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Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study
Journal of Neuroinflammation ( IF 9.3 ) Pub Date : 2020-11-12 , DOI: 10.1186/s12974-020-01979-y
Jeppe Sillesen Matzen 1 , Charlotte Loumann Krogh 1 , Julie Lyng Forman 2 , Peter Garred 3, 4 , Kirsten Møller 1, 4 , Søren Bache 1
Affiliation  

This exploratory study investigated the time-course of lectin complement pathway (LCP) initiators in cerebrospinal fluid (CSF) and plasma in patients with subarachnoid hemorrhage (SAH), as well as their relationship to delayed cerebral ischemia (DCI) and functional outcome. Concentrations of ficolin-1, ficolin-2, ficolin-3, and mannose-binding lectin (MBL) were analyzed in CSF and plasma from patients with SAH. Samples were collected daily from admission until day 9 (CSF; N_PATIENTS = 63, n_SAMPLES = 399) and day 8 (plasma; N_PATIENTS = 50, n_SAMPLES = 358), respectively. Twelve neurologically healthy patients undergoing spinal anesthesia and 12 healthy blood donors served as controls. The development of DCI during hospitalization and functional outcome at 3 months (modified Rankin Scale) were registered for patients. On admission, CSF levels of all LCP initiators were increased in SAH patients compared with healthy controls. Levels declined gradually over days in patients; however, a biphasic course was observed for ficolin-1. Increased CSF levels of all LCP initiators were associated with a poor functional outcome in univariate analyses. This relationship persisted for ficolin-1 and MBL in multivariate analysis after adjustments for confounders (age, sex, clinical severity, distribution and amount of blood on CT-imaging) and multiple testing (1.87 ng/mL higher in average, 95% CI, 1.17 to 2.99 and 1.69 ng/mL higher in average, 95% CI, 1.09 to 2.63, respectively). In patients who developed DCI compared with those without DCI, CSF levels of ficolin-1 and MBL tended to increase slightly more over time (p_interaction = 0.021 and 0.033, respectively); however, no association was found after adjustments for confounders and multiple testing (p-adj_interaction = 0.086 and 0.098, respectively). Plasma ficolin-1 and ficolin-3 were lower in SAH patients compared with healthy controls on all days. DCI and functional outcome were not associated with LCP initiator levels in plasma. Patients with SAH displayed elevated CSF levels of ficolin-1, ficolin-2, ficolin-3, and MBL. Increased CSF levels of ficolin-1 and MBL were associated with a poor functional outcome. This study was a retrospective analysis of samples, which had been prospectively sampled and stored in a biobank. Registered at clinicaltrials.gov ( NCT01791257 , February 13, 2013, and NCT02320539 , December 19, 2014).

中文翻译:

蛛网膜下腔出血后凝集素补体途径启动子——一项观察性研究

这项探索性研究调查了蛛网膜下腔出血 (SAH) 患者脑脊液 (CSF) 和血浆中凝集素补体途径 (LCP) 引发剂的时间过程,以及它们与迟发性脑缺血 (DCI) 和功能结果的关系。分析了 SAH 患者脑脊液和血浆中 ficolin-1、ficolin-2、ficolin-3 和甘露糖结合凝集素 (MBL) 的浓度。从入院到第 9 天(CSF;N_PATIENTS = 63,n_SAMPLES = 399)和第 8 天(血浆;N_PATIENTS = 50,n_SAMPLES = 358),每天收集样本。12 名接受脊髓麻醉的神经系统健康患者和 12 名健康献血者作为对照。登记患者住院期间 DCI 的发展和 3 个月时的功能结果(改良 Rankin 量表)。入学时,与健康对照相比,SAH 患者的所有 LCP 引发剂的 CSF 水平均增加。患者的水平在几天内逐渐下降;然而,观察到 ficolin-1 的双相过程。在单变量分析中,所有 LCP 引发剂的脑脊液水平升高与不良的功能结果相关。在调整混杂因素(年龄、性别、临床严重程度、CT 成像的分布和血量)和多次测试(平均高 1.87 ng/mL,95% CI,平均高 1.17 至 2.99 和 1.69 ng/mL,95% CI,分别为 1.09 至 2.63)。与没有 DCI 的患者相比,发生 DCI 的患者的 CSF 中 ficolin-1 和 MBL 的水平往往会随着时间的推移略有增加(分别为 p_interaction = 0.021 和 0.033);然而,在调整混杂因素和多重测试后未发现关联(分别为 p-adj_interaction = 0.086 和 0.098)。与健康对照组相比,SAH 患者的血浆 ficolin-1 和 ficolin-3 在所有天数中均较低。DCI 和功能结果与血浆中的 LCP 引发剂水平无关。SAH 患者的脑脊液 ficolin-1、ficolin-2、ficolin-3 和 MBL 水平升高。ficolin-1 和 MBL 的 CSF 水平升高与功能预后不良有关。这项研究是对样本的回顾性分析,这些样本已经预先取样并存储在生物库中。在clinicaltrials.gov注册(NCT01791257,2013年2月13日,NCT02320539,2014年12月19日)。与健康对照组相比,SAH 患者的血浆 ficolin-1 和 ficolin-3 在所有天数中均较低。DCI 和功能结果与血浆中的 LCP 引发剂水平无关。SAH 患者的脑脊液 ficolin-1、ficolin-2、ficolin-3 和 MBL 水平升高。ficolin-1 和 MBL 的 CSF 水平升高与功能预后不良有关。本研究是对样本的回顾性分析,这些样本已预先取样并存储在生物库中。在clinicaltrials.gov注册(NCT01791257,2013年2月13日,NCT02320539,2014年12月19日)。与健康对照组相比,SAH 患者的血浆 ficolin-1 和 ficolin-3 在所有天数中均较低。DCI 和功能结果与血浆中的 LCP 引发剂水平无关。SAH 患者的脑脊液 ficolin-1、ficolin-2、ficolin-3 和 MBL 水平升高。ficolin-1 和 MBL 的 CSF 水平升高与功能预后不良有关。本研究是对样本的回顾性分析,这些样本已预先取样并存储在生物库中。在clinicaltrials.gov注册(NCT01791257,2013年2月13日,NCT02320539,2014年12月19日)。ficolin-1 和 MBL 的 CSF 水平升高与功能预后不良有关。本研究是对样本的回顾性分析,这些样本已预先取样并存储在生物库中。在clinicaltrials.gov注册(NCT01791257,2013年2月13日,NCT02320539,2014年12月19日)。ficolin-1 和 MBL 的 CSF 水平升高与功能预后不良有关。本研究是对样本的回顾性分析,这些样本已预先取样并存储在生物库中。在clinicaltrials.gov注册(NCT01791257,2013年2月13日,NCT02320539,2014年12月19日)。
更新日期:2020-11-12
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