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Item Acute pancreatitis precedes chronic pancreatitis in the majority of patients: Results from the NAPS2 consortium(Elsevier, 2022-12) Singh, Vikesh K.; Whitcomb, David C.; Banks, Peter A.; AlKaade, Samer; Anderson, Michelle A.; Amann, Stephen T.; Brand, Randall E.; Conwel, Darwin L.; Cote, Gregory A.; Gardner, Timothy B.; Gelrud, Andres; Guda, Nalini; Forsmark, Christopher E.; Lewis, Michele; Sherman, Stuart; Muniraj, Thiruvengadam; Romagnuolo, Joseph; Tan, Xiaoqing; Tang, Gong; Sandhu, Bimaljit S.; Slivka, Adam; Wilcox, C. Mel; Yadav, Dhiraj; Medicine, School of MedicineIntroduction: The mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort. Methods: We evaluated data from 883 patients with CP prospectively enrolled in the North American Pancreatitis Studies across 27 US centers between 2000 and 2014. We determined how often patients had one or more episodes of AP and its occurrence in relationship to the diagnosis of CP. We used multivariable logistic regression to determine associations for prior AP. Results: There were 624/883 (70.7%) patients with prior AP, among whom 161 (25.8%) had AP within 2 years, 115 (18.4%) within 3–5 years, and 348 (55.8%) >5 years prior to CP diagnosis. Among 504 AP patients with available information, 436 (86.5%) had >1 episode. On multivariable analyses, factors associated with increased odds of having prior AP were a younger age at CP diagnosis, white race, abdominal pain, pseudocyst(s) and pancreatic duct dilatation/stricture, while factors associated with a lower odds of having prior AP were exocrine insufficiency and pancreatic atrophy. When compared with patients with 1 episode, those with >1 AP episode were diagnosed with CP an average of 5 years earlier. Conclusions: Nearly three-quarters of patients were diagnosed with AP prior to CP diagnosis. Identifying which AP patients are at-risk for future progression to CP may provide opportunities for primary and secondary prevention.Item Chronic pancreatitis: Pediatric and adult cohorts show similarities in disease progress despite different risk factors(Lippincott, Williams & Wilkins, 2020-04) Schwarzenberg, Sarah J.; Uc, Aliye; Zimmerman, Bridget; Wilschanski, Michael; Wilcox, C. Mel; Whitcomb, David C.; Werlin, Steven L.; Troendle, David; Tang, Gong; Slivka, Adam; Singh, Vikesh K.; Sherman, Stuart; Shah, Uzma; Sandhu, Bimaljit S.; Romagnuolo, Joseph; Rhee, Sue; Pohl, John F.; Perito, Emily R.; Ooi, Chee Y.; Nathan, Jaimie D.; Muniraj, Thiruvengadam; Morinville, Veronique D.; McFerron, Brian; Mascarenhas, Maria; Maqbool, Asim; Liu, Quin; Lin, Tom K.; Lewis, Michele; Husain, Sohail Z.; Himes, Ryan; Heyman, Melvin B.; Guda, Nalini; Gonska, Tanja; Giefer, Matthew J.; Gelrud, Andres; Gariepy, Cheryl E.; Gardner, Timothy B.; Freedman, Steven D.; Forsmark, Christopher E.; Fishman, Douglas S.; Cote, Gregory A.; Conwell, Darwin; Brand, Randall E.; Bellin, Melena; Barth, Bradley; Banks, Peter A.; Anderson, Michelle A.; Amann, Stephen T.; Alkaade, Samer; Abu-El-Haija, Maisam; Abberbock, Judah N.; Lowe, Mark E.; Yadav, Dhiraj; Medicine, School of MedicineObjectives: To investigate the natural history of chronic pancreatitis (CP), patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared. Methods: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1,063 adults were compared using appropriate statistical tests for categorical and continuous variables. Results: Alcohol was a risk in 53% of adults and 1% of children (p<0.0001); tobacco in 50% of adults and 7% of children (p<0.0001). Obstructive factors were more common in children (29% vs 19% in adults, p=0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, p=0.107). Diabetes was more common in adults than children (36% vs 4% respectively, p<0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared to INSPPIRE subjects. These two cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, p=0.011). Conclusions: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.Item Clinical Study Bedside Endoscopic Ultrasound in Critically Ill patients(Hindawi, 2011) Mohamadnejad, Mehdi; Leblanc, Julia K.; Sherman, Stuart; Al-haddad, Mohammad; Mchenry, Lee; Cote, Gregory A.; Dewitt, John M.Background. The aim of this study was to evaluate the role and impact of EUS in the management of critically ill patients. Methods. We retrospectively identified all patients at our institution over a 68-month period in whom bedside inpatient EUS was performed. EUS was considered to have a significant impact if a new diagnosis was established and/or the findings altered subsequent clinical management. Results. Fifteen patients (9 male; mean age 58 ± 15 years) underwent bedside EUS without complications. EUS-FNA (median 4 passes; range 2–7) performed in 12 (80%) demonstrated a malignant mediastinal mass/lymph node (5), pancreatic abscess (1), excluded a pelvic abscess (1), established enlarged gastric folds as benign (1) and excluded malignancy in enlarged mediastinal (1) and porta hepatis adenopathy (1). In two patients, EUS-FNA failed to diagnose mediastinal histoplasmosis (1) and a hemorrhagic pancreatic pseudocyst (1). In three diagnostic exams without FNA, EUS correctly excluded choledocholithaisis (n = 1) and cholangiocarcinoma (1), and found gastric varices successfully thrombosed after previous cyanoacrylate injection (1). EUS was considered to have an impact in 13/15 (87%) patients. Conclusions. In this series, bedside EUS in critically ill patients was technically feasible, safe and had a major impact on the majority of patients. 1.Item Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop(Wolters Kluwer, 2022) Hart, Phil A.; Andersen, Dana K.; Lyons, Erica; Cote, Gregory A.; Cruz-Monserrate, Zobeida; Dworkin, Robert H.; Elmunzer, B. Joseph; Fogel, Evan L.; Forsmark, Christopher E.; Gilron, Ian; Golden, Megan; Gozu, Aysegul; McNair, Lindsay; Pandol, Stephen J.; Perito, Emily R.; Evans Phillips, Anna; Rabbitts, Jennifer A.; Whitcomb, David C.; Windsor, John A.; Yadav, Dhiraj; Palermo, Tonya M.; Medicine, School of MedicineRecurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials.Item Development and initial validation of an instrument for video-based assessment of technical skill in ERCP(Elsevier, 2021) Elmunzer, B. Joseph; Walsh, Catharine M.; Guiton, Gretchen; Serrano, Jose; Chak, Amitabh; Edmundowicz, Steven; Kwon, Richard S.; Mullady, Daniel; Papachristou, Georgios I.; Elta, Grace; Baron, Todd H.; Yachimski, Patrick; Fogel, Evan L.; Draganov, Peter V.; Taylor, Jason R.; Scheiman, James; Singh, Vikesh K.; Varadarajulu, Shyam; Willingham, Field F.; Cote, Gregory A.; Cotton, Peter B.; Simon, Violette; Spitzer, Rebecca; Keswani, Rajesh; Wani, Sachin; SVI study group; U.S. Cooperative for Outcomes Research in Endoscopy; Medicine, School of MedicineBackground and aims: The accurate measurement of technical skill in ERCP is essential for endoscopic training, quality assurance, and coaching of this procedure. Hypothesizing that technical skill can be measured by analysis of ERCP videos, we aimed to develop and validate a video-based ERCP skill assessment tool. Methods: Based on review of procedural videos, the task of ERCP was deconstructed into its basic components by an expert panel that developed an initial version of the Bethesda ERCP Skill Assessment Tool (BESAT). Subsequently, 2 modified Delphi panels and 3 validation exercises were conducted with the goal of iteratively refining the tool. Fully crossed generalizability studies investigated the contributions of assessors, ERCP performance, and technical elements to reliability. Results: Twenty-nine technical elements were initially generated from task deconstruction. Ultimately, after iterative refinement, the tool comprised 6 technical elements and 11 subelements. The developmental process achieved consistent improvements in the performance characteristics of the tool with every iteration. For the most recent version of the tool, BESAT-v4, the generalizability coefficient (a reliability index) was .67. Most variance in BESAT scores (43.55%) was attributed to differences in endoscopists' skill, indicating that the tool can reliably differentiate between endoscopists based on video analysis. Conclusions: Video-based assessment of ERCP skill appears to be feasible with a novel instrument that demonstrates favorable validity evidence. Future steps include determining whether the tool can discriminate between endoscopists of varying experience levels and predict important outcomes in clinical practice.Item 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(Elsevier, 2020) Lewis, Michele D.; Talluri, Jyothsna; Wilcox, C. Mel; Abberbock, Judah N.; Tang, Gong; Conwell, Darwin L.; Banks, Peter A.; Cote, Gregory A.; Sherman, Stuart; Alkaade, Samer; Gardner, Timothy B.; Anderson, Michelle A.; Sandhu, Bimaljit S.; Muniraj, Thiruvengadam; Forsmark, Chris E.; Guda, Nalini; Gelrud, Andres; Romagnuolo, Joseph; Brand, Randall; LaRusch, Jessica; Amann, Stephen T.; Slivka, Adam; Whitcomb, David C.; Yadav, Dhiraj; Medicine, School of MedicineBackground & 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 years) and late-onset ICP (LO-ICP; median age, 56.2 years). 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, or ACP. Methods We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2 studies, 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 to about one-quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.Item Dynamic changes in the pancreatitis activity scoring system during hospital course in a multicenter, prospective cohort(Wiley, 2021) Paragomi, Pedram; Tuft, Marie; Pothoulakis, loannis; Singh, Vikesh K.; Stevens, Tyler; Nawaz, Haq; Easler, Jeffrey J.; Thakkar, Shyam; Cote, Gregory A.; Lee, Peter J.; Akshintala, Venkata; Kamal, Ayesha; Gougol, Amir; Evans Phillips, Anna; Machicado, Jorge D.; Whitcomb, David C.; Greer, Phil J.; Buxbaum, James L.; Hart, Phil; Conwell, Darwin; Tang, Gong; Wu, Bechien U.; Papachristou, Georgios I.; Medicine, School of MedicineBackground and aim: The primary aim was to validate the Pancreatitis Activity Scoring System (PASS) in a multicenter prospectively ascertained acute pancreatitis (AP) cohort. Second, we investigated the association of early PASS trajectories with disease severity and length of hospital stay (LOS). Methods: Data were prospectively collected through the APPRENTICE consortium (2015-2018). AP severity was categorized based on revised Atlanta classification. Delta PASS (ΔPASS) was calculated by subtracting activity score from baseline value. PASS trajectories were compared between severity subsets. Subsequently, the cohort was subdivided into three LOS subgroups as short (S-LOS): 2-3 days; intermediate (I-LOS): 3-7 days; and long (L-LOS): ≥7 days. The generalized estimating equations model was implemented to compare PASS trajectories. Results: There were 434 subjects analyzed including 322 (74%) mild, 86 (20%) moderately severe, and 26 (6%) severe AP. Severe AP subjects had the highest activity levels and the slowest rate of decline in activity (P = 0.039). Focusing on mild AP, L-LOS subjects (34%) had 28 points per day slower decline; whereas, S-LOS group (13%) showed 34 points per day sharper decrease compared with I-LOS (53%; P < 0.001). We noticed an outlier subset with a median admission-PASS of 466 compared with 140 in the rest. Morphine equivalent dose constituted 80% of the total PASS in the outliers (median morphine equivalent dose score = 392), compared with only 25% in normal-range subjects (score = 33, P value < 0.001). Conclusions: This study highlighted that PASS can quantify AP activity. Significant differences in PASS trajectories were found both in revised Atlanta classification severity and LOS groups, which can be harnessed in AP monitoring/management (ClincialTrials.gov number, NCT03075618).Item Improving the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration using microRNAs(ScienceDirect, 2014-10) Sina, Marsela; Cote, Gregory A.; Korc, Murray; Department of Medicine, IU School of MedicineComment on: A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer.Item Incidence and risk factors of oral feeding intolerance in acute pancreatitis: Results from an international, multicenter, prospective cohort study(Wiley, 2021-02) Pothoulakis, Ioannis; Nawaz, Haq; Paragomi, Pedram; Jeong, Kwonho; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh Kumar; Gulla, Aiste; Singh, Vikesh K.; Gonzalez, Jose A.; Ferreira, Miguel; Barbu, Sorin T.; Stevens, Tyler; Gutierrez, Silvia C.; Zarnescu, Narcis O.; Capurso, Gabriele; Easler, Jeffrey; Triantafyllou, Konstantinos; Pelaez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Wu, Bechien U.; Cote, Gregory A.; Abebe, Kaleab; Tang, Gong; Lahooti, Ali; Phillips, Anna E.; Papachristou, Georgios I.; Medicine, School of MedicineBackground: Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes. The factors related to oral feeding intolerance are not well studied. Objective: We aimed to determine the incidence and risk factors of oral feeding intolerance in acute pancreatitis. Methods: Patients were prospectively enrolled in the Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience, an international acute pancreatitis registry, between 2015 and 2018. Oral feeding intolerance was defined as worsening abdominal pain and/or vomiting after resumption of oral diet. The timing of the initial feeding attempt was stratified based on the day of hospitalization. Multivariable logistic regression was performed to assess for independent risk factors/predictors of oral feeding intolerance. Results: Of 1233 acute pancreatitis patients included in the study, 160 (13%) experienced oral feeding intolerance. The incidence of oral feeding intolerance was similar irrespective of the timing of the initial feeding attempt relative to hospital admission day (p = 0.41). Patients with oral feeding intolerance were more likely to be younger (45 vs. 50 years of age), men (61% vs. 49%), and active alcohol users (44% vs. 36%). They also had higher blood urea nitrogen (20 vs. 15 mg/dl; p < 0.001) and hematocrit levels (41.7% vs. 40.5%; p = 0.017) on admission; were more likely to have a nonbiliary acute pancreatitis etiology (69% vs. 51%), systemic inflammatory response syndrome of 2 or greater on admission (49% vs. 35%) and at 48 h (50% vs. 26%), develop pancreatic necrosis (29% vs. 13%), moderate to severe acute pancreatitis (41% vs. 24%), and have a longer hospital stay (10 vs. 6 days; all p < 0.04). The adjusted analysis showed that systemic inflammatory response syndrome of 2 or greater at 48 h (odds ratio 3.10; 95% confidence interval 1.83-5.25) and a nonbiliary acute pancreatitis etiology (odds ratio 1.65; 95% confidence interval 1.01-2.69) were independent risk factors for oral feeding intolerance. Conclusion: Oral feeding intolerance occurs in 13% of acute pancreatitis patients and is independently associated with systemic inflammatory response syndrome at 48 h and a nonbiliary etiology.Item Introduction and Validation of a Novel Acute Pancreatitis Digital Tool: Interrogating Large Pooled Data From 2 Prospectively Ascertained Cohorts(Wolters Kluwer, 2020) Paragomi, Pedram; Spagnolo, Daniel M.; Breze, Cameron R.; Gougol, Amir; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh Kumar; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh K.; Ferreira, Miguel; Stevens, Tyler; Barbu, Sorin T.; Nawaz, Haq; Gutierrez, Silvia C.; Zarnescu, Narcis O.; Archibugi, Livia; Easler, Jeffrey J.; Triantafyllou, Konstantinos; Pelaez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Wu, Bechien U.; Pothoulakis, Ioannis; Haupt, Mark; Whitcomb, David C.; Papachristou, Georgios I.; Medicine, School of MedicineObjectives: Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. Methods: Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). Results: The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. Conclusions: The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.
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