Vascularized Composite Allotransplantation最新文献

{"title":"2598: Experience with patient referrals for upper extremity transplantation at a US academic medical center","authors":"H. Kiwanuka, M. Aycart, E. Bueno, B. Pomahac, S. Talbot","doi":"10.1080/23723505.2016.1234211","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234211","url":null,"abstract":"2598: Experience with patient referrals for upper extremity transplantation at a US academic medical center Harriet Kiwanuka, Mario A. Aycart, MD, Ericka M. Bueno, Bohdan Pomahac, MD, and Simon G. Talbot, MD Brigham and Women’s Hospital, Boston, MA, USA Introduction To date, there have been over 100 upper extremity transplantations (UET) performed in 71 patients worldwide, with 3 bilateral transplants performed at our institution. Despite the growing number of procedures, there are little data regarding institutional screening practices or description of the population of patients that seek transplantation as a treatment modality for their upper extremity disabilities. In an attempt to better understand our institution’s referral patterns and identify factors that may be associated with successful screening, we performed a systematic review of our experience to date. Methods Contact demographic and injury characteristics were retrospectively reviewed from 2010 through 2015. We investigated the relationship between referral source (physician vs. self) with the contact’s demographic characteristics (age, gender, race, mechanism of injury, geographic location) and clinical trial status (e.g., accepted, excluded, transplanted). Results There were a total of 89UET contacts. The average age was 35.2 years, with most contacts beingWhite (nD 24). The majority were male (n D 67, 75.3%) and the most common indication for referral was trauma (n D 43, 55.8%). The majority of our contacts resided within the US (n D 55, 67.9%). Of the 89 contacts, 20 (22.5%) were physician referrals and 69 (77.5%) were self referrals. Physician referrals led to the most screened and transplanted contacts, whereas self-referral often led to immediate exclusion. Conclusions In this study, we provide a comprehensive overview of our center’s experience with patients interested in UET along with their demographic and injury characteristics and mode of referral. We also present a description of the clinical status of our 89 contacts, and illustrate the impact that mode of referral has had on successful screening and subsequent transplantation in our clinical trial. Figure 1. Overall clinical status of contacts. CONTACT Harriet Kiwanuka hkiwanuka@partners.org © 2016 Harriet Kiwanuka, Mario A. Aycart, Ericka M. Bueno, Bohdan Pomahac, and Simon G. Talbot. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. VASCULARIZED COMPOSITE ALLOTRANSPLANTATION 2016, VOL. 3, NOS. 1–2, 11 http://dx.doi.org/10.1080/23723505.2016.1234211","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117265136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2559: Clinical application of mathematical long bone ratios to calculate appropriate donor limb lengths in bilateral upper limb transplantations","authors":"J. Lutfy, A. Pietak, Shaun D. Mendenhall, M. Neumeister","doi":"10.1080/23723505.2016.1234199","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234199","url":null,"abstract":"2559: Clinical application ofmathematical long bone ratios to calculate appropriate donor limb lengths in bilateral upper limb transplantations Justyn Lutfy, Alexis Pietak, Shaun D. Mendenhall , and Michael W. Neumeister Southern Illinois University School of Medicine, Carbondale, IL, USA; Tufts University, Boston, MA, USA; The Institute for Plastic Surgery, Carbondale, IL, USA Background Limited methods exist to aid in deciding the appropriate donor limb lengths in bilateral upper limb amputees qualifying for vascularized composite allotransplantation. To aid in this decision, our hypothesis was that mathematical equations could be created using long bone length ratios to approximate the patient’s limb length prior to amputation. Methods A collection of 30 skeletons’ unilateral upper limb long bones were measured using osteometric board and calipers to create a base data set. Anatomic segment ratios were calculated based on humerus length for males and females after multivariate linear regression analysis indicated a statistical difference. For clinical application testing, 5 minimally preserved cadavers underwent standardized upper limb x-rays. Radiographic bone lengths were measured along the long axis of the humerus, forearm, and third ray. These measured radiographic anatomic lengths were then compared to the predicted bone lengths, generated from the skeleton data set ratios, for each cadaver. Results The Chi Square Goodness of Fit test showed excellent fit (p < 0.025 to p < 0.001) between the predicted and radiographically measured lengths for the 5 cadavers. Depending on the cadaver, percent error in total limb length predicted to measured ranged from 0.1% to 5%. Table 1 shows the variables to multiply an individual humerus length to calculate a given anatomic segment. Interobserver measurements showed no statistically significant difference using the Bland-Altman method. Conclusion If a bilateral upper limb amputee has one intact humerus, ratios to the humerus length can be reliably applied to calculate the pre-amputation limb length based on the patient’s radiographic humerus length. These formulas are indicated for finding the appropriate limb lengths, and smaller anatomic segments, for donor-recipient matching in upper limb transplantation.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129304960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2550: Chimeric cell transplant for the treatment of duchenne muscular dystrophy","authors":"E. Szilagyi, J. Cwykiel, A. Domaszewska-Szostek, M. Siemionow","doi":"10.1080/23723505.2016.1234238","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234238","url":null,"abstract":"2550: Chimeric cell transplant for the treatment of duchenne muscular dystrophy Erzsebet Szilagyi, Joanna Cwykiel, Anna Domaszewska-Szostek, and Maria Siemionow University of Illinois at Chicago, Chicago, IL, USA Background Duchenne Muscular Dystrophy (DMD), is a progressive lethal disease, caused by X-linked mutations affecting dystrophin production in the muscle cells. Allogeneic stem cell therapies are aiming to restore dystrophin in affected muscles, however, are challenged by rejection and limited engraftment. Chimeric Cells (CC), created via ex vivofusion of donor and recipient cells, represent a promising therapy option in the field of tissue regeneration and Vascularized Composite Allotransplant (VCA), as eliminate the need of life-long immunosuppression. The aim of this study was to test the feasibility of Chimeric Cell therapy of mesenchymal stem cell (MSC) and myoblast origin through in vitro characterization of human and murine CC and through in vivo assessment of survival, engraftment and efficacy of human and murine CC in DMD mdx/scid and mdx mice models. Methods Twelve ex vivo fusions of allogenic human myoblasts-myoblast and myoblast-MSC were performed, using polyethylene glycol technique. CC phenotype was evaluated by flow cytometry and confocal microscopy. CC were cultured for 30 d to test proliferation capacity and myogenic differentiation was induced in specific culture conditions. To test efficacy, mdx/scid mice (nD 4) received 0.5£ 10 human myoblast/MSC and myoblast/myoblast CC, while mdx mice received 0.5 £ 10 healthy snj myoblast/mdx MSC and snj myoblast/mdx myoblast CC through local injections to gastrocnemius muscle. Therapeutic effect was monitored by muscle function tests (grip strength and wire hanging). Muscle characteristics (weight, inflammation, fibrosis, dystrophin expression as well as in situ contraction ability) were assessed at day 7, 30 and 90 after transplant. Results After successful fusion procedure, CC expressed antigens of both parent cells, maintained proliferative capacity in long-term cultures and differentiated toward mature skeletal myocytes. Human CC treated recipients showed CC engraftment in gastrocnemius muscle and locally increased dystrophin expression (12%), at 7 day after cell delivery. Both human and murine CC recipients showed increased motor function and dystrophin expression that was maintained through the 1 to 3-months follow-up period. Conclusion This study confirmed feasibility and efficacy of CC therapy, which may represent a novel, universal approach for treatment of muscular dystrophies and can be applicable to restore muscle components of VCA. CONTACT Erzsebet Szilagyi eszilagy@uic.edu © 2016 Erzsebet Szilagyi, Joanna Cwykiel, Anna Domaszewska-Szostek, and Maria Siemionow. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/)","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122438692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2595: A novel bioresorbable/biointegratable/biocompatible dressing for negative pressure wound therapy","authors":"Kevin Wu, R. Cindass, S. Lawson, V. Gorantla, M. Davis","doi":"10.1080/23723505.2016.1234259","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234259","url":null,"abstract":"2595: A novel bioresorbable/biointegratable/biocompatible dressing for negative pressure wound therapy Kevin Wu, R. Cindass, S. D. Lawson, V. S. Gorantla, and M. R. Davis RESTOR Program, 59 Medical Wing, JBSA Lackland AFB, TX, USA Aims Negative pressure wound therapy (NPWT) aims to improve healing by secondary intention of acute and/ or chronic wounds by dynamic vacuum assisted removal of wound exudate, promoting granulation The standard of care in NPWT uses a polyurethane sponge dressing (PUSD) applied to the wound as a filler to help facilitate vacuum suction The PUSD is non-biodegradable and needs removal every 2–3 days, causing repetitive trauma during wound healing We developed 2 novel bioresorbable/biointegratable/biocompatible sponge-dressing scaffolds (3B-SDS) and evaluated their feasibility and efficacy in optimizing wound healing and limiting need for dressing changes in a pre-clinical porcine NPWT wound model. Methods Ten full thickness wounds were created on 6 swine Four randomly chosen wounds served as controls undergoing wet-to-dry (WTD) dressing changes (2 wounds) and PUSD NPWT (2 wounds) The remaining 6 wounds underwent treatment with the novel 3B-SDSs All wounds were assessed every 3 d until creation of a skin graftable area or until the project end date of 2 months The primary outcome measure was time to skin graftable area Wound planimetry, colorimetry, tensiometry, and histology were secondary outcome metrics. Results This is an ongoing study and end point results will be presented at the meeting We anticipate that the 3BSDSs will achieve faster time to a skin graftable area without the need for repeated dressing changes compared to WTD dressing or the PUSD NPWT. Conclusions The use of 3B-SDSs is anticipated to be superior in terms of time to creation of a skin graftable area compared to PUSD NWPT and WTD dressings. CONTACT Kevin Wu kwu72md@gmail.com © 2016 Kevin Wu, R. Cindass, S. D. Lawson, V. S. Gorantla, and M. R. Davis. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. VASCULARIZED COMPOSITE ALLOTRANSPLANTATION 2016, VOL. 3, NOS. 1–2, 52 http://dx.doi.org/10.1080/23723505.2016.1234259","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115776066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2602: GRAFT-implanted tacrolimus-eluting hydrogels prolong survival after vascularized composite allotransplantation","authors":"Kevin Wu, M. Davis, V. Gorantla, S. Lawson, R. Cindass, J. Karp, P. Vemula, A. Dhayani, K. Slaughter, N. Joshi","doi":"10.1080/23723505.2016.1234226","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234226","url":null,"abstract":"2602: GRAFT-implanted tacrolimus-eluting hydrogels prolong survival after vascularized composite allotransplantation Kevin Wu, M. R. Davis, V. S. Gorantla, S. D. Lawson, R. Cindass, J. Karp, P. Vemula, A. Dhayani, K. Slaughter, and N. Joshi RESTOR Program, 59 Medical Wing, JBSA Lackland AFB, TX, USA Background The shift to damage control resuscitation practice in forward combat hospitals and the many major advances over the years in combat gear has helped military troops to survive catastrophic extremity and maxillofacial trauma. Vascularized composite allotransplantation (VCA) is a superior restorative option compared to conventional reconstructive methods, however these patients require systemic multi-drug immunosuppression. We used a robust porcine preclinical VCA model to evaluate the efficacy of graftimplanted immunosuppression in preventing acute rejection (AR) and prolonging graft survival without systemic therapy. Methods Heterotopic gracilis myocutaneous flap VCA was performed between swine donor-recipient pairs with a single swine leukocyte antigen (SLA) mismatch. Group 1 (controls, n D 8) received no drug intervention. Group 2 (experimental, n D 3) and Group 3 (experimental, n D 3), a tacrolimus-eluting hydrogel injected subcutaneously into the donor flap at surgery with 28 mg/4cc and 49 mg/4cc, respectively. Serum and VCA tissues were collected for tacrolimus levels and grafts were clinically and histologically assessed for AR until the end point (23 days). Results All control animals developed Banff Grade 1 AR by post-operative day (POD) 7 and Grade 4 AR by POD 10. The tacrolimus-eluting hydrogel prolonged graft survival in both groups with an average of reaching Grade 4 AR by POD 20 and POD 28, respectively. Tissue and systemic tacrolimus levels showed no residual amount of the drug at time of euthanasia. Conclusion The use of injected tacrolimus-eluting hydrogel in VCA showed delaying of acute rejection and increasing graft survivability that is dose dependent. Donor graft tissue-specific immunomodulation with drugeluting compounds holds promise in VCA as a strategy to obviate need for systemic immunosuppression. Ultimately, propelling the field of reconstructive transplantation in the management of nonreconstructable","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121111305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2600: Axonal repair as a new paradigm for nerve coaptation","authors":"P. Henderson","doi":"10.1080/23723505.2016.1234266","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234266","url":null,"abstract":"2600: Axonal repair as a new paradigm for nerve coaptation Peter William Henderson, MD, MBA Memorial Sloan Kettering Cancer Center, New York, NY, USA Background The ideal outcome of nerve coaptation in vascularized composite allotransplantation (VCA) is complete and immediate recovery, but surgeons are largely resigned to the expectation that motor and sensory functional recovery will be incomplete and protracted This project aimed to synthesize a current paradigm for nerve coaptation, and to determine whether the latest technology and basic science research warrant a new, future paradigm that can finally realistically aim for nerve recovery that is complete and immediate. Methods For this study, “regeneration” is the process of axonal sprouts advancing toward the target organ (necessary because Wallerian degeneration rapidly destroys the nerve distal to the injury), while “repair” is the reestablishment of axonal membranous continuity (prior to the onset of Wallerian degeneration) The current paradigm and the proposed future paradigm were synthesized from primary resources from multiple databases (Pubmed, Google Scholar, SEC filings, and the US Patent and Trademark Office), as well as from personal communication with key thoughtleaders. Results The current paradigm for nerve coaptation focuses on optimizing the innate regenerative process In the research setting, this is done by manipulation of the local microenvironment In clinical practice, this is done by placement of epineurial sutures This regenerative approach, however, fails to address axonal discontinuity, and therefore has a low likelihood of effective recovery The future paradigm, in contrast, could instead focus on actual axonal membranous repair Early pre-clinical research has been identified that has achieved axonal membranous fusion, and in doing so has immediately reestablished electrical conduction and prevented Wallerian degeneration.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123558982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2604: Blood transfusion is not necessarily a sensitizing event precluding transplantation","authors":"J. W. Aston, K. Knott, D. Cooney, G. Rosson, Ricardo J. Bello, W. Lee, J. Shores, G. Brandacher, C. Cooney","doi":"10.1080/23723505.2016.1234271","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234271","url":null,"abstract":"","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127616796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2548: Tolerance induction to vascularized composite allografts by costimulation blockade","authors":"B. Oh, G. Furtmuller, Madeline L. Fryer, J. Grahammer, S. Schneeberger, D. Cooney, W. Lee, G. Raimondi, G. Brandacher","doi":"10.1080/23723505.2016.1232975","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232975","url":null,"abstract":"2548: Tolerance induction to vascularized composite allografts by costimulation blockade Byoung Chol Oh, DVM, PhD, Georg Furtmuller, MD, Madeline Fryer, BS, Johanna Grahammer, Stefan Schneeberger, Damon Cooney, MD, PhD, W. P. Andrew Lee, MD, Giorgio Raimondi, PhD, and Gerald Brandacher, MD Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD, USA; Dept. of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria Background Vascularized composite allotransplantation (VCA) has become a valid therapeutic option after devastating tissue loss While costimulation blockade (CoB) has shown considerable efficacy in preventing rejection, its efficacy in VCA remains poorly explored Here we investigated the immunoregulatory potential of CoB in a novel murine model of hind limb transplantation. Methods Fully MHC-mismatched allogeneic, orthotopic hind limb transplants were performed from Balb/c to C57BL/6 mice Recipient animals received combinations of total body irradiation (TBI), CTLA4-Ig, and anti-CD154 mAb (CoB) Mixed chimerism, clonal deletion of alloreactive T cells, and cytokine production were assessed by flow cytometry. Results CoB treated recipients showed increased survival compared to untreated and CTLA4-Ig only groups (Mean survival time [MST] 82 days) Adding non-myeloablative TBI to CoB enabled indefinite graft survival (MST,>210 days) Mixed chimerism induced by donorderived bone marrow (BM) was detected in the CoB treated group, and was even higher in TBICCoB treated recipients Decreased v̂I211C and v̂I25CCD4C T cells were detected in both groups treated with either CoB or TBICCoB, suggesting central thymic deletion of donor reactive T cells Donor specific tolerance was confirmed in long-term survivors (TBICCoB group) by acceptance of donor matched secondary skin grafts and rejection of third party ones In long term survivors treated with TBICCoB, decreased T cell responsiveness and increased graft-infiltrating regulatory T cells were detected on POD50. Conclusion Our results show that CoB enables the tolerogenicity of BM components carried by VCA, but requires TBI to establish durable donor-specific tolerance. CONTACT Byoung Chol Oh, DVM, PhD boh3@jhmi.edu © 2016 Byoung Chol Oh, Georg Furtmuller, Madeline Fryer, Johanna Grahammer, Stefan Schneeberger, Damon Cooney, W. P. Andrew Lee, Giorgio Raimondi, and Gerald Brandacher. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. VASCULARIZED COMPOSITE ALLOTRANSPLANTATION 2016, VOL. 3, NOS. 1–2, 9 http://dx.doi.org/10.1080/23723505.2016.1232975","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127853919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2523: Vascularized composite allograft tolerance with transient high-dose tacrolimus across a full MHC mismatch in a large animal model","authors":"Howard D. Wang, E. Swanson, Hsu-Tang Cheng, J. Walch, Jose C. Alonso-Escalante, K. Kolegraff, Joseph Lopez, G. Furtmuller, B. Oh, A. Quan, J. Budihardjo, Sara AlFadil, Sara Mulla, S. Fidder, Paul J. Akre, J. Sacks, S. Bonawitz, G. Raimondi, J. Shores, D. Cooney, W. Lee, G. Brandacher","doi":"10.1080/23723505.2016.1232941","DOIUrl":"https://doi.org/10.1080/23723505.2016.1232941","url":null,"abstract":"2523: Vascularized composite allograft tolerance with transient high-dose tacrolimus across a full MHC mismatch in a large animal model Howard D. Wang, MD, Edward W. Swanson, MD, Hsu-Tang Cheng, MD, Jeffrey Walch, MD, PhD, Jose C. Alonso-Escalante, MD, Keli Kolegraff, MD, PhD, Joseph Lopez, MD, MBA, Georg Furtmuller, MD, Byoung Chol Oh, DVM, PhD, Amy Quan, MPH, Joshua Budihardjo, Sara AlFadil, MD, Sara Mulla, MD, Samuel Fidder, MD, Paul Akre, MS, Justin M. Sacks, MD, Steven C. Bonawitz, MD, Giorgio Raimondi, PhD, Jaimie T. Shores, MD, Damon S. Cooney, MD, PhD, W. P. Andrew Lee, MD, and Gerald Brandacher, MD Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD, USA Background Vascularized composite allografts (VCA) can enhance the quality of life for patients with severe facial or extremity injuries, and induction of tolerance would avoid the risk of immunosuppression and increase application of VCA The purpose of this study is to investigate strategies for tolerance induction in a large animal model Methods Heterotopic osteomyocutaneous hind limb transplantation was performed in 19 MGHminiature swine across full swine leukocyte antigen mismatch All animals received non-myeloablative conditioning with 50cGy total body and 350cGy thymic irradiation for induction Group I was treated with high-dose tacrolimus (15–20 ng/ml) maintenance therapy Group II was treated with low-dose tacrolimus (4–6 ng/ml) Group III received low-dose tacrolimus and 20 mg/kg of CTLA4-Ig administered on POD2, 7, 14, 30, 60, 90, and 120 Group IV received transient high-dose tacrolimus until POD60 Group V received transient highdose tacrolimus until POD60 and was switched to CTLA4-Ig administered on POD60, 85, 100, 120 and 150 Graft rejection was monitored by clinical assessment and protocol skin biopsies Alloreactivity against donor antigens was assessed using an optimized CFSE-based mixed lymphocyte reaction (MLR) Results Prolonged high-dose tacrolimus led to maintenance of VCA in 3/3 animals but was associated with major infectious complications 2/3 animals in group II rejected their grafts by POD46 and 217 In group III, 2/5 animals demonstrated rejection prior to POD150, while 3/5 animals achieved long-term survival of their VCA beyond POD300 3/3 animals in group IV and 4/5 animals in group V achieved indefinite graft survival beyond POD300 despite weaning of all immunosuppression The one animal in group V that rejected its graft began to show evidence of rejection on POD277 Donor specific unresponsiveness was confirmed in all long-term survivors in vitro by CFSE-MLR Conclusions Tolerance of VCA containing vascularized bone marrow can be achieved with a regimen of peritransplant high-dose tacrolimus without myeloablative conditioning. These findings describe a potential induction regimen to eliminate the need for long-term immunosuppression after reconstructive transplantation. CONTACT Howard D. Wang, MD hdw","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133363791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2530: Unilateral facial artery is sufficient for vascularized composite allotransplantation of the lower two-thirds of the face - Case report on a face transplant recipient at the Brigham and Women's Hospital","authors":"S. Fischer, Thomas C. Lee, N. Krezdorn, M. Alhefzi, M. Aycart, H. Kiwanuka, T. Win, E. Bueno, S. Tullius, B. Pomahac","doi":"10.1080/23723505.2016.1234256","DOIUrl":"https://doi.org/10.1080/23723505.2016.1234256","url":null,"abstract":"2530: Unilateral facial artery is sufficient for vascularized composite allotransplantation of the lower two-thirds of the face Case report on a face transplant recipient at the Brigham and Women’s Hospital Sebastian Fischer, Thomas C. Lee, Nicco Krezdorn, Muayyad Alhefzi, Mario A. Aycart, Harriet Kiwanuka, Thet S. Win, Ericka M. Bueno, Stefan Tullius, and Bohdan Pomahac Brigham and Women’s Hospital, Boston, MA, USA Background Facial allotransplantation provides a unique opportunity to restore facial form and function in severely disfigured patients. Using a single unilateral facial artery for vascularization can significantly reduce surgical duration and thus facilitate the practice of face transplantation. Patient and methods A 33-year-old man with a history of high-energy ballistic trauma received a facial allograft comprising the lower 2-thirds of the face, including maxilla and mandible. Vascular anastomoses involved one unilateral facial artery and 2 veins. Vascularization patterns, airway volume and facial functions were assessed before and 1 y after transplantation. In addition, immunosuppressive therapy and rejection episodes were recorded.","PeriodicalId":372758,"journal":{"name":"Vascularized Composite Allotransplantation","volume":"52 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126613557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}