solid organ transplantation

实体器官移植
  • 文章类型: Journal Article
    线粒体动力学是细胞损伤和炎症反应的病理生理学的核心。在实体器官移植的背景下,线粒体与脑死亡后供体器官的免疫激活有关,因为它们对细胞应激反应的调节至关重要,细胞死亡,并通过根据细胞环境调整呼吸能力来显示能量适应性。线粒体损伤激活线粒体系统的裂变,聚变,生物发生,线粒体自噬,或线粒体自噬。已经研究了针对线粒体生理学的机制途径和疗法,作为减轻脑死亡对供体器官的负面影响的合理方法。尽管没有对整个领域的多重努力进行总结性评估。这篇小型评论旨在讨论供体脑死亡的相互作用,线粒体动力学,以及对同种异体移植功能的影响,肺,肝脏,和肾移植。
    Mitochondrial dynamics are central to the pathophysiology of cellular damage and inflammatory responses. In the context of solid organ transplantation, mitochondria are implicated in immune activation in donor organs that occurs after brain death, as they are critical to the regulation of cellular stress response, cell death, and display energetic adaptations through the adjustment of respiratory capacity depending on the cellular milieu. Mitochondrial damage activates mitochondrial systems of fission, fusion, biogenesis, and mitochondrial autophagy, or mitophagy. The mechanistic pathways as well as therapies targeting mitochondrial physiology have been studied as plausible ways to mitigate the negative effects of brain death on donor organs, though there is no summative evaluation of the multiple efforts across the field. This mini-review aims to discuss the interplay of donor brain death, mitochondrial dynamics, and impact on allograft function as it pertains to heart, lung, liver, and kidney transplants.
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  • 文章类型: Journal Article
    缺乏高质量的器官,次优器官质量评估,不令人满意的植入前程序,和较差的长期器官和患者存活率是目前实体器官移植(SOT)领域面临的主要挑战。植入前评估移植物质量的新生物标志物,检测,预测移植物损伤,拒绝,功能障碍,和生存对于为临床医生提供宝贵的预测工具和个性化患者治疗指导至关重要。此外,还需要新的治疗靶点来减少损伤和排斥反应,并改善移植结果.蛋白质,这是表型的基础,是健康和疾病状态和治疗目标的理想候选生物标志物。蛋白质可以以不同的分子形式存在,叫做变形。由于蛋白质的功能取决于其确切组成,与蛋白质相比,蛋白质形式可以为与复杂表型的联系提供更准确的基础。基于质谱的蛋白质组学已大量用于SOT研究,通过所谓的“自下而上”蛋白质组学(BUP)来识别候选生物标志物和治疗干预靶标。然而,这种BUP方法分析小肽代替完整的蛋白质,并提供关于感兴趣的蛋白质的确切分子组成的不完整信息。相比之下,“自上而下”蛋白质组学(TDP),分析保留蛋白质形式水平信息的完整蛋白质,直到最近才在移植研究中被采用,并且已经导致鉴定出有希望的蛋白质形式作为器官排斥和功能障碍的生物标志物。我们预计,使用自上而下的策略与单细胞和空间蛋白质组学的新技术进步相结合,可以推动SOT中生物标志物和治疗靶标发现的未来突破。
    Scarcity of high-quality organs, suboptimal organ quality assessment, unsatisfactory pre-implantation procedures, and poor long-term organ and patient survival are the main challenges currently faced by the solid organ transplant (SOT) field. New biomarkers for assessing graft quality pre-implantation, detecting, and predicting graft injury, rejection, dysfunction, and survival are critical to provide clinicians with invaluable prediction tools and guidance for personalized patients\' treatment. Additionally, new therapeutic targets are also needed to reduce injury and rejection and improve transplant outcomes. Proteins, which underlie phenotypes, are ideal candidate biomarkers of health and disease statuses and therapeutic targets. A protein can exist in different molecular forms, called proteoforms. As the function of a protein depends on its exact composition, proteoforms can offer a more accurate basis for connection to complex phenotypes than protein from which they derive. Mass spectrometry-based proteomics has been largely used in SOT research for identification of candidate biomarkers and therapeutic intervention targets by so-called \"bottom-up\" proteomics (BUP). However, such BUP approaches analyze small peptides in lieu of intact proteins and provide incomplete information on the exact molecular composition of the proteins of interest. In contrast, \"Top-down\" proteomics (TDP), which analyze intact proteins retaining proteoform-level information, have been only recently adopted in transplantation studies and already led to the identification of promising proteoforms as biomarkers for organ rejection and dysfunction. We anticipate that the use of top-down strategies in combination with new technological advancements in single-cell and spatial proteomics could drive future breakthroughs in biomarker and therapeutic target discovery in SOT.
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  • 文章类型: Journal Article
    我们试图了解安全文化在中断期间如何演变,以COVID-19大流行为例,以确定系统中可能影响患者治疗结果的漏洞。
    使用安全态度问卷(SAQ)对高容量移植中心的移植人员进行了横断面分析。调查回复在COVID-19前后(2019年和2021年)进行了缩放和评估。
    收集了两百三十八份反应(大流行前134份,大流行后104份)。代表器官组包括:肾脏(N=89;38%),心脏(N=18;8%),肝脏(N=54;23%),倍数(N=66;28%),和其他(N=10;4%)。响应者主要包括护士(N=75;34%),给药(N=50;23%),和医生(N=24;11%)。工人有很高的安全性,工作满意度,压力识别,以及大流行前后的工作条件满意度(评分>75),两个时间点的反应重叠。压力识别,安全,工作条件有所改善,但团队合作,工作满意度,和对管理的看法受到了一定程度的负面影响(所有p>0.05)。
    尽管大流行导致了严重的医疗保健中断,高领域评级是值得注意的,并且在高容量移植中心基本保持.SAQ是医疗保健单位的宝贵工具,可用于纵向评估移植文化的安全性,作为质量保证和性能改进计划的组成部分。
    UNASSIGNED: We sought to understand how safety culture may evolve during disruption, by using the COVID-19 pandemic as an example, to identify vulnerabilities in the system that could impact patient outcomes.
    UNASSIGNED: A cross-sectional analysis of transplant personnel at a high-volume transplant center was conducted using the Safety Attitudes Questionnaire (SAQ). Survey responses were scaled and evaluated pre- and post-COVID-19 (2019 and 2021).
    UNASSIGNED: Two-hundred and thirty-eight responses were collected (134 pre-pandemic and 104 post-pandemic). Represented organ groups included: kidney (N = 89;38%), heart (N = 18;8%), liver (N = 54;23%), multiple (N = 66;28%), and other (N = 10;4%). Responders primarily included nurses (N = 75;34%), administration (N = 50;23%), and physicians (N = 24;11%). Workers had high safety, job satisfaction, stress recognition, and working conditions satisfaction (score >75) both before and after the pandemic with overlapping responses across both timepoints. Stress recognition, safety, and working conditions improved post-COVID-19, but teamwork, job satisfaction, and perceptions of management were somewhat negatively impacted (all p > 0.05).
    UNASSIGNED: Despite the serious health care disruptions induced by the pandemic, high domain ratings were notable and largely maintained in a high-volume transplant center. The SAQ is a valuable tool for healthcare units and can be used in longitudinal assessments of transplant culture of safety as a component of quality assurance and performance improvement initiatives.
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  • 文章类型: Editorial
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    背景:虽然2019年冠状病毒病(COVID-19)不再是公共卫生紧急情况,某些患者仍有严重结局的风险.为了更好地了解不断变化的风险状况,我们通过大流行的各种浪潮研究了有和没有实体器官移植(SOT)的患者的危险因素。
    方法:使用国家COVID队列合作,我们研究了2020年1月1日至2022年5月2日期间COVID-19检测呈阳性的成年患者队列。我们将数据分成疾病控制中心定义的COVID-19波。在我们的主要结果中,我们使用多变量生存分析来观察有和无SOT患者住院的各种危险因素.
    结果:共捕获3,570,032名患者。我们发现,随着时间的推移,COVID-19相关不良结局的总体风险减弱。在非SOT和SOT群体中,糖尿病,慢性肾病,充血性心力衰竭是住院的危险因素。特别是对于SOT,移植和COVID-19之间的较长时间段是保护性的,年龄是一个危险因素。值得注意的是,哮喘不是主要不良肾脏心血管事件的危险因素,住院治疗,或任何一组的死亡率。
    结论:我们的研究提供了SOT和非SOT患者与COVID相关不良结局相关风险的纵向视图,以及这些风险因素如何随着时间的推移而演变。我们的工作将有助于告知提供者和政策制定者更好地针对高风险患者。
    BACKGROUND: While coronavirus disease 2019 (COVID-19) is no longer a public health emergency, certain patients remain at risk of severe outcomes. To better understand changing risk profiles, we studied the risk factors for patients with and without solid organ transplantation (SOT) through the various waves of the pandemic.
    METHODS: Using the National COVID Cohort Collaborative we studied a cohort of adult patients testing positive for COVID-19 between January 1, 2020, and May 2, 2022. We separated the data into waves of COVID-19 as defined by the Centers for Disease Control. In our primary outcome, we used multivariable survival analysis to look at various risk factors for hospitalization in those with and without SOT.
    RESULTS: A total of 3,570,032 patients were captured. We found an overall risk attenuation of adverse COVID-19-associated outcomes over time. In both non-SOT and SOT populations, diabetes, chronic kidney disease, and congestive heart failure were risk factors for hospitalization. For SOT specifically, longer time periods between transplant and COVID-19 were protective and age was a risk factor. Notably, asthma was not a risk factor for major adverse renal cardiovascular events, hospitalization, or mortality in either group.
    CONCLUSIONS: Our study provides a longitudinal view of the risks associated with adverse COVID-related outcomes amongst SOT and non-SOT patients, and how these risk factors evolved over time. Our work will help inform providers and policymakers to better target high-risk patients.
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  • 文章类型: Journal Article
    我们评估了在13例实体器官移植受者中使用maribavir(MBV)治疗15例难治性/耐药性巨细胞病毒感染。由于治疗引起的MBV抵抗或MBV停药后的早期病毒学复发导致的治疗失败发生在7次(47%)发作中。在6次(40%)发作中实现了持续的病毒清除。
    We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.
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  • 文章类型: Journal Article
    背景:2019年冠状病毒病(COVID-19)大流行已在全球范围内引起重大公共卫生关注。患有合并症的患者在COVID-19后有不良后果的风险。伴有免疫抑制和合并症的实体器官移植受者更容易受到严重的COVID-19感染。这可能导致该患者人群中住院并发症和死亡率更高。然而,关于肝移植(LT)受者COVID-19结局的研究得出的结果不一致。
    目的:评估COVID-19大流行对美国LT接受者医院相关结局的影响。
    方法:我们使用2019-2020年全国住院患者样本数据库进行了一项回顾性队列研究。使用国际疾病分类鉴定了原发性LT住院和继发性COVID-19诊断的患者,第十修订编码系统。主要结果包括COVID-19大流行之前和期间LT住院的趋势。次要结果包括LT受者住院死亡率和移植排斥反应的比较趋势。
    结果:共纳入15720例住院LT受者。大约0.8%的患者继发诊断为COVID-19感染。在这两个队列中,中位入院年龄为57岁.在大流行之前和期间,LT住院的线性趋势没有显着差异(P=0.84)。在2019年1月至2020年12月期间,LT接受者的住院死亡率从1.7%增加到4.4%。与大流行前相比,在大流行期间,LT接受者与住院死亡率之间的关联更高,比值比(OR)为1.69[95%置信区间(CI):1.55-1.84),P<0.001]。在2019年1月至2020年12月期间,住院LT接受者的移植排斥频率从0.2%增加到3.6%。COVID-19大流行期间的LT住院与移植排斥反应的相关性高于大流行前[OR:1.53(95CI:1.26-1.85),P<0.001]。
    结论:在大流行之前和期间,LT受者的住院率相当。在COVID-19大流行期间,住院LT接受者的住院死亡率和移植排斥率增加。
    BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings.
    OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States.
    METHODS: We conducted a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients.
    RESULTS: A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001].
    CONCLUSIONS: The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.
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  • 文章类型: Journal Article
    在过去的15年中,诊断流式细胞术服务的活动已经从监测HIV-1感染中的CD4T细胞亚群发展到筛查原发性和继发性免疫缺陷综合征以及评估B细胞消耗治疗和移植后的免疫构成。高收入国家实验室活动的变化是由HIV-1开始抗逆转录病毒治疗(ART)驱动的,无论CD4T细胞计数如何,增加对原发性免疫缺陷综合征的认识以及B细胞消耗治疗和移植在临床实践中的广泛应用。实验室应利用其在HIV-1感染中CD4T细胞计数标准化和质量保证方面的经验,为原发性和继发性免疫缺陷患者提供免疫监测服务。B细胞消耗剂和移植后免疫重建的评估也可以利用流式细胞术实验室获得的专业知识来检测CD34干细胞和评估血液恶性肿瘤中的MRD。本指南为临床实验室提供流式细胞术服务,筛查免疫缺陷及其在B细胞靶向治疗和移植后免疫重建的新作用提供建议。
    Over the last 15 years activity of diagnostic flow cytometry services have evolved from monitoring of CD4 T cell subsets in HIV-1 infection to screening for primary and secondary immune deficiencies syndromes and assessment of immune constitution following B cell depleting therapy and transplantation. Changes in laboratory activity in high income countries have been driven by initiation of anti-retroviral therapy (ART) in HIV-1 regardless of CD4 T cell counts, increasing recognition of primary immune deficiency syndromes and the wider application of B cell depleting therapy and transplantation in clinical practice. Laboratories should use their experience in standardization and quality assurance of CD4 T cell counting in HIV-1 infection to provide immune monitoring services to patients with primary and secondary immune deficiencies. Assessment of immune reconstitution post B cell depleting agents and transplantation can also draw on the expertise acquired by flow cytometry laboratories for detection of CD34 stem cell and assessment of MRD in hematological malignancies. This guideline provides recommendations for clinical laboratories on providing flow cytometry services in screening for immune deficiencies and its emerging role immune reconstitution after B cell targeting therapies and transplantation.
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  • 文章类型: Journal Article
    本研究旨在评估接种灭活COVID-19疫苗的实体器官移植受者的疗效和安全性。
    我们回顾性分析了非移植受试者和实体器官移植受者的抗体水平和相关不良事件,移植前(等待器官移植的个体)和移植后(经历过器官移植的个体),他们从2021年2月至2022年7月接受了灭活的COVID-19疫苗。
    该研究包括38个移植前疫苗接种组,129移植后疫苗接种组,和246非移植组。在最后一次注射后1-12个月内每月评估抗体滴度。3组抗体阳性率分别为36.84%、20.30%、61.17%(P<0.05)。三组的抗体阳性率与一组,两种疫苗剂量无显著差异(P>0.05),但三个剂量后差异显著(P<0.05)。两组间抗体滴度比较差异有统计学意义(P<0.05)。6名移植受者出现不良反应,治疗后缓解了,而不是非移植受试者。
    灭活COVID-19疫苗对实体器官移植受者安全有效,其中至少两剂应在器官移植手术前完成。
    UNASSIGNED: This study aimed to evaluate the efficacy and safety of solid organ transplantation recipients inoculated with an inactivated COVID-19 vaccine.
    UNASSIGNED: We retrospectively analyzed the antibody levels and related adverse events of non-transplantation subjects and solid organ transplant recipients, both pre-transplantation (individuals awaiting organ transplantation) and post-transplantation (individuals who have undergone organ transplantation), who received inactivated COVID-19 vaccines from February 2021 to July 2022.
    UNASSIGNED: The study included 38 pre-transplantation vaccination group, 129 post-transplantation vaccination group, and 246 non-transplantation group. The antibody titer was assessed monthly within the period of 1-12 months after the last injection. The antibody-positive rate among the three groups were 36.84, 20.30, 61.17% (P < 0.05). The antibody-positive rates among three groups with one, two doses vaccine were not significantly different (P > 0.05), but were significantly different after three doses (P < 0.05). The antibody titers among three groups were significantly different after two doses (P < 0.05). Adverse reactions occurred in six transplant recipients, which were relieved after treatment, and not in the non-transplantation subjects.
    UNASSIGNED: Inactivated COVID-19 vaccine is safe and effective for solid organ transplantation recipients, at least two doses of which should be completed before organ transplant surgery.
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