LIFEStyle, prevention and risk of Acute PaNcreatitis (LIFESPAN): protocol of a multicentre and multinational observational case-control study

Introduction Acute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements. Methods and analysis LIFESPAN is an observational, multicentre international case–control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values. Ethics and dissemination The study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access

Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.Peer reviewe

EASY-APP : An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis

Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed.The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP).The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/).The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model

Metabolic-Associated Fatty Liver Disease is associated with Acute Pancreatitis with More Severe Course: Post hoc Analysis of a Prospectively Collected International Registry

Non-alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic-associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP.We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in-hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis.MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate-to-severe AP (OR = 1.43, CI: 1.09-1.89). However, the odds of in-hospital mortality (OR = 0.89, CI: 0.42-1.89) and severe AP (OR = 1.70, CI: 0.97-3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39-5.09). In addition, the presence of one, two, and three diagnostic criteria dose-dependently increased the odds of moderate-to-severe AP (OR = 1.23, CI: 0.88-1.70, OR = 1.38, CI: 0.93-2.04, and OR = 3.04, CI: 1.63-5.70, respectively) and severe AP (OR = 1.13, CI: 0.54-2.27, OR = 2.08, CI: 0.97-4.35, and OR = 4.76, CI: 1.50-15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant.MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose-dependent effect on the outcomes of AP

Hypertriglyceridemia-induced acute pancreatitis: A prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases

Background Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are inadequate and contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. Methods AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (Peer reviewe

Development of disturbance of consciousness is associated with increased severity in acute pancreatitis

Background Disturbance of consciousness (DOC) may develop in acute pancreatitis (AP). In clinical practice, it is known that DOC may worsen the patient's condition, but we have no exact data on how DOC affects the outcome of AP. Methods From the Hungarian Pancreatic Study Groups' AP registry, 1220 prospectively collected cases were analysed, which contained exact data on DOC, included patients with confusion, delirium, convulsion, and alcohol withdrawal, answering a post hoc defined research question. Patients were separated to Non-DOC and DOC, whereas DOC was further divided into non-alcohol related DOC (Non-ALC DOC) and ALC DOC groups. For statistical analysis, independent sample t-test, Mann-Whitney, Chi-squared, or Fisher exact test were used. Results From the 1220 patients, 47 (3.9%) developed DOC, 23 (48.9%) cases were ALC DOC vs. 24 (51.1%) Non-ALC DOC. Analysis between the DOC and Non-DOC groups showed a higher incidence of severe AP (19.2% vs. 5.3%, p<0.001), higher mortality (14.9% vs. 1.7%, p<0.001), and a longer length of hospitalization (LOH) (Me=11; IQR: 8-17 days vs. Me=9; IQR: 6-13 days, p=0.049) respectively. Patients with ALC DOC developed more frequently moderate AP vs. Non-ALC DOC (43.5% vs. 12.5%), while the incidence of severe AP was higher in Non-ALC vs. ALC DOC group (33.3% vs. 4.4%) (p<0.001). LOH showed a tendency to be longer in Non-ALC DOC compared to ALC DOC, respectively (Me:13; IQR:7-20 days vs. Me:9.5; IQR:8-15.5 days, p=0.119). Conclusion DOC during AP is associated with a higher rate of moderate and severe AP and increases the risk of mortality

Multiple Hits in Acute Pancreatitis: Components of Metabolic Syndrome Synergize Each Other's Deteriorating Effects

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Aging and Comorbidities in Acute Pancreatitis II.: A Cohort-Analysis of 1203 Prospectively Collected Cases

Introduction: Our meta-analysis indicated that aging influences the outcomes of acute pancreatitis (AP), however, a potential role for comorbidities was implicated, as well. Here, we aimed to determine how age and comorbidities modify the outcomes in AP in a cohort-analysis of Hungarian AP cases.Materials and Methods: Data of patients diagnosed with AP by the revised Atlanta criteria were extracted from the Hungarian Registry for Pancreatic Patients. Outcomes of interest were mortality, severity, length of hospitalization, local, and systemic complications of AP. Comorbidities were measured by means of Charlson Comorbidity Index (CCI) covering pre-existing chronic conditions. Non-parametric univariate and multivariate statistics were used in statistical analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.Results: A total of 1203 patients from 18 centers were included. Median age at admission was 58 years (range: 18–95 years), median CCI was 2 (range: 0–10). Only severe comorbidities (CCI ≥ 3) predicted mortality (OR = 4.48; CI: 1.57–12.80). Although severe comorbidities predicted AP severity (OR = 2.10, CI: 1.08–4.09), middle (35–64 years) and old age (≥65 years) were strong predictors with borderline significance, as well (OR = 7.40, CI: 0.99–55.31 and OR = 6.92, CI: 0.91–52.70, respectively). Similarly, middle and old age predicted a length of hospitalization ≥9 days. Interestingly, the middle-aged patients (35–64 years) were three times more likely to develop pancreatic necrosis than young adults (OR = 3.21, CI: 1.26–8.19), whereas the old-aged (≥65 years) were almost nine times more likely to develop systemic complications than young adults (OR = 8.93, CI: 1.20–66.80), though having severe comorbidities (CCI ≥ 3) was a predisposing factor, as well.Conclusion: Our results proved that both aging and comorbidities modify the outcomes of AP. Comorbidities determine mortality whereas both comorbidities and aging predict severity of AP. Regarding complications, middle-aged patients are the most likely to develop local complications; in contrast, those having severe comorbidities are prone to develop systemic complications. Studies validating the implementation of CCI-based predictive scores are awaited