目的:探讨中心粒细胞中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在出血性脑卒中患者神经外科术后感染性脑脊液中的水平以及其在诊断术后细菌性感染的价值。方法:选取2019年6月至2021年10月之间安徽医科大学第一附属医院神经外科收治入院的出血性脑卒中患者72例,所有患者接受神经外科手术治疗,根据是否术后颅内感染分为感染组40例与对照组32例。使用酶联免疫吸附试验检测脑脊液中NGAL水平,采用单因素分析与多因素分析方法对脑脊液生化/常规指标与NGAL水平进行分析,判断PNBM的独立危险因素。结果:在单因素分析中,感染组脑脊液糖和脑脊液糖/血糖显著低于非感染组,而脑脊液总蛋白、脑脊液白细胞、脑脊液红细胞和脑脊液NGAL水平显著高于非感染组,具有明显的统计学差异(P < 0.05)。将这些具有显著性差异的指标纳入多因素分析,结果显示,仅脑脊液NGAL具有显著性(P = 0.013, OR = 0.871)。受试者工作曲线分析显示,NGAL的AUC为0.936,具有良好的诊断效能。结论:脑脊液NGAL是出血性脑卒中患者神经外科术后细菌性颅内感染患者的独立危险因素。 Objective: To investigate the diagnostic efficacy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) for post-neurosurgical bacterial meningitis (PNBM) in the patients with hemorrhagic stroke. Meth-od: A total of 72 patients were recruited from the First Affiliated Hospital of Anhui Medical Univer-sity during June 2019 to October 2021. All patients received neurosurgical treatments. According to the infection status, we divided all patients into infection group and non-infection group. En-zyme-linked immuno sorbent assay was applied for detection of NGAL level in cerebrospinal fluid (CSF). Univariate and multivariate analyses were applied in statistical analysis for determining the independent risk for PNBM. Results: In the univariate analysis, the levels of CSF glucose and CSF/blood glucose ratio in the infection group were significantly higher than that in the non-infection group (P < 0.05). The levels of CSF protein, white blood cell, red blood cell and NGAL were significantly lower than that in the non-infection group (P < 0.05). In the multivariate analysis, CSF NGAL was proved to be the independent risk for PNBM (P = 0.013, OR = 0.871). The receiver operating curve analysis showed that the area under the curve for NGAL was 0.936, indicating that it played an excellent diagnostic efficacy in PNBM. Conclusion: CSF NGAL could be served as an in-dependent risk for PNBM in the patients with hemorrhagic stroke.
目的:探讨中心粒细胞中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在出血性脑卒中患者神经外科术后感染性脑脊液中的水平以及其在诊断术后细菌性感染的价值。方法:选取2019年6月至2021年10月之间安徽医科大学第一附属医院神经外科收治入院的出血性脑卒中患者72例,所有患者接受神经外科手术治疗,根据是否术后颅内感染分为感染组40例与对照组32例。使用酶联免疫吸附试验检测脑脊液中NGAL水平,采用单因素分析与多因素分析方法对脑脊液生化/常规指标与NGAL水平进行分析,判断PNBM的独立危险因素。结果:在单因素分析中,感染组脑脊液糖和脑脊液糖/血糖显著低于非感染组,而脑脊液总蛋白、脑脊液白细胞、脑脊液红细胞和脑脊液NGAL水平显著高于非感染组,具有明显的统计学差异(P < 0.05)。将这些具有显著性差异的指标纳入多因素分析,结果显示,仅脑脊液NGAL具有显著性(P = 0.013, OR = 0.871)。受试者工作曲线分析显示,NGAL的AUC为0.936,具有良好的诊断效能。结论:脑脊液NGAL是出血性脑卒中患者神经外科术后细菌性颅内感染患者的独立危险因素。
细菌性脑膜炎,神经外科术,中性粒细胞明胶酶相关脂质运载蛋白,脑脊液,诊断
Ziao Xu, Hongwei Cheng*, Lei Ye, Xingliang Dai, Peng Gao, Yan Li
Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei Anhui
Received: Oct. 14th, 2022; accepted: Nov. 9th, 2022; published: Nov. 16th, 2022
Objective: To investigate the diagnostic efficacy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) for post-neurosurgical bacterial meningitis (PNBM) in the patients with hemorrhagic stroke. Method: A total of 72 patients were recruited from the First Affiliated Hospital of Anhui Medical University during June 2019 to October 2021. All patients received neurosurgical treatments. According to the infection status, we divided all patients into infection group and non-infection group. Enzyme-linked immuno sorbent assay was applied for detection of NGAL level in cerebrospinal fluid (CSF). Univariate and multivariate analyses were applied in statistical analysis for determining the independent risk for PNBM. Results: In the univariate analysis, the levels of CSF glucose and CSF/blood glucose ratio in the infection group were significantly higher than that in the non-infection group (P < 0.05). The levels of CSF protein, white blood cell, red blood cell and NGAL were significantly lower than that in the non-infection group (P < 0.05). In the multivariate analysis, CSF NGAL was proved to be the independent risk for PNBM (P = 0.013, OR = 0.871). The receiver operating curve analysis showed that the area under the curve for NGAL was 0.936, indicating that it played an excellent diagnostic efficacy in PNBM. Conclusion: CSF NGAL could be served as an independent risk for PNBM in the patients with hemorrhagic stroke.
Keywords:Bacterial Meningitis, Neurosurgery, Neutrophil Gelatinase-Associated Lipocalin, Cerebrospinal Fluid, Diagnosis
Copyright © 2022 by author(s) and Hans Publishers Inc.
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神经外科术后颅内感染(post-neurosurgical bacterial meningitis, PNBM)是一种严重的手术并发症,对接受神经外科手术的患者会造成严重的继发性损伤,影响患者神经功能的恢复 [
选取2019年6月至2021年10月之间安徽医科大学第一附属医院神经外科收治入院的出血性脑卒中患者72例,所有患者接受神经外科手术治疗。出血性脑卒中的诊断由2名副高级职称医师进行。术后颅内感染的诊断原则参考《神经外科中枢神经系统感染诊治中国专家共识(2021版)》 [
根据是否术后颅内感染分为感染组40例与对照组32例。分别记录所有患者年龄、性别、原发病、脑脊液生化、脑脊液常规等临床流行病学指标。两组间年龄、性别等均无统计学差异,见表1。本研究或安徽医科大学第一附属医院伦理委员会批准。所有患者或直系亲属均对本研究方案签署知情同意书。
感染组(n = 40) | 非感染组(n = 32) | 检验值(χ2/t/Z) | P值 | ||
---|---|---|---|---|---|
年龄(岁) | 54.73 ± 18.36 | 57.81 ± 15.05 | −0.767a | 0.446 | |
性别 | 1.611b | 0.204 | |||
男 | 19 | 12 | |||
女 | 21 | 20 | |||
原发疾病 | 0.101b | 0.751 | |||
蛛网膜下腔出血 | 21 | 18 | |||
脑出血 | 19 | 14 | |||
脑脊液指标 | |||||
糖(mmol/L) | 1.58 (1.13, 1.96) | 3.44 (2.81, 4.04) | −5.724c | <0.001 | |
总蛋白(g/L) | 3.00 (1.95, 4.88) | 0.80 (0.53, 1.25) | −5.890c | <0.001 | |
白细胞(x106/L) | 859.50 (340.75, 3653.50) | 23.00 (7.25, 99.50) | −6.108c | <0.001 | |
红细胞(x106/L) | 13000 (275, 94000) | 3000 (500, 9000) | −2.065c | 0.039 | |
多形核细胞比例(%) | 79.50 (52.40, 89.50) | 35.80 (19.03, 80.40) | −2.862c | 0.004 | |
氯(mmol/L) | 120.33 + 10.15 | 122.73 ± 8.59 | −1.065b | 0.290 | |
血糖(mmol/L) | 6.31 (5.37, 7.52) | 6.72 (5.35, 8.61) | −0.306c | 0.760 | |
脑脊液糖/血糖 | 0.25 (0.15, 0.33) | 0.57 (0.39, 0.64) | −5.610c | <0.001 | |
脑脊液压力 (mmH2O) | 180 (120, 270) | 165 (115, 274) | −0.140c | 0.888 | |
NGAL (ng/mL) | 61.28 ± 10.62 | 24.60 ± 17.52 | 10.971b | <0.001 |
表1. 患者的临床流行病学资料及单因素分析
注:a:t值;b:χ2值;c:Z值。
所有患者均在术后疑似颅内感染背景下行腰穿操作,该操作在无菌条件下进行。每名患者留取2 ml脑脊液样本,收集的脑脊液样本放入无菌无酶离心管中,置于−80℃冰箱长期保存。脑脊液NGAL水平检测采用酶联免疫吸附试验(enzyme-linked immuno sorbent assay, ELISA)。试剂盒由武汉Elabscience公司提供(货号:E-EL-H6127)。
对两组患者的脑脊液生化、脑脊液常规、脑脊液NGAL水平进行检测,利用受试者工作曲线(receiver operating curve, ROC)分析PNBM独立危险因素指标在神经外科术后颅内细菌性感染中的诊断效能,并判断其灵敏性和特异性。
以SPSS 19.0软件进行统计学分析。若连续变量符合正态分布,数据以均数 ± 标准差( x ¯ ± s )表示,两组之间的比较采用独立样本t检验;若连续变量不符合正态分布,数据以中位数[四分位数]形式表示,两组之间的比较采用Mann-Whitney U检验;计数资料采用卡方检验。多因素分析采用logistic回归模型进行分析。多种指标之间的相关性分析采用Spearman’s相关性分析进行。P < 0.05表示差异有统计学意义。
感染组与非感染组在脑脊液糖、脑脊液总蛋白、脑脊液白细胞、脑脊液红细胞、脑脊液糖/血糖和脑脊液NGAL含量之间存在显著的统计学意义(P < 0.05),感染组脑脊液糖和脑脊液糖/血糖显著低于非感染组,而脑脊液总蛋白、脑脊液白细胞、脑脊液红细胞和脑脊液NGAL水平显著高于非感染组。感染组与非感染组在年龄、性别、原发疾病、脑脊液氯、血糖和脑脊液压力等指标间无明显统计学差异(P > 0.05) (见表1)。
将单因素分析感染组与非感染组之间存在显著性差异的指标纳入多因素分析,结果显示,仅脑脊液NGAL显示出统计学差异。为PNBM的独立危险因素(见表2)。
将多因素分析中统计学阳性的脑脊液NGAL水平绘制受试者工作曲线(receiver operating curve, ROC) (见图1),计算其曲线下面积(area under the curve, AUC)。结果显示,脑脊液NGAL的AUC为0.936,灵敏性为84.38%,特异性为100% (见表3)。该结果提示脑脊液NGAL具有较好的诊断效能。
B值 | Wals值 | P值 | OR | 95% CI | |
---|---|---|---|---|---|
脑脊液糖 | 1.125 | 0.908 | 0.177 | 3.403 | 0.575~20.152 |
脑脊液蛋白 | −1.235 | 0.836 | 0.140 | 0.291 | 0.056~1.497 |
脑脊液白细胞 | <0.001 | 0.001 | 0.977 | 1.000 | 9.997~1.002 |
脑脊液多形核细胞 | −0.025 | 0.034 | 0.468 | 0.976 | 0.912~1.043 |
脑脊液红细胞 | <0.001 | <0.001 | 0.955 | 1.000 | 1.000~1.000 |
脑脊液糖/血糖 | 8.555 | 6.525 | 0.190 | 5192.197 | 0.015~1.859 * 109 |
NGAL | −0.138 | 0.056 | 0.013 | 0.871 | 0.781~0.972 |
表2. 脑脊液指标的多因素分析
图1. 脑脊液NGAL水平的ROC曲线
AUC | 灵敏性 | 特异性 | 截断值(ng/mL) |
---|---|---|---|
0.936 | 84.38 | 100 | 47.5 |
表3. NGAL诊断效能分析
神经外科术后颅内感染是一种严重的手术相关并发症,严重影响患者神经功能的恢复。接受神经外科手术的患者常因为血脑屏障的破坏,中枢神经系统的免疫功能长期降低。此外,引流管的应用会大大增加感染的风险等因素,导致颅内感染在一定程度上不可避免 [
细菌性颅内感染最常见的临床症状是发热和颅内高压。然而,在一些神经外科疾病当中,例如出血性脑卒中、脑室内出血等,常伴有颅内的炎症反应、脑损伤和温度调节失常等病理生理学变化。在这些疾病当中,也可能存在发热症状 [
NGAL可由中性粒细胞和单核细胞产生和储存,但也有报道显示星形胶质细胞和脉络膜细胞也可以产生NGAL [
本研究存在一定的缺陷。首先,在所纳入的所有患者中,仅有6人的细菌培养为阳性,所以我们无法判断NGAL在特定细菌感染中的价值。在后期研究中,我们需要尽量收集细菌培养阳性的样本,以便探索NGAL与特定细菌感染类型之间的关系。其次,所有纳入研究的样本为出血性脑卒中样本,缺乏正常人的脑脊液样本,故而我们不清楚出血性脑卒中这种神经系统原发性疾病对其是否会产生影响。
综上所述,脑脊液NGAL是出血性脑卒中患者神经外科术后细菌性颅内感染患者的独立危险因素,具有潜在的诊断价值,应在扩大的样本中进行进一步验证,以探索其临床实际应用价值。
国家自然科学基金,81901238。
许子骜,程宏伟,叶 雷,代兴亮,高 鹏,李 严. 脑脊液NGAL含量在出血性脑卒中患者神经外科术后颅内细菌性感染中的诊断效能分析Diagnostic Analysis of Neutrophil Gelatinase-Associated Lipocalin Levels in CSF on Post-Neurosurgical Bacterial Meningitis for the Patients with Hemorrhagic Stroke[J]. 临床医学进展, 2022, 12(11): 10206-10212. https://doi.org/10.12677/ACM.2022.12111471