内皮糖萼相关分子作为脓毒症相关性脑病潜在血清学标志物的系统评价和荟萃分析。
Endothelial glycocalyx-associated molecules as potential serological markers for sepsis-associated encephalopathy: A systematic review and meta-analysis.
机构信息
Morsani College of Medicine, University of South Florida, Tampa, FL, United States of America.
Department of Evidence Based Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, United States of America.
出版信息
PLoS One. 2023 Feb 21;18(2):e0281941. doi: 10.1371/journal.pone.0281941. eCollection 2023.
BACKGROUND
Sepsis-associated encephalopathy (SAE) is characterized by a diffuse cerebral dysfunction that accompanies sepsis in the absence of direct central nervous system infection. The endothelial glycocalyx is a dynamic mesh containing heparan sulfate linked to proteoglycans and glycoproteins, including selectins and vascular/intercellular adhesion molecules (V/I-CAMs), which protects the endothelium while mediating mechano-signal transduction between the blood and vascular wall. During severe inflammatory states, components of the glycocalyx are shed into the circulation and can be detected in soluble forms. Currently, SAE remains a diagnosis of exclusion and limited information is available on the utility of glycocalyx-associated molecules as biomarkers for SAE. We set out to synthesize all available evidence on the association between circulating molecules released from the endothelial glycocalyx surface during sepsis and sepsis-associated encephalopathy.
METHODS
MEDLINE (PubMed) and EMBASE were searched since inception until May 2, 2022 to identify eligible studies. Any comparative observational study: i) evaluating the association between sepsis and cognitive decline and ii) providing information on level of circulating glycocalyx-associated molecules was eligible for inclusion.
RESULTS
Four case-control studies with 160 patients met the inclusion criteria. Meta-analysis of biomarkers ICAM-1 (SMD 0.41; 95% CI 0.05-0.76; p = 0.03; I2 = 50%) and VCAM-1 (SMD 0.55; 95% CI 0.12-0.98; p = 0.01; I2 = 82%) revealed higher pooled mean concentration in patients with SAE compared to the patients with sepsis alone. Single studies reported elevated levels of P-selectin (MD 0.80; 95% CI -17.77-19.37), E-selectin (MD 96.40; 95% Cl 37.90-154.90), heparan sulfate NS2S (MD 19.41; 95% CI 13.37-25.46), and heparan sulfate NS+NS2S+NS6S (MD 67.00; 95% CI 31.00-103.00) in patients with SAE compared to the patients with sepsis alone.
CONCLUSION
Plasma glycocalyx-associated molecules are elevated in SAE and may be useful for early identification of cognitive decline in sepsis patients.
背景
脓毒症相关性脑病 (SAE) 的特征是在没有直接中枢神经系统感染的情况下，脓毒症伴弥漫性脑功能障碍。内皮糖萼是一种动态网格，包含与糖蛋白连接的肝素硫酸盐，包括选择素和血管/细胞间黏附分子（V/I-CAMs），它在介导血液与血管壁之间的机械信号转导的同时保护内皮细胞。在严重的炎症状态下，糖萼的成分会脱落到循环中，并以可溶性形式检测到。目前，SAE 仍然是一种排除性诊断，关于糖萼相关分子作为 SAE 生物标志物的效用的信息有限。我们旨在综合所有关于脓毒症期间从内皮糖萼表面释放到循环中的分子与脓毒症相关性脑病之间关联的现有证据。
方法
从开始到 2022 年 5 月 2 日，通过 MEDLINE（PubMed）和 EMBASE 搜索确定合格的研究。任何比较观察性研究：i）评估脓毒症与认知能力下降之间的关联，ii）提供关于循环糖萼相关分子水平的信息，均符合纳入标准。
结果
四项符合纳入标准的病例对照研究共纳入 160 名患者。对生物标志物 ICAM-1（SMD 0.41；95%CI 0.05-0.76；p = 0.03；I2 = 50%）和 VCAM-1（SMD 0.55；95%CI 0.12-0.98；p = 0.01；I2 = 82%）的荟萃分析显示，与单纯脓毒症患者相比，SAE 患者的平均浓度更高。单个研究报告了 P-选择素（MD 0.80；95%CI -17.77-19.37）、E-选择素（MD 96.40；95%Cl 37.90-154.90）、肝素硫酸盐 NS2S（MD 19.41；95%CI 13.37-25.46）和肝素硫酸盐 NS+NS2S+NS6S（MD 67.00；95%CI 31.00-103.00）水平升高。
结论
SAE 患者的血浆糖萼相关分子水平升高，可能有助于早期识别脓毒症患者的认知能力下降。
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