术后认知能力下降的免疫特征:前瞻性队列研究

IF 12.5 2区 医学 Q1 SURGERY
Franck Verdonk, Amélie Cambriel, Julien Hedou, Ed Ganio, Grégoire Bellan, Dyani Gaudilliere, Jakob Einhaus, Maximilian Sabayev, Ina A Stelzer, Dorien Feyaerts, Adam T Bonham, Kazuo Ando, Benjamin Choisy, David Drover, Boris Heifets, Fabrice Chretien, Nima Aghaeepour, Martin S Angst, Serge Molliex, Tarek Sharshar, Raphael Gaillard, Brice Gaudilliere
{"title":"术后认知能力下降的免疫特征:前瞻性队列研究","authors":"Franck Verdonk, Amélie Cambriel, Julien Hedou, Ed Ganio, Grégoire Bellan, Dyani Gaudilliere, Jakob Einhaus, Maximilian Sabayev, Ina A Stelzer, Dorien Feyaerts, Adam T Bonham, Kazuo Ando, Benjamin Choisy, David Drover, Boris Heifets, Fabrice Chretien, Nima Aghaeepour, Martin S Angst, Serge Molliex, Tarek Sharshar, Raphael Gaillard, Brice Gaudilliere","doi":"10.1097/JS9.0000000000002118","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Postoperative cognitive decline (POCD) is the predominant complication affecting patients over 60 years old following major surgery, yet its prediction and prevention remain challenging. Understanding the biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This study aimed to provide a comprehensive analysis of immune cell trajectories differentiating patients with and without POCD and to derive a predictive score enabling the identification of high-risk patients during the preoperative period.</p><p><strong>Material and methods: </strong>Twenty-six patients aged 60 years old and older undergoing elective major orthopedic surgery were enrolled in a prospective longitudinal study, and the occurrence of POCD was assessed seven days after surgery. Serial samples collected before surgery, and one, seven, and 90 days after surgery were analyzed using a combined single-cell mass cytometry and plasma proteomic approach. Unsupervised clustering of the high-dimensional mass cytometry data was employed to characterize time-dependent trajectories of all major innate and adaptive immune cell frequencies and signaling responses. Sparse machine learning coupled with data-driven feature selection was applied to the pre-surgery immunological dataset to classify patients at risk for POCD.</p><p><strong>Results: </strong>The analysis identified cell-type and signaling-specific immune trajectories differentiating patients with and without POCD. The most prominent trajectory features revealed early exacerbation of JAK/STAT and dampening of inhibitory κB and nuclear factor-κB immune signaling responses in patients with POCD. Further analyses integrating immunological and clinical data collected before surgery identified a preoperative predictive model comprising one plasma protein and ten immune cell features that classified patients at risk for POCD with excellent accuracy (AUC=0.80, P=2.21e-02 U-test).</p><p><strong>Conclusion: </strong>Immune system-wide monitoring of patients over 60 years old undergoing surgery unveiled a peripheral immune signature of POCD. A predictive model built on immunological data collected before surgery demonstrated greater accuracy in predicting POCD compared to known clinical preoperative risk factors, offering a concise list of biomarker candidates to personalize perioperative management.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An immune signature of postoperative cognitive decline: A prospective cohort study.\",\"authors\":\"Franck Verdonk, Amélie Cambriel, Julien Hedou, Ed Ganio, Grégoire Bellan, Dyani Gaudilliere, Jakob Einhaus, Maximilian Sabayev, Ina A Stelzer, Dorien Feyaerts, Adam T Bonham, Kazuo Ando, Benjamin Choisy, David Drover, Boris Heifets, Fabrice Chretien, Nima Aghaeepour, Martin S Angst, Serge Molliex, Tarek Sharshar, Raphael Gaillard, Brice Gaudilliere\",\"doi\":\"10.1097/JS9.0000000000002118\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Postoperative cognitive decline (POCD) is the predominant complication affecting patients over 60 years old following major surgery, yet its prediction and prevention remain challenging. Understanding the biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This study aimed to provide a comprehensive analysis of immune cell trajectories differentiating patients with and without POCD and to derive a predictive score enabling the identification of high-risk patients during the preoperative period.</p><p><strong>Material and methods: </strong>Twenty-six patients aged 60 years old and older undergoing elective major orthopedic surgery were enrolled in a prospective longitudinal study, and the occurrence of POCD was assessed seven days after surgery. Serial samples collected before surgery, and one, seven, and 90 days after surgery were analyzed using a combined single-cell mass cytometry and plasma proteomic approach. Unsupervised clustering of the high-dimensional mass cytometry data was employed to characterize time-dependent trajectories of all major innate and adaptive immune cell frequencies and signaling responses. Sparse machine learning coupled with data-driven feature selection was applied to the pre-surgery immunological dataset to classify patients at risk for POCD.</p><p><strong>Results: </strong>The analysis identified cell-type and signaling-specific immune trajectories differentiating patients with and without POCD. The most prominent trajectory features revealed early exacerbation of JAK/STAT and dampening of inhibitory κB and nuclear factor-κB immune signaling responses in patients with POCD. Further analyses integrating immunological and clinical data collected before surgery identified a preoperative predictive model comprising one plasma protein and ten immune cell features that classified patients at risk for POCD with excellent accuracy (AUC=0.80, P=2.21e-02 U-test).</p><p><strong>Conclusion: </strong>Immune system-wide monitoring of patients over 60 years old undergoing surgery unveiled a peripheral immune signature of POCD. A predictive model built on immunological data collected before surgery demonstrated greater accuracy in predicting POCD compared to known clinical preoperative risk factors, offering a concise list of biomarker candidates to personalize perioperative management.</p>\",\"PeriodicalId\":14401,\"journal\":{\"name\":\"International journal of surgery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.5000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of surgery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/JS9.0000000000002118\",\"RegionNum\":2,\"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":"International journal of surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/JS9.0000000000002118","RegionNum":2,"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

背景:术后认知功能衰退(POCD)是影响 60 岁以上大手术患者的主要并发症,但其预测和预防仍具有挑战性。了解 POCD 发病机制的生物学过程对于确定机制生物标志物以促进诊断和治疗至关重要。本研究旨在全面分析区分 POCD 患者和非 POCD 患者的免疫细胞轨迹,并得出一个预测分数,以便在术前识别高风险患者:一项前瞻性纵向研究共纳入了 26 名年龄在 60 岁及以上、接受择期骨科大手术的患者,并在术后 7 天评估了 POCD 的发生情况。研究人员采用单细胞质谱和血浆蛋白质组学相结合的方法,对术前、术后1天、7天和90天采集的序列样本进行了分析。对高维质谱数据进行无监督聚类,以描述所有主要先天性和适应性免疫细胞频率和信号反应的时间依赖性轨迹。稀疏机器学习结合数据驱动的特征选择被应用于手术前免疫学数据集,以对有POCD风险的患者进行分类:结果:分析确定了细胞类型和信号特异性免疫轨迹,从而区分出 POCD 患者和非 POCD 患者。最突出的轨迹特征显示,POCD 患者的 JAK/STAT 早期加剧,抑制性 κB 和核因子-κB 免疫信号反应减弱。通过对术前收集的免疫学和临床数据进行进一步分析,确定了一个由一种血浆蛋白和十种免疫细胞特征组成的术前预测模型,该模型能非常准确地对有 POCD 风险的患者进行分类(AUC=0.80,P=2.21e-02 U 检验):结论:对 60 岁以上接受手术的患者进行全免疫系统监测,揭示了 POCD 的外周免疫特征。与已知的临床术前风险因素相比,基于术前收集的免疫学数据建立的预测模型在预测 POCD 方面表现出更高的准确性,为个性化围手术期管理提供了一份简明的候选生物标记物清单。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An immune signature of postoperative cognitive decline: A prospective cohort study.

Background: Postoperative cognitive decline (POCD) is the predominant complication affecting patients over 60 years old following major surgery, yet its prediction and prevention remain challenging. Understanding the biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This study aimed to provide a comprehensive analysis of immune cell trajectories differentiating patients with and without POCD and to derive a predictive score enabling the identification of high-risk patients during the preoperative period.

Material and methods: Twenty-six patients aged 60 years old and older undergoing elective major orthopedic surgery were enrolled in a prospective longitudinal study, and the occurrence of POCD was assessed seven days after surgery. Serial samples collected before surgery, and one, seven, and 90 days after surgery were analyzed using a combined single-cell mass cytometry and plasma proteomic approach. Unsupervised clustering of the high-dimensional mass cytometry data was employed to characterize time-dependent trajectories of all major innate and adaptive immune cell frequencies and signaling responses. Sparse machine learning coupled with data-driven feature selection was applied to the pre-surgery immunological dataset to classify patients at risk for POCD.

Results: The analysis identified cell-type and signaling-specific immune trajectories differentiating patients with and without POCD. The most prominent trajectory features revealed early exacerbation of JAK/STAT and dampening of inhibitory κB and nuclear factor-κB immune signaling responses in patients with POCD. Further analyses integrating immunological and clinical data collected before surgery identified a preoperative predictive model comprising one plasma protein and ten immune cell features that classified patients at risk for POCD with excellent accuracy (AUC=0.80, P=2.21e-02 U-test).

Conclusion: Immune system-wide monitoring of patients over 60 years old undergoing surgery unveiled a peripheral immune signature of POCD. A predictive model built on immunological data collected before surgery demonstrated greater accuracy in predicting POCD compared to known clinical preoperative risk factors, offering a concise list of biomarker candidates to personalize perioperative management.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
17.70
自引率
3.30%
发文量
0
审稿时长
6-12 weeks
期刊介绍: The International Journal of Surgery (IJS) has a broad scope, encompassing all surgical specialties. Its primary objective is to facilitate the exchange of crucial ideas and lines of thought between and across these specialties.By doing so, the journal aims to counter the growing trend of increasing sub-specialization, which can result in "tunnel-vision" and the isolation of significant surgical advancements within specific specialties.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信