Dataset Information

Acinar injury and early cytokine response in human acute biliary pancreatitis.

ABSTRACT: Clinical acute pancreatitis (AP) is marked by an early phase of systemic inflammatory response syndrome (SIRS) with multiorgan dysfunction (MODS), and a late phase characterized by sepsis with MODS. However, the mechanisms of acinar injury in human AP and the associated systemic inflammation are not clearly understood. This study, for the first time, evaluated the early interactions of bile acid induced human pancreatic acinar injury and the resulting cytokine response. We exposed freshly procured resected human pancreata to taurolithocolic acid (TLCS) and evaluated for acinar injury, cytokine release and interaction with peripheral blood mononuclear cells (PBMCs). We observed autophagy in acinar cells in response to TLCS exposure. There was also time-dependent release of IL-6, IL-8 and TNF-? from the injured acini that resulted in activation of PBMCs. We also observed that cytokines secreted by activated PBMCs resulted in acinar cell apoptosis and further cytokine release from them. Our data suggests that the earliest immune response in human AP originates within the acinar cell itself, which subsequently activates circulating PBMCs leading to SIRS. These findings need further detailed evaluation so that specific therapeutic targets to curb SIRS and resulting early adverse outcomes could be identified and tested.

SUBMITTER: Jakkampudi A

PROVIDER: S-EPMC5681596 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Acinar injury and early cytokine response in human acute biliary pancreatitis.

Jakkampudi Aparna A Jangala Ramaiah R Reddy Ratnakar R Mitnala Sasikala S Rao G Venkat GV Pradeep Rebala R Reddy D Nageshwar DN Talukdar Rupjyoti R

Scientific reports 20171110 1

Clinical acute pancreatitis (AP) is marked by an early phase of systemic inflammatory response syndrome (SIRS) with multiorgan dysfunction (MODS), and a late phase characterized by sepsis with MODS. However, the mechanisms of acinar injury in human AP and the associated systemic inflammation are not clearly understood. This study, for the first time, evaluated the early interactions of bile acid induced human pancreatic acinar injury and the resulting cytokine response. We exposed freshly procur ...[more]

PMID: 29127325

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Project description:To investigate the clinical usefulness of early endoscopic ultrasonography (EUS) in the management of acute biliary pancreatitis (ABP).All consecutive patients entering the emergency department between January 2010 and December 2012 due to acute abdominal pain and showing biochemical and/or radiological findings consistent with possible ABP were prospectively enrolled. Patients were classi?ed as having a low, moderate, or high probability of common bile duct (CBD) stones, according to the established risk strati?cation. Exclusion criteria were: gastrectomy or patient in whom the cause of biliary obstruction was already identified by ultrasonography. All enrolled patients underwent EUS within 48 h of their admission. Endoscopic retrograde cholangiopancreatography was performed immediately after EUS only in those cases with proven CBD stones or sludge. The following parameters were investigated: (1) clinical: age, sex, fever; (2) radiological: dilated CBD; and (3) biochemical: bilirubin, AST, ALT, gGT, ALP, amylase, lipasis, PCR. Association between presence of CBD stone at EUS and the individual predictors were assessed by univariate logistic regression. Predictors significantly associated with CBD stones (P < 0.05) were entered in a multivariate logistic regression model.A total of 181 patients with pancreatitis were admitted to the emergency department between January 2010 and December 2012. After exclusion criteria a total of 71 patients (38 females, 53.5%, mean age 58 ± 20.12 years, range 27-89 years; 33 males, 46.5%, mean age 65 ± 11.86 years, range 41-91 years) were included in the present study. The probability of CBD stones was considered low in 21 cases (29%), moderate in 26 (37%), and high in the remaining 24 (34%). The 71 patients included in the study underwent EUS, which allowed for a complete evaluation of the target sites in all the cases. The procedure was completed in a mean time of 14.7 min (range 9-34 min), without any notable complications.The overall CBD stone frequency was 44% (31 of 71), with a significant increase from the group at low pretest probability to that at moderate (OR = 5.79, P = 0.01) and high (OR = 4.25, P = 0.03) pretest probability.Early EUS in ABP allows, if appropriate, immediate endoscopic treatment and significant spare of unnecessary operative procedures thus reducing possible related complications.

Project description:BackgroundAcute kidney injury (AKI) represents a frequent and grave complication associated with acute pancreatitis (AP), substantially elevating both mortality rates and the financial burden of hospitalization. The aim of our study is to construct a predictive model utilizing automated machine learning (AutoML) algorithms for the early prediction of AKI in patients with AP.MethodsWe retrospectively analyzed patients who were diagnosed with AP in our hospital from January 2017 to December 2021. These patients were randomly allocated into a training set and a validation set at a ratio of 7:3. To develop predictive models for each set, we employed the least absolute shrinkage and selection operator (LASSO) algorithm along with AutoML. A nomogram was developed based on multivariate logistic regression analysis outcomes. The model's efficacy was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Additionally, the performance of the model constructed via AutoML was evaluated using decision curve analysis (DCA), feature importance, SHapley Additive exPlanations (SHAP) plots, and locally interpretable model-agnostic explanations (LIME).ResultsThis study incorporated a total of 437 patients who met the inclusion criteria. Out of these, 313 were assigned to the training cohort and 124 to the validation cohort. In the training and validation cohorts, AKI occurred in 68 (21.7%) and 29(23.4%) patients, respectively. Comparative analysis revealed that the AutoML models exhibited enhanced performance over traditional logistic regression (LR). Furthermore, the deep learning (DL) model demonstrated superior predictive accuracy, evidenced by an area under the ROC curve of 0.963 in the training set and 0.830 in the validation set, surpassing other comparative models. The key variables identified as significant in the DL model within the training dataset included creatinine (Cr), urea (Urea), international normalized ratio (INR), etiology, smoking, alanine aminotransferase (ALT), hypertension, prothrombin time (PT), lactate dehydrogenase (LDH), and diabetes.ConclusionThe AutoML model, utilizing DL algorithm, offers considerable clinical significance in the early detection of AKI among patients with AP.

Dataset Information

Acinar injury and early cytokine response in human acute biliary pancreatitis.

Publications

Acinar injury and early cytokine response in human acute biliary pancreatitis.

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