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Retrospective studies suggest that coronavirus disease (COVID-19) commonly involves gastrointestinal (GI) symptoms and complications. Our aim was to prospectively evaluate GI manifestations in patients hospitalized for COVID-19.This international multicentre prospective cohort study recruited COVID-19 patients hospitalized at 31 centres in Spain, Mexico, Chile, and Poland, between May and September 2020. Patients were followed-up until 15 days post-discharge and completed comprehensive questionnaires assessing GI symptoms and complications. A descriptive analysis as well as a bivariate and multivariate analysis were performer using binary logistic regression. p0.05 was considered significant.Eight hundred twenty-nine patients were enrolled; 129 (15.6%) had severe COVID-19, 113 (13.7%) required ICU admission, and 43 (5.2%) died. Upon admission, the most prevalent GI symptoms were anorexia (n=413; 49.8%), diarrhoea (n=327; 39.4%), nausea/vomiting (n=227; 27.4%), and abdominal pain (n=172; 20.7%), which were mild/moderate throughout the disease and resolved during follow-up. One-third of patients exhibited liver injury. Non-severe COVID-19 was associated with ≥2 GI symptoms upon admission (OR 0.679; 95% CI 0.464-0.995; p=0.046) or diarrhoea during hospitalization (OR 0.531; 95% CI 0.328-0.860; p=0.009). Multivariate analysis revealed that worse hospital outcomes were not independently associated with liver injury or GI symptoms.GI symptoms were more common than previously documented, and were mild, rapidly resolved, and not independently associated with COVID-19 severity. Liver injury was a frequent complication in hospitalized patients not independently associated with COVID-19 severity.

Background: Acute on chronic pancreatitis (ACP) is a relatively common condition, but there are significant gaps in our knowledge on the definition, incidence, diagnosis, treatment and prognosis. Methods: A systematic review that followed PICO (Population; Intervention; Comparator; Outcome) recommendation for quantitative questions and PICo (Population, Phenomenon of Interest, Context) for qualitative research was done to answer 10 of the most relevant questions about ACP. Quality of evidence was judged by the GRADE criteria (Grades of Recommendation, Assessment, Development and Evaluation). The manuscript was sent for review to 12 international experts from various disciplines and continents using a Delphi process. Results: The quality of evidence, for most statements, was low to very low, which means that the recommendations in general are only conditional. Despite that, it was possible to reach strong levels of agreement by the expert panel for all 10 questions. A new consensus definition of ACP was reached. Although common, the real incidence of ACP is not known, with alcohol as a major risk factor. Although pain dominates, other non-specific symptoms and signs can be present. Serum levels of pancreatic enzymes may be less than 3 times the upper limit of normal and cross-sectional imaging is considered more accurate for the diagnosis in many cases. It appears that it is less severe and with a lower mortality risk than acute pancreatitis.Conclusions: Although the evidence base is poor, this position statement provides a foundation from which to advance management of ACP.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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: 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.

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.

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

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.

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.

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/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.

Background: One in every four patients with a first episode of non-gallstone-related acute pancreatitis (AP) develops recurrent disease. Recurrent episodes of AP or acute flares of chronic pancreatitis (CP) are associated with decreased quality of life and progression of the disease. Besides removing the etiology of pancreatitis (which sometimes is not possible), there are no effective measures to prevent recurrence. Meta-analyses of randomized controlled trials, as well as epidemiological and cohort studies, suggest that statins may be protective against the development of index AP.Methods: The SIMBA study is a triple-blind randomized placebo-controlled, parallel-group multicenter trial. Patients with recurrent AP or with acute flares of CP (at least two episodes in the last 12 months) will be randomized to receive simvastatin 40 mg daily or placebo. During a 3-year study period, 144 patients (72 per arm of treatment) from 26 centers will be enrolled. The patients will receive the study treatment for 1 year. The primary aim is to compare the recurrence of AP or acute flares in CP. Secondary endpoints include the incidence of new-onset diabetes mellitus, new-onset exocrine pancreatic insufficiency (EPI), new-onset imaging signs of CP, frequency of all-cause hospital admissions, severity of AP, adherence to treatment, and frequency of adverse events.Discussion: The SIMBA trial will ascertain whether simvastatin, a safe, widely used and inexpensive drug, can change the natural course of recurrent pancreatitis.Trial Registration: ClinicalTrials.gov Identifier: NCT04021498

Background Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF. Objective We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF. Methods We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders. Results 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p, Key Summary What is known? Persistent organ failure (POF; >48 h) is the strongest determinant of mortality in acute pancreatitis (AP).There is lack of evidence on the impact of different attributes of failing organs on AP mortality.The association of systemic inflammatory response syndrome (SIRS) characteristics with POF, has not been well studied. What is new here? Mortality risk in AP patients with POF is determined by the number, type, and sequence of organ systems affected.Multiple POF affecting the cardiovascular and respiratory systems first or concurrently carries the highest mortality in AP compared to the renal system.Involvement of the renal system as the first failing organ or concurrently with other organs during multiple POF is associated with lower mortality than respiratoy or cardiovascular systems as first failing organs.Onset and duration of POF are not associated with mortality in AP patients.SIRS on admission, persistent SIRS, and three to four SIRS criteria, are independently associated with higher risk of POF.

Case reports and retrospective cohort studies have reported an association between acute pancreatitis and COVID-19. As SARS-CoV-2 (the causative agent of COVID-19) receptors are expressed in the pancreas and endothelial damage can occur, this association is plausible. However, this hypothesis has many biases and needs further investigation.

Background The coronavirus disease 2019 (COVID-19) pandemic has impacted endoscopy services and education worldwide. This study aimed to characterize the impact of COVID-19 on gastroenterology trainees in Canada. Methods An analysis of Canadian respondents from the international EndoTrain survey, open from April 11 to May 2 2020 and distributed by program directors, trainees, and national and international gastroenterology societies’ representatives, was completed. The survey included questions on monthly endoscopy volume, personal protective equipment availability, trainee well-being and educational resources. The primary outcome was change in procedural volume during the COVID-19 pandemic. Secondary outcomes included trainee’s professional and personal concerns, anxiety and burnout. Results Thirty-four Canadian trainees completed the survey. Per month, participants completed a median of 30 esophagogastroduodenoscopies (interquartile range 16 to 50) prior to the pandemic compared to 2 (0 to 10) during the pandemic, 20 (8 to 30) compared to 2 (0 to 5) colonoscopies and 3 (1 to 10) compared to 0 (0 to 3) upper gastrointestinal bleeding procedures. There was a significant decrease in procedural volumes between the pre-COVID-19 and COVID-19 time periods for all procedures (P < 0.001). Thirty (88%) trainees were concerned about personal COVID-19 exposure, 32 (94%) were concerned about achieving and/or maintaining clinical competence and 24 (71%) were concerned about prolongation of training time due to the pandemic. Twenty-six (79%) respondents experienced some degree of anxiety, and 10 (31%) experienced some degree of burnout. Conclusion The COVID-19 pandemic has substantially impacted gastroenterology trainees in Canada. As the pandemic eases, it important for gastrointestinal programs to adapt to maximize resident learning, maintain effective clinical care and ensure development of endoscopic competence.

Treatment options are limited for acute pancreatitis (AP). Early aggressive fluid resuscitation (AFR) has been widely considered beneficial because of theoretical improvement in end-organ perfusion, including the pancreas and gut, with pancreatic necrosis and bacterial translocation as consequences of ischemia. There is scarce direct evidence for its association to improved outcomes. Furthermore, it has been described that AFR may be associated with poor outcomes in severe AP. WATERFALL is an investigator-initiated international multicenter open-label randomized controlled trial comparing AFR vs. moderate fluid resuscitation (MFR) in AP. The main outcome variable will be the incidence of moderate to severe AP (a clinically relevant outcome that has been validated). Aggressive fluid resuscitation will consist in lactated Ringer solution (LR) 20-mL/kg bolus (administered over 2 h) followed by LR 3 mL/kg per hour. Patients randomized to MFR will receive an LR bolus 10 mL/kg in case of hypovolemia or no bolus in patients with normal volemia, followed by LR 1.5 mL/kg per hour. The patients will be assessed at 3 (±1), 12 (±4), 24 (±4), 48 (±4), and 72 (±4) h from recruitment, and fluid resuscitation will be adjusted to the patient's clinical and analytical status according to a protocol. Based on a prospective multicenter study, the incidence of moderate to severe AP is 35%. Sample sizes of 372 patients per group (overall 744) achieve 80% power to detect a difference in the incidence of moderate to severe AP of 10%, at a significance level (α) of 0.05 using a two-sided z-test, assuming a 10% dropout rate. These results assume that three sequential tests are made using the O'Brien–Fleming spending function to determine the test boundaries.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic cancer are poorly investigated with heterogeneous results. We sought to determine the prevalence and clinical consequences of pancreatic exocrine insufficiency and the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer by systematic review and meta-analysis. METHODS: Scopus, Medline, and Embase were searched for cohort studies or randomised clinical trials reporting pancreatic exocrine insufficiency and/or the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer. We considered pancreatic exocrine insufficiency as an abnormal result on direct and/or indirect pancreatic exocrine function tests. Pancreatic enzyme replacement therapy was evaluated by its effect on survival and quality of life in patients with advanced pancreatic cancer. RESULTS: A total of 11 studies were included; seven studies reported the prevalence of pancreatic exocrine insufficiency and seven the effect of pancreatic enzyme replacement therapy in advanced pancreatic cancer. The pooled prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer was 72% (95% confidence interval: 55–86%), being significantly higher when tumours were located in the pancreatic head (relative risk = 3.36, 1.07–10.54; p = 0.04) six studies investigated the impact of pancreatic enzyme replacement therapy on survival/quality of life. Pancreatic enzyme replacement therapy was associated with 3.8 months (95% confidence interval: 1.37–6.19) survival benefit. Patients receiving pancreatic enzyme replacement therapy had a trend towards a better quality of life. Conclusions The prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer is substantial and its treatment can improve the outcomes of these patients.

Background and Aims Although coronavirus disease 2019 (COVID-19) has affected endoscopy services globally, the impact on trainees has not been evaluated. We aimed to assess the impact of COVID-19 on procedural volumes and on the emotional well-being of endoscopy trainees worldwide. Methods An international survey was disseminated over a 3-week period in April 2020. The primary outcome was the percentage reduction in monthly procedure volume before and during COVID-19. Secondary outcomes included potential variation of COVID-19 impact between different continents and rates and predictors of anxiety and burnout among trainees. Results Across 770 trainees from 63 countries, 93.8% reported a reduction in endoscopy case volume. The median percentage reduction in total procedures was 99% (interquartile range, 85%-100%), which varied internationally (P Conclusions The COVID-19 pandemic has led to restrictions in endoscopic volumes and endoscopy training, with high rates of anxiety and burnout among endoscopy trainees worldwide. Targeted measures by training programs to address these key issues are warranted to improve trainee well-being and support trainee education.

Background Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes. The factors related to oral feeding intolerance are not well studied. Objective We aimed to determine the incidence and risk factors of oral feeding intolerance in acute pancreatitis. Methods Patients were prospectively enrolled in the Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience, an international acute pancreatitis registry, between 2015 and 2018. Oral feeding intolerance was defined as worsening abdominal pain and/or vomiting after resumption of oral diet. The timing of the initial feeding attempt was stratified based on the day of hospitalization. Multivariable logistic regression was performed to assess for independent risk factors/predictors of oral feeding intolerance. Results Of 1233 acute pancreatitis patients included in the study, 160 (13%) experienced oral feeding intolerance. The incidence of oral feeding intolerance was similar irrespective of the timing of the initial feeding attempt relative to hospital admission day (p = 0.41). Patients with oral feeding intolerance were more likely to be younger (45 vs. 50 years of age), men (61% vs. 49%), and active alcohol users (44% vs. 36%). They also had higher blood urea nitrogen (20 vs. 15 mg/dl; p, Key Summary Current knowledge on this subject Oral feeding intolerance is a relatively common complication of acute pancreatitis.Oral feeding intolerance results in longer hospitalization and frequent readmissions. What is new in this study The incidence of oral feeding intolerance is similar irrespective of the timing of the initial feeding attempt.Oral feeding intolerance is independently associated with systemic inflammatory response syndrome at 48 h and nonbiliary etiology.

Acute pancreatitis is a heterogeneous illness. Most patients experience a mild course of disease, but one third will develop local complications and/or organ failure associated with increased morbidity and risk of mortality. Diagnosis of acute pancreatitis is based on typical epigastric pain, elevation of serum lipase or amylase levels, and/or characteristic findings on imaging. Personalised management is needed in patients with acute pancreatitis. Currently, analgesia, Ringer's lactate solution-based goal-directed fluid resuscitation and early oral refeeding providing enteral nutrition if not tolerated are the cornerstones for early management. Prophylactic antibiotics or endoscopic retrograde cholangiopancreatography in the absence of cholangitis are considered to be futile. Future clinical trials should address optimal fluid resuscitation, the early administration of anti-inflammatory drugs and the exact role of nutritional support in severe acute pancreatitis. Here, we present a patient case and review the diagnosis, treatment and prognosis of acute pancreatitis.

Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these alterations contribute to disease pathogenesis is largely unknown. To study the role of glycan changes in pancreatic disease, we inducibly expressed human Fucosyltransferase 3 and β1,3-Galactosyltransferase 5 in mice, reconstituting the glycan sialyl-Lewis (a)/Carbohydrate Antigen 19–9 (CA19–9). Notably, CA19–9 expression in mice resulted in rapid and severe pancreatitis with hyperactivation of epidermal growth factor receptor (EGFR) signaling. Mechanistically, CA19–9 modification of the matricellular protein Fibulin 3 increased its interaction with EGFR, and blockade of Fibulin 3, EGFR, or CA19–9 prevented EGFR hyperactivation in organoids. CA19–9-mediated pancreatitis was reversible and could be suppressed with CA19–9 antibodies. CA19–9 also cooperated with the Kras(G12D) oncogene to produce aggressive pancreatic cancer. These findings implicate CA19–9 in the etiology of pancreatitis and pancreatic cancer and nominate CA19–9 as a therapeutic target.

Severe acute pancreatitis complicated by infection is associated with high mortality. Invasive treatment is indicated in the presence of infected (suspected) pancreatic and/or peripancreatic necrosis (IPN) in the absence of response to intensive medical support. Step-up approach (SUA) has been demonstrated to lower complication rate compared to upfront open surgery. However, this approach has not been associated with lower mortality, and no factors have been studied that could help to identify the high risk patients. In this study, we aimed to analyse those factors associated with mortality following the invasive treatment of IPN, focusing on the role of surgical necrosectomy. A retrospective and observational study based on a multicentre prospective database was conducted. The database was coordinated by the Hospital General Universitario de Alicante, Spain and the Spanish Association of Pancreatology. Demographics, clinical data, and laboratory and imaging findings were collected. Atlanta 2012 criteria were considered to classify acute necrotizing pancreatitis and for the definition of IPN. Step-up approach was used in all centres with the intention of avoiding surgery whenever possible. Surgical necrosectomy was performed by open approach. From January 2013 to October 2014, a total of 1655 patients with the diagnosis of acute pancreatitis were included in our database. 1081 were recruited for the final analysis. Out of them, 205 (19%) were classified into acute necrotizing pancreatitis. 77 (8.3%) patients underwent invasive treatment of INP and were included in our study. Overall mortality was 29.9%. Upfront endoscopic or percutaneous drainage was performed in 60 (77.9%) patients and mortality was 26.6%. Out of 60, 22 (36.6%) patients subsequently received rescue surgery; mortality in rescue surgery group was 18.3%. Upfront surgery was carried out in 17 (22.1%) patients; mortality in this group was 41%. At univariate analysis, surgical necrosectomy, extrapancreatic infection, immunosuppression and de-novo haemodialysis were associated with mortality. At multivariate analysis, only surgical necrosectomy was significantly associated with mortality (p = 0.002 OR 3.89). Surgical approach for IPN is associated with high mortality rate. However, these data should be interpreted with caution, since we are not able to assess whether this occurs due to the need of surgery as the only resort when the other approaches are not feasible or fail.

Objectives Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. Methods Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). Results The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. Conclusions The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.

Objectives: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP. Methods: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated. Results: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P=0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94–2.99, P=0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P=0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49–2.13), P=0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20minutes, were risk factors. Conclusions: The use of statins or ASA is not associated with a lower risk or a milder course of PEP.

Background/Objective: Evidence from basic and clinical studies suggests that unsaturated fatty acids (UFAs) might be relevant mediators of the development of complications in acute pancreatitis (AP). Objective: The aim of this study was to analyze outcomes in patients with AP from regions in Spain with different patterns of dietary fat intake. Materials and Methods: A retrospective analysis was performed with data from 1,655 patients with AP from a Spanish prospective cohort study and regional nutritional data from a Spanish cross-sectional study. Nutritional data considered in the study concern the total lipid consumption, detailing total saturated fatty acids, UFAs and monounsaturated fatty acids (MUFAs) consumption derived from regional data and not from the patient prospective cohort. Two multivariable analysis models were used: (1) a model with the Charlson comorbidity index, sex, alcoholic etiology, and recurrent AP; (2) a model that included these variables plus obesity. Results: In multivariable analysis, patients from regions with high UFA intake had a significantly increased frequency of local complications, persistent organ failure (POF), mortality, and moderate-to-severe disease in the model without obesity and a higher frequency of POF in the model with obesity. Patients from regions with high MUFA intake had significantly more local complications and moderate-to-severe disease; this significance remained for moderate-to-severe disease when obesity was added to the model. Conclusions: Differences in dietary fat patterns could be associated with different outcomes in AP, and dietary fat patterns may be a pre-morbid factor that determines the severity of AP. UFAs, and particulary MUFAs, may influence the pathogenesis of the severity of AP., GG-R was supported by grant from the Instituto de Salud Carlos III and Instituto de Investigación Sanitaria (IIS) Aragón [Río Hortega grant CM17/00145].