Background

Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor expressed on myeloid cells 1 (sTREM1), and soluble urokinase-type plasminogen activator receptor (suPAR) have shown promising results for predicting all-cause mortality in critical care patients. The aim of our systematic review and meta-analysis was to assess the prognostic value of these biomarkers for mortality in adult patients with sepsis.

Methods

A systematic literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases, for articles in English published from 01.01.1990 onwards, was conducted. The systematic review focused exclusively on observational studies of adult patients with sepsis, any randomized trials were excluded. For the meta-analysis, only studies which provide biomarker concentrations within 24 h of admission in sepsis survivors and nonsurvivors were included. Results are presented as pooled mean differences (MD) between nonsurvivors and survivors with 95% confidence interval for each of the six biomarkers. Studies not included in the quantitative analysis were narratively summarized. The risk of bias was assessed in all included studies using the Quality in Prognosis Studies (QUIPS) tool.

Results

The systematic literature search retrieved 2285 articles. In total, we included 44 studies in the qualitative analysis, of which 28 were included in the meta-analysis. The pooled mean differences in biomarker concentration (nonsurvivors − survivors), measured at onset of sepsis, are listed as follows: (1) Ang-1: − 2.9 ng/ml (95% CI − 4.1 to − 1.7, p < 0.01); (2) Ang-2: 4.9 ng/ml (95% CI 2.6 to 7.1, p < 0.01); (3) HMGB1: 1.2 ng/ml (95% CI 0.0 to 2.4, p = 0.05); (4) sRAGE: 1003 pg/ml (95% CI 628 to 1377, p < 0.01); (5) sTREM-1: 87 pg/ml (95% CI 2 to 171, p = 0.04); (6) suPAR: 5.2 ng/ml (95% CI 4.5 to 6.0, p < 0.01).

Conclusions

Ang-1, Ang-2, and suPAR provide beneficial prognostic information about mortality in adult patients with sepsis. The further development of standardized assays and the assessment of their performance when included in panels with other biomarkers may be recommended.Trial registration This study was recorded on PROSPERO, prospective register of systematic reviews, under the registration ID: CRD42018081226

中文翻译：

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使用六种生物标记物对成年败血症患者的死亡率进行预测：系统评价和荟萃分析

背景

血管生成素1（Ang-1）和2（Ang-2），高迁移率族1（HMGB1），晚期糖基化终产物（sRAGE）的可溶性受体，在髓样细胞1（sTREM1）上表达的可溶性触发受体和可溶性尿激酶型纤溶酶原激活物受体（suPAR）在预测重症监护患者的全因死亡率方面显示出令人鼓舞的结果。我们系统评价和荟萃分析的目的是评估这些生物标记物对败血症成年患者死亡率的预后价值。

方法

对MEDLINE，PubMed，EMBASE和Cochrane图书馆数据库进行了系统的文献检索，以查找1990年1月1日以后发布的英文文章。该系统评价仅侧重于败血症成年患者的观察性研究，任何随机试验均不包括在内。对于荟萃分析，仅包括败血症幸存者和非幸存者在入院后24小时内提供生物标志物浓度的研究。结果以非存活者和幸存者之间的合并平均差异（MD）表示，六个生物标记物中每一个的置信区间为95％。叙述性总结了未包括在定量分析中的研究。在所有纳入的研究中，均使用了预后研究质量（QUIPS）工具评估了偏倚风险。

结果

系统的文献检索检索了2285篇文章。我们总共在定性分析中纳入了44项研究，其中28项纳入了荟萃分析。脓毒症发作时测量的生物标志物浓度的合并平均差异（非存活者-存活者）如下：（1）Ang-1：-2.9 ng / ml（95％CI-4.1至-1.7，p  <0.01） ; （2）Ang-2：4.9 ng / ml（95％CI 2.6至7.1，p  <0.01）; （3）HMGB1：1.2 ng / ml（95％CI 0.0至2.4，p  = 0.05）; （4）sRAGE：1003 pg / ml（95％CI 628至1377，p  <0.01）; （5）sTREM-1：87 pg / ml（95％CI 2至171，p  = 0.04）; （6）suPAR：5.2 ng / ml（95％CI 4.5至6.0，p  <0.01）。

结论

Ang-1，Ang-2和suPAR提供有关败血症成年患者死亡率的有益预后信息。当与其他生物标志物一起纳入标本中时，建议进一步发展标准化测定方法并评估其性能。试验注册本研究记录在PROSPERO（系统评价的前瞻性注册）中，注册ID：CRD42018081226