Feasibility of Absent in Melanoma 2 as a Serological Marker in Relation to Complicated Community-Acquired Pneumonia in Children: A Prospective Cohort Study

黑色素瘤缺失2基因作为儿童复杂性社区获得性肺炎血清学标志物的可行性:一项前瞻性队列研究

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Abstract

OBJECTIVE: Absent in melanoma 2 (AIM2) is associated with inflammation. We intended to determine whether serum AIM2 levels are related to severity and complications of community-acquired pneumonia (CAP) in children. METHODS: In this prospective cohort study, serum AIM2 levels were measured in 305 children with CAP and in 100 healthy controls at the Hangzhou Children's Hospital between January 2022 and June 2023. CAP severity was assessed using the pediatric critical illness score (PCIS) and clinical pulmonary infection score (CPIS). In-hospital complicated CAP was identified as the outcome variable. Univariate and multivariate analyses were sequentially performed to determine the correlation between severity, outcome and serum AIM2 levels. RESULTS: Children with CAP had higher serum AIM2 levels than controls (median, 1.45 ng/mL versus 0.36 ng/mL; P<0.001). Serum AIM2 levels in diseased children were independently correlated with PCIS (beta=-0.020; P=0.001) and CPIS (beta=0.092; P=0.002), were linearly related to likelihood of complicated CAP (P for nonlinear =0.057), and were independently associated with complicated CAP (odds ratio= 6.162; P=0.005). The outcome association was robust by calculating the E-value at 11.8 and was not moderated by age, sex, weight and more (all P interaction >0.05). Serum AIM2 levels and two independent predictors, PCIS and CPIS, were integrated to construct the model. The model was pictorially represented by the nomogram and exhibited satisfactory discrimination capability, validity, and stability under the receiver operating characteristic (ROC) curve, decision curve, and calibration curve. By computing the net reclassification improvement and integrated discrimination improvement indices and comparing the area under the ROC curve, the model significantly outperformed the combination of the PCIS and CPIS. CONCLUSION: Markedly enhanced serum AIM2 levels following CAP in children are highly linked to severity and complicated CAP, substantializing serum AIM2 as a biochemical metric for assessing the severity and identifying adverse outcomes of childhood CAP.

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