Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

BACKGROUND: Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined. OBJECTIVES: To determine the association between mortality and the development of early IPN. METHODS: International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses. RESULTS: A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63-3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70-13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05). CONCLUSION: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.

Scientific report: a case of acute pancreatitis due to liraglutide

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Scientific report: a case of acute pancreatitis due to liraglutide.

Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog. GLP-1 analogues are used as a second option treatment for type 2 diabetes and weight management in obese patients. Data in the literature suggests an association between GLP-1 agonist use and acute pancreatitis (AP). Furthermore, it has been suggested that acute pancreatitis is a potential complication of liraglutide therapy and liraglutide should be used cautiously in patients at risk of pancreatitis. This case reported herein was a 44-year-old female diagnosed with acute pancreatitis based on 2 of 3 criteria when she presented to the Emergency Department with epigastric pain, which radiated to her back.

Influence of age, body mass index and comorbidity on major outcomes in acute pancreatitis, a prospective nation-wide multicentre study.

BACKGROUND: There are few large prospective cohort studies evaluating predictors of outcomes in acute pancreatitis. OBJECTIVES: The purpose of this study was to determine the role of age and co-morbid disease in predicting major outcomes in acute pancreatitis. METHODS: Data points were collected according to a predefined electronic data collection form. Acute pancreatitis and its complications were defined according to the revised Atlanta classification. Univariable and multivariable analyses were conducted using Cox proportional hazard regression and multiple logistic regression. RESULTS: From June 2013-February 2015, 1655 adult patients were recruited from 23 centres across Spain. Co-morbid disease, obesity, open surgical necrosectomy within 30 days, and pancreatic necrosis were independently associated with both 30-day mortality and persistent organ failure (p < 0.05 for all). Age was not associated with persistent organ failure, however the extreme of age (>85 years) was associated with mortality (p < 0.05). Co-morbid disease and obesity were not independently associated with a prolonged length of stay or other markers of morbidity on adjusted analysis (p > 0.05). CONCLUSION: Comorbidity and obesity are important determinates of mortality and persistent organ failure in acute pancreatitis, but in the absence of organ failure they do not appear to independently contribute to morbidity. This has important implications for severity classification and predictive models of severity in acute pancreatitis.

Fluid resuscitation with lactated Ringer's solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial.

BACKGROUND: Little is known regarding the optimal type of fluid resuscitation in acute pancreatitis (AP). OBJECTIVE: The objective of this article was to compare the effect of lactated Ringer's solution (LR) vs normal saline (NS) in the inflammatory response in AP. METHODS: We conducted a triple-blind, randomized, controlled trial. Patients ≥ 18 admitted with AP were eligible. Patients were randomized to receive LR or NS. Primary outcome variables were number of systemic inflammatory response syndrome (SIRS) criteria at 24 hours, 48 hours and 72 hours and blood C-reactive protein (CRP) levels at 48 hours and 72 hours. In vitro complementary experiments were performed to further explore the interaction between pH, lactate and inflammation. RESULTS: Nineteen patients receiving LR and 21 receiving NS were analyzed. The median (p25-p75) number of SIRS criteria at 48 hours were 1 (1-2) for NS vs 1 (0-1) for LR, p = 0.060. CRP levels (mg/l) were as follows: at 48 hours NS 166 (78-281) vs LR 28 (3-124), p = 0.037; at 72 hours NS 217 (59-323) vs LR 25 (3-169), p = 0.043. In vitro, LR inhibited the induction of inflammatory phenotype of macrophages and NF-κB activation. This effect was not observed when using Ringer's solution without lactate, suggesting a direct anti-inflammatory effect of lactate. CONCLUSIONS: Lactated Ringer's is associated with an anti-inflammatory effect in patients with acute pancreatitis.

La enteropatía de intestino delgado por antiinflamatorios no esteroideos y la hemorragia digestiva de origen oscuro / Nonsteroidal anti-inflammatory drugs-induced small bowel enteropathy and obscure gastrointestinal bleeding

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An international multicenter study of early intravenous fluid administration and outcome in acute pancreatitis.

AIMS: Early aggressive fluid resuscitation in acute pancreatitis is frequently recommended but its benefits remain unproven. The aim of this study was to determine the outcomes associated with early fluid volume administration in the emergency room (FVER) in patients with acute pancreatitis. METHODS: A four-center retrospective cohort study of 1010 patients with acute pancreatitis was conducted. FVER was defined as any fluid administered from the time of arrival to the emergency room to 4 h after diagnosis of acute pancreatitis, and was divided into tertiles: nonaggressive (<500 ml), moderate (500 to 1000 ml), and aggressive (>1000 ml). RESULTS: Two hundred sixty-nine (26.6%), 427 (42.3%), and 314 (31.1%) patients received nonaggressive, moderate, and aggressive FVER respectively. Compared with the nonaggressive fluid group, the moderate group was associated with lower rates of local complications in univariable analysis, and interventions, both in univariable and multivariable analysis (adjusted odds ratio (95% confidence interval): 0.37 (0.14-0.98)). The aggressive resuscitation group was associated with a significantly lower need for interventions, both in univariable and multivariable analysis (adjusted odds ratio 0.21 (0.05-0.84)). Increasing fluid administration categories were associated with decreasing hospital stay in univariable analysis. CONCLUSIONS: Early moderate to aggressive FVER was associated with lower need for invasive interventions.

The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis.

BACKGROUND: Acute pancreatitis is an inflammatory disorder of the pancreas that is responsible for significant morbidity and mortality. The inflammasome pathway has acquired significant relevance in the pathogenesis of many inflammatory disorders, but its role in patients with acute pancreatitis still awaits clarification. METHODS: We performed a prospective study in which 27 patients with acute pancreatitis and 16 healthy controls were included. We isolated peripheral blood mononuclear cells (PBMCs) and we assessed the expression and activation of different inflammasomes as well as their association with the clinical course of the disease. RESULTS: Our results show that PBMCs from patients with acute pancreatitis have elevated expression of several components of the inflammasome complex, including the inflammasome-forming receptor absent in melanoma 2 (AIM2), early during the onset of the disease. Activation of the AIM2 or NLRP3 inflammasomes in PBMCs from patients with acute pancreatitis results in exacerbated IL-1ß and IL-18 production compared with PBMCs from healthy controls. Furthermore, both AIM2 mRNA expression and AIM2-mediated production of IL-1ß by PBMCs correlated with increased systemic inflammation in these patients. Last, AIM2 expression was further increased in those patients that developed transient or persistent organ failure (moderate or severe acute pancreatitis). CONCLUSIONS: Our data demonstrates that AIM2 inflammasome expression and activation is increased early during the course of acute pancreatitis, and suggests that AIM2 activation may affect systemic inflammation and organ failure in these patients.

Early Predictors of Fluid Sequestration in Acute Pancreatitis: A Validation Study.

OBJECTIVES: The primary aim of this retrospective study was to externally validate predictors of increased fluid sequestration at 48 hours (FS48) in acute pancreatitis (AP). METHODS: Patients admitted between January 10 and February 13 with a diagnosis of AP were evaluated. The FS48 was calculated as difference between total fluid input and output in the first 48 hours. Predictors of FS48, such as young age, alcoholic etiology, hemoconcentration, hyperglycemia, and systemic inflammatory response syndrome (SIRS), and outcomes in AP, such as increased length of stay, acute fluid collection(s), necrosis, and persistent organ failure (POF), were defined in accordance with the previous study. Linear regression analysis was performed to evaluate the association between predictors and outcome. RESULTS: Two hundred twenty-seven AP patients (mean age, 48 years; 54% men) with a median FS48 of 4.2 L were evaluated. Age younger than 40 years, alcoholic etiology, hemoconcentration, and SIRS independently predicted increased FS48 (P < 0.05). Increased FS48 was associated with persistent SIRS and POF (P < 0.01). There was a significant trend between number of predictors and FS (P < 0.001). The presence of 4 predictors or more was associated with higher rates of persistent SIRS and POF (P < 0.01). CONCLUSIONS: Our study validated 4 of 5 predictors of increased FS48 from the previous study. Presence of 4 predictors or more and increased FS48 are both associated with persistent SIRS and POF.

Intermediate-risk patients with three to four small adenomas should be considered low risk for colorectal cancer screening.

BACKGROUND AND AIM: Intermediate-risk patients following a colorectal cancer screening program may have differential risk of advanced lesions depending on the findings of an index colonoscopy. The aim of the present study was to comparatively assess advanced colorectal neoplasia risk at the first follow-up colonoscopy among the different intermediate-risk subgroups with a focus on patients with three to four adenomas. METHODS: All patients recruited for a baseline screening colonoscopy between 2006 and 2011 were included. Number, size and histopathological characteristics of adenomas were collected. Main outcome was an advanced colorectal neoplasia detection rate (invasive carcinoma or advanced adenoma) at the first follow-up colonoscopy. Low- and high-risk patients were excluded. RESULTS: Five hundred and sixty-one intermediate-risk patients (63.3% men, mean age: 59.01 ± 6.16 years) underwent indexing and follow-up colonoscopy. By multivariate analysis, three to four adenomas (OR: 3.613 [95% CI: 1.661-7.859], P = 0.001) and adenoma size ≥10 <20 mm (OR: 3.374 [95% CI: 1.618-7.034], P = 0.001) were independent factors associated with advanced colorectal neoplasia. Advanced lesions were detected in 7.66% of cases. Of patients with advanced colorectal neoplasia, 51.16% belonged to the three-to-four-adenoma group and ≥1 of ≥10 <20-mm subgroups (n = 132, 23.53%). These patients demonstrated a higher rate of advanced lesions [OR: 3.886 (95% CI: 2.061-7.325), P < 0.001] than patients with three to four small adenomas of <10 mm (16.67% vs 5.07%, P < 0.001). The association between patients with small adenomas (n = 217, 38.68%) and advanced lesions was not significant (OR: 0.521 [95% CI: 0257-1.056], P = 0.066). CONCLUSION: Intermediate-risk patients with three to four small adenomas achieved a very low advanced lesion rate at follow up. Surveillance interval should be lengthened because these patients should be considered low risk.