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血清Claudin-5水平有利于早期预测重症急性胰腺炎:一项前瞻性观察性研究

Serum Claudin-5 levels facilitate the early prediction of severe acute pancreatitis:a prospective observational study
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摘要 目的探讨急性胰腺炎(AP)患者早期血清紧密连接蛋白Claudin-5水平在重症方面的预测价值。方法采用前瞻性观察性研究方法,纳入2021年12月1日至2022年11月30日在江苏省苏北人民医院确诊AP并收入院的患者,随机纳入同期符合条件的健康志愿者作为健康对照组。根据2012年亚特兰大分级标准将AP患者分为轻症急性胰腺炎(MAP)组、中度急性胰腺炎(MSAP)组和重症急性胰腺炎(SAP)组;再根据住院时间将SAP患者分为入院1、3、7 d亚组。收集所有入选者的基线资料,包括性别、年龄、基础疾病及可能病因;采用酶联免疫吸附试验(ELISA)检测各组入选者血清Claudin-5水平;通过院内检验查询系统获得各组AP患者其他血清学指标数据〔血细胞比容(HCT)、白蛋白(Alb)、血清Ca^(2+)、C-反应蛋白(CRP)、降钙素原(PCT)水平〕;记录各组AP患者改良Marshall评分(mMarshall)、改良CT严重程度指数(mCTSI)评分、急性胰腺炎床旁严重程度指数(BISAP)评分、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)。分析并比较各组间上述指标的差异;采用Spearman相关法分析Claudin-5水平与各影响因素之间的相关性;绘制受试者工作特征曲线(ROC曲线)分析各影响因素对SAP的预测价值;采用多因素岭回归分析筛选SAP的独立危险因素。结果共纳入109例AP患者,其中MAP组66例,MSAP组15例,SAP组28例;同时有27例健康志愿者纳入健康对照组。各组入选者的性别和年龄比较差异均无统计学意义,3组AP患者在基础疾病和病因构成方面比较差异亦均无统计学意义。各组AP患者血清Claudin-5水平随病情加重呈明显升高趋势,且均显著高于健康对照组〔ng/L:888.58(574.52,1141.59)、3749.02(2784.93,5789.92)、4667.81(3935.21,7315.66)比291.13(250.19,314.75),均P<0.05〕。亚组分析显示,随病程延长,SAP组患者入院3 d的Claudin-5水平较入院1 d呈明显下降趋势〔ng/L:2052.59(1089.43,4006.47)比4667.81(3935.21,7315.66),P<0.05〕。Spearman相关性分析显示,AP患者血清Claudin-5水平与CRP、PCT、HCT及mMarshall、mCTSI、BISAP评分均呈显著正相关(r值分别为0.570、0.525、0.323、0.774、0.670、0.652,均P<0.001),与Alb呈显著负相关(r=-0.394,P<0.001)。而AP患者随病情加重HCT水平呈明显上升趋势,Alb水平呈明显下降趋势;SAP患者经治疗后上述现象有改善倾向,间接表明血清Claudin-5水平正向反映血管渗漏。ROC曲线分析显示,AP患者血清Claudin-5水平早期预测SAP的准确性最高,ROC曲线下面积(AUC)为0.948,当血清Claudin-5≥2997 ng/L时,早期筛查SAP的敏感度为100%,特异度为88.89%。多因素岭回归分析显示,血清Claudin-5、PCT水平和APACHEⅡ评分可作为早期预测SAP的独立危险因素(均P<0.05)。结论血清Claudin-5水平有利于早期预测SAP,并与炎症反应和血管渗漏密切相关。 Objective To investigate the value of early tight junction protein Claudin-5 levels in predicting the severity of acute pancreatitis(AP).Methods A prospective observational study was conducted,including patients diagnosed with AP and admitted to the Northern Jiangsu People's Hospital from December 1,2021 to November 30,2022.Eligible healthy volunteers were randomly selected to serve as healthy controls during the same period.Patients were classified into mild acute pancreatitis(MAP)group,moderate-severe acute pancreatitis(MSAP)group,and severe acute pancreatitis(SAP)group based on the 2012 Atlanta classification criteria.Patients with SAP were then divided into three subgroups of 1,3,and 7 days based on the duration of hospitalization.Baseline data,such as gender,age,underlying disease,and probable etiology,was collected from all enrolled individuals.The enzyme-linked immunosorbent assay(ELISA)was employed to detect serum Claudin-5 levels in each cohort of enrollees.Data on additional serologic indicators,including hematocrit(HCT),albumin(Alb),serum Ca^(2+),C-reactive protein(CRP),and procalcitonin(PCT)levels,were obtained via the in-hospital test query system in each group of patients with AP.The modified Marshall score(mMarshall),modified CT severity index(mCTSI)score,bedside severity index of severity in acute pancreatitis(BISAP)score,and acute physiology and chronic health evaluationⅡ(APACHEⅡ)were recorded for each group of patients with AP.Differences in the above indicators between groups were analyzed and compared.Spearman's correlation method was employed to examine the relationship between Claudin-5 levels and each influential factor.The receiver operator characteristic curve(ROC curve)was plotted to analyze the predictive value of each influencing factor on SAP.Ridge regression was used to screen for independent risk factors for SAP.Results A total of 109 patients with AP were enrolled,comprising 66 in the MAP group,15 in the MSAP group,and 28 in the SAP group.Additionally,27 healthy volunteers were enrolled as the healthy control group.No statistically significant differences were observed in gender and age among the enrolled groups,and no statistically significant differences were identified among the three groups of patients with AP in terms of underlying disease and etiologic composition.As the disease progressed,serum Claudin-5 levels exhibited a notable increase across all AP patient groups,and they were all significantly higher than those in the healthy control group[ng/L:888.58(574.52,1141.59),3749.02(2784.93,5789.92),4667.81(3935.21,7315.66)vs.291.13(250.19,314.75),all P<0.05].Subgroup analyses showed that as the disease duration prolonged,patients in the SAP group exhibited a notable decline in Claudin-5 levels at 3 days post-admission,compared with those at 1 day post-admission[ng/L:2052.59(1089.43,4006.47)vs.4667.81(3935.21,7315.66),P<0.05].Spearman correlation analysis showed that serum Claudin-5 levels in patients with AP were significantly positively correlated with CRP,PCT,HCT,and mMarshall,mCTSI,and BISAP scores(r values were 0.570,0.525,0.323,0.774,0.670,0.652,all P<0.001),and significantly negatively correlated with Alb(r=-0.394,P<0.001).A significant trend was observed in patients with AP,with an increase of HCT levels and a decrease of Alb levels as the disease progressed(both P<0.05).An improvement of aforementioned phenomena was observed in patients with SAP following treatment,indirectly indicating that serum Claudin-5 level was a positive indicator of vascular leakage.ROC curve analysis showed that serum Claudin-5 levels in patients with AP exhibited the highest accuracy for early prediction of SAP,with the area under the ROC curve(AUC)of 0.948.When serum Claudin-5 levels≥2997 ng/L,the sensitivity for early screening for SAP was 100%and the specificity was 88.89%.Multifactorial ridge regression analysis showed that serum Claudin-5 level,PCT and APACHEⅡscore could be used as independent risk factors for early prediction of SAP(all P<0.05).Conclusion Serum Claudin-5 levels facilitate early prediction of SAP and are strongly associated with inflammatory response and vascular leakage.
作者 陈欣蕾 王晖晖 耿平 凌冰玉 马爱闻 徐敏 谈定玉 Chen Xinlei;Wang Huihui;Geng Ping;Ling Bingyu;Ma Aiwen;Xu Min;Tan Dingyu(Department of Emergency Medicine,Northern Jiangsu People's Hospital,Yangzhou 225001,Jiangsu,China)
出处 《中华危重病急救医学》 CAS CSCD 北大核心 2024年第9期930-936,共7页 Chinese Critical Care Medicine
基金 江苏省扬州市科技计划项目(YZ2022095)。
关键词 紧密连接蛋白Claudin-5 急性胰腺炎 重症 早期评估 Tight junction protein Claudin-5 Acute pancreatitis Severe illness Early evaluation
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