Unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy: an updated meta-analysis
Abstract Background Sepsis-associated encephalopathy (SAE) is characterized by brain dysfunction in the context of sepsis and frequently leads to significant cognitive and neurological impairments, as well as an elevated risk of mortality. Accurate diagnosis of SAE is crucial for the timely initiati...
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2025-02-01
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| Online Access: | https://doi.org/10.1186/s13643-025-02784-5 |
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| author | Jiyun Hu Wenchao Li Shucai Xie Ya Liao Tao Chen Xinrun Wang Weiping Xia Fang Huang Zhaoxin Qian Lina Zhang |
| author_facet | Jiyun Hu Wenchao Li Shucai Xie Ya Liao Tao Chen Xinrun Wang Weiping Xia Fang Huang Zhaoxin Qian Lina Zhang |
| author_sort | Jiyun Hu |
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| description | Abstract Background Sepsis-associated encephalopathy (SAE) is characterized by brain dysfunction in the context of sepsis and frequently leads to significant cognitive and neurological impairments, as well as an elevated risk of mortality. Accurate diagnosis of SAE is crucial for the timely initiation of optimal treatment and appropriate patient management. Neurogenic biomarkers hold promise as reliable serum diagnostic tools for the detection and longitudinal monitoring of SAE. This meta-analysis seeks to evaluate the diagnostic and prognostic utility of serum neurogenic biomarkers in patients with SAE. Methods The study protocol was registered in the PROSPERO database (CRD42023408312) and conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis was conducted to comprehensively and critically evaluate the existing body of evidence regarding the use of serum neurogenic biomarkers: neuron-specific enolase (NSE), ubiquitin C-terminal hydrolase-L1 (UCH-L1), Tau, S100 calcium-binding protein β (S100β), and glial fibrillary acidic protein (GFAP) for the diagnosis and risk assessment of fatality in SAE. We conducted a systematic search of electronic bibliographic databases, including PubMed, Web of Science, Embase, Cochrane databases, CNKI, CQVIP, and WFSD. The quality and risk of bias of the selected studies were assessed using the QUADAS-2 tool. For biomarkers reported in two or more studies, pooled standardized mean differences and 95% confidence intervals were calculated. Heterogeneity among the included studies was examined using the I 2 statistic and random-effects model was applied owing to large heterogeneity. Results Forty-two studies were included in our meta-analysis. The levels of serum neurogenic biomarkers were significantly higher in patients with SAE as compared to septic patients with no-encephalopathy (NE): NSE (standardized mean difference (SMD) 1.98 (95% CI 1.55–2.42), P < 0.00001); UCH-L1 (SMD 1.75 (95% CI 0.90–2.59), P < 0.0001); Tau (SMD 1.14 (95% CI 1.01–1.28), P < 0.00001); S100β (SMD 1.82 (95% CI 1.45–2.19), P < 0.00001); and GFAP (SMD 3.63 (95% CI 1.85–5.41), P < 0.0001). In addition, significantly lower serum neurogenic biomarkers levels were noted in septic patients with survivors as compared to non-survivors: NSE (SMD − 1.87 (95% CI − 2.43 to − 1.32), P < 0.00001); UCH-L1 (SMD − 1. 71 (95% CI − 2.24 to − 1.19), P < 0.00001); Tau (SMD − 0.57 (95% CI − 0.79 to − 0.35), P < 0.00001); S100β (SMD − 1.34 (95% CI − 1.88 to − 0.80), P < 0.00001). However, no significant differences in serum GFAP levels [SMD -7.98 (95% CI − 22.23–6.27), P = 0.27) were found between the surviving and non-surviving groups. Conclusion The increased serum neurogenic biomarkers may be predictive of SAE and mortality for septic patients, which are expected to be applied as a reliable blood-based diagnostic tool for detection and longitudinal monitoring in SAE patients. However, results should be interpreted with caution due to the high heterogeneity among studies. |
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| institution | Kabale University |
| issn | 2046-4053 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Systematic Reviews |
| spelling | doaj-art-08ae256ce67646bb9cda792cdf7cef192025-02-09T12:15:06ZengBMCSystematic Reviews2046-40532025-02-0114111510.1186/s13643-025-02784-5Unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy: an updated meta-analysisJiyun Hu0Wenchao Li1Shucai Xie2Ya Liao3Tao Chen4Xinrun Wang5Weiping Xia6Fang Huang7Zhaoxin Qian8Lina Zhang9Department of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaDepartment of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ChangshaAbstract Background Sepsis-associated encephalopathy (SAE) is characterized by brain dysfunction in the context of sepsis and frequently leads to significant cognitive and neurological impairments, as well as an elevated risk of mortality. Accurate diagnosis of SAE is crucial for the timely initiation of optimal treatment and appropriate patient management. Neurogenic biomarkers hold promise as reliable serum diagnostic tools for the detection and longitudinal monitoring of SAE. This meta-analysis seeks to evaluate the diagnostic and prognostic utility of serum neurogenic biomarkers in patients with SAE. Methods The study protocol was registered in the PROSPERO database (CRD42023408312) and conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis was conducted to comprehensively and critically evaluate the existing body of evidence regarding the use of serum neurogenic biomarkers: neuron-specific enolase (NSE), ubiquitin C-terminal hydrolase-L1 (UCH-L1), Tau, S100 calcium-binding protein β (S100β), and glial fibrillary acidic protein (GFAP) for the diagnosis and risk assessment of fatality in SAE. We conducted a systematic search of electronic bibliographic databases, including PubMed, Web of Science, Embase, Cochrane databases, CNKI, CQVIP, and WFSD. The quality and risk of bias of the selected studies were assessed using the QUADAS-2 tool. For biomarkers reported in two or more studies, pooled standardized mean differences and 95% confidence intervals were calculated. Heterogeneity among the included studies was examined using the I 2 statistic and random-effects model was applied owing to large heterogeneity. Results Forty-two studies were included in our meta-analysis. The levels of serum neurogenic biomarkers were significantly higher in patients with SAE as compared to septic patients with no-encephalopathy (NE): NSE (standardized mean difference (SMD) 1.98 (95% CI 1.55–2.42), P < 0.00001); UCH-L1 (SMD 1.75 (95% CI 0.90–2.59), P < 0.0001); Tau (SMD 1.14 (95% CI 1.01–1.28), P < 0.00001); S100β (SMD 1.82 (95% CI 1.45–2.19), P < 0.00001); and GFAP (SMD 3.63 (95% CI 1.85–5.41), P < 0.0001). In addition, significantly lower serum neurogenic biomarkers levels were noted in septic patients with survivors as compared to non-survivors: NSE (SMD − 1.87 (95% CI − 2.43 to − 1.32), P < 0.00001); UCH-L1 (SMD − 1. 71 (95% CI − 2.24 to − 1.19), P < 0.00001); Tau (SMD − 0.57 (95% CI − 0.79 to − 0.35), P < 0.00001); S100β (SMD − 1.34 (95% CI − 1.88 to − 0.80), P < 0.00001). However, no significant differences in serum GFAP levels [SMD -7.98 (95% CI − 22.23–6.27), P = 0.27) were found between the surviving and non-surviving groups. Conclusion The increased serum neurogenic biomarkers may be predictive of SAE and mortality for septic patients, which are expected to be applied as a reliable blood-based diagnostic tool for detection and longitudinal monitoring in SAE patients. However, results should be interpreted with caution due to the high heterogeneity among studies.https://doi.org/10.1186/s13643-025-02784-5Sepsis-associated encephalopathyNSES100βGFAPUCH-1Tau |
| spellingShingle | Jiyun Hu Wenchao Li Shucai Xie Ya Liao Tao Chen Xinrun Wang Weiping Xia Fang Huang Zhaoxin Qian Lina Zhang Unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy: an updated meta-analysis Systematic Reviews Sepsis-associated encephalopathy NSE S100β GFAP UCH-1 Tau |
| title | Unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy: an updated meta-analysis |
| title_full | Unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy: an updated meta-analysis |
| title_fullStr | Unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy: an updated meta-analysis |
| title_full_unstemmed | Unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy: an updated meta-analysis |
| title_short | Unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy: an updated meta-analysis |
| title_sort | unveiling neurogenic biomarkers for the differentiation between sepsis patients with or without encephalopathy an updated meta analysis |
| topic | Sepsis-associated encephalopathy NSE S100β GFAP UCH-1 Tau |
| url | https://doi.org/10.1186/s13643-025-02784-5 |
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