Background: Identification of patients at risk for mortality early in the course of acute pancreatitis (AP) is an important step in improving outcome. Methods: Using Classification and Regression Tree (CART) analysis, a clinical scoring system was developed for prediction of in-hospital mortality in AP. The scoring system was derived on data collected from 17 992 cases of AP from 212 hospitals in 2000-2001. The new scoring system was validated on data collected from 18 256 AP cases from 177 hospitals in 2004-2005. The accuracy of the scoring system for prediction of mortality was measured by the area under the receiver operating characteristic curve (AUC). The performance of the new scoring system was further validated by comparing its predictive accuracy with that of Acute Physiology and Chronic Health Examination (APACHE) II. Results: CART analysis identified five variables for prediction of in-hospital mortality. One point is assigned for the presence of each of the following during the first 24 h: blood urea nitrogen (BUN) >25 mg/dl; impaired mental status; systemic inflammatory response syndrome (SIRS); age >60 years; or the presence of a pleural effusion (BISAP). Mortality ranged from >20% in the highest risk group to <1% in the lowest risk group. In the validation cohort, the BISAP AUC was 0.82 (95% Cl 0.79 to 0.84) versus APACHE II AUC of 0.83 (95% Cl 0.80 to 0.85). Conclusions: A new mortality-based prognostic scoring system for use in AP has been derived and validated. The BISAP is a simple and accurate method for the early identification of patients at increased risk for in-hospital mortality.

The early prediction of mortality in acute pancreatitis : a large population-based study. Commentary

Poor growth in the Neonatal Intensive Care Unit is associated with an increased risk for poor neurodevelopmental outcomes for preterm infants, however the mechanism is unclear. The microbiome has increasingly been recognized as a modifiable environmental factor to influence host development. Here we explore the hypothesis that the microbiome influences both growth phenotype and brain development. A germ free mouse transfaunation model was used to examine the effects of preterm infant microbiotas known to induce either high growth or low growth phenotypes on postnatal brain development. The microbiome which induced the low growth phenotype was associated with decreases in the neuronal markers NeuN and neurofilament-L as well as the myelination marker MBP when compared to the microbiome associated with the high growth phenotype. Additionally, poor growth phenotype-associated microbiota was associated with increased neuroinflammation marked by increased Nos1, as well as alteration in IGF-1 pathway including decreased circulating and brain IGF-1, decreased circulating IGFBP3, and increased Igfbp3 brain mRNA expression. This study suggests that growth-associated microbiota can influence early neuron and oligodendrocyte development and that this effect may be mediated by effects on neuroinflammation and circulating IGF-1.

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Effects of Intestinal Microbiota on Brain Development in Humanized Gnotobiotic Mice

The lack of effective therapeutic agents specifically tailored for chronic pancreatitis (CP) has hampered clinical care and negatively impacted patients' lives. New mechanistic insights now point to novel therapies, which involve both recently developed and/or repurposed agents. This working group focused on 2 main outcomes for CP: pain and progression of disease. The goal is to frame the essential aspects of trial design including patient-centered outcomes, proposed methods to measure the outcomes of pain and progression, and study design considerations for future trials to facilitate rapid drug development for patients with CP.

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Accelerating the drug delivery pipeline for acute and chronic pancreatitis: Summary of the working group on drug development and trials in chronic pancreatitis at the National Institute of Diabetes and Digestive and Kidney Diseases workshop

Background: Hyperlipasemia is frequently reported in critically ill people without evidence of acute pancreatitis (AP), and has been associated with increased morbidity and mortality.
Hypothesis/Objectives: To evaluate the prevalence of hyperlipasemia at admission and development of hyperlipasemia during hospitalization in critically ill dogs, explore factors associated with hyperlipasemia, and evaluate association with outcome. 
Animals: Critically ill, client owned dogs (n=1,360), presented onas emergencyies and admitted to the intensive care unit, which that had 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6’-methylresorufin) ester (DGGR) lipase activity measured within 24 hours of admission.
Methods: Retrospective cross-sectional study of clinical and laboratory records.
Results: The DGGR -lipase activity was increased >above 3×x the upper reference limit at admission in 216/1,360 (16%) dogs, of which 70/216 (32%) had a clinical diagnosis of AP. Other primary conditions associated with hyperlipasemia were renal, endocrine, and immune-mediated diseases, and upper airway obstruction. Predictors of hyperlipasemia at admission were prior glucocorticoid administration, vomiting and abdominal pain, increased age, plasma bilirubin and creatinine concentrations, and decreased hematocrit. Of dogs with repeat measurements, 78/345 (23%) had significantly increased lipase during hospitalization, of which 13/78 (17%) had a clinical diagnosis of AP. Other primary conditions associated with in-hospital hyperlipasemia were renal and immune-mediated disorders. Predictors of developing hyperlipasemia during hospitalization were hemodialysis events, increased plasma bilirubin and creatinine concentrations, and decreased hematocrit. Hyperlipasemia both at admission and during hospitalization was associated with longer hospitalization and higher mortality.
Conclusions and Clinical Importance: Significant DGGR-hyperlipasemia is frequent in critically ill dogs and is associated with a variety of nonpancreatic conditions and a negative outcome.

Hyperlipasemia in critically ill dogs with and without acute pancreatitis: Prevalence, underlying diseases, predictors, and outcome.

Purpose of reviewTo review recent literature on the management of patients with severe acute pancreatitis (SAP) admitted to an ICU.Recent findingsSAP is a devastating disease associated with a high morbidity and mortality. Recent evidence advocates adequate risk assessment and severity prediction (i

How to deal with severe acute pancreatitis in the critically ill.

Defining the diagnostic value of hyperlipasemia for acute pancreatitis in the critically ill.

Background and aims Patients in the intensive care unit (ICU) with acute pancreatitis (AP) are at risk for extra-pancreatic complications given their severe illness and prolonged length of stay. We sought to determine the rate of extra-pancreatic complications and its effect on length of stay (LOS) and mortality in ICU patients with AP. Methods We performed a retrospective cohort study of ICU patients admitted to a tertiary-care center with a diagnosis of AP. A total of 287 ICU patients had a discharge diagnosis of AP, of which 163 met inclusion criteria. We calculated incidence rates of extra-pancreatic complications and performed a univariate and multi-variable analysis to determine predictors of LOS and mortality. Results There were a total of 158 extra-pancreatic complications (0.97 extra-pancreatic complications per patient). Ninety-five patients had at least one extra-pancreatic complication, whereas 68 patients had no extra-pancreatic complications. Patients with extra-pancreatic complications had a significantly longer LOS (14.7 vs 8.8 days, p < 0.01) when controlling for local pancreatic complications. Patients with non-infectious extra-pancreatic complications had a higher rate of mortality (24.0% vs 16.2%, p = 0.04). Patients requiring dialysis was an independent predictor for LOS and mortality (incidence risk ratio [IRR] 1.73, 95% confidence interval [CI]: 1.263-2.378 and IRR 1.50, 95% CI 1.623-6.843, p < 0.01) on multi-variable analysis. Coronary events were also a predictor for mortality (p = 0.05). Other extra-pancreatic complications were not significant. Conclusions Extra-pancreatic complications occur frequently in ICU patients with AP and impact LOS. Patients with non-infectious extra-pancreatic complications have a higher mortality rate. After controlling for local pancreatic complications, patients requiring dialysis remained an independent predictor for LOS and mortality.

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Extra-pancreatic complications, especially hemodialysis predict mortality and length of stay, in ICU patients admitted with acute pancreatitis.

Use of a novel docosahexaenoic acid formulation vs control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA.

Michael C. Perillo

Papers

Defining the diagnostic value of hyperlipasemia for acute pancreatitis in the critically ill.

Extra-pancreatic complications, especially hemodialysis predict mortality and length of stay, in ICU patients admitted with acute pancreatitis.

Use of a novel docosahexaenoic acid formulation vs control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA.