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Outcomes of urgent lung transplantation in critically ill patients versus standard lung transplantation: A systematic review and meta-analysis 危重患者紧急肺移植与标准肺移植的结果:系统回顾和荟萃分析
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-04-23 DOI: 10.1016/j.trre.2025.100933
Xiaohan Jin , Haoji Yan , Zengwei Yu , Jier Ma , Xiangyun Zheng , Weiyang Chen , Yaling Liu , Jiaze Li , Qiang Pu , Dong Tian

Background

Whether survival differs between urgent lung transplantation (ULTx) and standard lung transplantation (LTx) remains unclear. This systematic review and meta-analysis aimed to evaluate survival and other post-transplant outcomes between ULTx and standard LTx.

Methods

PubMed, Embase, and Cochrane Library were searched up to July 31, 2024 for relevant studies. A meta-analysis of baseline characteristics and postoperative outcomes was then performed, with subgroup analyses by study designs and indications. Overall survival (OS) was set as the primary outcome in this study. Risk ratio (RR), mean differences (MD) with 95 % confidence interval (CI) were assessed using fixed-effects or random-effects models.

Results

Nine studies with 934 ULTx and 2980 standard LTx patients were included. ULTx group exhibited lower donor PaO2/FiO2 (P = 0.03) and higher pre-operative life support use (P < 0.001) than standard LTx group. No statistical difference in waiting list mortality was found between groups (28.4 % vs. 12.6 %; P = 0.54). ULTx was associated with significantly lower 1-year, 3-year, and 5-year OS than standard LTx (70.2 % vs. 80.0 %, 57.7 % vs. 66.7 %, 46.5 % vs. 56.2 %; all P < 0.001). At each time point, about 10 % OS rate differences were found consistently. In most subgroups, ULTx was associated with worse outcomes, but no difference in OS was observed in cystic fibrosis (CF) patients.

Conclusions

ULTx reduces waiting list mortality in critical patients, but is associated with worse OS than standard LTx. ULTx may limit short-term survival rather than long-term survival compared with standard LTx.
背景急诊肺移植(ULTx)和标准肺移植(LTx)的存活率是否不同仍不清楚。本系统综述和荟萃分析旨在评估ULTx和标准LTx的存活率及其他移植后结果。方法检索了PubMed、Embase和Cochrane图书馆截至2024年7月31日的相关研究。然后对基线特征和术后结果进行了荟萃分析,并根据研究设计和适应症进行了亚组分析。本研究将总生存期(OS)作为主要结果。采用固定效应或随机效应模型评估了风险比(RR)、平均差异(MD)及 95% 置信区间(CI)。与标准 LTx 组相比,ULTx 组的供体 PaO2/FiO2 更低(P = 0.03),术前生命支持使用率更高(P < 0.001)。两组之间的候诊死亡率无统计学差异(28.4% vs. 12.6%;P = 0.54)。ULTx的1年、3年和5年OS明显低于标准LTx(70.2% vs. 80.0%、57.7% vs. 66.7%、46.5% vs. 56.2%;所有P均为0.001)。在每个时间点,OS率差异均在10%左右。在大多数亚组中,ULTx与较差的预后相关,但在囊性纤维化(CF)患者中未观察到OS差异。与标准LTx相比,ULTx可能会限制短期生存而非长期生存。
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引用次数: 0
Use of decision algorithms for viscoelastic tests and use of blood products in patients undergoing liver transplantation: A systematic review with meta-analysis 在肝移植患者中使用决策算法进行粘弹性测试和使用血液制品:一项具有荟萃分析的系统综述
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-04-18 DOI: 10.1016/j.trre.2025.100932
Gilvandro Lins de Oliveira Júnior , Viviane Maria Bezerra Cavalcanti Lins , Virgínia Maria Bezerra Cavalcanti , Francisco Tustumi , Cassio Virgílio , Wellington Andraus
Introduction: Viscoelastic tests (VETs), including thromboelastography (TEG) and rotational thromboelastometry (ROTEM), provide a global assessment of hemostatic function. The use of a TEG or ROTEM system to guide the administration of blood products has been shown to reduce transfusion requirements in certain types of surgeries, but the decision algorithms for Viscoelastic tests needs to be assessed. This review aimed to assess all published evidence on viscoelastic testing in the context the use of decision algorithms for VETs on liver transplantation. Methods: A systematic review was performed in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies assessing VETs for liver transplantation were considered for inclusion, analyzed according to the use or non-use of algorithms for VETs. Results: Out of the 279 studies initially identified, 17 studies were included in this review. Algorithms for VETs reduced red blood cell transfusion (−0.44 (95 % CI -0.62; −0.25; p < 0.01), while there was no significant difference with VETs without algorithms, and the overall measure showed a smaller reduction (−0.33; 95 % CI -0.61 to −0.04; p = 0.02). Conclusion: The results highlight the potential of algorithms for VETs to reduce the use of blood products in liver transplants.
粘弹性试验(vet),包括血栓弹性成像(TEG)和旋转血栓弹性测量(ROTEM),提供止血功能的全面评估。使用TEG或ROTEM系统来指导血液制品的管理已被证明可以减少某些类型手术的输血需求,但粘弹性试验的决策算法需要评估。本综述旨在评估所有已发表的关于肝移植VETs决策算法中粘弹性测试的证据。方法:在PubMed、EMBASE和Cochrane中央对照试验登记册中进行系统评价。评估肝移植VETs的研究被纳入考虑,并根据VETs算法的使用或不使用进行分析。结果:在最初确定的279项研究中,本综述纳入了17项研究。VETs算法减少红细胞输血(- 0.44 (95% CI -0.62;−0.25;p & lt;0.01),而未加算法的VETs无显著差异,总体测量显示较小的降低(- 0.33;95% CI -0.61 ~ - 0.04;p = 0.02)。结论:该结果突出了VETs算法在减少肝移植中血液制品使用方面的潜力。
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引用次数: 0
Mechanism and regulation of the complement activity in kidney xenotransplantation 异种肾移植补体活性的机制及调控
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-04-13 DOI: 10.1016/j.trre.2025.100931
Takayuki Hirose , Kiyohiko Hotta , Ryo Otsuka , Ken-Ichiro Seino
Xenotransplantation is emerging as one of several potential solutions for addressing organ donor shortages, with significant progress bringing it closer to clinical application. However, challenges remain, particularly concerning complement system dysregulation caused by species differences, as well as xenoantigens and coagulopathy. Complement regulatory proteins expressed on endothelial cells of donor xenografts are less compatible with complement components in recipients. These difficulties contribute to hyperacute rejection, characterized by antibody-mediated complement activation that destroys the graft within 24 h. Moreover, because molecules are incompatible across different species, ischemia-reperfusion injury or infection can easily elicit complement activity via all three pathways, resulting in xenograft loss via complement-mediated vascular injury. Complement activity also stimulate innate and adaptive immune cells. To address this issue, genetic modifications in donor pigs and the development of novel medicines have been tested in preclinical models with promising results. Pigs modified to express human complement-regulating molecules such as CD46, CD55, and CD59 have shown longer kidney xenograft survivals over years in preclinical models with nonhuman primates, paving the way for clinical trials. Anti-complement component agents such as C1 esterase and C5 inhibitors have also been shown to increase xenograft survivals. This review examines the role of the complement system in kidney xenotransplantation, emphasizing new research and clinical trial advancements.
异种移植正在成为解决器官捐献者短缺问题的几种潜在解决方案之一,并取得了重大进展,使其更接近临床应用。然而,挑战依然存在,尤其是物种差异以及异种抗原和凝血病导致的补体系统失调。供体异种移植物内皮细胞上表达的补体调节蛋白与受体中的补体成分不太兼容。此外,由于不同物种的分子不兼容,缺血再灌注损伤或感染很容易通过三种途径引起补体活性,导致异种移植物因补体介导的血管损伤而死亡。补体活性还能刺激先天性和适应性免疫细胞。为解决这一问题,人们在临床前模型中测试了供体猪的基因修饰和新型药物的开发,结果令人欣喜。在与非人灵长类动物的临床前模型中,表达人类补体调节分子(如 CD46、CD55 和 CD59)的改良猪显示出更长的肾脏异种移植存活时间,为临床试验铺平了道路。C1 酯酶和 C5 抑制剂等抗补体成分药物也被证明能提高异种移植物的存活率。这篇综述探讨了补体系统在肾脏异种移植中的作用,强调了新的研究和临床试验进展。
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引用次数: 0
Advances in biomarkers of acute allograft rejection and interstitial fibrosis/tubular atrophy in kidney transplantation; future perspective and challenges in clinical implementation 肾移植急性排斥反应和肾间质纤维化/肾小管萎缩生物标志物研究进展临床实施的未来展望与挑战
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-04-08 DOI: 10.1016/j.trre.2025.100930
Tanguy Lafont , Subhankar Mukhopadhyay , Sohani N. Dassanayake , Maria Hernández-Fuentes , Paramit Chowdhury , Theodoros Kassimatis
Acute rejection (AR) and interstitial fibrosis/tubular atrophy (IFTA) are significant complications of kidney transplantation that have a negative impact on renal graft lifespan. Kidney transplant monitoring is currently performed with the use of on nonspecific biomarkers (serum creatinine and proteinuria) which have significant limitations and detect AR and IFTA only after significant damage to the kidney has been done. Moreover, many transplant patients are found to have histological evidence of rejection despite a stable creatinine (subclinical rejection – SCR). The “gold standard” diagnostic test for AR and IFTA is the transplant biopsy that also comes with limitations and can have major complications; therefore, it is not an ideal test for routine graft monitoring. The use of novel non-invasive (blood and urine) and invasive (graft biopsy) biomarkers, partly driven by advances in omics technologies, can lead to earlier and more accurate detection of AR/SCR and IFTA and to improved graft monitoring. The identification of the immunological pathways of AR/IFTA may also enable the design of tailormade treatments. This minireview provides a state-of-the-art update on current evidence and limitations from key studies on non-invasive and invasive biomarkers of AR/SCR and IFTA and gives a perspective on their potential future implementation and the underlying challenges.
急性排斥反应(AR)和间质纤维化/肾小管萎缩(IFTA)是肾移植的重要并发症,对移植肾的寿命有负面影响。肾移植监测目前使用非特异性生物标志物(血清肌酐和蛋白尿)进行,这些标志物具有明显的局限性,只有在肾脏受到严重损害后才能检测到AR和IFTA。此外,许多移植患者在肌酐稳定(亚临床排斥反应- SCR)的情况下仍有组织学排斥反应的证据。AR和IFTA的“金标准”诊断测试是移植活检,但也有局限性,并可能产生主要并发症;因此,它不是常规移植物监测的理想测试。在组学技术进步的推动下,使用新的非侵入性(血液和尿液)和侵入性(移植物活检)生物标志物,可以更早、更准确地检测AR/SCR和IFTA,并改善移植物监测。识别AR/IFTA的免疫途径也可能使设计量身定制的治疗成为可能。这篇小型综述提供了最新的AR/SCR和IFTA的非侵入性和侵入性生物标志物关键研究的最新证据和局限性,并对其潜在的未来实施和潜在的挑战进行了展望。
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引用次数: 0
Spanish guidelines for kidney transplantation in highly sensitized patients with donor-specific anti-HLA antibodies 具有供体特异性抗hla抗体的高度敏感患者的西班牙肾移植指南
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-04-03 DOI: 10.1016/j.trre.2025.100919
Esther Mancebo , Fritz Diekmann , Eduard Palou , Carlos Vilches , Marta Crespo , Auxiliadora Mazuecos , José L. Caro , Josep M. Cruzado , David San Segundo , Manuel Muro , Jesús Ontañón , Antonia Álvarez , Oriol Bestard , Constantino Fernández , M. Francisca González , Antonio Nieto , Rocío Vega , Estela Paz-Artal , Elisabeth Coll , Amado Andrés , Beatriz Domínguez-Gil
Highly sensitized patients awaiting kidney transplantation face substantial challenges due to the presence of potential donor-specific anti-HLA antibodies (DSA). These antibodies increase the risk of antibody-mediated rejection (ABMR), but also complicate their access to HLA compatible transplantation. Although advancements in allocation priority programs, such as the Spanish Program for the Access of Highly Sensitized Patients to Kidney Transplantation (PATHI), have introduced virtual crossmatching (v-XM) to streamline compatibility assessments, patients with >99,5 % virtual panel reactive antibodies (vPRA) often remain on waiting lists for extended periods with minimal chances of receiving a transplant.
This article summarizes Spanish guidelines for a harmonized and comprehensive framework for the management of highly sensitized patients. These guidelines focus on strategies to facilitate transplantation in the presence of DSA, including a stepwise approach to delist HLA antigens, prioritizing those recognized as “less deleterious” antibodies, to expand transplant options while minimizing immunological risks. Conventional desensitization techniques are discussed, alongside the innovative use of imlifidase to enable transplants in particularly complex cases. Post-transplant monitoring protocols are also exposed, with a focus on early detection of antibody rebound and effective management of ABMR.
Ultimately, this resource offers clinicians a structured framework to navigate the intricate challenges of kidney transplantation in high-risk populations, aiming to enhance access to life-saving procedures and improve patient outcomes.
由于存在潜在的供体特异性抗hla抗体(DSA),等待肾移植的高度敏感患者面临着巨大的挑战。这些抗体增加了抗体介导的排斥反应(ABMR)的风险,但也使他们获得HLA兼容移植变得复杂。尽管在分配优先项目方面取得了进展,如西班牙高敏感患者肾移植项目(PATHI),引入了虚拟交叉匹配(v-XM)来简化兼容性评估,但携带99.5%虚拟面板反应性抗体(vPRA)的患者通常仍在等待名单上等待较长时间,接受移植的机会很小。这篇文章总结了西班牙指导方针的协调和全面的框架管理高度敏感的病人。这些指南侧重于在存在DSA的情况下促进移植的策略,包括逐步摘掉HLA抗原的方法,优先考虑那些被认为“危害较小”的抗体,扩大移植选择,同时最大限度地降低免疫风险。讨论了传统的脱敏技术,以及在特别复杂的病例中使用imlifidase进行移植的创新应用。移植后的监测方案也被曝光,重点是早期检测抗体反弹和有效管理ABMR。最终,该资源为临床医生提供了一个结构化的框架,以应对高危人群肾移植的复杂挑战,旨在提高获得救生程序的机会并改善患者的预后。
{"title":"Spanish guidelines for kidney transplantation in highly sensitized patients with donor-specific anti-HLA antibodies","authors":"Esther Mancebo ,&nbsp;Fritz Diekmann ,&nbsp;Eduard Palou ,&nbsp;Carlos Vilches ,&nbsp;Marta Crespo ,&nbsp;Auxiliadora Mazuecos ,&nbsp;José L. Caro ,&nbsp;Josep M. Cruzado ,&nbsp;David San Segundo ,&nbsp;Manuel Muro ,&nbsp;Jesús Ontañón ,&nbsp;Antonia Álvarez ,&nbsp;Oriol Bestard ,&nbsp;Constantino Fernández ,&nbsp;M. Francisca González ,&nbsp;Antonio Nieto ,&nbsp;Rocío Vega ,&nbsp;Estela Paz-Artal ,&nbsp;Elisabeth Coll ,&nbsp;Amado Andrés ,&nbsp;Beatriz Domínguez-Gil","doi":"10.1016/j.trre.2025.100919","DOIUrl":"10.1016/j.trre.2025.100919","url":null,"abstract":"<div><div>Highly sensitized patients awaiting kidney transplantation face substantial challenges due to the presence of potential donor-specific anti-HLA antibodies (DSA). These antibodies increase the risk of antibody-mediated rejection (ABMR), but also complicate their access to HLA compatible transplantation. Although advancements in allocation priority programs, such as the Spanish Program for the Access of Highly Sensitized Patients to Kidney Transplantation (PATHI), have introduced virtual crossmatching (v-XM) to streamline compatibility assessments, patients with &gt;99,5 % virtual panel reactive antibodies (vPRA) often remain on waiting lists for extended periods with minimal chances of receiving a transplant.</div><div>This article summarizes Spanish guidelines for a harmonized and comprehensive framework for the management of highly sensitized patients. These guidelines focus on strategies to facilitate transplantation in the presence of DSA, including a stepwise approach to delist HLA antigens, prioritizing those recognized as “less deleterious” antibodies, to expand transplant options while minimizing immunological risks. Conventional desensitization techniques are discussed, alongside the innovative use of imlifidase to enable transplants in particularly complex cases. Post-transplant monitoring protocols are also exposed, with a focus on early detection of antibody rebound and effective management of ABMR.</div><div>Ultimately, this resource offers clinicians a structured framework to navigate the intricate challenges of kidney transplantation in high-risk populations, aiming to enhance access to life-saving procedures and improve patient outcomes.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 3","pages":"Article 100919"},"PeriodicalIF":3.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of donor body weight on en bloc pediatric kidney transplantation in adults: A systematic review and meta-analysis 供体体重对成人整体儿童肾移植的影响:系统回顾和荟萃分析
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-28 DOI: 10.1016/j.trre.2025.100918
Haichen Yan , Yitian Fang , Jacqueline van de Wetering , Hendrikus J.A.N. Kimenai , Ron W.F. de Bruin , Robert C. Minnee

Background

The shortage of donor grafts for kidney transplantation remains a critical challenge. En bloc kidney transplantation (EBKT) using small deceased pediatric donors has the potential to expand the donor pool. This review aimed to investigate the outcomes of pediatric-donor EBKT in adults compared with standard single kidney transplantation (SKT).

Methods

Relevant databases, including Ovid, Web of Knowledge, Google Scholar, Wiley, and Embase, were searched for eligible studies. Demographic data and transplant outcomes were extracted from the included studies. The primary outcome was graft survival. A random-effects model was used for the meta-analysis.

Results

Thirteen studies were included. The median 1-year graft survival rates were 83.8 % and 89.2 % for EBKT and SKT, respectively (risk ratio [RR], 0.97; 95 % confidence interval [CI], 0.93–1.01). The median 5-year graft survival rates were 78.7 % and 72.7 % for EBKT and SKT, respectively (RR, 1.05; 95 % CI, 0.93–1.19). For donors with a body weight > 10 kg (EBKT >10 kg) and ≤ 10 kg (EBKT ≤10 kg), the median 1-year graft survival rates were 100.0 % and 90.0 %, respectively (RR, 1.08; 95 % CI, 1.05–1.12). Vascular complications were identified as the primary cause of graft loss.

Conclusions

Pediatric-donor EBKT in adults is a safe approach with excellent long-term functional outcomes comparable to those of SKT. EBKT represents an effective option to further utilizing pediatric donor kidneys. Outcomes of EBKT vary based on donor body weight. EBKT ≤10 kg was associated with higher short-term graft failure rates despite long-term performance being comparable to EBKT >10 kg.
肾移植供体的短缺仍然是一个严峻的挑战。整体肾移植(EBKT)使用小的死亡儿童供体有可能扩大供体池。本综述旨在研究成人儿童供体EBKT与标准单肾移植(SKT)的比较结果。方法检索Ovid、Web of Knowledge、谷歌Scholar、Wiley、Embase等相关数据库,检索符合条件的研究。从纳入的研究中提取人口统计数据和移植结果。主要结局是移植物存活。meta分析采用随机效应模型。结果共纳入13项研究。EBKT和SKT的1年移植存活率中位数分别为83.8%和89.2%(风险比[RR], 0.97;95%可信区间[CI], 0.93-1.01)。EBKT和SKT的中位5年移植存活率分别为78.7%和72.7% (RR, 1.05;95% ci, 0.93-1.19)。对于体重>;10 kg (EBKT >10 kg)和≤10 kg (EBKT≤10 kg),移植骨1年中位存活率分别为100.0%和90.0% (RR, 1.08;95% ci, 1.05-1.12)。血管并发症被认为是移植物丢失的主要原因。结论成人儿童供体EBKT是一种安全的方法,与SKT相比具有良好的长期功能预后。EBKT是进一步利用儿童供肾的有效选择。EBKT的结果因供体体重而异。EBKT≤10 kg的患者短期移植物失败率较高,尽管长期表现与EBKT≤10 kg的患者相当。
{"title":"Effect of donor body weight on en bloc pediatric kidney transplantation in adults: A systematic review and meta-analysis","authors":"Haichen Yan ,&nbsp;Yitian Fang ,&nbsp;Jacqueline van de Wetering ,&nbsp;Hendrikus J.A.N. Kimenai ,&nbsp;Ron W.F. de Bruin ,&nbsp;Robert C. Minnee","doi":"10.1016/j.trre.2025.100918","DOIUrl":"10.1016/j.trre.2025.100918","url":null,"abstract":"<div><h3>Background</h3><div>The shortage of donor grafts for kidney transplantation remains a critical challenge. En bloc kidney transplantation (EBKT) using small deceased pediatric donors has the potential to expand the donor pool. This review aimed to investigate the outcomes of pediatric-donor EBKT in adults compared with standard single kidney transplantation (SKT).</div></div><div><h3>Methods</h3><div>Relevant databases, including Ovid, Web of Knowledge, Google Scholar, Wiley, and Embase, were searched for eligible studies. Demographic data and transplant outcomes were extracted from the included studies. The primary outcome was graft survival. A random-effects model was used for the meta-analysis.</div></div><div><h3>Results</h3><div>Thirteen studies were included. The median 1-year graft survival rates were 83.8 % and 89.2 % for EBKT and SKT, respectively (risk ratio [RR], 0.97; 95 % confidence interval [CI], 0.93–1.01). The median 5-year graft survival rates were 78.7 % and 72.7 % for EBKT and SKT, respectively (RR, 1.05; 95 % CI, 0.93–1.19). For donors with a body weight &gt; 10 kg (EBKT &gt;10 kg) and ≤ 10 kg (EBKT ≤10 kg), the median 1-year graft survival rates were 100.0 % and 90.0 %, respectively (RR, 1.08; 95 % CI, 1.05–1.12). Vascular complications were identified as the primary cause of graft loss.</div></div><div><h3>Conclusions</h3><div>Pediatric-donor EBKT in adults is a safe approach with excellent long-term functional outcomes comparable to those of SKT. EBKT represents an effective option to further utilizing pediatric donor kidneys. Outcomes of EBKT vary based on donor body weight. EBKT ≤10 kg was associated with higher short-term graft failure rates despite long-term performance being comparable to EBKT &gt;10 kg.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 3","pages":"Article 100918"},"PeriodicalIF":3.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Survival after heart transplants from circulatory-dead versus brain-dead donors: Meta-analysis of reconstructed time-to-event data 循环死亡与脑死亡供者心脏移植后的生存:重建时间-事件数据的荟萃分析
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-21 DOI: 10.1016/j.trre.2025.100917
Mohammed Al-Tawil , William Wang , Ashwini Chandiramani , Feras Zaqout , Abdel Hannan Diab , Serge Sicouri , Basel Ramlawi , Assad Haneya

Background

Heart transplantation (HTx) using donors after circulatory death (DCD) has the potential to significantly boost overall transplant rates. This study aims to reconstruct data from individual studies comparing survival between HTx from DCD recipients and donation after brain (DBD) recipients.

Methods

MEDLINE, Embase, Scopus, were searched up to August 2024. We included studies that reported a Kaplan-Meier summary of survival comparing DCD and DBD HTx. Digitization of the Kaplan-Meier curves and reconstruction of individual patient data followed by survival analysis that was conducted using R software.

Results

Six studies including a total of 3240 patients (2242 DBD and 998 DCD) were included in the final analysis. There was no significant difference in the overall survival rates between DCD and DBD patients (Hazard Ratio (HR): 1.01, 95 % CI [0.81–1.25], P = 0.91). However, the proportional hazard assumption was violated, deeming such results inconclusive. Time-varying flexible parametric model revealed a significantly declining survival in DCD recipients 3 years after surgery. Landmark analyses further suggest this declining trend in the DCD group at the two-year landmark (HR: 1.67, p = 0.021) and the four-year mark (HR: 2.78, p = 0.002). However, data beyond 6 years is limited. Evidence comparing direct procurement and normothermic regional perfusion is scarce, with no significant survival differences observed.

Conclusion

This meta-analysis shows that, despite similar early survival outcomes, DCD heart transplants showed a trend towards a lower long-term survival, with the difference becoming evident around three years post-transplantation. These findings highlight the need for enhanced monitoring and optimized post-transplant care in DCD recipients. Further studies with strict and long-term follow-up are warranted to confirm these results.
背景:循环死亡(DCD)后使用供体进行心脏移植(HTx)有可能显著提高总体移植率。本研究旨在重建比较DCD受者HTx和脑后捐赠(DBD)受者HTx存活率的个体研究数据。方法检索至2024年8月的medline、Embase、Scopus数据库。我们纳入了报告了比较DCD和DBD HTx的Kaplan-Meier生存总结的研究。Kaplan-Meier曲线的数字化和个体患者数据的重建,随后使用R软件进行生存分析。结果6项研究共纳入3240例患者,其中DBD 2242例,DCD 998例。DCD和DBD患者的总生存率差异无统计学意义(危险比(HR): 1.01, 95% CI [0.81-1.25], P = 0.91)。然而,违反了比例风险假设,认为这些结果不具有决定性。时变柔性参数模型显示DCD患者术后3年生存率显著下降。里程碑分析进一步表明,DCD组在两年里程碑(HR: 1.67, p = 0.021)和四年标记(HR: 2.78, p = 0.002)时呈下降趋势。然而,6年以上的数据有限。比较直接获取和常温区域灌注的证据很少,没有观察到明显的生存差异。本荟萃分析显示,尽管早期生存结果相似,但DCD心脏移植的长期生存趋势较低,在移植后3年左右差异变得明显。这些发现强调了加强监测和优化DCD受者移植后护理的必要性。需要进一步的研究和严格的长期随访来证实这些结果。
{"title":"Survival after heart transplants from circulatory-dead versus brain-dead donors: Meta-analysis of reconstructed time-to-event data","authors":"Mohammed Al-Tawil ,&nbsp;William Wang ,&nbsp;Ashwini Chandiramani ,&nbsp;Feras Zaqout ,&nbsp;Abdel Hannan Diab ,&nbsp;Serge Sicouri ,&nbsp;Basel Ramlawi ,&nbsp;Assad Haneya","doi":"10.1016/j.trre.2025.100917","DOIUrl":"10.1016/j.trre.2025.100917","url":null,"abstract":"<div><h3>Background</h3><div>Heart transplantation (HTx) using donors after circulatory death (DCD) has the potential to significantly boost overall transplant rates. This study aims to reconstruct data from individual studies comparing survival between HTx from DCD recipients and donation after brain (DBD) recipients.</div></div><div><h3>Methods</h3><div>MEDLINE, Embase, Scopus, were searched up to August 2024. We included studies that reported a Kaplan-Meier summary of survival comparing DCD and DBD HTx. Digitization of the Kaplan-Meier curves and reconstruction of individual patient data followed by survival analysis that was conducted using R software.</div></div><div><h3>Results</h3><div>Six studies including a total of 3240 patients (2242 DBD and 998 DCD) were included in the final analysis. There was no significant difference in the overall survival rates between DCD and DBD patients (Hazard Ratio (HR): 1.01, 95 % CI [0.81–1.25], <em>P</em> = 0.91). However, the proportional hazard assumption was violated, deeming such results inconclusive. Time-varying flexible parametric model revealed a significantly declining survival in DCD recipients 3 years after surgery. Landmark analyses further suggest this declining trend in the DCD group at the two-year landmark (HR: 1.67, <em>p</em> = 0.021) and the four-year mark (HR: 2.78, <em>p</em> = 0.002). However, data beyond 6 years is limited. Evidence comparing direct procurement and normothermic regional perfusion is scarce, with no significant survival differences observed.</div></div><div><h3>Conclusion</h3><div>This meta-analysis shows that, despite similar early survival outcomes, DCD heart transplants showed a trend towards a lower long-term survival, with the difference becoming evident around three years post-transplantation. These findings highlight the need for enhanced monitoring and optimized post-transplant care in DCD recipients. Further studies with strict and long-term follow-up are warranted to confirm these results.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100917"},"PeriodicalIF":3.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ex-situ normothermic machine perfusion prevents ischemic cholangiopathy after liver transplantation: A meta-regression analysis 离地恒温机灌注预防肝移植后缺血性胆管病:一项荟萃回归分析
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.trre.2025.100915
Quirino Lai , Roberta Angelico , Nicola Guglielmo , Duilio Pagano , Paulo N. Martins , Davide Ghinolfi

Background & aims

Liver transplantation (LT) is the gold standard for end-stage liver disease, but ischemic cholangiopathy (IC) remains a significant complication. Ex-situ normothermic machine perfusion (ESNMP) has emerged as a potential strategy to mitigate ischemic injury. However, the effect of ESNMP on reducing post-LT IC remains controversial. This study aimed to perform an updated meta-analysis to evaluate the impact of ESNMP on IC incidence.

Methods

A systematic review and meta-analysis were conducted following PRISMA guidelines. The literature search included studies from 2015 to 2025 comparing LT outcomes using ESNMP vs. static cold storage (SCS). The primary outcome was the incidence of IC. Risk of bias was assessed using the ROBINS-E tool. Statistical analysis, including random-effects meta-analysis, sensitivity analysis, and meta-regression, was performed to evaluate heterogeneity, potential confounders, and the impact of follow-up duration.

Results

Seventeen studies, including 76,045 patients (4843 ESNMP; 71,202 SCS), were analyzed. No statistically significant difference in IC incidence was found between ESNMP and SCS (1.3 % vs. 0.6 %; RR = 0.68, 95 %CI = 0.41–1.13; P = 0.14). Sensitivity analysis excluding one outlier study revealed a reduction in IC risk with ESNMP (RR = 0.62, 95 %CI = 0.38–1.01; P = 0.054).
Two sub-analyses of studies with ≥12 months of follow-up (RR = 0.51, 95 %CI = 0.26–0.99; P = 0.049) and DCDs (RR = 0.33, 95 %CI = 0.16–0.67; P = 0.002) showed risk reduction. The meta-regression revealed that the back-to-base perfusion approach was associated with the occurrence of IC, with an OR of 1.03 (95 %CI = 1.00–1.07, P = 0.035).

Conclusions

a correlation between ESNMP use and IC reduced risk appears to exist, especially with longer follow-up periods and DCDs, though more high-quality studies are needed to confirm this finding.
背景,银移植(LT)是治疗终末期肝病的金标准,但缺血性胆管病(IC)仍然是一个重要的并发症。体外常温机器灌注(ESNMP)已成为减轻缺血性损伤的潜在策略。然而,ESNMP对降低lt后IC的作用仍存在争议。本研究旨在进行一项更新的荟萃分析,以评估ESNMP对IC发病率的影响。方法按照PRISMA指南进行系统评价和荟萃分析。文献检索包括2015年至2025年的研究,比较了使用ESNMP和静态冷库(SCS)的LT结果。主要终点是IC的发生率。使用ROBINS-E工具评估偏倚风险。统计分析包括随机效应荟萃分析、敏感性分析和荟萃回归,以评估异质性、潜在混杂因素和随访时间的影响。结果17项研究纳入76045例患者(4843例ESNMP;71202个SCS)进行分析。ESNMP和SCS之间IC发生率无统计学差异(1.3% vs 0.6%;Rr = 0.68, 95% ci = 0.41-1.13;p = 0.14)。排除一项异常研究的敏感性分析显示,ESNMP可降低IC风险(RR = 0.62, 95% CI = 0.38-1.01;p = 0.054)。随访≥12个月的两个亚组分析(RR = 0.51, 95% CI = 0.26-0.99;P = 0.049)和论证(RR = 0.33, 95% CI = 0.16 - -0.67;P = 0.002)显示风险降低。meta回归分析显示,颅底灌注与IC的发生相关,OR为1.03 (95% CI = 1.00-1.07, P = 0.035)。结论:ESNMP使用与IC风险降低之间似乎存在相关性,特别是在随访期和dcd较长的情况下,尽管需要更多高质量的研究来证实这一发现。
{"title":"Ex-situ normothermic machine perfusion prevents ischemic cholangiopathy after liver transplantation: A meta-regression analysis","authors":"Quirino Lai ,&nbsp;Roberta Angelico ,&nbsp;Nicola Guglielmo ,&nbsp;Duilio Pagano ,&nbsp;Paulo N. Martins ,&nbsp;Davide Ghinolfi","doi":"10.1016/j.trre.2025.100915","DOIUrl":"10.1016/j.trre.2025.100915","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Liver transplantation (LT) is the gold standard for end-stage liver disease, but ischemic cholangiopathy (IC) remains a significant complication. Ex-situ normothermic machine perfusion (ESNMP) has emerged as a potential strategy to mitigate ischemic injury. However, the effect of ESNMP on reducing post-LT IC remains controversial. This study aimed to perform an updated meta-analysis to evaluate the impact of ESNMP on IC incidence.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis were conducted following PRISMA guidelines. The literature search included studies from 2015 to 2025 comparing LT outcomes using ESNMP vs. static cold storage (SCS). The primary outcome was the incidence of IC. Risk of bias was assessed using the ROBINS-E tool. Statistical analysis, including random-effects meta-analysis, sensitivity analysis, and meta-regression, was performed to evaluate heterogeneity, potential confounders, and the impact of follow-up duration.</div></div><div><h3>Results</h3><div>Seventeen studies, including 76,045 patients (4843 ESNMP; 71,202 SCS), were analyzed. No statistically significant difference in IC incidence was found between ESNMP and SCS (1.3 % vs. 0.6 %; RR = 0.68, 95 %CI = 0.41–1.13; <em>P</em> = 0.14). Sensitivity analysis excluding one outlier study revealed a reduction in IC risk with ESNMP (RR = 0.62, 95 %CI = 0.38–1.01; <em>P</em> = 0.054).</div><div>Two sub-analyses of studies with ≥12 months of follow-up (RR = 0.51, 95 %CI = 0.26–0.99; <em>P</em> = 0.049) and DCDs (RR = 0.33, 95 %CI = 0.16–0.67; <em>P</em> = 0.002) showed risk reduction. The meta-regression revealed that the back-to-base perfusion approach was associated with the occurrence of IC, with an OR of 1.03 (95 %CI = 1.00–1.07, <em>P</em> = 0.035).</div></div><div><h3>Conclusions</h3><div>a correlation between ESNMP use and IC reduced risk appears to exist, especially with longer follow-up periods and DCDs, though more high-quality studies are needed to confirm this finding.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100915"},"PeriodicalIF":3.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Donor–derived cell–free dna as a diagnostic biomarker for acute rejection in heart transplantation: A systematic review and meta–analysis 供体来源的无细胞dna作为心脏移植急性排斥反应的诊断生物标志物:系统回顾和荟萃分析
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.trre.2025.100916
Shujun Liu, Lixing Wang, Shan Liu, Yinlong Zhao

Background

Endomyocardial biopsy is widely acknowledged as the gold standard for detecting rejection following heart transplantation. However, the operation itself carries a risk of myocardial tissue damage and associated complications during and after surgery. Given the limitations of existing diagnostic approaches, non-invasive biomarkers are crucial.

Objective

This study assessed the diagnostic utility of donor-derived cell-free DNA (dd-cfDNA) in detecting AR in heart transplant recipients.

Methods

A systematic literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from inception to August 1, 2024, to identify studies evaluating the diagnostic performance of dd-cfDNA for AR in heart transplant recipients. Retrieved studies were screened using EndNote X9. Meta-analysis was performed using Meta-Disc software version 1.4 and STATA/SE 14.0.

Results

Ten studies were included in the meta-analysis. The pooled sensitivity, specificity, and area under the receiver operating characteristic curve with 95 % confidence intervals (CIs) were 65 % (95 % CI, 61–68 %), 79 % (95 % CI, 78–80 %), and 0.83, respectively.

Conclusions

This meta-analysis indicates that plasma dd-cfDNA may serve as a promising non-invasive biomarker for the diagnosis of acute rejection in heart transplant recipients. However, further research is warranted to investigate factors influencing diagnostic performance and optimize clinical utility.
背景:心肌内膜活检被广泛认为是检测心脏移植后排斥反应的金标准。然而,手术本身存在心肌组织损伤的风险以及手术期间和手术后的相关并发症。鉴于现有诊断方法的局限性,非侵入性生物标志物至关重要。目的评价供体来源无细胞DNA (dd-cfDNA)检测心脏移植受者AR的诊断价值。方法系统检索PubMed、Embase、Cochrane Library和Web of Science自成立以来至2024年8月1日的文献,以确定评估dd-cfDNA对心脏移植受者AR诊断性能的研究。使用EndNote X9对检索到的研究进行筛选。采用Meta-Disc软件1.4版和STATA/SE 14.0进行meta分析。结果10项研究被纳入meta分析。在95%置信区间(CI)下,患者工作特征曲线下的总灵敏度、特异度和面积分别为65% (95% CI, 61 ~ 68%)、79% (95% CI, 78 ~ 80%)和0.83。结论:血浆dd-cfDNA可作为诊断心脏移植受者急性排斥反应的无创生物标志物。然而,需要进一步研究影响诊断性能的因素并优化临床应用。
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引用次数: 0
Assessing cumulative exposure to maintenance immunosuppressive drugs: Metrics, outcomes, and implications for transplant patients 评估维持免疫抑制药物的累积暴露:移植患者的指标、结果和影响
IF 3.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-09 DOI: 10.1016/j.trre.2025.100914
Cavizshajan Skanthan , Emily Nguyen , Lakindu Somaweera , Madhumitha Rabindranath , Ani Orchanian-Cheff , Alexandra Viau-Trudel , Myriam Khalili , Olusegun Famure , S. Joseph Kim
Immunosuppressive drugs are used in the management of transplant patients to prevent organ rejection. However, immunosuppression can be associated with adverse effects such as infections and cancers. This study aimed to characterize the measures of cumulative immunosuppressive drug exposure (CIDE) used in the literature and their associated outcomes in transplant patients. A literature search was conducted in Ovid MEDLINE, Ovid EMBASE, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews using search terms related to maintenance immunosuppressants and CIDE. Study risk of bias was assessed using the Quality in Prognostic Studies tool. Thirty-one articles were included in this qualitative synthesis. Sixteen articles (52 %) calculated the total dose of immunosuppression over the treatment period, while eight (26 %) used area-under-the-curve of trough level concentrations to quantify CIDE. Five (16 %) articles investigated time-weighted metrics of calcineurin inhibitors and four (13 %) used other metrics that could not be categorized into the previous groups. Most studies investigated CIDE with calcineurin inhibitors and used additive dosing methods. This approach was also popular with corticosteroids and multi-drug exposures. The variety of metrics used in the literature reveals a lack of standardization in the evaluation of CIDE and long-term outcomes. Future studies should validate these metrics for clinical application, especially pertaining to infectious outcomes.
免疫抑制药物用于移植患者的管理,以防止器官排斥反应。然而,免疫抑制可能与感染和癌症等不良反应有关。本研究旨在描述文献中使用的累积免疫抑制药物暴露(CIDE)的测量方法及其在移植患者中的相关结果。在Ovid MEDLINE、Ovid EMBASE、Cochrane CENTRAL和Cochrane系统评价数据库中检索与维护性免疫抑制剂和CIDE相关的文献。使用预后研究质量工具评估研究偏倚风险。这一定性综合纳入了31篇文章。16篇文章(52%)计算了整个治疗期间免疫抑制的总剂量,而8篇(26%)使用谷水平浓度曲线下面积来量化CIDE。五篇(16%)研究了钙调磷酸酶抑制剂的时间加权指标,四篇(13%)使用了其他不能归入前一组的指标。大多数研究用钙调磷酸酶抑制剂研究CIDE,并使用添加剂给药方法。这种方法在皮质类固醇和多种药物暴露中也很流行。文献中使用的各种指标表明,在CIDE和长期结果的评估中缺乏标准化。未来的研究应该验证这些指标的临床应用,特别是关于感染结果。
{"title":"Assessing cumulative exposure to maintenance immunosuppressive drugs: Metrics, outcomes, and implications for transplant patients","authors":"Cavizshajan Skanthan ,&nbsp;Emily Nguyen ,&nbsp;Lakindu Somaweera ,&nbsp;Madhumitha Rabindranath ,&nbsp;Ani Orchanian-Cheff ,&nbsp;Alexandra Viau-Trudel ,&nbsp;Myriam Khalili ,&nbsp;Olusegun Famure ,&nbsp;S. Joseph Kim","doi":"10.1016/j.trre.2025.100914","DOIUrl":"10.1016/j.trre.2025.100914","url":null,"abstract":"<div><div>Immunosuppressive drugs are used in the management of transplant patients to prevent organ rejection. However, immunosuppression can be associated with adverse effects such as infections and cancers. This study aimed to characterize the measures of cumulative immunosuppressive drug exposure (CIDE) used in the literature and their associated outcomes in transplant patients. A literature search was conducted in Ovid MEDLINE, Ovid EMBASE, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews using search terms related to maintenance immunosuppressants and CIDE. Study risk of bias was assessed using the Quality in Prognostic Studies tool. Thirty-one articles were included in this qualitative synthesis. Sixteen articles (52 %) calculated the total dose of immunosuppression over the treatment period, while eight (26 %) used area-under-the-curve of trough level concentrations to quantify CIDE. Five (16 %) articles investigated time-weighted metrics of calcineurin inhibitors and four (13 %) used other metrics that could not be categorized into the previous groups. Most studies investigated CIDE with calcineurin inhibitors and used additive dosing methods. This approach was also popular with corticosteroids and multi-drug exposures. The variety of metrics used in the literature reveals a lack of standardization in the evaluation of CIDE and long-term outcomes. Future studies should validate these metrics for clinical application, especially pertaining to infectious outcomes.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100914"},"PeriodicalIF":3.6,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Transplantation Reviews
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