Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

Body impedance analysis to estimate malnutrition in inflammatory bowel disease patients - A cross-sectional study.

OBJECTIVE: Malnutrition is a common clinical problem in patients with inflammatory bowel diseases (IBD). However, a gold standard for the detection of malnutrition in IBD patients is lacking. METHODS: A cross-sectional study to assess malnutrition in patients with IBD and healthy controls (HCs). Clinical characteristics (Montreal classification, disease activity, previous surgery) and mutations in the NOD2 gene in patients with Crohn's disease (CD) were obtained. We performed a nutritional assessment with screening for nutritional risk and diagnosis for malnutrition (Malnutrition Universal Screening Tool [MUST]) score, NRS-2002, European Society for Clinical Nutrition and Metabolism (ESPEN), and Global Leadership Initiative on Malnutrition (GLIM) criteria and performed body impedance analysis (BIA). RESULTS: 101 IBD patients (57 CD and 44 ulcerative colitis (UC) and 50 HC were included in a single northern German tertiary center. GLIM criteria detected malnutrition significantly more often compared to the ESPEN criteria. Active disease, a long-standing disease course, and previous surgery were associated with reduced muscle mass. IBD patients had a higher fat mass index compared to HC. Mutations in the NOD2 gene had no effect on nutritional status. CONCLUSIONS: The GLIM criteria detect malnutrition at a higher rate compared to ESPEN. Specific disease factors might put IBD patients at a higher risk for the development of malnutrition, so these patients might benefit from a frequently performed screening, which might result in a favorable disease course.

Does etiology of acute pancreatitis matter? A review of 391 consecutive episodes.

CONTEXT: Acute pancreatitis can be triggered by a variety of factors ranging from short lasting to sustained disruptions. It is plausible that the characteristics and course of disease differ among etiologies. Data distinguishing characteristics of patients with pancreatitis of biliary, alcoholic, idiopathic or other origin are scarce and conflicting. OBJECTIVE: To compare patients' characteristics, baseline parameters on admission, and outcome in patients with an episode of acute pancreatitis in whom the etiology was thoroughly determined. DESIGN: Retrospective study. SETTING: Single center. PATIENTS: Three-hundreds and 91 consecutive episodes of acute pancreatitis through the years 2008 to 2011. MAIN OUTCOME MEASURES: Gender, age, body mass index, Charlson comorbidity index, history of pancreatitis, heart rate, blood pressure, plasma lipase, hematocrit, plasma creatinine, white blood cell count, rate of persistent organ failure and necrosis, maximum C-reactive protein, duration of hospitalization, mortality. RESULTS: There were marked differences between the groups. Biliary etiology was associated with higher age and body weight, female predominance, higher plasma lipase, and a favourable outcome. Alcoholic etiology had male predominance, a tendency for initial hemoconcentration, a lower plasma lipase, and the highest rate of necrosis. Idiopathic etiology had the highest rate of persistent organ failure and the highest mortality. CONCLUSIONS: Biliary, alcoholic and idiopathic acute pancreatitis should be treated as distinct entities. While alcoholic episodes have the highest risk of necrosis, the worst outcome was observed in the idiopathic group. Hence, finding no causality for an episode of acute pancreatitis after thorough investigation might be a predictor for poor outcome. Larger studies are warranted to confirm this.

Detrimental effect of high volume fluid administration in acute pancreatitis - a retrospective analysis of 391 patients.

BACKGROUND: Early fluid resuscitation is recommended for the therapy of acute pancreatitis in order to prevent complications. There are, however, no convincing data supporting this approach. METHODS: We reviewed 391 consecutive cases of confirmed acute pancreatitis. Admitting physicians had been advised to administer an aggressive fluid resuscitation in the early phase of disease, if possible. We tested whether disease severity according to the revised Atlanta Classification, local complications, and maximum C-reactive protein levels were predictable by the initial volume therapy in logistic and linear regression models, respectively. We also determined which parameters on admission encouraged a more aggressive fluid resuscitation. RESULTS: The recorded fluid administered within the first 24 h was 5300 [3760; 7100] ml (median [1st; 3rd quartile]). More aggressive volume therapy was associated with disease severity and a higher rate of local complications. There was a linear relationship between administered volume and the maximum C-reactive protein. The amount of administered fluid was significantly attributed to age, hematocrit, and white blood cell count on admission. When adjusted for these parameters the impact of administered volume on outcome was still present but attenuated. CONCLUSIONS: We found detrimental effects of fluid therapy on major outcome parameters throughout the whole range of administered volume. More volume was administered in younger patients and in patients with evidence of hemoconcentration and inflammation. The adverse effects of volume therapy persisted after elimination of these parameters. Caution should therefore be advised with regards to volume therapy in patients with acute pancreatitis.