{"title":"机器灌注还是直接移植?人肝移植冲洗液中黄素单核苷酸水平的预测价值。","authors":"Khaled Ali,Beatrice Cazzaniga,Qiang Liu,Yuki Miyazaki,Munkhbold Tuul,Roma Raj,Ahmed Hussein,Chase Wehrle,Mingyi Zhang,Esteban Calderon,Jiro Kusakabe,Kumaran Shanmugarajah,Glenn Wakam,Mazhar Khalil,Alejandro Pita,Federico Aucejo,Choon David Kwon Md,Jaekun Kim,Masato Fujiki,Charles Miller,Cristiano Quintini,Andrea Schlegel,Koji Hashimoto","doi":"10.1097/sla.0000000000006576","DOIUrl":null,"url":null,"abstract":"OBJECTIVE\r\nThis study examined the predictive value of Flavin Mononucleotide (FMN) levels in the flush solution used during cold storage of donor livers on outcomes post-transplantation.\r\n\r\nBACKGROUND\r\nStatic cold storage for liver grafts induces hypoxia with subsequent impaired mitochondrial function and Flavin Mononucleotide (FMN) release upon reperfusion.\r\n\r\nMETHODS\r\nThis study enrolled 62 recipients who received whole liver grafts from donation after brain death (n=50) and circulatory death donors (n=12) between June 2022 and July 2023. FMN concentrations were measured in flush solutions on the back-table. ROC-curve analysis identified an FMN level cut-off for graft survival. Post-transplant outcomes were examined according to FMN levels.\r\n\r\nRESULTS\r\nFMN level was significantly associated with graft survival, with an area-under-the-curve (AUC) of 0.858 (95%CI: 0.754-0.963, P<0.001), outperforming the donor risk index (AUC 0.571, 95%CI: 0.227-0.915, P=0.686). The study cohort was divided into low-FMN (<37.5 ng/mL, n=40) and high-FMN groups (≥37.5 ng/mL, n=22). The low-FMN group had superior one-year graft survival compared with the high-FMN group (100% vs. 77%, P=0.003). Levels of transaminases within 7 days post-transplant were significantly higher in the high-FMN group (P=0.003). The high-FMN group developed acute rejections (41% vs. 15%, P=0.023) and early allograft dysfunction (50% vs. 20%, P=0.014) more frequently. Median comprehensive complication index in the high-FMN group was significantly higher (54 [interquartile range, 40-78] vs. 42 [interquartile range, 28-52], P=0.017).\r\n\r\nCONCLUSION\r\nThe FMN level measured in donor livers' cold storage flush solution is a valid biomarker to predict post-transplant outcomes. Liver grafts with high FMN levels may benefit from machine perfusion to improve outcomes.","PeriodicalId":8017,"journal":{"name":"Annals of surgery","volume":null,"pages":null},"PeriodicalIF":7.5000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Machine Perfusion or Straight to Transplant? Predictive Value of Flavin Mononucleotide Levels in Flush Solution of Human Liver Allograft.\",\"authors\":\"Khaled Ali,Beatrice Cazzaniga,Qiang Liu,Yuki Miyazaki,Munkhbold Tuul,Roma Raj,Ahmed Hussein,Chase Wehrle,Mingyi Zhang,Esteban Calderon,Jiro Kusakabe,Kumaran Shanmugarajah,Glenn Wakam,Mazhar Khalil,Alejandro Pita,Federico Aucejo,Choon David Kwon Md,Jaekun Kim,Masato Fujiki,Charles Miller,Cristiano Quintini,Andrea Schlegel,Koji Hashimoto\",\"doi\":\"10.1097/sla.0000000000006576\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVE\\r\\nThis study examined the predictive value of Flavin Mononucleotide (FMN) levels in the flush solution used during cold storage of donor livers on outcomes post-transplantation.\\r\\n\\r\\nBACKGROUND\\r\\nStatic cold storage for liver grafts induces hypoxia with subsequent impaired mitochondrial function and Flavin Mononucleotide (FMN) release upon reperfusion.\\r\\n\\r\\nMETHODS\\r\\nThis study enrolled 62 recipients who received whole liver grafts from donation after brain death (n=50) and circulatory death donors (n=12) between June 2022 and July 2023. FMN concentrations were measured in flush solutions on the back-table. ROC-curve analysis identified an FMN level cut-off for graft survival. Post-transplant outcomes were examined according to FMN levels.\\r\\n\\r\\nRESULTS\\r\\nFMN level was significantly associated with graft survival, with an area-under-the-curve (AUC) of 0.858 (95%CI: 0.754-0.963, P<0.001), outperforming the donor risk index (AUC 0.571, 95%CI: 0.227-0.915, P=0.686). The study cohort was divided into low-FMN (<37.5 ng/mL, n=40) and high-FMN groups (≥37.5 ng/mL, n=22). The low-FMN group had superior one-year graft survival compared with the high-FMN group (100% vs. 77%, P=0.003). Levels of transaminases within 7 days post-transplant were significantly higher in the high-FMN group (P=0.003). The high-FMN group developed acute rejections (41% vs. 15%, P=0.023) and early allograft dysfunction (50% vs. 20%, P=0.014) more frequently. Median comprehensive complication index in the high-FMN group was significantly higher (54 [interquartile range, 40-78] vs. 42 [interquartile range, 28-52], P=0.017).\\r\\n\\r\\nCONCLUSION\\r\\nThe FMN level measured in donor livers' cold storage flush solution is a valid biomarker to predict post-transplant outcomes. Liver grafts with high FMN levels may benefit from machine perfusion to improve outcomes.\",\"PeriodicalId\":8017,\"journal\":{\"name\":\"Annals of surgery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2024-10-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of surgery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/sla.0000000000006576\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/sla.0000000000006576","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
摘要
目的本研究探讨了冷藏供体肝脏时使用的冲洗液中黄素单核苷酸(FMN)水平对移植后预后的预测价值。背景肝脏移植物的静态冷藏会导致缺氧,进而损害线粒体功能和再灌注时黄素单核苷酸(FMN)的释放。方法这项研究在2022年6月至2023年7月期间招募了62名受者,他们接受了脑死亡后捐献者(50人)和循环死亡捐献者(12人)的全肝移植物。在后台上测量了冲洗溶液中的 FMN 浓度。ROC曲线分析确定了移植物存活率的FMN水平临界值。结果FMN水平与移植物存活率显著相关,曲线下面积(AUC)为0.858(95%CI:0.754-0.963,P<0.001),优于供体风险指数(AUC 0.571,95%CI:0.227-0.915,P=0.686)。研究队列分为低FMN组(<37.5纳克/毫升,n=40)和高FMN组(≥37.5纳克/毫升,n=22)。低FMN组的一年移植物存活率高于高FMN组(100% vs. 77%,P=0.003)。高FMN组移植后7天内的转氨酶水平明显更高(P=0.003)。高FMN组发生急性排斥反应(41%对15%,P=0.023)和早期异体移植功能障碍(50%对20%,P=0.014)的频率更高。高FMN组的综合并发症指数中位数明显更高(54[四分位间范围,40-78] vs. 42 [四分位间范围,28-52],P=0.017)。FMN水平较高的肝脏移植物可能受益于机器灌注以改善预后。
Machine Perfusion or Straight to Transplant? Predictive Value of Flavin Mononucleotide Levels in Flush Solution of Human Liver Allograft.
OBJECTIVE
This study examined the predictive value of Flavin Mononucleotide (FMN) levels in the flush solution used during cold storage of donor livers on outcomes post-transplantation.
BACKGROUND
Static cold storage for liver grafts induces hypoxia with subsequent impaired mitochondrial function and Flavin Mononucleotide (FMN) release upon reperfusion.
METHODS
This study enrolled 62 recipients who received whole liver grafts from donation after brain death (n=50) and circulatory death donors (n=12) between June 2022 and July 2023. FMN concentrations were measured in flush solutions on the back-table. ROC-curve analysis identified an FMN level cut-off for graft survival. Post-transplant outcomes were examined according to FMN levels.
RESULTS
FMN level was significantly associated with graft survival, with an area-under-the-curve (AUC) of 0.858 (95%CI: 0.754-0.963, P<0.001), outperforming the donor risk index (AUC 0.571, 95%CI: 0.227-0.915, P=0.686). The study cohort was divided into low-FMN (<37.5 ng/mL, n=40) and high-FMN groups (≥37.5 ng/mL, n=22). The low-FMN group had superior one-year graft survival compared with the high-FMN group (100% vs. 77%, P=0.003). Levels of transaminases within 7 days post-transplant were significantly higher in the high-FMN group (P=0.003). The high-FMN group developed acute rejections (41% vs. 15%, P=0.023) and early allograft dysfunction (50% vs. 20%, P=0.014) more frequently. Median comprehensive complication index in the high-FMN group was significantly higher (54 [interquartile range, 40-78] vs. 42 [interquartile range, 28-52], P=0.017).
CONCLUSION
The FMN level measured in donor livers' cold storage flush solution is a valid biomarker to predict post-transplant outcomes. Liver grafts with high FMN levels may benefit from machine perfusion to improve outcomes.
期刊介绍:
The Annals of Surgery is a renowned surgery journal, recognized globally for its extensive scholarly references. It serves as a valuable resource for the international medical community by disseminating knowledge regarding important developments in surgical science and practice. Surgeons regularly turn to the Annals of Surgery to stay updated on innovative practices and techniques. The journal also offers special editorial features such as "Advances in Surgical Technique," offering timely coverage of ongoing clinical issues. Additionally, the journal publishes monthly review articles that address the latest concerns in surgical practice.