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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.

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.

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.

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.

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.

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.

BACKGROUND AND AIMS: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield. METHODS: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders. RESULTS: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1–4)]. ERCP was more common in those with obstructed pancreatic duct (p=0.0009), pancreas divisum (p=0.0009), prior pancreatic surgery (p=0.005), and longer disease duration (p=0.004). A greater number of ERCPs was associated with disease duration (p

OBJECTIVES: Endoscopic pancreatic function tests are used to diagnose pancreatic diseases and are a viable source for the discovery of biomarkers to better characterize pancreatic disorders. However, pancreatic fluid (PF) contains active enzymes that degrade biomolecules. Therefore, we tested how preservation methods and time to storage influences the integrity and quality of proteins and nucleic acids. METHODS: We obtained PF from 9 subjects who underwent an endoscopic pancreatic function test. Samples were snap frozen at the time of collection, after 1, 2, 4 hours on ice, or after storage overnight at 4°C with or without RNase or protease inhibitors. Electrophoresis and mass spectrometry analysis determined protein abundance and quality while nucleic acid integrity values determined DNA and RNA degradation. RESULTS: Protein degradation increased after 4 hours on ice and DNA degradation after 2 hours on ice. Adding protease inhibitors delayed degradation. RNA was significantly degraded under all conditions compared to the snap frozen samples. Isolated RNA from PF-derived exosomes exhibited similar poor quality as RNA isolated from matched PF samples. CONCLUSIONS: Adding protease inhibitors immediately after collecting PF and processing the fluid within 4 hours of collection maintains the protein and nucleic acid integrity for use in downstream molecular analyses.

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.

Objectives The incidence rates of acute pancreatitis (AP) and the prevalence of class III obesity, and metabolic syndrome (MetS) are increasing in the US. Since class III obesity was associated with adverse clinical outcomes of AP, we sought to understand if the presence of metabolic comorbidities collectively recognized, as MetS were associated with worse clinical outcomes and increased health-care utilization. Methods The Nationwide Readmissions Database (NRD) (2010–2014) was reviewed to identify all adult subjects with a principal discharge diagnosis of AP. Inpatient mortality, severe AP (SAP), and 30-day readmissions were the primary outcomes analyzed. Propensity score weighted analyses were used to compare AP subjects with and without MetS and were further stratified by class III obesity status. Results MetS was associated with 12.91% (139,165/1,078,183) of all admissions with AP. Propensity score weighted analyses showed that MetS was associated with an increased proportion of SAP (OR 1.21, 95% CI 1.17, 1.25), but decreased mortality (OR 0.62, 95% CI 0.54, 0.70) and 30-day readmissions (OR 0.86, 95% CI 0.83, 0.89). Propensity score weighted analyses also revealed that class III obesity was independently associated with increased mortality in AP subjects with (OR 1.92, 95% CI 1.41, 2.61) and without MetS (OR 1.55, 95% CI 1.26, 1.92), and increased SAP in subjects with and without MetS. Conclusions Class III obesity appears to be the primary factor associated with adverse clinical outcomes in subjects with MetS admitted with AP. This has significant implications for patient management and future research targeting AP.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes.We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included.Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7).CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.

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.

Incidental pancreatic cysts are common, and management strategies continue to evolve. This review summarizes diagnostic and management recommendations in older patients with these lesions based on guidelines and best clinical evidence. Diagnosis of cyst type has been enhanced with improved imaging and cyst fluid analysis and visualization. Recent outcome studies indicate that certain cyst types should be followed independent of patient age as long as certain criteria which are reviewed are met. Differentiation of pancreatic cyst type is important as this dictates the need for long-term follow-up. Because most cyst-related neoplasia occurs in older patients, surveillance should continue within certain guidelines.

Cathepsin E (CTSE) is an intracellular, hydrolytic aspartic protease found to be expressed in cells of the immune and gastrointestinal systems, lymphoid tissues, erythrocytes, and cancer cells. The precise functions are not fully understood; however, various studies have investigated its numerous cell-type specific roles. CTSE expression has been shown to be a potential early biomarker for pancreatic ductal adenocarcinoma (PDAC). PDAC patients have low survival rates; mostly due to the lack of early detection methods. CTSE-specific activity probes have been developed and tested to assist in tumor imaging and functional studies investigating the role of CTSE expression in PDAC tumors. Furthermore, a CTSE protease-specific, photodynamic therapy pro-drug was developed to explore its potential use to treat tumors that express CTSE. Since CTSE is expressed in pancreatic diseases that are risk factors for PDAC, such as pancreatic cysts and chronic pancreatitis, learning about its function in these disease types could assist in early PDAC detection and in understanding the biology of PDAC progression. Overall, CTSE expression and activity shows potential to detect PDAC and other pancreatic diseases. Further research is needed to fully understand its functions and potential translational applicability.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol.To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF.A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups.A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients (CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

Objectives Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown. Methods We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes. Results Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005). Conclusions Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed.

Merkel cell carcinoma (MCC) in an uncommon neuroendocrine neoplasia that originates in the skin in which testicular metastasis is atypical. There are only eight cases reported to date. A 65-year-old patient with a history of MCC in the right thigh who had been treated in 2015 with surgery, chemotherapy and radiation therapy; presented to hospital with pain and right testicular enlargement of one-month duration and with normal testicular tumor markers. An ultrasound study confirmed multiple hypoechoic nodular solid lesions compatible with neoplasia and orchiectomy was subsequently performed. The histological examination reported an immunohistochemical pattern compatible with a diagnosis of MCC. The patient received adjuvant immunotherapy with Avelumab. MCC rarely spreads to the testicle and, due to the shortage of studies, the best treatment of testicular metastasis remains uncertain; however, immunotherapy may be appropriate.

Objectives Cannabis legalization has increased its use. The incidence of acute pancreatitis (AP) and severe acute pancreatitis (SAP) has also increased. In this study, data on pancreatitis were obtained from 2 states before and after cannabis legalization and compared with 2 states without legalized cannabis. Methods Data were extracted from State Inpatient Databases from the states of Colorado and Washington before recreational cannabis legalization (2011) and after legalization (2015). Arizona and Florida were used as the nonlegalized cannabis states. Multivariable logistic regression models were fit for AP and SAP to determine a trend difference between legalized and nonlegalized cannabis states. Results Cannabis use, AP, and SAP increased in all states. The increase in AP and SAP was not significantly different between the states that legalized cannabis use and those that did not. Legalized cannabis states had lower charges for AP and SAP and shorter length of hospitalizations. Conclusions The trend of AP and SAP increased during the study period, but this was not correlated to cannabis use. Cannabis users had lower hospitalization costs and hospital stay. The effects of other confounders such as cannabis dose and delivery methods, alcohol, tobacco, and others need to be studied further as use increases.

OBJECTIVES We hypothesized that hospitalizations in cystic fibrosis (CF) would reflect the development of age-related comorbidities. METHODS A retrospective analysis was performed using the Nationwide Inpatient Sample (2002-2017). Hospitalizations for which the principal diagnosis was CF were analyzed regarding age at discharge and presence of comorbidities. Trends were assessed for significance using the Cochran-Armitage test. RESULTS The mean age of patients hospitalized for CF increased from 19.7 years in 2002 to 23.0 years in 2017 (P = 0.017). Several comorbidities are more than 10 times more prevalent among adults as compared with children, including congestive heart failure, substance abuse, and chronic kidney disease (P < 0.001). In addition, diabetes with chronic complications was more prevalent in adults than children (10.0% vs 3.9%; P < 0.001), as was hypertension (7.2% vs 1.3%; P < 0.001) and osteoporosis (10.2% vs 1.9%; P < 0.001). More than 65% of CF hospitalizations in 2017 were in individuals older than 18 years. CONCLUSIONS Hospitalizations for adults with CF are increasing, and individuals with CF are developing age-related comorbidities. Providers equipped to manage the health care needs of adults need to be ready and able to care for this unique and growing patient population.

Symptomatic Zenker's diverticulum management has evolved from an open intervention to an endoscopic management. At our center, both an otolaryngologist and a gastroenterologist are present in the operating room when treating these lesions. An intra-procedural consensus is reached to undergo either rigid endoscopy or flexible endoscopic diverticulotomy with ENT guidance. We evaluated the real-world efficacy with a cooperative gastroenterology-otolaryngology approach.Single-center retrospective study of patients who underwent a cooperative endoscopic diverticulotomy by a gastroenterologist and otolaryngologist at Cleveland Clinic Florida between 2012 and 2019. Demographic and clinical data, intra-procedural findings/complications, post-procedural symptoms, recurrence rate, and reintervention variables were extracted. Patients included in the study were 17 years old, with symptomatic confirmed typical single Zenker's diverticulum.63 subjects were identified. Patients were predominantly males (63.5%) and white (84.1%), with mean age 73.5 years (53-95). Most subjects presented dysphagia (98.4%), mostly to solids (79.4%). Other demographic and clinical data are described in Table 1. The diverticula had a mean size of 36.3 mm. In 30.1% of the cases food debris was found during the procedure. The mean procedure length was 38.4 minutes. All cases were performed as outpatient. Technical success was achieved in all cases. Patients were followed for a mean of 3.24 months post-procedure. Clinical success was achieved in 92% subjects. One intra-procedural perforation was treated with endoclip. Table 1 Pre-procedural demographic and clinical variables in patients undergoing Zenker's diverticulum cooperative approach Variable Value (n = 63) Sex, n (%) Male Female 40 (63.5) 23 (36.5) Ethnicity/Race, n (%) Non-Hispanic White Hispanic Black 53 (84.1) 7 (11.1) 3 (4.8) Smoking status, n (%) Never Former Active 29 (46.0) 26 (41.3) 8 (10.7) Previous intervention for Zenker's diverticulum, n (%) 12 (19.1) Dysphagia, n (%) Only to solids Only to liquids Both solids and liquids 50 (79.4) 0 (0) 12 (19.0) Regurgitation of food, n (%) Chronic cough, n (%) 13 (20.6) Halitosis, n (%) 9 (14.3) CONCLUSION: A cooperative endoscopic approach by gastroenterology and otolaryngology for symptomatic Zenker's diverticulum management offered excellent technical and clinical success. This approach proved to be safe and effective.

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples ( n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p ( P = 0.03), hsa-miR-148a-3p ( P = 0.04) and hsa-miR-221-3p ( P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p ( P = 0.04) and hsa-miR-7-5p ( P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p ( P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p ( P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg ( r = −0.20, P = 0.02). Also, hsa-miR-200c ( r = 0.18, P = 0.03) and hsa-miR-221-3p ( r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.

BACKGROUND AND AIM Despite higher rates of gallstones in patients with cirrhosis, there are no population-based studies evaluating outcomes of acute biliary pancreatitis (ABP). Therefore, we sought to evaluate the predictors of early readmission and mortality in this high-risk population. METHODS We utilized the Nationwide Readmission Database (2011-2014) to evaluate all adults admitted with ABP. Multivariable logistic regression models were used to assess independent predictors for 30-day readmission, index admission mortality, and calendar year mortality. RESULTS Among 184 611 index admissions with ABP, 4344 (2.4%) subjects had cirrhosis (1649 with decompensation). Subjects with cirrhosis, when compared with those without, incurred higher rates of 30-day readmission (20.9% vs 11.2%; P

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation. METHODS: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n=84) with adults (n=195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP. RESULTS: Children more commonly underwent splenectomy (100% versus 91%, p=0.002), pylorus preservation (93% versus 67%; p

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.

Objectives We describe the methodology of Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency (PAPPEI), a prospective, observational, multicenter cohort study. The objectives of PAPPEI are to estimate the incidence rate of post-acute pancreatitis (AP) pancreatic exocrine insufficiency (PEI), define factors that determine the development of post-AP PEI, and evaluate the impact of post-AP PEI on nutritional status and quality of life. Methods Enrollment started in June 2017 in 3 expert academic centers in the United States. Data were collected during hospitalization (baseline) at 3 and 12 months after enrollment. Fecal elastase-1 was used to assess PEI. Study questionnaires are completed by patient interview and review of electronic medical records. Blood is obtained to evaluate vitamin deficiencies and nutritional markers. Results As of August 2020, 77 subjects have completed the baseline evaluation. The median age was 58 years (interquartile range, 39-67 years), 38% were male, and 90% were white. The etiology of AP was biliary in 39 subjects (51%), and 51 subjects (66%) had mild AP. Three- and 12-month follow-up data have been collected in 29 and 13 subjects, respectively. Conclusion The PAPPEI study aims to expand our understanding of post-AP PEI incidence, including its impact on nutritional status and quality of life.

OBJECTIVES: There is a paucity of studies evaluating predictors of new-onset diabetes mellitus (DM) following acute pancreatitis (AP-related DM). We utilized a population-based database to evaluate predictors of AP-related DM. METHODS: The Nationwide Readmissions Database (2010–2014) was utilized to identify all non-diabetic adults with an index primary diagnosis of acute pancreatitis (AP). Multiple exclusions were applied to identify cohorts with and without AP-related DM. A case-control study was conducted to identify risk factors for developing AP-related DM within the calendar year. RESULTS: We identified 2510 subjects with AP-related DM and 40,308 controls with AP who did not develop DM. Multivariable analysis revealed that increasing age (50–64 years, adjusted Odds Ratio [aOR], 1.35, 95% confidence interval [CI], 1.14–1.60), male sex (aOR, 1.2, 95% CI, 1.03–1.40), lowest income quartile (aOR, 1.48, 95% CI, 1.18–1.84), Elixhauser comorbidity index ≥3 (aOR, 1.47, 95% CI, 1.23–1.75), components of metabolic syndrome (aOR, 2.12, 95% CI, 1.21–3.70), severe AP (aOR, 1.60, 95% CI, 1.34–1.90), and recurrent AP (aOR, 1.46, 95% CI, 1.24–1.72) were independently associated with increased risk of AP-related DM. CONCLUSION: These population-level variables predictive of developing AP-related DM can potentially identify patients who may benefit from closer follow-up, intensive education, and implementation of preventative strategies.

Background: Compared with patients who undergo pancreatic surgery for chronic pancreatitis and malignancy, patients with pancreatic cystic lesions (PCLs) generally have normal adjacent pancreatic parenchyma. There is a paucity of literature evaluating new-onset diabetes mellitus (NODM) following PCL resection. We sought to characterize the incidence and risk factors associated with NODM following partial pancreatectomy for PCLs. Methods: We utilized the IBM MarketScan Database (2012-2018) to identify all non-diabetic adult patients who underwent elective partial pancreatectomy for PCLs. Rigorous stepwise exclusion criteria were applied to identify patients without other pancreatic disease. We performed time-to-event analyses using Kaplan-Meier curves and multivariable Cox proportional hazards regression to define the incidence and risk factors associated with postoperative NODM. Findings: Among 311 patients with PCLs who underwent partial pancreatectomy, the overall risk of NODM was 9.1% (95% CI 6.3-12.9%), 15.1% (95% CI 11.3-20.2%), and 20.2% (95% CI 15.3-26.4%) at six, 12 and 24 months, respectively. Multivariable analysis revealed that older age (55-64 years, adjusted Hazard Ratio (aHR) 1.97, 95% CI 1.04-3.72 vs. 18-54 years), obesity (aHR 2.63, 95% CI 1.35-5.12), hypertension (aHR 1.79, 95% CI 1.01-3.17), and cardiovascular disease (aHR 2.54, 95% CI 1.02-6.28) were independent predictors of postoperative NODM. Rates of NODM were similar following distal pancreatectomy versus pancreaticoduodenectomy. Interpretation: Within two years, approximately one in five patients will develop NODM following partial pancreatectomy for PCLs. Those with advanced age, metabolic syndrome features, and/or cardiovascular disease may benefit from preoperative counselling for risk-reduction and intensive postoperative monitoring, education, and treatment strategies for DM. Funding: National Center for Advancing Translational Sciences, award number UL1TR002733. Declaration of Interests: None of the authors have any conflicts of interest or financial ties to disclose related to the current study. Ethics Approval Statement: This database is a publicly available population-based dataset. As such, the study was exempt from approval by the Ohio State University Institutional Review Board.

Heat stress is associated with impaired meat quality and disruption of redox balance. This study investigated the effect of chronic exposure to high temperature on meat quality and antioxidant markers of muscles (longissimus lumborum and gluteus medius) of growing Iberian pigs. Twenty-four pure Iberian pigs were allocated during 28 days to one of three treatments (n = 8/treatment): thermoneutral conditions (20C) and ad libitum feeding (TN), heat stress conditions (30C) and ad libitum feeding (HS) and thermoneutral and pair-fed with HS (TN-pf). Muscles of the HS group had greater intramuscular fat content than the TN-pf group and higher Zn levels than TN and TN-pf, whereas differences on fatty acid composition were negligible. Heat exposure did not affect pH, color coordinates of redness (a*) and yellowness (b*) and MDA values but had a positive influence on lightness and drip losses. Moreover, chronic heat stress stimulated the activity of antioxidant defenses SOD, CAT and GPx. The statistical factor analysis adequately classified the muscles studied, but was unable to differentiate samples according with treatments. Findings of the present study support an adaptive response of the Iberian pig to high temperatures and show the high Iberian meat quality even under adverse climate situations., This research has been funded by the Spanish Ministry of Economy and Competitiveness of the Spanish Government through Research Project AGL2016-80231-R. This work is part of the doctoral thesis of Zaira Pardo, Ph.D. student from the Official Doctoral Program “Nutrition and Food Sciences” of the Granada University, who received a grant FPI with reference BES-2017-081486.

Background & Aims The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. Methods Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. Results A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76–1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80–2.12) were not associated independently with mechanical ventilation or death. Conclusions Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

BackgroundThe prevalence and significance of digestive manifestations in COVID-19 remain uncertain.MethodsConsecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were manually abstracted from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19.ResultsA total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were elevated to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio 0.93, 95% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death.ConclusionsAmong patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common but the majority were mild and their presence was not associated with a more severe clinical course

Immunocastration (IC, vaccination against gonadotropin releasing hormone (GnRH)) is one alternative to surgical castration (SC) for preventing sexual development and boar taint in male pigs. A temporal increase in performance has been described for IC pigs before the second vaccination against GnRH. The objective of this work was to assess the effects of IC on Iberian male and female pigs (fed diets of increasing CP content) on performance, nitrogen retention (NR) and digestibility, and carcass traits. Fifty-four pure Iberian pigs individually housed were allocated to a 3 × 3 factorial arrangement with three sex groups (IC males, IC females and SC males), three diets (153, 137 and 119 g CP/kg DM; 14 MJ metabolisable energy/kg DM) and six pigs per treatment combination. Pigs were vaccinated at 18 weeks of age (40 kg BW) and seven weeks later (70–80 kg BW) and fed at 0.9 × ad libitum on BW basis. Two digestibility and nitrogen balance assays were performed before and after the second vaccination, respectively. Pigs were slaughtered at 105 kg BW. Before the second vaccination, Iberian IC males showed higher growth rate (g/day), feed efficiency, NR (g/day) and efficiency of NR than the other groups (P < 0.001). The NR and efficiency of NR was 40% greater in IC v. SC males (P < 0.001). After the second vaccination, no differences in performance between sex groups were detected (P > 0.05). Growth rate and feed efficiency were higher in IC males than in the other groups for the whole experimental period (from the first vaccination to slaughter; P < 0.001). After the second vaccination, differences among sex groups in NR and the efficiency of NR disappeared (P > 0.05). NR efficiency was 0.177 on average. No significant effects of dietary CP were detected on performance. The NR was greater in pigs fed the 153 CP diet (17 to 37%; P > 0.05). Lean components of carcass (sirloin, loin and butt lean) were greater in IC males than in the other groups (0.001 < P < 0.05). There were no significant sex group × dietary CP interactions. Iberian IC males grew at higher rate, deposited more protein, and more efficiently, than Iberian SC males before the second vaccination against GnRH. Iberian IC females showed similar growth performance to SC males and intermediate protein deposition efficiency between IC and SC males. Despite the higher growth performance, protein deposition rate, and efficiency of protein deposition of IC males v. SC males, no significant differences in amino acid requirements were detected between them., Funded by European Union's Horizon 2020 research and innovation programme (Grant agreement 634476, project acronym TREASURE). The content of this paper reflects only the author's view, and the European Union Agency is not responsible for any use that may be made of the information it contains.

Immediate Post-Operative Insulin Requirements may Predict Metabolic Outcome after Total Pancreatectomy and Islet Autologous Cell Transplant (TPIAT) Introduction: Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Patients with CP experience abdominal pain, which in some instances can be refractory to medical and endoscopic intervention. Total pancreatectomy and islet auto transplantation (TPIAT) is a treatment option however predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield as well as post-TPIAT glucose management data to further understand their relationship.Methods:A total of 13 TPIAT subjects were included who underwent beta cell function assessment via intravenous glucose tolerance tests and oral mixed meal tolerance tests. Islet yield, glucose level and insulin requirement for 72 hours postoperatively were collected. In addition, their glucose control and insulin requirements at 3, 6 and 12-month post TPIAT were analyzed.Results:The median age was 45 years with median duration of CP for 5 years. The main cause of CP was idiopathic. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median post-operative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour post operatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6 and 12 month showed a positive correlation. Despite the new finding of inverse correlation of islet yield with long-term insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies.Conclusion: The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long term insulin management following TPIAT. This observation may identify a high risk group of patients in need of more intensive diabetes education and treatment prior to hospital discharge.