Lafon Thomas, Cazalis Marie-Angélique, Hart Kimberly W, Hennessy Cassandra, Tazarourte Karim, Self Wesley H, Akhavan Arvin Radfar, Laribi Saïd, Viglino Damien, Douplat Marion, Ginde Adit A, Tolou Sophie, Mahler Simon A, Le Borgne Pierrick, Claessens Yann-Erick, Yordanov Youri, Le Bastard Quentin, Pancher Agathe, Ducharme Jim, Lindsell Christopher J, Shapiro Nathan I
Emergency Department and Inserm CIC 1435, Dupuytren University Hospital, 2 Avenue Martin Luther King, 87042, Limoges, France.
Medical Diagnostic Discovery Department MD3, bioMerieux SA, Marcy L'Etoile, France.
Intern Emerg Med. 2024 Oct 30. doi: 10.1007/s11739-024-03802-5.
Because 20-30% of patients with sepsis deteriorate to critical illness, biomarkers that provide accurate early prognosis may identify which patients need more intensive treatment versus safe early discharge. The objective was to test the performance of sVEGFR2, suPAR and PCT, alone or combined with clinical signs and symptoms, for the prediction of clinical deterioration. This prospective observational study enrolled patients with suspected infection who met SIRS criteria without organ dysfunction (delta SOFA <2 from baseline) from 16 emergency departments. The primary endpoint was clinical deterioration (increased SOFA score ≥2 points, new or increased organ support, or death) within 72 hours of enrollment. Diagnosis and classification of infection status were adjudicated. 724 patients were enrolled, (54% men, median age 55 [38-70] y-o). Infection origin was abdominopelvic (21%), skin and soft tissues (17%), urinary (16%) and pulmonary (15%). 176 (24%) patients deteriorated, with a 28-day mortality of 1.4%. They had lower sVEGFR2 level (6.17 [5.00-7.40] vs 6.52 [5.40-7.84], p=0.024), higher circulating suPAR (5.25 [3.86-7.50] vs 4.18 [3.16-5.68], p<0.001) and higher PCT level (0.32 [0.08-1.80] vs 0.18 [0.05-0.98], p=0.004). suPAR demonstrated superior performance (AUC=0.65 [0.60-0.70]), compared to other biomarkers (PCT, AUC=0.57 [0.52-0.62] and sVEGFR2, AUC=0.58 [0.53-0.64]). Maximum accuracy was achieved from the combination of clinical information, sVEGFR2 and suPAR, yielding an AUC of 0.74 [0.69-0.78] and NPV 0.90 [0.88-0.94]. sVEGFR2 and suPAR were insufficiently accurate to rule out clinical deterioration. Panels of biomarkers will likely be needed to capture the heterogeneous mechanistic pathways involved in sepsis-related organ failure.
由于20%-30%的脓毒症患者会恶化为危重症，能够提供准确早期预后的生物标志物可识别哪些患者需要更强化的治疗，哪些患者可安全地早期出院。目的是测试可溶性血管内皮生长因子受体2（sVEGFR2）、可溶性尿激酶型纤溶酶原激活物受体（suPAR）和降钙素原（PCT）单独或与临床体征和症状联合使用时预测临床恶化的性能。这项前瞻性观察性研究纳入了来自16个急诊科的符合全身炎症反应综合征（SIRS）标准且无器官功能障碍（序贯器官衰竭评估量表（SOFA）评分较基线升高<2分）的疑似感染患者。主要终点是入组后72小时内的临床恶化（SOFA评分增加≥2分、新出现或增加器官支持或死亡）。对感染状态进行诊断和分类。共纳入724例患者（54%为男性，中位年龄55[38-70]岁）。感染源为腹盆腔（21%）、皮肤和软组织（17%）、泌尿系统（16%）和肺部（15%）。176例（24%）患者病情恶化，28天死亡率为1.4%。他们的sVEGFR2水平较低（6.17[5.00-7.40]对6.52[5.40-7.84]，p=0.024），循环suPAR水平较高（5.25[3.86-7.50]对4.18[3.16-5.68]，p<0.001），PCT水平较高（0.32[0.08-1.80]对0.18[0.05-0.98]，p=0.004）。与其他生物标志物相比（PCT，曲线下面积（AUC）=0.57[0.52-0.62]；sVEGFR2，AUC=0.58[0.53-0.64]），suPAR表现更优（AUC=0.65[0.60-0.70]）。临床信息、sVEGFR2和suPAR联合使用时准确性最高，AUC为0.74[0.69-0.78]，阴性预测值为0.90[0.88-0.94]。sVEGFR2和suPAR在排除临床恶化方面准确性不足。可能需要多种生物标志物组合来捕捉脓毒症相关器官衰竭中涉及的异质机制途径。
