Data_Sheet_1_Time Course of Peripheral Leukocytosis and Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage.pdf

Objective: Systemic inflammation after subarachnoid hemorrhage (SAH) is implicated in delayed cerebral ischemia (DCI) and adverse clinical outcomes. We hypothesize that early changes in peripheral leukocytes will be associated with outcomes after SAH.
Methods: SAH patients admitted between January 2009 and December 2016 were enrolled into a prospective observational study and were assessed for Hunt Hess Scale (HHS) at admission, DCI, and modified Ranked Scale (mRS) at discharge. Total white blood cell (WBC) counts and each component of the differential cell count were determined on the day of admission (day 0) to 8 days after bleed (day 8). Global cerebral edema (GCE) was assessed on admission CT, and presence of any infection was determined. Statistical tests included student's t-test, Chi-square test, and multivariate logistic regression (MLR) models.
Results: A total of 451 subjects were analyzed. Total WBCs and neutrophils decreased initially reaching a minimum at day 4–5 after SAH. Monocyte count increased gradually after SAH and peaked between day 6–8, while basophils and lymphocytes decreased initially from day 0 to 1 and steadily increased thereafter. Neutrophil to lymphocyte ratio (NLR) reached a peak on day 1 and decreased thereafter. WBCs, neutrophils, monocytes, and NLR were higher in patients with DCI and poor functional outcomes. WBCs, neutrophils, and NLR were higher in subjects who developed infections. In MLR models, neutrophils and monocytes were associated with DCI and worse functional outcomes, while NLR was only associated with worse functional outcomes. Occurrence of infection was associated with poor outcome. Neutrophils and NLR were associated with infection, while monocytes were not. Monocytes were higher in males, and ROC curve analysis revealed improved ability of monocytes to predict DCI and poor functional outcomes in male subjects.
Conclusions: Monocytosis was associated with DCI and poor functional outcomes after SAH. The association between neutrophils and NLR and infection may impact outcomes. Early elevation in monocytes had an improved ability to predict DCI and poor functional outcomes in males, which was independent of the occurrence of infection.

【研究目的】蛛网膜下腔出血（subarachnoid hemorrhage, SAH）后发生的全身炎症反应与迟发性脑缺血（delayed cerebral ischemia, DCI）及不良临床结局密切相关。本研究假设外周白细胞的早期变化与SAH后的临床结局存在关联。

【研究方法】本研究纳入2009年1月至2016年12月期间入院的SAH患者，开展前瞻性观察研究。于患者入院时评估其亨特-赫斯量表（Hunt Hess Scale, HHS）评分，于出院时评估其DCI发生情况及改良Rankin量表（modified Rankin Scale, mRS）评分。分别于入院当日（第0天）至出血后第8天（第8天）检测白细胞（white blood cell, WBC）总数及白细胞分类计数的各项组分。于入院时的CT影像中评估全脑水肿（global cerebral edema, GCE）情况，并明确患者是否合并感染。本研究采用的统计学方法包括学生t检验、卡方检验及多因素logistic回归（multivariate logistic regression, MLR）模型。

【研究结果】本研究共纳入451例受试者并完成分析。SAH患者的白细胞总数及中性粒细胞计数初始呈下降趋势，于出血后第4~5天降至最低值。单核细胞计数在SAH后逐渐升高，并于第6~8天达到峰值；而嗜碱性粒细胞及淋巴细胞计数初始于第0~1天出现下降，此后逐步回升。中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio, NLR）于第1天达到峰值，此后逐渐下降。合并DCI及功能预后不良的患者，其白细胞总数、中性粒细胞、单核细胞计数及NLR水平均更高。发生感染的受试者，其白细胞总数、中性粒细胞计数及NLR水平均更高。多因素logistic回归分析显示，中性粒细胞及单核细胞计数与DCI及较差的功能预后相关，而NLR仅与较差的功能预后相关。感染的发生与不良临床结局显著相关。中性粒细胞计数及NLR与感染发生相关，而单核细胞计数与感染无关。男性受试者的单核细胞计数更高；受试者工作特征曲线（ROC curve）分析显示，单核细胞计数对男性受试者DCI发生及不良功能预后的预测能力更佳。

【研究结论】SAH后单核细胞增多与DCI发生及不良功能预后密切相关。中性粒细胞、NLR与感染的关联可能会对临床结局产生影响。男性受试者中，早期单核细胞计数升高对DCI发生及不良功能预后的预测能力更佳，且该关联不受感染发生的影响。