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游离核DNA和线粒体DNA作为评估脓毒症严重程度的潜在生物标志物

Cell-Free Nuclear and Mitochondrial DNA as Potential Biomarkers for Assessing Sepsis Severity.

作者信息

de Miranda Felipe Silva, Claudio Livia Maria A M, de Almeida Dayanne Silva M, Nunes Juliana Braga, Barauna Valério Garrone, Luiz Wilson Barros, Vassallo Paula Frizzera, Campos Luciene Cristina Gastalho

机构信息

Department of Biological Science State, University of Santa Cruz, Ilhéus 45662-900, Bahia, Brazil.

Postgraduate Program in Biology and Biotechnology of Microorganisms State, University of Santa Cruz, Ilhéus 45662-900, Bahia, Brazil.

出版信息

Biomedicines. 2024 Apr 23;12(5):933. doi: 10.3390/biomedicines12050933.

DOI:10.3390/biomedicines12050933
PMID:38790895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11117867/
Abstract

Sepsis continues to be a significant public health challenge despite advances in understanding its pathophysiology and management strategies. Therefore, this study evaluated the value of cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) for assessing the severity and prognosis of sepsis. Ninety-four patients were divided into three groups: infection (n = 32), sepsis (n = 30), and septic shock (n = 32). Plasma samples were collected at the time of diagnosis, and cfDNA concentrations were determined by qPCR assay. The results showed that plasma cfDNA levels increased with the severity of the disease. To distinguish between patients with infection and those with sepsis, the biomarker L1PA2 achieved the highest AUC of 0.817 (95% CI: 0.725-0.909), demonstrating a sensitivity of 77.0% and a specificity of 79.3%. When cf-nDNA was combined with the SOFA score, there was a significant improvement in the AUC (0.916 (0.853-0.979)), sensitivity (88.1%), and specificity (80.0%). Moreover, patients admitted to the ICU after being diagnosed with sepsis had significantly higher cf-nDNA concentrations. In patients admitted to the ICU, combining cf-nDNA with the SOFA score yielded an AUC of 0.753 (0.622-0.857), with a sensitivity of 95.2% and a specificity of 50.0%. cfDNA can differentiate between patients with infection and those with sepsis. It can also identify patients who are likely to be admitted to the ICU by predicting those with indications for intensive care, suggesting its potential as a biomarker for sepsis.

摘要

尽管在脓毒症病理生理学和管理策略的理解方面取得了进展,但脓毒症仍然是一个重大的公共卫生挑战。因此,本研究评估了游离核DNA(cf-nDNA)和游离线粒体DNA(cf-mtDNA)在评估脓毒症严重程度和预后方面的价值。94例患者分为三组:感染组(n = 32)、脓毒症组(n = 30)和脓毒性休克组(n = 32)。在诊断时采集血浆样本,并通过qPCR测定法确定cfDNA浓度。结果表明,血浆cfDNA水平随疾病严重程度增加而升高。为区分感染患者和脓毒症患者,生物标志物L1PA2的曲线下面积(AUC)最高,为0.817(95%可信区间:0.725 - 0.909),灵敏度为77.0%,特异性为79.3%。当cf-nDNA与序贯器官衰竭评估(SOFA)评分相结合时,AUC(0.916(0.853 - 0.979))、灵敏度(88.1%)和特异性(80.0%)均有显著提高。此外,脓毒症诊断后入住重症监护病房(ICU)的患者cf-nDNA浓度显著更高。在入住ICU的患者中,cf-nDNA与SOFA评分相结合的AUC为0.753(0.622 - 0.857),灵敏度为95.2%,特异性为50.0%。cfDNA可区分感染患者和脓毒症患者。它还可以通过预测有重症监护指征的患者来识别可能入住ICU的患者,表明其作为脓毒症生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/c42b0ae73210/biomedicines-12-00933-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/9ff49a298d73/biomedicines-12-00933-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/c42b0ae73210/biomedicines-12-00933-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/9ff49a298d73/biomedicines-12-00933-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/c8314ce3a338/biomedicines-12-00933-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/db3ded32030c/biomedicines-12-00933-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/344063ab863b/biomedicines-12-00933-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/2266cabf887e/biomedicines-12-00933-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e51/11117867/c42b0ae73210/biomedicines-12-00933-g006.jpg

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