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  • 刊频： Quarterly, 2013
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  • 1.

    【2hr】Current techniques for AB0-incompatible living donor liver transplantation

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    机译 AB0不相容的活体供肝移植的当前技术
    摘要：For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible (AB0i) grafts. Improvements in AB0i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0i living donor liver transplantation (LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients’ graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0i LDLT is a feasible option today and almost free of severe complications.
  • 2.

    【2hr】Tregs and kidney: From diabetic nephropathy to renal transplantation

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    机译 Tregs和肾脏：从糖尿病肾病到肾脏移植
    摘要：Kidney transplantation is recognised as the most effective treatment for patients with end-stage renal disease (ESRD). Kidney transplantation continues to face several challenges including long-term graft and patient survival, and the side effects of immunosuppressive therapy. The tendency in kidney transplantation is to avoid the side effects of immunosuppresants and induce immune tolerance. Regulatory T-cells (Tregs) contribute to self-tolerance, tolerance to alloantigen and transplant tolerance, mainly by suppressing the activation and function of reactive effector T-cells. Additionally, Tregs are implicated in the pathogenesis of diabetes, which is the leading cause of ESRD, suggesting that these cells play a role both in the pathogenesis of chronic kidney disease and the induction of transplant tolerance. Several strategies to achieve immunological tolerance to grafts have been tested experimentally, and include combinations of co-stimulatory blockade pathways, T-cell depletion, in vivo Treg-induction and/or infusion of ex-vivo expanded Tregs. However, a successful regimen that induces transplant tolerance is not yet available for clinical application. This review brings together certain key studies on the role of Tregs in ESRD, diabetes and kidney transplantation, only to emphasize that many more studies are needed to elucidate the clinical significance and the therapeutic applications of Tregs.
  • 3.

    【2hr】Updates on antibody-mediated rejection in intestinal transplantation

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    机译 肠移植中抗体介导排斥反应的最新进展
    • 作者：Guo-Sheng Wu
    • 刊名：World Journal of Transplantation
    • 2016年第3期
    摘要：Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.
  • 4.

    【2hr】Pharmacological Tie2 activation in kidney transplantation

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    机译 Tie2激活在肾脏移植中的药理作用
    摘要：AIMTo investigate the therapeutic potential of vasculotide (VT) - a Tie2 activating therapeutic - in kidney transplantation.
  • 5.

    【2hr】Thromboelastographic reference ranges for a cirrhotic patient population undergoing liver transplantation

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    机译 肝移植肝硬化患者的血栓弹力图参考范围
    摘要：AIMTo describe the thromboelastography (TEG) “reference” values within a population of liver transplant (LT) candidates that underline the differences from healthy patients.
  • 6.

    【2hr】Underutilization of palliative care services in the liver transplant population

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    机译 肝移植人群中姑息治疗服务的利用不足
    摘要：AIMTo evaluate use of palliative care services in patients with end-stage liver disease who do not have access to liver transplant.
  • 7.

    【2hr】Evaluating twenty-years of follow-up after orthotopic liver transplantation, best practice for donor-recipient matching: What can we learn from the past era?

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    机译 评估原位肝移植后二十年的随访，供体-受体匹配的最佳实践：我们可以从过去的时代中学到什么？
    摘要：AIMTo characterize major determinants of 20-year survival after liver transplantation (LT).
  • 8.

    【2hr】New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

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    机译 增加肠长的新方法：用于肠再生和生物工程的方法
    摘要：Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option.
  • 9.

    【2hr】High-risk corneal allografts: A therapeutic challenge

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    机译 高危角膜同种异体移植：治疗上的挑战
    摘要：Corneal transplantation is the most common surgical procedure amongst solid organ transplants with a high survival rate of 86% at 1-year post-grafting. This high success rate has been attributed to the immune privilege of the eye. However, mechanisms originally thought to promote immune privilege, such as the lack of antigen presenting cells and vessels in the cornea, are challenged by recent studies. Nevertheless, the immunological and physiological features of the cornea promoting a relatively weak alloimmune response is likely responsible for the high survival rate in “low-risk” settings. Furthermore, although corneal graft survival in “low-risk” recipients is favourable, the prognosis in “high-risk” recipients for corneal graft is poor. In “high-risk” grafts, the process of indirect allorecognition is accelerated by the enhanced innate and adaptive immune responses due to pre-existing inflammation and neovascularization of the host bed. This leads to the irreversible rejection of the allograft and ultimately graft failure. Many therapeutic measures are being tested in pre-clinical and clinical studies to counter the immunological challenge of “high-risk” recipients. Despite the prevailing dogma, recent data suggest that tissue matching together with use of systemic immunosuppression may increase the likelihood of graft acceptance in “high-risk” recipients. However, immunosuppressive drugs are accompanied with intolerance/side effects and toxicity, and therefore, novel cell-based therapies are in development which target host immune cells and restore immune homeostasis without significant side effect of treatment. In addition, developments in regenerative medicine may be able to solve both important short comings of allotransplantation: (1) graft rejection and ultimate graft failure; and (2) the lack of suitable donor corneas. The advances in technology and research indicate that wider therapeutic choices for patients may be available to address the worldwide problem of corneal blindness in both “low-risk” and “high-risk” hosts.
  • 10.

    【2hr】Proteomics for rejection diagnosis in renal transplant patients: Where are we now?

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    机译 蛋白质组学在肾移植患者中的排斥反应诊断：我们现在在哪里？
    摘要：Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic.
  • 11.

    【2hr】Immunological aspects of liver cell transplantation

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    机译 肝细胞移植的免疫学方面
    摘要：Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation (OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation (LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where long-term graft survival is observed on a regular basis and, hence, the liver has been deemed an immune-privileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells.
  • 12.

    【2hr】Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

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    机译 肾移植局灶性节段性肾小球硬化治疗的最新进展
    摘要：Focal segmental glomerulosclerosis (FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts (30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called “de novo” type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.
  • 13.

    【2hr】Survival of encapsulated islets: More than a membrane story

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    机译 封装的胰岛的生存：不仅仅是膜故事
    摘要：At present, proven clinical treatments but no cures are available for diabetes, a global epidemic with a huge economic burden. Transplantation of islets of Langerhans by their infusion into vascularized organs is an experimental clinical protocol, the first approach to attain cure. However, it is associated with lifelong use of immunosuppressants. To overcome the need for immunosuppression, islets are encapsulated and separated from the host immune system by a permselective membrane. The lead material for this application is alginate which was tested in many animal models and a few clinical trials. This review discusses all aspects related to the function of transplanted encapsulated islets such as the basic requirements from a permselective membrane (e.g., allowable hydrodynamic radii, implications of the thickness of the membrane and relative electrical charge). Another aspect involves adequate oxygen supply, which is essential for survival/performance of transplanted islets, especially when using large retrievable macro-capsules implanted in poorly oxygenated sites like the subcutis. Notably, islets can survive under low oxygen tension and are physiologically active at > 40 Torr. Surprisingly, when densely crowded, islets are fully functional under hyperoxic pressure of up to 500 Torr (> 300% of atmospheric oxygen tension). The review also addresses an additional category of requirements for optimal performance of transplanted islets, named auxiliary technologies. These include control of inflammation, apoptosis, angiogenesis, and the intra-capsular environment. The review highlights that curing diabetes with a functional bio-artificial pancreas requires optimizing all of these aspects, and that significant advances have already been made in many of them.
  • 14.

    【2hr】Key psychosocial challenges in vascularized composite allotransplantation

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    机译 血管化复合同种异体移植的关键社会心理挑战
    摘要：Psychosocial factors are important elements in the assessment and follow-up care for vascularized composite allotransplantation (VCA) and require multidisciplinary evaluation protocols. This review will highlight differences between VCA with solid organ transplantation (SOT), provide information on the psychosocial selection of VCA candidates, ethical issues, psychological outcomes, and on the need for multicenter research. VCA is primarily a life-enhancing procedure to improve recipients’ quality of life and psychological well-being and it represents a potential option to provide reproduction in case of penile or uterine transplantation. The risk benefit ratio is distinctly different than SOT with candidates desiring life enhancing outcomes including improved body image, return to occupations, restored touch, and for uterine transplant, pregnancy. The Chauvet Workgroup has been convened with membership from a number of transplant centers to address these issues and to call for multicenter research. A multicenter research network would share similar evaluation approaches so that meaningful research on psychosocial variables could inform the transplant community and patients about factors that increase risk of non-adherence and other adverse psychosocial and medical outcomes.
  • 15.

    【2hr】Renal transplantation with expanded criteria donors: Which is the optimal immunosuppression?

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    机译 扩大标准供体的肾移植：哪种免疫抑制是最佳的？
    摘要：The growing gap between demand and supply for kidney transplants has led to renewed interest in the use of expanded criteria donor (ECD) kidneys in an effort to increase the donor pool. Although most studies of ECD kidney transplantation confirm lower allograft survival rates and, generally, worse outcomes than standard criteria donor kidneys, recipients of ECD kidneys generally have improved survival compared with wait-listed dialysis patients, thus encouraging the pursuit of this type of kidney transplantation. The relative benefits of transplantation using kidneys from ECDs are dependent on patient characteristics and the waiting time on dialysis. Because of the increased risk of poor graft function, calcineurin inhibitor (CNI)-induced nephrotoxicity, increased incidence of infections, cardiovascular risk, and malignancies, elderly recipients of an ECD kidney transplant are a special population that requires a tailored immunosuppressive regimen. Recipients of ECD kidneys often are excluded from transplant trials and, therefore, the optimal induction and maintenance immunosuppressive regimen for them is not known. Approaches are largely center specific and based upon expert opinion. Some data suggest that antithymocyte globulin might be the preferred induction agent for elderly recipients of ECD kidneys. Maintenance regimens that spare CNIs have been advocated, especially for older recipients of ECD kidneys. CNI-free regimens are not universally accepted due to occasionally high rejection rates. However, reduced CNI exposure and CNI-free regimens based on mammalian target of rapamycin inhibitors have shown acceptable outcomes in appropriately selected ECD transplant recipients.
  • 16.

    【2hr】Continuous internal counterpulsation as a bridge to recovery in acute and chronic heart failure

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    机译 持续的内部反搏是急性和慢性心力衰竭恢复的桥梁
    摘要：Cardiac recovery from cardiogenic shock (CS) and end-stage chronic heart failure (HF) remains an often insurmountable therapeutic challenge. The counterpulsation technique exerts numerous beneficial effects on systemic hemodynamics and left ventricular mechanoenergetics, rendering it attractive for promoting myocardial recovery in both acute and chronic HF. Although a recent clinical trial has questioned the clinical effectiveness of short-term hemodynamic support with intra-aortic balloon pump (IABP, the main representative of the counterpulsation technique) in CS complicating myocardial infarction, the issue remains open to further investigation. Moreover, preliminary data suggest that long-term IABP support in patients with end-stage HF is safe and may mediate recovery of left- or/and right-sided cardiac function, facilitating long-term weaning from mechanical support or enabling the application of other permanent, life-saving solutions. The potential of long-term counterpulsation could possibly be enhanced by implementation of novel, fully implantable counterpulsation devices.
  • 17.

    【2hr】Post-transplant dyslipidemia: Mechanisms, diagnosis and management

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    机译 移植后血脂异常：机制，诊断和管理
    摘要：Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to consider with post-transplant therapies for dyslipidemia are preserving or improving allograft function, and reducing cardiovascular risk. Although there are other cardiovascular risk factors such as graft dysfunction, hypertension, and diabetes, attention to dyslipidemia is warranted because interventions for dyslipidemia have an impact on reducing cardiac events in clinical trials specific to the transplant population. Dyslipidemia is not synonymous with hyperlipidemia. Numerous mechanisms exist for the occurrence of post-transplant dyslipidemia, including those mediated by immunosuppressive drug therapy. Statin therapy has received the most attention in all solid organ transplant recipient populations, although the effect of proper dietary advice and adjuvant pharmacological and non-pharmacological agents should not be dismissed. At all stages of treatment appropriate monitoring strategies for side effects should be implemented so that the benefits from these therapies can be achieved. Clinicians have a choice when there is a conflict between various transplant society and lipid society guidelines for therapy and targets.
  • 18.

    【2hr】Kidney transplantation in obese patients

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    机译 肥胖患者的肾脏移植
    摘要：The World Health Organization estimated that in 2014, over 600 million people met criteria for obesity. In 2011, over 30% of individuals undergoing kidney transplant had a body mass index (BMI) 35 kg/m2 or greater. A number of recent studies have confirmed the relationship between overweight/obesity and important comorbidities in kidney transplant patients. As with non-transplant surgeries, the rate of wound and soft tissue complications are increased following transplant as is the incidence of delayed graft function. These two issues appear to contribute to longer length of stay compared to normal BMI. New onset diabetes after transplant and cardiac outcomes also appear to be increased in the obese population. The impact of obesity on patient survival after kidney transplantation remains controversial, but appears to mirror the impact of extremes of BMI in non-transplant populations. Early experience with (open and laparoscopic) Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy support excellent weight loss (in the range of 50%-60% excess weight lost at 1 year), but experts have recommended the need for further studies. Long term nutrient deficiencies remain a concern but in general, these procedures do not appear to adversely impact absorption of immunosuppressive medications. In this study, we review the literature to arrive at a better understanding of the risks related to renal transplantation among individuals with obesity.
  • 19.

    【2hr】Overview of extended release tacrolimus in solid organ transplantation

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    机译 他克莫司缓释固体器官移植概述
    摘要：Tacrolimus (Prograf©, Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf©, Astagraf XL©) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patient’s due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher.
  • 20.

    【2hr】Donor to recipient sizing in thoracic organ transplantation

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    机译 胸器官移植中供体的大小
    摘要：Donor-to-recipient organ size matching is a critical aspect of thoracic transplantation. In the United States potential recipients for lung transplant and heart transplant are listed with limitations on donor height and weight ranges, respectively. Height is used as a surrogate for lung size and weight is used as a surrogate for heart size. While these measures are important predictors of organ size, they are crude surrogates that fail to incorporate the influence of sex on organ size. Independent of other measures, a man’s thoracic organs are approximately 20% larger than a woman’s. Lung size can be better estimated using the predicted total lung capacity, which is derived from regression equations correcting for height, sex and age. Similarly, heart size can be better estimated using the predicted heart mass, which adjusts for sex, age, height, and weight. These refined organ sizing measures perform better than current sizing practice for the prediction of outcomes after transplantation, and largely explain the outcome differences observed after sex-mismatch transplantation. An undersized allograft is associated with worse outcomes. In this review we examine current data pertaining to size-matching in thoracic transplantation. We advocate for a change in the thoracic allocation mechanism from a height-or-weight-based strategy to a size-matching process that utilizes refined estimates of organ size. We believe that a size-matching approach based on refined estimates of organ size would optimize outcomes in thoracic transplantation without restricting or precluding patients from thoracic transplantation.
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