Pleuropulmonary pathologies in the early phase of acute pancreatitis correlate with disease severity

Background Respiratory failure worsens the outcome of acute pancreatitis (AP) and underlying factors might be early detectable. Aims To evaluate the prevalence and prognostic relevance of early pleuropulmonary pathologies and pre-existing chronic lung diseases (CLD) in AP patients. Methods Multicentre retrospective cohort study. Caudal sections of the thorax derived from abdominal contrast enhanced computed tomography (CECT) performed in the early phase of AP were assessed. Independent predictors of severe AP were identified by binary logistic regression analysis. A one-year survival analysis using Kaplan-Meier curves and log rank test was performed. Result 358 patients were analysed, finding pleuropulmonary pathologies in 81%. CECTs were performed with a median of 2 days (IQR 1-3) after admission. Multivariable analysis identified moderate to severe or bilateral pleural effusions (PEs) (OR = 4.16, 95%CI 2.05-8.45, p Conclusions Increasing awareness of the prognostic impact of large and bilateral PEs and pre-existing CLD could facilitate the identification of patients at high risk for severe AP in the early phase and thus improve their prognosis.Peer reviewe

Mean muscle attenuation correlates with severe acute pancreatitis unlike visceral adipose tissue and subcutaneous adipose tissue

Background: Acute pancreatitis (AP) is a frequent disorder with considerable morbidity and mortality. Obesity has previously been reported to influence disease severity. Objective The aim of this study was to investigate the association of adipose and muscle parameters with the severity grade of AP. Methods: In total 454 patients were recruited. The first contrast-enhanced computed tomography of each patient was reviewed for adipose and muscle tissue parameters at L3 level. Associations with disease severity were analysed through logistic regression analysis. The predictive capacity of the parameters was investigated using receiver operating characteristic (ROC) curves. Results: No distinct variation was found between the AP severity groups in either adipose tissue parameters (visceral adipose tissue and subcutaneous adipose tissue) or visceral muscle ratio. However, muscle mass and mean muscle attenuation differed significantly with p-values of 0.037 and 0.003 respectively. In multivariate analysis, low muscle attenuation was associated with severe AP with an odds ratio of 4.09 (95% confidence intervals: 1.61-10.36, p-value 0.003). No body parameter presented sufficient predictive capability in ROC-curve analysis. Conclusions: Our results demonstrate that a low muscle attenuation level is associated with an increased risk of severe AP. Future prospective studies will help identify the underlying mechanisms and characterise the influence of body composition parameters on AP.Peer reviewe

Acute Pancreatitis. Biomarkers and radiology assessment

Background: Acute pancreatitis (AP) is a common and potentially severe disease. Early identification of severity grade is crucial for the outcome of the patient. For study approaches and comparison of inter-institutional data the AP patients need to be uniformly classified.The aims of this thesis were to investigate the early stratifiation capacity of biomarkers in AP and to assess the morphological criteria of the revised Atlanta classification (RAC).Methods: The studies are based on two cohorts. The first cohort encompasses 285 AP patients from six European centers. All patients had at least one CT performed during the first three months after onset of disease. In total 388 CTs were scored by six local radiologists and one central expert radiologist according to the morphological criteria of the RAC. The results were compared using interobserver agreement levels.The second cohort was enrolled at Skåne University Hospital Malmö. Blood samples from 232 AP patients were collected upon admission and daily as long as the pancreatic amylase was elevated. Exact time for onset of pain was requested at inclusion. From the serum samples selected biomarkers were analysed and compared with severity outcome of the patients.Results: In general the interobserver agreement between the local radiologists and the central expert radiologist was good regarding clinically important radiological features. Two areas of interpretation inconsistensies were identified: presence of extrapancreatic necrosis and necrotic debris of peripancreatic or pancreatic collections.In biomarker analysis we found that cut-off levels for severe disease established by previous studies did not reach sufficient stratification capacity in our cohort. However, a combination of IL-6 and CRP (with cut-off levels 23.6 pg/ml and 57 mg/L respectively) demonstrated good potential in differentiating mild from non-mild (moderately severe and severe AP according to the RAC) disease. When investigating the temporal development of biomarkers we found that the mean values of IL-6 and IL-1β increased significantly in the severe group between 0-24 and 25-48 hours after onset of disease. Additionally, differences in mean values (i.e. delta-values) varied significantly between the mild and severe group for IL-6, IL-1β and IL-10.Conclusions: Our results indicate that radiologists are unfamiliar with some of the new morphological categories of the RAC, potentially resulting in inconsistent reporting of necrotising pancreatitis. Among prognostic biomarkers in AP, in general CRP, IL-6, IL-1β and IL-10 demonstrated superior stratification capacity in our cohort

Acute pancreatitis–can evidence-based guidelines be transferred to an optimized comprehensive treatment program?

Acute pancreatitis is a common cause of hospitalization and has an incidence of about 300 per 1,000,000 inhabitants. A majority of patients with acute pancreatitis have mild disease, with an absence of local and systemic complications [1]. The clinical, translational, and experimental research in the field of acute pancreatitis is enormous and various guidelines exist. The guidelines have improved, and now increasingly use evidence-based grading, although expert opinion is still part of numerous recommendations.A persistent problem, however, is the uptake of and compliance with these guidelines. For every guideline recommendation, we should need an implementation plan and an audit. This was pointed out in an editorial in the Scandinavian Journal of Gastroenterology in 2008 [2]. It is reasonable to assume that adherence to existing management recommendations improves clinical outcomes for patients with acute pancreatitis

The initial course of il1β, il-6, il-8, il-10, il-12, ifn-γ and tnf-α with regard to severity grade in acute pancreatitis

Clinical reports on early immune dysregulation in acute pancreatitis (AP) are scarce. Herein we investigate the initial temporal development of selected biomarkers. Blood samples were taken at 0–24 and 25–48 h after onsets of AP were acquired. Mean values and temporal intermediate difference (delta-values) of IL-1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were calculated. Differences between severity groups, predictive capacity of the biomarkers and association with severe disease were analyzed. Paired comparison of samples (n = 115) taken at 0–24 and 25–48 h after onsets of AP showed a change over time for IL-1β, IL-6, IL-8 and IL-10 (p < 0.05) and a significant difference between severity groups after 24 h. In ROC-analysis an IL-6 cut-off level of 196.6 pg/mL could differentiate severe AP (sensitivity 81.9, specificity 91.3). The delta-values of IL-1β and IL-6 were significantly associated with severe outcomes (odds ratios 1.085 and 1.002, respectively). Data of this work demonstrate a distinct change in IL-1β, IL-8, IL-10 and IL-6 over the first 48 h after onset of AP. The temporal development of biomarkers can assist in the early stratification of the disease. Herein IL-1β and IL-6 were associated with severe disease, however the prognostic capacity of investigated biomarkers is low

IL-6 and CRP are superior in early differentiation between mild and non-mild acute pancreatitis

Background The revised Atlanta classification on acute pancreatitis (AP) presents distinct criteria for severity categorization. Due to the lack of reliable prognostic markers, a majority of patients with AP are currently hospitalized and initially managed identically. As incidence and financial costs are rising the need for early severity differentiation will increase. This study aimed to investigate the capacity of biomarkers to stratify AP patients during the initial course of the disease. Methods Patients with AP were prospectively enrolled and dichotomized into mild or non-mild (moderately severe and severe AP) according to the revised Atlanta classification. Serum samples taken within 13–36 h after onset of disease were analyzed for 20 biomarkers. Through receiver operating curves cut-off levels were set for 5 biomarkers whose stratifying ability was further analyzed. Additionally, the patients were classified according to the harmless acute pancreatitis score (HAPS). Results Among the 175 patients, 70.9% had mild and 29.1% non-mild AP. CRP and IL-6 combined, with cut-off levels 57.0 and 23.6 respectively, demonstrated superior discriminative capacity with an area under the curve of 0.803, sensitivity 98%, specificity 54% and a positive and negative likelihood ratio of 2.1 and 0.06 for the non-mild group. Regarding the mild group likelihood ratios were positive 26.5 and negative 0.48. The identification potential of the HAPS was generally inferior when compared to CRP plus IL-6. Conclusions In this study CRP and IL-6 demonstrate a clinically relevant capacity to differentiate mild from non-mild AP early in the course of AP

Heparin-binding protein is significantly increased in acute pancreatitis

BACKGROUND: Most patients with acute pancreatitis (AP) experience mild, self-limiting disease with little or no need for hospital care. However, 20-25% of patients develop a more severe and potentially life-threatening condition with progressive systemic inflammatory response syndrome (SIRS) and multiorgan failure, resulting in high morbidity and mortality rates. Predicting disease severity at an early stage is important, as immediate supportive care has been demonstrated to reduce the incidence of SIRS and organ failure, improving patient outcome. Several studies have demonstrated elevated levels of heparin-binding protein (HBP) in patients with sepsis and septic shock, and HBP is believed to play a part in endothelial dysfunction leading to vascular leakage. As HBP levels increase prior to other known biomarkers, HBP has emerged as a promising early predictor of severe sepsis with organ dysfunction.METHODS: Patients admitted to Skåne University Hospital in Malmö between 2010 and 2013 fulfilling the criteria for AP were identified in the emergency department and prospectively enrolled in this study. The primary outcome was measured levels of HBP upon hospital admission in patients with confirmed AP. Correlations among HBP concentrations, disease severity and fluid balance were considered secondary endpoints. The correlation between HBP levels and fluid balance were analysed using Pearson correlation, and the ability of HBP to predict moderately severe/severe AP was assessed using a receiver operating characteristic (ROC) curve.RESULTS: The overall median HBP level in this study was 529 (307-898) ng/ml. There were no significant group differences in HBP levels based on AP severity. Fluid balance differed significantly between patients with mild versus moderately severe and severe pancreatitis, but we found no correlation between HBP concentration and fluid balance.CONCLUSIONS: HBP levels are dramatically increased in patients with AP, and these levels far exceed those previously reported in other conditions. In this study, we did not observe any significant correlation between HBP levels and disease severity or the need for intravenous fluid. Additional studies on HBP are needed to further explore the role of HBP in the pathogenesis of AP and its possible clinical implications