American Journal of Transplantation最新文献_第4页

Serum and tissue biomarkers of plasma cell-rich rejection in liver transplant recipients 肝移植受者富含浆细胞排斥反应的血清和组织生物标志物。

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2024.10.006

Nivetha Saravanan , Anthony Demetris , Maria Isabel Fiel , Claire Harrington , Nigar Anjuman Khurram , Thomas D. Schiano , Josh Levitsky

The distinction between autoimmune and alloimmune reactions in liver transplant recipients can be challenging. Plasma cell-rich rejection (PCRR), previously known as de novo autoimmune hepatitis or plasma cell hepatitis, is an atypical and underrecognized form of allograft rejection observed post-liver transplantation, often in conjunction with features of T cell–mediated and antibody-mediated rejection. If PCRR is not recognized and treated with prompt immunosuppressive augmentation, patients can develop advanced hepatic fibrosis, necroinflammation, and allograft failure. Given the significant morbidity and mortality associated with PCRR, there exists a need to develop noninvasive biomarkers which can be used in screening, diagnosis, and treatment monitoring of PCRR. This study is a literature review of candidate serum-based and tissue-based biomarkers in adult and pediatric liver transplant PCRR. We also discuss biomarkers from plasma cell-rich processes observed in other disease states and other organ transplant recipients that might be tested in liver transplant PCRR. We conclude with proposed future directions in which biomarker implementation into clinical practice could lead to advances in personalized management of PCRR.

区分肝移植受者的自身免疫反应和同种免疫反应可能很有难度。富含浆细胞的排斥反应（PCRR）以前被称为 "新生自身免疫性肝炎 "或 "浆细胞肝炎"，是肝移植术后出现的一种非典型、未得到充分认识的异体移植排斥反应，通常与T细胞介导的排斥反应和抗体介导的排斥反应并存。如果 PCRR 没有被及时发现并通过增强免疫抑制进行治疗，患者可能会发展为晚期肝纤维化、坏死性炎症和异体移植失败。鉴于 PCRR 会导致严重的发病率和死亡率，因此有必要开发可用于 PCRR 筛查、诊断和治疗监测的无创生物标志物。本文对成人和儿童肝移植 PCRR 的候选血清和组织生物标志物进行了文献综述。我们还讨论了在其他疾病状态和其他器官移植受者中观察到的血浆细胞丰富过程中的生物标记物，这些标记物可能会在肝移植 PCRR 中进行测试。最后，我们提出了未来的发展方向，将生物标志物应用于临床实践可促进 PCRR 的个性化管理。

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引用次数: 0

Bartonella quintana infection in kidney transplant recipients from donor experiencing homelessness, United States, 2022 无家可归者肾移植受者的金通体感染，美国，2022。

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2024.11.032

Marcus R. Pereira

引用次数: 0

OPTN/SRTR 2023 Annual Data Report: Deceased Organ Donation

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2025.01.026

Ajay K. Israni , David A. Zaun , Alina Martinez , Cory R. Schaffhausen , Cinthia Lozano , Warren T. McKinney , Jonathan M. Miller , Jon J. Snyder

The Annual Data Report is created using data from the Scientific Registry of Transplant Recipients (SRTR) to calculate variables such as organs recovered per donor, organs transplanted per donor, and organs recovered for transplant but not transplanted (ie, nonuse). SRTR uses data collected by the Organ Procurement and Transplantation Network. In 2023, there were 16,335 deceased donors, a 9.6% increase from 14,904 in 2022 and continuing the trend of increasing donors over the past decade. Donor characteristics have changed compared with 2013, with more donors with drug intoxication and cardiovascular mechanisms of death. In contrast, gunshot wound, blunt injury, and stroke have decreased as mechanisms of death in 2023 compared with 2013. The number of organs transplanted increased to 40,588 in 2023 (from 37,316 in 2022), including 10,818 left kidneys, 10,659 right kidneys, 372 en bloc kidneys, 917 pancreata, 9,910 livers, 95 intestines, 4,596 hearts, and 3,016 lungs. Compared with 2022, transplants of all organs increased. In 2023, 4,038 left kidneys, 4,220 right kidneys, 160 en block kidneys, 279 pancreata, 1,056 livers, 4 intestines, 68 hearts, and 260 lungs were not used. This nonuse of organs represents an opportunity to increase the number of transplants.

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引用次数: 0

Contemporary prevalence and practice patterns of out-of-sequence kidney allocation 非等位肾脏分配的当代流行与实践模式。

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2024.08.016

Luckmini N. Liyanage , Daniyar Akizhanov , Suhani S. Patel , Dorry L. Segev , Allan B. Massie , Darren E. Stewart , Sommer E. Gentry

Since 2021, the Organ Procurement and Transplantation Network has reported a nearly 10-fold rise in out-of-sequence (OOS) kidney allocation, generating concern and halting development of continuous distribution policies. We report contemporary (2022-2023) practice patterns in OOS allocation using Organ Procurement and Transplantation Network data. We examined in sequence vs OOS donors with multivariable logistic regression and skipped vs OOS-accepting recipients with conditional logistic regression. Nearly 20% of kidney placements were OOS, varying from 0% to 43% acsoss organ procurement organizations; the 5 highest OOS-organ procurement organizations accounted for 29% of all OOS. Of OOS kidneys, 33% were declined ≥100 times in the standard allocation sequence and 51% were declined by ≥10 centers before OOS allocation began; 4.5% were made without any in-sequence declines. Nearly, all OOS offers were open offers. OOS kidneys were more likely to be from female, Black, older, donation after cardiac death, hypertensive, diabetic, and elevated creatinine donors. Candidates receiving OOS kidneys were more likely female, Asian, and older than skipped candidates. Higher-volume centers and centers with more White, fewer Hispanic, and more educated waiting list patients underwent transplantation disproportionately with more OOS kidneys. These findings suggest that the current, highly variable, discretionary use of OOS might exacerbate disparities, yet the impact of OOS on organ utilization cannot be determined with data now collected.

自 2021 年以来，OPTN 报告的顺序外（OOS）肾脏分配增加了近 10 倍，引起了人们的关注，并阻碍了连续分配政策的发展。我们利用 OPTN 的数据报告了当代（2022-2023 年）OOS 分配的实践模式。我们通过多变量逻辑回归研究了顺序捐献者与OOS捐献者的关系，并通过条件逻辑回归研究了跳过捐献者与接受OOS捐献者的关系。近20%的肾脏配售为OOS，各OPO的OOS率从0%到43%不等；OOS率最高的5个OPO占所有OOS的29%。在 OOS 肾脏中，33% 的肾脏在标准分配序列中被拒绝超过 100 次，51% 的肾脏在 OOS 分配开始前被超过 10 个中心拒绝；4.5% 的肾脏在标准分配序列中未被任何中心拒绝。几乎所有的 OOS 供肾都是公开供肾。OOS肾更可能来自女性、黑人、老年人、DCD、高血压、糖尿病和肌酐升高的供体。接受 OOS 肾脏的候选者中，女性、亚裔和老年人的比例高于跳过的候选者。数量较多的中心以及白人较多、西班牙裔较少和受教育程度较高的候选者中心移植的OOS肾脏数量多得不成比例。这些研究结果表明，目前随意使用OOS的情况非常多变，可能会加剧差异，但目前收集的数据还无法确定OOS对器官利用率的影响。

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引用次数: 0

Crossing national borders for transplantation: A focused evaluation of deceased donor lung exports from the United States 跨越国界进行移植：对美国已故捐献者肺移植的重点评估。

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2024.08.025

Rocio Lopez , Sumit Mohan , Seyd Ali Husain , Miko Yu , Susana Arrigain , Deena Brosi , Jordan R.H. Hoffman , Kenneth R. McCurry , Bruce Kaplan , Elizabeth A. Pomfret , Jesse D. Schold

Organ transplantation is a life-saving treatment for end-stage organ failure patients, but the United States (US) faces a shortage of available organs. US policies incentivize identifying recipients for all recovered organs. Technological advancements have extended donor organ viability, creating new opportunities for long-distance transport and international sharing. We aimed to assess organ exports from deceased US donors to candidates abroad, a component of allocation policy allowed without suitable domestic candidates. Based on the national Scientific Registry of Transplant Recipients data from January 2014 to September 2023, 388 342 organs were recovered for transplantation, with 511 (0.13%) exported. Most exported organs were lungs (80%). Exported lung donors were older (41 vs 34 years, P < .001), more likely hepatitis C positive (22% vs 4%, P < .001), and more likely donors after circulatory death (20% vs 7%, P < .001). Lungs that were eventually exported were offered to more US potential transplant recipients (median = 65) than those kept in the US (median = 21 and 41 for lungs recovered by nonexporting and exporting organ procurement organizations, respectively; P < .001). Our study highlights the necessity for further research and clear policy initiatives to balance the benefits of cross-border sharing while considering potential opportunities for more aggressive organ allocation within the US.

器官移植是挽救终末期器官衰竭患者生命的治疗方法，但美国面临可用器官短缺的问题。美国的政策鼓励为所有回收的器官确定受体。技术进步延长了捐献者器官的存活时间，为长途运输和国际共享创造了新的机会。我们旨在评估美国已故捐献者向国外候选者输出器官的情况，这是在没有合适国内候选者的情况下允许的分配政策的一部分。根据 2014 年 1 月至 2023 年 9 月的全国 SRTR 数据，共有 388342 个器官被回收用于移植，其中 511 个（0.13%）被出口。大部分出口器官为肺脏（80%）。出口的肺捐献者年龄较大（41 岁对 34 岁，p

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引用次数: 0

Unique multidisciplinary approach in living donor liver transplantation to achieve total physiological revascularization in a patient with complete occlusion of portal vein system with combined chronic and subacute thrombosis 在活体肝移植手术中采用独特的多学科方法，为一名门静脉系统完全闭塞并合并慢性和亚急性血栓形成的患者实现完全生理性血管再通。

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2024.09.033

Francesca Albanesi , Jae-Yoon Kim , Kwang-Woong Lee , YoungRok Choi , Nam-Joon Yi , Suk-Kyun Hong , Kyung-Suk Suh

Patients receiving liver transplantation in a setting of complete portal vein (PV) and superior mesenteric vein (SMV) thrombosis (Yerdel grade 4) experience lower outcomes after surgery; prognosis is independently influenced by the portal flow reconstruction technique, showing better outcomes in physiological surgical strategies. We describe a case of living donor liver transplantation in which the patient could not receive common physiological reconstructions preoperatively due to multiple small collaterals and extensive thrombosis down to first branches of SMV. We performed thromboendovenectomy of the PV and SMV first, but acute thrombosis developed recurrently even with interposition venous homograft between pericholedochal collateral vein and proximal recipient PV. Immediate after surgery, an intervention radiologist performed stent insertion into 3 stenotic points. Through multidisciplinary approach, complete physiological recanalization was obtained with normal liver function.

在门静脉（PV）和肠系膜上静脉（SMV）完全血栓形成（耶德尔4级）的情况下接受肝移植的患者术后预后较差；预后受门静脉血流重建技术的独立影响，生理手术策略的预后较好。我们描述了一例活体肝移植病例，患者术前无法接受普通的生理性重建，原因是存在多条小分支和SMV第一分支的广泛血栓形成。我们首先对门静脉和 SMV 进行了血栓内静脉切除术，但即使在胆总管旁静脉和受体门静脉近端之间进行了静脉同种异体移植，急性血栓仍反复形成。手术后，放射科介入医生立即对 3 个狭窄点进行了支架植入术。通过多学科合作，手术后肝功能恢复正常，实现了完全的生理性再通畅。

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引用次数: 0

Evaluation for genetic disease in kidney transplant candidates: A practice resource 肾移植候选者遗传病评估：实践资源。

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2024.10.019

Elizabeth G. Ames , Prince M. Anand , Mir Reza Bekheirnia , Mona D. Doshi , Mireille El Ters , Margaret E. Freese , Rasheed A. Gbadegesin , Lisa M. Guay-Woodford , Anuja Java , Daniel Ranch , Nancy M. Rodig , Xiangling Wang , Christie P. Thomas

The increasing availability of clinically approved genetic tests for kidney disease has spurred the growth in the use of these tests in kidney transplant practice. Neither the testing options nor the patient population where this should be deployed has been defined, and its value in kidney transplant evaluation has not been demonstrated. Transplant providers may not always be aware of the limitations of genetic testing and may need guidance on comprehending test results and providing counsel, as many centers do not have easy access to a renal genetic counselor or a clinical geneticist. In this practice resource, a working group of nephrologists, geneticists, and a genetic counselor provide a pragmatic, tailored approach to genetic testing, advocating for its use only where the genetic diagnosis or its exclusion can impact the choices available for transplantation or posttransplant management or the workup of living donor candidates at increased risk for heritable disease.

临床认可的肾脏疾病基因检测方法越来越多，推动了这些检测方法在肾移植实践中的应用。但无论是检测方案还是应使用基因检测的患者人群都尚未确定，而且基因检测在肾移植评估中的价值也未得到证实。肾移植服务提供者可能并不总能意识到基因检测的局限性，在理解检测结果和提供咨询方面可能需要指导，因为许多中心并不容易找到肾脏遗传咨询师或临床遗传学家。在这一实践资源中，由肾脏病专家、遗传学家和遗传咨询师组成的工作小组为基因检测提供了一种务实的、量身定制的方法，主张只有在基因诊断或排除基因诊断会影响移植或移植后管理的选择，或影响遗传性疾病风险增加的活体捐赠候选者的检查时，才使用基因检测。

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引用次数: 0

OPTN/SRTR 2023 Annual Data Report: Introduction

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2025.01.019

David P. Schladt , Ajay K. Israni

The OPTN/SRTR 2023 Annual Data Report presents the status of the solid organ transplant system in the United States from 2012 through 2023. Organ-specific chapters are presented for kidney, pancreas, liver, intestine, heart, and lung transplant. Each organ-specific chapter is organized to present waitlist information, donor information (both deceased and living, as appropriate), transplant information, and patient outcomes. Data pertaining to pediatric patients are generally presented separately from the adult data; however, many chapters now have a Donation section, which includes data on adult and pediatric organ donation. The data presented in the Annual Data Report are descriptive in nature. In other words, most tables and figures present raw data without statistical adjustment for possible confounding or changes over time. Therefore, the reader should keep in mind the observational nature of the data when attempting to draw inferences before trying to ascribe a cause to any observed patterns or trends. This introduction provides a brief overview of trends in candidates on the waiting list, new additions to the waiting list, transplant activity, and posttransplant patient survival, with a focus on 2013-2023. More detailed descriptions can be found in the respective organ-specific chapters.

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引用次数: 0

Sexual bother and sexual activity before and after kidney transplantation 肾移植前后的性困扰和性活动。

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2024.09.010

Jane J. Long , Natasha Gupta , Yi Liu , Jingyao Hong , Yiting Li , Nicole M. Ali , Aarti Mathur , Dorry L. Segev , Mara A. McAdams-DeMarco

Among patients awaiting kidney transplantation (KT), sexual dysfunction is common owing to end-stage kidney disease, but may improve post-KT. Leveraging a 2-center prospective study, 2422 adult KT candidates and 490 adult KT recipients (May 2014 to December 2023) were identified. Using the Kidney Disease Quality of Life Short Form, participants reported on the negative impact of sexual dysfunction due to end-stage kidney disease (ie, sexual bother) at KT evaluation, admission, and post-KT follow-ups. Using mixed-effect logistic regression models, we estimated odds and trajectories for odds of sexual bother. At evaluation, 46.1% of male and 29.6% of female candidates reported sexual bother; 39.0% and 34.5%, respectively, had been sexually active in the past 4 weeks. At admission, 53.8% male and 27.0% female recipients reported sexual bother; 41.6% and 41.8%, respectively, had been sexually active in the past 4 weeks. The estimated prevalence of sexual bother decreased during the first 3 years post-KT (odds ratio per year: 0.39; 95% CI: 0.25-0.60). Sexual activity increased and peaked 1-year post-KT. At 3 years post-KT, 48.9% of male and 50.0% of female recipients were sexually active. Sexual bother is common pre-KT and improves post-KT, and sexual activity increases post-KT. Sexual health is important and should be considered during KT management.

在等待肾移植（KT）的患者中，性功能障碍因终末期肾病（ESKD）而常见，但在肾移植后可能会有所改善。通过一项双中心前瞻性研究，确定了 2422 名成年 KT 候选者和 490 名成年 KT 受者（2014 年 5 月至 2023 年 12 月）。通过肾脏病生活质量量表简表（KDQOL-SF），参与者在KT评估、入院和KT后随访时报告了ESKD导致的性功能障碍（即性困扰）的负面影响。我们使用混合效应逻辑回归模型估算了性困扰几率和轨迹。在评估时，46.1% 的男性和 29.6% 的女性受试者报告有性困扰；分别有 39.0% 和 34.5% 的受试者在过去 4 周内有过性行为。入院时，53.8% 的男性和 27.0% 的女性受试者表示有性困扰；在过去 4 周内，分别有 41.6% 和 41.8% 的受试者有过性生活。在接受 KT 后的头 3 年中，性困扰的估计发生率有所下降（每年 OR：0.39，95%CI：0.25-0.60）。性活动有所增加，并在 KT 后 1 年达到高峰。接受 KT 后 3 年，48.9% 的男性和 50.0% 的女性性生活活跃。性困扰在 KT 前很常见，KT 后有所改善，KT 后性活动增加。性健康非常重要，应在 KT 管理过程中加以考虑。

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引用次数: 0

Immunomodulation of T cell-mediated alloimmunity by proximity to endothelial cells under the mammalian target of rapamycin blockade 在 mTOR 阻断作用下，通过接近内皮细胞对 T 细胞介导的异体免疫进行免疫调节。

IF 8.9 2区医学 Q1 SURGERY

American Journal of Transplantation

Pub Date : 2025-02-01 DOI: 10.1016/j.ajt.2024.10.008

Shu Li , Liuyang Wang , Victoria A. Bendersky , Qimeng Gao , Jun Wang , He Xu , Allan D. Kirk

Endothelial cells (ECs) are an initial barrier between vascularized organ allografts and the host immune system and are thus well positioned to initiate and influence alloimmune rejection. The mammalian target of rapamycin inhibitor rapamycin is known to inhibit T cell activation and attenuate acute allograft rejection. It also has numerous effects on ECs. We hypothesized that A mammalian target of rapamycin blockade might directly alter EC alloimmunogenicity and reduce alloimmune responses independent of its effects on T cell function. Here we report that rapamycin treatment modulates EC coinhibitory ligand expression and alters cytokine/chemokine production. It alters the EC transcriptome broadly associated with negative regulation of immune responses. Rapamycin-treated ECs suppress EC-specific T cell proliferation independent of programmed cell death 1/programmed death-ligand interaction and inhibit T cells responding to adjacent allogeneic cells in a contact-independent manner via secreted inhibitory mediators above 10 kDa. The T cell hyporesponsiveness induced by rapamycin-pretreated ECs was rescued by exogenous interleukin 2. Preexposing donor hearts to rapamycin improves the effect of B7 costimulation blockade in prolonging heart allograft survival in a major histocompatibility complex-mismatched mouse model. Our results indicate that rapamycin-treated ECs have reduced alloimmunogenicity and created a local, contact-independent environment that limits T cell alloreactivity via anergy induction and improves the efficacy of B7 costimulation blockade.

内皮细胞（EC）是血管化器官同种异体移植物与宿主免疫系统之间的初始屏障，因此能很好地启动和影响同种异体免疫排斥反应。众所周知，mTOR抑制剂雷帕霉素能抑制T细胞活化，减轻急性同种异体移植排斥反应（AR）。它对EC也有许多影响。我们推测，mTOR阻断剂可能会直接改变EC的异体免疫原性并减少异体免疫反应，而不依赖于其对T细胞功能的影响。在这里，我们报告了雷帕霉素治疗可调节EC共抑制配体的表达并改变细胞因子/趋化因子的产生。雷帕霉素改变了与免疫反应负调控广泛相关的EC转录组。雷帕霉素处理的EC会抑制EC特异性T细胞的增殖，而不依赖于PD1/PD配体的相互作用，并通过分泌10 kDa以上的抑制介质，以不依赖于接触的方式抑制T细胞对邻近的异体细胞产生反应。经雷帕霉素预处理的EC诱导的T细胞低反应性可被外源IL-2所挽救。在MHC不匹配的小鼠模型中，供体心脏预先暴露于雷帕霉素可改善B7成本刺激阻断在延长心脏异体移植存活率方面的效果。我们的研究结果表明，雷帕霉素处理过的心肌降低了异体免疫原性，并创造了一个不依赖接触的局部环境，通过诱导过敏限制了T细胞异体活性，提高了B7成本刺激阻断的效果。

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引用次数: 0