidney transplantation
    • Authors: Erica Pieroni; Niccolò Napoli, Carlo Lombardo, Piero Marchetti, Margherita Occhipinti, Carla Cappelli, Davide Caramella, Giovanni Consani, Gabriella Amorese, Maurizio De Maria, Fabio Vistoli, Ugo Boggi
      Abstract: Duodenal graft complications are poorly reported complications of pancreas transplantation that can result in graft loss. Excluding patients with early graft failure, after a median follow-up period of 126 months (range 23-198) duodenectomy was required in 14 of 312 pancreas transplants (4.5%). All patients were insulin-independent at the time of diagnosis. Reasons for duodenectomy included delayed duodenal graft perforation (n=10, 71.5%) and refractory duodenal graft bleeding (n=4, 28.5%).In patients with duodenal graft bleeding, a total duodenectomy was performed. In patients with duodenal graft perforation, preservation of a duodenal segment was possible in 5 patients but completion duodenectomy was necessary in one patient. After total duodenectomy, immediate enteric duct drainage was feasible in seven patients. In two patients, a pancreaticocutaneous fistula was created that was subsequently converted to enteric drainage in one patient. In the other patient, enteric fistulization occurred as a consequence of silent pressure perforation of the draining catheter on the ascending colon.After a mean follow-up period of 52 months (21-125), all patients were alive, well, and insulin-independent.An aggressive and timely surgical approach may permit graft rescue in patients with severe duodenal graft complications occurring after pancreas transplantation. Generalization of these results remains to be established.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-04T09:27:18.141876-05:
      DOI: 10.1111/ajt.14613
       
  • Response to: Renal Allograft Histology at 10 Years After Transplantation
           in the Tacrolimus Era: Evidence of Pervasive Chronic Injury
    • Authors: Renaud Snanoudj; Christophe Legendre
      Abstract: We read with great interest the study by Stegall (1) and colleagues regarding histological lesions observed on 10-year protocol biopsies in 145 kidney transplant recipients who had received standard-of-care immunosuppression (tacrolimus and mycophenolic acid). Of interest, these biopsies displayed severe arteriolar hyalinosis in 66% of cases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T07:35:22.82334-05:0
      DOI: 10.1111/ajt.14612
       
  • Personal Viewpoint: The Bridge Between Transplantation and Regenerative
           Medicine. Beginning a New Banff Classification of Tissue Engineering
           Pathology
    • Authors: K. Solez; K. C. Fung, K. A. Saliba, V. L. C. Sheldon, A. Petrosyan, L. Perin, J. F. Burdick, W. H. Fissell, A. J. Demetris, L. D. Cornell
      Abstract: The science of regenerative medicine is arguably older than transplantation - the first major textbook was published in 1901 - and a major regenerative medicine meeting took place in 1988, three years before the first Banff transplant pathology meeting. However, the subject of regenerative medicine/tissue engineering pathology has never received focused attention. Defining and classifying tissue engineering pathology is long overdue. In the next decades, the field of transplantation will enlarge at least tenfold, through a hybrid of tissue engineering combined with existing approaches to lessening the organ shortage. Gradually transplantation pathologists will become tissue-(re-) engineering pathologists with enhanced skill sets to address concerns involving the use of bioengineered organs. We outline ways of categorizing abnormalities in tissue-engineered organs through traditional light microscopy or other modalities including biomarkers. We propose creating a new Banff Classification of tissue engineering pathology to standardize and assess de novo bioengineered solid organs transplantable success in vivo. We recommend constructing a framework for a classification of tissue engineering pathology now with interdisciplinary consensus discussions to further develop and finalize the classification at future Banff Transplant Pathology meetings, in collaboration with the human cell atlas project. A possible nosology of pathologic abnormalities in tissue-engineered organs is suggested.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T02:55:52.478568-05:
      DOI: 10.1111/ajt.14610
       
  • The causes, significance and consequences of inflammatory fibrosis in
           kidney transplantation: The Banff i-IFTA lesion
    • Authors: Brian J. Nankivell; Meena Shingde, Karen L. Keung, Caroline L-S. Fung, Richard J. Borrows, Philip J. O'Connell, Jeremy R. Chapman
      Abstract: Inflammation within areas of interstitial fibrosis and tubular atrophy (i-IFTA) is associated with adverse outcomes in kidney transplantation.We evaluated i-IFTA in 429 indication- and 2052 protocol-biopsies from a longitudinal cohort of 362 kidney-pancreas recipients to determine its prevalence, time-course, and relationships with T cell mediated rejection (TCMR), immunosuppression, and outcome.Sequential histology demonstrated that i-IFTA was preceded by cellular interstitial inflammation, and followed by IF/TA. The prevalence and intensity of i-IFTA increased with developing chronic fibrosis, and correlated with inflammation, tubulitis and immunosuppression era (P
      PubDate: 2017-12-01T02:55:37.402393-05:
      DOI: 10.1111/ajt.14609
       
  • Sex-Based Disparities in Delisting for Being “Too Sick” for
           Liver Transplantation
    • Authors: Giuseppe Cullaro; Monika Sarkar, Jennifer C. Lai
      Abstract: Women with cirrhosis awaiting liver transplantation (LT) experience higher rates of waitlist mortality than men – it is unknown if practices surrounding delisting for being “too sick” for LT contribute to this disparity beyond death alone. We conducted an analysis of patients listed for LT in the UNOS/OPTN network not receiving exception points from 5/1/07 to 7/1/14 with a primary outcome of delisting with removal codes of “too sick” or “medically unsuitable.” A total of 44,388 patients were included, 4,458 were delisted for being “too sick” for LT. Delisting was more frequent in women (11v.9%, p
      PubDate: 2017-12-01T02:00:26.956259-05:
      DOI: 10.1111/ajt.14608
       
  • Triptolide Inhibits Donor Specific Antibody Production and Attenuates
           Mixed Antibody-Mediated Renal Allograft Injury
    • Authors: Daqiang Zhao; Siwen Li, Tao Liao, Yuan Wei, Mingyu Liu, Fei Han, Zihuan Luo, Xiaonan Liu, Qiquan Sun
      Abstract: Donor specific antibodies (DSAs) are major mediators of renal allograft injury, and strategies to inhibit DSA are important in promoting long term graft survival. Triptolide exhibits a wide spectrum of anti-inflammatory and immuno- suppressive activities, and in autoimmune diseases it inhibits autoantibody levels. In this study, we investigated the suppressive role of triptolide in the generation of donor specific antibodies in transplant recipients. We found that triptolide treatment of skin allograft recipients in the mouse significantly suppressed the development of circulating anti-donor specific IgG and effectively alleviated DSAs-mediated renal allograft injury, which led to prolonged allograft survival. In vitro studies revealed that triptolide inhibited the differentiation of B cells into CD138+CD27++ plasma cells, reduced the levels of IgA, IgG and IgM secreted by plasma cells, and repressed somatic hypermutation and class switch recombination of B cells. Moreover, triptolide treated recipients showed reduced number of B cells, plasma cells and memory B cells in spleens and decreased number of T, B, NK cells and macrophages infiltrating in grafts. These findings highlight the importance of triptolide in suppressing DSAs and establish triptolide as a novel therapeutic agent for antibody-mediated allograft rejection.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-27T02:30:21.344378-05:
      DOI: 10.1111/ajt.14602
       
  • Review: The transcripts associated with organ allograft rejection
    • Authors: Philip F Halloran; Jeffery M. Venner, Katelynn Madill-Thomsen, Gunilla Einecke, Michael Parkes, Luis G. Hidalgo, Konrad S. Famulski
      Abstract: The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants. Associations can be universal (all rejection), TCMR-selective, or ABMR-selective, with universal being strongest and ABMR-selective weakest. Top universal transcripts are IFNG-inducible (e.g. CXCL11; IDO1, WARS) or shared by effector T cells (ETCs) and NK cells (e.g. KLRD1, CCL4). TCMR-selective transcripts are expressed in activated ETCs (e.g. CTLA4, IFNG); activated (e.g. ADAMDEC1) or IFNG-induced macrophages (e.g. ANKRD22). ABMR-selective transcripts are expressed in NK cells (e.g. FGFBP2, GNLY) and endothelial cells (e.g. ROBO4, DARC). Transcript associations are highly reproducible between biopsy sets when the same rejection definitions, case mix, algorithm, and technology are applied, but exact ranks will vary. Previously published rejection-associated transcripts resemble universal and TCMR-selective transcripts due to incomplete representation of ABMR. Rejection-associated transcripts are never completely rejection-specific because they are shared with the stereotyped response-to-injury and innate immunity.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-25T11:15:28.865361-05:
      DOI: 10.1111/ajt.14600
       
  • Comprehensive Review of Post-Organ Transplant Hematologic Cancers
    • Authors: Vikas R. Dharnidharka
      Abstract: A higher risk for a variety of cancers is among the major complications of post-transplant immunosuppression. In this part of a continuing series on cancers post-transplant, this review focuses on the hematologic cancers after solid organ transplant. Post-transplant lymphoproliferative disorders (PTLDs), which comprise the great majority of hematologic cancers, represent a spectrum of conditions that include, but are not limited to, the Hodgkin and non-Hodgkin lymphomas. The oncogenic Epstein-Barr virus is a key pathogenic driver in many PTLD cases, through known and unknown mechanisms. The other hematologic cancers include leukemias and plasma cell neoplasms (multiple myeloma and plasmacytoma). Clinical features vary across malignancies and location. Preventive screening strategies have been attempted mainly for PTLDs. Treatments include the chemotherapy regimens for the specific cancers, but also include reduction of immunosuppression, rituximab and other therapies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-25T11:15:26.965672-05:
      DOI: 10.1111/ajt.14603
       
  • Early Barriers to Neonatal Porcine Islet Engraftment in a Dual Transplant
           Model
    • Authors: K P Samy; R P Davis, Q Gao, B M Martin, M Song, J Cano, A B Farris, A McDonald, E K Gall, C R Dove, F V Leopardi, T How, K D Williams, G R Devi, B H Collins, A D Kirk
      Abstract: Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including, the poorly understood instant blood mediated inflammatory reaction (IBMIR), and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses to allo-islet responses in primates. We recently developed a dual islet transplant model, which enables direct histological comparison of early engraftment immunobiology. In this study, we investigate early immune responses to neonatal porcine islet (NPI) xenografts compared to rhesus islet allografts at 1 hour, 24 hours, and 7 days. Within the first 24 hours after intraportal infusion, we identified greater apoptosis (caspase 3 activity and TUNEL positive cells) of NPIs when compared to alloislets (AIs). Macrophage infiltration was significantly greater at 24 hours compared with 1 hour in both NPI (WT) and AIs. At 7 days, IgM and macrophages were highly specific for NPIs (GTKO) compared to AIs. These findings demonstrate an augmented macrophage and antibody response towards xenografts compared to allografts. These data may inform future immune or genetic manipulations required to improve xenoislet engraftment.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-25T11:15:24.808902-05:
      DOI: 10.1111/ajt.14601
       
  • Improvement in Pancreas Transplant Evaluation and Surgical Volume Using a
           Multidisciplinary Approach
    • Authors: Joseph R. Scalea; Samuel Sultan, Elizabeth Lamos, Stephen T. Bartlett, Rolf N. Barth
      Abstract: Pancreas numbers are down: Pancreas transplantation is the only long-term treatment for diabetes which restores glucose homeostasis, without the risks of hypoglycemia.1-3 Further, receiving a simultaneous pancreas kidney (SPK) transplant improves life expectancy over kidney transplantation alone.4,5 Despite this, the total number of pancreas transplants in the United States has decreased since 2006. Experts in the field recently reported that, while this drop in volume is multifactorial, the lack of a steady referral source is partly to blame.1This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-22T12:51:19.510128-05:
      DOI: 10.1111/ajt.14598
       
  • Shipping Living Donor Kidneys and Transplant Recipient Outcomes
    • Authors: Eric Treat; Eric K H Chow, John D Peipert, Amy Waterman, Lorna Kwan, Allan B Massie, Alvin G. Thomas, Mary Grace Bowring, David Leeser, Stuart Flechner, Marc L Melcher, Sandip Kapur, Dorry L Segev, Jeffrey Veale
      Abstract: Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1,267 shipped and 205 non-shipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008-2015, compared to 4,800 unrelated, non-shipped, non-KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25 to 23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non-KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% CI: 1.02-1.09, p0.9). This study of KPD-facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow-up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-22T10:05:23.048278-05:
      DOI: 10.1111/ajt.14597
       
  • Thymic function is a major determinant of antibody-mediated rejection
           onset in heart transplantation
    • Authors: A. Sannier; N. Stroumza, G. Caligiuri, M. Le Borgne-Moynier, F. Andreata, J. Senemaud, L. Louedec, G. Even, A. T. Gaston, C. Deschildre, A. Couvelard, P. Ou, R. Cheynier, P. Nataf, R. Dorent, A. Nicoletti
      Abstract: Thymic function progressively decreases with age but may be boosted in certain circumstances. We questioned whether heart transplantation was such a situation and whether the thymic function was related to the onset of rejection. Twenty-eight antithymocyte globulin-treated heart transplant recipients were included. Patients diagnosed for an antibody-mediated rejection on endomyocardial biopsy had higher proportion of circulating recent thymic emigrant CD4+ T cells and T cell receptor excision circle levels than other transplanted subjects. Thymus volume and density, assessed by computed tomography in a subset of patients, was also higher in patient experiencing antibody-mediated rejection. We demonstrate that thymic function is a major determinant of antibody-mediated rejection onset and question whether thymectomy could be a prophylactic strategy to prevent alloimmune humoral responses.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T11:45:33.251899-05:
      DOI: 10.1111/ajt.14595
       
  • Islet allo-autotransplantation: allogeneic pancreas transplantation
           followed by transplant pancreatectomy and islet transplantation
    • Authors: M.F. Nijhoff; J. Dubbeld, A.R. van Erkel, P.J.M van der Boog, T.J. Rabelink, M.A. Engelse, E.J.P de Koning
      Abstract: Simultaneous pancreas/kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end stage renal disease (ESRD). Due to complications, in up to 10% of cases allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39-year-old woman with T1D and ESRD who had received an SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft and almost 480,000 islet equivalents were infused into the portal vein. The patient recovered fully. After three months near-normal mixed meal test (fasting glucose 7.0 mmol/L, 2-hour glucose 7.5 mmol/L, maximal stimulated C-peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. HbA1c while taking a low dose of long-acting insulin was 32.7 mmol/mol Hb (5.3%). When a donor pancreas is lost after transplantation, rescue beta cell therapy by islet allo-autotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA allo-antigen exposure.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T11:45:19.621809-05:
      DOI: 10.1111/ajt.14593
       
  • Invited response to Recurrence of oxalate nephropathy after isolated
           kidney transplantation for primary hyperoxaluria type 2
    • Authors: Tsering Dhondup; Elizabeth C. Lorenz, Dawn S. Milliner, John C. Lieske
      Abstract: We read with interest the letter from Dr. Del Bello and colleagues regarding our recent case report of successful combined liver/kidney transplantation in a patient with primary hyperoxaluria type 2 (PH2) that resulted in normalization of urine and plasma oxalate levels. They describe a patient with PH2 who, unfortunately, developed renal allograft failure 6 months after a kidney alone transplant (1). The reasons for renal allograft failure in their patient are not entirely clear.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T09:20:19.93494-05:0
      DOI: 10.1111/ajt.14596
       
  • Heme Oxygenase-1 Regulates Sirtuin-1 – Autophagy Pathway in Liver
           Transplantation: From Mouse-to-Human
    • Authors: Kojiro Nakamura; Shoichi Kageyama, Shi Yue, Jing Huang, Takehiro Fujii, Bibo Ke, Rebecca A. Sosa, Elaine F. Reed, Nakul Datta, Ali Zarrinpar, Ronald W. Busuttil, Jerzy W. Kupiec-Weglinski
      Abstract: Liver ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although graft autophagy is essential for resistance against hepatic IRI, its significance in clinical OLT remains unknown. Despite recent data identifying heme oxygenase-1 (HO-1) as a putative autophagy inducer, its role in OLT and interactions with Sirtuin-1 (SIRT1), a key autophagy regulator, have not been studied. We aimed to examine HO-1 mediated autophagy induction in human OLT and in a murine OLT model with extended (20h) cold storage, as well as to analyze the requirement for SIRT1 in autophagy regulation by HO-1. Fifty-one hepatic biopsies from OLT patients were collected under an IRB protocol two hours after portal reperfusion, followed by Western blot analyses. High HO-1 levels correlated with well-preserved hepatocellular function and enhanced SIRT1/LC3B expression. In mice, HO-1 overexpression by genetically-modified HO-1 macrophage therapy, was accompanied by decreased OLT damage, increased SIRT1/LC3B expression, whereas adjunctive inhibition of SIRT1 signaling diminished HO-1 mediated hepatoprotection and autophagy induction. Our translational study confirms the clinical relevance of HO-1 cytoprotection and identifies SIRT1-mediated autophagy pathway as a new essential regulator of HO-1 function in IR-stressed OLT.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-14T10:17:02.172312-05:
      DOI: 10.1111/ajt.14586
       
  • Salvage therapy with topical posaconazole in lung transplant recipients
           with invasive scedosporium infection
    • Authors: Amparo Solé; Ana A. García-Robles, Carlos Jordá, Enrique Cases Viedma, Nuria Mancheño, José Luis Poveda-Andrés, Juan Pablo Reig Mezquida, Javier Pemán
      Abstract: Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplant, but it rarely causes invasive infection. Treatment remains challenging, particularly due to the inherent resistance to multiple antifungal agents. We present three complicated invasive tracheobronchial and lung Scedosporium apiospermum infections following lung transplant. In two of three cases, the infection was clinically and radiologically cured with frequent cleansing bronchoscopies, combining triazole with terbinafine therapy and nebulized posaconazole. These cases highlight the importance of adjunctive nebulized therapy in addition to prolonged triazole treatment to manage complex invasive Scedosporium infections in immunosuppressed patients. Posaconazole (PSZ) was delivered during the bronchoscopy procedure through intrabronchial administration, whereas an eFlow rapid® device was used for nebulized therapy. Topical posaconazole was well tolerated in two patients, with only a slight cough during administrations; the third patient suffered local irritation with poor tolerance, which led to its withdrawal. This is the first report on compassionate use of topical posaconazole as salvage therapy for resistant mold infections in lung transplantation recipients. These three cases represent the entire experience using this approach; no additional patients have received this therapy due to not having received any additional cases of Scedosporium tracheobronchitis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T08:40:41.749785-05:
      DOI: 10.1111/ajt.14580
       
  • Emergency Department Utilization among Kidney Transplant Recipients in the
           United States
    • Authors: Brendan P. Lovasik; Rebecca Zhang, Jason M. Hockenberry, Justin D. Schrager, Stephen O. Pastan, Andrew B. Adams, Sumit Mohan, Christian P. Larsen, Rachel E. Patzer
      Abstract: Patients with End Stage Renal Disease (ESRD) use the emergency department (ED) at a 6-fold higher rate than U.S. adults. No national studies have described ED utilization rates among kidney transplant (KTx) recipients, and the factors associated with higher ED utilization. We examined a cohort of 132,725 adult KTx recipients in the United States Renal Data System (2005-2013). ED visits, hospitalization, and outpatient nephrology visits were obtained from Medicare claims databases. Nearly half (46.1%) of KTx recipients had at least one ED visit (1.61 ED visits/patient year) and 39.7% of ED visits resulted in hospitalization in the first year post-transplant. ED visit rate was high in the first 30 days (5.26 visits/person year (PY)), but declined substantially thereafter (1.81 visits/ PY in months 1-3; 1.13 visits/PY in months 3-12 post-transplant). ED visit rates were higher in the first 30 days vs. dialysis patients, but less than half the rate thereafter. Female sex, public insurance, medical comorbidities, longer pre-transplant dialysis vintage, and delayed graft function were associated with higher ED utilization in the first year post-KTx. Policies and strategies addressing potentially preventable ED visits should be promoted to help improve patient care and increase efficient utilization of ED resources.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T08:40:39.540979-05:
      DOI: 10.1111/ajt.14578
       
  • Beneficial effect of recombinant rC1rC2 collagenases on human islet
           function: Efficacy of low dose enzymes on pancreas digestion and yield
    • Authors: Gopalakrishnan Loganathan; Subhashree Venugopal, Andrew G. Breite, William W. Tucker, Siddharth Narayanan, Maheswaran Dhanasekaran, SriPrakash Mokshagundam, Michael L. Green, Michael G. Hughes, Stuart K. Williams, Francis E. Dwulet, Robert C. McCarthy, Appakalai N Balamurugan
      Abstract: High number of human islets can be isolated using modern purified tissue dissociation enzymes, however it requires using>20 Wunsch Unit (WU)/gram of pancreas for digestion. Attempts to reduce this dose have resulted in pancreas under-digestion and poor islet recovery but improved islet function. In this study, we achieved high number of functional islets using low dose of recombinant collagenase enzyme mixture (RCEM). The collagenase dose used in these isolations is about 42% of the natural collagenase enzyme mixture (NCEM) dose commonly used to digest a 100g pancreas. Low dose RCEM was efficient in digesting entire pancreases to obtain higher yield (5,535±830 IEQ/gram and 2,582±925 IEQ/gram, P
      PubDate: 2017-10-16T11:25:18.928893-05:
      DOI: 10.1111/ajt.14542
       
  • Innate allorecognition by monocytic cells and its role in graft rejection
    • Authors: F. G. Lakkis; X. C. Li
      Pages: 289 - 292
      Abstract: Innate recognition of microbial products and danger molecules by monocytes and macrophages has been well established; this is mediated primarily by pattern-recognition receptors and is central to the activation of innate and adaptive immune cells required for productive immunity. Whether monocytes and macrophages are equipped with an allorecognition system that allows them to respond directly to allogeneic grafts is a topic of much debate. Recent studies provide compelling evidence that these cells can recognize allogeneic entities and that they mediate graft rejection via direct cytotoxicity and priming of alloreactive T cells. In addition, these studies have uncovered a mechanism of innate allorecognition based on detection of the polymorphic molecule signal regulatory protein α (SIRPα) on donor cells. Further understanding of innate allorecognition and its consequences would provide essential insight into allograft rejection and lead to better therapies for transplant patients.
      PubDate: 2017-08-24T09:44:46.017652-05:
      DOI: 10.1111/ajt.14436
       
  • iNKT cell activation plus T-cell transfer establishes complete chimerism
           in a murine sublethal bone marrow transplant model
    • Authors: Rumi Ishii; Toshihito Hirai, Satoshi Miyairi, Kazuya Omoto, Masayoshi Okumi, Yasuyuki Ishii, Kazunari Tanabe
      Pages: 328 - 340
      Abstract: Transplant tolerance induction makes it possible to preserve functional grafts for a lifetime without immunosuppressants. One powerful method is to generate mixed hematopoietic chimeras in recipients by adoptive transfer of donor-derived bone marrow cells (BMCs). In our murine transplantation model, we established a novel method for mixed chimera generation using sublethal irradiation, CD40-CD40L blockade, and invariant natural killer T-cell activation. However, numerous BMCs that are required to achieve stable chimerism makes it difficult to apply this model for human transplantation. Here, we show that donor-derived splenic T cells could contribute to not only the reduction of BMC usage but also the establishment of complete chimerism in model mice. By cotransfer of T cells together even with one-fourth of the BMCs used in our original method, the recipient mice yielded complete chimerism and could acquire donor-specific skin-allograft tolerance. The complete chimeric mice did not show any remarks of graft versus host reaction in vivo and in vitro. Inhibition of the apoptotic signal resulted in increase in host-derived CD8+ T cells and chimerism brake. These results suggest that donor-derived splenic T cells having veto activity play a role in the depletion of host-derived CD8+ T cells and the facilitation of complete chimerism.
      PubDate: 2017-09-15T07:41:52.740024-05:
      DOI: 10.1111/ajt.14453
       
  • CD4+CD28null T cells are not alloreactive unless stimulated by
           interleukin-15
    • Authors: B. Dedeoglu; N. H. R. Litjens, M. Klepper, R. Kraaijeveld, W. Verschoor, C. C. Baan, M. G. H. Betjes
      Pages: 341 - 350
      Abstract: Proinflammatory, cytotoxic CD4+CD28null T cells can be substantially expanded in patients with end-stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4+CD28null T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated based on proliferation, degranulation, cytotoxicity, and cytokine production. Further, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28+ T cells. CD4+CD28null T cells contained alloreactive (CD137+) T cells but did not proliferate in response to allogeneic stimulation, unless interleukin (IL)-15 was added. However, they could proliferate on stimulation with cytomegalovirus antigen without exogenous cytokines. IL-15 increased the frequency of proliferating alloreactive CD4+CD28null T cells to 30.5% without inducing CD28 expression (P 
      PubDate: 2017-10-02T08:45:25.284405-05:
      DOI: 10.1111/ajt.14480
       
  • Longitudinal assessment of T cell inhibitory receptors in liver transplant
           recipients and their association with posttransplant infections
    • Authors: Krupa R. Mysore; Rafik M. Ghobrial, Sunil Kannanganat, Laurie J. Minze, Edward A. Graviss, Duc T. Nguyen, Katherine K. Perez, Xian C. Li
      Pages: 351 - 363
      Abstract: Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, T cells are also critical in protective immunity, especially in immune-compromised patients. In this study, we examined the association of T cell dysfunction, as marked by expression of T cell exhaustion molecules, and posttransplant infections in a cohort of liver transplant patients. We focused on Programmed Death 1 (PD-1) and T cell Ig- and mucin-domain molecule 3 (Tim-3), which are potent co-inhibitory receptors, and their persistent expression often leads to T cell dysfunction and compromised protective immunity. We found that patients with the highest expression of PD-1 +Tim-3+ T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days. Longitudinal analysis in the first year showed a strong association between variability of PD-1 and Tim-3 expression by T cells and infectious episodes in transplant patients. Furthermore, T cells that expressed PD-1 and Tim-3 had a significantly reduced capacity in producing interferon (IFN)-γ in vitro, and this reduced IFN-γ production could be partially reversed by blocking PD-1 and Tim-3. Interestingly, the percentage of Foxp3+ regulatory T cells in liver transplant patients was stable in the study period. We concluded that the functional status of T cells before and after liver transplantation, as shown by PD-1 and Tim-3 expression, may be valuable in prognosis and management of posttransplant infections.
      PubDate: 2017-11-20T09:45:29.995203-05:
      DOI: 10.1111/ajt.14546
       
  • T cell–mediated rejection is a major determinant of inflammation in
           scarred areas in kidney allografts
    • Authors: Carmen Lefaucheur; Clément Gosset, Marion Rabant, Denis Viglietti, Jérôme Verine, Olivier Aubert, Kevin Louis, Denis Glotz, Christophe Legendre, Jean-Paul Duong Van Huyen, Alexandre Loupy
      Pages: 377 - 390
      Abstract: Inflammation in fibrosis areas (i-IF/TA) of kidney allografts is associated with allograft loss; however, its diagnostic significance remains to be determined. We investigated the clinicohistologic phenotype and determinants of i-IF/TA in a prospective cohort of 1539 kidney recipients undergoing evaluation of i-IF/TA and tubulitis in atrophic tubules (t-IF/TA) on protocol allograft biopsies performed at 1 year posttransplantation. We considered donor, recipient, and transplant characteristics, immunosuppression, and histological diagnoses in 2260 indication biopsies performed within the first year posttransplantation. Nine hundred forty-six (61.5%) patients presented interstitial fibrosis/tubular atrophy (IF/TA Banff grade > 0) at 1 year posttransplant, among whom 394 (41.6%) showed i-IF/TA. i-IF/TA correlated with concurrent t-IF/TA (P 
      PubDate: 2017-11-21T07:45:41.856285-05:
      DOI: 10.1111/ajt.14565
       
  • Kidney allograft offers: Predictors of turndown and the impact of late
           organ acceptance on allograft survival
    • Authors: J. B. Cohen; J. Shults, D. S. Goldberg, P. L. Abt, D. L. Sawinski, P. P. Reese
      Pages: 391 - 401
      Abstract: There is growing interest in understanding patterns of organ acceptance and reducing discard. Little is known about how donor factors, timing of procurement, and geographic location affect organ offer decisions. We performed a retrospective cohort study of 47 563 deceased donor kidney match-runs from 2007 to 2013. Several characteristics unrelated to allograft quality were independently associated with later acceptance in the match-run: Public Health Service increased-risk donor status (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 2.29-2.69), holiday or weekend procurement (aOR 1.11, 95% CI 1.07-1.16), shorter donor stature (aOR 1.53 for 180 cm, 95% CI 1.28-1.94), and procurement in an area with higher intensity of market competition (aOR 1.71, 95% CI 1.62-1.78) and with the longest waiting times (aOR 1.41, 95% CI 1.34-1.49). Later acceptance in the match-run was associated with delayed graft function but not all-cause allograft failure (adjusted hazard ratio 1.01, 95% CI 0.96-1.07). Study limitations include a lack of match-run data for discarded organs and the possibility of sequence inaccuracies for some nonlocal matches. Interventions are needed to reduce turndowns of viable organs, especially when decisions are driven by infectious risk, weekend or holiday procurement, geography, or other donor characteristics unrelated to allograft quality.
      PubDate: 2017-09-02T11:16:02.608845-05:
      DOI: 10.1111/ajt.14449
       
  • Harms of unsuccessful donation after circulatory death: An exploratory
           study
    • Authors: Lauren J. Taylor; Anne Buffington, Joseph R. Scalea, Norman Fost, Kenneth D. Croes, Joshua D. Mezrich, Margaret L. Schwarze
      Pages: 402 - 409
      Abstract: While donation after circulatory death (DCD) has expanded options for organ donation, many who wish to donate are still unable to do so. We conducted face-to-face interviews with family members (N = 15) who had direct experience with unsuccessful DCD and 5 focus groups with professionals involved in the donation process. We used qualitative content analysis to characterize the harms of nondonation as perceived by participants. Participants reported a broad spectrum of harms affecting organ recipients, donors, and donor families. Harms included waste of precious life-giving organs and hospital resources, inability to honor the donor's memory and character, and impaired ability for families to make sense of tragedy and cope with loss. Donor families empathized with the initial hope and ultimate despair of potential recipients who must continue their wait on the transplant list. Focus group members reinforced these findings and highlighted the struggle of families to navigate the uncertainty regarding the timing of death during the donation process. While families reported significant harm, many appreciated the donation attempt. These findings highlight the importance of organ donation to donor families and the difficult experiences associated with current processes that could inform development of alternative donation strategies.
      PubDate: 2017-09-18T08:51:10.243238-05:
      DOI: 10.1111/ajt.14464
       
  • Laparoscopic sleeve gastrectomy improves renal transplant candidacy and
           posttransplant outcomes in morbidly obese patients
    • Authors: Y. Kim; A. D. Jung, V. K. Dhar, J. S. Tadros, D. P. Schauer, E. P. Smith, D. J. Hanseman, M. C. Cuffy, R. R. Alloway, A. R. Shields, S. A. Shah, E. S. Woodle, T. S. Diwan
      Pages: 410 - 416
      Abstract: Morbid obesity is a barrier to kidney transplantation due to inferior outcomes, including higher rates of new-onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. Laparoscopic sleeve gastrectomy (LSG) increases transplant eligibility by reducing BMI in kidney transplant candidates, but the effect of surgical weight loss on posttransplantation outcomes is unknown. Reviewing single-center medical records, we identified all patients who underwent LSG before kidney transplantation from 2011-2016 (n = 20). Post-LSG kidney recipients were compared with similar-BMI recipients who did not undergo LSG, using 2:1 direct matching for patient factors. McNemar's test and signed-rank test were used to compare groups. Among post-LSG patients, mean BMI ± standard deviation (SD) was 41.5 ± 4.4 kg/m2 at initial encounter, which decreased to 32.3 ± 2.9 kg/m2 prior to transplantation (P 
      PubDate: 2017-09-12T08:45:26.208965-05:
      DOI: 10.1111/ajt.14463
       
  • Exercise capacity in young adults after hematopoietic cell transplantation
           in childhood
    • Authors: Anders Öberg; Margareta Genberg, Andrei Malinovschi, Hans Hedenström, Per Frisk
      Pages: 417 - 423
      Abstract: A symptom-limited incremental cycle ergometer test was performed in 17 young adult patients treated with hematopoietic cell transplantation and total body irradiation for hematologic malignancies during childhood. These 17 young adult patients were compared with 17 sex- and age-matched healthy control subjects. Assessments of pulmonary function, cardiac function, body composition, and levels of growth hormone were made. The median follow-up was 17.7 years. Patients achieved 63.2% of the predicted peak workload, whereas controls achieved 96.1% (P 80% (P 
      PubDate: 2017-09-05T09:55:32.287625-05:
      DOI: 10.1111/ajt.14456
       
  • Dual-graft adult living donor liver transplantation with ABO-incompatible
           graft: short-term and long-term outcomes
    • Authors: J. H. Kwon; G. W. Song, S. Hwang, K. H. Kim, C. S. Ahn, D. B. Moon, T. Y. Ha, D. H. Jung, G. C. Park, S. H. Kim, W. H. Kang, H. D. Cho, E. K. Jwa, E. Y. Tak, V. A. Kirchner, S. G. Lee
      Pages: 424 - 433
      Abstract: ABO-incompatible (ABOi) dual-graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short- and long-term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end-stage liver disease score was 12.2 ± 4.6. The 1-, 3-, and 5-year patient survival rate was 96.4% during the mean follow-up period of 57.0 ± 22.4 months. The 1-, 3-, and 5-year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO-compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.
      PubDate: 2017-09-01T08:45:30.054366-05:
      DOI: 10.1111/ajt.14448
       
  • Pure laparoscopic living donor hepatectomy: Focus on 55 donors undergoing
           right hepatectomy
    • Authors: K. S. Suh; S. K. Hong, K. W. Lee, N. J. Yi, H. S. Kim, S. W. Ahn, K. C. Yoon, J. Y. Choi, D. Oh, H. Kim
      Pages: 434 - 443
      Abstract: Although laparoscopic donor hepatectomy is increasingly common, few centers with substantial experience have reported the results of pure laparoscopic donor right hepatectomy (PLDRH). Here, we report the experiences of 60 consecutive liver donors undergoing pure laparoscopic donor hepatectomy (PLDH), with most undergoing right hepatectomy. None of the 60 donors who underwent PLDH had intraoperative complications and none required transfusions, reoperation, or conversion to open hepatectomy. Forty-five donors who underwent PLDRH between November 2015 and December 2016 were compared with 42 who underwent conventional donor right hepatectomy (CDRH) between May 2013 and February 2014. The total operation time was longer (330.7 vs 280.0 minutes; P 
      PubDate: 2017-09-07T12:30:39.690668-05:
      DOI: 10.1111/ajt.14455
       
  • Heparin-binding protein, lysozyme, and inflammatory cytokines in
           bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection
           in lung transplanted patients
    • Authors: Anna Stjärne Aspelund; Helena Hammarström, Malin Inghammar, Hillevi Larsson, Lennart Hansson, Bertil Christensson, Lisa I. Påhlman
      Pages: 444 - 452
      Abstract: Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin-binding protein (HBP), lysozyme, and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung-transplanted patients. One hundred thirteen BALF samples from 29 lung transplant recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable, or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme, and cytokines were analyzed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, whereas patients with rejection presented low levels that were comparable to noninfection samples. HBP, IL-1β, and IL-8 were the best diagnostic markers of infection with area under the receiver-operating characteristic curve values of 0.88, 0.91, and 0.90, respectively. In conclusion, HBP, IL-1β, and IL-8 could be useful diagnostic markers of pulmonary infection in lung-transplanted patients.
      PubDate: 2017-09-15T10:10:40.71787-05:0
      DOI: 10.1111/ajt.14458
       
  • Incidence and outcomes of primary central nervous system lymphoma in solid
           organ transplant recipients
    • Authors: Parag Mahale; Meredith S. Shiels, Charles F. Lynch, Eric A. Engels
      Pages: 453 - 461
      Abstract: Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed human immunodeficiency virus–infected people. Using data from the US transplant registry linked with 17 cancer registries (1987-2014), we studied PCNSL and systemic non-Hodgkin lymphoma (NHL) in 288 029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio = 65.1; N = 168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11.5; N = 2043). Compared to kidney recipients, PCNSL incidence was lower in liver recipients (adjusted incidence rate ratio [aIRR] = 0.52), similar in heart and/or lung recipients, and higher in other/multiple organ recipients (aIRR = 2.45). PCNSL incidence was higher in Asians/Pacific Islanders than non-Hispanic whites (aIRR = 2.09); after induction immunosuppression with alemtuzumab (aIRR = 3.12), monoclonal antibodies (aIRR = 1.83), or polyclonal antibodies (aIRR = 2.03); in recipients who were Epstein-Barr virus–seronegative at the time of transplant and at risk of primary infection (aIRR = 1.95); and within the first 1.5 years after transplant. Compared to other recipients, those with PCNSL had increased risk of death (adjusted hazard ratio [aHR] = 11.79) or graft failure/retransplantation (aHR = 3.24). Recipients with PCNSL also had higher mortality than those with systemic NHL (aHR = 1.48). In conclusion, PCNSL risk is highly elevated among transplant recipients, and it carries a poor prognosis.
      PubDate: 2017-09-02T11:20:39.751485-05:
      DOI: 10.1111/ajt.14465
       
  • Taking the challenge: A protocolized approach to optimize Pneumocystis
           pneumonia prophylaxis in renal transplant recipients
    • Authors: K. F. Urbancic; F. Ierino, E. Phillips, P. F. Mount, A. Mahony, J. A. Trubiano
      Pages: 462 - 466
      Abstract: While trimethoprim-sulfamethoxazole is considered first-line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim-sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Forty-two patients (35%) had 48 trimethoprim-sulfamethoxazole adverse drug reactions documented either at baseline or during the prophylaxis period, of which 83% were non-immune-mediated and 17% were immune-mediated. Significantly more patients underwent trimethoprim-sulfamethoxazole rechallenge after protocol implementation (4/22 vs 23/27; P = .0001), with no recurrence of adverse drug reactions in 74%. In those who experienced a new or recurrent reaction (26%), all were mild and self-limiting with only 1 recurrence of an immune-mediated reaction. After protocol implementation, aerosolized pentamidine-associated costs were reduced. The introduction of a standard approach to trimethoprim-sulfamethoxazole rechallenge in the context of both prior immune and non-immune-mediated reactions was safe and successful in improving the uptake of first-line Pneumocystis pneumonia prophylaxis in renal transplant recipients.
      PubDate: 2017-10-03T09:20:23.771513-05:
      DOI: 10.1111/ajt.14498
       
  • Prevalence and outcomes of cystic lesions of the transplant pancreas: The
           University of Wisconsin Experience
    • Authors: Talal M. Al-Qaoud; Eric J. Martinez, Hans W. Sollinger, Dixon B. Kaufman, Robert R. Redfield, Bridget Welch, Glen Leverson, Jon S. Odorico
      Pages: 467 - 477
      Abstract: Literature on the behavior of cystic lesions in pancreas transplants is scarce, and hence a better understanding is warranted. Data on recipients and their respective donors that underwent simultaneous kidney and pancreas, pancreas transplant alone, and pancreas after kidney between 1994 and 2015 were reviewed (n = 1185). Cystic lesions of the transplant pancreas developed in 22 patients (1.8%): 12 pseudocysts, 2 cysts/remnants, 4 intraductal papillary mucinous neoplasms (IPMN), 2 adenocarcinomas, 1 low-grade intraepithelial pancreatic neoplasia, and 1 case of polycystic kidney disease. The median size was 3.6 cm (1.6-5.5 cm), and occurred at a median time of 65.5 months (2-183 months) posttransplant. The median age of the graft at time of diagnosis was 42 years (25.7-54.5), with 17 of 22 grafts (77%) functioning at time of diagnosis. Triggers for investigation were elevations in pancreatic enzymes, re-admissions for abdominal pain, and incidentalomas. High-resolution imaging and diagnostic biopsy/aspiration with ancillary tests were the main diagnostic tests. Most pseudocysts were managed by percutaneous drainage, and although no firm inference can be made from such a small series, we have observed that the behavior and management of IPMN and adenocarcinoma in the pancreas graft appears congruent to that of the native pancreas.
      PubDate: 2017-11-15T08:16:01.080597-05:
      DOI: 10.1111/ajt.14540
       
  • Potential yield of imminent death kidney donation
    • Authors: Ryan A. Denu; Eneida A. Mendonca, Norman Fost
      Pages: 486 - 491
      Abstract: About 99 000 people are waiting for a kidney in the United States, and many will die waiting. The concept of “imminent death” donation, a type of living donation, has been gaining attention among physicians, patients, and ethicists. We estimated the number of potential imminent death kidney donors at the University of Wisconsin Hospital and Clinics by assessing the number of annual deaths in individuals with normal kidney function. Based on a previous survey suggesting that one-third of patients might be willing to donate at imminent death, we estimate that between 76 and 396 people in the state of Wisconsin would be medically eligible and willing to donate each year at the time of imminent death. We extrapolated these numbers to all transplant centers in the United States, estimating that between 5925 and 31 097 people might be eligible and willing to donate each year. Our results suggest that allowing donation at imminent death and including discussions about organ donation in end-of-life planning could substantially reduce the nation's kidney waiting list while providing many more donors the opportunity to give this gift.
      PubDate: 2017-11-11T10:15:24.942178-05:
      DOI: 10.1111/ajt.14524
       
  • Outcomes of organ transplants when the donor is a prior recipient
    • Authors: G. S. Lee; D. S. Goldberg, M. H. Levine, P. L. Abt
      Pages: 492 - 503
      Abstract: Organ shortage continues to challenge the field of transplantation. One potential group of donors are those who have been transplant recipients themselves, or Organ Donation After Transplant (ODAT) donors. We conducted a retrospective cohort study to describe ODAT donors and to compare outcomes of ODAT grafts versus conventional grafts. From October 1, 1987 to June 30, 2015, 517 former recipients successfully donated 803 organs for transplant. Former kidney recipients generally survived a median of approximately 4 years before becoming an ODAT donor whereas liver, lung, and heart recipients generally survived less than a month prior to donation. In the period June 1, 2005 to December 31, 2014, liver grafts from ODAT donors had a significantly higher risk of graft failure compared to non-ODAT liver transplants (P = .008). Kidney grafts donated by ODAT donors whose initial transplant occurred>1 year prior were associated with significantly increased graft failure (P = .012). Despite increased risk of graft failure amongst certain ODAT grafts, 5-year survival was still high. ODAT donors should be considered another form of expanded criteria donor under these circumstances.
      PubDate: 2017-11-21T07:25:25.403074-05:
      DOI: 10.1111/ajt.14536
       
  • Donor-derived Kaposi's sarcoma in a liver–kidney transplant
           recipient
    • Authors: S. C. Dollard; D. Douglas, S. V. Basavaraju, D. S. Schmid, M. Kuehnert, B. Aqel
      Pages: 510 - 513
      Abstract: Human herpes virus 8 (HHV-8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi's sarcoma (KS). KS can develop following organ transplantation through reactivation of the recipient's latent HHV-8 infection, or less commonly through donor-derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor-derived KS in the recipient of a liver–kidney transplant. The donor had multiple risk factors for HHV-8 infection. The KS was successfully treated by switching immunosuppression from tacrolimus to sirolimus. With an increasing number of human immunodeficiency virus (HIV)-positive persons seeking organ transplantation and serving as organ donors for HIV-positive recipients, HHV-8 prevalence among donors and recipients will likely increase and with that the risk for post-transplant KS. Predetermination of HHV-8 status can be useful when considering organ donors and recipients with risk factors, although there are currently no validated commercial tests for HHV-8 antibody screening.
      PubDate: 2017-10-25T10:08:57.9145-05:00
      DOI: 10.1111/ajt.14516
       
  • Predicted indirectly recognizable HLA epitopes (PIRCHE): Only the tip of
           the iceberg'
    • Authors: Gwendaline Guidicelli; Jean-Luc Taupin, Jonathan Visentin
      Pages: 521 - 522
      PubDate: 2017-09-05T10:01:06.092192-05:
      DOI: 10.1111/ajt.14474
       
  • Invited letter in response to “Predicted indirectly recognizable HLA
           epitopes (PIRCHE): Only the tip of the iceberg'”
    • Authors: Nils Lachmann; Matthias Niemann, Petra Reinke, Klemens Budde, Danilo Schmidt, Fabian Halleck, Axel Pruß, Constanze Schönemann, Eric Spierings, Oliver Staeck
      Pages: 523 - 524
      PubDate: 2017-11-04T10:25:22.741929-05:
      DOI: 10.1111/ajt.14535
       
  • Recurrence of oxalate nephropathy after isolated kidney transplantation
           for primary hyperoxaluria type 2
    • Authors: Arnaud Del Bello; Olivier Cointault, Audrey Delas, Nassim Kamar
      Pages: 525 - 526
      PubDate: 2017-11-11T10:36:07.594102-05:
      DOI: 10.1111/ajt.14550
       
  • A helpful approach to organ donation: From end-of-life care to effective
           organ transplantation
    • Authors: F. Caballero; M. Puig, J. Leal, O. Trejo, I. Díaz, S. Herrera, M. Turbau, J. Ris, S. Benito
      Pages: 528 - 529
      PubDate: 2017-10-05T11:20:21.213923-05:
      DOI: 10.1111/ajt.14493
       
 
 
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