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Enlightening Young Minds: A Small Step in the Curriculum, a Giant Leap in Organ Donation—A Survey of 996 Respondents on Organ Donation and Transplantation
Hakeem, Abdul Rahman; Ramesh, Vasanthi; Sapkota, Pradez; Priya, Gokula; Rammohan, Ashwin; Narasimhan, Gomathy; Reddy, Mettu Srinivas; Rela, Mohamed
doi : 10.1097/TP.0000000000003403
Transplantation: March 2021 - Volume 105 - Issue 3 - p 459-463
Research Highlights
Luo, Xunrong PhD, MD1
doi : 10.1097/TP.0000000000003655
Transplantation: March 2021 - Volume 105 - Issue 3 - p 464-465
Immunomodulation of Islet Organoids and the Promise of Sustainable Beta Cell Replacement: Has the Challenge Been Met?
Rogers, Natasha M. MBBS, PhD1,2; Ghimire, Kedar MSc, PhD1
doi : 10.1097/TP.0000000000003493
Transplantation: March 2021 - Volume 105 - Issue 3 - p 466-467
Stanley C. Jordan, MD
doi : 10.1097/TP.0000000000003546
Transplantation: March 2021 - Volume 105 - Issue 3 - p 468-470
Transplantoux. Beyond the Successful Climb of Mont Ventoux: The Road to Sustained Physical Activity in Organ Transplantation
Cappelle, Marie; Masschelein, Evi; De Smet, Stefan; Vos, Robin; Vanbekbergen, Jonas; Gryp, Sabine; Van Craenenbroeck, Amaryllis H.; Cornelissen, Veronique; Verreydt, Joris; Van Belleghem, Yves; Peperstraete, Harlinde; De Paepe, Lucien; Buelens, Louis; Put, Johan; De Geest, Sabina; Monbaliu, Diethard
doi : 10.1097/TP.0000000000003564
Transplantation: March 2021 - Volume 105 - Issue 3 - p 471-473
Preliver Transplant Aspergillus Colonization: An Ounce of Prevention
Pereira, Marcus R. MD, MPH
doi : 10.1097/TP.0000000000003277
Transplantation: March 2021 - Volume 105 - Issue 3 - p 474-475
Red Blood Cells’ Prestorage Leukoreduction and Reduced Risk of Posttransplant Hepatocellular Cancer Recurrence: Another Piece of the Tumor–immune System Puzzle?
Lerut, Jan P. MD, PhD1; Lai, Quirino MD, PhD2
doi : 10.1097/TP.0000000000003266
Transplantation: March 2021 - Volume 105 - Issue 3 - p 476-477
Chronic-active Antibody-mediated Rejection: To Belatacept or Not, That Is the HOT Question
van der Zwan, Marieke MD1,2; Hesselink, Dennis A. MD, PhD1,2; Baan, Carla C. PhD1,2; Clahsen-van Groningen, Marian C. MD, PhD1,3
doi : 10.1097/TP.0000000000003279
Transplantation: March 2021 - Volume 105 - Issue 3 - p 478-479
Ureaplasma and Lung Transplantation: A Pinch of Prophylaxis May Mollify a Not-So-Cute Infection
Glanville, Allan R. MD1
doi : 10.1097/TP.0000000000003541
Transplantation: March 2021 - Volume 105 - Issue 3 - p 480-481
Enabling Clinical Trials for AMR in the Era of Precision Medicine
Cumpelik, Arun MD, PhD1; Zhang, Zhongyang PhD2; Menon, Madhav C. MBBS, MD1
doi : 10.1097/TP.0000000000003275
Transplantation: March 2021 - Volume 105 - Issue 3 - p 482-483
Thirty Years of Tacrolimus in Clinical Practice
Ong, Song C. MD1; Gaston, Robert S. MD, FAST1,2
doi : 10.1097/TP.0000000000003350
Transplantation: March 2021 - Volume 105 - Issue 3 - p 484-495
Tacrolimus was discovered in 1984 and entered clinical use shortly thereafter, contributing to successful solid organ transplantation across the globe. In this review, we cover development of tacrolimus, its evolving clinical utility, and issues affecting its current usage. Since earliest use of this class of immunosuppressant, concerns for calcineurin-inhibitor toxicity have led to efforts to minimize or eliminate these agents in clinical regimens but with limited success. Current understanding of the role of tacrolimus focuses more on its efficacy in preventing graft rejection and graft loss. As we enter the fourth decade of tacrolimus use, newer studies utilizing novel combinations (as with the mammalian target of rapamycin inhibitor, everolimus, and T-cell costimulation blockade with belatacept) offer potential for enhanced benefits.
Peritransplant Cardiometabolic and Mitochondrial Function: The Missing Piece in Donor Heart Dysfunction and Graft Failure
Wells, Matthew A. BExSc (Hons)1,2; See Hoe, Louise E. PhD2,3; Heather, Lisa C. PhD4; Molenaar, Peter PhD5; Suen, Jacky Y. PhD2,3; Peart, Jason PhD1; McGiffin, David FRACS2,6; Fraser, John F. PhD1,2,3
doi : 10.1097/TP.0000000000003368
Transplantation: March 2021 - Volume 105 - Issue 3 - p 496-508
Primary graft dysfunction is an important cause of morbidity and mortality after cardiac transplantation. Donor brain stem death (BSD) is a significant contributor to donor heart dysfunction and primary graft dysfunction. There remain substantial gaps in the mechanistic understanding of peritransplant cardiac dysfunction. One of these gaps is cardiac metabolism and metabolic function. The healthy heart is an “omnivore,” capable of utilizing multiple sources of nutrients to fuel its enormous energetic demand. When this fails, metabolic inflexibility leads to myocardial dysfunction. Data have hinted at metabolic disturbance in the BSD donor and subsequent heart transplantation; however, there is limited evidence demonstrating specific metabolic or mitochondrial dysfunction. This review will examine the literature surrounding cardiometabolic and mitochondrial function in the BSD donor, organ preservation, and subsequent cardiac transplantation. A more comprehensive understanding of this subject may then help to identify important cardioprotective strategies to improve the number and quality of donor hearts.
The Monitoring of Donor-derived Cell-free DNA in Kidney Transplantation
Filippone, Edward John MD, FASN1; Farber, John L. MD2
doi : 10.1097/TP.0000000000003393
Transplantation: March 2021 - Volume 105 - Issue 3 - p 509-516
Cell-free DNA (cfDNA) exists in plasma and can be measured by several techniques. It is now possible to differentiate donor-derived cfDNA (ddcfDNA) from recipient cfDNA in the plasma or urine of solid organ transplant recipients in the absence of donor and recipient genotyping. The assessment of ddcfDNA is being increasingly studied as a noninvasive means of identifying acute rejection (AR) in solid organ transplants, including subclinical AR. We herein review the literature on the correlation of ddcfDNA with AR in kidney transplantation. There have been at least 15 observational studies that have assessed ddcfDNA in urine or plasma using various methodologies with various thresholds for abnormality. Overall, elevated ddcfDNA indicates allograft injury as may occur with AR, infection, or acute tubular injury but may also be found in clinically stable patients with normal histology. Sensitivity is greater for antibody-mediated AR than for cell-mediated AR, and normal levels do not preclude significant cell-mediated rejection. Measurement of ddcfDNA is not a replacement for biopsy that remains the gold standard for diagnosing AR. Serial monitoring of stable patients may allow earlier detection of subclinical AR, but the efficacy of this approach remains to be established. Normal levels should not preclude planned protocol biopsies. There may be roles for following ddcfDNA levels to assess the adequacy of treatment of AR and to guide the intensity of immunosuppression in the individual patient. Randomized controlled trials are necessary to validate the benefit and cost-effectiveness for these various uses. No firm recommendations can be made at this time.
Ex Vivo Administration of Mesenchymal Stromal Cells in Kidney Grafts Against Ischemia-reperfusion Injury—Effective Delivery Without Kidney Function Improvement Posttransplant
Lohmann, Stine; Eijken, Marco; M?ldrup, Ulla; M?ller, Bjarne K.; Hunter, James; Moers, Cyril; Leuvenink, Henri; Ploeg, Rutger J.; Clahsen-van Groningen, Marian C.; Hoogduijn, Martin; Baan, Carla C.; Keller, Anna Krarup; Jespersen, Bente
doi : 10.1097/TP.0000000000003429
Transplantation: March 2021 - Volume 105 - Issue 3 - p 517-528
Mesenchymal stromal cell (MSC) therapy may improve renal function after ischemia-reperfusion injury in transplantation. Ex vivo renal intraarterial administration is a targeted delivery method, avoiding the lung vasculature, a known barrier for cellular therapies. In a randomized and blinded study, we tested the feasibility and effectiveness of MSC therapy in a donation after circulatory death autotransplantation model to improve posttransplant kidney function, using an ex vivo MSC delivery method similar to the clinical standard procedure of pretransplant cold graft flush.
microRNA-145 Inhibition Upregulates SIRT1 and Attenuates Autophagy in a Mouse Model of Lung Ischemia/Reperfusion Injury via NF-?B-dependent Beclin 1
Dai, Shao-Hua; Chen, Lu-Jie; Qi, Wang-Hong; Ye, Chun-Lin; Zou, Guo-Wen; Liu, Wei-Cheng; Yu, Ben-Tong; Tang, Jian
doi : 10.1097/TP.0000000000003435
Transplantation: March 2021 - Volume 105 - Issue 3 - p 529-539
MicroRNA-145 (miR-145) has been shown to play a critical role in ischemia/reperfusion (I/R) injury; however, the expression and function of miR-145 in lung I/R injury have not been reported yet. This study aimed to elucidate the potential effects of miR-145 in lung I/R injury.
DNA-PKcs Inhibition Extends Allogeneic Skin Graft Survival
Harrison, David K.; Waldrip, Zachary J.; Burdine, Lyle; Shalin, Sara C.; Burdine, Marie Schluterman
doi : 10.1097/TP.0000000000003442
Transplantation: March 2021 - Volume 105 - Issue 3 - p 540-549
Organ transplantation is life-saving and continued investigations into immunologic mechanisms that drive organ rejection are needed to improve immunosuppression therapies and prevent graft failure. DNA-dependent protein kinase catalytic subunit, DNA dependent-protein kinase catalytic subunit (DNA-PKcs), is a critical component of both the cellular and humoral immune responses. In this study, we investigate the contribution of DNA-PKcs to allogeneic skin graft rejection to potentially highlight a novel strategy for inhibiting transplant rejection.
Inhibition of Carnitine Palmitoyltransferase 1A Aggravates Fatty Liver Graft Injury via Promoting Mitochondrial Permeability Transition
Xue, Yan; Liu, Hui; Yang, Xin-Xiang; Pang, Li; Liu, Jiang; Ng, Kevin T.P.; Yeung, Oscar W.H.; Lam, Yin-Fan; Zhang, Wei-Yi; Lo, Chung-Mau; Man, Kwan
doi : 10.1097/TP.0000000000003437
Transplantation: March 2021 - Volume 105 - Issue 3 - p 550-560
Hepatic steatosis is a major risk factor for graft failure due to increased susceptibility of fatty liver to ischemia-reperfusion injury (IRI) during transplantation. Here, we aimed to investigate the role of carnitine palmitoyltransferase 1A (CPT1A) in fatty liver graft injury and to explore the underlying mechanism and therapeutic potential on attenuating hepatic IRI.
When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts
Weiss, Emmanuel; Saner, Fuat; Asrani, Sumeet K.; Biancofiore, Gianni; Blasi, Annabel; Lerut, Jan; Durand, François; Fernandez, Javier; Findlay, James Y.; Fondevila, Constantino; Francoz, Claire; Gustot, Thierry; Jaber, Samir; Karvellas, Constantine; Kronish, Kate; Laleman, Wim; Laterre, Pierre François; Levesque, Eric; Mandell, M. Susan; Mc Phail, Mark; Muiesan, Paolo; Olson, Jody C.; Olthoff, Kim; Daniele Pinna, Antonio; Reiberger, Thomas; Reyntjens, Koen; Saliba, Faouzi; Scatton, Olivier; Simpson, Kenneth J.; Soubrane, Olivier; Subramanian, Ram M.; Tacke, Frank; Tomescu, Dana; Xia, Victor; Wagener, Gebhard; Paugam-Burtz, Catherine
doi : 10.1097/TP.0000000000003364
Transplantation: March 2021 - Volume 105 - Issue 3 - p 561-568
Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility.
Outcome of Liver Transplantation for Neonatal-onset Citrullinemia Type I
Liu, Yuan; Luo, Yi; Xia, Lei; Qiu, Bijun; Zhou, Tao; Feng, Mingxuan; Wang, Chenchen; Xue, Feng; Chen, Xiaosong; Han, Longzhi; Zhang, Jianjun; Xia, Qiang
doi : 10.1097/TP.0000000000003261
Transplantation: March 2021 - Volume 105 - Issue 3 - p 569-576
We evaluated the outcome of liver transplantation (LT) in neonatal-onset citrullinemia type I patients, especially its impact on neurological deficits and developmental retardation.
Decrease in the Risk of Posttransplant Hepatocellular Carcinoma Recurrence After the Conversion to Prestorage Leukoreduction for Transfused Red Blood Cells
Kwon, Ji-Hye; Han, Sangbin; Jang, Jin Sung; Lee, Kyo Won; Ahn, Joong Hyun; Kim, Kyunga; Jeon, Suyong; Gwak, Mi Sook; Ko, Justin S.; Kim, Gaab Soo; Joh, Jae-Won; Cho, Duck
doi : 10.1097/TP.0000000000003265
Transplantation: March 2021 - Volume 105 - Issue 3 - p 577-585
Prestorage leukoreduction has the advantage over poststorage leukoreduction in reducing leukocyte-derived molecules in red blood cells (RBC) unit, which induce immunomodulation. Our institution newly introduced prestorage leukoreduction, instead of conventional poststorage leukoreduction, for liver transplant recipients since March 2012. In this study, we aimed to evaluate the risk of posttransplant hepatocellular carcinoma (HCC) recurrence after the conversion of poststorage leukoreduction into prestorage leukoreduction for transfused allogeneic RBCs.
Liver Transplantation in Patients With Pretransplant Aspergillus Colonization: Is It Safe to Proceed?
Amin, Arpit; Molina, Alfonso; Quach, Lisa; Ito, Takahiro; McMillan, Robert; DiNorcia, Joseph; Agopian, Vatche G.; Kaldas, Fady M.; Farmer, Douglas G.; Busuttil, Ronald W.; Winston, Drew J
doi : 10.1097/TP.0000000000003276
Transplantation: March 2021 - Volume 105 - Issue 3 - p 586-592
Patients with end-stage liver disease and pretransplant Aspergillus colonization are problematic for determining liver transplant candidacy and timing of transplantation because of concerns for posttransplant invasive aspergillosis.
Prediction of Perioperative Cardiovascular Events in Liver Transplantation
Koshy, Anoop N.; Farouque, Omar; Cailes, Benjamin; Ko, Jefferson; Han, Hui-Chen; Weinberg, Laurence; Testro, Adam; Robertson, Marcus; Teh, Andrew W.; Lim, Han S.; Gow, Paul J
doi : 10.1097/TP.0000000000003306
Transplantation: March 2021 - Volume 105 - Issue 3 - p 593-601
Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis with poor survival in the absence of liver transplantation (LT). HRS represents a state of profound circulatory and cardiac dysfunction. Whether it increases risk of perioperative major adverse cardiovascular events (MACE) following LT remains unclear.
Expanding Indications of Liver Transplantation in Spain: Consensus Statement and Recommendations by the Spanish Society of Liver Transplantation
Rodr?guez-Per?lvarez, Manuel; G?mez-Bravo, Miguel ?ngel; S?nchez-Antol?n, Gloria; De la Rosa, Gloria; Bilbao, Itxarone; Colmenero, Jordi; on behalf of the Spanish Society of Liver Transplantation (SETH) Consensus Panel* Less
doi : 10.1097/TP.0000000000003281
Transplantation: March 2021 - Volume 105 - Issue 3 - p 602-607
The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain.
The Preimplantation Psychosocial Evaluation and Prediction of Clinical Outcomes During Mechanical Circulatory Support: What Information Is Most Prognostic?
Dew, Mary Amanda; Hollenberger, Jennifer C.; Obregon, Laura L.; Hickey, Gavin W.; Sciortino, Christopher M.; Lockard, Kathleen L.; Kunz, Nicole M.; Mathier, Michael A.; Ramani, Ravi N.; Kilic, Arman; McNamara, Dennis M.; Simon, Marc A.; Keebler, Mary E.; Kormos, Robert L
doi : 10.1097/TP.0000000000003287
Transplantation: March 2021 - Volume 105 - Issue 3 - p 608-619
Psychosocial evaluations are required for long-term mechanical circulatory support (MCS) candidates, no matter whether MCS will be destination therapy (DT) or a bridge to heart transplantation. Although guidelines specify psychosocial contraindications to MCS, there is no comprehensive examination of which psychosocial evaluation domains are most prognostic for clinical outcomes. We evaluated whether overall psychosocial risk, determined across all psychosocial domains, predicted outcomes, and which specific domains appeared responsible for any effects.
The Impact of Donor Asphyxiation or Drowning on Pediatric Lung Transplant Recipients
Seese, Laura; Kilic, Arman; Turbendian, Harma K.; Sanchez, Pablo G.; Diaz-Castrillon, Carlos E.; Morell, Victor O
doi : 10.1097/TP.0000000000003262
Transplantation: March 2021 - Volume 105 - Issue 3 - p 620-627
Donors with drowning or asphyxiation (DA) as a mechanism of death (MOD) are considered high risk in pediatric lung transplantation. We sought to evaluate whether recipients of DA donors had negatively impacted outcomes.
Financial Feasibility Analysis of a Culturally and Linguistically Competent Hispanic Kidney Transplant Program
Wang, Andrew; Caicedo, Juan Carlos; McNatt, Gwen; Abecassis, Michael; Gordon, Elisa J
doi : 10.1097/TP.0000000000003269
Transplantation: March 2021 - Volume 105 - Issue 3 - p 628-636
In 2006, Northwestern Medicine implemented a culturally targeted and linguistically congruent Hispanic Kidney Transplant Program (HKTP). The HKTP has been associated with a reduction in Hispanic/Latino disparities in live donor kidney transplantation. This article assessed the financial feasibility of implementing the HKTP intervention at 2 other transplant centers.
Complex Linkage Disequilibrium Effects in HLA-DPB1 Expression and Molecular Mismatch Analyses of Transplantation Outcomes
Shieh, Mengkai; Hayeck, Tristan J.; Dinh, Anh; Duke, Jamie L.; Chitnis, Nilesh; Mosbruger, Timothy; Morlen, Ryan P.; Ferriola, Deborah; Kneib, Carolina; Hu, Taishan; Huang, Yanping; Monos, Dimitri S
doi : 10.1097/TP.0000000000003272
Transplantation: March 2021 - Volume 105 - Issue 3 - p 637-647
HLA molecular mismatch (MM) is a risk factor for de novo donor-specific antibody (dnDSA) development in solid organ transplantation. HLA expression differences have also been associated with adverse outcomes in hematopoietic cell transplantation. We sought to study both MM and expression in assessing dnDSA risk.
Change in Estimated GFR and Risk of Allograft Failure in Patients Diagnosed With Late Active Antibody-mediated Rejection Following Kidney Transplantation
Irish, William; Nickerson, Peter; Astor, Brad C.; Chong, Edward; Wiebe, Chris; Moreso, Francesc; Seron, Daniel; Crespo, Marta; Gache, Larry; Djamali, Arjang
doi : 10.1097/TP.0000000000003274
Transplantation: March 2021 - Volume 105 - Issue 3 - p 648-659
There are challenges in designing adequate, well-controlled studies of patients with active antibody-mediated rejection (AMR) after kidney transplantation (KTx).
Impact of Belatacept Conversion on Renal Function, Histology, and Gene Expression in Kidney Transplant Patients With Chronic Active Antibody-mediated Rejection
Kumar, Dhiren; Raynaud, Marc; Chang, Jessica; Reeve, Jeff; Yakubu, Idris; Kamal, Layla; Levy, Marlon; Bhati, Chandra; Kimball, Pamela; King, Anne; Massey, Davis; Halloran, Philip; Gupta, Gaurav Less
doi : 10.1097/TP.0000000000003278
Transplantation: March 2021 - Volume 105 - Issue 3 - p 660-667
Here, we present our initial experience with a prospective protocol of belatacept conversion in patients with chronic active antibody-mediated rejection (caAMR) and a high degree of chronicity at the time of diagnosis.
Competing Risk Analysis in Renal Allograft Survival: A New Perspective to an Old Problem
El Ters, Mireille; Smith, Byron H.; Cosio, Fernando G.; Kremers, Walter K
doi : 10.1097/TP.0000000000003285
Transplantation: March 2021 - Volume 105 - Issue 3 - p 668-676
Graft survival after kidney transplant (KTX) is often estimated by the Kaplan-Meier (KM) method censoring for competing endpoints, primarily death. This method overestimates the incidence of graft loss.
Daratumumab for Antibody-mediated Rejection in Heart Transplant—A Novel Therapy: Successful Treatment of Antibody-mediated Rejection
Aguilera Agudo, Cristina; G?mez Bueno, Manuel; Krsnik Castello, Isabel
doi : 10.1097/TP.0000000000003505
Transplantation: March 2021 - Volume 105 - Issue 3 - p e30-e31
Do Liver Transplantation Criteria Differ According to the Type of Donor and the Severity of the Recipient?
Weiss, Emmanuel; Giabicani, Mikhael; Saner, Fuat
doi : 10.1097/TP.0000000000003563
Transplantation: March 2021 - Volume 105 - Issue 3 - p e32
Successful Control of AA Amyloidosis by Bilateral Lung Transplantation for Bronchiectasis
Yutaka, Yojiro; Sugimoto, Akihiko; Yuasa, Itsuki; Yamada, Yosuke; Date, Hiroshi
doi : 10.1097/TP.0000000000003517
Transplantation: March 2021 - Volume 105 - Issue 3 - p e33-e34
Prophylactic Ureaplasma-directed Antimicrobials in Lung Donors Can Prevent Fatal Hyperammonemia
Kurihara, Chitaru; Manerikar, Adwaiy; Kandula, Viswajit; Cerier, Emily; Bharat, Ankit
doi : 10.1097/TP.0000000000003540
Transplantation: March 2021 - Volume 105 - Issue 3 - p e35-e36
Pretransplant Body Composition Abnormality Has a Negative Impact Especially on Living Donor Liver Transplantation
Okumura, Shinya; Yagi, Shintaro; Hamaguchi, Yuhei; Yoshioka, Yuji; Yao, Siyuan; Kamo, Naoko; Taura, Kojiro; Kaido, Toshimi; Uemoto, Shinji
doi : 10.1097/TP.0000000000003562
Transplantation: March 2021 - Volume 105 - Issue 3 - p e37-e38
Do Not Delay: Safe Operation for Pediatric Living-donor Liver Transplantation Programs in the COVID-19 Era
Yamada, Masaki; Funaki, Takanori; Shoji, Kensuke; Miyairi, Isao; Fukuda, Akinari; Sakamoto, Seisuke; Imadome, Ken-Ichi; Kasahara, Mureo
doi : 10.1097/TP.0000000000003594
Transplantation: March 2021 - Volume 105 - Issue 3 - p e39-e40
The Second Wave of COVID-19 Disease in a Kidney Transplant Recipient Cohort: A Single-center Experience in Belgium
Georgery, Hélène; Devresse, Arnaud; Scohy, Anais; Kabamba, Benoit; Darius, Tom; Buemi, Antoine; De Greef, Julien; Belkhir, Leila; Yombi, Jean-Cyr; Goffin, Eric; Kanaan, Nada
doi : 10.1097/TP.0000000000003596
Transplantation: March 2021 - Volume 105 - Issue 3 - p e41-e42
