Acute pancreatitis precedes chronic pancreatitis in the majority of patients: Results from the NAPS2 consortium.

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.

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

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.

Characteristics of 30-Day All-Cause Hospital Readmissions Among Patients with Acute Pancreatitis and Substance Use.

BACKGROUND/OBJECTIVES: Previous studies on healthcare resource utilization and 30-day readmission risks among patients with acute pancreatitis (AP) have focused upon opioid and alcohol use. The data on other substance types are lacking. In this study we aim to estimate the 30-day readmission rates, predictors of readmission, impact of readmission on patient outcomes and resulting economic burden among patients with AP and substance use in the USA. METHODS: This was a retrospective cohort study, based upon data from 2017 National Readmission Database of adult patients with AP and substance use (alcohol in combination, opioid, cannabis, cocaine, sedatives, other stimulants, other hallucinogens, other psychoactive, inhalant and miscellaneous). We estimated the 30-day readmission rates and predictors of 30-day readmission. RESULTS: Among 25,795 eligible patients, most were male, belonged to the lower income quartile, resided in the urban facility and had a Charlson comorbidity score of 0 or 1. The use of a combination of substances was the most common in 17,265 (66.9%) patients followed by only opioids in 4691 (18.2%) patients and only marijuana in 3839 (14.9%) patients. A total of 14.6% patients were readmitted within 30 days after discharge for non-elective causes with the highest risk of readmission within the 1st week after discharge with 5.2% readmissions. Among top ten causes of readmission, most of the principal diagnosis were related to AP in 53.1%. Compared to index admission, readmitted patients had significantly higher rates of acute cardiac failure, shock, and higher in-hospital mortality rate. Overall, readmission attributed to an additional 17,801 days of hospitalization resulting in a total of $150 million in hospitalization charges and $36 million in hospitalization costs in 2017. On multivariate analysis, chronic pancreatitis, self-discharge against medical advice, treatment at the highest volume centers, higher Charlson comorbidity index, increasing length of stay and severe disease were associated with higher odds of readmission while female gender and private insurance were associated with lower odds. CONCLUSION: Readmission was associated with higher morbidity and in-hospital mortality among patients with AP and substance use and resulted in a significant monetary burden on the US healthcare system. Several factors identified in this study may be useful for categorizing patients at higher risk of readmission warranting special attention during discharge planning.

Differences in Age at Onset of Symptoms, and Effects of Genetic Variants, in Patients With Early vs Late-Onset Idiopathic Chronic Pancreatitis in a North American Cohort.

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.

Provider type influences adherence to lifestyle changes in chronic pancreatitis.

BACKGROUND: /Objectives: Alcohol and smoking cessation are recommended in chronic pancreatitis. The aim of this study is to measure the rates of alcohol and smoking cessation counselling among providers and adherence to recommendations. METHODS: Retrospective cohort study of chronic pancreatitis patients at a tertiary hospital. Provider types were defined as primary care (PCP), gastroenterologist, or pancreas specialist. Pairwise comparisons and multivariable analysis were conducted to assess the relation between provider type and smoking/alcohol cessation. RESULTS: Of 256 patients with chronic pancreatitis, 142 (55.5%) consumed alcohol and 130 (91.5%) were advised to stop. Alcohol cessation was advised to 88.9, 96.0 and 92.5% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively. Sixty-one patients (46.9%) were compliant with the recommendation: 31.3, 44.0 and 54.1% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, others nonsignificant). In multivariable analysis, patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation compared to those followed by PCP (OR = 4.31, CI 1.52-12.20, p = 0.006). Smoking cessation was advised to all the 127 current smokers (100%). Fifty-six (44.1%) were compliant with the recommendation: 24.1, 58.3 and 47.3% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, PCP vs. Gastroenterologist: p = 0.01, others nonsignificant). Multivariable analysis did not confirm this finding. CONCLUSIONS: The majority of providers counsel for alcohol/smoking cessation. Less than half the patients follow the recommendations. Patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation.

Serum biomarkers for chronic pancreatitis pain patterns.

OBJECTIVES: Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns. METHODS: Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes. RESULTS: The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P. DISCUSSION: The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis.

The necessity of periodic boundary conditions for the accurate calculation of crystalline terahertz spectra.

Terahertz vibrational spectroscopy has emerged as a powerful spectroscopic technique, providing valuable information regarding long-range interactions - and associated collective dynamics - occurring in solids. However, the terahertz sciences are relatively nascent, and there have been significant advances over the last several decades that have profoundly influenced the interpretation and assignment of experimental terahertz spectra. Specifically, because there do not exist any functional group or material-specific terahertz transitions, it is not possible to interpret experimental spectra without additional analysis, specifically, computational simulations. Over the years simulations utilizing periodic boundary conditions have proven to be most successful for reproducing experimental terahertz dynamics, due to the ability of the calculations to accurately take long-range forces into account. On the other hand, there are numerous reports in the literature that utilize gas phase cluster geometries, to varying levels of apparent success. This perspective will provide a concise introduction into the terahertz sciences, specifically terahertz spectroscopy, followed by an evaluation of gas phase and periodic simulations for the assignment of crystalline terahertz spectra, highlighting potential pitfalls and good practice for future endeavors.

Does Provider Type Affect Bone Health Surveillance in Chronic Pancreatitis?

BACKGROUND: Bone density screening (DEXA) and vitamin D serum assay (Vit-D) are recommended in chronic pancreatitis, but adherence by providers is unknown. AIMS: Assess DEXA/Vit-D testing according to provider type. METHODS: A retrospective cohort study of chronic pancreatitis patients followed in a tertiary hospital (August 2017-2018) was conducted. Provider type was primary care (PCP), gastroenterologist, and pancreas specialist. Chi-square test and multivariable analysis were conducted to assess the relation between provider type and DEXA/Vit-D testing. Subset analyses were performed among patients with fecal elastase < 200 mcg/g. RESULTS: A total of 478 charts were reviewed, and 256 (53.6%) met diagnosis of chronic pancreatitis; 184 (71.9%) definite, 45 (17.6%) probable, and 27 (10.6%) borderline chronic pancreatitis. DEXA was tested in 112/256 (43%) patients; 16/57(28%) patients followed by PCP, 11/38 (28.9%) by gastroenterologists, and 85/161(52.2%) by pancreas specialists (p = 0.001). Vit-D was tested in 210/256 (82.0%) patients; 42/57(73.7%) followed by PCP, 29/38 (76.3%) by gastroenterologists, and 139/161(86.3%) by pancreas specialists (p = 0.06). Multivariate analysis assessing DEXA/Vit-D testing showed pancreas specialists were more likely to test compared to PCP (DEXA: OR 3.70, CI 1.77-7.74, p = 0.001. Vit-D: OR 3.24, CI 1.43-7.38, p = 0.005), but gastroenterologists were not. In patients with low fecal elastase, pancreas specialists were more likely to test DEXA (pancreas specialists: 62.1%, PCP: 40.0%, Gastroenterologists: 11.1%, p = 0.01) and all patients received Vit-D testing. CONCLUSIONS: Chronic pancreatitis patients often do not receive optimal preventive care. Pancreas specialists were more likely to perform DEXA and Vit-D testing compared to PCP and gastroenterologists. More physician education is needed.

Prevalence of imaging findings of acute pancreatitis in emergency department patients with elevated serum lipase.

PURPOSE: To assess the association of imaging features of acute pancreatitis (AP) with the magnitude of lipase elevation in Emergency Department (ED) patients. METHODS: This Institutional Review Board-approved retrospective study included 509 consecutive patients presenting from 9/1/13-8/31/15 to a large academic ED with serum lipase levels ≥3× the upper limit of normal (ULN) (≥180 U/L). Patients were excluded if they did not have imaging (n = 131) or had a history of trauma, abdominal metastases, altered mental status, or transfer from an outside hospital (n = 190); the final study population was 188 patients. Imaging exams were retrospectively evaluated, and a consensus opinion of two subspecialty-trained abdominal radiologists was used to diagnose AP. Primary outcome was presence of imaging features of AP stratified by lipase level (≥3×-10× ULN and > 10× ULN). Secondary outcome was rate of discordant consensus evaluation compared to original radiologist's report. RESULTS: 25.0% of patients (47/188) had imaging features of AP. When lipase was >10× ULN (n = 94), patients were more likely to have imaging features of AP (34%) vs. those with mild elevation (16%) (p = 0.0042). There was moderately strong correlation between lipase level and presence of imaging features of AP (r = 0.48, p < 0.0001). Consensus review of CT and MRI images was discordant with the original report in 14.9% (28/188) of cases. CONCLUSION: Prevalence of imaging signs of AP in an ED population with lipase ≥3× ULN undergoing imaging is low. However, the probability of imaging features of AP increases as lipase value increases.

Resolving Anharmonic Lattice Dynamics in Molecular Crystals with X-Ray Diffraction and Terahertz Spectroscopy.

Molecular crystals are increasingly being used for advanced applications, ranging from pharmaceutics to organic electronics, with their utility dictated by a combination of their three-dimensional structures and molecular dynamics-with anharmonicity in the low-frequency vibrations crucial to numerous bulk phenomena. Through the use of temperature-dependent x-ray diffraction and terahertz time-domain spectroscopy, the structures and dynamics of a pair of isomeric molecular crystals exhibiting nearly free rotation of a CF_{3} functional group at ambient conditions are fully characterized. Using a recently developed solid-state anharmonic vibrational correction, and applying it to a molecular crystal for the first time, the temperature-dependent spatial displacements of atoms along particular terahertz modes are obtained, and are found to be in excellent agreement with the experimental observations, including the assignment of a previously unexplained absorption feature in the low-frequency spectrum of one of the solids.

Opiate Prescriptions at Discharge Are Not Associated with Early Readmissions in Acute Pancreatitis.

BACKGROUND: Early readmissions in acute pancreatitis (AP) are common. The impact of opiate prescriptions on readmissions is unknown. AIMS: To determine whether the prescription of opiates at hospital discharge and the dose prescribed are associated with early readmissions in AP. METHODS: Direct admissions from the Emergency Department (ED) for AP from September 1, 2013, to August 31, 2016 were identified. Opiate prescription was defined as a new prescription at discharge in an opiate-naïve patient. Early readmission was ED visit or hospitalization within 30 days for an AP-related reason. Multivariable logistic regression was performed, adjusted for age, Charlson Comorbidity Index, pancreatic necrosis, baseline opiate use, non-opiate analgesics, and pain score at discharge. RESULTS: A total of 318 AP patients were identified; the overall early readmission rate was 18%. One hundred and twenty-one (38%) were prescribed opiates at discharge, and 22% had an early readmission. One hundred and ninety-seven (62%) were not prescribed opiates, and 16% had an early readmission. Median opiate dose was 48 mg (24-h morphine equivalents). On multivariable analysis, neither the prescription of opiates (OR 1.2, 95% CI 0.6-2.4, p = 0.55) nor the dose of opiates (OR 0.99, 95% CI 0.99-1.00, p = 0.39) was associated with early readmission. In subset analysis of patients discharged with an opiate prescription, those on opiates at baseline were significantly more likely to have an early readmission (OR 4.19, 95% CI 1.04-16.94, p = 0.04). CONCLUSIONS: In AP patients, neither prescription of opiates at discharge nor prescribed dose was associated with early readmission. Patients on opiates at baseline discharged with an opiate prescription were more likely to have an early readmission.

Increased awareness enhances physician recognition of the role of smoking in chronic pancreatitis.

BACKGROUND: We have previously reported that physicians under-recognize smoking as a chronic pancreatitis (CP) risk factor. We hypothesized that availability of empiric data will influence physician recognition of this relationship. METHODS: We analyzed data from 508 CP patients prospectively enrolled in the North American Pancreatitis Study-2 Continuation and Validation (NAPS2-CV) or NAPS2-Ancillary (AS) studies (2008-2014) from 26 US centers who self-reported ever-smoking. Information on smoking status, physician-defined etiology and identification of smoking as a CP risk factor was obtained from structured patient and physician questionnaires. We compared how often physician identified smoking as a CP risk factor in NAPS2-CV/NAPS2-AS studies with NAPS2-original study (2000-2006). RESULTS: Enrolling physician identified smoking as a risk factor in significantly (all p < 0.001) greater proportion of patients in NAPS2-CV/AS studies when compared with NAPS2-original study among ever (80.7 vs. 45.3%), current (91.3 vs. 53%), past (60.3 vs. 30.2%) smokers, in those who smoked ≤1 pack/day (79.3 vs. 39.5%) or ≥1 packs/day (83 vs. 49.8%). In multivariable analyses, the enrolling physician was 3.32-8.49 times more likely to cite smoking as a CP risk factor in the NAPS2-CV/NAPS2-AS studies based on smoking status and amount after controlling for age, sex, race and alcohol etiology. The effect was independent of enrolling site in a sub-analysis limited to sites participating in both phases of enrollment. CONCLUSIONS: Availability of empiric data likely enhanced physician recognition of the association between smoking and CP. Wide-spread dissemination of this information could potentially curtail smoking rates in subjects with and those at risk of CP.

Chronic Pancreatitis: Pediatric and Adult Cohorts Show Similarities in Disease Progress Despite Different Risk Factors.

OBJECTIVES: The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared. METHODS: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables. RESULTS: Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, P = 0.011). CONCLUSIONS: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.

Recurrent Acute Pancreatitis Significantly Reduces Quality of Life Even in the Absence of Overt Chronic Pancreatitis.

OBJECTIVES: The impact of recurrent acute pancreatitis (RAP) on quality of life (QOL) is unknown. We hypothesized that RAP would reduce QOL even in the absence of chronic pancreatitis (CP). METHODS: Data were pooled from three prospective, cross-sectional studies conducted across 27 U.S. centers (the North American Pancreatitis Studies); these included subjects with chronic pancreatitis (n = 1086), RAP alone (n = 508), and non-disease controls (n = 1025). QOL was measured using the Short Form 12 (SF-12), generating a Physical Component Summary (PCS) and the Mental Component Summary score (MCS). Multivariable regression models were developed to measure the effect of RAP on QOL, the predictors of lower QOL in those with RAP, and the differential effect QOL predictors between CP and RAP. RESULTS: Compared to controls (51.0 ± 9.4), subjects with RAP (41.1 ± 11.4) and CP (37.2 ± 11.8) had lower PCS (p < 0.01). Subjects with CP had lower PCS compared to those with RAP (p < 0.01). Similarly, MCS was lower among RAP (44.6 ± 11.5) and CP (42.8 ± 12.2) subjects compared to controls (51.7 ± 9.1, p < 0.01). Subjects with CP had lower MCS compared to those with RAP (p < 0.01). After controlling for independent predictors of PCS, RAP was associated with lower PCS (estimate -8.46, p < 0.01) and MCS (estimate -6.45, p < 0.0001) compared to controls. The effect of endocrine insufficiency on PCS was differentially greater among RAP subjects (-1.28 for CP vs. -4.9 for RAP, p = 0.0184). CONCLUSIONS: Even in the absence of CP, subjects with RAP have lower physical and mental QOL. This underscores the importance of identifying interventions to attenuate RAP before the development of overt CP.

Known genetic susceptibility factors for chronic pancreatitis in patients of European ancestry are rare in patients of African ancestry.

BACKGROUND: Multiple pathogenic genetic variants are associated with pancreatitis in patients of European (EA) and Asian ancestries, but studies on patients of African ancestry (AA) are lacking. We evaluated the prevalence of known genetic variations in African-American subjects in the US. METHODS: We studied prospectively enrolled controls (n = 238) and patients with chronic (CP) (n = 232) or recurrent acute pancreatitis (RAP) (n = 45) in the NAPS2 studies from 2000-2014 of self-identified AA. Demographic and phenotypic information was obtained from structured questionnaires. Ancestry and admixture were evaluated by principal component analysis (PCA). Genotyping was performed for pathogenic genetic variants in PRSS1, SPINK1, CFTR and CTRC. Prevalence of disease-associated variants in NAPS2 subjects of AA and EA was compared. RESULTS: When compared with CP subjects of EA (n = 862), prevalence of established pathogenic genetic variants was infrequent in AA patients with CP, overall (29 vs. 8.19%, OR 4.60, 95% CI 2.74-7.74, p < 0.001), and after stratification by alcohol etiology (p < 0.001). On PCA, AA cases were more heterogeneous but distinct from EA subjects; no difference was observed between AA subjects with and without CP-associated variants. Of 19 A A patients with CP who had pathogenic genetic variants, 2 had variants in PRSS1 (R122H, R122C), 4 in SPINK1 (all N34S heterozygotes), 12 in CFTR (2 CFTRsev, 9 CFTRBD, 1 compound heterozygote with CFTRsev and CFTRBD), and 1 in CTRC (R254W). CONCLUSION: Pathogenic genetic variants reported in EA patients are significantly less common in AA patients. Further studies are needed to determine the complex risk factors for AA subjects with pancreatitis.

Outcomes of Chronic Pancreatitis in the Emergency Department.

OBJECTIVES: Chronic pancreatitis (CP) is a debilitating chronic illness. We sought to assess the most common reasons patients with CP visit the Emergency Department (ED), the disposition of ED visit [admission, discharge, death], and evaluate predictors of admission and discharge. METHODS: Within the Health Care Utilization Project Nationwide Emergency Department Sample (NEDS), we focused on patients, 18 years and older, presenting to the emergency department with CP (ICD-9 code 577.1) (2006-2009). Model was fitted to predict the likelihood of admission. RESULTS: Overall, a weighted sample of 638,310 patients visits for CP were identified, of which 399,559 (62.6%) were admitted, 228,523 (35.8%) were discharged from the ED, 5572 (0.9%) discharged against medical advice, and 4656 (0.7%) had an unknown destination. Of those admitted, 4370 (0.7%) died during the hospital episode. The most associated diagnoses for ED visit were diabetes (28.8%), abdominal pain (25.4%), acute pancreatitis (22.5%), cardiac complication (11.1%), infection (10.1%), and dehydration (8.8%). Multivariable analyses revealed that older (OR = 1.02 P < 0.001), sicker patients (Charlson Comorbidity Index ≥ 3, OR = 2.28 P < 0.001), patients presenting with C. difficile colitis (OR = 23.85 P < 0.001), alcohol withdrawal (OR = 6.71 P < 0.001), and acute pancreatitis (OR = 6.46 P < 0.001) were associated with increased odds of hospitalization. CONCLUSIONS: In this national database, our study demonstrates that diabetes, followed by abdominal pain, acute pancreatitis and cardiac complication, were the most common diagnoses associated with ED visits in patients with chronic pancreatitis. Most patients were admitted following the ED visit. Although C. Difficile colitis was a rare associated diagnosis with an ED visit, it was the strongest predictor of admission.

Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis.

OBJECTIVE: To evaluate mid-term outcomes and predictors of survival in non-operated patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) with worrisome features or high-risk stigmata as defined by International Consensus Guidelines for IPMN. Reasons for non-surgical options were physicians' recommendation, patient personal choice or comorbidities precluding surgery. METHODS: In this retrospective, multicentre analysis, IPMNs were classified as branch duct (BD) and main duct (MD), the latter including mixed IPMNs. Univariate and multivariate analysis for overall survival (OS) and disease-specific survival (DSS) were obtained. RESULTS: Of 281 patients identified, 159 (57%) had BD-IPMNs and 122 (43%) had MD-IPMNs; 50 (18%) had high-risk stigmata and 231 (82%) had worrisome features. Median follow-up was 51 months. The 5-year OS and DSS for the entire cohort were 81% and 89.9%. An invasive pancreatic malignancy developed in 34 patients (12%); 31 had invasive IPMNs (11%) and 3 had IPMN-distinct pancreatic ductal adenocarcinoma (1%). Independent predictors of poor DSS in the entire cohort were age >70 years, atypical/malignant cyst fluid cytology, jaundice and MD >15 mm. Compared with MD-IPMNs, BD-IPMNs had significantly better 5-year OS (86% vs 74.1%, p=0.002) and DSS (97% vs 81.2%, p<0.0001). Patients with worrisome features had better 5-year DSS compared with those with high-risk stigmata (96.2% vs 60.2%, p<0.0001). CONCLUSIONS: In elderly patients with IPMNs that have worrisome features, the 5-year DSS is 96%, suggesting that conservative management is appropriate. By contrast, presence of high-risk stigmata is associated with a 40% risk of IPMN-related death, reinforcing that surgical resection should be offered to fit patients.

Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities.

OBJECTIVES: Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. METHODS: We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. RESULTS: Mean PCS and MCS scores were 36.7±11.7 and 42.4±12.2, respectively. Significant (P<0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P<0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. CONCLUSIONS: Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses.

Patient and Disease Characteristics Associated With the Presence of Diabetes Mellitus in Adults With Chronic Pancreatitis in the United States.

OBJECTIVES: Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP). Past studies for DM risk factors in CP have been limited to single centers or highly focused on a single etiology such as alcoholic or hereditary disease. We studied risk factors for DM in a large population of patients with CP of all etiologies enrolled in the North American Pancreatitis 2 studies. METHODS: Participants (1,171) with CP (n=383 with DM, n=788 without DM) were enrolled prospectively from 26 participating centers. Questionnaires were completed by patients and physicians in a cross-sectional assessment. Patient demographics and disease characteristics were compared for CP with DM vs. without DM. Logistic regression was performed to assess the variables associated with DM diagnosis in a multivariable model. RESULTS: Diabetics were more likely to be black (P=0.02), overweight, or obese (P<0.001), and with a family history of DM (P=0.0005). CP patients with DM were more likely to have pancreatic calcifications (63% vs. 54%, P=0.002), atrophy (44% vs. 32%, P<0.0001), and prior pancreas surgery (26.9% vs. 16.9%, P<0.0001). In multivariate logistic regression modeling, the strongest risk factors for DM were obesity (odds ratio (OR) 2.8, 95% confidence interval (CI) 1.9, 4.2) and exocrine insufficiency (OR 2.4, 95% CI 1.8, 3.2). CONCLUSIONS: In this large multicenter cohort of patients with CP, exocrine insufficiency, calcifications, and pancreas surgery conveyed higher odds of having DM. However, the traditional 'type 2 DM' risk factors of obesity and family history were similarly important in conveying risk for DM.

Early Abdominal Imaging Remains Over-Utilized in Acute Pancreatitis.

BACKGROUND: Early abdominal computed tomography (CT) or magnetic resonance (MR) imaging is common in acute pancreatitis (AP). Guidelines (2007-2013) indicate routine use is unwarranted. AIMS: To compare the frequency and evaluate the predictors of early CT/MR utilization for AP between September 2006-2007 (period A) and September 2014-2015 (period B). METHODS: AP patients presenting directly to a large academic emergency department were prospectively enrolled during each period. Cases requiring imaging to fulfill diagnostic criteria were excluded. Early CT/MR (within 24 h of presentation) utilization rates were compared using Fisher's exact test. Predictors of early imaging usage were assessed with multivariate logistic regression. RESULTS: The cohort included 96 AP cases in period A and 97 in period B. There were no significant differences in patient demographics, comorbidity scores, or AP severity. Period B cases manifested decreased rates of the systemic inflammatory response syndrome (SIRS) during the first 24 h of hospitalization (67% period A vs. 43% period B, p = 0.001). Independent predictors of early imaging included age >60 and SIRS or organ failure on day 1. No significant decrease in early CT/MR usage was observed from period A to B on both univariate (49% period A vs. 40% period B, p = 0.25) and multivariate (OR 1.0 for period B vs. A, 95% CI 0.5-1.9) analysis. CONCLUSIONS: In a comparison of imaging practices for AP, there was no significant decrease in early abdominal CT/MR utilization from 2007 to 2015. Quality improvement initiatives specifically targeting early imaging overuse are needed.