Impact of stress on cardiac phenotypes in mice harboring an ankyrin-B disease variant.

Encoded by ANK2, ankyrin-B (AnkB) is a multifunctional adapter protein critical for the expression and targeting of key cardiac ion channels, transporters, cytoskeletal-associated proteins, and signaling molecules. Mice deficient for AnkB expression are neonatal lethal, and mice heterozygous for AnkB expression display cardiac structural and electrical phenotypes. Human ANK2 loss-of-function variants are associated with diverse cardiac manifestations; however, human clinical 'AnkB syndrome' displays incomplete penetrance. To date, animal models for human arrhythmias have generally been knock-out or transgenic overexpression models and thus the direct impact of ANK2 variants on cardiac structure and function in vivo is not clearly defined. Here, we directly tested the relationship of a single human ANK2 disease-associated variant with cardiac phenotypes utilizing a novel in vivo animal model. At baseline, young AnkBp.E1458G+/+ mice lacked significant structural or electrical abnormalities. However, aged AnkBp.E1458G+/+ mice displayed both electrical and structural phenotypes at baseline including bradycardia and aberrant heart rate variability, structural remodeling, and fibrosis. Young and old AnkBp.E1458G+/+ mice displayed ventricular arrhythmias following acute (adrenergic) stress. In addition, young AnkBp.E1458G+/+ mice displayed structural remodeling following chronic (transverse aortic constriction) stress. Finally, AnkBp.E1458G+/+ myocytes harbored alterations in expression and/or localization of key AnkB-associated partners, consistent with the underlying disease mechanism. In summary, our findings illustrate the critical role of AnkB in in vivo cardiac function as well as the impact of single AnkB loss-of-function variants in vivo. However, our findings illustrate the contribution and in fact necessity of secondary factors (aging, adrenergic challenge, pressure-overload) to phenotype penetrance and severity.

Molecular Pathways and Animal Models of Arrhythmias.

Arrhythmias account for over 300,000 annual deaths in the United States, and approximately half of all deaths are associated with heart disease. Mechanisms underlying arrhythmia risk are complex; however, work in humans and animal models over the past 25 years has identified a host of molecular pathways linked with both arrhythmia substrates and triggers. This chapter will focus on select arrhythmia pathways solved by linking human clinical and genetic data with animal models.

Lactated Ringers Use in the First 24 Hours of Hospitalization Is Associated With Improved Outcomes in 999 Patients With Acute Pancreatitis.

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.

Mortality Trends, Outcomes, and Predictors of Portal Vein Thrombosis in Acute Pancreatitis Patients: A Propensity-Matched National Study.

BACKGROUND: Portal vein thrombosis (PVT) is a rare complication of acute pancreatitis (AP) and might be associated with worse outcomes. We aimed to study trends, outcomes, and predictors of PVT in AP patients. METHODS: The National Inpatient Sample database was utilized to identify the adult patients (≥ 18 years) with primary diagnosis of AP from 2004 to 2013 using International Classification of Disease, Ninth Revision. Patients with and without PVT were entered into propensity matching model based on baseline variables. Outcomes were compared between both groups and predictors of PVT in AP were identified. RESULTS: Among the total of 2,389,337 AP cases, 7046 (0.3%) had associated PVT. The overall mortality of AP decreased throughout the study period (p trend ≤ 0.0001), whereas mortality of AP with PVT remained stable (1-5.7%, p trend = 0.3). After propensity matching, AP patients with PVT patients had significantly higher in-hospital mortality (3.3% vs. 1.2%), AKI (13.4% vs. 7.7%), shock (6.9% vs. 2.5%), and need for mechanical ventilation (9.2% vs. 2.5%) along with mean higher cost of hospitalization and length of stay (p < 0.001 for all). Lower age (Odd ratio [OR] 0.99), female (OR 0.75), and gallstone pancreatitis (OR 0.79) were negative predictors, whereas alcoholic pancreatitis (OR 1.51), cirrhosis (OR 2.19), CCI > 2 (OR 1.81), and chronic pancreatitis (OR 2.28) were positive predictors of PVT (p < 0.001 for all) in AP patients. CONCLUSION: PVT in AP is associated with significantly higher risk of death, AKI, shock, and need for mechanical ventilation. Chronic and alcoholic pancreatitis is associated with higher risk of PVT in AP.

Incidence and risk factors for recurrence of ampullary adenomas after endoscopic papillectomy: Comparative analysis of familial adenomatous polyposis and sporadic ampullary adenomas in an international multicenter cohort.

OBJECTIVES: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA. METHODS: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease. RESULTS: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence. CONCLUSION: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients.

Superiority of Self-Expandable Metallic Stents Over Plastic Stents in Treatment of Malignant Distal Biliary Strictures.

BACKGROUND & AIMS: Treatment of malignant biliary strictures with endoscopic retrograde cholangiopancreatography (ERCP) guided stent placement is highly effective. Our objective was to compare the efficacy and adverse outcomes between plastic stents (PS) and self-expandable metallic stents (SEMS). METHODS: A cohort study was performed of all consecutive patients who underwent ERCP with stent placement for the management of malignant biliary stricture. Comparisons on clinical success, patency duration, stent dysfunction, unplanned reintervention and adverse outcomes were performed. Univariate and multivariable analyses were performed to identify factors associated with clinical success, need for reintervention, and stent dysfunction. RESULTS: From 2012 to 2019, 1139 patients underwent ERCP with PS placement while 1008 patients received SEMS for the management of malignant biliary stricture. In distal strictures, SEMS reported a significantly higher rate of clinical success compared with PS (94.1% vs 87.4%, P < 0.001) and a lower rate of unplanned reintervention (17.1% vs 27.4%, P < 0.001). In hilar strictures, the rates of clinical success and unplanned intervention were comparable. The patency duration and time to unplanned reintervention were significantly longer with SEMS than PS, irrespective of stricture location. In distal stricture, PS was associated with a significantly higher rate of cholangitis than SEMS (6.9% vs 2.4%; P < .001) but a lower rate of pancreatitis (3.6% vs 6%; P = 0.021). CONCLUSION: Given superior efficacy, durability and lower rates of cholangitis, SEMS should be offered as the first line endoscopic treatment option for malignant distal biliary stricture. For malignant hilar stricture, SEMS is an attractive alternative to PS in some cases by offering a comparable efficacy with a superior durability.

The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study.

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.

Prospective Study Assessing Impact of Ethylene Oxide Sterilization on Endoscopic Ultrasound Image Quality.

BACKGROUND & AIMS: Duodenoscope-associated transmission of infections has raised questions about efficacy of endoscope reprocessing using high-level disinfection (HLD). Although ethylene oxide (ETO) gas sterilization is effective in eradicating microbes, the impact of ETO on endoscopic ultrasound (EUS) imaging equipment remains unknown. In this study, we aimed to compare the changes in EUS image quality associated with HLD vs HLD followed by ETO sterilization. METHODS: Four new EUS instruments were assigned to 2 groups: Group 1 (HLD) and Group 2 (HLD + ETO). The echoendoscopes were assessed at baseline, monthly for 6 months, and once every 3 to 4 months thereafter, for a total of 12 time points. At each time point, review of EUS video and still image quality was performed by an expert panel of reviewers along with phantom-based objective testing. Linear mixed effects models were used to assess whether the modality of reprocessing impacted image and video quality. RESULTS: For clinical testing, mixed linear models showed minimal quantitative differences in linear analog score (P = .04; estimated change, 3.12; scale, 0-100) and overall image quality value (P = .007; estimated change, -0.12; scale, 1-5) favoring ETO but not for rank value (P = .06). On phantom testing, maximum depth of penetration was lower for ETO endoscopes (P < .001; change in depth, 0.49 cm). CONCLUSIONS: In this prospective study, expert review and phantom-based testing demonstrated minimal differences in image quality between echoendoscopes reprocessed using HLD vs ETO + HLD over 2 years of clinical use. Further studies are warranted to assess the long-term clinical impact of these findings. In the interim, these results support use of ETO sterilization of EUS instruments if deemed clinically necessary.

The relationship between pre-existing diabetes mellitus and the severity of acute pancreatitis: Report from a large international registry.

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.

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.

Spontaneous Internal Pancreatic Fistulae Complicating Acute Pancreatitis.

Spontaneous pancreatic fistula (PF) is a rare but challenging complication of acute pancreatitis (AP). The fistulae could be internal (draining into another viscera or cavity, e.g., pancreaticocolonic, gastric, duodenal, jejunal, ileal, pleural, or bronchial) or external (draining to skin, i.e., pancreaticocutaneous). Internal fistulae constitute the majority of PF and will be discussed in this review. Male sex, alcohol abuse, severe AP, and infected necrosis are the major risk factors for development of internal PF. A high index of suspicion is required to diagnose PF. Broad availability of computed tomography makes it the initial test of choice. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography have higher sensitivity compared with computed tomography scan and also allow for assessment of pancreatic duct for leak or disconnection, which affects treatment approaches. Certain complications of PF including hemorrhage and sepsis could be life-threatening and require urgent intervention. In nonurgent/chronic cases, management of internal PF involves control of sepsis, which requires effective drainage of any residual pancreatic collection/necrosis, sometimes by enlarging the fistula. Decreasing fistula output with somatostatin analogs (in pancreaticopleural fistula) and decreasing intraductal pressure with endoscopic retrograde cholangiopancreatography or endoscopic ultrasound/interventional radiology-guided interventions or surgery are commonly used strategies for management of PF. More than 60% of the internal PF close with medical and nonsurgical interventions. Colonic fistula, medical refractory-PF, or PF associated with disconnected pancreatic duct can require surgical intervention including bowel resection or distal pancreatectomy. In conclusion, AP-induced spontaneous internal PF is a complex complication requiring multidisciplinary care for successful management.

Impact of margin status on outcomes after endoscopic resection of well-differentiated duodenal neuroendocrine tumors.

BACKGROUND AND AIMS: Duodenal neuroendocrine tumors (DNETs) are known to have low metastatic potential and follow an indolent course. Although DNETs <1 cm in size are amenable to endoscopic resection, little is known about the long-term outcomes and recurrence rates of this approach. METHODS: Sixty-three patients with DNETs from 3 centers were retrospectively studied from 2003 to 2018. We analyzed their resection modality (EMR, snare polypectomy, or forceps polypectomy), margin status, risk factors for recurrence, recurrence rate, and endoscopic surveillance patterns. RESULTS: Of the 63 patients who underwent endoscopic resection, 13 (20.6%) had recurrence. The presence of R1 margins was found to be a statistically significant risk factor for recurrence (P = .048). Mean surveillance time for all DNETs was 2.8 ± 2.6 years. Ninety-two percent of recurrences were detected within 3 years of resection. CONCLUSIONS: Our data suggest that the main predictor of recurrence in low-grade DNETs <1.0 cm is the presence of positive tumor margins at the initial endoscopic resection. More frequent, earlier surveillance after resection than that currently recommended by European Neuroendocrine Tumor Society guidelines may be warranted to promptly capture DNET recurrences. Additionally, no recurrences occurred in our cohort after 4 years of surveillance.

Endoscopic ultrasound-directed transgastric ERCP (EDGE): a retrospective multicenter study.

BACKGROUND: Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. The aims of this study were: (1) to determine the rates of long-term adverse events after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; (2) to identify predictors of persistent fistula; (3) to assess the outcomes of endoscopic closure when persistent fistula is encountered. METHODS: This was a multicenter retrospective study involving 13 centers between February 2015 and March 2019. Adverse events were defined according to the ASGE lexicon. Persistent fistula was defined as an upper gastrointestinal series or esophagogastroduodenoscopy showing evidence of fistula. RESULTS: 178 patients (mean age 58 years, 79 % women) underwent EDGE. Technical success was achieved in 98 % of cases (175/178), with a mean procedure time of 92 minutes. Periprocedural adverse events occurred in 28 patients (15.7 %; mild 10.1 %, moderate 3.4 %, severe 2.2 %). The four severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10 % of those sent for objective testing (9/90). Following identification of a fistula, 5 /9 patients underwent endoscopic closure procedures, which were successful in all cases. CONCLUSIONS: The EDGE procedure is associated with high clinical success rates and an acceptable risk profile. Persistent fistulas after lumen-apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistulas are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

Dynamic changes in the pancreatitis activity scoring system during hospital course in a multicenter, prospective cohort.

BACKGROUND AND AIM: The primary aim was to validate the Pancreatitis Activity Scoring System (PASS) in a multicenter prospectively ascertained acute pancreatitis (AP) cohort. Second, we investigated the association of early PASS trajectories with disease severity and length of hospital stay (LOS). METHODS: Data were prospectively collected through the APPRENTICE consortium (2015-2018). AP severity was categorized based on revised Atlanta classification. Delta PASS (ΔPASS) was calculated by subtracting activity score from baseline value. PASS trajectories were compared between severity subsets. Subsequently, the cohort was subdivided into three LOS subgroups as short (S-LOS): 2-3 days; intermediate (I-LOS): 3-7 days; and long (L-LOS): ≥7 days. The generalized estimating equations model was implemented to compare PASS trajectories. RESULTS: There were 434 subjects analyzed including 322 (74%) mild, 86 (20%) moderately severe, and 26 (6%) severe AP. Severe AP subjects had the highest activity levels and the slowest rate of decline in activity (P = 0.039). Focusing on mild AP, L-LOS subjects (34%) had 28 points per day slower decline; whereas, S-LOS group (13%) showed 34 points per day sharper decrease compared with I-LOS (53%; P < 0.001). We noticed an outlier subset with a median admission-PASS of 466 compared with 140 in the rest. Morphine equivalent dose constituted 80% of the total PASS in the outliers (median morphine equivalent dose score = 392), compared with only 25% in normal-range subjects (score = 33, P value < 0.001). CONCLUSIONS: This study highlighted that PASS can quantify AP activity. Significant differences in PASS trajectories were found both in revised Atlanta classification severity and LOS groups, which can be harnessed in AP monitoring/management (ClincialTrials.gov number, NCT03075618).

Clinical Outcomes of Acute Pancreatitis in Patients with Cirrhosis According to Liver Disease Severity Scores.

BACKGROUND: Literature on acute pancreatitis (AP) outcomes in patients with cirrhosis is limited. We aim to investigate the mortality and morbidity of AP in patients with cirrhosis. METHODS: We conducted a retrospective cohort study, and propensity score matching was done to match cirrhotic with non-cirrhotic patients on a 1:2 basis. Outcomes included inpatient mortality, organs failure, systemic inflammatory response syndrome, and length of hospital stay. We performed subgroup analysis of cirrhotics according to Child-Pugh and MELD scores. Multivariable logistic regression models were tested. RESULTS: From 819 AP patients, cirrhosis prevalence was 4.9% (40). There was no significant difference between cirrhotics and non-cirrhotics for inpatient mortality (7.5% vs. 1.3%, p = 0.1), severe AP (17.5% vs. 7.5%), shock (7.9% vs. 3%), respiratory failure (10% vs. 3.8%), need for intensive care unit (15% vs. 6.3%), systemic inflammatory response syndrome (SIRS) on admission (22.5% vs. 32.5%), and SIRS on day 2 (25% vs. 15%). Cirrhotics had similar rates of pancreatic necrosis, ileus, BISAP score, Marshall score, admission hematocrit, BUN, and hospital length of stay. Finally, cirrhotics who had severe AP, required ICU, and/or die in-hospital appeared to have more severe liver diseases (Child-C, higher MELD score > 17) and had lower AP severity scores (BISAP < 3, Marshall scores < 2). CONCLUSION: In our study, cirrhotics hospitalized with AP had similar morbidity and mortality when compared to non-cirrhotics.

The Risk of Acute and Chronic Pancreatitis in Celiac Disease.

BACKGROUND AND AIMS: Celiac disease (CD) is a chronic immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals. A few studies reported a higher incidence of pancreatitis in the CD population. Using a large US database, we sought to describe the epidemiology, risk, and outcomes of acute pancreatitis (AP) and chronic pancreatitis (CP) in CD patients. METHODS: We queried a multiple health system data analytics and research platform (Explorys Inc, Cleveland, OH, USA). A cohort of patients with a diagnosis of CD was identified. Subsequently, individuals who developed a new diagnosis of AP and CP after at least 30 days of being diagnosed with CD were identified. A multivariate regression model was performed to adjust for multiple confounding factors. RESULTS: Of the 72,965,940 individuals in the database, 133,400 (0.18%), 362,050 (0.50%), and 95,190 (0.13%) had CD, AP, and CP, respectively. New diagnosis of AP and CP after at least 30 days of CD diagnosis was 1.06%, 0.52%, respectively, compared to non-CD patients with 0.49% for AP and 0.13% for CP, P < .0001. In multivariate regression analysis, patients with CD were at higher risk of developing AP [OR 2.66; 95% CI 2.55-2.77] and CP [OR 2.18; 95% CI 2.04-2.34]. Idiopathic AP was the most common etiology among CD patients [OR 1.54; 95% CI 1.34-1.77]. CONCLUSIONS: In this largest US population database and after adjusting for several confounders, patients with CD were at increased risk of developing AP and CP. Celiac disease patients had worse outcomes and higher medical burden compared to non-CD patients. Recurrent abdominal pain that suggests pancreatic etiology, idiopathic pancreatitis, or elevation of pancreatic enzymes should warrant investigation for CD as a potential cause of pancreatic disease.

Trends and risk factors for 30-day readmissions in patients with acute cholangitis: analysis from the national readmission database.

INTRODUCTION: Acute cholangitis (AC) can be associated with significant mortality and high risk of readmissions, if not managed promptly. We used national readmission database (NRD) to identify trends and risk factors associated with 30-day readmissions in patients with AC. METHODS: We conducted a retrospective cohort study of adult patients admitted with AC from 2010-2014 and Q1-Q3 of 2015 by extracting data from NRD. Initial admission with a primary diagnosis of acute cholangitis (ICD-9 code: 576.1) was considered as the index admission and any admission after index admission was considered a readmission regardless of the primary diagnosis. Multivariable regression analyses were performed to assess the association. RESULTS: From 52,906 AC index admissions, overall 30-day readmission rate was 21.48% without significant differences in the readmission rates across the study period. There was significant increase in the overall hospital charges for readmissions, while a significant reduction in the death rate was observed during the first readmission. Recurrent cholangitis (14%), septicemia (6.4%), and mechanical complication of bile duct prosthesis (3%) were the most common reasons for readmissions. The risk of readmission was significantly higher in patients with pancreatic neoplasm (OR 1.6, 95% CI 1.4-1.8), those who underwent percutaneous biliary procedures (OR 1.4, 95% CI 1.2-1.6), and who had an acute respiratory failure (OR 1.2, 95% CI 1.0-1.15). Other factors contributing to increased risk of readmissions included patients with Charleston comorbidity index > 3, diabetes, and length of stay > 3 days. Readmission risk was significantly lower in patients who underwent ERCP (OR 0.80, 95% CI 0.73-0.88) or cholecystectomy (OR 0.54, 95% CI 0.43-0.69). CONCLUSIONS: AC is associated with a high 30-day readmission rate of over 21%. Patients with malignant biliary obstruction, increased comorbidities, and those who undergo percutaneous drainage rather than ERCP seem to be at the highest risk.

Worldwide Variations in Demographics, Management, and Outcomes of Acute Pancreatitis.

BACKGROUND & AIMS: Few studies have compared regional differences in acute pancreatitis. We analyzed data from an international registry of patients with acute pancreatitis to evaluate geographic variations in patient characteristics, management, and outcomes. METHODS: We collected data from the APPRENTICE registry of patients with acute pancreatitis, which obtains information from patients in Europe (6 centers), India (3 centers), Latin America (5 centers), and North America (8 centers) using standardized questionnaires. Our final analysis included 1612 patients with acute pancreatitis (median age, 49 years; 53% male, 62% white) enrolled from August 2015 through January 2018. RESULTS: Biliary (45%) and alcoholic acute pancreatitis (21%) were the most common etiologies. Based on the revised Atlanta classification, 65% of patients developed mild disease, 23% moderate, and 12% severe. The mean age of patients in Europe (58 years) was older than mean age for all 4 regions (46 years) and a higher proportion of patients in Europe had comorbid conditions (73% vs 50% overall). The predominant etiology of acute pancreatitis in Latin America was biliary (78%), whereas alcohol-associated pancreatitis accounted for the highest proportion of acute pancreatitis cases in India (45%). Pain was managed with opioid analgesics in 93% of patients in North America versus 27% of patients in the other 3 regions. Cholecystectomies were performed at the time of hospital admission for most patients in Latin America (60% vs 15% overall). A higher proportion of European patients with severe acute pancreatitis died during the original hospital stay (44%) compared with the other 3 regions (15%). CONCLUSIONS: We found significant variation in demographics, etiologies, management practices, and outcomes of acute pancreatitis worldwide. ClinicalTrials.gov number: NCT03075618.

Clinical outcomes of acute pancreatitis in patients with cirrhosis.

BACKGROUND: AP outcomes in cirrhotic patients have not yet been studied. We aim to investigate the outcomes of cirrhotics patients with acute pancreatitis. METHODS: The National Inpatient Sample (NIS) database (2003-2013) was queried for patients with a discharge diagnosis of AP and liver cirrhosis. Cirrhosis was further classified as compensated and decompensated using the validated Baveno IV criteria. Primary outcome was inpatient mortality. The analysis was adjusted for age, gender, race, Charlson comorbidity index (CCI), median income quartile, and hospital characteristics. RESULTS: Over 2.8 million patients with acute pancreatitis were analyzed. Cirrhosis prevalence was 2.8% (80,093). Both compensated and decompensated cirrhosis subjects had significantly higher mortality. Highest odds ratios (OR) were: inpatient mortality (OR 3.4, P < 0.001), Shock (OR 1.5, P = 0.02), Ileus (OR: 1.3, p = 0.02, ARDS (OR 1.2, p = 0.03), upper endoscopy performed (OR 2.0, p < 0.001), blood transfusions (OR 3.1, p < 0.001), gastrointestinal bleed (OR 5.5, p < 0.001), sepsis (OR 1.3, p = 0.005), portal vein thrombosis (PVT) (OR 7.2, p < 0.001), acute cholecystitis (OR 1.3, p < 0.001). Interestingly, cirrhosis patients had lower hospital length of stay, (OR 0.16, p < 0.001), AKI (OR 0.93, p = 0.06), myocardial infarction (OR 0.31, p < 0.001), SIRS (OR 0.62, p < 0.001), parenteral nutrition requirement (OR 0.84, p = 0.002). Decompensated cirrhosis had higher inflation-adjusted hospital charges (+$3896.60; p < 0.001). CONCLUSION: AP patients with cirrhosis have higher inpatient mortality, but it is unlikely to be due to AP severity as patients had lower incidence of SIRS and AKI. Higher mortality is possibly related to complications of cirrhosis and portal hypertension itself such as GI bleed, shock, PVT, AC and sepsis.

The utility of intracystic glucose levels in differentiating mucinous from non-mucinous pancreatic cysts.

BACKGROUND: Differentiating benign non-mucinous from potentially malignant mucinous pancreatic cysts is still a challenge. This study aims to improve this distinction with cyst fluid analysis. METHODS: A cohort study of pancreatic cyst undergoing EUS/FNA was performed from a prospectively maintained database between 2014 and 2018 was performed. RESULTS: 113 patients were analyzed (40 non-mucinous and 73 mucinous). For differentiating mucinous from non-mucinous cyst: intracyst glucose ≤41 mg/dl had a sensitivity of 92% and a specificity of 92%; positive predictive value (PPV) of 96 and negative predictive value (NPV) of 86. Glucose ≤21 mg/dl had a sensitivity of 88%, specificity of 97%, PPV of 98 and NPV of 81. CEA ≥192 ng/mL had a sensitivity of 50% and a specificity of 92%; PPV of 92 and NPV of 50. Glucose ≤21 mg/dl or CEA ≥192 ng/mL combined had a sensitivity of 93%, specificity of 92%, PPV of 96 and NPV of 87 (Fig. 1, Table 1). CONCLUSION: Intra-cyst glucose levels (≤41 mg/dl) outperforms classic CEA testing for differentiation of mucinous from non-mucinous pancreatic cysts. It was found to be an excellent diagnostic test with an AUC of 0.95 (95% CI: 0.81, 0.97).