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Current treatments for chronic pancreatitis focus on symptom management and therapeutics targeting disease reversal are lacking. Given the role of the cyclooxygenase-2 (COX-2) enzyme in producing prostaglandin EThis pilot two-center randomized controlled trial seeks to examine 32 subjects with chronic pancreatitis who have no contraindications to indomethacin. Subjects will be randomized to either oral indomethacin 50 mg twice a day or placebo twice a day for a total of 28 days. Baseline (pre-treatment) assessment of pain and quality of life will be performed using the Brief Pain Inventory and the PROMIS-10 questionnaires, respectively. Biological specimens including blood, urine, and saliva will be collected at pre-treatment and post-treatment(day 28). Endoscopic pancreatic function testing with concomitant pancreatic fluid collection will also be performed pre- and post-treatment to assess the change in pancreatic fluid PGEThis study will elucidate the effect of oral indomethacin on PGE

OBJECTIVE Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. RESEARCH DESIGN AND METHODS This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. RESULTS Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease–related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease–related factors were predominant for diabetes occurring after pancreatitis. CONCLUSIONS Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.

Background & Aims Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP. Methods We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy. Results The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs 26.4%; P = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [CI], 1.15–1.45), female sex (OR, 3.08; 95% CI, 1.75–5.43), white race (OR, 2.68; 95% CI, 1.20–6.01), and underweight body mass index category (OR, 7.40; 95% CI, 1.56–34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and other patient and disease-related features of CP. Conclusion In the largest study of patients with CP who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP. ClinicalTrials.gov number, NCT03099850.

Recruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such preemptive and detailed planning can help prospective, longitudinal studies focusing on exocrine and endocrine complications of AP in accurately measuring outcomes. This manuscript highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.

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 following AP and understanding the underlying mechanisms. The Diabetes RElated to Acute Pancreatitis and its Mechanisms (DREAM) 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 following AP. In the following article, we summarize literature regarding the epidemiology of DM following AP, and provide the rationale and an overview of the DREAM study.

Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.

There is a paucity of literature evaluating new-onset diabetes mellitus (NODM) after resection of pancreatic cystic lesions (PCLs). We sought to characterize the incidence and risk factors associated with NODM after partial pancreatectomy for PCLs.We utilized the IBM MarketScan Database (2012-2018) to identify all nondiabetic adults who underwent partial pancreatectomy for PCLs. Patients with any other pancreatic disease were excluded. We performed Kaplan-Meier analysis and multivariable Cox proportional hazards regression to define the incidence and risk factors of postoperative NODM.Among 311 patients, the overall risk (95% confidence interval) of NODM was 9.1% (6.3-12.9%), 15.1% (11.3-20.2%), and 20.2% (15.3-26.4%) at 6, 12 and 24 months, respectively. Multivariable analysis (adjusted hazard ratio; 95% confidence interval) revealed that older age (1.97; 1.04-3.72; 55-64 vs 18-54 years), obesity (2.63; 1.35-5.12), hypertension (1.79; 1.01-3.17), and cardiovascular disease (2.54; 1.02-6.28) were independent predictors of NODM. Rates of NODM were similar after distal pancreatectomy versus pancreaticoduodenectomy.Within 2 years, 1 in 5 patients without any other pancreatic disease will develop NODM after partial pancreatectomy for PCLs. Those with advanced age, metabolic syndrome features, and/or cardiovascular disease may benefit from preoperative counseling and intensive postoperative monitoring, education, and treatment for diabetes mellitus.

Background and Aims : EUS-guided needle-based confocal laser endomicroscopy (nCLE) improves the diagnostic accuracy of pancreatic cystic lesions (PCLs) but concerns regarding its expense have limited widespread adoption of this technology. We conducted a cost-benefit analysis to assess the healthcare resource implications of adding EUS-nCLE to the standard of care (SOC) management of PCLs. Methods : A post-hoc analysis of a prospective study (2015-2018) evaluating EUS-nCLE for the diagnosis of PCLs was performed. The SOC diagnosis was based on clinical history, PCL morphology, and cyst fluid analysis. A minimum of 5-years of surveillance was included, the cost of EUS and MRI/MRCP was derived from institutional billing data (US$), and the total hospital costs (adjusted for inflation) for pancreatic operations were derived from the National (US) Readmission Database. Results : A reference diagnosis was available in 93 subjects (mean cyst size=36.4±15.7 mm; surgical histopathology, n=67 and diagnostic molecular markers in cyst fluid, n=26). SOC and nCLE were discordant in 13 (14%) subjects. The addition of nCLE led to 11 subjects being clinically downstaged from mucinous to non-mucinous not warranting surgery (total cost savings= $1,080,418), 1 subject upstaged from non-mucinous to mucinous, warranting surgical resection (cost savings of 5-years surveillance: $46,200), and 1 subject incorrectly classified as non-mucinous (cost excess of 5-years surveillance: $46,200). Overall, the addition of nCLE led to a net savings of $ 442,438 (mean: $ 4,757.40 /patient) for this cohort. Conclusions : EUS-nCLE is potentially cost-beneficial in the management of PCLs (≥ 3 cm) by preventing at least one unnecessary pancreatic surgery for every ten subjects undergoing evaluation by current practices. ClinicalTrials.gov number: NCT02516488.

ObjectivesChronic pancreatitis (CP) is an inflammatory disease that affects the absorption of nutrients like fats. Molecular signaling in pancreatic cells can be influenced by fatty acids (FAs) and changes in FA abundance could impact CP-associated complications. Here, we investigated FA abundance in CP compared to controls and explored how CP-associated complications and risk factors affect FA abundance.MethodsBlood and clinical parameters were collected from subjects with (n=47) and without CP (n=22). Plasma was analyzed for relative FA abundance using gas chromatography and compared between controls and CP. Changes in FA abundance due to clinical parameters were also assessed in both groups.ResultsDecreased relative abundance of polyunsaturated fatty acids (PUFAs) and increased monounsaturated fatty acids (MUFAs) were observed in subjects with CP in a sex-dependent manner. The relative abundance of linoleic acid increased, and oleic acid decreased in CP subjects with exocrine pancreatic dysfunction and a history of substance abuse.ConclusionsPlasma FAs like linoleic acid are dysregulated in CP in a sex-dependent manner. Additionally, risk factors and metabolic dysfunction further dysregulate FA abundance in CP. These results enhance our understanding of CP and highlight potential novel targets and metabolism-related pathways for treating CP.

Purpose Clinically severe obesity (SO) is a known risk factor for worsened outcomes and recurrence of acute diverticulitis. Paucity of data exist on outcomes of diverticulitis after bariatric surgery. Methods The Nationwide Readmissions Database was queried for diverticulitis hospitalizations between the years 2010 and 2014. We restricted analysis to patients with SO and those who had bariatric surgery (BRS). Outcomes of mortality, surgical events, and recurrent diverticulitis admissions were compared using multivariable analysis and one-to-one propensity score matching. Results Among 52,274 diverticulitis admissions, 91.2% (47,694) patients had SO and 8.8% (4580) had prior BRS. Patients with SO had higher odds of suffering mortality on index diverticulitis admission when compared to those with prior BRS [adjusted odds ratio (aOR): 10.55; 95%CI 1.45,76.75]. Patients with SO were also more likely to undergo emergency surgery (aOR: 1.71; 95%CI 1.25,2.34) and colectomy (aOR: 1.45; 95%CI 1.26,1.68). Rates of recurrent diverticulitis readmissions within 30 days and 6 months were also higher in patients with SO compared to BRS patients (aOR: 7.94; 95%CI 1.09,57.83 and aOR: 1.98; 95%CI 1.14,3.43, respectively). Propensity score matching confirmed our findings of increased rates of mortality (OR: 17.28; 95%CI 2.02,147.6), recurrent diverticulitis, and worsened surgical outcomes within 30 days in patients with SO compared to BRS. Conclusion This study is first to show improved outcomes and less recurrent hospitalizations for diverticulitis after bariatric surgery compared to patients with clinically severe obesity. Further studies are needed to understand mechanisms leading to this improvement and the role of weight loss in prevention of severe diverticulitis.

Introduction Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. Methods MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. Results A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. Discussion CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

BACKGROUND Symptomatic biliary and gallbladder disorders are common in adults with cystic fibrosis (CF) and the prevalence may rise with increasing CF transmembrane conductance regulator modulator use. Cholecystectomy may be considered, but the outcomes of cholecystectomy are not well described among modern patients with CF. AIM To determine the risk profile of inpatient cholecystectomy in patients with CF. METHODS The Nationwide Inpatient Sample was queried from 2002 until 2014 to investigate outcomes of cholecystectomy among hospitalized adults with CF compared to controls without CF. A propensity weighted sample was selected that closely matched patient demographics, patient's individual comorbidities, and hospital characteristics. The propensity weighted sample was used to compare outcomes among patients who underwent laparoscopic cholecystectomy. Hospital outcomes of open and laparoscopic cholecystectomy were compared among adults with CF. RESULTS A total of 1239 inpatient cholecystectomies were performed in patients with CF, of which 78.6% were performed laparoscopically. Mortality was < 0.81%, similar to those without CF (P = 0.719). In the propensity weighted analysis of laparoscopic cholecystectomy, there was no difference in mortality, or pulmonary or surgical complications between patients with CF and controls. After adjusting for significant covariates among patients with CF, open cholecystectomy was independently associated with a 4.8 d longer length of stay (P = 0.018) and an $18449 increase in hospital costs (P = 0.005) compared to laparoscopic cholecystectomy. CONCLUSION Patients with CF have a very low mortality after cholecystectomy that is similar to the general population. Among patients with CF, laparoscopic approach reduces resource utilization and minimizes post-operative complications.

BACKGROUND Pancreatic endotherapy provides treatment options for the management of chronic pancreatitis-related structural complications such as pancreatic duct stones, strictures, and pancreatic fluid collections. Most studies detailing endotherapy, however, have focused on technical success outcomes such as stone clearance or stricture resolution. AIM To review the effect of pancreatic endotherapy on patient-centered outcomes. METHODS Systematic review of studies examining pancreatic endotherapy. RESULTS A total of 13 studies including 3 randomized clinical trials were included. The majority of studies found an improvement in quality of life with pancreatic endotherapy. CONCLUSION While pancreatic endotherapy does appear to improve quality of life, there are clear gaps in knowledge regarding many pancreatic endotherapy modalities. Furthermore, qualitative analysis is lacking in these studies and further work is needed to elucidate the patient experience with pancreatic endotherapy.

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.

Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities.We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile, which captures 7 symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database.Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes, 2.54-7.03) and had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes, 4.08-10.37) and clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, 2.80-5.38).Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP. (ClinicalTrials.gov, Number: NCT03099850).

Background/aims Gastroparesis is a chronic gastrointestinal disorder that frequently presents with symptoms that are difficult to manage, necessitating frequent hospitalizations. We sought to determine the predictors of early readmission due to gastroparesis based on etiology. Methods We identified all adults discharged with a principal diagnosis of gastroparesis after hospitalization from the 2014 Nationwide Readmission Database. We compared etiology wise (diabetes, post-surgical, and idiopathic) early readmission. Multivariate regression analyses were performed to identify significant predictors of 30-day readmission. Results A total of 12 689 patients were identified, 30.7% diabetic, 2.6% post-surgical, and 66.7% were idiopathic. Patients with diabetic gastroparesis were more likely to be readmitted within 30 days than idiopathic (adjusted odds ratio [aOR], 0.81; 95% confidence interval [CI], 0.69-0.94) and post-surgical gastroparesis (aOR, 0.58; 95% CI, 0.34-0.98). Pyloroplasty was associated with less likelihood of 30-day readmission (aOR, 0.45; 95% CI, 0.20-0.97). In addition, male gender (aOR, 1.18; 95% CI, 1.02-1.37), modified Elixhauser comorbidity score ≥ 3 (aOR, 1.38; 95% CI, 1.18-1.61), chronic pain syndrome (aOR, 1.41; 95% CI, 1.11-1.78), younger (18-64 years) age (aOR, 1.64; 95% CI, 1.34-2.00), need for percutaneous endoscopic gastrostomy/jejunostomy tube (aOR, 2.06; 95% CI, 1.21-3.52), and need for total parenteral nutrition (aOR, 1.70; 95% CI, 1.24-2.35) were associated with increased risk of 30-day readmission. Conclusion s One in 5 patients was readmitted with gastroparesis within 30 days. In the diabetic group, diabetes-related complications contributed to readmissions than gastroparesis. Pyloroplasty is associated with reduced early hospital readmission. Prospective studies are needed for validation of these results.

Purpose of review Management of abdominal pain in patients with chronic pancreatitis is often suboptimal. We review recent data on the epidemiology and new approaches for managing pain in chronic pancreatitis. Recent findings Chronic pancreatitis duration does not appear to affect the pain experience. Pain pattern in chronic pancreatitis patients frequently changes and is not related to traditional patient and disease-related factors. Psychologic comorbidities, i.e. anxiety and depression, are frequent in patients with chronic pancreatitis, and are associated with more severe pain and pain interference. Adjunctive treatments, such as cognitive behavioral therapy, may positively influence pain management in chronic pancreatitis. Total pancreatectomy with islet autotransplantation (TPIAT) is an increasingly adopted treatment option in painful chronic pancreatitis. Ongoing multicenter studies will help define optimal candidates, predictors of successful pain remission and diabetes outcomes after TPIAT. Pancreatic quantitative sensory testing, a promising technique to interrogate nociception and sensory response, holds promise to identify patients with central sensitization. Initial studies show feasibility to stratify patients into defined pain profiles, and future studies will explore if these can help in prognostication of pain therapy. Summary Several lines of investigations currently under evaluation are likely to have a positive impact on the management of pain in chronic pancreatitis.

Same-admission cholecystectomy (CCY) is recommended for mild acute biliary pancreatitis (biliary-AP). However, there is a paucity of research investigating reasons for early (30-day) unplanned readmissions in patients who undergo CCY for biliary-AP. Hence, we sought to investigate this gap using a large population database. Using the Nationwide Readmission Database (2010–2014), we identified all adults (age ≥ 18 years) with a principal diagnosis of biliary-AP who had undergone CCY during the index hospitalization. Multivariable logistic regression models were obtained to assess independent predictors for 30-day readmission. Principal diagnosis for all readmissions was collected to ascertain the indications for early readmission. During the study period, 118,224 patients underwent same-admission CCY for biliary-AP. Three-fourths of all patients underwent invasive cholangiography during the hospitalization (intraoperative cholangiogram (IOC) = 57,038, ERCP = 31,500). The rate of early (30-day) readmission was 7.25% (n = 8574). Exacerbation of prior medical conditions (42.2%), sequelae of biliary-AP (resolving and recurrent pancreatitis, pseudocysts) (27.6%), surgical site and other postoperative complications (16%), choledocholithiasis and/or bile leak (9.6%), and preventable hospital-acquired conditions (4.6%) accounted for early readmissions. On multivariable analysis, predictors for readmission included male sex (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.08–1.28), insurance type (Medicare insurance [OR 1.26, 95% CI 1.13–1.40]; Medicaid [OR 1.22, 95% CI 1.09–1.38]), outside-facility discharge (OR 1.35, 95% CI 1.16–1.57), severe AP (OR 1.35, 95% CI 1.21–1.50), and ≥ 3 Elixhauser comorbidities (OR 1.55, 95% CI 1.41–1.69). Performance of IOC (OR 0.90, 95% CI 0.82–0.97) and ERCP (OR 0.81, 95% CI 0.73–0.89) were associated with decreased risk of early readmission. In this study, using a national population database evaluating patients who underwent same-admission CCY after biliary-AP, we identified potentially modifiable risk factors and causes for early readmission as well as opportunities to improve clinical care.

The coronavirus disease 2019 pandemic led to changes in individuals' behaviors and healthcare delivery. We examined the impact of these changes on the rates and clinical course of acute pancreatitis (AP).Hospitalizations for AP from March 1 through August 31 in 2019 (baseline group) and the same period in 2020 (pandemic group) were retrospectively reviewed. Univariate and multivariate analyses were used for demographics and outcomes.Two hundred eighty subjects (315 admissions) were identified in 2019 and 237 subjects (264 admissions) in 2020. Subjects in the pandemic group were more likely to have systemic inflammatory response syndrome (40% vs 25%, P0.01), pancreatic necrosis (14% vs 10%, P = 0.03), and persistent organ failure (17% vs 9%, P = 0.01) compared with prepandemic. There was no difference in etiology of AP. A multivariable model indicates that increased comorbidities, prior pancreatitis, pancreatic necrosis, and prescription of opiates at discharge were associated with 30-day readmissions during the pandemic.Fewer patients were admitted for AP during the pandemic, suggesting that patients with milder symptoms avoided hospital interaction. Practices followed during the pandemic, especially avoidance of hospitalization and improved efficiency of hospital management, may reduce the burden of pancreatitis care in the future.

To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study.This study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n = 50) and CP (n = 51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI).There was significantly higher T1 relaxation time; mean 669 ms (± 171) vs. 593 ms (± 82) (p = 0.006), ECV fraction; 40.2% (± 14.7) vs. 30.3% (± 11.9) (p 0.001), and pancreatic fat signal fraction; 12.2% (± 5.5) vs. 8.2% (± 4.4) (p 0.001) in the CP group compared to controls. The ADC was similar between groups (p = 0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76).Quantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups.

Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study.The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0-6) based on their clinical history, MRCP, and CT findings.The mean pancreas-to-spleen T1 score was 1.30 in participants with chronic abdominal pain, 1.22 in those with acute or recurrent acute pancreatitis, and 1.03 in definite CP. After adjusting for covariates, we observed a linear, progressive decline in the pancreas-to-spleen T1 score with increasing MSCP from 0 to 6. The mean pancreas-to-spleen T1 scores were 1.34 (MSCP 0), 1.27 (MSCP 1), 1.21 (MSCP 2), 1.16 (MSCP 3), 1.18 (MSCP 4), 1.12 (MSCP 5), and 1.05 (MSCP 6) (p 0.0001). The pancreas-to-liver and pancreas-to-muscle T1 scores showed less linear trends and wider confidence intervals.The T1 score calculated by SIR of the pancreas-to-spleen shows a negative linear correlation with the progression of chronic pancreatitis. It holds promise as a practical imaging biomarker in evaluating disease severity in clinical research and practice.

Objectives: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for refractory chronic pancreatitis-related pain. Despite the known clinical implications of TPIAT, the molecular effects remain poorly investigated. We performed the first hypothesis-generating study of the urinary proteome before and after TPIAT.Methods: Twenty-two patients eligible for TPIAT were prospectively enrolled. Urine samples were collected the week before and 12 to 18 months after TPIAT. The urine samples were prepared for bottom-up label-free quantitative proteomics using the "MStern" protocol.Results: Using 17 paired samples, we identified 2477 urinary proteins, of which 301 were significantly changed post-TPIAT versus pre-TPIAT. Our quantitative analysis revealed that the molecular response to TPIAT was highly sex-specific, with pronounced sex differences pre-TPIAT but minimal differences afterward. Comparing post-TPIAT versus pre-TPIAT, we found changes in cell-cell adhesion, intracellular vacuoles, and immune response proteins. After surgery, immunoglobulins, complement proteins, and cathepsins were increased, findings that may reflect glomerular damage. Finally, we identified both known and novel markers for immunoglobulin A nephropathy after 1 patient developed the disease 2 years after TPIAT.Conclusions: We found distinct changes in the urinary proteomic profile after TPIAT and the response to TPIAT is highly sex-specific.

Chronic pancreatitis (CP) is a risk factor for pancreatic ductal adenocarcinoma (PDAC); nevertheless, the true incidence of PDAC in CP patients in the United States remains unclear. We evaluated the risk of developing PDAC two or more years after a new diagnosis of CP. Retrospective study of veterans from September 1999 to October 2015. A three-year washout period was applied to exclude patients with preexisting CP and PDAC. PDAC risk was evaluated in patients with new-diagnosis CP and compared with controls without CP using Cox-proportional hazards model. CP, PDAC, and other covariates were extracted using ICD-9 codes. After exclusions, we identified 7,883,893 patients [new-diagnosis CP − 21,765 (0.28%)]. PDAC was diagnosed in 226 (1.04%) patients in the CP group and 15,858 (0.20%) patients in the control group (p 2 years [adjusted hazard ratio (HR) 4.28, 95% confidence interval (CI) 3.74–4.89, p

Introduction Chronic cannabis use had been associated with hyperemesis. We sought to determine whether cannabis liberalization contributed to increased hospitalizations for hyperemesis. Methods Cannabis use and admissions for hyperemesis in legalized states were compared with those of nonlegalized states, before and after cannabis legalization, using state inpatient databases. Results From 2011 to 2015, cannabis use increased 2.2 times in legalized states and 1.8 times in nonlegalized states. The odds of presentation with hyperemesis were higher in 2015 compared with those of 2011 in all states. Discussion Recreational legalization may be contributing to rising cannabis use. Hospitalizations for hyperemesis have also increased but did not seem to be solely due to cannabis legalization.

BACKGROUND Gastrointestinal (GI) and liver diseases contribute to substantial inpatient morbidity, mortality, and healthcare resource utilization. Finding ways to reduce the economic burden of healthcare costs and the impact of these diseases is of crucial importance. Thirty-day readmission rates and related hospital outcomes can serve as objective measures to assess the impact of and provide further insights into the most common GI ailments. AIM To identify the thirty-day readmission rates with related predictors and outcomes of hospitalization of the most common GI and liver diseases in the United States. METHODS A cross-sectional analysis of the 2012 National Inpatient Sample was performed to identify the 13 most common GI diseases. The 2013 Nationwide Readmission Database was then queried with specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary outcomes were mortality (index admission, calendar-year), hospitalization costs, and thirty-day readmission and secondary outcomes were predictors of thirty-day readmission. RESULTS For the year 2013, the thirteen most common GI diseases contributed to 2.4 million index hospitalizations accounting for about $25 billion. The thirty-day readmission rates were highest for chronic liver disease (25.4%), Clostridium difficile (C. difficile) infection (23.6%), functional/motility disorders (18.5%), inflammatory bowel disease (16.3%), and GI bleeding (15.5%). The highest index and subsequent calendar-year hospitalization mortality rates were chronic liver disease (6.1% and 12.6%), C. difficile infection (2.3% and 6.1%), and GI bleeding (2.2% and 5.0%), respectively. Thirty-day readmission correlated with any subsequent admission mortality (r = 0.798, P = 0.001). Medicare/Medicaid insurances, ≥ 3 Elixhauser comorbidities, and length of stay > 3 d were significantly associated with thirty-day readmission for all the thirteen GI diseases. CONCLUSION Preventable and non-chronic GI disease contributed to a significant economic and health burden comparable to chronic GI conditions, providing a window of opportunity for improving healthcare delivery in reducing its burden.

Background & Aims Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early onset ICP (EO-ICP; median age, 19.2 y) and late-onset ICP (LO-ICP; median age, 56.2 y). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, and ACP. Methods We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal–Wallis test was used to compare continuous variables across groups and based on genetic variants. Results Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P = .04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P = .001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P = .001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP. Conclusions We confirmed previously reported ages at onset of symptoms for EO-ICP and LO-ICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared with approximately one quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.

OBJECTIVE The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk. RESEARCH DESIGN AND METHODS We calculated dietary scores from baseline (1993–1998) food frequency questionnaires among 73,495 postmenopausal women in the Women’s Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes. RESULTS During a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32–1.68; Ptrend < 0.0001) and EDIP 1.45 (1.29–1.63; Ptrend < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88–1.12; Ptrend = 0.46) and GL 1.01 (0.89–1.16; Ptrend = 0.30). CONCLUSIONS Our findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.

There is limited research in prognosticators of hospital transfer in acute pancreatitis (AP). Hence, we sought to determine the predictors of hospital transfer from small/medium-sized hospitals and outcomes following transfer to large acute-care hospitals.Using the 2010-2013 Nationwide Inpatient Sample (NIS), patients ≥18 years of age with a primary diagnosis of AP were identified. Hospital size was classified using standard NIS Definitions. Multivariable analyses were performed for predictors of "transfer-out" from small/medium-sized hospitals and mortality in large acute-care hospitals.Among 381,818 patients admitted with AP to small/medium-sized hospitals, 13,947 (4%) were transferred out to another acute-care hospital. Multivariable analysis revealed that older patients (OR = 1.04; 95%CI 1.03-1.06), men (OR = 1.15; 95%CI 1.06-1.24), lower income quartiles (OR = 1.54; 95%CI 1.35-1.76), admission to a non-teaching hospital (OR = 3.38; 95%CI 3.00-3.80), gallstone pancreatitis (OR = 3.32; 95%CI 2.90-3.79), pancreatic surgery (OR = 3.14; 95%CI 1.76-5.58), and severe AP (OR = 3.07; 95%CI 2.78-3.38) were predictors of "transfer-out". ERCP (OR = 0.53; 95%CI 0.43-0.66) and cholecystectomy (OR = 0.14; 95%CI 0.12-0.18) were associated with decreased odds of "transfer-out". Among 507,619 patients admitted with AP to large hospitals, 31,058 (6.1%) were "transferred-in" from other hospitals. The mortality rate for patients "transferred-in" was higher than those directly admitted (2.54% vs. 0.91%, p 0.001). Multivariable analysis revealed that being "transferred-in" from other hospitals was an independent predictor of mortality (OR = 1.47; 95% CI 1.22-1.77).Patients with AP transferred into large acute-care hospitals had a higher mortality than those directly admitted likely secondary to more severe disease. Early implementation of published clinical guidelines, triage, and prompt transfer of high-risk patients may potentially offset these negative outcomes.