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Choledocholithiasis causing acute biliary pancreatitis (ABP) may migrate to the duodenum or persist in the common bile duct (CBD). We developed a model for predicting persistent choledocholithiasis (PC) in patients with ABP.This retrospective cohort study included 204 patients, age ≥18 years (mean age: 73 years, 65.7% women), admitted for ABP in 2013-2018, with at least a magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS), and/or endoscopic retrograde cholangiopancreatography (ERCP). Epidemiological, analytical, imaging, and endoscopic variables were compared between patients with and without PC. Multivariate logistic regression analyses were performed to develop a predictive model of PC.Patients underwent MRCP (n=145, 71.1), MRCP and ERCP (n=44, 21.56%), EUS and ERCP (n=1, 0.49%), or ERCP (n=14, 6.86%). PC was detected in 49 patients (24%). PC was strongly associated with CBD dilation, detected in the emergency ultrasound (p0.001; OR=27; 95% CI: 5.8-185.5), increased blood levels of gamma glutamyl transpeptidase, detected at 72h (p=0.008; OR=3.4; 95% CI: 1.5-8.9); and biliary sludge in the gallbladder (p=0.008; OR=0.03; 95% CI: 0.001-0.3).The predictive model showed a validated area under the curve (AUC) of 0.858 for detecting PC in patients with ABP. A nomogram was developed based on model results.The predictive model was highly effective in detecting PC in patients with ABP. Therefore, this model could be useful in clinical practice.

The objective of this study is to generate a core clinical dataset (CD) containing the minimum acceptable amount of information that should be collected for each patient presenting with triglyceride-induced acute pancreatitis within global treatment centres or sites.The Jandhyala Method, including systematic literature review and SMART interviews, was used to observe expert opinion from ten leaders in the treatment of triglyceride-induced acute pancreatitis (TG-IAP) across the US and EU.Using the PRISMA Literature Review Protocol, data were extracted from 123 of the 6718 identified studies. A total of 243 items were identified from the data extracted from these studies and, combined with the unique items coded from the Awareness Round (1) survey, formed the Consensus Round (2) survey. One hundred and ninety-five of the 243 items (80%) met the consensus threshold and were included for appraisal in the SMART interview phase. A total of 109 items were agreed to form part of the current clinical diagnostic and monitoring procedure by all experts once the weights across all the stakeholder disciplines were balanced to eliminate bias. These items were further condensed to form the core dataset, comprising a total of 87 items.Once validated and adopted, the TG-IAP CD will improve the overall management of patients with TG-IAP by speeding up diagnosis and detecting changes in disease severity and subsequent disease progression, informing personalized patient management plans, and improving patient outcomes.

BACKGROUND: Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited. METHODS: At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer's solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the patient's clinical status. The primary outcome was the development of moderately severe or severe pancreatitis during the hospitalization. The main safety outcome was fluid overload. The planned sample size was 744, with a first planned interim analysis after the enrollment of 248 patients. RESULTS: A total of 249 patients were included in the interim analysis. The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P = 0.004). The median duration of hospitalization was 6 days (interquartile range, 4 to 8) in the aggressive-resuscitation group and 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group. CONCLUSIONS: In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes. (Funded by Instituto de Salud Carlos III and others; WATERFALL ClinicalTrials.gov number, NCT04381169.).

Background Assessment of mucosal visualization during esophagogastroduodenoscopy (EGD) can be improved with a standardized scoring system. To address this need, we created the Toronto Upper Gastrointestinal Cleaning Score (TUGCS). Methods We developed the TUGCS using Delphi methodology, whereby an international group of endoscopy experts iteratively rated their agreement with proposed TUGCS items and anchors on a 5-point Likert scale. After each Delphi round, we analyzed responses and refined the TUGCS using an 80 % agreement threshold for consensus. We used the intraclass correlation coefficient (ICC) to assess inter-rater and test–retest reliability. We assessed internal consistency with Cronbach’s alpha and item-total and inter-item correlations with Pearson’s correlation coefficient. We compared TUGCS ratings with an independent endoscopist’s global rating of mucosal visualization using Spearman’s ρ. Results We achieved consensus with 14 invited participants after three Delphi rounds. Inter-rater reliability was high at 0.79 (95 %CI 0.64–0.88). Test–retest reliability was excellent at 0.83 (95 %CI 0.77–0.87). Cronbach’s α was 0.81, item-total correlation range was 0.52–0.70, and inter-item correlation range was 0.38–0.74. There was a positive correlation between TUGCS ratings and a global rating of visualization (r = 0.41, P = 0.002). TUGCS ratings for EGDs with global ratings of excellent were significantly higher than those for EGDs with global ratings of fair (P = 0.01). Conclusion The TUGCS had strong evidence of validity in the clinical setting. The international group of assessors, broad variety of EGD indications, and minimal assessor training improves the potential for dissemination.

IntroductionDespite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency.MethodsAn online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years.ResultsOverall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency.ConclusionThis survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence. Introduction: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. Methods: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. Results: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. Conclusion: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

BACKGROUND: Acute pancreatitis (AP) has variable clinical courses. This systematic review and meta-analysis aimed to determine the safety, efficacy, and impact of epidural anaesthesia (EA) use in AP.METHODS: The PubMed, EMBASE, SCOPUS and Cochrane library databases were systematically searched between 1980 and 2022 using the PRISMA guidelines, to identify observational and comparative studies reporting on EA in AP. The meta-analysis was performed in R Foundation for Statistical Computing using the meta R Package for Meta-Analysis.RESULTS: A total of 9 studies with 2006 patients of which 726 (36%) patients had EA were included. All studies demonstrated high safety and feasibility of EA in AP with no reported major local or neurological complications. One randomised controlled trial demonstrated an improvement in pain severity using a 0-10 visual analogue scale (VAS) at the outset (1.6 in EA vs 3.5 in non-EA, P = 0.02) and on day 10 (0.2 in EA vs 2.33 in non-EA, P = 0.034). There was also improvement in pancreatic perfusion with EA measured with computerised tomography 13 (43%) in EA vs 2 (7%) in non-EA, P = 0.003. The need for ventilatory support and overall mortality was lower in EA patients 40 (19%) vs 285 (24%) P = 0.025 (OR: 0.49, 95% CI: 0.28-0.84) and 16 (7%) vs 214 (20%), P = 0.050 (OR: 0.39, 95% CI: 0.15-1.00), respectively.CONCLUSION: EA is infrequently used for pain management in AP and yet the available evidence suggests that it is safe and effective in reducing pain severity, improving pancreatic perfusion, and decreasing mortality.

Background: Predicting Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis (PEP) risk can be determinant in reducing its incidence and managing patients appropriately, however studies conducted thus far have identified single-risk factors with standard statistical approaches and limited accuracy. Aim: To build and evaluate performances of machine learning (ML) models to predict PEP probability and identify relevant features. Methods: A proof-of-concept study was performed on ML application on an international, multicenter, prospective cohort of ERCP patients. Data were split in training and test set, models used were gradient boosting (GB) and logistic regression (LR). A 10-split random cross-validation (CV) was applied on the training set to optimize parameters to obtain the best mean Area Under Curve (AUC). The model was re-trained on the whole training set with the best parameters and applied on test set. Shapley-Additive-exPlanation (SHAP) approach was applied to break down the model and clarify features impact. Results: One thousand one hundred and fifty patients were included, 6.1% developed PEP. GB model outperformed LR with AUC in CV of 0.7 vs 0.585 (p-value=0.012). GB AUC in test was 0.671. Most relevant features for PEP prediction were: bilirubin, age, body mass index, procedure time, previous sphincterotomy, alcohol units/day, cannulation attempts, gender, gallstones, use of Ringer's solution and periprocedural NSAIDs. Conclusion: In PEP prediction, GB significantly outperformed LR model and identified new clinical features relevant for the risk, most being pre-procedural.

Introduction Fluid resuscitation is the keystone of treatment for acute pancreatitis. Though clinical guidelines and expert opinions agree on large volume resuscitation, debate remains on the optimal fluid type. The most commonly used fluids are Lactated Ringer's (LR) and Normal Saline (NS), but the studies published to date comparing LR vs NS yield conflicting results. We aimed to identify and quantitatively synthesize existing high quality data of the topic of fluid type or acute pancreatitis resuscitation. Methods In collaboration with the study team, an information specialist performed a comprehensive literature review to identify reports addressing type of fluid resuscitation. Studies were screened using the Covidence system by two independent reviewers in order to identify Randomized controlled trials comparing LR versus NS. The main outcome was the development of moderately severe or severe pancreatitis and additional outcomes included local complications, ICU admission, and length of stay. Pooled odds ratios were estimated using the random effects model and standardized mean difference to compare continuous variables. Results We reviewed 7964 abstracts and 57 full text documents. Four randomized controlled trials were identified and included in our meta-analyses. There were a total of 122 patients resuscitated with LR versus 126 with NS. Patients resuscitated with LR were less likely to develop moderately severe/severe pancreatitis (OR 0.49; 95 % CI 0.25–0.97). There was no difference in development of SIRS at 24 or 48 h or development of organ failure between the two groups. Patients resuscitated with LR were less likely to require ICU admission (OR 0.33; 95 % CI 0.13–0.81) and local complications (OR 0.42; 95 % CI 0.2–0.88). While there was a trend towards shorter hospitalizations for LR (SMD -0.18, 99 % CI -0.44-0.07), it was not statistically significant. Conclusion Resuscitation with LR reduces the development of moderately severe-severe pancreatitis relative to NS. Nevertheless, no difference in SIRS development or organ failure underscores the need for further studies to verify this finding and define its mechanism.

We aimed to evaluate the association between three previously defined pro-vegetarian (PVG) food patterns and the cancers of the oesophagus, stomach, and pancreas in a multi case-control study. We analyzed data from a multi-case hospital-based study carried out in two Mediterranean provinces in Spain. A total of 1233 participants were included in the analyses: 778 incident cancer cases, histologically confirmed (199 oesophagus, 414 stomach, and 165 pancreas) and 455 controls. A dietary assessment was performed using a validated food frequency questionnaire (FFQ). Three PVG food patterns (general, healthful, and unhealthful) were estimated using 12 food groups for the general PVG (gPVG), scoring positive plant-based foods and negative animal-based foods, and 18 food groups, for the healthful (hPVG) and unhealthful (uPVG) food patterns. Multinomial logistic regression was used to estimate relative risk ratios (RRR) and confidence intervals (95% CI) for quintiles of adherence to PVG patterns and as a continuous variable. The RRR (95% CI) for the highest vs. the lowest quintile of gPVG were, RRR = 0.37 (0.32, 0.42) for the oesophagus, RRR = 0.34 (0.27, 0.43) for the stomach, and RRR = 0.43 (0.35, 0.52) for pancreas cancer. For the hPVG, the RRR were RRR = 0.72 (0.58, 0.90) for the oesophagus, RRR = 0.42 (0.34, 0.52) for the stomach, and RRR = 0.74 (0.59, 0.92) for pancreas cancer. The uPVG was associated with a higher risk of stomach cancer RRR = 1.76 (1.42, 2.18). Higher adherence to gPVG and hPVG food patterns is associated with a lower risk of oesophageal, stomach, and pancreas cancers, while a higher adherence to a uPVG food pattern is associated with a higher risk of stomach cancer. Funding: This work was supported by the Spanish Ministry of Health (FIS 91/0435, RCESP C03/09), the Generalitat Valenciana (EVES 030/2005, CTGCA/2002/06, G03/136), CIBERESP.

Background: The initial management of patients with acute pancreatitis impacts both morbidity and mortality. Point-of-care decisions have been reported to differ from clinical guideline recommendations. Methods: An online anonymous questionnaire was distributed through scientific associations and social media using REDCap. Multivariable logistic regression was used to identify the characteristics of participants associated with compliance with the recommendations. Results: A total of 1054 participants from 94 countries completed the questionnaire; median age (IQR) was 39 (32–47) years; 30.7% were women. Among the participants, 37% opted for nonmoderate flow of i.v. fluid, 31% for fluid type other than Ringer’s lactate; 73.4% were in favor of nil per os to patients who could eat, 75.5% for other than enteral feeding to patients with oral intolerance; 15.5% used prophylactic antibiotic in patients with severe acute pancreatitis, 34.1% in necrotizing acute pancreatitis, and 27.4% in patients with systemic inflammatory response syndrome; 27.8% delayed cholecystectomy after biliary acute pancreatitis. Participants with publications in PubMed on acute pancreatitis showed better compliance (OR, 1.62; 95% CI: 1.15–2.32; P =.007) with recommendations of the clinical guidelines. Conclusions: Feeding and nutrition require the greatest improvement efforts, but also the use of prophylactic antibiotics and timing of cholecystectomy should be improved.

Contains fulltext : 252197.pdf (Publisher’s version ) (Closed access) GASTROSWOT is a strategic analysis of the current and projected states of the different subspecialties in gastroenterology that aims to provide guidance for research, clinical, and financial planning in gastroenterology. We executed a consensus-based international strengths, weaknesses, opportunities, and threats (SWOT) analysis. Four general coordinators, six field coordinators, and 12 experts participated in the study. SWOTs were provided for the following fields: neurogastroenterology, functional gastrointestinal disorders, and upper gastrointestinal diseases; inflammatory bowel disease; pancreatology and biliary diseases; endoscopy; gastrointestinal oncology; and hepatology. The GASTROSWOT analysis highlights the following in the current state of the field of gastroenterology: the incidence and complexity of several gastrointestinal diseases, including malignancies, are increasing; the COVID-19 pandemic has affected patient care on several levels; and with the advent of technical innovations in gastroenterology, a well trained workforce and strategic planning are required to optimise health-care utilisation. The analysis calls attention to the following in the future of gastroenterology: artificial intelligence and the use of big data will speed up discovery and smarter health-care provision in the field; the growth and diversification of gastroenterological specialties will improve specialised care for patients, but could promote fragmentation of care and health system inefficiencies; and furthermore, thoughtful planning is needed to reach an effective balance between the need for subspecialists and the value of general gastroenterology services.

BACKGROUND: The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown.OBJECTIVE: The present systematic review and meta-analysis aims to compare the efficacy of different analgesic modalities trialled in AP.METHODS: A systematic search of PubMed, MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science conducted up until June 2021, identified all randomised control trials (RCTs) comparing analgesic modalities in AP. A pooled analysis was undertaken of the improvement in pain scores as reported on visual analogue scale (VAS) on day 0, day 1 and day 2.RESULTS: Twelve RCTs were identified including 542 patients. Seven trial drugs were compared: opiates, non-steroidal anti-inflammatories (NSAIDs), metamizole, local anaesthetic, epidural, paracetamol, and placebo. Across all modalities, the pooled VAS scores showed global improvement from baseline to day 2. Epidural analgesia appears to provide the greatest improvement in VAS within the first 24 h but is equivalent to opiates by 48 h. Within 24 h, NSAIDs offered similar pain-relief to opiates, while placebo also showed equivalence to other modalities but then plateaued. Local anaesthetics demonstrated least overall efficacy. VAS scores for opiate and non-opiate analgesics were comparable at baseline and day 1. The identified RCTs demonstrated significant statistical and methodological heterogeneity in pain-relief reporting.CONCLUSIONS: There is remarkable paucity of level 1 evidence to guide pain management in AP with small datasets per study. Epidural administration appears effective within the first 24 h of AP although infrequently used and featured in only a single RCT. NSAIDs are an effective opiate sparing alternative during the first 24 h.

ObjectiveThis study aimed to develop and validate a patient-reported outcome measure (PROM) in acute pancreatitis (AP) as an endpoint centred on the patient.DesignA PROM instrument (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, PAN-PROMISE scale) was designed based on the opinion of patients, professionals and an expert panel. The scale was validated in an international multicentre prospective cohort study, describing the severity of AP and quality of life at 15 days after discharge as the main variables for validation. The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) methodology was applied. Both the design and validation stages considered the content and face validity of this new instrument; the metric properties of the different items, reliability (reproducibility and internal consistence), the construct, structural and criterion validity, responsiveness and interpretability of this scale.ResultsPAN-PROMISE consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. The validation cohort involved 15 countries, 524 patients. The intensity of symptoms changed from higher values during the first 24 hours to lower values at discharge and 15 days thereafter. Items converged into a unidimensional ordinal scale with good fit indices. Internal consistency and split-half reliability at discharge were adequate. Reproducibility was confirmed using test–retest reliability and comparing the PAN-PROMISE score at discharge and 15 days after discharge. Evidence is also provided for the convergent-discriminant and empirical validity of the scale.ConclusionThe PAN-PROMISE scale is a useful tool to be used as an endpoint in clinical trials, and to quantify patient well-being during the hospital admission and follow-up.Trial registration numberNCT03650062

CA19-9 serum has been suggested as a marker of unresectability but different cut-off levels have been published. A cut-off of 500 U/ml is currently considered in an international consensus as biological criteria of borderline resectable pancreatic adenocarcinoma. To evaluate whether serum CA19-9 threshold of 500 U/ml could be adequate predictor of resectability in pancreatic adenocarcinoma. Multicenter, observational, prospective study performed in Spain including 203 patients diagnosed with pancreatic adenocarcinoma. 43 (21.2%) cases were resectable and 160 (78.8%) unresectable. Among the 176 preoperative CA19-9 available values, 98 (58.3%) were ≤ 500 U/ml and 73 (42.7%) > 500 U/ml. Resectability rate in those patients with CA19-9 ≤ 500 U/ml was 60% while it was found to be 18% when CA19-9 > 500 U/ml. Statistical model to predict resectability based on CA19-9 provide an AUC of 0.6618 (95% CI 0.53–0.83) when only CA19-9 values > 500 U/ml are studied. Serum levels of CA19-9 higher than 500 U/ml are indicative of unresectable disease, however reduced sensitivity and specificity lead to a limited clinical applicability for resectability.

Background/objectivesAcute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP.Methods and analysisThe REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort.Ethics and disseminationThe study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals.Trial registration numberNCT04647097

BACKGROUND & AIMS: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. METHODS: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. RESULTS: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). CONCLUSION: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.

As acute pancreatitis progresses to the severe form, a life-threatening systemic inflammation is triggered. Although the mechanisms involved in this process are not yet well understood, it has been proposed that circulating exosomes may be involved in the progression of inflammation from the pancreas to distant organs. Here, the inflammatory capacity and protein profile of plasma exosomes obtained during the first 24 h of hospitalization of patients diagnosed with acute pancreatitis were characterized and compared with the final severity of the disease. We found that the final severity of the disease strongly correlates with the inflammatory capacity of exosomes in the early stages of acute pancreatitis. Exosomes isolated from patients with mild pancreatitis had no effect on macrophages, while exosomes isolated from patients with severe pancreatitis triggered NFκB activation, TNFα and IL1β expression, and free radical generation. To delve deeper into the mechanism involved, we performed a proteomic analysis of the different exosomes that allowed us to identify different groups of proteins whose concentration was also correlated with the clinical classification of pancreatitis. In particular, an increase in the amount of S100A8 and S100A9 carried by exosomes of severe pancreatitis suggests that the mechanism of action of exosomes is mediated by the effect of these proteins on NADPH oxidase. This enzyme is activated by S100A8/S100A9, thus generating free radicals and promoting an inflammatory response. Along these lines, we observed that inhibition of this enzyme abolished all the pro-inflammatory effects of exosomes from severe pancreatitis. All this suggests that the systemic effects, and therefore the final severity of acute pancreatitis, are determined by the content of circulating exosomes generated in the early hours of the process. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland., This work was supported by the projects PI16/00060 from Instituto de Salud Carlos III, 2019AEP057 CVSCI, and a grant ‘Gonzalo Miño’ from the Asociación Española de Gastroenterología. The Biologial and Environmental Proteomics group is a member of Proteored-PRB3 and is supported by Grant PT17/0019/0008 of the PE I+D+I 2013–2016, funded by ISCIII and FEDER.

Background The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown. The present systematic review and meta-analysis aims to compare the efficacy of several analgesic modalities trialled in AP. Methods A systematic search of PubMed, MEDLINE and EMBASE was conducted up until June 2021, according to PRISMA Guidelines to identify all randomised control trials (RCTs) comparing analgesic modalities in AP. The primary outcome measure was improvement in pain scores as reported on visual analogue scale (VAS) on day 0, day 1 and day 2. Results Twelve RCTs were identified including 542 patients. Seven trial drugs were compared: opiates, non-steroidal anti-inflammatories (NSAIDs), placebo, local anaesthetic, epidural, paracetamol and metamizole. A weighted single-arm effects estimate showed global improvement in VAS across all modalities from baseline to day 2. On visual inspection, epidural analgesia appears to provide the greatest improvement in pain scores within the first 24hrs, however at 48hrs it was comparable to opiates. Within the first 24hrs, NSAIDs offered similar pain-relief to opiates, while placebo also showed equivalence to other modalities but then plateaued. Local anaesthetics demonstrated least overall efficacy. VAS scores for opiate and non-opiate analgesics were comparable at baseline and day 1. The identified RCTs demonstrated significant heterogeneity in pain-relief reporting with relatively small datasets per study. Conclusions Given the incidence of AP there is remarkable paucity of level 1 evidence to guide pain management. Epidural administration is most effective analgesic modality within the first 24hrs of AP. NSAIDs are an effective opiate sparing alternative during the first 24hrs.

The World Health Organization declared coronavirus disease-2019 (COVID-19) a global pandemic in March 2020. Since then, there are more than 34 million cases of COVID-19 leading to more than 1 million deaths worldwide. Numerous studies suggest that celiac disease (CeD), a chronic immune-mediated gastrointestinal condition triggered by gluten, is associated with an increased risk of respiratory infections.(1-3) However, how it relates to the risk of COVID-19 is unknown. To address this gap, we conducted a cross-sectional study to evaluate whether patients with self-reported CeD are at an increased risk of contracting COVID-19.

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 0.05). CONCLUSION: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.

Objectives Quantify the risk of drug-induced pancreatitis (DIP) from angiotensin-converting enzyme inhibitors (ACEis) and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins). Methods Retrospective cohort analysis using IBM Explorys (1999-2019), a pooled, deidentified clinical database of more than 63 million patients across the United States. Odds ratios were calculated to determine the risk of DIP from ACEi, statins, and both medications together. χ2 testing assessed the relationship between age, sex, ethnicity, insurance status, and mortality among patients with DIP from ACEi, statins, or both combined. Results Acute pancreatitis (AP) was found in 280,740 patients. Odds ratios for ACEi, statins, and both combined were 6.12, 4.97, and 5.72, respectively. Thirty-eight percent of all-cause AP occurs in adults older than 65 years. Acute pancreatitis from ACEi and statins occurs in 49% and 56% of patients older than 65 years, respectively. Men and patients older than 65 years are at higher risk of DIP from ACEi and statins. Patients on Medicaid are at higher risk of DIP from statins, and Asian patients are at highest risk of DIP from ACEi. Conclusions We found that ACEi and statins increase the odds of DIP. Although ACEis and statins are critical medications for many patients, clinicians should consider using alternatives in patients with AP of unclear etiology.

BACKGROUND/OBJECTIVES: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. METHODS: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. RESULTS: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p

INTRODUCTION: Experimental data suggest that nonsteroidal antiinflammatory drugs may prevent disease severity and mortality in acute pancreatitis (AP). The aim of this study was to compare the efficacy of rectal indomethacin vs placebo in reducing the systemic inflammatory response syndrome (SIRS) score in a high-risk AP population for clinical progression. METHODS: We conducted a single-center, quadruple-blinded, randomized, placebo-controlled trial. Eligible criteria were subjects with AP and SIRS within 72 hours of presentation and those without organ failure. Subjects were allocated in a 1:1 ratio to indomethacin or placebo using simple randomization. Both interventions were administered rectally every 8 hours for 6 doses and compared using both intention-to-treat and per-protocol analyses. RESULTS: A total of 42 subjects (mean age 52 years, 55% men) were randomized to indomethacin (n = 18) or placebo (n = 24). There was no significant difference between the indomethacin and placebo groups in the change of SIRS score, proportion of subjects with SIRS, and distribution of SIRS scores at 24, 48, and 72 hours from randomization. There were no significant differences in the change of C-reactive protein levels at 48 hours or clinical outcomes between both treatment groups. Indomethacin was as safe as placebo, with 2 adverse events occurring in the placebo and none in the indomethacin arm. DISCUSSION: Rectal indomethacin can be safely administered over 48 hours; however, it is not superior to placebo in reducing the SIRS or clinical progression in a high-risk population with AP (ClinicalTrials.gov: NCT02692391).

BACKGROUND We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk. AIM To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception. METHODS We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visits, and social media. Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population. Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception, such as age, sex, adherence to a gluten-free diet (GFD), and comorbidities such as cardiac conditions, respiratory conditions, and diabetes. Data was presented as adjusted odds ratios (aORs) RESULTS A total of 10737 participants with CeD completed the survey. From them, 6019 (56.1%) patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population. A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD (56.1% vs 26.7%, P < 0.0001). Consequently, 34.8% reported taking extra COVID-19 precautions as a result of their CeD. Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members (49.5% vs 57.4%, P < 0.0001). Older age (aOR: 0.99; 95%CI: 0.99 to 0.99, P < 0.001), male sex (aOR: 0.84; 95%CI: 0.76 to 0.93, P = 0.001), and strict adherence to a GFD (aOR: 0.89; 95%CI: 0.82 to 0.96, P = 0.007) were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk (aOR: 1.38; 95%CI: 1.22 to 1.54, P < 0.001). CONCLUSION Overall, high levels of risk perceptions, such as those found in patients with CeD, may increase an individual's pandemic-related stress and contribute to negative mental health consequences. Therefore, it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community. Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population.