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全身炎症和抗炎反应与急性胰腺炎不良结局的关联:一项正在进行的研究的初步结果

Association of Systemic Inflammatory and Anti-inflammatory Responses with Adverse Outcomes in Acute Pancreatitis: Preliminary Results of an Ongoing Study.

作者信息

Sharma Deepesh, Jakkampudi Aparna, Reddy Ratnakar, Reddy Panyala Balakumar, Patil Aasish, Murthy H V V, Rao G Venkat, Reddy D Nageshwar, Talukdar Rupjyoti

机构信息

Department of Medical Gastroenterology, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, Telangana, 500082, India.

Division of Basic and Translational Sciences, Asian Healthcare Foundation, Hyderabad, India.

出版信息

Dig Dis Sci. 2017 Dec;62(12):3468-3478. doi: 10.1007/s10620-017-4813-6. Epub 2017 Oct 27.

Abstract

INTRODUCTION

This paper reports preliminary data of an ongoing study that evaluates the association of systemic inflammatory response (SIRS) with early severe acute pancreatitis (ESAP) and compensatory anti-inflammatory response syndrome (characterized by HLA-DR down-regulation) with infected pancreatic necrosis (IPN).

METHODS

Consecutive patients presenting within 72 h of symptom onset with organ dysfunction and/or local complications were included. Following parameters were recorded: demographics, etiology, SIRS, APACHE II, creatinine, BUN. Circulating IL-8, IL-6, IL-10, TNF-alpha concentrations and expression of HLA-DR and IL-10 by qRT-PCR in PBMCs were measured. Strength of associations of cytokine concentration and HLA-DR/IL-10 expression with outcomes was expressed as Hedges' G and relative risk (95% CI).

RESULTS

Twenty-eight patients (10 MSAP; 18 SAP) fulfilled inclusion criteria. Twelve patients had ESAP and eight presented with organ failure. Admission SIRS worsened in eight (28.6%) patients over 48 h. Sixteen (57.1%) patients developed primary IPN. Twenty-one (75%) patients had HLA-DR down-regulation during the first week, which persisted to the second week in 12 (42.9%) patients. IL-8, IL-6, and TNF-α progressively increased from healthy controls to MAP to MSAP to SAP. IL-6 and TNF-α was higher in the patients who developed ESAP (p = 0.01 and 0.05, respectively). Patients who died within the first week also had a significantly elevated concentration of IL-6 and TNF-α (p = 0.02 and 0.01, respectively). The relative risk (95% CI) of developing primary IPN with persistent HLA-DR down-regulation till the second week of illness was 11.3 (1.6-82.4; p = 0.01).

CONCLUSIONS

Our study objectively demonstrates significant association of ESAP and early mortality with primary cytokine response, and development of IPN with persistent HLA-DR down-regulation.

摘要

引言

本文报告了一项正在进行的研究的初步数据,该研究评估全身炎症反应(SIRS)与早期重症急性胰腺炎(ESAP)的关联,以及代偿性抗炎反应综合征(以HLA-DR下调为特征)与感染性胰腺坏死(IPN)的关联。

方法

纳入症状出现72小时内出现器官功能障碍和/或局部并发症的连续患者。记录以下参数:人口统计学、病因、SIRS、急性生理与慢性健康状况评分系统II(APACHE II)、肌酐、尿素氮。测量循环中的白细胞介素-8(IL-8)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)浓度,以及通过qRT-PCR检测外周血单核细胞(PBMC)中HLA-DR和IL-10的表达。细胞因子浓度以及HLA-DR/IL-10表达与结局的关联强度以Hedges' G和相对风险(95%置信区间)表示。

结果

28例患者(10例中度重症急性胰腺炎;18例重症急性胰腺炎)符合纳入标准。12例患者患有ESAP,8例出现器官衰竭。8例(28.6%)患者在48小时内入院时的SIRS恶化。16例(57.1%)患者发生原发性IPN。21例(75%)患者在第一周出现HLA-DR下调,其中12例(42.9%)患者持续至第二周。从健康对照到轻症急性胰腺炎(MAP)到中度重症急性胰腺炎(MSAP)再到重症急性胰腺炎(SAP),IL-8、IL-6和TNF-α逐渐升高。发生ESAP的患者中IL-6和TNF-α更高(分别为p = 0.01和0.05)。在第一周内死亡的患者中IL-6和TNF-α浓度也显著升高(分别为p = 0.02和0.01)。疾病持续至第二周时,持续性HLA-DR下调发生原发性IPN的相对风险(95%置信区间)为11.3(1.6 - 82.4;p = 0.01)。

结论

我们的研究客观地证明了ESAP和早期死亡率与原发性细胞因子反应的显著关联,以及IPN的发生与持续性HLA-DR下调的关联。

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