Resistin Concentration in Early Sepsis and All-Cause Mortality at a Safety-Net Hospital in Riverside County.
Resistin Concentration in Early Sepsis and All-Cause Mortality at a Safety-Net Hospital in Riverside County.
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DOI：
10.2147/jir.s370788
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发表时间：
2022
影响因子：
4.5
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中科院分区：
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败血症死亡率十多年来一直保持不变，早期识别仍然是死亡率结果的最重要因素。脓毒症患者血浆抵抗素浓度升高，但其机制和临床意义尚不清楚。作为一种功能，抵抗素与toll样受体4相互作用，与脂多糖竞争，脂多糖是革兰氏阴性细菌细胞壁的主要成分。目前尚不清楚导致败血症的感染类型是否会影响抵抗素的产生。本研究的目的是探讨1)早期血浆抵抗素浓度是否可以预测死亡率，2)血浆抵抗素浓度升高与临床疾病严重程度评分（如SOFA、mSOFA和APACHE II）相关，以及3)革兰氏阴性与其他病因的败血症的血浆抵抗素浓度差异。这是一项前瞻性观察设计框架下的探索性研究。在临床确认脓毒症（0小时）、6小时和24小时时，从入住重症监护病房的受试者采集外周静脉血样本。血管加压素的使用并不是纳入的必要条件。ELISA法检测血浆抵抗素浓度。细胞因子头阵列检测细胞因子IL-6、IL-8、IL-10浓度。细胞因子数据与公开可用的败血症RNA表达数据集进行评估，以比较蛋白质和RNA表达水平在预测临床疾病状态中的作用。临床数据从电子健康记录中收集，用于临床严重程度指数计算和解释抵抗素和细胞因子浓度的背景。受试者被随访60天，或直至死亡，以先到者为准。统计分析采用R包和SPSS软件完成。抵抗素水平升高的受试者入院重症监护病房与败血症。筛选了400名受试者，最终分析了45名受试者。45例患者中有13例未存活。60天内的死亡率与抵抗素浓度显著高于幸存者相关。临床识别败血症时抵抗素浓度>126 ng/mL和24小时内>197 ng/mL与60天内死亡率相关，曲线下面积分别为0.82和0.88。大多数抵抗素浓度高于这些阈值的受试者在30天前死亡。抵抗素浓度除了与炎症和败血症生物标志物的增加相关外，还与SOFA、mSOFA和APACHE II评分相关。这些关联通过RNA表达数据集的分析得到验证。临床识别败血症时血浆抵抗素浓度为>126 ng/mL，临床识别败血症后24小时内血浆抵抗素浓度为>197 ng/mL与全因死亡率相关。该时间段内的抵抗素浓度也与经过验证的临床严重程度指标SOFA、mSOFA和APACHE II评分具有可比的死亡率关联。
Sepsis mortality has remained unchanged for greater than a decade, and early recognition continues to be the most important factor in mortality outcome. Plasma resistin concentration is increased in sepsis, but its mechanism and clinical relevance is unclear. As one function, resistin interacts with toll-like receptor 4 in competition with lipopolysaccharide, a main component of the gram-negative bacterial cell wall. It is not known if the type of infection leading to sepsis influences resistin production. The objective of this study was to investigate whether 1) early plasma resistin concentration can predict mortality, 2) elevated plasma resistin concentration is associated with clinical disease severity scores, such as SOFA, mSOFA and APACHE II, and 3) plasma resistin concentrations differ between gram negative versus other etiologies of sepsis. This was an exploratory study in the framework of a prospective observational design. Peripheral venous blood samples were obtained from subjects admitted to the intensive care unit at clinical recognition of sepsis (0 hour) and at 6 and 24 hours. Vasopressor utilization was not a requirement for inclusion. Plasma was analyzed for resistin concentration by ELISA. Cytokine concentrations including IL-6, IL-8, and IL-10 were determined by cytokine bead array. Cytokine data were evaluated against publicly available sepsis RNA expression datasets to compare protein versus RNA expression levels in predicting clinical disease state. Clinical data were collected from electronic health records for clinical severity index calculations and context for interpretation of resistin and cytokine concentrations. Subjects were followed up to 60 days, or until death, whichever came first. Statistical analysis was completed with R package and SPSS software. Resistin levels were elevated in subjects admitted to the intensive care unit with sepsis. Four-hundred subjects were screened with 45 subjects included in the final analysis. Thirteen of 45 patients were non-survivors. Mortality within 60 days correlated with significantly higher resistin concentrations than in survivors. A resistin concentration of >126 ng/mL at clinical recognition of sepsis and >197 ng/mL within the first 24 hours were associated with mortality within 60 days with an area under the curve of 0.82 and 0.88, respectively. Most subjects with resistin concentration greater than these threshold values were deceased prior to 30 days. Resistin concentrations correlated with SOFA, mSOFA, and APACHE II scores in addition to having association with increases in inflammatory and sepsis biomarkers. These associations were validated with analysis of RNA expression datasets. Plasma resistin concentrations of >126 ng/mL at clinical recognition of sepsis and >197 ng/mL within the first 24 hours of clinical sepsis recognition are associated with all-cause mortality. Resistin concentration within this timeframe also has comparable mortality association to well-validated clinical severity indices of SOFA, mSOFA, and APACHE II scores.