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Pancreas transplant rejection

Yohichi Yasunami, Yuki Nakafusa, Naoyoshi Nitta, Masafumi Nakamura, Masafumi Goto, Junko Ono, Masaru Taniguchi
BACKGROUND: Islet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved. METHODS: We developed a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue (ISWAT) of mice and described functional and morphological characteristics of transplanted syngeneic islets...
March 8, 2018: Transplantation
Luis Muñoz-Bellvis, María Del Carmen Esteban, Manuel Iglesias, Luis González, Juan Ignacio González-Muñoz, Cristina Muñoz-González, José E Quiñones, Guadalupe Tabernero, Rosa Ana Iglesias, José María Sayagués, Pilar Fraile
INTRODUCTION: Simultaneous kidney-pancreas transplantation for patients with type 1 diabetes and end-stage chronic renal disease is widely performed. However, the rate of surgical morbidity from pancreatic complications remains high. The aim of this study was to describe the development and results of a new program, from the point of view of the pancreatic surgeon. METHODS: We analyzed 53 simultaneous kidney-pancreas transplantations performed over a period of seven years (2009-2016), with a median follow up of 39 months (range: 1-86 months)...
February 28, 2018: Cirugía Española
Nemin Zhu, Neal E Rowe, Paul R Martin, Sean S Luke, Thomas B Mcgregor, Frank Myslik, Vivian C Mcalister, Alp Sener, Patrick P Luke
INTRODUCTION: We sought to determine whether protocol biopsies could be used to guide treatment and improve outcomes in simultaneous pancreas-kidney (SPK) patients. METHODS: Between 2004 and 2013, protocol biopsies were performed on SPK patients at 3-6 months and one year post-transplant. Maintenance immunosuppression consisted of a calcineurin inhibitor, anti-proliferative agent, and corticosteroid. Corticosteroid was withdrawn in negative early biopsies, maintained in subclinical/borderline biopsies, and increased if Banff IB or greater rejection was identified...
February 23, 2018: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
Gorka Orive, Dwaine Emerich, Ali Khademhosseini, Shinichi Matsumoto, R M Hernández, J L Pedraz, Tejal Desai, Riccardo Calafiore, Paul de Vos
Encapsulating, or immunoisolating, insulin-secreting cells within implantable, semipermeable membranes is an emerging treatment for type 1 diabetes. This approach can eliminate the need for immunosuppressive drug treatments to prevent transplant rejection and overcome the shortage of donor tissues by utilizing cells derived from allogeneic or xenogeneic sources. Encapsulation device designs are being optimized alongside the development of clinically viable, replenishable, insulin-producing stem cells, for the first time creating the possibility of widespread therapeutic use of this technology...
February 15, 2018: Trends in Biotechnology
Andrea Proneth, Andreas A Schnitzbauer, Peter Schenker, Andreas Wunsch, Falk Rauchfuss, Helmut Arbogast, Steffen Manekeller, Silvio Nadalin, Michael Heise, Michael A Ströhlein, Bernhard Banas, Peter Schemmer, Thomas Becker, Wolf O Bechstein, Andreas Pascher, Richard Viebahn, Edward K Geissler, Hans J Schlitt, Stefan A Farkas
BACKGROUND: Pancreas transplantation is the only curative treatment option for patients with juvenile diabetes. Organ shortage and restrictive allocation criteria are the main reasons for increasing waitlists leading to severe morbidity and mortality. We designed a study to increase the donor pool with extended donor criteria (EDC) organs (donor age 50-60 years or BMI 30-34kg/m). METHODS: Utilization of EDC organs required the implementation of a new allocation system within Eurotransplant...
February 5, 2018: Transplantation
Ji Yoon Choi, Joo Hee Jung, Hyun Wook Kwon, Sung Shin, Young Hoon Kim, Duck Jong Han
BACKGROUND Although bladder drainage is effective for monitoring urine amylase levels to detect graft rejection, enteric drainage is performed more frequently. The optimal method for monitoring pancreatic enzyme secretions remains unclear. We investigated graft survival in recipients of bladder drainage and assessed the risk of graft rejection and failure after enteric conversion. MATERIAL AND METHODS From January 1999 to October 2015, we performed 318 pancreas transplantations at our institution. We enrolled 180 recipients who underwent pancreas transplantation with bladder drainage (82 underwent enteric conversion and the rest did not)...
February 2, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Thomas Schachtner, Marina Zaks, Natalie M Otto, Andreas Kahl, Petra Reinke
As immunosuppressive therapy has improved in simultaneous pancreas/kidney transplant recipients (SPKTRs), infection has become the major limitation of disease-free survival. We studied all SPKTRs and deceased-donor kidney transplant recipients (KTRs) between 2003 and 2015. 36/134 SPKTRs (26.9%) were diagnosed with sepsis among which 13/36 SPKTRs (36.1%) developed severe sepsis/septic shock. A control group of 98 SPKTRs without sepsis and 61/538 KTRs (11.3%) with sepsis were used for comparison. Among SPKTRs, female sex, low BMI, CMV-seronegativity, CMV-disease, and acute cellular rejection increased the risk for sepsis (p<0...
January 23, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Kunal Yadav, Adrian Cotterell, Pamela Kimball, Laura Warmke, Melissa Contos, Gaurav Gupta, Anne King, Dhiren Kumar, Marlon Levy
This case describes a 34year old female who underwent an HLA identical living donor kidney transplant with a positive flow cytometric crossmatch (FCXM), but without any donor specific antibody (DSA). Tests to detect non-HLA antibody and autoantibody were negative. Allograft functioned well without rejection. She later received a pancreas allograft, again with a weakly positive FCXM, without DSA. After good initial graft function, she developed hyperglycemia six weeks posttransplant. Cross-sectional imaging demonstrated non-enhancing pancreas allograft with new vein thrombosis...
January 6, 2018: Transplant Immunology
E Nordheim, R Horneland, E M Aandahl, K Grzyb, L Aabakken, V Paulsen, K Midtvedt, A Hartmann, T Jenssen
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)...
January 9, 2018: American Journal of Transplantation
Adam L Burrack, Laurie G Landry, Janet Siebert, Marilyne Coulombe, Ronald G Gill, Maki Nakayama
The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets...
February 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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
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...
December 29, 2017: American Journal of Transplantation
Genaro A Paredes-Juarez, Paul de Vos, Jeff W M Bulte
Introduction: Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the pancreas produces insufficient amounts of insulin. T1DM patients require exogenous sources of insulin to maintain euglycemia. Transplantation of naked or microencapsulated pancreatic islets represents an alternative paradigm to obtain an autonomous regulation of blood glucose levels in a controlled and personalized fashion. However, once transplanted, the fate of these personalized cellular therapeutics is largely unknown, justifying the development of non-invasive tracking techniques...
2017: Expert Review of Precision Medicine and Drug Development
Adam L Burrack, Tijana Martinov, Brian T Fife
Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications...
2017: Frontiers in Endocrinology
Bahareh Rajaei, Mehdi Shamsara, Mohammad Hossein Sanati
Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing transcription factor family, is a key transcription factor for pancreas development and mature β-cell function. In this study, induced overexpression of PDX1 resulted in producing susceptible cells for pancreatic differentiation and was well beneficial to enhance β-cell production, maturation, function, and survival. Induced PDX1 overexpression in harmony with a set of signaling molecules involves in guiding the signaling pathways toward pancreas development, leaded to high-efficient in vitro generation of ectopic insulin-producing cells (IPCs) with the effectively reduced number of polyhormonal cells and increased number of INS single-positive cells...
November 27, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
J A Fridell, R S Mangus, C M Thomas, C A Kubal, J A Powelson
INTRODUCTION: Transplantation of pancreas allografts procured from donation after circulatory death (DCD) remains uncommon. This study reviews a series of pancreas transplants at a single center to assess the donor and recipient characteristics for DCD pancreas transplant and to compare clinical outcomes. METHODS: DCD procurement was performed with a 5-minute wait time from pronouncement of death to first incision. In 2 patients, tissue plasminogen activator was infused as a thrombolytic during the donor flush...
December 2017: Transplantation Proceedings
Brian J Nankivell, Meena Shingde, Karen L Keung, Caroline L-S Fung, Richard J Borrows, Philip J O'Connell, Jeremy R Chapman
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-driven biopsy samples 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...
February 2018: American Journal of Transplantation
Carlos Jiménez-Romero, Alberto Marcacuzco Quinto, Alejandro Manrique Municio, Iago Justo Alonso, Jorge Calvo Pulido, Félix Cambra Molero, Óscar Caso Maestro, Álvaro García-Sesma, Enrique Moreno González
INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPKT) constitutes the therapy of choice for diabetes type1 or type2 associated with end-stage renal disease, because is the only proven method to restore normo-glicemic control in the diabetic patient. METHODS: Retrospective and descriptive study of a series of 175 patients who underwent SPKT from March 1995 to April 2016. We analyze donor and recipient characteristics, perioperative variables and immunosuppression, post-transplant morbi-mortality, patient and graft survival, and risk factors related with patient and graft survival...
October 28, 2017: Cirugía Española
Hironori Hayashi, Hiroyuki Takamura, Ryosuke Gabata, Isamu Makino, Yoshinao Ohbatake, Shinichi Nakanuma, Tomoharu Miyashita, Hidehiro Tajima, Kazuhiro Hanazaki, Tetsuo Ohta
BACKGROUND We investigated the impact of using an artificial pancreas for glycemic control in liver transplant recipients. MATERIAL AND METHODS Between January 2014 and December 2016, glycemic control using an artificial pancreas was performed 13 times. The target blood glucose level was set at 80-110 mg/dL. We retrospectively analyzed the clinical course, including achievement rate of the target blood glucose range. RESULTS For perioperative glycemic control, an artificial pancreas was used 9 times. The total insulin dose and achievement rate of the target blood glucose level were 113...
October 3, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Irfan Moinuddin, Muhammad Sohail Yaqub, Tim Taber, John Powelson, Jonathan Fridell, Asif Sharfuddin
BACKGROUND AND OBJECTIVES: Diabetic Kidney Disease is associated with excessive mortality and morbidity. Simultaneous pancreas kidney transplantation (SPK) significantly improves quality of life and increases life expectancy of uremic diabetic patients. It is not known whether pancreas and kidney rejections in these transplant patients is concordant or discordant. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We analyzed clinical data on all SPK transplants performed between 2003 and 2014 at Indiana University to assess the impact of isolated or combined pancreas and kidney rejections on patient and allograft outcomes...
September 16, 2017: Journal of Nephrology
Jaeseok Yang, Jong Cheol Jeong, Joongyub Lee, Young Hoon Kim, Hyo Chae Paik, Jae-Joong Kim, Hyun-Young Park, Myoung Soo Kim, Curie Ahn
BACKGROUND: Beneficial aspects of solid organ transplantation, which encompass survival benefit, improved quality of life, and cost efficacy, have been clearly demonstrated. However, regional and ethnic differences require further studies to identify prognostic factors and transplant outcomes against various backgrounds. After previous efforts of a nationwide, retrospective study on the kidney transplant outcomes in Korea, a new prospective-designed version of the Korean Organ Transplantation Registry (KOTRY) was launched in 2014...
August 2017: Transplantation Direct
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