Sepsis remains one of the most serious medical emergencies. It develops when the body responds to an infection in a way that injures its own organs. Patients can deteriorate quickly, and delays in treatment raise the risk of severe complications or death. Diagnosing sepsis early is challenging because symptoms may be subtle or resemble other conditions. Clinicians use criteria such as Sepsis-2 or Sepsis-3 and laboratory markers, and blood cultures are considered the traditional test for confirming infection. However, blood cultures can take time and may be negative even in patients who clearly show signs of sepsis. These limitations have motivated researchers to examine new biomarkers that could support faster and more reliable diagnosis.
A new meta-analysis takes a comprehensive look at one such biomarker: presepsin, a molecule released as part of the immune system’s response to infection. Individual studies over the past decade have explored presepsin’s diagnostic usefulness, but the results have varied. To bring clarity, the authors systematically reviewed data from multiple studies to evaluate how accurately presepsin helps identify sepsis across different clinical settings and patient groups.
A Broad Review of the Evidence
The researchers examined almost two thousand articles and ultimately included 47 studies involving more than 7,000 patients. Most of these studies were prospective and conducted in hospital settings such as emergency departments, wards, and intensive care units. The authors evaluated each study using established quality assessment methods and applied statistical models commonly used for diagnostic accuracy research.
Their analysis produced clear, overarching results: presepsin demonstrated high diagnostic accuracy. Across all included studies, it showed strong ability to correctly identify patients with sepsis as well as those without it. The summary measures of accuracy indicate that presepsin performs consistently well overall.
Notable Strength in Neonates
One of the most striking findings of the meta-analysis was the difference in presepsin’s performance across age groups. When the authors compared adults, children, and neonates, neonates showed the most robust diagnostic accuracy. In this group, presepsin reached the highest levels of sensitivity, specificity, and overall diagnostic performance.
The authors suggest that physiological and immune differences in newborns may contribute to these results. For clinicians and researchers working in neonatal intensive care units—where early recognition of sepsis is critically important—this finding highlights presepsin as a particularly promising tool.
Children also showed good diagnostic performance, though fewer studies were available. Adults displayed strong but slightly lower accuracy than neonates. These age-related differences provide valuable direction for future research and potential clinical application.
The Role of Diagnostic Standards
A key contribution of the study is its exploration of how different diagnostic standards used in the original research affected presepsin’s performance. Some studies used positive blood culture results, others relied on Sepsis-2 or Sepsis-3 criteria, and some used clinical judgment alone.
Presepsin showed its highest accuracy in studies that used blood culture as the reference standard. Performance was lower in studies that relied solely on clinical criteria. This variation illustrates the difficulty of sepsis research more broadly: without a single, universally applied diagnostic standard, biomarker results can differ depending on how “sepsis” is defined in each study.
The authors note that these inconsistencies are one reason why earlier research on presepsin seemed contradictory. Their work helps place these varied results into a clearer, more organized context.
Laboratory Method and Sample Type Matter
Beyond clinical factors, the meta-analysis also examined how laboratory procedures influenced diagnostic accuracy. Studies that used whole blood samples reported stronger performance than those using other sample types. Most studies used chemiluminescent enzyme immunoassay as the testing method, and these tended to produce high sensitivity and specificity.
These findings suggest that standardized laboratory approaches may improve consistency in presepsin measurement. For researchers developing future studies, the analysis offers guidance on which methods yield more stable results.
Interpreting the Findings: A Supportive, Not Standalone, Tool
Even with these encouraging results, the authors do not present presepsin as a replacement for current diagnostic approaches. Instead, they describe it as a supportive tool that can complement clinical evaluation and existing criteria. The biomarker’s ability to improve early recognition could be valuable in multiple hospital settings, especially neonatal care.
The authors also acknowledge several limitations of the current evidence. The studies they analyzed showed substantial variation in patient populations, laboratory methods, and diagnostic standards. Most studies were conducted in intensive care or emergency settings, which may not represent all patient groups. Pediatric data, apart from neonates, remain limited. In addition, many studies did not distinguish between different types of infection such as bacterial, fungal, or viral causes of sepsis.
While these factors introduce uncertainty, they do not diminish the overall conclusion: presepsin shows genuine potential to support earlier and more reliable detection of sepsis.
Implications for Researchers
For researchers, this meta-analysis provides a consolidated and structured overview of presepsin’s diagnostic value. It highlights:
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strong overall accuracy across diverse clinical settings
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particularly high performance in neonates
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the impact of diagnostic standards and laboratory methods
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areas where evidence remains limited and where further research is needed
The findings may guide future study designs, encourage more standardized methods, and support investigations into how presepsin might work alongside other biomarkers or clinical scoring systems.
The translation of the preceding English text in Chinese:
脓毒症仍然是最严重的医疗急症之一。它发生在身体对感染作出反应并导致自身器官受损时。患者可能迅速恶化，而治疗延迟会增加严重并发症或死亡的风险。早期诊断脓毒症具有挑战性，因为症状可能不明显，或类似其他疾病。临床医生使用 Sepsis-2 或 Sepsis-3 等诊断标准以及实验室指标，而血培养被视为确认感染的传统方法。然而，血培养需要时间，即使患者明显符合脓毒症表现，其结果也可能为阴性。这些局限性促使研究者继续寻找能够帮助实现更快速、更可靠诊断的新型生物标志物。
一项新的荟萃分析全面评估了其中一种候选标志物：presepsin，它是在免疫系统对感染作出反应时释放的分子。过去十年的多项研究探讨了 presepsin 的诊断价值，但结果有所差异。为此，作者系统地整合了多项研究的数据，以评估 presepsin 在不同临床环境和不同患者群体中的诊断准确性。
对现有证据的广泛审查
研究者检索了近两千篇文献，最终纳入了 47 项研究，共涉及 7,000 多名患者。大多数研究为前瞻性研究，开展于急诊、普通病房或重症监护病房。作者使用既定的质量评估方法对每项研究进行评价，并应用常用于诊断准确性研究的统计模型。
分析结果清晰而一致：presepsin 显示出较高的诊断准确性。在所有纳入研究中，它都表现出良好的能力去区分有无脓毒症的患者。整体准确性指标说明 presepsin 的诊断表现总体稳定。
在新生儿中的显著优势
荟萃分析最引人注目的发现之一是 presepsin 在不同年龄组中的表现差异。当作者比较成人、儿童和新生儿三组时，新生儿组表现出最强的诊断准确性。在这一人群中，presepsin 的敏感度、特异度和总体诊断表现均达到最高水平。
作者指出，新生儿在生理和免疫方面的差异可能促成了这一结果。对于在新生儿重症监护室工作的临床医生和研究人员而言——在这一领域，早期识别脓毒症至关重要——这一发现显示 presepsin 是极具潜力的工具。
儿童组也表现出良好的诊断能力，但相关研究数量较少。成人组的准确性较强，但略低于新生儿。不同年龄段的这一差异为未来研究方向和潜在应用提供了重要线索。
诊断标准的影响
该研究的一项重要贡献是探讨了原始研究中采用的不同诊断标准如何影响 presepsin 的表现。有些研究使用血培养阳性作为标准，另一些使用 Sepsis-2 或 Sepsis-3 标准，还有一些仅依赖临床判断。
在使用血培养作为参考标准的研究中，presepsin 的准确性最高；而仅使用临床标准时，表现较弱。这一差异反映了脓毒症研究的普遍困境：由于缺乏单一、统一的诊断标准，不同研究对“脓毒症”的定义并不一致，导致生物标志物的研究结果出现差异。
作者指出，这些不一致性是先前研究结果互相矛盾的重要原因，而本研究的整理为这些差异提供了更清晰的解释框架。
实验方法与样本类型的重要性
除了临床因素外，该荟萃分析还研究了实验室操作对诊断准确性的影响。使用全血样本的研究报告了更强的诊断性能，而使用其他样本类型的表现略弱。多数研究采用化学发光酶免疫分析方法，而这些研究往往获得较高的敏感度和特异度。
这些发现提示，标准化实验流程可能有助于提升 presepsin 测量的稳定性。对于未来开展相关研究的团队，该分析为实验方法选择提供了参考。
结果解读：辅助工具，而非独立诊断手段
尽管结果令人鼓舞，作者并未将 presepsin 视为替代现有诊断方法的工具。相反，他们认为它是一个辅助指标，可与临床评估和现行标准互补。其提升早期识别能力的潜力在多种医院环境中可能具有价值，特别是在新生儿领域。
作者也指出了当前证据的多个局限性。纳入研究在人群、实验方法和诊断标准方面存在较大差异；多数研究在重症或急诊环境中进行，可能不适用于所有患者；除了新生儿外，儿童数据仍然有限。此外，许多研究未区分由细菌、真菌或病毒引起的不同类型感染。
尽管存在这些不确定性，总体结论仍然明确：presepsin 在提高脓毒症的早期和可靠识别方面具有真实潜力。
对研究者的意义
对于研究者而言，这项荟萃分析提供了一个结构化、整合性的综述，展示了 presepsin 的诊断价值。其要点包括：
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在多种临床环境中具有较强的总体准确性
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在新生儿人群中表现尤为突出
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诊断标准和实验方法对结果有明显影响
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仍存在证据不足之处，需要进一步研究
这些发现可为未来研究设计提供方向，促进实验方法更标准化，并支持探索 presepsin 与其他生物标志物或临床评分系统的联合应用。
Reference:
Presepsin as a diagnostic biomarker for sepsis across neonates, children, and adults: A meta-analysis.
Biomol Biomed [Internet]. 2025 Aug. 20 [cited 2025 Dec. 10];26(2):307–319.
Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/12909
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