Clinical Research On The Relationship Between The Severity Of Acute Pancreatitis And The Level Of Ischemic Modified Albumin

BackgroundAcute pancreatitis(AP)is a non-infectious inflammatory reaction of the pancreas,associated with autodigestion of the organ caused by premature activation of zymogens due to various reasons,one of the Gastrointestinal disorders,and one of common clinical acute abdominal disease.lt is reported that the annual incidence of acute pancreatitis is about 13-45 cases per 100000,and the population is on the rise along with the growth in the living standard.Most patients suffer a mild self-limiting disease,but still about one-fifth of cases develop into multiple extrapancreatic organ dysfunction,with or without local complication,that is severe acute pancreatitis with high mortality up to 35%-50%Therefore,differentiating the order of severity of the acute pancreatits at the early stage is beneficial to diagnose early,therapy aerly,and prevent the complication.At present,the classification criterion of the severity of the acute pancreatitis has been updated and the content is more detailed,but the APACHEII scores,the Ranson scores,the CT imaging scores and so on are complicated and can not be acquired in time.Now,a lot of studys have suggested that biomarkers such as C-reactive prtein,amylase,procalcitonin,blood calcium,plasma albumin and so on which can not only illuminate the physioathologic machanism,but are also simple and acquired fast are associated with the severity of the acutepancreatitis.These biomarkers above are helpful for the early diagnosis and treatment of the acute pancreatitis.The ischemic modified protein(IMA)has found wide application among the acute coronary syndrome,the pulmonary embolism,cerebrovascular disease and so on,especially as a highly sensitive biomarkers of the early diagnosis for acute myocardial ischemia,which has gotten widespread attention at home and abroad.The N-terminal end of the human serum albumin which is the temporary binding site of the divalent metal ions such ascobalt,cooper and nickel is composed of aspartis acid,alanine,histidine and lysine.Ischemic modified protein(IMA)a variant form of serum albumin of which N-terminal end has been altered after it was exposed in the state of ischemia and oxidative stress.Metal bianding ability of the N-terminal end is decreased after this molecular alteration.Ischemia in any organ before infarction can lead to IMA elevation.The systemic inflammation plays a crucial role in the pthogenetic mechanism of the acute pancreatitis,but many scholars raise that the microcirculation disturbance is also important.There's accumulamating evidence in human and animal studies that microvascular compromise has been suggested as the critical event in the development of severe pancreatitis,and treatment aimed at the microvasculature may decrease necrosis and disease severity.Therefore,we speculate that ischemic modified protein(IMA)can serve as a biomarker to assess the microcirculation disturbance of the acute pancreatitis,be connected with the severity of the acute pancreatitis,and serve as the new biomarker to assess the severity.ObjectiveThis retrospective study in which the patients with acute pancreatitis andgastric or colonic polyps was treated in Digestive Department of Qilu Hospital of Shandong University from January 2015 to December 2017 was implemented to evaluate value of ischemic modified protein(IMA)in microcirculatory disorder of acute pancreatitis and in assessing the severity of acute pancreatitis when compared with blood calcium and albumin which have higher specificity.So we can provide useful and reliable reference for diagnosis and treatment.Methods1.Data collection:Clinical date of all cases including AP and control group in Digestive Department of Qilu Hospital of Shandong University from January2015 to December 2017 wre collected.According to the diagnostic criterion and the standard of classification of AP,the 137 AP patients including 90 males and 47 females were divided into mild acute pancreatitis group(MAP)including 43 patients,moderately severe acute pancreatitis group(MSAP)including 53 patients,and severe acute pancreatitis group(SAP)including 42 patients.The control group patients including 59 males and 39 females were diagnosed of gastric or colonic polyps.The data collected includes age,sex,IMA,Ca,ALB,APACHEII scores,the Ranson scores,the CT imaging scores,local and systemic complications and so on.The exclusion criteria includes incomplete clinical data,acute coronary syndrome,the pulmonary embolism,cerebrovascular disease,chronic pancreatitis,pancreatic cancer and serious infection in other organs.2.Data processing:The statistic analysis of total data in this study is by the SPSS 19.0 software.Enumeration data uses the chi-squared Test.Measurement data is recorded with mean±standard deviation(X±SD),those conforming to normal distribution using t test and the rest using Mann-Whitney U-test when compared between two groups;Measurement data conforming to normal distribution between three groups uses the one-way analysis of variance,then pairwise comparison adopts SNK test;otherwise,we can use the Kruskal-Wallis H-test and Dunnett^s T3 for pairwise comparison.Then,we chose the statistically different factors as independent variables applying logistic regression analysis to explore the independent risk factors for AP,draw ROC curve,and calculate the AUC.P<0.05 is considered statistically significant.Results1.Comparison results between AP patients and control group:The age ranges from 44 to 87 years and the average age is 55.62±14.11 years in the AP group.The age ranges from 40 to 80 years and the average age is 57.28111.15 years in the control group.No difference was observed in the terms of age and sex,but statistically significant difference was observed in the terms of ischemic modified protein(IMA),blood calcium,and plasma albumin in comparison done between AP patients and control group(Table 1).2.Further comparison of IMA,Ca and ALB among MAP,MSAP and SAP group:As indicated in the Tabel 2,the level of ischemic modified protein(IMA)was significantly high in SAP group compared to MAP and MSAP group,nevertheless,the levels of blood calcium,and plasma albumin in SAP group were considerably lower than in MAP and MSAP group.In MSAP,the level of the ischemic modified protein(IMA)is higher than in MAP,but the levels of blood calcium,and plasma albumin were lower than in MAP group(Table2).3.Multivariable logistic regression analysis imply that ischemic modified protein(IMA)(OR=0.916,p=0.000)is positively related to the incidence of the AP,while blood calcium(OR=1.007,p=0.010)and plasma albumin(OR=1.393,p=0.001)are negatively related to it.All of the above are independent factors for AP(Table3).4.The ROC curve for AP suggested that the AUCs of ischemic modified protein(IMA),blood calcium,and plasma albumin are respectively 0.916(95%CI 0.887-0.954,P=0.000),0.877(95%CI 0.835-0.920,P=0.000),0.919(95%CI 0.886-0.953,P=0.000).Then,the AUCs for AP of two index association are respectively 0.932(IMA and ALB,95%CI 0.902-0.963,P=0.000),0.929(IMA and Ca,95%CI 0.898-0.961,P=0.000),0.926(Ca and ALB,95%CI 0.894-0.957,P=0.000).Finally,the combined AUC of ischemic modified protein(IMA),blood calcium,and plasma albumin is 0.942(95%CI 0.915-0.970,P=0.000,)5.The ROC curve for SAP suggested that the AUCs of ischemic modified protein(IMA),blood calcium,and plasma albumin are respectively 0.965(95%CI 0.914-1.000,P=0.000),0.984(95%CI 0.960-1.000,P=0.000),0.989(95%CI 0.974-1.000,P=0.000).Furthermore,the AUCs for AP of two index association arerespectively0.989(IMA and Ca,95%CI 0.967-1.000,P=0.000),0.993(IMA and ALB,95%CI 0.981-1.000,P=0.000),0.993(Ca and ALB,95%CI 0.993-1.000,P=0.000).Finally,the combined AUC of ischemic modified protein(IMA),blood calcium,and plasma albumin is 0.992(95%CI 0.977-1.000,P=0.000).ConclusionsThe IMA,Ca and ALB are considered as independent risk factous for AP,being also related to the severity of AP.IMA is positi-vely correlated with the AP severity,but Ca and ALB are negatively correlated with the AP severity,which is consistent with previous studies In addition,the accuracy for predicting AP of IMA and ALB is higher than Ca.The accuracies of two or three indexes combination are apparently higher than that of single factor.The respective accuracy for predicting SAP of IMA,Ca and ALB is higher than for predicting AP,and the accuracies to predict SAP of two or three indexes combination are apparently higher than that of single factor to predict AP.To sum up,IMA can serves a biomarker to assess the AP severity,and the acuuracy is higher when combined with other hypersensitive biomarkers.Meanwhile,we speculate that IMA can serve as the biomarker of the microcirculation disturbance of AP,because it is always considered as a ischemia indicator.