Timing and impact of infections in acute pancreatitis

Contains fulltext : 81117.pdf (publisher's version ) (Closed access)BACKGROUND: Although infected necrosis is an established cause of death in acute pancreatitis, the impact of bacteraemia and pneumonia is less certain. METHODS: This was a cohort study of 731 patients with a primary episode of acute pancreatitis in 2004-2007, including 296 patients involved in a randomized controlled trial to investigate the value of probiotic treatment in severe pancreatitis. Time of onset of bacteraemia, pneumonia, infected pancreatic necrosis, persistent organ failure and death were recorded. RESULTS: The initial infection in 173 patients was diagnosed a median of 8 (interquartile range 3-20) days after admission (infected necrosis, median day 26; bacteraemia/pneumonia, median day 7). Eighty per cent of 61 patients who died had an infection. In 154 patients with pancreatic parenchymal necrosis, bacteraemia was associated with increased risk of infected necrosis (65 versus 37.9 per cent; P = 0.002). In 98 patients with infected necrosis, bacteraemia was associated with higher mortality (40 versus 16 per cent; P = 0.014). In multivariable analysis, persistent organ failure (odds ratio (OR) 18.0), bacteraemia (OR 3.4) and age (OR 1.1) were associated with death. CONCLUSION: Infections occur early in acute pancreatitis, and have a significant impact on mortality, especially bacteraemia. Prophylactic strategies should focus on early intervention

Association Analysis of Genetic Variants in the Myosin IXB Gene in Acute Pancreatitis

Introduction: Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis. Methods: Five single nucleotide polymorphisms (SNPs) in MYO9B, two SNPs in PARD3, and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls, and in a German cohort of 235 patients and 250 controls. Results: Association to MYO9B and PARD3 was observed in the Dutch cohort, but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort (p <0.05). Joint analysis of the combined cohorts showed that, after correcting for multiple testing, only two SNPs in MYO9B remained associated (rs7259292, p = 0.0031, odds ratio (OR) 1.94, 95% confidence interval (95% CI) 1.35-2.78; rs1545620, p = 0.0006, OR 1.33, 95% CI 1.16-1.53). SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis. None of the SNPs showed association to disease severity or etiology. Conclusion: Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2

Intestinal barrier dysfunction in a randomized trial of a specific probiotic composition in acute pancreatitis.

Contains fulltext : 80110.pdf (publisher's version ) (Closed access)OBJECTIVES: To determine the relation between intestinal barrier dysfunction, bacterial translocation, and clinical outcome in patients with predicted severe acute pancreatitis and the influence of probiotics on these processes. SUMMARY OF BACKGROUND DATA: Randomized, placebo-controlled, multicenter trial on probiotic prophylaxis (Ecologic 641) in patients with predicted severe acute pancreatitis (PROPATRIA). METHODS: Excretion of intestinal fatty acid binding protein (IFABP, a parameter for enterocyte damage), recovery of polyethylene glycols (PEGs, a parameter for intestinal permeability), and excretion of nitric oxide (NOx, a parameter for bacterial translocation) were assessed in urine of 141 patients collected 24 to 48 h after start of probiotic or placebo treatment and 7 days thereafter. RESULTS: IFABP concentrations in the first 72 hours were higher in patients who developed bacteremia (P = 0.03), infected necrosis (P = 0.01), and organ failure (P = 0.008). PEG recovery was higher in patients who developed bacteremia (PEG 4000, P = 0.001), organ failure (PEG 4000, P < 0.0001), or died (PEG 4000, P = 0.009). Probiotic prophylaxis was associated with an increase in IFABP (median 362 vs. 199 pg/mL; P = 0.02), most evidently in patients with organ failure (P = 0.001), and did not influence intestinal permeability. Overall, probiotics decreased NOx (P = 0.05) but, in patients with organ failure, increased NOx (P = 0.001). CONCLUSIONS: Bacteremia, infected necrosis, organ failure, and mortality were all associated with intestinal barrier dysfunction early in the course of acute pancreatitis. Overall, prophylaxis with this specific combination of probiotic strains reduced bacterial translocation, but was associated with increased bacterial translocation and enterocyte damage in patients with organ failure