Research On The Establishment Of Subgroups And Treatment Strategy In Severe Acute Pancreatitis Complicated With Early Persistent Organ Failure

Severe acute pancreatitis(SAP)is a common critical disease with a mortality of 17%to 39% and is charactered by persistent organ failure(POF).Patients with POF developing in the early stage(within one week)is one of the most severe kind of SAP,which is usually associated with poor prognosis.Current guidelines showed that the intervention of necrosis should be delayed to four weeks,until pancreatic necrosis being mature / wrapped.However,these patients often developed "clinical decompensation" within four weeks,which even lead to death.Drainage of necrosis can obviously improve the inflammation by draining inflammatory substances and decrease the abdominal pressure.We hypothesized that aggressive intervention of pancreatic necrosis is more beneficial to SAP patients with early POF.Therefore,we invesigated it in three parts.In the first part,the clinical subtypes of SAP patients with early POF from 2012 to2017 were established by using group-based multi-dimensional trajectory analysis(GBMDTA).All 258 patients had POF within 7 days of onset,including respiratory failure(84.5%),renal failure(53.5%)and circulatory failure(37.2%).The organ function scores at the 3rd / 7th / 10 th / 14 th / 21 st day were selected for GBMDTA analysis.OF development were divided into four groups with,and were further clinical empowered: "Organ failure recoevered group"(Group 1),"multiple organ failure recovered group"(Group 2),"organ failure deteriorated"(Group 3),"multiple organ failure without recovered"(Group 4).We found group1 patients had better outcomes in terms of pancreatic necrosis infection(PNI),abdominal hemorrhage and hospital mortality,The prognosis of group 2 / 3 / 4 was poorer,and had more need for intervention of ANC;ROC analysis showed that GBDMTA was more effective than traditional predictors in predicting mortality(AUROC = 0.856)and PNI(auroc = 0.742).These results suggest that the trajectory of organ function can divide SAP patients with early POF into different subtypes and has good predictive effect.Aggressive intervention may affect the trajectory of organ failure of and improve the prognosis.In the second part,we compared the effect of aggressive intervention strategy(≤ 4weeks,group A)and standard intervention strategy(> 4 weeks,group B)on the prognosis of patients with SAP complicated with early POF.A total of 186 patients were included,of which 119(64.0%)received aggressive intervention,67 patients(36.0%)with standard intervention.There was no significant difference in demographic characteristics between the two groups.But the severity of group A was more serious.The intervention time points of the two groups were significantly different.Group A patients had significantly higher rate of PNI,more steps of necrosectomy.They had lower mortality rate but not significantly.In addition,necrotic sampling showed that the liquefaction level of necrosis increased with the interval from onset.These findings suggest that aggressive intervention strategy may increase the risk of PNI and require more intervention steps,but the prognosis of the patients with more severity is similar to that of the standard treatment,suggesting that active intervention may be more beneficial to such patients.In the last part,we performed a multicenter randomized controlled trial in the Chinese Acute Pancreatitis Clinical Trail Group,and recruited five tertiary centers of pancreatitis in five provinces.120 SAP patients with early POF were included.Group A is intervened according to the deterioration of POF(deterioration,new onset,lasting for 7 days)after 7 days,and group B received standard treatment.Up until March 2021,74 patients(38 in group A and 36 in group B)was enrolled.And we completed the midterm examination in September 2020.There was no significant difference in baseline level between the two groups: PNI,gastrointestinal fistula,abdominal bleeding,open surgery rate and adverse events.These outcomes suggested that the clinical study of early on-demand intervention has passed the safety check,and the trial is expected to be completed in 2023.In conclusion,this study targeted at SAP with early POF.We established different subtypes according to the development of POF by GBMDTA,and provided potential routine for individualized treatment.Secondly,we compared the impact of aggressive intervention and standard treatment and found the former may reverse the condition of such patients.Finally,a multi-center randomized control trial was conducted to provide the highest quality evidence of effect of early on-demand intervention on patients with early POF and new treatment strategies for such patients.