Publications by authors named "Darwin L Conwell"

190 Publications

Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation.

Cell Transplant 2021 Jan-Dec;30:963689721999330

University of Minnesota Medical School, Minneapolis, MN, USA.

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 ( = 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 ( = 0.03), hsa-miR-148a-3p ( = 0.04) and hsa-miR-221-3p ( = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p ( = 0.04) and hsa-miR-7-5p ( = 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 ( < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p ( < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, = 0.18; hsa-miR-148a-3p, = 0.21; hsa-miR-320d, = 0.19; and hsa-miR-221-3p, = 0.21; all < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg ( = -0.20, = 0.02). Also, hsa-miR-200c ( = 0.18, = 0.03) and hsa-miR-221-3p ( = 0.19, = 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.
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http://dx.doi.org/10.1177/0963689721999330DOI Listing
April 2021

Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected.

United European Gastroenterol J 2021 Mar;9(2):139-149

Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF.

Objective: We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF.

Methods: We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders.

Results: 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3-34.9) and three (48%, OR = 20.2, 5.9-68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality.

Conclusion: In AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.
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http://dx.doi.org/10.1002/ueg2.12057DOI Listing
March 2021

Dietary Patterns of Insulinemia, Inflammation and Glycemia, and Pancreatic Cancer Risk: Findings from the Women's Health Initiative.

Cancer Epidemiol Biomarkers Prev 2021 Apr 7. Epub 2021 Apr 7.

Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio.

Background: Pancreatic cancer risk is increasing in countries with high consumption of Western dietary patterns and rising obesity rates. We examined the hypothesis that specific dietary patterns reflecting hyperinsulinemia (empirical dietary index for hyperinsulinemia; EDIH), systemic inflammation (empirical dietary inflammatory pattern; EDIP), and postprandial glycemia [glycemic index (GI); glycemic load (GL)] are associated with pancreatic cancer risk, including the potential modifying role of type 2 diabetes (T2D) and body mass index (BMI).

Methods: We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 129,241 women, 50-79 years-old in the Women's Health Initiative. We used multivariable-adjusted Cox regression to estimate HRs and 95% confidence intervals (95% CI) for pancreatic cancer risk.

Results: During a median 19.9 years of follow-up, 850 pancreatic cancer cases were diagnosed. We observed no association between dietary scores and pancreatic cancer risk overall. However, risk was elevated among participants with longstanding T2D (present >3 years before pancreatic cancer diagnosis) for EDIH. For each 1 SD increment in dietary score, the HRs (95% CIs) were: EDIH, 1.33 (1.06-1.66); EDIP, 1.26 (0.98-1.63); GI, 1.26 (0.96-1.67); and GL, 1.23 (0.96-1.57); although interactions were not significant (all >0.05). Separately, we observed inverse associations between GI [0.86 (0.76-0.96), = 0.0068] and GL [0.83 (0.73-0.93), = 0.0075], with pancreatic cancer risk among normal-weight women.

Conclusions: We observed no overall association between the dietary patterns evaluated and pancreatic cancer risk, although women with T2D appeared to have greater cancer risk.

Impact: The elevated risk for hyperinsulinemic diets among women with longstanding T2D and the inverse association among normal-weight women warrant further examination.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1478DOI Listing
April 2021

Impact of Recreational Cannabis Legalization on Hospitalizations for Hyperemesis.

Am J Gastroenterol 2021 03;116(3):609-612

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

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.
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http://dx.doi.org/10.14309/ajg.0000000000001182DOI Listing
March 2021

Hospital outcomes and early readmission for the most common gastrointestinal and liver diseases in the United States: Implications for healthcare delivery.

World J Gastrointest Surg 2021 Feb;13(2):141-152

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States.

Background: Gastrointestinal (GI) and liver diseases contribute to substantial inpatient morbidity, mortality, and healthcare resource utilization. Finding ways to reduce the economic burden of healthcare costs and the impact of these diseases is of crucial importance. Thirty-day readmission rates and related hospital outcomes can serve as objective measures to assess the impact of and provide further insights into the most common GI ailments.

Aim: To identify the thirty-day readmission rates with related predictors and outcomes of hospitalization of the most common GI and liver diseases in the United States.

Methods: A cross-sectional analysis of the 2012 National Inpatient Sample was performed to identify the 13 most common GI diseases. The 2013 Nationwide Readmission Database was then queried with specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary outcomes were mortality (index admission, calendar-year), hospitalization costs, and thirty-day readmission and secondary outcomes were predictors of thirty-day readmission.

Results: For the year 2013, the thirteen most common GI diseases contributed to 2.4 million index hospitalizations accounting for about $25 billion. The thirty-day readmission rates were highest for chronic liver disease (25.4%), () infection (23.6%), functional/motility disorders (18.5%), inflammatory bowel disease (16.3%), and GI bleeding (15.5%). The highest index and subsequent calendar-year hospitalization mortality rates were chronic liver disease (6.1% and 12.6%), infection (2.3% and 6.1%), and GI bleeding (2.2% and 5.0%), respectively. Thirty-day readmission correlated with any subsequent admission mortality ( = 0.798, = 0.001). Medicare/Medicaid insurances, ≥ 3 Elixhauser comorbidities, and length of stay > 3 d were significantly associated with thirty-day readmission for all the thirteen GI diseases.

Conclusion: Preventable and non-chronic GI disease contributed to a significant economic and health burden comparable to chronic GI conditions, providing a window of opportunity for improving healthcare delivery in reducing its burden.
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http://dx.doi.org/10.4240/wjgs.v13.i2.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898184PMC
February 2021

Incidence and Risk of Pancreatic Cancer in Patients with a New Diagnosis of Chronic Pancreatitis.

Dig Dis Sci 2021 Feb 25. Epub 2021 Feb 25.

Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: Chronic pancreatitis (CP) is a risk factor for pancreatic ductal adenocarcinoma (PDAC); nevertheless, the true incidence of PDAC in CP patients in the United States remains unclear.

Aims: We evaluated the risk of developing PDAC two or more years after a new diagnosis of CP.

Methods: Retrospective study of veterans from September 1999 to October 2015. A three-year washout period was applied to exclude patients with preexisting CP and PDAC. PDAC risk was evaluated in patients with new-diagnosis CP and compared with controls without CP using Cox-proportional hazards model. CP, PDAC, and other covariates were extracted using ICD-9 codes.

Results: After exclusions, we identified 7,883,893 patients [new-diagnosis CP - 21,765 (0.28%)]. PDAC was diagnosed in 226 (1.04%) patients in the CP group and 15,858 (0.20%) patients in the control group (p < 0.001). CP patients had a significantly higher PDAC risk compared to controls > 2 years [adjusted hazard ratio (HR) 4.28, 95% confidence interval (CI) 3.74-4.89, p < 0.001], 5 years (adjusted HR 3.32, 95% CI 2.75-4.00, p < 0.001) and 10 years of follow-up (adjusted HR 3.14, 95% CI 1.99-4.93, p < 0.001), respectively. By multivariable analysis, age (odds ratio 1.02, 95% CI 1.00-1.03, p = 0.03), current smoker (odds ratio 1.67, 95% CI 1.02-2.74, p = 0.042), current smoker + alcoholic (odds ratio 2.29, 95% CI 1.41-3.52, p < 0.001), and diabetes (odds ratio 1.51, 95% CI 1.14-1.99, p = 0.004) were the independent risk factors for PDAC.

Conclusion: Our data show that after controlling for etiology of CP and other cofactors, the risk of PDAC increased in CP patients after two years of follow-up, and risk was consistent and sustained beyond 5 years and 10 years of follow-up.
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http://dx.doi.org/10.1007/s10620-021-06886-7DOI Listing
February 2021

Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency: Rationale and Methodology of a Prospective, Observational, Multicenter Cohort Study.

Pancreas 2021 Feb;50(2):147-152

Division of Gastroenterology, Hepatology, & Nutrition, Department of Internal Medicine, Ohio State University, Wexner Medical Center, Columbus, OH.

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.
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http://dx.doi.org/10.1097/MPA.0000000000001743DOI Listing
February 2021

Biomarkers of Chronic Pancreatitis: A systematic literature review.

Pancreatology 2021 Mar 22;21(2):323-333. Epub 2021 Jan 22.

Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Chronic pancreatitis (CP) does not have diagnostic or prognostic biomarkers. CP is the end stage of a progressive inflammatory syndrome that is diagnosed at late stages by morphologic features. To diagnose earlier stages of the disease, a new mechanistic definition was established based on identifying underlying pathogenic processes and biomarker evidence of disease activity and stage. Although multiple risk factors are known, the corresponding biomarkers needed to make a highly accurate diagnosis of earlier disease stages have not been established. The goal of this study is to systematically analyze the literature to identify the most likely candidates for development into biomarkers of CP.

Methods: We conducted a systematic review of candidate analytes from easily accessible biological fluids and identified 67 studies that compared CP to nonpancreatic-disease controls. We then ranked candidate biomarkers for sensitivity and specificity by area under the receiver operator curves (AUROCs).

Results: Five biomarkers had a large effect size (an AUROC > 0.96), whereas 30 biomarkers had a moderate effect size (an AUROC between 0.96 and 0.83) for distinguishing CP cases from controls or other diseases. However, the studies reviewed had marked variability in design, enrollment criteria, and biospecimen sample handling and collection.

Conclusions: Several biomarkers have the potential for evaluation in prospective cohort studies and should be correlated with risk factors, clinical features, imaging studies and outcomes. The Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreas Cancer provides recommendations for avoiding design biases and heterogeneity in sample collection and handling in future studies.
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http://dx.doi.org/10.1016/j.pan.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969447PMC
March 2021

High performance in risk stratification of intraductal papillary mucinous neoplasms by confocal laser endomicroscopy image analysis with convolutional neural networks (with video).

Gastrointest Endosc 2021 Jan 16. Epub 2021 Jan 16.

Division of Gastroenterology, Hepatology, and Nutrition, Division of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background And Aims: EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) can differentiate high-grade dysplasia/adenocarcinoma (HGD-Ca) in intraductal papillary mucinous neoplasms (IPMNs) but requires manual interpretation. We sought to derive predictive computer-aided diagnosis (CAD) and artificial intelligence (AI) algorithms to facilitate accurate diagnosis and risk stratification of IPMNs.

Methods: A post hoc analysis of a single-center prospective study evaluating EUS-nCLE (2015-2019; INDEX study) was conducted using 15,027 video frames from 35 consecutive patients with histopathologically proven IPMNs (18 with HGD-Ca). We designed 2 CAD-convolutional neural network (CNN) algorithms: (1) a guided segmentation-based model (SBM), where the CNN-AI system was trained to detect and measure papillary epithelial thickness and darkness (indicative of cellular and nuclear stratification), and (2) a reasonably agnostic holistic-based model (HBM) where the CNN-AI system automatically extracted nCLE features for risk stratification. For the detection of HGD-Ca in IPMNs, the diagnostic performance of the CNN-CAD algorithms was compared with that of the American Gastroenterological Association (AGA) and revised Fukuoka guidelines.

Results: Compared with the guidelines, both n-CLE-guided CNN-CAD algorithms yielded higher sensitivity (HBM, 83.3%; SBM, 83.3%; AGA, 55.6%; Fukuoka, 55.6%) and accuracy (SBM, 82.9%; HBM, 85.7%; AGA, 68.6%; Fukuoka, 74.3%) for diagnosing HGD-Ca, with comparable specificity (SBM, 82.4%; HBM, 88.2%; AGA, 82.4%; Fukuoka, 94.1%). Both CNN-CAD algorithms, the guided (SBM) and agnostic (HBM) models, were comparable in risk stratifying IPMNs.

Conclusion: EUS-nCLE-based CNN-CAD algorithms can accurately risk stratify IPMNs. Future multicenter validation studies and AI model improvements could enhance the accuracy and fully automatize the process for real-time interpretation.
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http://dx.doi.org/10.1016/j.gie.2020.12.054DOI Listing
January 2021

Insulinemic and Inflammatory Dietary Patterns Show Enhanced Predictive Potential for Type 2 Diabetes Risk in Postmenopausal Women.

Diabetes Care 2021 Mar 8;44(3):707-714. Epub 2021 Jan 8.

Interdisciplinary PhD Program in Nutrition, The Ohio State University, Columbus, OH

Objective: The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk.

Research Design And Methods: We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 73,495 postmenopausal women in the Women's Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes.

Results: During a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32-1.68; < 0.0001) and EDIP 1.45 (1.29-1.63; < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88-1.12; = 0.46) and GL 1.01 (0.89-1.16; = 0.30).

Conclusions: Our findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.
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http://dx.doi.org/10.2337/dc20-2216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896263PMC
March 2021

Delayed Processing of Secretin-Induced Pancreas Fluid Influences the Quality and Integrity of Proteins and Nucleic Acids.

Pancreas 2021 Jan;50(1):17-28

From the Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine.

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 influence 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, and 4 hours on ice; or after storage overnight at 4°C with or without RNase or protease inhibitors (PIs). Electrophoresis and mass spectrometry analysis determined protein abundance and quality, whereas 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 PIs delayed degradation. RNA was significantly degraded under all conditions compared with the snap frozen samples. Isolated RNA from PF-derived exosomes exhibited similar poor quality as RNA isolated from matched PF samples.

Conclusions: Adding PIs 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.
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http://dx.doi.org/10.1097/MPA.0000000000001717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883383PMC
January 2021

Predictors of hospital transfer and associated risks of mortality in acute pancreatitis.

Pancreatology 2021 Jan 14;21(1):25-30. Epub 2020 Dec 14.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1016/j.pan.2020.12.001DOI Listing
January 2021

Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort.

Pancreatology 2021 Jan 24;21(1):275-281. Epub 2020 Nov 24.

University of Minnesota Minneapolis, MN, USA.

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 < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement.

Conclusions: ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.
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http://dx.doi.org/10.1016/j.pan.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924984PMC
January 2021

Soy-tomato enriched diet reduces inflammation and disease severity in a pre-clinical model of chronic pancreatitis.

Sci Rep 2020 12 11;10(1):21824. Epub 2020 Dec 11.

James Comprehensive Cancer Center, The Ohio State University, Columbus, USA.

Chronic pancreatitis (CP) is a fibro-inflammatory syndrome in individuals who develop persistent pathological responses to parenchymal injury or stress. Novel therapeutic or dietary interventions that could lessen inflammation in this disease could significantly improve quality of life in patients with CP. Complex dietary foods like soy and tomatoes are composed of active metabolites with anti-inflammatory effects. Data from our group reports that bioactive agents in soy and tomatoes can reduce pro-inflammatory cytokines and suppressive immune populations. Additionally, our team has developed a novel soy-tomato juice currently being studied in healthy individuals with no toxicities, and good compliance and bioavailability. Thus, we hypothesize that administration of a soy-tomato enriched diet can reduce inflammation and severity of CP. C57BL/6 mice were injected intraperitoneally with 50 μg/kg caeurlein (7 hourly injections, twice weekly) for 6 weeks to induce CP. After 4 weeks of caerulein injections, mice were administered a control or a soy-tomato enriched diet for 2 weeks. Disease severity was measured via immunohistochemical analysis of pancreata measuring loss of acini, fibrosis, inflammation, and necrosis. Serum lipase and amylase levels were analyzed at the end of the study. Inflammatory factors in the serum and pancreas, and immune populations in the spleen of mice were analyzed by cytokine multiplex detection, qRT-PCR, and flow cytometry respectively. Infra-red (IR) sensing of mice was used to monitor spontaneous activity and distress of mice. Mice fed a soy-tomato enriched diet had a significantly reduced level of inflammation and severity of CP (p = 0.032) compared to mice administered a control diet with restored serum lipase and amylase levels (p < 0.05). Mice with CP fed a soy-tomato diet had a reduction in inflammatory factors (TNF-α, IL-1β, IL-5) and suppressive immune populations (myeloid-derived suppressor cells; MDSC) compared to control diet fed mice (p < 0.05). Infra-red sensing to monitor spontaneous activity of mice showed that soy-tomato enriched diet improved total activity and overall health of mice with CP (p = 0.055) and CP mice on a control diet were determined to spend more time at rest (p = 0.053). These pre-clinical results indicate that a soy-tomato enriched diet may be a novel treatment approach to reduce inflammation and pain in patients with CP.
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http://dx.doi.org/10.1038/s41598-020-78762-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733503PMC
December 2020

Psychological Health Among Gastroenterologists During the COVID-19 Pandemic: A National Survey.

Clin Gastroenterol Hepatol 2021 04 3;19(4):836-838.e3. Epub 2020 Dec 3.

Division of Gastroenterology, Hepatology & Nutrition, The Ohio State Wexner Medical Center, Columbus, Ohio. Electronic address:

The COVID-19 pandemic poses unprecedented and unique challenges to gastroenterologists eager to maintain clinical practice, patients' health, and their own physical/mental well-being. We aimed to estimate the prevalence and critical determinants of psychological distress in gastroenterologists during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.cgh.2020.11.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955767PMC
April 2021

Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

Clin Gastroenterol Hepatol 2020 Oct 1. Epub 2020 Oct 1.

Division of Gastroenterology, Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

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.
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http://dx.doi.org/10.1016/j.cgh.2020.09.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527302PMC
October 2020

Class III obesity rather than metabolic syndrome impacts clinical outcomes of acute pancreatitis: A propensity score weighted analysis.

Pancreatology 2020 Oct 23;20(7):1287-1295. Epub 2020 Aug 23.

Division of Gastroenterology, Hepatology, and Nutrition, Division of Internal Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH, 43210, USA; The Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, 43210, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.pan.2020.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780090PMC
October 2020

Reduction of inflammation in chronic pancreatitis using a soy bread intervention: A feasibility study.

Pancreatology 2020 Jul 6;20(5):852-859. Epub 2020 Jun 6.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Introduction: Chronic pancreatitis is a chronic inflammatory disease, which progresses to fibrosis. Currently there are no interventions to delay or stop the progression to irreversible organ damage. In this study, we assessed the tolerability and feasibility of administering soy bread to reduce circulating inflammatory mediators.

Methods: Subjects with chronic pancreatitis diagnosed using the American Pancreatic Association diagnostic guidelines were enrolled. During the dose escalation (DE) phase, subjects received one week of soy bread based using a 3 + 3 dose-escalation design, which was then followed by a maximally tolerated dose (MTD) phase with four weeks of intervention. Dose-limiting toxicities (DLTs) were monitored. Plasma cytokine levels were measured using a Meso Scale Discovery multiplex assay kit. Isoflavonoid excretion in 24-h urine collection was used to measure soy bread compliance.

Results: Nine subjects completed the DE phase, and one subject completed the MTD phase without any DLTs at a maximum dosage of three slices (99 mg of isoflavones) per day. Reported compliance to soy bread intervention was 98%, and this was confirmed with urinary isoflavones and their metabolites detected in all subjects. There was a significant decline in the TNF-α level during the DE phase (2.667 vs 2.382 pg/mL, p = 0.039); other levels were similar.

Conclusions: In this feasibility study, there was excellent compliance with a short-term intervention using soy bread in chronic pancreatitis. Reduction was seen in at least one pro-inflammatory cytokine with short-term intervention. Larger cohorts and longer interventions with soy are warranted to assess the efficacy of reducing pro-inflammatory mediators of disease.
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http://dx.doi.org/10.1016/j.pan.2020.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780088PMC
July 2020

CD200 promotes immunosuppression in the pancreatic tumor microenvironment.

J Immunother Cancer 2020 06 23;8(1). Epub 2020 Jun 23.

The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States

Background: A significant challenge to overcome in pancreatic ductal adenocarcinoma (PDAC) is the profound systemic immunosuppression that renders this disease non-responsive to immunotherapy. Our supporting data provide evidence that CD200, a regulator of myeloid cell activity, is expressed in the PDAC microenvironment. Additionally, myeloid-derived suppressor cells (MDSC) isolated from patients with PDAC express elevated levels of the CD200 receptor (CD200R). Thus, we hypothesize that CD200 expression in the PDAC microenvironment limits responses to immunotherapy by promoting expansion and activity of MDSC.

Methods: Immunofluorescent staining was used to determine expression of CD200 in murine and human PDAC tissue. Flow cytometry was utilized to test for CD200R expression by immune populations in patient blood samples. In vivo antibody blocking of CD200 was conducted in subcutaneous MT-5 tumor-bearing mice and in a genetically engineered PDAC model (KPC-Brca2 mice). Peripheral blood mononuclear cells (PBMC) from patients with PDAC were analyzed by single-cell RNA sequencing. MDSC expansion assays were completed using healthy donor PBMC stimulated with IL-6/GM-CSF in the presence of recombinant CD200 protein.

Results: We found expression of CD200 by human pancreatic cell lines (BxPC3, MiaPaca2, and PANC-1) as well as on primary epithelial pancreatic tumor cells and smooth muscle actin+ stromal cells. CD200R expression was found to be elevated on CD11b+CD33+HLA-DR MDSC immune populations from patients with PDAC (p=0.0106). Higher expression levels of CD200R were observed in CD15+ MDSC compared with CD14+ MDSC (p<0.001). In vivo studies demonstrated that CD200 antibody blockade limited tumor progression in MT-5 subcutaneous tumor-bearing and in KPC-Brca2 mice (p<0.05). The percentage of intratumoral MDSC was significantly reduced in anti-CD200 treated mice compared with controls. Additionally, in vivo blockade of CD200 can also significantly enhance the efficacy of PD-1 checkpoint antibodies compared with single antibody therapies (p<0.05). Single-cell RNA sequencing of PBMC from patients revealed that CD200R+ MDSC expressed genes involved in cytokine signaling and MDSC expansion. Further, in vitro cytokine-driven expansion and the suppressive activity of human MDSC was enhanced when cocultured with recombinant CD200 protein.

Conclusions: These results indicate that CD200 expression in the PDAC microenvironment may regulate MDSC expansion and that targeting CD200 may enhance activity of checkpoint immunotherapy.
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http://dx.doi.org/10.1136/jitc-2019-000189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312341PMC
June 2020

Report on the Short Endoscopic Exocrine Pancreatic Function Test in Children and Young Adults.

Pancreas 2020 May/Jun;49(5):642-649

From the Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL.

Objectives: Endoscopic pancreatic function test (ePFT) has been in use for exocrine function testing since the 1990s. In patients, short ePFT assesses acinar function, unlike the longer version for ductal function in adults. The present study summarizes characteristics of 1913 short ePFTs (S-ePFT) performed at 2 centers since 2001.

Methods: The main indications in patients presenting at ages infancy to 24.3 years, for the S-ePFT were failure to thrive, weight loss, diarrhea, and abdominal pain with bloating. Secretin was administered as bolus, and 4 aliquots of fluid were collected between 4 and 10 minutes after administration. Amylase, lipase, trypsin, and chymotrypsin activities were measured in the laboratory.

Results: The pH of consecutive samples increased by 0.3 to 0.7. Overall, 36.7% had abnormal S-ePFT with selective amylase deficiency (9.5%) and generalized enzyme deficiency (8.9%) being the most frequent. Retest reproducibility, repeatability, and clinical validity were high. By adding S-ePFT to endoscopy for the suspicion of malabsorption, the abnormal findings increased by 36.9%.

Conclusions: Short ePFT assesses pancreatic acinar function in a reliable and clinically meaningful way in patients. Diagnostic yield of endoscopy increased substantially albeit with increased sedation time. By S-ePFT ductal function, cytokines and proteomics can also be assessed.
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http://dx.doi.org/10.1097/MPA.0000000000001540DOI Listing
May 2020

Identification of Individuals at Increased Risk for Pancreatic Cancer in a Community-Based Cohort of Patients With Suspected Chronic Pancreatitis.

Clin Transl Gastroenterol 2020 04;11(4):e00147

Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA.

Objectives: We lack reliable methods for identifying patients with chronic pancreatitis (CP) at increased risk for pancreatic cancer. We aimed to identify radiographic parameters associated with pancreatic cancer in this population.

Methods: We conducted a retrospective cohort study of patients with suspected CP within an integrated healthcare system in Southern California in 2006-2015. Patients were identified by a diagnostic code and confirmed by imaging findings (parenchymal calcification, ductal stones, glandular atrophy, pseudocyst, main duct dilatation, duct irregularity, abnormal side branch, or stricture) defined by the natural language processing of radiographic reports. We used Cox regression to determine the relationship of smoking, alcohol use, acute pancreatitis, diabetes, body mass index, and imaging features with the risk of incident pancreatic cancer at least 1 year after abnormal pancreas imaging.

Results: We identified 1,766 patients with a diagnostic code and an imaging feature for CP with a median follow-up of 4.5 years. There were 46 incident pancreatic cancer cases. Factors that predicted incident pancreatic cancer after 1-year of follow-up included obesity (hazard ratio 2.7, 95% confidence interval: 1.2-6.1) and duct dilatation (hazard ratio 10.5, 95% confidence limit: 4.0-27). Five-year incidence of pancreatic cancer in this population with duct dilatation was 6.3%.

Discussion: High incidence of pancreatic cancer in suspected patients with CP with pancreatic duct dilatation warrants regular surveillance for pancreatic cancer.
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http://dx.doi.org/10.14309/ctg.0000000000000147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263650PMC
April 2020

Inter-observer variability of radiologists for Cambridge classification of chronic pancreatitis using CT and MRCP: results from a large multi-center study.

Abdom Radiol (NY) 2020 05;45(5):1481-1487

Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Purpose: Determine inter-observer variability among radiologists in assigning Cambridge Classification (CC) of chronic pancreatitis (CP) based on magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) and contrast-enhanced CT (CECT).

Methods: Among 422 eligible subjects enrolled into the PROCEED study between 6/2017 and 8/2018, 39 were selected randomly for this study (chronic abdominal pain (n = 8; CC of 0), suspected CP (n = 22; CC of 0, 1 or 2) or definite CP (n = 9; CC of 3 or 4). Each imaging was scored by the local radiologist (LRs) and three of five central radiologists (CRs) at other consortium sites. The CRs were blinded to clinical data and site information of the participants. We compared the CC score assigned by the LR with the consensus CC score assigned by the CRs. The weighted kappa statistic (K) was used to estimate the inter-observer agreement.

Results: For the majority of subjects (34/39), the group assignment by LR agreed with the consensus composite CT/MRCP score by the CRs (concordance ranging from 75 to 89% depending on cohort group). There was moderate agreement (63% and 67% agreed, respectively) between CRs and LRs in both the CT score (weighted Kappa [95% CI] = 0.56 [0.34, 0.78]; p-value = 0.57) and the MR score (weighted Kappa [95% CI] = 0.68 [0.49, 0.86]; p-value = 0.72). The composite CT/MR score showed moderate agreement (weighted Kappa [95% CI] = 0.62 [0.43, 0.81]; p-value = 0.80).

Conclusion: There is a high degree of concordance among radiologists for assignment of CC using MRI and CT.
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http://dx.doi.org/10.1007/s00261-020-02521-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233445PMC
May 2020

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.

Clin Gastroenterol Hepatol 2021 Feb 30;19(2):349-357. Epub 2020 Mar 30.

Division of Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania.

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.
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http://dx.doi.org/10.1016/j.cgh.2020.03.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529676PMC
February 2021

Lipocalin-2 expression and function in pancreatic diseases.

Pancreatology 2020 Apr 7;20(3):419-424. Epub 2020 Jan 7.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA; The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Lipocalin-2 (LCN2) is a secreted molecule, expressed in various cell types, that is involved in the progression of numerous diseases and disorders. The biological functions and expression levels of LCN2 in diseases including pancreatic cancer, pancreatitis (acute and chronic), and diabetes mellitus, suggest the potential role of LCN2 as a biomarker and/or therapeutic target. However, findings on the role of LCN2 in pancreatic diseases have been contradictory. In pancreatic cancer and pancreatitis, LCN2 has been identified as a potential biomarker; increased expression levels in various biological specimens correlate with the presence of the disease and may be able to differentiate cancer and chronic pancreatitis from healthy subjects. LCN2 is also known to be an adipokine; it is upregulated in obesity and is a common co-factor in the development of pancreatic diseases. Emerging research suggests LCN2 is elevated in type 2 diabetes mellitus, but the exact role of LCN2 in this disease is not clear. In this review, we summarize research on LCN2 as it relates to pancreatic diseases, highlighting the discrepancies in the literature. By explaining and clarifying the role of LCN2 in these disorders, we aim to promote research in developing novel diagnostic and treatment strategies to reduce the burden of pancreatic diseases.
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http://dx.doi.org/10.1016/j.pan.2020.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160010PMC
April 2020

Diverticulitis in Morbidly Obese Adults: A Rise in Hospitalizations with Worse Outcomes According to National US Data.

Dig Dis Sci 2020 09 3;65(9):2644-2653. Epub 2020 Jan 3.

Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.

Background And Aims: Obesity is a known risk factor for diverticulitis. Our objective was to examine the less investigated impact of morbid obesity (MO) on admissions and clinical course of diverticulitis in a US representative database.

Methods: We retrospectively queried the 2010-2014 Nationwide Readmission Database to compare diverticulitis hospitalizations in 48,651 MO and 841,381 non-obese patients. Outcomes of mortality, clinical course, surgical events, and readmissions were compared using multivariable and propensity-score-matched analyses.

Results: The number of MO patients admitted with diverticulitis increased annually from 7570 in 2010 to 11,935 in 2014, while the total number of patients admitted with diverticulitis decreased (p = 0.003). Multivariable analysis demonstrates that MO was associated with increased mortality (adjusted odds ratio [aOR] 1.54; 95% confidence internal [CI]: 1.16, 2.05), intensive care admissions (aOR = 1.92; 95% CI: 1.61, 2.31), emergent surgery (aOR = 1.20; 95% CI: 1.11, 1.30), colectomy (aOR = 1.13; 95% CI: 1.08, 1.18), open laparotomy (aOR = 1.28; 95% CI: 1.21, 1.34), and colostomy (aOR = 1.34; 95% CI: 1.25, 1.43). Additionally, MO was associated with higher risk for multiple readmissions for diverticulitis within 30 days (aOR = 1.45; 95% CI: 1.08, 1.96) and 6 months (aOR = 1.21; 95% CI: 1.03, 1.42). A one-to-one matched propensity-score analysis confirmed our multivariable analysis findings.

Conclusions: Analysis of national data demonstrates an increasing trend of MO patients' admissions for diverticulitis, with a presentation at a younger age. Furthermore, MO is associated with an increased risk of adverse outcomes and readmissions of diverticulitis. Future strategies are needed to ameliorate these outcomes.
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http://dx.doi.org/10.1007/s10620-019-06002-wDOI Listing
September 2020

Unavailability of Endoscopic Retrograde Cholangiography Adversely Impacts Hospital Outcomes of Acute Biliary Pancreatitis: A National Survey and Propensity-Matched Analysis.

Pancreas 2020 01;49(1):39-45

From the Division of Gastroenterology, Hepatology, and Nutrition.

Objectives: There is a paucity of literature assessing the impact of endoscopic retrograde cholangiopancreatography (ERCP) availability at hospitals and the management of acute biliary pancreatitis (ABP). Thus, we sought to evaluate the impact of ERCP availability on the clinical outcomes of ABP.

Methods: The Nationwide Inpatient Sample (2004-2013) was reviewed to identify adult inpatients (≥18 years) with ABP. Clinical outcomes (mortality, severe acute pancreatitis, and health care resource utilization) between hospitals that perform ERCP versus hospitals that do not perform ERCP were compared using multivariate and propensity score-matched analyses.

Results: A majority of the non-ERCP hospitals were rural (73%) in location. Multivariate analysis demonstrated that the lack of ERCP availability was independently associated with increased mortality from ABP (odds ratio, 1.83; 95% confidence interval, 1.16-2.88). A propensity score-matched cohort analysis confirmed a significant increase in mortality from ABP in non-ERCP hospitals (1.1% vs 0.53%; odds ratio, 2.08; 95% confidence interval, 1.05-4.15, P = 0.037) compared with ERCP hospitals.

Conclusions: This national survey reveals increased mortality for patients with ABP admitted to hospitals lacking ERCP services. While there is a need to increase ERCP availability in rural areas, optimizing strategies for early transfer of patients with ABP to hospitals with ERCP availability can potentially offset these limitations.
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http://dx.doi.org/10.1097/MPA.0000000000001435DOI Listing
January 2020

Chronic Pancreatitis: Managing a Difficult Disease.

Am J Gastroenterol 2020 01;115(1):49-55

Section of Pancreatic Disorders, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Chronic pancreatitis is characterized by progressive, irreversible morphologic and functional changes that are most commonly attributed to environmental insults, particularly when there is a genetic or anatomic predisposition. Heavy alcohol use and cigarette smoking are the most common environmental risk factors, but both may be absent. Antecedent episodes of acute pancreatitis occur in about half of patients. Abdominal pain is the most common symptom and requires a tailored approach depending on the anatomic changes in the pancreas. Other clinical manifestations include diabetes mellitus, exocrine pancreatic insufficiency, metabolic bone disease, pancreatic cancer, and anatomic complications. Current disease management is centered on risk factor reduction and screening for and treating disease complications. There are no current therapies to delay or retard disease progression, but there are ongoing efforts to more fully understand the natural history of chronic pancreatitis and underlying mechanisms of disease. These studies are expected to provide insights that will transform our approach to disease management and provide increased hope to patients.
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http://dx.doi.org/10.14309/ajg.0000000000000421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940526PMC
January 2020

Pancreatic Cysts in the Elderly.

Curr Treat Options Gastroenterol 2019 Dec;17(4):457-469

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Room 226, Columbus, OH, 43210, USA.

Purpose Of Review: 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.

Recent Findings: 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.
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http://dx.doi.org/10.1007/s11938-019-00260-3DOI Listing
December 2019

A Study on the Effect of Patient Characteristics, Geographical Utilization, and Patient Outcomes for Total Pancreatectomy Alone and Total Pancreatectomy With Islet Autotransplantation in Patients With Pancreatitis in the United States.

Pancreas 2019 10;48(9):1204-1211

From the Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH.

Objectives: A selective therapy for pancreatitis is total pancreatectomy and islet autotransplantation. Outcomes and geographical variability of patients who had total pancreatectomy (TP) alone or total pancreatectomy with islet autotransplantation (TPIAT) were assessed.

Methods: Data were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample database. Weighed univariate and multivariate analyses were performed to determine the effect of measured variables on outcomes.

Results: Between 2002 and 2013, there were 1006 TP and 825 TPIAT in patients with a diagnosis of chronic pancreatitis, and 1705 TP and 830 TPIAT for any diagnosis of pancreatitis. The majority of the TP and TPIAT were performed in larger urban hospitals. Costs were similar for TP and TPIAT for chronic pancreatitis but were lower for TPIAT compared with TP for any type of pancreatitis. The trend for TP and TPIAT was significant in all geographical areas during the study period.

Conclusions: There is an increasing trend of both TP and TPIAT. Certain groups are more likely to be offered TPIAT compared with TP alone. More data are needed to understand disparities and barriers to TPIAT, and long-term outcomes of TPIAT such as pain control and glucose intolerance need further study.
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http://dx.doi.org/10.1097/MPA.0000000000001405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952005PMC
October 2019