Acute Pancreatitis in Western Sydney

Background: Acute pancreatitis (AP) has a mortality of 30% in severe cases. Major causes worldwide are gallstones and alcohol misuse. The first aim was to characterise the aetiology, epidemiology and outcomes for patients with AP in Western Sydney (WS). The second aim was to explore pathogenesis of AP and identify potential biomarkers of severe AP using RNA sequencing. Methods: 1) A retrospective cohort analysis of 932 patients with AP presenting to 4 tertiary hospitals in WS was performed. Data from medical records was analysed using SPSS software 2) A RNA sequencing study was performed in a separate cohort of 84 patients with AP (mild=55, moderately severe=19, severe=10) from 2 tertiary hospitals in WS. RNA sequencing was performed on peripheral venous blood collected within 24h of presentation to hospital and data analysis conducted using DESeq2 and Ingenuity Pathway Analysis software. Results: The majority of patients had gallstone AP (40%). 11.1% had severe AP and mortality was 1%. Females were less likely to develop severe AP. There was a failure to comply with guidelines for early management of AP. RNA sequencing identified 1914 differentially expressed genes (DEG) in severe AP compared to moderately severe and mild AP. Lipocalin 2, IL10 and olfactomedin 4 are potential biomarkers for severe AP and pathways dysregulated in severe AP had immunological and mitochondrial functions. There were 1468 DEG between females and males with AP and pathways unique to females were involved in B cell function. There were no DEG between the different aetiological groups. Conclusion: The majority of patients have mild AP with a low risk of mortality. T cell suppression and mitochondrial dysfunction are important pathways in severe AP. We demonstrated clear differences in the pathophysiology of AP between genders, with women demonstrating up-regulation of B cell functions. The differences in clinical outcomes between genders in AP may be due to underlying immune system differences

Acute Pancreatitis in Western Sydney

Background: Acute pancreatitis (AP) has a mortality of 30% in severe cases. Major causes worldwide are gallstones and alcohol misuse. The first aim was to characterise the aetiology, epidemiology and outcomes for patients with AP in Western Sydney (WS). The second aim was to explore pathogenesis of AP and identify potential biomarkers of severe AP using RNA sequencing. Methods: 1) A retrospective cohort analysis of 932 patients with AP presenting to 4 tertiary hospitals in WS was performed. Data from medical records was analysed using SPSS software 2) A RNA sequencing study was performed in a separate cohort of 84 patients with AP (mild=55, moderately severe=19, severe=10) from 2 tertiary hospitals in WS. RNA sequencing was performed on peripheral venous blood collected within 24h of presentation to hospital and data analysis conducted using DESeq2 and Ingenuity Pathway Analysis software. Results: The majority of patients had gallstone AP (40%). 11.1% had severe AP and mortality was 1%. Females were less likely to develop severe AP. There was a failure to comply with guidelines for early management of AP. RNA sequencing identified 1914 differentially expressed genes (DEG) in severe AP compared to moderately severe and mild AP. Lipocalin 2, IL10 and olfactomedin 4 are potential biomarkers for severe AP and pathways dysregulated in severe AP had immunological and mitochondrial functions. There were 1468 DEG between females and males with AP and pathways unique to females were involved in B cell function. There were no DEG between the different aetiological groups. Conclusion: The majority of patients have mild AP with a low risk of mortality. T cell suppression and mitochondrial dysfunction are important pathways in severe AP. We demonstrated clear differences in the pathophysiology of AP between genders, with women demonstrating up-regulation of B cell functions. The differences in clinical outcomes between genders in AP may be due to underlying immune system differences