Transplant Research and Risk Management最新文献_第7页

Potential benefits and risks of clinical xenotransplantation 临床异种器官移植的潜在益处和风险

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Transplant Research and Risk Management Pub Date : 2012-07-03 DOI: 10.2147/TRRM.S31481

D. Cooper, D. Ayares

{"title":"Potential benefits and risks of clinical xenotransplantation","authors":"D. Cooper, D. Ayares","doi":"10.2147/TRRM.S31481","DOIUrl":"https://doi.org/10.2147/TRRM.S31481","url":null,"abstract":"David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USAAbstract: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets (for the treatment of diabetes), neuronal cells (for the treatment of Parkinson's disease), and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs","PeriodicalId":41597,"journal":{"name":"Transplant Research and Risk Management","volume":"4 1","pages":"7-17"},"PeriodicalIF":0.9,"publicationDate":"2012-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TRRM.S31481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68495399","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}

引用次数: 6

The value of prophylactic vaccinations and antibiotic treatment in post-splenectomy patients: a review 脾切除术后预防性接种疫苗和抗生素治疗的价值综述

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Transplant Research and Risk Management Pub Date : 2012-06-28 DOI: 10.2147/TRRM.S25198

A. Lammers

{"title":"The value of prophylactic vaccinations and antibiotic treatment in post-splenectomy patients: a review","authors":"A. Lammers","doi":"10.2147/TRRM.S25198","DOIUrl":"https://doi.org/10.2147/TRRM.S25198","url":null,"abstract":"Although spleen preservation surgery and non-operative management are first- line treatment options, total splenectomy is frequently performed. Splenectomy is performed for a number of indications including idiopathic thrombocytopenic purpura, high-energetic trauma, and hematological malignancy. Following splenectomy, patients are at risk for over- whelming post-splenectomy infection (OPSI), a syndrome that presents with mild symptoms at onset but irreversible multi-organ-failure occurs within hours to days. Since the spleen plays an important role in the immune response to polysaccharide antigens, encapsulated bacteria such as pneumococci are the most frequently described causative organisms of OPSI. Although the incidence of OPSI is low, the associated mortality is reported to be as high as 80%. Because of the overwhelming and frequently irreversible nature of this syndrome, prophylactic measures to prevent OPSI have been recommended. These recommendations include vaccination, use of antibiotics, and continuous patient education. After splenectomy, patients should receive immunizations against the encapsulated bacteria S. pneumoniae, H. influenza , and N. meningitidis. Antibiotic therapy should include prophylaxis as well as \"on-demand\" antibiotics when infection is suspected. Importantly, patients should receive ongoing education regarding the risks associated with asplenia and precautions to take when infection occurs and when traveling.","PeriodicalId":41597,"journal":{"name":"Transplant Research and Risk Management","volume":"4 1","pages":"19-24"},"PeriodicalIF":0.9,"publicationDate":"2012-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TRRM.S25198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68495267","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}

引用次数: 3

Sirolimus-associated hepatotoxicity: Case report and review of the literature 西罗莫司相关肝毒性:病例报告和文献回顾

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Transplant Research and Risk Management Pub Date : 2012-01-18 DOI: 10.2147/TRRM.S21313

B. Macdonald, Evi Vakiani, R. Yantiss, J. Lee, Robert S. Brown, S. Sigal

引用次数: 1

Facial transplantation: a review of ethics, progress, and future targets 面部移植:伦理、进展和未来目标的回顾

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Transplant Research and Risk Management Pub Date : 2011-09-05 DOI: 10.2147/TRRM.S6883

J. A. Edwards, D. Mathes

{"title":"Facial transplantation: a review of ethics, progress, and future targets","authors":"J. A. Edwards, D. Mathes","doi":"10.2147/TRRM.S6883","DOIUrl":"https://doi.org/10.2147/TRRM.S6883","url":null,"abstract":"Correspondence: David w Mathes Chief, Seattle veterans Affairs Hospital, University of washington Medical Center, 1959 NE Pacific Street, Box 356410, Seattle, wA 98115, USA Tel +1 206 543-5516 Fax +1 206 543-8136 Email dwmathes@u.washington.edu Abstract: The surgical history of transplantation in the modern era begins in 1956 with the successful transplantation of a kidney between identical twins. Since then the field of transplantation has seen remarkable advancements in both surgical techniques and our understanding and ability to manipulate the immune response. Composite tissue allotransplantation involves the transplantation of any combination of vascularized skin, subcutaneous tissue, blood vessels, nerves, muscle, and bone. Orthotopic hand transplantation is considered the first clinical example of CTA and has seen success at many different centers worldwide. Facial allotransplantation is a recent development in the field of CTA and the first successful case was performed as recently as November 2005. Since then there have been a number of successful facial transplants. The purpose of this paper is to examine some of the issues surrounding facial transplantation including the complex ethical issues, the surgical and clinical issues, cost and administrative issues, and future directions for this new, exciting, and controversial field.","PeriodicalId":41597,"journal":{"name":"Transplant Research and Risk Management","volume":"3 1","pages":"113-125"},"PeriodicalIF":0.9,"publicationDate":"2011-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TRRM.S6883","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68497142","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}

引用次数: 8

Everolimus in kidney transplantation 依维莫司在肾移植中的应用

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Transplant Research and Risk Management Pub Date : 2011-07-08 DOI: 10.2147/TRRM.S13782

J. Cooper, U. Christians, A. Wiseman

引用次数: 4

Evaluation of medication errors via a computerized physician order entry system in an inpatient renal transplant unit 利用计算机化医嘱输入系统对肾移植住院病人用药错误进行评估

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Transplant Research and Risk Management Pub Date : 2011-05-18 DOI: 10.2147/TRRM.S17819

K. Marfo, D. García, S. Khalique, K. Berger, A. Lu

{"title":"Evaluation of medication errors via a computerized physician order entry system in an inpatient renal transplant unit","authors":"K. Marfo, D. García, S. Khalique, K. Berger, A. Lu","doi":"10.2147/TRRM.S17819","DOIUrl":"https://doi.org/10.2147/TRRM.S17819","url":null,"abstract":"correspondence: Kwaku Marfo Montefiore-Einstein Center for Transplantation, Department of Pharmacy, Montefiore Medical Center, The University hospital for Albert einstein college of Medicine, 111 east 210th street, Bronx, nY 10467, UsA Tel +1 718 920 3752 Fax +1 718 798 0722 email kmarfo@montefiore.org Background: Medication errors are a prime concern for all in healthcare. As such the use of information technologies in drug prescribing and administration has received considerable attention in recent years, with the hope of improving patient safety. Because of the complexity of drug regimens in renal transplant patients, occurrence of medication errors is inevitable even with a well adopted computerized physician order entering (CPOE) system. Our objective was to quantify medication error type and frequency in an inpatient renal transplant unit. Methods: Systemic evaluation of all medication errors during an initial 10-day audit and a 28-day follow-up audit in an inpatient renal transplant unit. Each error was concurrently evaluated for potential to result in adverse patient consequences (category), error type and associated medication class. Results: A total of 103 clinically significant medication errors were detected during the 10-day (43 errors) and 28-day audit (60 errors) time periods. The most common errors were wrong medication dose ordered and wrong time of drug administration. Thirty-six out of 66 prescribing/ ordering errors reached the patient. Conclusions: Even with utilization of computerized physician order entry system in an inpatient renal transplant unit, post-kidney transplant patients are at risk for adverse outcomes due to medication errors. The risk factors may be multifactorial and will require both organizational and technical approaches to resolve.","PeriodicalId":41597,"journal":{"name":"Transplant Research and Risk Management","volume":"3 1","pages":"91-96"},"PeriodicalIF":0.9,"publicationDate":"2011-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TRRM.S17819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68495125","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}

引用次数: 5

Long-term outcome of everolimus treatment in transplant patients 依维莫司治疗移植患者的长期疗效

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Transplant Research and Risk Management Pub Date : 2011-05-13 DOI: 10.2147/TRRM.S12212

M. Salvadori, E. Bertoni

{"title":"Long-term outcome of everolimus treatment in transplant patients","authors":"M. Salvadori, E. Bertoni","doi":"10.2147/TRRM.S12212","DOIUrl":"https://doi.org/10.2147/TRRM.S12212","url":null,"abstract":"Correspondence: Maurizio Salvadori Renal Unit, Careggi University Hospital, viale Pieraccini 18, 50139 Florence, italy Tel +39 055 794 9269 Fax +39 055 435 878 email maurizio.salvadori@unifi.it Abstract: The authors review the use of everolimus in long-term studies both in renal and heart transplantation. The pharmacokinetic and pharmacodynamic differences between everolimus and its parent drug, sirolimus are discussed. The improved pharmacokinetic, in particular the improved bioavailability, the reduced half-time and the reduced binding to plasma protein makes everolimus the first choice among the proliferation signal inhibitors. Everolimus is given in almost all studies in association with cyclosporine, but fixed doses of this drug can cause nephrotoxicity. The first studies used everolimus and CsA in fixed doses, but later studies with reduced CsA doses revealed which revealed improved outcomes. Finally, therapeutic drug monitoring became the better choice for both drugs. Recently very high everolimus exposure allowed the use of very low CsA exposure with improvement of the worse side effects linked to the CsA standard dose. The Zeus study revealed a complete and safe CsA withdrawal, thanks to everolimus and mycophenolic acid. In heart transplantation, everolimus resulted in improved outcomes with respect to antiproliferative drugs such as mycophenolic acid and azathioprine. Along with antirejection properties, everolimus provided evidence for antiproliferative effects on several cells. This resulted in fewer viral infections (mainly CMV), anti-atherosclerotic properties (mainly important in heart transplantation, and antineoplastic effect. The latter activity resulted in lower cancer incidence in transplant patients treated by everolimus. An important piece of evidence for this activity is documented by the use of everolimus in the treatment of some cancers, including renal cancer, neuroendocrine cancers and hepatocellular cancers, also outside the field of transplantation.","PeriodicalId":41597,"journal":{"name":"Transplant Research and Risk Management","volume":"3 1","pages":"77-90"},"PeriodicalIF":0.9,"publicationDate":"2011-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TRRM.S12212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68494791","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}

引用次数: 11

Critical appraisal of belatacept for prophylaxis of rejection in kidney transplant patients 肾移植患者预防排斥反应的关键评价

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Transplant Research and Risk Management Pub Date : 2011-04-12 DOI: 10.2147/TRRM.S11538

Spencer T. Martin, D. Tsapepas, S. Gabardi, A. Chandraker

{"title":"Critical appraisal of belatacept for prophylaxis of rejection in kidney transplant patients","authors":"Spencer T. Martin, D. Tsapepas, S. Gabardi, A. Chandraker","doi":"10.2147/TRRM.S11538","DOIUrl":"https://doi.org/10.2147/TRRM.S11538","url":null,"abstract":"Belatacept (LEA29Y) is an intravenous biologic for long-term maintenance immunosuppressive therapy in renal transplant recipients. It is currently being reviewed by the United States Food and Drug Administration (FDA) as a prophylactic therapy against acute cellular rejection (ACR) in de novo renal transplant recipients. To provide an in-depth review of the pharmacology, clinical efficacy, safety, and applications of belatacept, a MEDLINE database search was performed for all English-language articles evaluating the pharmacology and efficacy of belatacept, as well as abstracts from recent scientific meetings. Belatacept is a potent inhibitor of B7 binding to CD28, a potent T-cell co-stimulatory signal. The B7 ligands are found on the surface of antigen-presenting cells, specifically B7-1 (CD80) and B7-2 (CD86). CD80 and CD86 are essential ligands for CD28, a critical component of costimulation in the three-signal transplant model of T-cell activation. Belatacept has proven noninferiority compared with calcineurin-inhibitor (CNI)-based regimens in the incidence of patient and allograft survival. However, the incidence and severity of ACR has been shown to be increased in patients receiving belatacept therapy. Although rates of ACR are increased in patients receiving belata- cept, an overall improvement in allograft function has been described with average improve- ments in glomerular filtration rates of up to 12-15 mL/min higher than CNI-based regimens. The side-effect profile of belatacept has been shown to be similar or improved compared with CNI therapy; however, the risk of malignancy, specifically post-transplant lymphoproliferative disorder is notably higher. Because of the marked increase in the risk of malignancy and ACR, approval of belatacept by the FDA will rely on more robust data from long-term follow-up of currently available data.","PeriodicalId":41597,"journal":{"name":"Transplant Research and Risk Management","volume":"3 1","pages":"65-75"},"PeriodicalIF":0.9,"publicationDate":"2011-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TRRM.S11538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68494423","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}

引用次数: 2

Development and utility of pirfenidone in the treatment of idiopathic pulmonary fibrosis: review of preclinical science and recent clinical trials 吡非尼酮治疗特发性肺纤维化的发展和应用:临床前科学和最近的临床试验综述

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Transplant Research and Risk Management Pub Date : 2011-04-11 DOI: 10.2147/TRRM.S16205

R. Jackson, O. Gómez-Marín

{"title":"Development and utility of pirfenidone in the treatment of idiopathic pulmonary fibrosis: review of preclinical science and recent clinical trials","authors":"R. Jackson, O. Gómez-Marín","doi":"10.2147/TRRM.S16205","DOIUrl":"https://doi.org/10.2147/TRRM.S16205","url":null,"abstract":"Pirfenidone is a pyridine-derived, double-ringed molecule that has a number of biologic effects including anti-inflammatory and antifibrotic properties in rodent models of acute lung injury and fibrosis, in addition to scavenging reactive oxygen species. These effects are clinically relevant, because idiopathic pulmonary fibrosis (IPF) is a progressive and increasingly prevalent disease characterized by diffuse lung scarring due to alveolar epithelial cell injury, which typically leads to death 3-5 years after diagnosis. No proven therapy for IPF exists, and many IPF patients eventually require lung transplantation, making the need for pharmacologic therapy great. Pirfenidone is rapidly distributed in body water and metabolized by the liver. Several clinical trials have tested pirfenidone in patients with IPF and found it well-tolerated with acceptable side effects. Pirfenidone in clinical trials has been found to improve progression-free survival and pulmonary function of IPF patients. Although the specific mechanism accounting for its benefits is not known, pirfenidone decreases collagen synthesis and fibroblast prolifera- tion, and it may down-regulate inflammation by virtue of its effects on mitogen-activated protein kinases. Pirfenidone has gained regulatory approval for marketing in Japan and in the European Union. It could prove to be a useful therapeutic agent for patients with IPF.","PeriodicalId":41597,"journal":{"name":"Transplant Research and Risk Management","volume":"3 1","pages":"55-63"},"PeriodicalIF":0.9,"publicationDate":"2011-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TRRM.S16205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68495050","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}

引用次数: 9

Mycophenolic acid agents: is enteric coating the answer? 霉酚酸制剂:肠溶性包衣是答案吗?

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Transplant Research and Risk Management Pub Date : 2011-03-29 DOI: 10.2147/TRRM.S12210

Wana Manitpisitkul, Sabrina Lee, M. Cooper

{"title":"Mycophenolic acid agents: is enteric coating the answer?","authors":"Wana Manitpisitkul, Sabrina Lee, M. Cooper","doi":"10.2147/TRRM.S12210","DOIUrl":"https://doi.org/10.2147/TRRM.S12210","url":null,"abstract":"Correspondence: Matthew Cooper Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD, USA Tel +1 410 328 7336 Fax +1 410 328 6343 email mcooper@smail.umaryland.edu Abstract: Addition of mycophenolate mofetil (MMF) to calcineurin-based immunosuppressive therapy has led to a significant improvement in graft survival and reduction of acute rejection in renal transplant recipients. However, in clinical practice, MMF dose reduction, interruption, or discontinuation due to hematological and gastrointestinal (GI) side-effects occurred in up to 50% of the patients. Large retrospective analyses have demonstrated that patients requiring MMF dose manipulation due to adverse events experienced a higher rate of rejection and graft loss. Enteric-coated mycophenolate sodium (EC-MPS) was developed with the goal of improving upper GI side-effects. Here, we review the efficacy and safety of EC-MPS in de novo kidney transplant recipient, and in stable renal transplant patients who were converted from MMF. The changes in GI-related adverse events using patient-reported outcome instruments are also reviewed.","PeriodicalId":41597,"journal":{"name":"Transplant Research and Risk Management","volume":"3 1","pages":"45-53"},"PeriodicalIF":0.9,"publicationDate":"2011-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TRRM.S12210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68494582","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}

引用次数: 3