生物标志物在脓毒性关节炎和骨髓炎早期诊断中的应用——一项初步研究。

The Use of Biomarkers in the Early Diagnosis of Septic Arthritis and Osteomyelitis-A Pilot Study.

机构信息

Departments of Orthopedic Surgery.

Shriners Hospitals for Children, St. Louis, MO.

出版信息

J Pediatr Orthop. 2022;42(5):e526-e532. doi: 10.1097/BPO.0000000000002052.

DOI:10.1097/BPO.0000000000002052

PMID:35405729

Abstract

BACKGROUND

The diagnosis of septic arthritis (SA) and osteomyelitis (OM) has remained challenging in the pediatric population, often accompanied by delays and requiring invasive interventions. The purpose of this pilot study is to identify a novel panel of biomarkers and cytokines that can accurately differentiate SA and OM at initial presentation using serum alone.

METHODS

Twenty patients below 18 years old whose working diagnosis included SA (n=10) and OM (n=10) were identified. Serum was collected at initial evaluation. Each sample underwent seven ELISA [C1-C2, COMP, CS-846, hyaluronan, procalcitonin, PIIANP, C-terminal telopeptide of type II collagen (CTX-II)] and 65-plex cytokine panels. Principal component and Lasso regression analysis were performed to identify a limited set of predictive biomarkers.

RESULTS

Mean age was 4.7 and 9.5 years in SA and OM patients, respectively (P=0.029). 50% of SA patients presented within 24 hours of symptom onset, compared with 0% of OM patients (P=0.033). 30% of SA patients were discharged home with an incorrect diagnosis and re-presented to the emergency department days later. At time of presentation: temperature ≥38.5°C was present in 10% of SA and 40% of OM patients (P=0.12), mean erythrocyte sedimentation rate (mm/h) was 51.6 in SA and 44.9 in OM patients (P=0.63), mean C-reactive protein (mg/dL) was 55.8 in SA and 71.8 in OM patients (P=0.53), and mean white blood cells (K/mm3) was 12.5 in SA and 10.4 in OM patients (P=0.34). 90% of SA patients presented with ≤2 of the Kocher criteria. 100% of SA and 40% of OM patients underwent surgery. 70% of SA cultures were culture negative, 10% MSSA, 10% Kingella, and 10% Strep pyogenes. 40% of OM cultures were culture negative, 50% MSSA, and 10% MRSA. Four biomarkers [CTx-II, transforming growth factor alpha (TGF-α), monocyte chemoattractant protein 1 (MCP-1), B cell-attracting chemokine 1] were identified that were able to classify and differentiate 18 of the 20 SA and OM cases correctly, with 90% sensitivity and 80% specificity.

CONCLUSIONS

This pilot study identifies a panel of biomarkers that can differentiate between SA and OM at initial presentation using serum alone.

LEVEL OF EVIDENCE

Level II-diagnostic study.

摘要

背景

儿童脓毒性关节炎（SA）和骨髓炎（OM）的诊断一直具有挑战性，通常伴有延迟，并需要侵入性干预。本研究旨在通过血清来识别一组新的生物标志物和细胞因子，以在初始表现时准确区分 SA 和 OM。

方法

鉴定了 20 名年龄在 18 岁以下的患者，他们的初步诊断包括 SA（n=10）和 OM（n=10）。在初始评估时采集血清。每个样本均进行 7 种 ELISA[C1-C2、COMP、CS-846、透明质酸、降钙素原、PIIANP、Ⅱ型胶原 C 端肽（CTX-II）]和 65 种细胞因子检测。进行主成分和套索回归分析，以确定一组有限的预测生物标志物。

结果

SA 和 OM 患者的平均年龄分别为 4.7 和 9.5 岁（P=0.029）。50%的 SA 患者在症状出现后 24 小时内就诊，而 OM 患者中无此情况（P=0.033）。30%的 SA 患者出院时被误诊，几天后再次到急诊就诊。就诊时：体温≥38.5°C 的 SA 和 OM 患者分别占 10%和 40%（P=0.12），SA 和 OM 患者的平均红细胞沉降率（mm/h）分别为 51.6 和 44.9（P=0.63），平均 C 反应蛋白（mg/dL）分别为 55.8 和 71.8（P=0.53），平均白细胞（K/mm3）分别为 12.5 和 10.4（P=0.34）。90%的 SA 患者符合≤2 项 Kocher 标准。100%的 SA 和 40%的 OM 患者接受了手术。70%的 SA 培养结果为阴性，10%为 MSSA，10%为 Kingella，10%为 Streptococcus pyogenes。40%的 OM 培养结果为阴性，50%为 MSSA，10%为 MRSA。有 4 种生物标志物[CTX-II、转化生长因子α（TGF-α）、单核细胞趋化蛋白 1（MCP-1）、B 细胞趋化因子 1]能够正确分类和区分 20 例 SA 和 OM 中的 18 例，敏感性为 90%，特异性为 80%。