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Machine wars and policy provisions: how the landscape of organ procurement and allocation is changing in the United States. 机器大战和政策规定:美国器官获取和分配的格局正在发生怎样的变化。
IF 1.8 4区 医学 Q3 TRANSPLANTATION Pub Date : 2024-06-01 Epub Date: 2024-05-01 DOI: 10.1097/MOT.0000000000001145
Anji Wall
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引用次数: 0
Current challenges in xenotransplantation. 异种移植目前面临的挑战。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-04-16 DOI: 10.1097/MOT.0000000000001146
Marta Vadori, Emanuele Cozzi

Purpose of review: In recent years, the xenotransplantation science has advanced tremendously, with significant strides in both preclinical and clinical research. This review intends to describe the latest cutting-edge progress in knowledge and methodologies developed to overcome potential obstacles that may preclude the translation and successful application of clinical xenotransplantation.

Recent findings: Preclinical studies have demonstrated that it is now possible to extend beyond two years survival of primate recipients of life saving xenografts. This has been accomplished thanks to the utilization of genetic engineering methodologies that have allowed the generation of specifically designed gene-edited pigs, a careful donor and recipient selection, and appropriate immunosuppressive strategies.In this light, the compassionate use of genetically modified pig hearts has been authorized in two human recipients and xenotransplants have also been achieved in human decedents. Although encouraging the preliminary results suggest that several challenges have yet to be fully addressed for a successful clinical translation of xenotransplantation. These challenges include immunologic, physiologic and biosafety aspects.

Summary: Recent progress has paved the way for the initial compassionate use of pig organs in humans and sets the scene for a wider application of clinical xenotransplantation.

综述目的:近年来,异种移植科学突飞猛进,在临床前和临床研究方面都取得了重大进展。本综述旨在介绍最新的前沿知识和方法进展,以克服可能阻碍异种移植转化和成功应用于临床的潜在障碍:临床前研究表明,现在有可能将拯救生命的异种移植的灵长类受体存活期延长到两年以上。有鉴于此,转基因猪心脏已被授权在两名人类受者身上同情性使用,异种移植也已在人类死者身上实现。尽管初步结果令人鼓舞,但异种移植要成功应用于临床,仍有一些难题需要全面解决。这些挑战包括免疫学、生理学和生物安全方面:最近的进展为猪器官在人类身上的初步同情使用铺平了道路,并为异种器官移植在临床上的更广泛应用创造了条件。
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引用次数: 0
Squaring the Circle. Brain death and organ transplantation. 方圆。脑死亡与器官移植
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-14 DOI: 10.1097/MOT.0000000000001104
Howard R Doyle

Purpose of review: The adoption of brain death played a crucial role in the development of organ transplantation, but the concept has become increasingly controversial. This essay will explore the current state of the controversy and its implications for the field.

Recent developments: The brain death debate, long limited to the bioethics community, has in recent years burst into the public consciousness following several high-profile cases. This has culminated in the reevaluation of the Uniform Determination of Death Act (UDDA), which is in the process of being updated. Any change to the UDDA has the potential to significantly impact the availability of organs.

Summary: The current update to the UDDA introduces an element of uncertainty, one the brain death debate had not previously had.

回顾的目的:脑死亡概念的采用在器官移植的发展过程中起到了至关重要的作用,但这一概念的争议也越来越大。本文将探讨这一争议的现状及其对器官移植领域的影响:长期以来,脑死亡的争论仅限于生命伦理学界,近年来,随着几起备受瞩目的案例的发生,脑死亡的争论逐渐进入公众视野。这最终导致了对《统一死亡判定法》(UDDA)的重新评估,该法正在更新过程中。对《统一死亡判定法》的任何修改都有可能对器官的可用性产生重大影响。摘要:目前对《统一死亡判定法》的更新带来了不确定性因素,这是脑死亡辩论以前所没有的。
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引用次数: 0
Normothermic regional perfusion procurement for abdominal organ donors: techniques and troubleshooting. 为腹部器官捐献者进行常温区域灌注采购:技术和故障排除。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-11 DOI: 10.1097/MOT.0000000000001140
Stephanie Silpe, Eric Martinez, Anji Wall

Purpose of review: Normothermic regional perfusion (NRP) is a novel procurement technique for donation after circulatory death (DCD) in the United States. It was pioneered by cardiothoracic surgery programs and is now being applied to abdominal-only organ donors by abdominal transplant programs. Multiple technical approaches can be used for abdominal-only NRP DCD donors and this review describes these techniques.

Recent findings: NRP has been associated with higher utilization of organs, particularly liver and heart grafts, from DCD donors and with better recipient outcomes. There are lower rates of delayed graft function in kidney transplant recipients and lower rates of ischemic cholangiopathy in liver transplant recipients. These benefits are driving increased interest from abdominal transplant programs in using NRP for DCD procurements.

Summary: This paper describes the technical aspects of NRP DCD that allow for maximization of its use based on different donor and policy characteristics.

审查目的:在美国,常温区域灌注(NRP)是一种用于循环死亡(DCD)后捐献的新型采购技术。该技术由心胸外科项目首创,目前腹腔移植项目正将其应用于腹腔器官捐献者。多种技术方法可用于腹部 NRP DCD 供体,本综述介绍了这些技术:最近的研究结果:NRP 与更高的 DCD 供体器官(尤其是肝脏和心脏移植物)利用率和更好的受体预后有关。肾移植受者移植功能延迟率较低,肝移植受者缺血性胆管病变率较低。摘要:本文介绍了 NRP DCD 的技术方面,根据不同的捐献者和政策特点,最大限度地利用 NRP DCD。
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引用次数: 0
Normothermic machine perfusion for liver transplantation: current state and future directions. 肝移植的常温机器灌注:现状与未来方向。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-14 DOI: 10.1097/MOT.0000000000001141
Jessica Lindemann, Jennifer Yu, Mb Majella Doyle

Purpose of review: The number of patients on the liver transplant waitlist continues to grow and far exceeds the number of livers available for transplantation. Normothermic machine perfusion (NMP) allows for ex-vivo perfusion under physiologic conditions with the potential to significantly increase organ yield and expand the donor pool.

Recent findings: Several studies have found increased utilization of donation after cardiac death and extended criteria brain-dead donor livers with implementation of NMP, largely due to the ability to perform viability testing during machine perfusion. Recently, proposed viability criteria include lactate clearance, maintenance of perfusate pH more than 7.2, ALT less than 6000 u/l, evidence of glucose metabolism and bile production. Optimization of liver grafts during NMP is an active area of research and includes interventions for defatting steatotic livers, preventing ischemic cholangiopathy and rejection, and minimizing ischemia reperfusion injury.

Summary: NMP has resulted in increased organ utilization from marginal donors with acceptable outcomes. The added flexibility of prolonged organ storage times has the potential to improve time constraints and transplant logistics. Further research to determine ideal viability criteria and investigate ways to optimize marginal and otherwise nontransplantable liver grafts during NMP is warranted.

审查目的:肝移植等待名单上的患者人数不断增加,远远超过了可供移植的肝脏数量。常温机器灌注(NMP)允许在生理条件下进行体外灌注,有可能显著提高器官产量并扩大捐献者库:最近的研究结果:多项研究发现,随着 NMP 的实施,心脏死亡后捐献的利用率增加,脑死亡捐献者肝脏的标准也有所提高,这主要归功于在机器灌注过程中进行存活率测试的能力。最近提出的存活标准包括乳酸清除率、维持灌注液 pH 值大于 7.2、ALT 小于 6000 u/l、葡萄糖代谢和胆汁生成的证据。在 NMP 期间优化肝脏移植物是一个活跃的研究领域,包括对脂肪肝进行脱脂、预防缺血性胆管病变和排斥反应以及最大限度地减少缺血再灌注损伤等干预措施。延长器官储存时间增加了灵活性,有可能改善时间限制和移植物流。有必要进一步研究确定理想的存活标准,并探讨如何在NMP期间优化边缘和无法移植的肝脏移植物。
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引用次数: 0
Editorial introduction. 编辑介绍。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-01 DOI: 10.1097/MOT.0000000000001148
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引用次数: 0
Expanding MELD exceptions for colorectal liver metastasis: data and policy. 扩大结直肠肝转移的 MELD 例外:数据与政策。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-14 DOI: 10.1097/MOT.0000000000001142
Jenna N Whitrock, Catherine G Pratt, Shimul A Shah

Purpose of review: While liver transplant for unresectable colorectal cancer liver metastases (CRLM) has been demonstrated to be a promising treatment in selected patients, the typically low MELD score of these patients and lack of exception points may lead to challenges in receiving a deceased donor liver for transplant.

Recent findings: Several studies have shown improved outcomes in select patients with CRLM who undergo liver transplant, and several trials are ongoing and will conclude in the next several years. MELD exception points have recently been proposed in qualifying patients with CRLM to help this group obtain more timely quality allografts. Under the current proposal, patients with CRLM would receive a score of the median MELD at transplant (MMaT) for their center minus 20 with a minimum score of 15 in cases where MMaT minus 20 would be less than 15. This would allow them to receive transplants faster without competing unnecessarily with those with greater medical need.

Summary: Giving MELD exception points to patients with colorectal cancer liver metastases in need of transplant may decrease time on the waitlist and improve outcomes for these patients.

审查目的:虽然肝移植治疗无法切除的结直肠癌肝转移灶(CRLM)已被证明是一种很有前景的治疗方法,但这些患者的MELD评分通常较低,而且缺乏特例点,这可能会导致在接受死亡供体肝脏移植时遇到困难:多项研究表明,接受肝移植的部分 CRLM 患者的预后有所改善,目前正在进行的几项试验将在未来几年内结束。最近,有人建议对符合条件的 CRLM 患者采用 MELD 例外点,以帮助这类患者更及时地获得高质量的同种异体肝移植。根据目前的建议,CRLM 患者将获得其所在中心的移植时 MELD 中位数(MMaT)减去 20 的分数,如果 MMaT 减去 20 后小于 15,则最低分数为 15。摘要:为需要移植的结直肠癌肝转移患者提供 MELD 例外分数可缩短这些患者的等待时间并改善其预后。
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引用次数: 0
Thoraco-abdominal normothermic regional perfusion for thoracic transplantation in the United States: current state and future directions. 美国用于胸腔移植的胸腹腔常温区域灌注:现状与未来方向。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-14 DOI: 10.1097/MOT.0000000000001143
Swaroop Bommareddi, Brian Lima, Ashish S Shah, John M Trahanas

Purpose of review: To provide an update regarding the state of thoracoabdominal normothermic regional perfusion (taNRP) when used for thoracic organ recovery.

Recent findings: taNRP is growing in its utilization for thoracic organ recovery from donation after circulatory death donors, partly because of its cost effectiveness. taNRP has been shown to yield cardiac allograft recipient outcomes similar to those of brain-dead donors. Regarding the use of taNRP to recover donor lungs, United Network for Organ Sharing (UNOS) analysis shows that taNRP recovered lungs are noninferior, and taNRP has been used to consistently recover excellent lungs at high volume centers. Despite its growth, ethical debate regarding taNRP continues, though clinical data now supports the notion that there is no meaningful brain perfusion after clamping the aortic arch vessels.

Summary: taNRP is an excellent method for recovering both heart and lungs from donation after circulatory death donors and yields satisfactory recipient outcomes in a cost-effective manner. taNRP is now endorsed by the American Society of Transplant Surgeons, though ethical debate continues.

综述目的:最近的研究结果:taNRP越来越多地被用于循环死亡后捐献者胸部器官的恢复,部分原因是其成本效益。taNRP已被证明可产生与脑死亡捐献者相似的心脏异体移植受体结果。关于使用 taNRP 恢复捐献者肺脏的问题,器官共享联合网络(UNOS)的分析表明,taNRP 恢复的肺脏效果并不差,而且高容量中心使用 taNRP 恢复的肺脏一直很好。小结:taNRP 是一种从循环死亡后捐献的供体中恢复心脏和肺的极佳方法,并能以经济有效的方式获得令人满意的受体结果,目前已获得美国器官移植外科医生协会的认可,但伦理争议仍在继续。
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引用次数: 0
Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy. 肝细胞癌移植免疫疗法:辅助疗法的下一个前沿。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-01 Epub Date: 2023-12-26 DOI: 10.1097/MOT.0000000000001133
Parissa Tabrizian, Marcus Zeitlhoefler, Ahmed Talaat Hassan, Rebecca Marino

Purpose of review: The increasing success of liver transplantation in hepatocellular carcinoma (HCC) drives an ever-evolving search for innovative strategies to broaden eligible patients' pools. Recent advances in immuno-oncology have turned the spotlight on immune checkpoint inhibitors (ICIs). This review offers an updated overview of ICIs in liver transplantation for HCC, exploring neoadjuvant and adjuvant approaches and addressing unanswered questions on safety, patients' selection, and response predictors.

Recent findings: ICIs have transitioned from being a last-chance therapeutic hope to becoming an integral cornerstone in the treatment of advanced HCC, holding great promise as a compelling option not only to downstage patients for transplantation but also as an alternative strategy in addressing posttransplantation disease recurrence. Despite ongoing refinements in immunotherapeutic agents, the complex molecular pathways involved emphasize the need for a comprehensive approach to integrate immunotherapy in liver transplantation.

Summary: Initial concerns about graft rejection, with ICIs as a bridging therapy to liver transplantation, were successfully addressed using adequate immunosuppressants strategies and minimized with a sufficient washout period. Post-liver transplantation disease recurrence remains challenging, requiring a balance between effective therapy and preserving graft function. Emphasis should be placed on clinical trials validating the risk-benefit ratio of ICIs for liver transplantation, guiding appropriate patients' selection, and establishing clear management pathways.

综述目的:肝细胞癌(HCC)肝移植的成功率越来越高,这促使人们不断寻求创新策略,以扩大合格患者的范围。免疫肿瘤学的最新进展使免疫检查点抑制剂(ICIs)成为关注的焦点。本综述概述了ICIs在HCC肝移植中的最新应用,探讨了新辅助和辅助方法,并探讨了安全性、患者选择和反应预测等方面的未决问题:ICIs 已从最后的治疗希望转变为治疗晚期 HCC 不可或缺的基石,不仅是降低患者移植分期的令人信服的选择,也是解决移植后疾病复发的替代策略,前景广阔。尽管免疫治疗药物不断改进,但其中涉及的复杂分子通路强调了在肝移植中整合免疫疗法的综合方法的必要性。摘要:最初人们担心ICIs作为肝移植的桥接疗法会出现移植物排斥反应,但通过使用适当的免疫抑制剂策略和足够的冲洗期,成功地解决了这一问题,并将排斥反应降至最低。肝移植后疾病复发仍是一个挑战,需要在有效治疗和保护移植物功能之间取得平衡。应重视临床试验,验证 ICIs 在肝移植中的风险效益比,指导选择合适的患者,并建立明确的管理路径。
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引用次数: 0
Regulatory dendritic cell therapy in organ transplantation. 器官移植中的树突状细胞调节性治疗。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-01 Epub Date: 2023-11-22 DOI: 10.1097/MOT.0000000000001127
Yannis Hadjiyannis, Angus W Thomson

Purpose of review: Regulatory dendritic cells (DCregs; also 'tolerogenic DCs'), innate immune cells that regulate the alloimmune response, are a novel cellular therapy for organ transplantation. Preliminary results from early-phase clinical trials in live donor kidney and liver transplantation are promising. This follows many years of research elucidating mechanisms of action and utility of DCregs. Herein, we review early-phase clinical trial observations and recent advances in the production, modification, and future-trajectory of DCreg in organ transplantation.

Recent findings: Preclinical work has demonstrated the ability of adoptively transferred DCreg to abrogate ischemia-reperfusion injury and promote long-term allograft survival. Good Manufacturing Practice-grade DCregs have been generated in adequate numbers for early-phase trials of autologous DCregs in kidney transplantation and donor-derived DCreg in liver transplantation. These trials have demonstrated feasibility and safety, with preliminary evidence of an influence on host immune reactivity. In both kidney and liver transplantation, reduced effector CD8 + T-cells have been noted, together with other changes that may be conducive to reduced dependence on immunosuppressive therapy.

Summary: Substantial progress has been made in bringing DCreg to clinical testing in organ transplantation. Additional clinical and mechanistic studies are now needed to further explore and garner the full potential of DCreg in organ transplantation.

综述目的:调节性树突状细胞(DCregs);也称为“耐受性dc”),是调节同种免疫反应的先天免疫细胞,是器官移植的一种新的细胞疗法。活体供体肾脏和肝脏移植的早期临床试验的初步结果是有希望的。这是多年来研究阐明DCregs的作用机制和效用的结果。在此,我们回顾了早期临床试验的观察结果以及DCreg在器官移植中的生产、修饰和未来发展的最新进展。最近的发现:临床前工作已经证明,过继转移DCreg能够消除缺血再灌注损伤,促进同种异体移植物的长期存活。良好生产规范级别的DCreg已经在肾移植自体DCreg和肝移植供体来源DCreg的早期试验中产生了足够数量的DCreg。这些试验已经证明了可行性和安全性,初步证据表明对宿主免疫反应性有影响。在肾和肝移植中,已经注意到效应CD8+ t细胞减少,以及其他可能有助于减少对免疫抑制治疗依赖的变化。摘要:将DCreg用于器官移植的临床试验已经取得了实质性进展。现在需要更多的临床和机制研究来进一步探索和获得DCreg在器官移植中的全部潜力。
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引用次数: 0
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Current Opinion in Organ Transplantation
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