供肺短缺一直以来都是限制肺移植数量增长的主要问题.对于一些胸腔较小的成年人或是儿童来说,等待一个适合的供肺更是路阻且长.劈裂式肺叶移植(split lobar lung transplantation,SLLTx)是传统肺叶移植基础上的一项技术革新,其目的是通过对供肺进行解剖性劈裂,得到分别有着完整的支气管、动脉、心房袖的上、下肺叶可供受体吻合,使得一个肺脏可以给2例小胸腔受者行双侧肺叶移植,每一叶肺都"物尽其用".本文通过概述劈裂式肺叶移植手术技术及介绍分析典型案例,以期为国内肺移植外科医生在面对小胸腔受者肺移植时提供新思路.
Background. Primary graft dysfunction, which is directly related to cold ischemia–reperfusion (CI/R) injury, is a major obstacle in lung transplantation (LTx). Ferroptosis, a novel mode of cell death elicited by iron-dependent lipid peroxidation, has been implicated in ischemic events. This study aimed to investigate the role of ferroptosis in LTx-CI/R injury and the effectiveness of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, in alleviating LTx-CI/R injury. Methods. LTx-CI/R-induced signal pathway alterations, tissue injury, cell death, inflammatory responses, and ferroptotic features were examined in human lung biopsies, the human bronchial epithelial (BEAS-2B) cells, and the mouse LTx-CI/R model (24-h CI/4-h R). The therapeutic efficacy of Lip-1 was explored and validated both in vitro and in vivo. Results. In human lung tissues, LTx-CI/R activated ferroptosis-related signaling pathway, increased the tissue iron content and lipid peroxidation accumulation, and altered key protein (GPX4, COX2, Nrf2, and SLC7A11) expression and mitochondrial morphology. In BEAS-2B cells, the hallmarks of ferroptosis were significantly evidenced at the setting of both CI and CI/R compared with the control, and the effect of adding Lip-1 only during CI was much better than that of only during reperfusion by Cell Counting Kit-8. Furthermore, Lip-1 administration during CI markedly relieved LTx-CI/R injury in mice, as indicated by significant improvement in lung pathological changes, pulmonary function, inflammation, and ferroptosis. Conclusions. This study revealed the existence of ferroptosis in the pathophysiology of LTx-CI/R injury. Using Lip-1 to inhibit ferroptosis during CI could ameliorate LTx-CI/R injury, suggesting that Lip-1 administration might be proposed as a new strategy for organ preservation.
ImportanceAlthough numerous prognostic factors have been found for patients after lung transplantation (LTx) over the years, an accurate prognostic tool for LTx recipients remains unavailable. ObjectiveTo develop and validate a prognostic model for predicting overall survival in patients after LTx using random survival forests (RSF), a machine learning algorithm. Design, Setting, and ParticipantsThis retrospective prognostic study included patients who underwent LTx between January 2017 and December 2020. The LTx recipients were randomly assigned to training and test sets in accordance with a ratio of 7:3. Feature selection was performed using variable importance with bootstrapping resampling. The prognostic model was fitted using the RSF algorithm, and a Cox regression model was set as a benchmark. The integrated area under the curve (iAUC) and integrated Brier score (iBS) were applied to assess model performance in the test set. Data were analyzed from January 2017 to December 2019. Main Outcomes And MeasuresOverall survival in patients after LTx. ResultsA total of 504 patients were eligible for this study, consisting of 353 patients in the training set (mean [SD] age, 55.03 [12.78] years; 235 [66.6%] male patients) and 151 patients in the test set (mean [SD] age, 56.79 [10.95] years; 99 [65.6%] male patients). According to the variable importance of each factor, 16 were selected for the final RSF model, and postoperative extracorporeal membrane oxygenation time was identified as the most valuable factor. The RSF model had excellent performance with an iAUC of 0.879 (95% CI, 0.832-0.921) and an iBS of 0.130 (95% CI, 0.106-0.154). The Cox regression model fitted by the same modeling factors to the RSF model was significantly inferior to the RSF model with an iAUC of 0.658 (95% CI, 0.572-0.747; P<.001) and an iBS of 0.205 (95% CI, 0.176-0.233; P<.001). According to the RSF model predictions, the patients after LTx were stratified into 2 prognostic groups displaying significant difference, with mean overall survival of 52.91 months (95% CI, 48.51-57.32) and 14.83 months (95% CI, 9.44-20.22; log-rank P<.001), respectively. Conclusions and relevanceIn this prognostic study, the findings first demonstrated that RSF could provide more accurate overall survival prediction and remarkable prognostic stratification than the Cox regression model for patients after LTx.
肺移植作为终末期肺病最后的治疗手段,不仅可以明显延长患者的生存时间,还能很大程度改善患者的生活质量.在过去的几十年里,随着外科技术、免疫抑制药和移植术后管理方面的进步,全球肺移植手术量激增.但供肺短缺极大限制了肺移植的发展,需要开发创新方法来扩大供者库.捐献者数量以及潜在供肺的有效保存与功能维护是扩大供者库的关键,供肺质量是保证肺移植受者术后长期生存的重要前提,移植肺的保存与功能维护在保证供肺质量方面尤为重要.本文总结了获取前供肺的管理与维护、供肺获取及移植肺的保存与功能维护的最新进展,以期为临床肺移植的发展提供参考.
目的 评价连续性肾脏替代治疗在边缘性供肺维护中的应用价值.方法 2019年1月1日~2019年10月31日经无锡市人民医院肺移植中心维护的脑死亡边缘性供肺30例,根据维护方法 不同,将其分为两组,实验组12例,在获取前予以常规+持续性肾脏替代治疗(CRRT)联合方案维护48小时;对照组18例,仅进行常规方案维护.两组每24小时留取外周血样,行胸片及气道纤支镜检查,动态监测并对比两种维护方式在血流动力学、氧合指数、感染指标、气道黏膜水肿以及供肺最终使用情况等的差异.结果 经两种方法 维护后,两组供肺质量均较前有不同程度改善,实验组和对照组氧合指数增加分别为(93.58±16.92)% 和(57.72±11.41)%,C-反应蛋白(CRP)下降分别为(36.04±22.30)mg/L和(18.01±6.78)mg/L,降钙素原(PCT)下降分别为1.09±0.45和0.59±0.82,两组比较,差异有统计学意义(P<0.05).实验组肺影像学的渗出改变、气道黏膜水肿程度改善显著.实验组中8例、对照组中5例达到供肺使用标准,实验组使用率显著高于对照组(P<0.05).结论 早期予以CRRT联合方案,能显著改善边缘性供肺肺功能,提高供体器官利用率.
The combined liver-lung transplantation (CLLT) is performed in patients with dual-organ failure in whom survival is not expected with single-organ transplantation alone. Due to the difficulty of the operation and the scarcity of donated organs, only a few transplant centers worldwide have reported relevant cases. This review evaluates the existing literature regarding CLLT, describing the indication, operation choosing, complications, and prognosis.
肺尘埃沉着病(尘肺病)是世界上最严重且患病人数最多的职业病,目前治疗的主要方法有药物治疗、肺灌洗技术及肺移植.当前的药物治疗主要起缓解症状的作用,不能有效清除肺部粉尘.肺灌洗技术能清除部分肺部粉尘,但是存在远期效果不佳以及并发症发生率较高等问题.肺移植治疗尘肺病的效果得到越来越多医师和患者的肯定,但诸多因素限制了肺移植治疗尘肺病的发展.本文就尘肺病的概况、尘肺病的治疗、肺移植治疗尘肺病的问题与困境进行综述,以期给临床医师选择治疗方案时提供一些参考.