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Background and Aims: Difficult biliary cannulation (DBC) is a known risk factor for developing post-ERCP pancreatitis (PEP). To better understand how DBC increases PEP risk, we examined the interplay between technical aspects of DBC and known PEP risk factors., Methods: This was a secondary analysis of a multicenter, randomized controlled trial comparing rectal indomethacin alone with the combination of rectal indomethacin and prophylactic pancreatic duct (PD) stent placement for PEP prophylaxis in high-risk patients. Participants were categorized into 3 groups: DBC with high preprocedure risk for PEP, DBC without high preprocedure risk for PEP, and non-DBC at high preprocedure risk for PEP., Results: In all, 1601 participants (84.1%) experienced DBC, which required a mean of 12 cannulation attempts (standard deviation, 10) and mean duration of 14.7 minutes (standard deviation, 14.9). PEP rate was highest (20.7%) in DBC with a high preprocedure risk, followed by non-DBC with a high preprocedure risk (13.5%), and then DBC without a high preprocedure risk (8.8%). Increasing number of PD wire passages (adjusted odds ratio [aOR], 1.97; 95% confidence interval [CI], 1.25-3.1) was associated with PEP in DBC, but PD injection, pancreatic sphincterotomy, and number of cannulation attempts were not associated with PEP. Combining indomethacin with PD stent placement lowered the risk of PEP (aOR, .61; 95% CI, .44-.84) in DBCs. This protective effect was evident in up to at least 4 PD wire passages., Conclusions: DBC confers higher PEP risk in an additive fashion to preprocedural risk factors. PD wire passages appear to add the greatest PEP risk in DBCs, but combining indomethacin with PD stent placement reduces this risk, even with increasing PD wire passages., Competing Interests: Disclosure Dr. Andrew Y. Wang discloses owning publicly traded stock in Pfizer and GE HealthCare Technologies. Dr. Mouen Khashab is a consultant for Boston Scientific and Olympus and he receives royalties from Elsevier and UpToDate. Dr. Andy Ross is a consultant for Boston Scientific and Olympus. Dr. Samuel Han is a consultant for Boston Scientific. Dr. Ji Young Bang is a consultant for Boston Scientific and Olympus. Dr. Shyam Varadarajulu is a consultant for Boston Scientific and Olympus. Dr. Field F. Willingham is a consultant for Boston Scientific and Cook Medical. Dr. Somashekar G. Krishna receives honoraria and grant support from Taewoong. Dr. Rajesh Keswani is a consultant for Boston Scientific. Dr. Steven A. Edmundowivcz is a consultant for Olympus and receives honoraria from Boston Scientific. Dr. Raj J. Shah is a consultant for Boston Scientific and Cook Medical. Dr. Nauzer Forbes is a consultant for Boston Scientific and Pentax. Dr. Yen-I Chen is a consultant for Boston Scientific. Dr. Alan Barkun is a Research support, consultation, Advisory board in Medtronic; Research support in Cook; Consultant, Payment or honoraria for lectures and trave in Takeda Canada Inc.; Consultant, Payment or honoraria for lectures and travel fees in Olympus Inc.; Payment or honoraria for lectures and travel fees in AstraZeneca Inc.; Advisory board in Pendopharm Canada Inc. The other authors disclosed no financial relationships. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under award number: U01DK104833. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain., Methods: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP)., Results: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37-1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73-3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63-1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65-1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49-1.41)., Discussion: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach., (Copyright © 2024 by The American College of Gastroenterology.)

Background and Aims: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision making related to periprocedural prophylaxis selection and postprocedural monitoring., Methods: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk, and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a 1-month period., Results: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on 20 PEP risk factors and 5 prophylactic interventions (rectal nonsteroidal anti-inflammatory drugs [NSAIDs], aggressive hydration, combined rectal NSAIDs and aggressive hydration, pancreatic duct stenting, and combined rectal NSAIDs and pancreatic duct stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, and 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74., Conclusions: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended postprocedure monitoring., Competing Interests: Disclosure The following authors disclosed financial relationships: A. Kuo: Equity holder in Apollo Endosurgery and patent applications for intellectual property related to cancer early detection. S. S. Mok: Consultant for Sovereign Laboratories, ConMed, and Medtronic-Covidien Corporation. M. A. Khashab: Advisory board member and consultant for Boston Scientific. E. J. M. van Geenen: Grants from Mylan and Olympus and personal fees outside the submitted work from MTW-Endoskopie. V. K. Singh: Grant support and personal fees outside the submitted work from AbbVie; advisory board participant for Ariel Precision Medicine, and Envara; grants from Orgenesis and Theraly; and advisory board participant for and stock options from Kyttaro. C. Tomasetti: Scientific advisory board member for PrognomiQ, Inc; royalty distributions from Exact Sciences (under a license agreement between Exact Sciences Corp and the Johns Hopkins University, C. Tomasetti and the university are entitled to royalty distributions); paid consultant for Bayer A; and patent applications for intellectual property related to cancer early detection (these arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies). V. S. Akshintala: Cofounder and chief medical officer for Origin Endoscopy and Solv Endotherapy and consultant for Dragonfly Endoscopy and Olympus. All other authors disclosed no financial relationships. C. Tomasetti received funding from the John Templeton Foundation., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort., Methods: In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 μg/g; severe FE-1 level ≤100 μg/g; mild FE-1 101-200 μg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398., Findings: EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%)., Interpretation: EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening., Funding: This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc., Competing Interests: VKS declares being a Consultant to Ariel Precision Medicine, Panafina, and Horizon Therapeutics; a Scientific Advisory Board Member of and equity holder in Kyttaro, Origin Endoscopy and Solv Endotherapy. SC declares funding for research, including salary, paid to her institution by Abbvie. MLR declares support from the Cystic Fibrosis Foundation and the American Society for Parenteral and Enteral Nutrition, and position as Chair for the Young Trainees Committee for the Collaborative Alliance for Pancreatic Education and Research (CAPER). PJL declares the Investigator Initiated Research funding from Abbvie for the project execution and administration. GIP declares the Investigator Initiated Research funding that supported this study from Abbvie. All other authors declare no financial or other conflicts of interest., (© 2024 The Authors.)

Background: Symptom assessment is the key factor in determining disease status and optimal management of exocrine pancreatic insufficiency (EPI). There is a need for a standardized patient-reported outcome (PRO) questionnaire to assess symptoms in patients diagnosed with EPI. The purpose of this qualitative study was to increase understanding of the EPI symptom experience from the patients' perspective, and to develop and evaluate the content validity of the EPI Symptom Questionnaire (EPI-SQ) in US patients with EPI., Methods: Concept elicitation interviews (Phase I) were conducted to understand the symptom experience in patients with a clinical diagnosis of EPI (i.e., fecal pancreatic elastase value of ≤ 200 mcg/g based on most recent value) due to chronic pancreatitis or pancreatectomy. The EPI-SQ was developed based on the data extracted from Phase I interviews and feedback from clinical experts. Next, separate cognitive interviews (Phase II) were conducted to evaluate participants' understanding of the instructions, items, response scales, and recall periods of the instrument., Results: During Phase I interviews (n = 21), 19 participants (90%) reported abdominal pain as the most frequent EPI symptom and lifestyle changes were the most frequently endorsed impacts (n = 18; 86%). Phase II results indicated that all participants (n = 7) felt the 12-item EPI-SQ was relevant to their symptom experience and that they understood the items, instructions, and response options as intended., Conclusion: The qualitative data from this study support the content validity of the EPI-SQ in measuring EPI symptom severity in US patient populations diagnosed with EPI., (© 2024. The Author(s).)

Background: In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes., Methods: We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses., Results: In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures (P < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity (P = 0.002) or overweight status pre-TPIAT (P < 0.001) and lower with non-White race (P = 0.03), genetic pancreatitis (P = 0.02), history of lateral pancreaticojejunostomy (P = 0.03), and presence of atrophy (P = 0.006) or ductal changes (P = 0.014) on imaging. IEQ/kg was higher in females (P = 0.01) and Hispanic participants (P = 0.046) and generally lower with older age (nonlinear association, P < 0.001) and pancreatic atrophy (P < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively., Conclusions: Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results., Competing Interests: M.D.B. received research support from Dexcom and Viacyte and had advisory board or consultant roles with Insulet, Vertex, and Emerging Therapy Solutions. G.J.B. was supported by US Army Medical Acquisitions (grant W81XWH1810687). S.J.S. was consultant to UpToDate, Renexxion, Abbvie, and Mirum. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Total pancreatectomy with islet autotransplantation (TPIAT) treats refractory pain in chronic pancreatitis, prevents episodes of acute exacerbation, and mitigates postoperative brittle diabetes. The minimally invasive (MIS) approach offers a decreased surgical access trauma and enhanced recovery. Having established a laparoscopic TPIAT program, we adopted a robotic approach (R-TPIAT) and studied patient outcomes compared to open TPIAT., Methods: Between 2013 and 2021, 61 adult patients underwent TPIAT after a comprehensive evaluation (97% chronic pancreatitis). Pancreatic islets were isolated on-site during the procedure. We analyzed and compared intraoperative surgical and islet characteristics, postoperative morbidity and mortality, and 1-year glycemic outcomes., Results: MIS-TPIAT was performed in 41 patients (67%, 15 robotic and 26 laparoscopic), and was associated with a shorter mean length of intensive care unit stay compared to open TPIAT (2.9 vs 4.5 days, p = 0.002). R-TPIAT replaced laparoscopic TPIAT in 2017 as the MIS approach of choice and demonstrated decreased blood loss compared to open TPIAT (324 vs 843 mL, p = 0.004), similar operative time (609 vs 562 min), 30-day readmission rate (7% vs 15%), and 90-day complication rate (13% vs 20%). The glycemic outcomes including C-peptide detection at 1-year (73% vs 88%) and insulin dependence at 1-year (75% vs 92%) did not differ. The mean length of hospital stay after R-TPIAT was 8.6 days, shorter than for laparoscopic (11.5 days, p = 0.031) and open TPIAT (12.6 days, p = 0.017). Both MIS approaches had a 1-year mortality rate of 0%., Conclusions: R-TPIAT was associated with a 33% reduction in length of hospital stay (4-day benefit) compared to open TPIAT. R-TPIAT was similar to open TPIAT on measures of feasibility, safety, pain control, and 1-year glycemic outcomes. Our data suggest that robotic technology, a new component in the multidisciplinary therapy of TPIAT, is poised to develop into the primary surgical approach for experienced pancreatic surgeons., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/objectives: No simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP., Methods: This was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional predictive models. EPI misclassification rate (mRate) served as primary endpoint metric., Results: 274 patients with definite CP from 6 pancreatitis centers across the United States were included, of which 58 % had EPI based on predetermined criteria. The optimal CART decision tree included 10 variables. The mRate without/with 5-fold cross-validation of the CART was 0.153 (training error) and 0.314 (prediction error), and the area under the receiver operating characteristic curve was 0.889 and 0.682, respectively. Sensitivity and specificity without/with 5-fold cross-validation was 0.888/0.789 and 0.794/0.535, respectively. A trained second CART without pancreas imaging variables (n = 6), yielded 8 variables. Training error/prediction error was 0.190/0.351; sensitivity was 0.869/0.650, and specificity was 0.728/0.649, each without/with 5-fold cross-validation., Conclusion: We developed two CART models that were integrated into one digital screening tool to assess for EPI in patients with definite CP and with two to six input variables needed for predicting EPI status., (Published by Elsevier B.V.)

Background & Aim: Extracorporeal shock wave lithotripsy (ESWL) is used for the treatment of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). We aimed to develop a CT based index to predict the required number of ESWL sessions for technical success., Methods: We retrospectively evaluated patients with PDS secondary to CP who underwent ESWL. Technical success was defined as the complete fragmentation of stones to <3 mm. CT features including PDS size, number, location, and density in Hounsfield units (HU) were noted. We analyzed the relationship between PDS characteristics and the number of ESWL sessions required for technical success. A multiple linear regression model was used to combine size and density into the pancreatic duct stone (PDS) index that was translated into a web-based calculator., Results: There were 206 subjects (mean age 38.6 ± 13.7 years, 59.2% male) who underwent ESWL. PDS size showed a moderate correlation with the number of ESWL sessions (r = 0.42, p < 0.01). PDS in the head required a fewer number of sessions in comparison to those in the body (1.4 ± 0.6 vs. 1.6 ± 0.7, p = 0.01). There was a strong correlation between PDS density and the number of ESWL sessions (r = 0.617, p-value <0.01). The PDS index {0.3793 + [0.0009755 x PDS density (HU)] + [0.02549 x PDS size (mm)]} could accurately predict the required number of ESWL sessions with an AUC of 0.872 (p < 0.01)., Conclusion: The PDS index is a useful predictor of the number of ESWL sessions needed for technical success that can help in planning and patient counseling., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The management of acute necrotizing pancreatitis (ANP) has changed dramatically over the past 20 years including the use of less invasive techniques, the timing of interventions, nutritional management, and antimicrobial management. This study sought to create a core outcome set (COS) to help shape future research by establishing a minimal set of essential outcomes that will facilitate future comparisons and pooling of data while minimizing reporting bias., Methods: A modified Delphi process was performed through involvement of ANP content experts. Each expert proposed a list of outcomes for consideration, and the panel anonymously scored the outcomes on a 9-point Likert scale. Core outcome consensus defined a priori as >70% of scores receiving 7 to 9 points and <15% of scores receiving 1 to 3 points. Feedback and aggregate data were shared between rounds with interclass correlation trends used to determine the end of the study., Results: A total of 19 experts agreed to participate in the study with 16 (84%) participating through study completion. Forty-three outcomes were initially considered with 16 reaching consensuses after four rounds of the modified Delphi process. The final COS included outcomes related to mortality, organ failure, complications, interventions/management, and social factors., Conclusion: Through an iterative consensus process, content experts agreed on a COS for the management of ANP. This will help shape future research to generate data suitable for pooling and other statistical analyses that may guide clinical practice., Level of Evidence: Therapeutic/Care Management; Level V., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: No randomized controlled trials have substantiated endoscopic decompression of the pancreatic duct in patients with painful chronic pancreatitis., Objective: To investigate the pain-relieving effect of pancreatic duct decompression in patients with chronic pancreatitis and intraductal stones., Design: 24-week, parallel-group, randomized controlled trial (ClinicalTrials.gov: NCT03966781)., Setting: Asian Institute of Gastroenterology in India from February 2021 to July 2022., Participants: 106 patients with chronic pancreatitis., Intervention: Combined extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde pancreatography (ERP) compared with sham procedures., Measurements: The primary end point was pain relief on a 0- to 10-point visual analog scale (VAS) at 12 weeks. Secondary outcomes were assessed after 12 and 24 weeks and included 30% pain relief, opioid use, pain-free days, questionaries, and complications to interventions., Results: 52 patients in the ESWL/ERP group and 54 in the sham group were included. At 12 weeks, the ESWL/ERP group showed better pain relief compared with the sham group (mean difference in change, -0.7 [95% CI, -1.3 to 0] on the VAS; P  = 0.039). The difference between groups was not sustained at the 24-week follow-up, and no differences were seen for 30% pain relief at 12- or 24-week follow-up. The number of pain-free days was increased (median difference, 16.2 days [CI, 3.9 to 28.5 days]), and the number of days using opioids was reduced (median difference, -5.4 days [CI, -9.9 to -0.9 days]) in the ESWL/ERP group compared with the sham group at 12-week follow-up. Safety outcomes were similar between groups., Limitation: Single-center study and limited duration of follow-up., Conclusion: In patients with chronic pancreatitis and intraductal stones, ESWL with ERP provided modest short-term pain relief., Primary Funding Source: Asian Institute of Gastroenterology and Aalborg University Hospital., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0210.

Exocrine pancreatic dysfunction (EPD) is a malabsorptive complication of pancreatic disorders that can lead to a host of symptoms ranging from flatulence to diarrhea and contribute to weight loss and metabolic bone disease. It is increasingly recognized to occur after acute pancreatitis (AP), including episodes with mild severity. The risk of developing EPD after AP is influenced by a range of factors, including the degree of acinar cell destruction and inflammation during AP, and persistent structural derangements following AP. In this article, we discuss the epidemiology, pathophysiology, and clinical management of EPD after AP while highlighting key knowledge gaps., Competing Interests: Declaration of competing interest No conflicts of interest exist., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Acute pancreatitis (AP) is a sudden-onset inflammatory disease of the pancreas. The severity of AP is classified into mild, moderate, and severe categories based on the presence and persistence of organ failure. Severe acute pancreatitis (SAP) can be associated with significant morbidity and mortality. It requires early recognition for appropriate timely management. Prognostic scores for predicting SAP incorporating many clinical, laboratory, and radiological parameters have been developed in the past. However, all of these prognostic scores have low positive predictive value for SAP and some of these scores require >24 h for assessment. There is a need to develop biomarkers that can accurately identify patients at risk for SAP early in the course of the presentation. In this review, we aim to provide a summary of the most commonly utilized prognostic scores for AP and discuss future directions., Competing Interests: All authors have no personal or financial disclosures., (© 2024 The Authors.)

Introduction: Treatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent pain stimuli. This is suspected to render affected individuals less likely to respond to conventional therapies. Endotherapy or surgical decompression is offered to patients with pancreatic duct obstruction. However, the response to treatment is unpredictable. Pancreatic quantitative sensory testing (P-QST), an investigative technique of standardised stimulations to test the pain system in CP, has been used for phenotyping patients into three mutually exclusive groups: no central sensitisation, segmental sensitisation (pancreatic viscerotome) and widespread hyperalgesia suggestive of supraspinal central sensitisation. We will test the predictive capability of the pretreatment P-QST phenotype to predict the likelihood of pain improvement following invasive treatment for painful CP., Methods and Analysis: This observational clinical trial will enrol 150 patients from the University of Pittsburgh, Johns Hopkins and Indiana University. Participants will undergo pretreatment phenotyping with P-QST. Treatment will be pancreatic endotherapy or surgery for clearance of painful pancreatic duct obstruction., Primary Outcome: average pain score over the preceding 7 days measured by Numeric Rating Scale at 6 months postintervention. Secondary outcomes will include changes in opioid use during follow-up, and patient-reported outcomes in pain and quality of life at 3, 6 and 12 months after the intervention. Exploratory outcomes will include creation of a model for individualised prediction of response to invasive treatment., Ethics and Dissemination: The trial will evaluate the ability of P-QST to predict response to invasive treatment for painful CP and develop a predictive model for individualised prediction of treatment response for widespread use. This trial was approved by the University of Pittsburgh Institutional Review Board. Data and results will be reported and disseminated in conjunction with National Institutes of Health policies., Trial Registration Number: NCT04996628., Competing Interests: Competing interests: AEP: Board Member, National Pancreas Foundation. VKS: Consultant to Abbvie, Ariel Precision Medicine, Horizon Therapeutics and Panafina; Medical Advisory Board participant to Organon; Scientific advisory board participant for Kyttaro, Origin Endoscopy and Solv Endoscopy; Equity holder in Kyttaro, Origin Endoscopy, Solv Endoscopy. The other authors have no financial or personal competing interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention., Methods: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete., Findings: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups., Interpretation: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines., Funding: US National Institutes of Health., Competing Interests: Declaration of interests The following authors have received honoraria, consulting fees, or research support from companies that manufacture prophylactic pancreatic stents or indomethacin within the last 2 years: SAE (consulting fees from Olympus, honoraria from Boston Scientific), NF (consulting fees and payment or honoraria for lectures or receipt of equipment or materials from Boston Scientific and Pentax), FFW (consulting fees from Cook/Boston Scientific), SV (consulting fees from Boston Scientific/Olympus), JYB (consulting fees from Boston Scientific/Olympus), MK (consulting fees from Boston Scientific), RK (consulting fees from Boston Scientific), Y-IC (consulting fees, honoraria, research grants, and travel payments from Boston Scientific), AB (financial interest in Olympus), ARo (payment or honoraria for lectures or presentations and travel from Boston Scientific), and study group members SGK (honoraria and grant support from Taewoong Medical) and SG (consulting fees and honoraria from Boston Scientific). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Recent pilot trials in acute pancreatitis (AP) found that lactated ringers (LR) usage may result in decreased risk of moderately severe/severe AP compared with normal saline, but their small sample sizes limit statistical power. We investigated whether LR usage is associated with improved outcomes in AP in an international multicenter prospective study., Methods: Patients directly admitted with the diagnosis of AP were prospectively enrolled at 22 international sites between 2015 and 2018. Demographics, fluid administration, and AP severity data were collected in a standardized prospective manner to examine the association between LR and AP severity outcomes. Mixed-effects logistic regression analysis was performed to determine the direction and magnitude of the relationship between the type of fluid administered during the first 24 hours and the development of moderately severe/severe AP., Results: Data from 999 patients were analyzed (mean age 51 years, female 52%, moderately severe/severe AP 24%). Usage of LR during the first 24 hours was associated with reduced odds of moderately severe/severe AP (adjusted odds ratio 0.52; P = 0.014) compared with normal saline after adjusting for region of enrollment, etiology, body mass index, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume., Discussion: LR administration in the first 24 hours of hospitalization was associated with improved AP severity. A large-scale randomized clinical trial is needed to confirm these findings., (Copyright © 2023 by The American College of Gastroenterology.)

Pancreatic duct pressure (PDP) dynamics comprise an intricately modulated system that helps maintain homeostasis of pancreatic function. It is affected by various factors, including the rate of pancreatic fluid secretion, patency of the ductal system, sphincter of Oddi function, and pancreatic fluid characteristics. Disease states such as acute and chronic pancreatitis can alter the normal PDP dynamics. Ductal hypertension or increased PDP is suspected to be involved in the pathogenesis of pancreatic pain, endocrine and exocrine pancreatic insufficiency, and recurrent pancreatitis. This review provides a comprehensive appraisal of the available literature on PDP, including the methods used in the measurement and clinical implications of elevated PDP., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure for the management of pancreato-biliary disorders. Pancreatitis remains the most frequent complication of the ERCP procedure, and it is, therefore, necessary to recognize the pathophysiology and risk factors contributing to the development of pancreatitis and understand the methods to prevent this complication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: Total pancreatectomy with islet autotransplantation (TPIAT) can relieve pain for individuals with acute recurrent or chronic pancreatitis. However, TPIAT may increase the risk of poor nutritional status with complete exocrine pancreatic insufficiency, partial duodenectomy, and intestinal reconstruction. Our study's objective was to evaluate nutritional status, anthropometrics, and vitamin levels before and after TPIAT., Methods: The multicenter Prospective Observational Study of TPIAT (POST) collects measures including vitamins A, D, and E levels, pancreatic enzyme dose, and multivitamin (MVI) administration before and 1-year after TPIAT. Using these data, we studied nutritional and vitamin status before and after TPIAT., Results: 348 TPIAT recipients were included (68% adult, 37% male, 93% Caucasian). In paired analyses at 1-year follow-up, vitamin A was low in 23% (vs 9% pre-TPIAT, p < 0.001); vitamin E was low in 11% (vs 5% pre-TPIAT, p = 0.066), and 19% had vitamin D deficiency (vs 12% pre-TPIAT, p = 0.035). Taking a fat-soluble multivitamin (pancreatic MVI) was associated with lower risk for vitamin D deficiency (p = 0.002). Adults were less likely to be on a pancreatic MVI at follow-up (34% vs 66% respectively, p < 0.001). Enzyme dosing was adequate. More adults versus children were overweight or underweight pre- and post-TPIAT. Underweight status was associated with vitamin A (p = 0.014) and E (p = 0.02) deficiency at follow-up., Conclusions: Prevalence of fat-soluble vitamin deficiencies increased after TPIAT, especially if underweight. We strongly advocate that all TPIAT recipients have close post-operative nutritional monitoring, including vitamin levels. Pancreatic MVIs should be given to minimize risk of developing deficiencies., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background/aims: Early and accurate identification of patients with acute pancreatitis (AP) at high risk of persistent acute respiratory failure (PARF) is crucial. We sought to determine the accuracy of simplified Lung Injury Prediction Score (sLIPS) and simplified Early Acute Lung Injury (sEALI) for predicting PARF in ward AP patients., Methods: Consecutive AP patients in a training cohort from West China Hospital of Sichuan University (n = 912) and a validation cohort from The First Affiliated Hospital of Nanchang University (n = 1033) were analyzed. PARF was defined as oxygen in arterial blood/fraction of inspired oxygen < 300 mmHg that lasts for > 48 h. The sLIPS was composed by shock (predisposing condition), alcohol abuse, obesity, high respiratory rate, low oxygen saturation, high oxygen requirement, hypoalbuminemia, and acidosis (risk modifiers). The sEALI was calculated from oxygen 2 to 6 L/min, oxygen > 6 L/min, and high respiratory rate. Both indices were calculated on admission., Results: PARF developed in 16% (145/912) and 22% (228/1033) (22%) of the training and validation cohorts, respectively. In these patients, sLIPS and sEALI were significantly increased. sLIPS ≥ 2 predicted PARF in the training (AUROC 0.87, 95% CI 0.84-0.89) and validation (AUROC 0.81, 95% CI 0.78-0.83) cohorts. sLIPS was significantly more accurate than sEALI and current clinical scoring systems in both cohorts (all P < 0.05)., Conclusions: Using routinely available clinical data, the sLIPS can accurately predict PARF in ward AP patients and outperforms the sEALI and current existing clinical scoring systems., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs)., Methods: The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality., Results: One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48)., Conclusions: The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: To systematically evaluate the patient and procedural risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among patients receiving rectal indomethacin., Methods: Data from a randomized controlled trial (RCT) of high-risk patients undergoing ERCP who received rectal indomethacin with or without topical epinephrine was evaluated. PEP was defined based on the consensus criteria. Pancreatic stenting was excluded to avoid confounding results with the role of epinephrine spray. Multivariable logistic regression analysis was used to identify patient and procedural risk factors for PEP., Results: Among 960 patients enrolled in the RCT, the PEP incidence was 6.4%. An increased risk of PEP was seen with age <50 years and female gender (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.35-4.26), malignant biliary stricture(s) (OR 3.51, 95% CI 1.52-8.10), >2 guidewire passes into the pancreatic duct (PD) (OR 2.84, 95% CI 1.43-5.64), and pancreatic brush cytology (OR 6.37, 95% CI 1.10-36.90), whereas a decreased risk of PEP was seen with contrast- over guidewire-assisted cannulation (OR 0.14, 95% CI 0.02-0.99) and the use of lactated Ringer's (LR) over other fluid types (OR 0.52, 95% CI 0.27-0.98). There was a significant trend between the number of guidewire passes into the PD and PEP risk (P = 0.002)., Conclusions: More than two guidewire passes into the PD and pancreatic brush cytology increased while the use of LR decreased the risk of PEP among high-risk patients receiving rectal indomethacin. Pancreatic stent placement and/or LR should be considered in patients with >2 guidewire passes into the PD., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objectives: To determine the factors associated with serial lipase measurement in patients with acute pancreatitis (AP)., Methods: Patients admitted to Johns Hopkins Health System between September 2019 and August 2020 with lipase ≥3 times upper limit normal were prospectively identified. Acute pancreatitis was defined using revised Atlanta criteria. Serial lipase measurement was defined as >2 lipase measurements on consecutive days within 7 days of presentation., Results: There were 294 patients with AP with mean age 52.4 ± 16 years (SD), and 155 (52.7%) were male. A total of 227 (77.2%) were admitted to a medical service. There were 111 (37.7%) who underwent serial lipase measurements. There were 89 (30.8%), 36 (12.2%), 6 (1%), and 40 (13.6%) patients with systemic inflammatory response syndrome at time of initial lipase measurement, persistent organ failure, necrosis on admission, and intensive care unit admission. Serial lipase measurements were more likely to be obtained in patients admitted to surgical services (odds ratio, 4.3; 95% confidence interval, 1.4-13.2; P = 0.01) and nontertiary hospitals (odds ratio, 1.8; 95% confidence interval, 1.0-2.9; P = 0.04)., Conclusion: More than one-third of AP patients undergo serial lipase measurements. This practice is more likely to occur on surgical services and in nontertiary hospitals., Competing Interests: V.K.S. has participated on an advisory board for Vertex, is a consultant to AbbVie and Ariel Precision Medicine, is on the scientific advisory board for and has stock options in Kyttaro, and receives grant support from AbbVie. E.A. participated on an advisory board for Nestlé. These financial interests do not pertain directly to this work. The other authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes., Methods: We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included., Results: Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values <200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7)., Conclusions: CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Sympatico-vagal balance is essential for regulating cardiac electrophysiology and plays an important role in arrhythmogenic conditions. Various noninvasive methods, including electrocardiography (ECG), have been used for clinical assessment of the sympatico-vagal balance. This study aimed to use a custom-designed wearable device to record ECG and ECG-based cardiac function biomarkers to assess sympatico-vagal balance during tonic pain in healthy controls. Nineteen healthy volunteers were included for the ECG measurements using the custom-designed amplifier based on the Texas Instruments ADS1299. The ECG-based biomarkers of the sympatico-vagal balance, (including heart rate variability, deceleration capacity of the heart rate, and periodic repolarization dynamic), were calculated and compared between resting and pain conditions (tonic pain). The custom-designed device provided technically satisfactory ECG recordings. During exposure to tonic pain, the periodic repolarization dynamics increased significantly ( p = 0.02), indicating enhancement of sympathetic nervous activity. This study showed that custom-designed wearable devices can potentially be useful in healthcare as a new telemetry technology. The ECG-based novel biomarkers, including periodic repolarization dynamic and deceleration capacity of heart rate, can be used to identify the cold pressor-induced activation of sympathetic and parasympathetic systems, making it useful for future studies on pain-evoked biomarkers.

Background: Developing effective gastrointestinal (GI) bleeding animal models is necessary to advance endoscopic hemostasis methods and train endoscopists on their use. Our aim, therefore, was to develop an effective and safe porcine GI bleeding model in the stomach and colon of large and small-sized oozing-type ulcers., Methods: Gastric and colonic bleeding ulcers were created using either a hybrid endoscopic submucosal dissection (ESD) technique or a cap-assisted endoscopic mucosal resection (EMR-C) technique in 14 pigs. Prior to ulcer creation, animals were treated with either oral apixaban or intravenous (IV) unfractionated heparin anticoagulation in combination with clopidogrel and aspirin. The primary outcome was the technical success of inducing oozing-type Forrest Ib bleeding ulcers. Secondary outcomes included ulcer diameter, number, creation time and the number of complications associated with each technique., Results: Using hybrid ESD and IV heparin anticoagulation, bleeding was observed in 21/23 (91.3%) gastric ulcers and 6/7 (85.7%) colonic ulcers created. The mean diameter and ulcer creation time were 2.3 ± 0.3 cm and 5.3 ± 0.5 min, respectively, for gastric ulcers and 2.2 ± 0.4 cm and 4.06 ± 0.6 min, respectively, for colonic ulcers. Using EMR-C and IV heparin anticoagulation, bleeding was observed in 14/15 (93.3%) gastric ulcers and 6/6 (100%) colonic ulcers created. The mean diameter and ulcer creation time were 0.8 ± 0.2 cm and 2.1 ± 0.5 min, respectively, for gastric ulcers and 0.7 ± 0.2 cm and 1.7 ± 0.3 min, respectively, for colonic ulcers. None of the ulcers created in animals anticoagulated with apixaban developed bleeding. None of the 14 pigs developed any complications., Conclusion: We have demonstrated the effectiveness and safety of a porcine GI bleeding model utilizing IV heparin anticoagulation and either hybrid ESD or EMR-C techniques to create oozing-type bleeding ulcers in the stomach and colon with customizable size., (© 2023. Indian Society of Gastroenterology.)

Objective: 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., Method: 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., Results: 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., Conclusion: 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.

Introduction: Pancreatic duct obstruction is the primary indication for endoscopic and/or surgical therapy in patients with chronic pancreatitis (CP). However, the clinical course of medically managed patients in relation to pancreatic duct obstruction is largely unknown., Methods: This was a retrospective cohort study of medically managed patients with CP. We classified patients based on pancreatic duct obstruction from a stricture or stone using cross-sectional imaging (i.e., large vs small duct CP). We compared prevalence of diabetes and exocrine insufficiency (EPI) between subgroups at inclusion and investigated risk of new-onset diabetes, EPI, and all-cause mortality over a follow-up period of 5 years. Changes in pancreatic morphology were studied in patients who underwent follow-up imaging., Results: A total of 198 patients (mean age 58 ± 12 years, 70% male, 60% alcoholic etiology, 38% large duct CP) were evaluated. At inclusion, patients with large vs small duct CP had a higher prevalence of both diabetes (43% vs 24%, P = 0.004) and EPI (47% vs 28%, P = 0.007). There was an increased risk of new-onset EPI in patients with large duct CP (hazard ratio 1.72; 95% confidence interval [1.05-2.80], P = 0.031) and higher rates of pancreatic atrophy ( P < 0.001). No differences between groups were observed for new-onset diabetes and all-cause mortality. Conversion from small to large duct CP or vice versa during follow-up was observed in 14% of patients., Discussion: In a medically managed cohort of patients, large duct CP was associated with increased risk of EPI and pancreatic atrophy compared with small duct CP., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objective: Several factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs)., Design: We performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses., Results: Clinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (p<0.001) and pain interference scores (p<0.001), and a reduction in quality of life (p<0.001). All factors had independent and direct effects on PROs, with the strongest effect size observed for psychological distress., Conclusion: Pain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management., Trial Registration Number: The study was registered with ClinicalTrials.gov (NCT03434392)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort., Methods: We evaluated data from 883 patients with CP prospectively enrolled in the North American Pancreatitis Studies across 27 US centers between 2000 and 2014. We determined how often patients had one or more episodes of AP and its occurrence in relationship to the diagnosis of CP. We used multivariable logistic regression to determine associations for prior AP., Results: There were 624/883 (70.7%) patients with prior AP, among whom 161 (25.8%) had AP within 2 years, 115 (18.4%) within 3-5 years, and 348 (55.8%) >5 years prior to CP diagnosis. Among 504 AP patients with available information, 436 (86.5%) had >1 episode. On multivariable analyses, factors associated with increased odds of having prior AP were a younger age at CP diagnosis, white race, abdominal pain, pseudocyst(s) and pancreatic duct dilatation/stricture, while factors associated with a lower odds of having prior AP were exocrine insufficiency and pancreatic atrophy. When compared with patients with 1 episode, those with >1 AP episode were diagnosed with CP an average of 5 years earlier., Conclusions: Nearly three-quarters of patients were diagnosed with AP prior to CP diagnosis. Identifying which AP patients are at-risk for future progression to CP may provide opportunities for primary and secondary prevention., Competing Interests: Declaration of competing interest V.K.S. is a consultant for AbbVie, Vertex, and Ariel Precision Medicine; scientific advisory board member and equity holder in Kyttaro; and receives grant support from AbbVie. D.C.W is co-founder and Chief Scientific Officer of Ariel Precision Medicine and may have equity., (Copyright © 2022. Published by Elsevier B.V.)

Background: Acute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users., Methods: The INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1-2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas., Conclusions: The INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs., Trial Registration: NCT05252754, registered on February 14, 2022., Competing Interests: Declaration of competing interest Mouen Khashab reports advisory board member and consultant for Boston Scientific. Erwin J.M. van Geenen reports grants from Mylan and Olympus, personal fees from MTW-Endoskopie, outside the submitted work. Vikesh Singh reports personal fees from Abbvie, advisory board participant for Cook Medical, and grants from Orgenesis and Theraly. Venkata Akshintala is co-founder and chief medical officer of Origin Endoscopy Inc. All other authors declare no competing interests., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Early prediction of persistent organ failure (POF) is important for triage and timely treatment of patients with acute pancreatitis (AP)., Methods: All AP patients were consecutively admitted within 48 h of symptom onset. A nomogram was developed to predict POF on admission using data from a retrospective training cohort, validated by two prospective cohorts. The clinical utility of the nomogram was defined by concordance index (C-index), decision curve analysis (DCA), and clinical impact curve (CIC), while the performance by post-test probability., Results: There were 816, 398, and 880 patients in the training, internal and external validation cohorts, respectively. Six independent predictors determined by logistic regression analysis were age, respiratory rate, albumin, lactate dehydrogenase, oxygen support, and pleural effusion and were included in the nomogram (web-based calculator: https://shina.shinyapps.io/DynNomapp/). This nomogram had reasonable predictive ability (C-indexes 0.88/0.91/0.81 for each cohort) and promising clinical utility (DCA and CIC). The nomogram had a positive likelihood ratio and post-test probability of developing POF in the training, internal and external validation cohorts of 4.26/31.7%, 7.89/39.1%, and 2.75/41%, respectively, superior or equal to other prognostic scores., Conclusions: This nomogram can predict POF of AP patients and should be considered for clinical practice and trial allocation., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract: Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study., Competing Interests: E.A. is on the advisory board for Nestle. M.D.B. receives research support from Viacyte and Dexcom and is on advisory board for Insulet. K.M.D. receives research support from Sanofi, Viacyte, Abbott, and Dexcom; has consulting activities with Eli Lilly, Boehringer Ingelheim, Elsevier; and receives honoraria from UptoDate, Elsevier, Medscape, and Academy for Continued Healthcare Learning. C.E.F. receives research support from AbbVie and has consulting activities with Nestle. G.I.P. receives research support from AbbVie and has consulting activities with Nestle. C.S. is on the advisory board for Vertex Pharmaceuticals. F.G.S.T. receives research support from Dompé Pharmaceuticals and has consulting activities with Sanofi, Eli Lilly, and AstraZeneca. The other authors declare no conflict of interest., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure for the management of pancreaticobiliary disorders. ERCP is, however, associated with the risk of complications including pancreatitis, bleeding, perforation, infection, and instrument failure, which can often be fatal. It is, therefore, necessary to recognize the risk of ERCP-associated complications and understand the methods to prevent and treat such complications., Competing Interests: Disclosure The authors have no disclosures relevant to this publication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Pain is the primary symptom of chronic pancreatitis (CP) and has been associated with abnormal pain processing and psychologic distress. Little is known about these phenomena in patients with painless disease. The aim of this study was to characterize patterns of pain processing and psychologic distress in patients with primary painless vs painful CP., Methods: This was a cross-sectional multicenter study of 235 patients with definitive CP. Patients were categorized based on current and past pain history; current pain (79%), no current (but prior) pain (11%), and painless CP (10%). Demographic information and clinical data including symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale were collected. All patients underwent quantitative sensory testing to assess patterns of pain processing., Results: A total of 235 patients (57% males, mean age 53.9 ± 14.0 years, 41% alcohol etiology) were included. Compared to patients with painless CP, enhanced pain sensitivity was observed in both patients with current pain (odds ratio [OR] 3.29; 95% confidence interval [CI] [1.11-9.77], P  = .032) and no current pain (OR 4.07; 95% CI [1.10-15.03], P  = .035). Patients with current pain also had increased depression prevalence compared to patients with painless CP (OR 6.15; 95% CI [1.28-29.41], P  = .023), while no difference was seen for patients with no current pain (OR 1.24; 95% CI [0.19-8.26], P  = .824)., Conclusion: Total absence of pain in CP is associated with normal pain processing and low prevalence of psychologic distress, whereas patients with prior pain experience appear to have persistent and enhanced pain sensitivity even in the absence of clinical pain and psychologic distress., (© 2022 The Authors.)

Background/aims: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients., Methods: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared., Results: There were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4-14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7-34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone., Conclusions: This study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes., (© 2021. The Author(s).)

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., Competing Interests: Declaration of interests EdM is a consultant for Takeda Pharmaceutical Company, Abbott, and Mylan. WA received consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Dynacare, Janssen, Merck, Novartis, Pfizer, Sandoz, and Takeda. SL received speaker and advisor fees from Gilead and AbbVie, and grants from Gilead. RP is a consultant to HCL Technologies, and on the scientific advisory board at Nestlé. VKS is consultant to AbbVie and Nestlé Health Science and has received grant funding from Orgenesis and Theraly. JV is a consultant to Olympus America, and on the scientific advisory board at Aspero Medical. AC consults for, is on the advisory board of, and has received education grants from from AbbVie, Takeda, Janssen, and Pfizer. The Radboud University Medical Center, on behalf of JPHD, received honoraria or research grants from Gilead and AbbVie. All other authors declare no competing interests., (Crown Copyright © 2022 Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Pain is the foremost complication to chronic pancreatitis (CP), but no validated questionnaires for assessment exist. The COMPAT questionnaire includes all relevant pain dimensions in CP, but a short form is needed to make it usable in clinical practice., Methods: The full COMPAT questionnaire was completed by 91 patients and systematically reduced to 6 questions. Pain severity and analgesic use were merged, leaving 5 pain dimensions. The pain dimension ratings were normalized to a 0-100 scale, and the weighted total score was calculated, where 3 dimensions were weighted double. Reliability of the short form was tested in a test-retest study in 76 patients, and concurrent validity tested against the Brief Pain Inventory and Izbicki pain questionnaire. Convergent validity was verified using confirmatory factor analysis, and criterion validity tested against quality-of-life and hospitalization rates., Results: The COMPAT-SF questionnaire consisted of the following pain dimensions: a) pain severity, b) pain pattern, c) factors provoking pain, d) widespread pain, and e) a qualitative pain-describing dimension. Quality of life correlated with the total score and all pain dimensions (P <.05). The total score, pain severity, pain pattern, and factors provoking pain were correlated with hospitalization rates (P <.05). The total score correlated with the Izbicki and Brief Pain Inventory scores (P <.0001). The reliability of the questionnaire in patients in a stable phase was good with an interclass correlation coefficient of 0.89., Conclusion: The COMPAT-SF questionnaire includes the most relevant aspects of pain in CP and is a feasible, reliable, and valid pain assessment instrument recommended to be used in future trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prior studies have evaluated clinical characteristics associated with opioid dose requirements in hospitalized patients with acute pancreatitis (AP) but did not incorporate morphologic findings on CT imaging., Aims: We sought to determine whether morphologic severity on imaging is independently associated with opioid dose requirements in AP., Methods: Adult inpatients with a diagnosis of AP from 2006 to 2017 were reviewed. The highest modified CT severity index (MCTSI) score and the daily oral morphine equivalent (OME) for each patient over the first 7 days of hospitalization were used to grade the morphologic severity of AP and calculate mean OME per day(s) of treatment (MOME), respectively. Multiple regression analysis was used to evaluate the association of MOME with MCSTI., Results: There were 249 patients with AP, of whom 196 underwent contrast-enhanced CT. The mean age was 46 ± 13.6 years, 57.9% were male, and 60% were black. The mean MOME for the patient cohort was 60 ± 52.8 mg/day. MCTSI (β = 3.5 [95% CI 0.3, 6.7], p = 0.03), early hemoconcentration (β = 21 [95% CI 4.6, 39], p = 0.01) and first episode of AP (β =  - 17 [95% CI - 32, - 2.7], p = 0.027) were independently associated with MOME. Among the 19 patients undergoing ≥ 2 CT scans, no significant differences in MOME were seen between those whose MCTSI score increased (n = 12) versus decreased/remained the same (n = 7)., Conclusion: The morphologic severity of AP positively correlated with opioid dose requirements. No difference in opioid dose requirements were seen between those who did versus those who did not experience changes in their morphologic severity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Quantitative sensory testing (QST) has been previously used to study pain in chronic pancreatitis (CP) but included methods that are not suitable for clinical purposes. The aims of this study were to determine if pancreatic QST (P-QST) can differentiate patients into distinct pain phenotypes and to determine the association of these with their clinical pain and psychiatric comorbidities., Methods: A multicenter cross-sectional study was conducted where patients completed validated questionnaires assessing quality of life (QoL), depression and anxiety scores as well as clinical pain symptoms followed by P-QST which included a cold pressor test, repetitive pinprick stimuli and pressure stimulation of the upper abdominal (T10) and control dermatomes. P-QST categorized patients into pain phenotypes based on a previously established nomogram. QoL, clinical pain and psychiatric assessment scores were compared across these groups., Results: A total of 179 patients were enrolled with a mean age of 54.1±13.6 years among whom 59% were males and 42% had an alcoholic etiology. P-QST showed no hyperalgesia in 91 (51%), segmental hyperalgesia in 50 (28%) and widespread hyperalgesia in 38 (21%) patients. Patients with widespread hyperalgesia had significantly higher pain intensity scores (P = .03) and rates of constant pain (P = .002) as well as decreased QoL (P < .001) and physical functioning (P =.03) in comparison with the other two pain phenotypes. In contrast, psychiatric comorbidities were similar across all groups., Conclusions: P-QST may serve as a novel unbiased pain assessment tool in CP as it categorizes patients into distinct pain phenotypes independent of their psychiatric comorbidities., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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 < 0.001 and HR: 4.88 (95% CI: 1.70-13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05)., Conclusion: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality., Competing Interests: Declaration of competing interest Mouen Khashab is a consultant for Boston Scientific, Olympus and Medtronic. Robert A. Moran is a consultant for Cook medical. Vikesh K Singh is a consultant to Abbvie and Theraly, advisory board participant for Cook Medical, and receives grant funding from Orgenesis. Tyler Stevens is a consultant for Boston Scientific. All other authors have no conflicts of interest to disclose., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of the present study is to assess the impact of smoking dose and duration on the distribution of risk factor(s) in patients with RAP and CP, and the impact of genetic testing on the distribution of risk factor(s) in patients with idiopathic RAP and CP., Methods: All adult patients with RAP and CP referred to a multidisciplinary pancreatitis clinic between 2010 and 2017 were evaluated. Risk factors included alcohol and smoking, hypertriglyceridemia, biliary, and other etiologies. Genetic testing was only pursued in patients with idiopathic RAP or CP., Results: Among the 1770 patients evaluated, 167 had RAP and 303 had CP. After genetic testing and smoking, the most common risk factors for RAP and CP were pathogenic variant(s) (23%) and the combination of alcohol and smoking (23%), respectively. Genetic testing and smoking assessment decreased the proportion of patients with alcoholic RAP from 17% to 5%, alcoholic CP from 33% to 10%, idiopathic RAP from 49% to 12%, and idiopathic CP from 54% to 14%. Pathogenic CFTR variants were the most common variant in patients with RAP (51%) and CP (43%). Among the 68 patients with pancreas divisum, other risk factor(s) were identified in 72%., Conclusion: Genetic testing and a detailed assessment of smoking dose and duration reduce the proportion of patients with alcoholic and idiopathic pancreatitis. Other risk factor(s) for pancreatitis are found in the majority of patients with pancreas divisum further questioning its role as an independent risk factor.1. What is the current knowledge?Approximately 30% of patients with pancreatitis have no clear risk factor(s) and are categorized as having an idiopathic etiology.Pathogenic variant(s) as well as smoking dose and duration are well-established risk factors for recurrent acute and chronic pancreatitis but are not widely recognized or incorporated into clinical practice.2. What is new here?Genetic testing and a detailed assessment of smoking dose and duration reduced the proportion of patients with alcoholic and idiopathic acute recurrent and chronic pancreatitis.Approximately three-fourths of patients with pancreas divisum have a risk factor for pancreatitis.

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 < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent., Conclusion: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP., (Copyright © 2021. Published by Elsevier B.V.)

Background: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation., Methods: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n = 84) with adults (n = 195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP., Results: Children more commonly underwent splenectomy (100% versus 91%, p = 0.002), pylorus preservation (93% versus 67%; p < 0.0001), Roux-en-Y duodenojejunostomy reconstruction (92% versus 35%; p < 0.0001), and enteral feeding tube placement (93% versus 63%; p < 0.0001). Median islet equivalents/kg transplanted was higher in children (4577; IQR 2816-6517) than adults (2909; IQR 1555-4479; p < 0.0001), with COBE purification less common in children (4% versus 15%; p = 0.0068). Median length of hospital stay was higher in children (15 days; IQR 14-22 versus 11 days; IQR 8-14; p < 0.0001), but 30-day readmissions were lower in children (13% versus 26%, p = 0.018). Rate of portal vein thrombosis was significantly lower in children than in adults (2% versus 10%, p = 0.028). There were no mortalities in the first 90 days post-TPIAT., Conclusions: Pancreatectomy techniques differ between children and adults, with islet yields higher in children. The rates of portal vein thrombosis and early readmission are lower in children., Competing Interests: Declaration of competing interest MDB discloses the following: research support from Viacyte and Dexcom; advisory role (DSMB) for Insulet. LFL discloses the following: research support from Abbvie, consultant for Abbvie, speaker for Abbvie and Nestle. SJS discloses funding from Gilead and UpToDate. VKS is a consultant for Abbvie and Nestle, and he receives research support from Orgenesis and Theraly., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)