9 results on '"Roan, Jun-Neng"'
Search Results
2. Ex Vivo Gene Delivery to Porcine Cardiac Allografts Using a Myocardial-Enhanced Adeno-Associated Viral Vector.
- Author
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Mendiola Pla M, Chiang Y, Roki A, Wang C, Lee FH, Smith MF, Gross RT, Roan JN, Bishawi M, Evans A, Gault LE, Ho S, Glass C, Schroder JN, Lezberg P, Milano CA, and Bowles DE
- Subjects
- Swine, Animals, Humans, Perfusion methods, Tissue Donors, Genetic Therapy methods, Allografts, Heart Transplantation methods
- Abstract
Transplantation, the gold standard intervention for organ failure, is a clinical field that is ripe for applications of gene therapy. One of the major challenges in applying gene therapy to this field is the need for a method that achieves consistent and robust gene delivery to allografts. Normothermic ex vivo perfusion is a growing organ preservation method and a device for cardiac preservation was recently approved by the Food and Drug Administration (FDA) (Organ Care System, OCS™; TransMedics, Inc., Andover, MA); this device maintains donor hearts in a near physiologic state while they are transported from the donor to the recipient. This study describes the administration of recombinant adeno-associated viral vectors (rAAVs) during ex vivo normothermic perfusion for the delivery of transgenes to porcine cardiac allografts. We utilized a myocardial-enhanced AAV3b variant, SASTG, assessing its transduction efficiency in the OCS perfusate relative to other AAV serotypes. We describe the use of normothermic ex vivo perfusion to deliver SASTG carrying the Firefly Luciferase transgene to porcine donor hearts in four heterotopic transplant procedures. Durable and dose-dependent transgene expression was achieved in the allografts in 30 days, with no evidence of off-target transgene expression. This study demonstrates the feasibility and efficiency of delivering genes to a large animal allograft utilizing AAV vectors during ex vivo perfusion. These findings support the idea of gene therapy interventions to enhance transplantation outcomes.
- Published
- 2023
- Full Text
- View/download PDF
3. A Case Report of Posttransplant Lymphoproliferative Disorder After AstraZeneca Coronavirus Disease 2019 Vaccine in a Heart Transplant Recipient.
- Author
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Tang WR, Hsu CW, Lee CC, Huang WL, Lin CY, Hsu YT, Chang C, Tsai MT, Hu YN, Hsu CH, Chen PL, Chow NH, and Roan JN
- Subjects
- Humans, Herpesvirus 4, Human, ChAdOx1 nCoV-19 adverse effects, COVID-19 prevention & control, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections diagnosis, Heart Transplantation, Lymphoproliferative Disorders chemically induced, Lymphoproliferative Disorders diagnosis
- Abstract
We report a case of a heart transplant recipient who presented with a rapidly growing Epstein-Barr virus (EBV)-positive, diffuse large B-cell lymphoma 7 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Because of the atypical radiologic presentation, the initial tentative diagnosis was a mediastinal abscess. This observation indicates a potential risk of EBV reactivation after coronavirus disease 2019 (COVID-19) vaccination, which might lead to or aggravate the presentation of posttransplant lymphoproliferative disorder in transplantation patients. Transplant surgeons should be aware of the potential immunomodulatory effects of the COVID-19 vaccination., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
4. A normothermic ex vivo organ perfusion delivery method for cardiac transplantation gene therapy.
- Author
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Bishawi M, Roan JN, Milano CA, Daneshmand MA, Schroder JN, Chiang Y, Lee FH, Brown ZD, Nevo A, Watson MJ, Rowell T, Paul S, Lezberg P, Walczak R, and Bowles DE
- Subjects
- Adenoviridae genetics, Allografts chemistry, Animals, Feasibility Studies, Female, Genes, Reporter genetics, Genetic Vectors genetics, Heart Failure genetics, Humans, Liver chemistry, Luciferases analysis, Luciferases genetics, Models, Animal, Myocardium chemistry, Organ Preservation methods, Organ Preservation Solutions chemistry, Sus scrofa, Transplantation, Homologous methods, Gene Transfer Techniques, Genetic Therapy methods, Heart Failure therapy, Heart Transplantation methods, Perfusion methods
- Abstract
Clinically, both percutaneous and surgical approaches to deliver viral vectors to the heart either have resulted in therapeutically inadequate levels of transgene expression or have raised safety concerns associated with extra-cardiac delivery. Recent developments in the field of normothermic ex vivo cardiac perfusion storage have now created opportunities to overcome these limitations and safety concerns of cardiac gene therapy. This study examined the feasibility of ex vivo perfusion as an approach to deliver a viral vector to a donor heart during storage and the resulting bio distribution and expression levels of the transgene in the recipient post-transplant. The influence of components (proprietary solution, donor blood, and ex vivo circuitry tubing and oxygenators) of the Organ Care System (OC) (TransMedics, Inc., Andover MA) on viral vector transduction was examined using a cell-based luciferase assay. Our ex vivo perfusion strategy, optimized for efficient Adenoviral vector transduction, was utilized to deliver 5 × 10
13 total viral particles of an Adenoviral firefly luciferase vector with a cytomegalovirus (CMV) promotor to porcine donor hearts prior to heterotopic implantation. We have evaluated the overall levels of expression, protein activity, as well as the bio distribution of the firefly luciferase protein in a series of three heart transplants at a five-day post-transplant endpoint. The perfusion solution and the ex vivo circuitry did not influence viral vector transduction, but the serum or plasma fractions of the donor blood significantly inhibited viral vector transduction. Thus, subsequent gene delivery experiments to the explanted porcine heart utilized an autologous blood recovery approach to remove undesired plasma or serum components of the donor blood prior to its placement into the circuit. Enzymatic assessment of luciferase activity in tissues (native heart, allograft, liver etc.) obtained post-transplant day five revealed wide-spread and robust luciferase activity in all regions of the allograft (right and left atria, right and left ventricles, coronary arteries) compared to the native recipient heart. Importantly, luciferase activity in recipient heart, liver, lung, spleen, or psoas muscle was within background levels. Similar to luciferase activity, the luciferase protein expression in the allograft appeared uniform and robust across all areas of the myocardium as well as in the coronary arteries. Importantly, despite high copy number of vector genomic DNA in transplanted heart tissue, there was no evidence of vector DNA in either the recipient's native heart or liver. Overall we demonstrate a simple protocol to achieve substantial, global gene delivery and expression isolated to the cardiac allograft. This introduces a novel method of viral vector delivery that opens the opportunity for biological modification of the allograft prior to implantation that may improve post-transplant outcomes.- Published
- 2019
- Full Text
- View/download PDF
5. Use of Two Intracorporeal Ventricular Assist Devices As a Total Artificial Heart.
- Author
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Bishawi M, Roan JN, Richards J, Brown Z, Blue L, Daneshmand MA, Schroder JN, Bowles DE, and Milano CA
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- Animals, Cattle, Heart Failure physiopathology, Humans, Heart Failure therapy, Heart Transplantation methods, Heart, Artificial, Heart-Assist Devices
- Abstract
Mechanical circulatory support (MCS) has been introduced as a viable alternative to heart transplantation primarily through the use of intracorporeal ventricular assist devices (VADs) for support of the left ventricle. However, certain clinical scenarios warrant biventricular mechanical support. One strategy for some patients is the excision of both ventricles and the implantation of two VAD pumps as a total artificial heart (TAH). This has recently been made possible by the improvements in device design and the small profile of centrifugal devices. This TAH approach remains experimental with many important challenges such as the device settings to balance the right and left circulation, the orientation of the devices and the outflow graft with their influence on hemolysis and stability, and the outcome of chronic support using such an orientation. This protocol aims to provide a reproducible approach for total artificial heart replacement with two intracorporeal centrifugal VADs in a cow model.
- Published
- 2018
- Full Text
- View/download PDF
6. High-dose calcineurin inhibitor-free everolimus as a maintenance regimen for heart transplantation may be a risk factor for Pneumocystis pneumonia.
- Author
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Hu YN, Lee NY, Roan JN, Hsu CH, and Luo CY
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- Adult, Calcineurin Inhibitors therapeutic use, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Pneumonia, Pneumocystis diagnostic imaging, Pneumonia, Pneumocystis etiology, Pneumonia, Pneumocystis microbiology, Retrospective Studies, Survival Analysis, Tacrolimus therapeutic use, Taiwan, Everolimus therapeutic use, Heart Transplantation adverse effects, Immunosuppressive Agents therapeutic use, Pneumocystis carinii isolation & purification, Pneumonia, Pneumocystis drug therapy
- Abstract
Background: Everolimus reduces the incidence of cardiac-allograft vasculopathy (CAV) and is less renally toxic than are calcineurin inhibitors (CNIs). We evaluated the safety of CNI-free everolimus for post-heart transplant (HTx) patients., Methods: We retrospectively reviewed the records of 36 consecutive patients who had undergone an HTx between January 2006 and December 2013 in National Cheng Kung University Hospital. All patients initially had been treated with the standard tacrolimus regimen. The Study group-12 patients with CAV, renal impairment, or a history of malignancy-were switched from tacrolimus to everolimus. The Control group consisted of 19 patients who remained on the standard regimen. The target everolimus trough concentration was 8-14 ng/mL. The primary outcome was survival, and the secondary outcomes were bacterial, viral, fungal, and other infections; Pneumocystis jirovecii pneumonia (PJP); and rejection (≥2R)., Results: During a 53.3±25.6-month follow-up, the survival rate, rejection rate, and number of infections, except for PJP, were not significantly different between the two groups. In the Study group, 6 patients were diagnosed with PJP 33±18.2 months after switching. None of the Control group patients were diagnosed with PJP during follow-up., Conclusions: A high-dose CNI-free everolimus maintenance regimen might yield a higher incidence of post-transplantation PJP., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2017
- Full Text
- View/download PDF
7. Obscured hemorrhagic pancreatitis after orthotopic heart transplantation complicated with acute right heart failure and hepatic dysfunction: a case report.
- Author
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Lin TW, Tsai MT, Roan JN, Liu YS, Tsai HM, and Luo CY
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- Adult, Heart Failure etiology, Hemorrhage diagnosis, Humans, Liver Diseases etiology, Male, Pancreatitis diagnosis, Shock, Hemorrhagic etiology, Embolization, Therapeutic, Heart Transplantation adverse effects, Hemorrhage etiology, Hemorrhage therapy, Pancreatitis etiology, Postoperative Complications diagnosis
- Abstract
Background: Pancreatitis is a serious complication after cardiac surgery and can lead to significant morbidities and mortality. The incidence of pancreatitis is even higher in patients undergoing heart transplantation than in those undergoing other cardiac surgeries. Nevertheless, the clinical presentations of pancreatitis are frequently atypical in these patients., Case Presentation: We report a heart recipient who was complicated with acute right heart failure initially after orthotopic heart transplantation and developed devastating unanticipated hemorrhagic pancreatitis 1 month after the transplantation. This crypto-symptomatic pancreatitis was not diagnosed until massive internal bleeding and hemorrhagic shock occurred, because the typical presentations of acute pancreatitis were masked by the intra-abdominal manifestations caused by right heart failure and congestive liver dysfunction. The patient underwent a successful transarterial embolization., Conclusions: The causes of pancreatitis after heart transplantation include low cardiac output, immunosuppressant use and cytomegalovirus infection. The typical symptoms of pancreatitis might be not apparent in patients after heart transplantation because of their immunosuppressive status. Furthermore, in patients complicated with right heart failure after transplantation, the manifestation of pancreatitis could be even more obscure. The prompt diagnosis is highly depended on the clinician's astuteness.
- Published
- 2016
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8. Dose-normalization for exposure to mycophenolic acid and the early clinical outcome in patients taking tacrolimus after heart transplantation.
- Author
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Roan JN, Chou CH, Hsu CH, Wu SY, Huang YC, Yang YJ, and Luo CY
- Subjects
- Adult, Area Under Curve, Female, Glucuronides blood, Humans, Immunosuppressive Agents adverse effects, Male, Middle Aged, Mycophenolic Acid administration & dosage, Mycophenolic Acid adverse effects, Prospective Studies, Time Factors, Treatment Outcome, Heart Transplantation, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents blood, Mycophenolic Acid analogs & derivatives, Mycophenolic Acid blood, Tacrolimus administration & dosage
- Abstract
Background: The early phase of MPA exposure has rarely been investigated after solid organ transplantation, especially in heart transplantation patients. We evaluated the association between exposure to mycophenolic acid (MPA), a main metabolite of mycophenolate mofetil (MMF), and clinical events within 3 months after heart transplantation., Material and Methods: Trough (C0) and area under the curve (AUC)0-12h levels of MPA and its metabolite, mycophenolic acid glucuronide (MPAG), were determined using high-performance liquid chromatography. Corresponding clinical endpoints included acute rejection or MMF-related adverse events (gastrointestinal symptoms, leucopenia, and anemia). AUC measurements (n=77) were collected from 21 patients. Dose-normalized C0 and AUC0-12h levels were used to evaluate the association between MPA or MPAG exposure and MMF-related adverse events., Results: No acute rejection or mortality occurred during the follow-up period. Twelve patients (57%) developed 13 MMF-related adverse events. The MMF dose was tapered from 2.50 g/day on D1 to 1.55±0.54 g/day on D90. Significantly higher levels of dose-normalized MPA C0 and AUC0-12h were associated with the events than with the absence of the events (C0: 1.04±0.42 vs. 0.84±0.85 µg/mL/g [p=0.047]; AUC0-12h: 20.37±3.21 vs. 14.97±1.13 µg × h/mL/g; [p=0.038]). Conclusions Dose-normalized MPA exposure may protect against MMF toxicity in the early stage after heart transplantation. The MMF dose can be decreased to near 1.5 g/day 3 months post-transplantation without jeopardizing patient safety; a well-planned, tapered MMF regimen should also be considered.
- Published
- 2013
- Full Text
- View/download PDF
9. Pulmonary nodules caused by Schizophyllum commune after cardiac transplantation.
- Author
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Roan JN, Hsieh HY, Tsai HW, Wu CJ, Hsu CH, Wu SY, Yang YJ, and Chang TC
- Subjects
- Antifungal Agents therapeutic use, DNA, Fungal chemistry, DNA, Fungal genetics, DNA, Ribosomal Spacer chemistry, DNA, Ribosomal Spacer genetics, Female, Fluconazole therapeutic use, Humans, Middle Aged, Mycoses drug therapy, Mycoses microbiology, Pneumonia pathology, Schizophyllum classification, Schizophyllum genetics, Sequence Analysis, DNA, Heart Transplantation adverse effects, Mycoses diagnosis, Pneumonia microbiology, Schizophyllum isolation & purification
- Abstract
The incidence of pulmonary nodules after cardiac transplantation is not uncommon, and prompt diagnostic procedures are necessary to minimize disease-related morbidity and mortality. We report a 56-year-old woman who was found to have bilateral pulmonary nodules four months after cardiac transplantation. The microorganism was identified with a molecular diagnostic method as Schizophyllum commune, which had not been reported in English literature as a pathogen inducing pulmonary nodules after transplantation. She remained asymptomatic during the therapeutic period and the pulmonary nodules resolved six months later.
- Published
- 2009
- Full Text
- View/download PDF
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