Reuken Philipp A, Brozat Jonathan F, Quickert Stefanie, Ibidapo-Obe Oluwatomi, Reißing Johanna, Franz Anika, Stengel Sven, Teichgräber Ulf K-M, Kiehntopf Michael, Trautwein Christian, Stallmach Andreas, Koch Alexander, Bruns Tony
Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747, Jena, Germany.
Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
J Intensive Care. 2022 Jun 11;10(1):28. doi: 10.1186/s40560-022-00619-2.
In acute pancreatitis (AP), microcirculatory dysfunction and leukocyte activation contribute to organ damage, inflammation, and mortality. Given the role of macrophage activation, monocyte recruitment, and microthrombus formation in the early pathogenesis of AP, we examined the macrophage activation marker soluble mannose receptor (sCD206) and the endothelial function marker von Willebrand factor (vWF) in patients admitted for AP.
In an exploratory analysis, serum sCD206 and plasma vWF were prospectively analyzed on day 1 and day 3 in 81 patients with AP admitted to the hospital. In addition, blood samples from 59 patients with early AP admitted to the intensive care unit and symptom onset < 24 h were retrospectively analyzed. Patients were dichotomized as per study protocol into two groups: (i) "non-severe edematous AP" including patients with mild AP without organ failure and patients with transient organ failure that resolves within 48 h and (ii) "severe/necrotizing AP" including patients with severe AP and persistent organ failure > 48 h and/or patients with local complications.
In the prospective cohort, 17% developed severe/necrotizing pancreatitis compared with 56% in the ICU cohort. Serum concentrations of sCD206 on admission were higher in patients with severe/necrotizing AP than in patients with non-severe edematous AP (prospective: 1.57 vs. 0.66 mg/l, P = 0.005; ICU: 1.76 vs. 1.25 mg/l, P = 0.006), whereas other inflammatory markers (leukocytes, C-reactive protein, procalcitonin) and disease severity (SOFA, SAPS II, APACHE II) did not show significant differences. Patients with severe/necrotizing AP had a greater increase in sCD206 than patients with non-severe edematous AP at day 3 in the prospective cohort. In contrast to routine coagulation parameters, vWF antigen levels were elevated on admission (prospective cohort: 375 vs. 257%, P = 0.02; ICU cohort: 240 vs. 184%, P = 0.03). When used as continuous variables, sCD206 and VWF antigen remained predictors of severe/necrotizing AP after adjustment for etiology and age in both cohorts.
sCD206 identifies patients at risk of severe AP at earlier timepoints than routine markers of inflammation and coagulation. Prospective studies are needed to investigate whether incorporating early or repeated measurements into the existing scoring system will better identify patients at increased risk for complications of AP.
在急性胰腺炎（AP）中，微循环功能障碍和白细胞激活会导致器官损伤、炎症及死亡。鉴于巨噬细胞激活、单核细胞募集和微血栓形成在AP早期发病机制中的作用，我们检测了因AP入院患者的巨噬细胞激活标志物可溶性甘露糖受体（sCD206）和内皮功能标志物血管性血友病因子（vWF）。
在一项探索性分析中，对81例入院的AP患者在第1天和第3天进行了血清sCD206和血浆vWF的前瞻性分析。此外，对入住重症监护病房且症状发作时间＜24小时的59例早期AP患者的血样进行了回顾性分析。根据研究方案，将患者分为两组：（i）“非重症水肿性AP”，包括轻度AP无器官功能衰竭的患者以及48小时内缓解的短暂性器官功能衰竭患者；（ii）“重症/坏死性AP”，包括重症AP和持续器官功能衰竭＞48小时的患者和/或有局部并发症的患者。
在前瞻性队列中，17%的患者发展为重症/坏死性胰腺炎，而重症监护病房队列中的这一比例为56%。重症/坏死性AP患者入院时血清sCD206浓度高于非重症水肿性AP患者（前瞻性队列：1.57 vs. 0.66mg/l，P = 0.005；重症监护病房队列：1.76 vs. 1.25mg/l，P = 0.006），而其他炎症标志物（白细胞、C反应蛋白、降钙素原）和疾病严重程度（序贯器官衰竭评估、简化急性生理学评分II、急性生理与慢性健康状况评分II）无显著差异。在前瞻性队列中，重症/坏死性AP患者在第3天时sCD206的升高幅度大于非重症水肿性AP患者。与常规凝血参数不同，vWF抗原水平在入院时升高（前瞻性队列：375 vs. 257%，P = 0.02；重症监护病房队列：240 vs. 184%，P = 0.03）。当作为连续变量使用时，在两个队列中对病因和年龄进行调整后，sCD206和vWF抗原仍然是重症/坏死性AP的预测指标。
与炎症和凝血的常规标志物相比，sCD206能在更早的时间点识别出有重症AP风险的患者。需要进行前瞻性研究，以调查将早期或重复测量纳入现有评分系统是否能更好地识别AP并发症风险增加的患者。
