Supplementary Material for: Early Diagnosis of Intra-Abdominal Inflammation and Sepsis by Neutrophil CD64 Expression in Newborns

<i>Background:</i> Newborn infants with intra-abdominal inflammation/sepsis often present with nonspecific signs in the early stages of the disease, but can rapidly develop life-threatening complications. A reliable ‘early’ biomarker would be invaluable. <i>Objective:</i> To evaluate the effectiveness of neutrophil CD64 as an ‘early’ biomarker of intra-abdominal inflammation/sepsis. <i>Methods:</i> Blood was collected from newborns with suspected intra-abdominal pathology for neutrophil CD64 and C-reactive protein (CRP) determination at the onset of clinical presentation and 24 h later. They were classified into three groups: intra-abdominal inflammation/sepsis (group 1), extra-abdominal sepsis (group 2) and nonsepsis (group 3). Between-group comparisons were made by Kruskal-Wallis and χ² tests. Receiver-operating characteristic curves and diagnostic utilities for single and combination of tests were determined. <i>Results:</i> 310 infants were recruited (102, 34 and 174 in groups 1, 2 and 3, respectively). CD64 (conventional cutoff = 6,010 antibody-PE molecules bound/cell) had substantially better sensitivity (0.81 vs. 0.56) and negative predictive value (0.90 vs. 0.79) for diagnosing intra-abdominal sepsis than CRP, at presentation. Pairing CD64 with routine abdominal radiograph (AXR) substantially increased the sensitivity and negative predictive value for group 1 to 0.99 and 0.99, respectively. By adjusting the CD64 cutoff to 12,500 units, a substantial improvement in specificity could be achieved (0.62 to 0.80) without significantly compromising sensitivity (0.99 to 0.97). <i>Conclusions:</i> CD64 is a sensitive and ‘early’ biomarker for diagnosing intra-abdominal inflammation/sepsis. Intra-abdominal catastrophes, including necrotizing enterocolitis, intestinal necrosis, perforation and peritonitis can confidently be excluded using CD64 and AXR early in the course of the disease.

<i>背景：</i>合并腹腔内炎症/脓毒症的新生儿在疾病早期常表现为非特异性体征，但可快速进展为危及生命的并发症。可靠的“早期”生物标志物具有极高的临床应用价值。<i>研究目的：</i>评估中性粒细胞CD64（neutrophil CD64）作为腹腔内炎症/脓毒症“早期”生物标志物的诊断效能。<i>研究方法：</i>对疑似腹腔病变的新生儿，在临床症状初发时及发病24小时后采集血液样本，用于检测中性粒细胞CD64（neutrophil CD64）与C反应蛋白（C-reactive protein, CRP）水平。将研究对象分为三组：腹腔内炎症/脓毒症组（第1组）、腹腔外脓毒症组（第2组）及非脓毒症组（第3组）。组间比较采用克鲁斯卡尔-沃利斯（Kruskal-Wallis）检验与卡方（χ²）检验；同时绘制受试者工作特征（Receiver-operating characteristic, ROC）曲线，并评估单项检测及联合检测的诊断效能。<i>研究结果：</i>本研究共纳入310例新生儿，第1、2、3组分别包含102例、34例、174例。在临床症状初发时，以常规临界值6010个抗体-藻红蛋白（PE）结合分子/细胞计算的CD64指标，诊断腹腔内脓毒症的灵敏度（0.81 vs 0.56）与阴性预测值（0.90 vs 0.79）均显著优于CRP。将CD64与常规腹部X线平片（abdominal radiograph, AXR）联合检测，可使第1组的灵敏度与阴性预测值分别提升至0.99与0.99。将CD64临界值调整至12500单位后，可在未显著降低灵敏度（0.99降至0.97）的前提下，将特异性从0.62提升至0.80。<i>研究结论：</i>中性粒细胞CD64是诊断腹腔内炎症/脓毒症的灵敏且可靠的“早期”生物标志物。在疾病早期阶段，联合检测CD64与腹部X线平片，可可靠排除坏死性小肠结肠炎、肠坏死、肠穿孔及腹膜炎等腹腔危重症。