Supplementary data: Blood neurofilament light chain as a predictive biomarker for functional outcome of acute ischemic stroke: a systematic review and meta-analysis

These are peer-reviewed supplementary materials for the article 'Blood neurofilament light chain as a predictive biomarker for functional outcome of acute ischemic stroke: a systematic review and meta-analysis' published in the Journal of Comparative Effectiveness Research.Supplemental Table 1: Search strategyAim: Ischemic stroke continues to be a significant contributor to mortality and disability on a global scale. The blood neurofilament light chain (bNfL) as a prognostic indicator for stroke functional outcomes is a topic of ongoing debate. Thus, the objective of this systematic review is to assess the efficacy of bNfL as a predictor of stroke functional outcomes. Materials & methods: A systematic search was conducted in Pubmed, Cochrane and Embase databases from their inception to 21 October 2023. Two reviewers independently screened the search results to identify studies reporting on the association between bNfL and acute ischemic stroke outcomes. The quality of the studies was assessed using the Newcastle–Ottawa scale. Meta-analysis was conducted using the Comprehensive Meta-Analysis software Stata 12.0, utilizing a random effects model to estimate the pooled effect. Results: Nine studies involving 2302 patients were included in the analysis. A pooled analysis of adjusted odds ratios (ORs) from multivariate regression models in the meta-analysis revealed a pooled adjusted OR of 1.929 [95% CI:1.459, 2.550], suggesting that the patients with higher bNfL levels are at a greater risk of experiencing unfavorable functional outcomes compared with those with lower bNfL levels. Subgroup analysis indicated that factors such as sampling time, study region, participant age, blood specimen and sample size, may contributed to high heterogeneity in the results. After conducting a thorough analysis using funnel plot and Egger’s test, no significant evidence of publication bias was found in our study. Conclusion: In summary, bNfL demonstrates potential as a predictive biomarker for functional outcomes in acute ischemic stroke patients, albeit subject to influence from confounding variables. Additional rigorously designed and meticulously executed prospective studies on a larger scale are warranted to validate these findings.

本材料为发表于《比较效果研究杂志》（Journal of Comparative Effectiveness Research）的论文《血液神经丝轻链作为急性缺血性卒中功能结局的预测生物标志物：一项系统评价与荟萃分析》的经同行评议补充材料。
补充表1：检索策略
研究背景与目的：缺血性卒中仍是全球范围内致死与致残的重要病因之一。血液神经丝轻链（blood neurofilament light chain，bNfL）作为卒中功能结局的预后指标，目前仍存在诸多争议。因此，本系统评价旨在评估bNfL作为卒中功能结局预测因子的效能。
研究方法：本研究于2023年10月21日前，检索自建库起的PubMed、Cochrane图书馆及Embase数据库。由2名研究者独立筛选检索结果，纳入报道bNfL与急性缺血性卒中结局关联的研究。采用纽卡斯尔-渥太华量表（Newcastle–Ottawa scale）对纳入研究的质量进行评价。使用Comprehensive Meta-Analysis软件及Stata 12.0进行荟萃分析，采用随机效应模型合并效应量。
研究结果：本研究共纳入9项研究，涉及2302例患者。对荟萃分析中多因素回归模型的校正比值比（adjusted odds ratios，ORs）进行合并分析后，得到校正合并OR值为1.929[95%置信区间（CI）：1.459, 2.550]，提示bNfL水平较高的患者相较于水平较低者，发生不良功能结局的风险更高。亚组分析显示，采样时间、研究地区、受试者年龄、血液标本类型及样本量等因素可能是导致研究结果存在高异质性的原因。通过漏斗图及Egger检验进行全面分析后，本研究未发现显著的发表偏倚证据。
结论：综上，bNfL具备作为急性缺血性卒中患者功能结局预测生物标志物的潜力，但其效能易受混杂变量的影响。未来需开展设计严谨、实施规范的大规模前瞻性研究，以验证本研究结果。