Research Progress of Biomarkers of Sepsis-Associated Encephalopathy

Tang, ChengXin; Zhou, WuShuang; Chen, Xiaoying; Wang, FengLin; Men, WenXian; Liu, JingLun; Zhang, Dan

doi:10.1007/s44231-022-00023-2

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…Early identification of sepsis-associated encephalopathy, one of the most serious clinical manifestations of sepsis (31), would provide a more accurate diagnosis and prognosis, which now relies on nonspecific clinical manifestations and imaging features, often followed by lumbar punctures and electroencephalograms. Several biomarkers have been proposed for the rapid detection of sepsis-related brain injury (32), including serum GFAP and UCH-L1, which correlate with the occurrence, severity, and prognosis of sepsis-associated encephalopathy (33, 34). We found higher levels of GFAP in acute CNS-involved sepsis, and these higher levels of serum GFAP at the time of hospitalization correlated with cognitive decline up to twelve months after symptom onset in our group 3 cohort.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of Blood Biomarkers of Neurological Injury in Human Cases of Viral Infection and Bacterial Sepsis

Bartlett,

Goux,

Johnson

et al. 2024

Preprint

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BackgroundBlood biomarkers of neurological injury could provide a rapid diagnosis of central nervous system (CNS) injury caused by infections. An FDA-approved assay for mild traumatic brain injury (TBI) measures glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), which signal astrocyte and neuronal injury, respectively. Here, we assessed the applicability of this biomarker assay for determining infection-induced brain injury.MethodsWe measured serum levels of GFAP and UCH-L1 retrospectively in serum samples from three study populations: 1) human cases infected with Venezuelan equine encephalitis virus (VEEV) and Madariaga virus (MADV) (n = 73), 2) human sepsis patients who were severely ill or diagnosed with encephalitis (n = 66), and 3) sepsis cases that were subsequently evaluated for cognitive impairment (n = 64).ResultsIn the virus infection group, we found elevated GFAP for VEEV (p = 0.014) and MADV (p = 0.011) infections, which correlated with seizures (p = 0.006). In the bacterial sepsis group, GFAP was elevated in cases diagnosed with encephalitis (p = 0.0007) and correlated with headaches (p = 0.0002). In the bacterial sepsis cases with a later cognitive assessment, elevated GFAP (p = 0.0057) at study enrollment was associated with cognitive impairment six months later with a positive prognostic capacity of 79% (CI: 66–95%; p = 0.0068).ConclusionsGFAP and UCH-L1 levels measured using an FDA-approved assay for TBI may indicate brain injury resulting from viral or bacterial infections and could predict the development of neurological sequelae.

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Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of Blood Biomarkers of Neurological Injury in Human Cases of Viral Infection and Bacterial Sepsis

Bartlett,

Goux,

Johnson

et al. 2024

Preprint

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“…Sepsis remains a major public health problem ( Tang et al., 2023 ). In this study, we employed GSVA to identify two differential pathways (angiogenesis and myc targets v2) between sepsis patients and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Classification of subtypes and identification of dysregulated genes in sepsis

Tong,

Ding,

Liu

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundSepsis is a clinical syndrome with high mortality. Subtype identification in sepsis is meaningful for improving the diagnosis and treatment of patients. The purpose of this research was to identify subtypes of sepsis using RNA-seq datasets and further explore key genes that were deregulated during the development of sepsis.MethodsThe datasets GSE95233 and GSE13904 were obtained from the Gene Expression Omnibus database. Differential analysis of the gene expression matrix was performed between sepsis patients and healthy controls. Intersection analysis of differentially expressed genes was applied to identify common differentially expressed genes for enrichment analysis and gene set variation analysis. Obvious differential pathways between sepsis patients and healthy controls were identified, as were developmental stages during sepsis. Then, key dysregulated genes were revealed by short time-series analysis and the least absolute shrinkage and selection operator model. In addition, the MCPcounter package was used to assess infiltrating immunocytes. Finally, the dysregulated genes identified were verified using 69 clinical samples.ResultsA total of 898 common differentially expressed genes were obtained, which were chiefly related to increased metabolic responses and decreased immune responses. The two differential pathways (angiogenesis and myc targets v2) were screened on the basis of gene set variation analysis scores. Four subgroups were identified according to median expression of angiogenesis and myc target v2 genes: normal, myc target v2, mixed-quiescent, and angiogenesis. The genes CHPT1, CPEB4, DNAJC3, MAFG, NARF, SNX3, S100A9, S100A12, and METTL9 were recognized as being progressively dysregulated in sepsis. Furthermore, most types of immune cells showed low infiltration in sepsis patients and had a significant correlation with the key genes. Importantly, all nine key genes were highly expressed in sepsis patients.ConclusionThis study revealed novel insight into sepsis subtypes and identified nine dysregulated genes associated with immune status in the development of sepsis. This study provides potential molecular targets for the diagnosis and treatment of sepsis.

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Prognostic values of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and neuron-specific enolase in patients with sepsis-associated encephalopathy

Zhu,

Liu,

Jia

et al. 2024

VOJNOSANIT PREGL

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Background/Aim. Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis, characterized by brain dysfunction and associated with a poor prognosis. SAE has a complex pathogenesis, and its severity is in close association with the levels of various serum factors. The aim of the study was to investigate the correlation of tumor necrosis factor (TNF)-?, monocyte chemoattractant protein (MCP)-1, and neuron-specific enolase (NSE) levels with the severity of SAE and to analyze the prognostic values of the three parameters. Methods. This prospective study enrolled 126 patients treated for SAE from June 2020 to June 2022. The levels of TNF-?, MCP-1, and NSE were measured, and the severity of SAE was evaluated using the Sequential Organ Failure Assessment (SOFA) score. Based on the SOFA score, the patients were assigned to two groups: a group with a bad prognosis and a group with a good prognosis. The correlations of TNF-?, MCP-1, and NSE levels with the severity of SAE were analyzed, and their prognostic values were evaluated during a 28-day follow- up. Results. The mean levels of TNF-?, MCP-1, and NSE and the SOFA score of the 126 patients with SAE were 6.52 ? 1.48 pg/mL, 62.53 ? 18.49 pg/mL, 8.61 ? 2.17 ng/mL, and 10.24 ? 2.86 points, respectively. Pearson?s analysis demonstrated significant correlations between TNF-?, MCP-1, and NSE levels and the SOFA score of patients with SAE (r > 0, p < 0.05). Of the 126 patients, 61 (48.4%) had a poor prognosis, while 65 (51.6%) had a good prognosis. Increased serum TNF-?, MCP-1, and NSE levels were risk factors for the poor prognosis of patients with SAE [odds ratio (OR) > 1, p < 0.05]. The areas under the receiver operating characteristic (ROC) curves of serum TNF-?, MCP-1, and NSE levels were all > 0.7, suggesting high predictive values of these parameters. Conclusion. Serum TNF-?, MCP-1, and NSE levels are closely correlated with the severity of SAE and may work as valuable predictors of treatment outcome.

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Research Progress of Biomarkers of Sepsis-Associated Encephalopathy

Cited by 3 publications

References 54 publications

Retrospective Analysis of Blood Biomarkers of Neurological Injury in Human Cases of Viral Infection and Bacterial Sepsis

Retrospective Analysis of Blood Biomarkers of Neurological Injury in Human Cases of Viral Infection and Bacterial Sepsis

Classification of subtypes and identification of dysregulated genes in sepsis

Prognostic values of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and neuron-specific enolase in patients with sepsis-associated encephalopathy

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