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1
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Mangus RS. Liver-Intestine/Multivisceral Perspective: Indications, Patient Selection, and Allocation Policy. Clin Liver Dis (Hoboken) 2019; 14:142-145. [PMID: 31709042 PMCID: PMC6832100 DOI: 10.1002/cld.848] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 05/28/2019] [Indexed: 02/04/2023] Open
Affiliation(s)
- Richard S. Mangus
- Department of Surgery, Transplant DivisionIndiana University School of MedicineIndianapolisIN
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2
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Paediatric Intestinal Pseudo-obstruction: Evidence and Consensus-based Recommendations From an ESPGHAN-Led Expert Group. J Pediatr Gastroenterol Nutr 2018; 66:991-1019. [PMID: 29570554 DOI: 10.1097/mpg.0000000000001982] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Chronic intestinal pseudo-obstructive (CIPO) conditions are considered the most severe disorders of gut motility. They continue to present significant challenges in clinical care despite considerable recent progress in our understanding of pathophysiology, resulting in unacceptable levels of morbidity and mortality. Major contributors to the disappointing lack of progress in paediatric CIPO include a dearth of clarity and uniformity across all aspects of clinical care from definition and diagnosis to management. In order to assist medical care providers in identifying, evaluating, and managing children with CIPO, experts in this condition within the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as well as selected external experts, were charged with the task of developing a uniform document of evidence- and consensus-based recommendations. METHODS Ten clinically relevant questions addressing terminology, diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to June 2017 using a number of established electronic databases as well as repositories. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcome measures for the research questions. Levels of evidence and quality of evidence were assessed using the classification system of the Oxford Centre for Evidence-Based Medicine (diagnosis) and the GRADE system (treatment). Each of the recommendations were discussed, finalized, and voted upon using the nominal voting technique to obtain consensus. RESULTS This evidence- and consensus-based position paper provides recommendations specifically for chronic intestinal pseudo-obstruction in infants and children. It proposes these be termed paediatric intestinal pseudo-obstructive (PIPO) disorders to distinguish them from adult onset CIPO. The manuscript provides guidance on the diagnosis, evaluation, and treatment of children with PIPO in an effort to standardise the quality of clinical care and improve short- and long-term outcomes. Key recommendations include the development of specific diagnostic criteria for PIPO, red flags to alert clinicians to the diagnosis and guidance on the use of available investigative modalities. The group advocates early collaboration with expert centres where structured diagnosis and management is guided by a multi-disciplinary team, and include targeted nutritional, medical, and surgical interventions as well as transition to adult services. CONCLUSIONS This document is intended to be used in daily practice from the time of first presentation and definitive diagnosis PIPO through to the complex management and treatment interventions such as intestinal transplantation. Significant challenges remain to be addressed through collaborative clinical and research interactions.
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3
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Pre-emptive Intestinal Transplant: The Surgeon's Point of View. Dig Dis Sci 2017; 62:2966-2976. [PMID: 28918445 DOI: 10.1007/s10620-017-4752-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 09/06/2017] [Indexed: 12/13/2022]
Abstract
Pre-emptive transplantation is a well-established practice for certain types of end-organ failure such as in the use of kidney transplantation. For irreversible intestinal failure, total parenteral nutrition (TPN) remains the gold standard, due to the suboptimal long-term results of intestinal transplantation. As such, the only role for pre-emptive transplantation, if at all, will be for patients identified to be at high risk of complications and mortality while on definitive long-term TPN. In these patients, the timing of early listing and transplantation could become life-saving, taking into account that mortality on the waiting list is still the highest for intestinal candidates. The development of simulation models or pre-transplant scoring systems could help in selecting patients based on potential outcome on TPN or with transplantation, and recent reports from high-volume centers identify few underlying pathologic conditions and some TPN complications as at higher risk of increased morbidity and mortality. A pre-emptive transplant could be used as a rehabilitative procedure in a well-selected case-by-case scenario, among TPN patients at risk of liver failure, repeated central line infections, mesenteric infarction, short bowel syndrome (SBS) <50 cm or with end stoma, congenital mucosal disease, desmoid tumors: These conditions must be carefully evaluated, not to underestimate the clinical stage nor to over-estimate the impact of a temporary situation. At the present time, diseases with a variable and unpredictable course, such as intestinal dysmotility disorders, or quality of life and financial issues are still far from being considered as indications for a pre-emptive transplant.
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4
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Nazzal M, Sun Y, Okoye O, Diggs L, Evans N, Osborn T, Etesami K, Varma C. Reno-portal shunt for liver transplant, an alternative inflow for recipients with grade III-IV portal vein thrombosis: Tips for a better outcome. Int J Surg Case Rep 2017; 41:251-254. [PMID: 29102862 PMCID: PMC5742012 DOI: 10.1016/j.ijscr.2017.09.028] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 09/18/2017] [Accepted: 09/18/2017] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Portal vein thrombosis (PVT) poses an extremely difficult problem in cirrhotic patients who are in need of a liver transplant. The prevalence of PVT in patients with cirrhosis ranges from 0.6% to 26% Nery et al. (2015) [1]. The presence of PVT is associated with more technically difficult liver transplant and in certain cases can be a contraindication to liver transplant. The only option for these patients with extensive PVT would be a multi-visceral transplant, the later unfortunately has a much higher morbidity and mortality compared to liver only transplant Smith et al. (2016) [2]. An alternative approach is needed to provide a safe and reliable outcome. PRESENTATION OF CASE In this case series, we present our experience with reno-portal shunt as an alternative inflow for the liver allograft. DISCUSSION This approach appears to be safe with good long-term outcome.Although this technique has been described before, we provide additional considerations that produced good outcomes in our patients. CONCLUSION We believe that meticulous preoperative planning with high-resolution triple phase CT imaging with a measurement of the diameter of the spleno-renal shunt along with a duplex scan measuring flow through the shunt is key to a successful transplantation. Moreover, appropriate donor liver size is also of extreme importance to avoid portal hypoperfusion.
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Affiliation(s)
- Mustafa Nazzal
- Center for Abdominal Transplantation, Saint Louis University, United States.
| | - Yifei Sun
- Department of General Surgery, Saint Louis University, United States
| | - Obi Okoye
- Department of General Surgery, Saint Louis University, United States
| | - Laurence Diggs
- Department of General Surgery, Saint Louis University, United States
| | - Neil Evans
- Saint Louis University School of Medicine, United States
| | - Tamara Osborn
- Saint Louis University School of Medicine, United States
| | - Kambiz Etesami
- Center for Abdominal Transplantation, Saint Louis University, United States
| | - Chintalapati Varma
- Center for Abdominal Transplantation, Saint Louis University, United States
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5
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Kitano K, Schwartz DM, Zhou H, Gilpin SE, Wojtkiewicz GR, Ren X, Sommer CA, Capilla AV, Mathisen DJ, Goldstein AM, Mostoslavsky G, Ott HC. Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts. Nat Commun 2017; 8:765. [PMID: 29018244 PMCID: PMC5635127 DOI: 10.1038/s41467-017-00779-y] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 07/25/2017] [Indexed: 11/29/2022] Open
Abstract
Patients with short bowel syndrome lack sufficient functional intestine to sustain themselves with enteral intake alone. Transplantable vascularized bioengineered intestine could restore nutrient absorption. Here we report the engineering of humanized intestinal grafts by repopulating decellularized rat intestinal matrix with human induced pluripotent stem cell-derived intestinal epithelium and human endothelium. After 28 days of in vitro culture, hiPSC-derived progenitor cells differentiate into a monolayer of polarized intestinal epithelium. Human endothelial cells seeded via native vasculature restore perfusability. Ex vivo isolated perfusion testing confirms transfer of glucose and medium-chain fatty acids from lumen to venous effluent. Four weeks after transplantation to RNU rats, grafts show survival and maturation of regenerated epithelium. Systemic venous sampling and positron emission tomography confirm uptake of glucose and fatty acids in vivo. Bioengineering intestine on vascularized native scaffolds could bridge the gap between cell/tissue-scale regeneration and whole organ-scale technology needed to treat intestinal failure patients. There is a need for humanised grafts to treat patients with intestinal failure. Here, the authors generate intestinal grafts by recellularizing native intestinal matrix with human induced pluripotent stem cell-derived epithelium and human endothelium, and show nutrient absorption after transplantation in rats.
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Affiliation(s)
- Kentaro Kitano
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Dana M Schwartz
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Haiyang Zhou
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA.,Department of General Surgery, Changzheng Hospital, Second Military Medical University, No.415, Fengyang Road, Shanghai, 200003, China
| | - Sarah E Gilpin
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Gregory R Wojtkiewicz
- Center for Systems Biology, Massachusetts General Hospital, Richard B. Simches Research Center, 185 Cambridge St, Boston, MA, 02114, USA
| | - Xi Ren
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Cesar A Sommer
- Center for Regenerative Medicine, Boston University School of Medicine, 72 E. Concord St., Boston, MA, 02118, USA
| | - Amalia V Capilla
- Center for Regenerative Medicine, Boston University School of Medicine, 72 E. Concord St., Boston, MA, 02118, USA
| | - Douglas J Mathisen
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Founders 7, Boston, MA, 02114, USA
| | - Allan M Goldstein
- Division of Pediatric Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Gustavo Mostoslavsky
- Center for Regenerative Medicine, Boston University School of Medicine, 72 E. Concord St., Boston, MA, 02118, USA.,Section of Gastroenterology, Department of Medicine, Boston Medical Center, 830 Harrison Ave, Boston, MA, 02118, USA
| | - Harald C Ott
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Founders 7, Boston, MA, 02114, USA. .,Harvard Stem Cell Institute, 7 Divinity Ave, Cambridge, MA, 02138, USA.
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6
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Lauro A, Vaidya A. Role of “reduced-size” liver/bowel grafts in the “abdominal wall transplantation” era. World J Gastrointest Surg 2017; 9:186-192. [PMID: 29081901 PMCID: PMC5633532 DOI: 10.4240/wjgs.v9.i9.186] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 03/24/2017] [Accepted: 07/10/2017] [Indexed: 02/06/2023] Open
Abstract
The evolution of multi-visceral and isolated intestinal transplant techniques over the last 3 decades has highlighted the technical challenges related to the closure of the abdomen at the end of the procedure. Two key factors that contribute to this challenge include: (1) Volume/edema of donor graft; and (2) loss of abdominal domain in the recipient. Not being able to close the abdominal wall leads to a variety of complications and morbidity that range from complex ventral hernias to bowel perforation. At the end of the 90’s this challenge was overcome by graft reduction during the donor operation or bench table procedure (especially reducing liver and small intestine), as well as techniques to increase the volume of abdominal cavity by pre-operative expansion devices. Recent reports from a few groups have demonstrated the ability of transplanting a full-thickness, vascularized abdominal wall from the same donor. Thus, a spectrum of techniques have co-evolved with multi-visceral and intestinal transplantation, ranging from graft reduction to enlarging the volume of the abdominal cavity. None of these techniques are free from complications, however in large-volume centers the combinations of both (graft reduction and abdominal widening, sometimes used in the same patient) could decrease the adverse events related to recipient’s closure, allowing a faster recovery. The quest for a solution to this unique challenge has led to the proposal and implementation of innovative solutions to enlarge the abdominal cavity.
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Affiliation(s)
- Augusto Lauro
- Liver and Multiorgan Transplant Unit, St Orsola University Hospital, 40138 Bologna, Italy
| | - Anil Vaidya
- Department of Transplant Surgery, Oxford University Hospital, Oxford OX3 7LE, United Kingdom
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7
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Abbes S, Metjian A, Gray A, Martinu T, Snyder L, Chen DF, Ellis M, Arepally GM, Onwuemene O. Human Leukocyte Antigen Sensitization in Solid Organ Transplantation: A Primer on Terminology, Testing, and Clinical Significance for the Apheresis Practitioner. Ther Apher Dial 2017; 21:441-450. [PMID: 28880430 DOI: 10.1111/1744-9987.12570] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 03/24/2017] [Accepted: 04/25/2017] [Indexed: 01/02/2023]
Abstract
The human leukocyte antigen (HLA) system is an important immunologic barrier that must be considered for successful solid organ transplantation. Formation of donor-specific HLA antibodies in solid organ transplantation is an important cause of allograft injury and may contribute to recipient morbidity and mortality. Therapeutic plasma exchange is often requested to lower HLA antibody levels prior to or after transplantation and for management of HLA antibodies in the context of organ rejection. In this review, we summarize the current terminology, laboratory testing, and clinical significance of HLA sensitization in the solid organ transplant population. Furthermore, to illustrate applications of HLA testing in clinical practice, we summarize our own lung and kidney institutional protocols for managing HLA antibodies in the peri-transplant setting.
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Affiliation(s)
- Sarah Abbes
- Institut du thorax, Service de pneumologie et unite de transplantation thoracique, Centre Hospitalier Universitaire, Nantes, France.,Department of Medicine, Division of Hematology, Duke University School of Medicine, Durham, NC, USA
| | - Ara Metjian
- Department of Medicine, Division of Hematology, Duke University School of Medicine, Durham, NC, USA
| | - Alice Gray
- Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Tereza Martinu
- Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, NC, USA.,Department of Medicine, Division of Respirology, University of Toronto, Toronto, ON, Canada
| | - Laurie Snyder
- Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Dong-Feng Chen
- Department of Pathology, Division of Pathology Clinical Services, Duke University School of Medicine, Durham, NC, USA
| | - Matthew Ellis
- Department of Medicine, Division of Nephrology, Duke University School of Medicine, Durham, NC, USA
| | - Gowthami M Arepally
- Department of Medicine, Division of Hematology, Duke University School of Medicine, Durham, NC, USA
| | - Oluwatoyosi Onwuemene
- Department of Medicine, Division of Hematology, Duke University School of Medicine, Durham, NC, USA
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8
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AlKukhun A, Caturegli G, Munoz-Abraham AS, Judeeba S, Patron-Lozano R, Morotti R, Rodriguez-Davalos MI, Geibel JP. Use of Fluorescein Isothiocyanate-Inulin as a Marker for Intestinal Ischemic Injury. J Am Coll Surg 2017; 224:1066-1073. [DOI: 10.1016/j.jamcollsurg.2016.12.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 10/09/2016] [Accepted: 12/05/2016] [Indexed: 12/14/2022]
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9
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The impact of antibodies and virtual crossmatching on intestinal transplant outcomes. Curr Opin Organ Transplant 2017; 22:149-154. [DOI: 10.1097/mot.0000000000000393] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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10
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Zerillo J, Kim S, Hill B, DeMaria S, Sakai T. Noteworthy Literature Published in 2016 for Abdominal Organ Transplant Anesthesiologists. Semin Cardiothorac Vasc Anesth 2017; 21:70-80. [PMID: 28107792 DOI: 10.1177/1089253216688538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
More than 400 peer-reviewed publications on the topic of pancreas transplantation, more than 400 on intestine transplantation, and more than 3000 on renal transplantation were published in 2016. This review will highlight the most pertinent literature for anesthesiologists caring for patients undergoing non-liver abdominal organ transplantation. This review is the second part in an annual series to review relevant contributions in the field of abdominal organ transplantation focusing on pancreas, intestine, and renal transplantation. We explore a myriad of topics, including outcomes determined by center size, novel assessment of intestine graft function, the effect of Zika virus on the transplant population, appropriate fluid management for renal transplantation, cardiovascular risk assessment in the transplant population, and several topics pertinent to optimizing patient and graft survival.
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Affiliation(s)
- Jeron Zerillo
- 1 Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sang Kim
- 1 Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Bryan Hill
- 1 Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Samuel DeMaria
- 1 Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Tetsuro Sakai
- 2 University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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11
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Gerlach UA, Vrakas G, Sawitzki B, Macedo R, Reddy S, Friend PJ, Giele H, Vaidya A. Abdominal Wall Transplantation: Skin as a Sentinel Marker for Rejection. Am J Transplant 2016; 16:1892-900. [PMID: 26713513 DOI: 10.1111/ajt.13693] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 11/24/2015] [Accepted: 12/20/2015] [Indexed: 01/25/2023]
Abstract
Abdominal wall transplantation (AWTX) has revolutionized difficult abdominal closure after intestinal transplantation (ITX). More important, the skin of the transplanted abdominal wall (AW) may serve as an immunological tool for differential diagnosis of bowel dysfunction after transplant. Between August 2008 and October 2014, 29 small bowel transplantations were performed in 28 patients (16 male, 12 female; aged 41 ± 13 years). Two groups were identified: the solid organ transplant (SOT) group (n = 15; 12 ITX and 3 modified multivisceral transplantation [MMVTX]) and the SOT-AWTX group (n = 14; 12 ITX and 2 MMVTX), with the latter including one ITX-AWTX retransplantation. Two doses of alemtuzumab were used for induction (30 mg, 6 and 24 h after reperfusion), and tacrolimus (trough levels 8-12 ng/mL) was used for maintenance immunosuppression. Patient survival was similar in both groups (67% vs. 61%); however, the SOT-AWTX group showed faster posttransplant recovery, better intestinal graft survival (79% vs. 60%), a lower intestinal rejection rate (7% vs. 27%) and a lower rate of misdiagnoses in which viral infection was mistaken and treated as rejection (14% vs. 33%). The skin component of the AW may serve as an immune modulator and sentinel marker for immunological activity in the host. This can be a vital tool for timely prevention of intestinal graft rejection and, more important, avoidance of overimmunosuppression in cases of bowel dysfunction not related to graft rejection.
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Affiliation(s)
- U A Gerlach
- Department of Transplant Surgery, Oxford University Hospitals and University of Oxford, Oxford, UK.,Department of General, Visceral and Transplantation Surgery, Charité-Universitaetsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - G Vrakas
- Department of Transplant Surgery, Oxford University Hospitals and University of Oxford, Oxford, UK
| | - B Sawitzki
- Institute for Medical Immunology, Charité-Universitaetsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - R Macedo
- Department of Transplant Surgery, Oxford University Hospitals and University of Oxford, Oxford, UK
| | - S Reddy
- Department of Transplant Surgery, Oxford University Hospitals and University of Oxford, Oxford, UK
| | - P J Friend
- Department of Transplant Surgery, Oxford University Hospitals and University of Oxford, Oxford, UK
| | - H Giele
- Department of Plastic and Reconstructive Surgery, Oxford University Hospitals and University of Oxford, Oxford, UK
| | - A Vaidya
- Department of Transplant Surgery, Oxford University Hospitals and University of Oxford, Oxford, UK
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