Search

Your search keyword '"Whitcomb, David C."' showing total 2,301 results
Start Over Author "Whitcomb, David C."
2,301 results on '"Whitcomb, David C."'

2. Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases: Workshop Proceedings.

Author

Mastracci, Teresa L, Apte, Minoti, Amundadottir, Laufey T, Alvarsson, Alexandra, Artandi, Steven, Bellin, Melena D, Bernal-Mizrachi, Ernesto, Caicedo, Alejandro, Campbell-Thompson, Martha, Cruz-Monserrate, Zobeida, El Ouaamari, Abdelfattah, Gaulton, Kyle J, Geisz, Andrea, Goodarzi, Mark O, Hara, Manami, Hull-Meichle, Rebecca L, Kleger, Alexander, Klein, Alison P, Kopp, Janel L, Kulkarni, Rohit N, Muzumdar, Mandar D, Naren, Anjaparavanda P, Oakes, Scott A, Olesen, Søren S, Phelps, Edward A, Powers, Alvin C, Stabler, Cherie L, Tirkes, Temel, Whitcomb, David C, Yadav, Dhiraj, Yong, Jing, Zaghloul, Norann A, Pandol, Stephen J, and Sander, Maike

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Rare Diseases, Cancer, Pancreatic Cancer, Diabetes, Metabolic and endocrine, Good Health and Well Being, Humans, Diabetes Mellitus, Islets of Langerhans, Pancreas, Pancreas, Exocrine, Pancreatic Diseases, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

The Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report provides a summary of the proceedings from the workshop. The goals of the workshop were to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into six major theme areas, including 1) pancreas anatomy and physiology, 2) diabetes in the setting of exocrine disease, 3) metabolic influences on the exocrine pancreas, 4) genetic drivers of pancreatic diseases, 5) tools for integrated pancreatic analysis, and 6) implications of exocrine-endocrine cross talk. For each theme, multiple presentations were followed by panel discussions on specific topics relevant to each area of research; these are summarized here. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.

Published
2023

3. Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases

Author

Mastracci, Teresa L, Apte, Minoti, Amundadottir, Laufey T, Alvarsson, Alexandra, Artandi, Steven, Bellin, Melena D, Bernal-Mizrachi, Ernesto, Caicedo, Alejandro, Campbell-Thompson, Martha, Cruz-Monserrate, Zobeida, Ouaamari, Abdelfattah El, Gaulton, Kyle J, Geisz, Andrea, Goodarzi, Mark O, Hara, Manami, Hull-Meichle, Rebecca L, Kleger, Alexander, Klein, Alison P, Kopp, Janel L, Kulkarni, Rohit N, Muzumdar, Mandar D, Naren, Anjaparavanda P, Oakes, Scott A, Olesen, Søren S, Phelps, Edward A, Powers, Alvin C, Stabler, Cherie L, Tirkes, Temel, Whitcomb, David C, Yadav, Dhiraj, Yong, Jing, Zaghloul, Norann A, Sander, Maike, and Pandol, Stephen J

Subjects
Diabetes, Digestive Diseases, Rare Diseases, Cancer, Pancreatic Cancer, Metabolic and endocrine, Good Health and Well Being, Humans, Diabetes Mellitus, Islets of Langerhans, Pancreas, Pancreas, Exocrine, Pancreatic Diseases, exocrine pancreas, endocrine pancreas, exocrine-endocrine crosstalk, integrated physiology, interpancreatic communication, AP, acute pancreatitis, AP-D, acute pancreatitis-related diabetes, CCK, cholecystokinin, cCRE, cis-regulatory element, CF, cystic fibrosis, CFRD, cystic fibrosis-related diabetes, CFTR, cystic fibrosis transmembrane conductance regulator, CP, chronic pancreatitis, CP-D, chronic pancreatitis-related diabetes, ECM, extracellular matrix, eIF5A, eukaryotic initiation factor 5A, EPI, exocrine pancreatic insufficiency, GWAS, genome-wide association study, MRI, magnetic resonance imaging, MRCP, magnetic resonance cholangiopancreatography, NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, National Institutes of Health, PSC, pancreatic stellate cells, PDAC, pancreatic ductal adenocarcinoma, PDLO, pancreatic-duct-like organoid, PRSS1, trypsinogen, T1D, type 1 diabetes, T2D, type 2 diabetes, Clinical Sciences, Gastroenterology & Hepatology
Abstract

AbstractThe "Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases" Workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report summarizes the workshop proceedings. The goal of the workshop was to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into 6 major themes, including (a) Pancreas Anatomy and Physiology; (b) Diabetes in the Setting of Exocrine Disease; (c) Metabolic Influences on the Exocrine Pancreas; (d) Genetic Drivers of Pancreatic Diseases; (e) Tools for Integrated Pancreatic Analysis; and (f) Implications of Exocrine-Endocrine Crosstalk. For each theme, there were multiple presentations followed by panel discussions on specific topics relevant to each area of research; these are summarized herein. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of the normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.

Published
2022

4. Estrogen-Related Receptor γ Maintains Pancreatic Acinar Cell Function and Identity by Regulating Cellular Metabolism

Author

Choi, Jinhyuk, Oh, Tae Gyu, Jung, Hee-Won, Park, Kun-Young, Shin, Hyemi, Jo, Taehee, Kang, Du-Seock, Chanda, Dipanjan, Hong, Sujung, Kim, Jina, Hwang, Hayoung, Ji, Moongi, Jung, Minkyo, Shoji, Takashi, Matsushima, Ayami, Kim, Pilhan, Mun, Ji Young, Paik, Man-Jeong, Cho, Sung Jin, Lee, In-Kyu, Whitcomb, David C, Greer, Phil, Blobner, Brandon, Goodarzi, Mark O, Pandol, Stephen J, Rotter, Jerome I, Consortium, North American Pancreatitis Study 2, Fan, Weiwei, Bapat, Sagar P, Zheng, Ye, Liddle, Chris, Yu, Ruth T, Atkins, Annette R, Downes, Michael, Yoshihara, Eiji, Evans, Ronald M, and Suh, Jae Myoung

Subjects
Digestive Diseases, Cancer, Genetics, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Acinar Cells, Animals, Estrogens, Humans, Mice, Mice, Knockout, Pancreas, Pancreas, Exocrine, Pancreatitis, Chronic, ERR gamma, Pancreatic Acinar Cells, Mitochondrial Oxidative Phosphorylation, Reactive Oxygen Species, Acinar-to-Ductal Metaplasia, North American Pancreatitis Study 2 (NAPS2) Consortium, ERRγ, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Background & aimsMitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production.MethodsTwo models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histologic and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in 2 distinct human pancreatitis cohorts.ResultsBlocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss of ERRγ in primary acini abrogates messenger RNA expression and protein levels of mitochondrial oxidative phosphorylation complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, endoplasmic reticulum stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics, indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared with normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants for ERRγ that are associated with chronic pancreatitis.ConclusionsCollectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.

Published
2022

6. Lifetime smoking history and cohort-based smoking prevalence in chronic pancreatitis

Author

Jeon, Christie Y, Feldman, Robert, Althouse, Andrew, AlKaade, Samer, Brand, Randall E, Guda, Nalini, Sandhu, Bimaljit S, Singh, Vikesh K, Wilcox, C Mel, Slivka, Adam, Gelrud, Andres, Whitcomb, David C, and Yadav, Dhiraj

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Chronic Pain, Tobacco, Clinical Research, Substance Misuse, Pediatric, Cancer, Digestive Diseases, Pain Research, Tobacco Smoke and Health, Prevention, Respiratory, Chronic Pancreatitis, Epidemiology, Smoking, Cohort, Clinical Sciences, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background/objectiveSmoking prevalence in patients with chronic pancreatitis [CP] is high. We aimed to understand lifetime history of smoking and cohort trends in CP patients to inform effective strategies for smoking cessation.MethodData on 317 CP patients from the North American Pancreatitis Study 2 [NAPS2] Continuation and Validation Study and the NAPS2 Ancillary Study were analyzed. Smoking history was assessed for each phase of life from the onset of smoking to study enrollment. Data on second-hand smoke and drinking history were also collected. We compared demographic factors, drinking history, pain level and pancreas morphology by smoking status at age 25 (non-smoking,

Published
2021

9. Pancreatitis-Associated PRSS1-PRSS2 Haplotype Alters T-Cell Receptor Beta (TRB) Repertoire More Strongly Than PRSS1 Expression

Author

Bellin, Melena D., Beilman, Greg, Brand, Randall E., Shelton Ohlsen, Celeste, Saloman, Jami L., Whitcomb, David C., Park, H.J., Lee, Kenneth K., Paniccia, Alessandro, Zureikat, Amer, Alkaade, Samer, Amann, Stephen, Anderson, Michelle A., Banks, Peter, Conwell, Darwin L., Cote, Gregory A., Forsmark, Christopher E., Gardner, Timothy B., Gelrud, Andres, Guda, Nalini M., Lewis, Michele D., Muniraj, Thiruvengadam, Papachristou, Georgios I., Romagnuolo, Joseph, Sandhu, Bimaljit S., Sherman, Stuart, Singh, Vikesh K., Slivka, Adam, Melbern Wilcox, Charles, Yadav, Dhiraj, Fu, Dongni, Blobner, Brandon M., Greer, Phil J., and Lafyatis, Robert

Published
2023
Full Text
View/download PDF

12. Autoimmunity May Explain Diabetes in a Subset of Patients With Recurrent Acute and Chronic Pancreatitis: A Pilot Study

Author

AlKaade, Samer, Amann, Stephen T., Anderson, Michelle A., Banks, Peter, Conwell, Darwin, Brand, Randall E., Cote, Gregory A., Romagnuolo, Joseph, Forsmark, Christopher E., Gardner, Timothy, Gelrud, Andres, Guda, Nalini, Lewis, Michele, Muniraj, Thiruvengadam, Sandhu, Bimaljit S., Sherman, Stuart, Singh, Vikesh, Wilcox, C. Mel, Yadav, Dhiraj, Whitcomb, David C., Tang, Gong, Slivka, Adam, and Bellin, Melena

Published
2023
Full Text
View/download PDF

13. Diagnostic and Prognostic Biomarkers of Chronic Pancreatitis: A Conceptual Framework Based on the PRoBE Design

Author

Yadav, Dhiraj, primary, Conwell, Darwin L., additional, Pandol, Stephen J., additional, Steen, Hanno, additional, Feng, Ziding, additional, Li, Liang, additional, Andersen, Dana, additional, Bellin, Melena, additional, Chari, Suresh T., additional, Cruz-Monserrate, Zobeida, additional, Fisher, William E., additional, Fogel, Evan L., additional, Forsmark, Christopher E., additional, Hart, Phil A., additional, Lesinski, Gregory B., additional, Park, Walter G., additional, Rinaudo, Jo Ann, additional, Saloman, Jami L., additional, Serrano, Jose, additional, Tirkes, Temel, additional, Topazian, Mark D., additional, van Den Eeden, Stephen, additional, Vege, Santhi Swaroop, additional, and Whitcomb, David C., additional

Published
2024
Full Text
View/download PDF

14. Reply

Author

Whitcomb, David C., primary, Buchner, Anna M., additional, and Forsmark, Chris E., additional

Published
2024
Full Text
View/download PDF

15. Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer.

Author

Saloman, Jami L, Albers, Kathryn M, Cruz-Monserrate, Zobeida, Davis, Brian M, Edderkaoui, Mouad, Eibl, Guido, Epouhe, Ariel Y, Gedeon, Jeremy Y, Gorelick, Fred S, Grippo, Paul J, Groblewski, Guy E, Husain, Sohail Z, Lai, Keane KY, Pandol, Stephen J, Uc, Aliye, Wen, Li, and Whitcomb, David C

Subjects
Pancreas, Exocrine, Animals, Humans, Mice, Rats, Pancreatic Neoplasms, Pancreatitis, Disease Models, Animal, Acute Disease, Genetic Engineering, Cancer, Digestive Diseases, Rare Diseases, Pancreatic Cancer, pancreatitis, pancreatic cancer, animal models, Clinical Sciences, Gastroenterology & Hepatology
Abstract

At the 2018 PancreasFest meeting, experts participating in basic research met to discuss the plethora of available animal models for studying exocrine pancreatic disease. In particular, the discussion focused on the challenges currently facing the field and potential solutions. That meeting culminated in this review, which describes the advantages and limitations of both common and infrequently used models of exocrine pancreatic disease, namely, pancreatitis and exocrine pancreatic cancer. The objective is to provide a comprehensive description of the available models but also to provide investigators with guidance in the application of these models to investigate both environmental and genetic contributions to exocrine pancreatic disease. The content covers both nongenic and genetically engineered models across multiple species (large and small). Recommendations for choosing the appropriate model as well as how to conduct and present results are provided.

Published
2019

16. Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus

Author

Goodarzi, Mark O, Nagpal, Tanvi, Greer, Phil, Cui, Jinrui, Chen, Yii-Der I, Guo, Xiuqing, Pankow, James S, Rotter, Jerome I, Alkaade, Samer, Amann, Stephen T, Baillie, John, Banks, Peter A, Brand, Randall E, Conwell, Darwin L, Cote, Gregory A, Forsmark, Christopher E, Gardner, Timothy B, Gelrud, Andres, Guda, Nalini, LaRusch, Jessica, Lewis, Michele D, Money, Mary E, Muniraj, Thiruvengadam, Papachristou, Georgios I, Romagnuolo, Joseph, Sandhu, Bimaljit S, Sherman, Stuart, Singh, Vikesh K, Wilcox, C Mel, Pandol, Stephen J, Park, Walter G, Andersen, Dana K, Bellin, Melena D, Hart, Phil A, Yadav, Dhiraj, and Whitcomb, David C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Clinical Research, Diabetes, Genetics, Genetic Testing, Metabolic and endocrine, Aged, Case-Control Studies, Comorbidity, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Genotype, Humans, Male, Middle Aged, Pancreatitis, Chronic, Polymorphism, Single Nucleotide, Risk Factors, Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer, Clinical sciences
Abstract

IntroductionDiabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to manage CP-DM. We approached this question from a unique standpoint, hypothesizing that if CP-DM and T2DM are separate disorders, they should be genetically distinct. To test this hypothesis, we sought to determine whether a genetic risk score (GRS) based on validated single nucleotide polymorphisms for T2DM could distinguish between groups with CP-DM and T2DM.MethodsWe used 60 T2DM single nucleotide polymorphisms to construct a weighted GRS in 1,613 subjects from the North American Pancreatitis Study 2 and 2,685 subjects from the Multi-Ethnic Study of Atherosclerosis, all of European origin.ResultsThe mean GRS was identical between 321 subjects with CP-DM and 423 subjects with T2DM (66.53 vs 66.42, P = 0.95), and the GRS of both diabetic groups was significantly higher than that of nondiabetic controls (n = 3,554, P < 0.0001). Exploratory analyses attempting to enrich the CP-DM group for pancreatogenic diabetes, such as eliminating diabetes diagnosed before CP, requiring pancreas-specific comorbidities, or removing those with a family history of diabetes, did not improve the ability of the GRS to distinguish between CP-DM and T2DM.DiscussionRecognizing that we lacked a gold standard to define CP-DM, our study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.

Published
2019

17. Chronic Pancreatitis

Author

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, and Yadav, Dhiraj

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Digestive Diseases, Prevention, Pediatric, 2.1 Biological and endogenous factors, Aetiology, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Oral and gastrointestinal, Good Health and Well Being, Adolescent, Adult, Alcohol Drinking, Child, Cohort Studies, Cross-Sectional Studies, Demography, Disease Progression, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, North America, Pancreatitis, Chronic, Risk Factors, Socioeconomic Factors, Surveys and Questionnaires, Tobacco Smoking, children, diabetes, endoscopy, environmental, genetic, pain, Medical and Health Sciences, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics, Paediatrics
Abstract

ObjectivesThe aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.MethodsDemographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.ResultsAlcohol was a risk in 53% of adults and 1% of children (P

Published
2019

18. Standard Operating Procedures for Biospecimen Collection, Processing, and Storage

Author

Fisher, William E, Cruz-Monserrate, Zobeida, McElhany, Amy L, Lesinski, Gregory B, Hart, Phil A, Ghosh, Ria, Van Buren, George, Fishman, Douglas S, Rinaudo, Jo Ann S, Serrano, Jose, Srivastava, Sudhir, Mace, Thomas, Topazian, Mark, Feng, Ziding, Yadav, Dhiraj, Pandol, Stephen J, Hughes, Steven J, Liu, Robert Y, Lu, Emily, Orr, Robert, Whitcomb, David C, Abouhamze, Amer S, Steen, Hanno, Sellers, Zachary M, Troendle, David M, Uc, Aliye, Lowe, Mark E, and Conwell, Darwin L

Subjects
Digestive Diseases, Cancer, Rare Diseases, Clinical Research, Diabetes, Pancreatic Cancer, Metabolic and endocrine, Biological Specimen Banks, Biomedical Research, Child, Diabetes Mellitus, Guidelines as Topic, Humans, Pancreatic Neoplasms, Pancreatitis, Chronic, Preservation, Biological, Specimen Handling, biorepository, biospecimens, pancreas, standard operating procedures, Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer, Clinical Sciences, Gastroenterology & Hepatology
Abstract

High-quality and well-annotated biorepositories are needed to better understand the pathophysiology and biologic mechanisms of chronic pancreatitis (CP) and its consequences. We report a methodology for the development of a robust standard operating procedure (SOP) for a biorepository based on the experience of the clinical centers within the consortium to study Chronic Pancreatitis, Diabetes and Pancreas Cancer Clinical Centers (CPDPC), supported by the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases as a unique multidisciplinary model to study CP, diabetes, and pancreatic cancer in both children and adults. Standard operating procedures from the CPDPC centers were evaluated and consolidated. The literature was reviewed for standard biorepository operating procedures that facilitated downstream molecular analysis. The existing literature on biobanking practices was harmonized with the SOPs from the clinical centers to produce a biorepository for pancreatic research. This article reports the methods and basic principles behind the creation of SOPs to develop a biorepository for the CPDPC. These will serve as a guide for investigators developing biorepositories in pancreas research. Rigorous and meticulous adherence to standardized biospecimen collection will facilitate investigations to better understand the pathophysiology and biologic mechanisms of CP, diabetes, and pancreatic cancer.

Published
2018

19. PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies

Author

Yadav, Dhiraj, Park, Walter G, Fogel, Evan L, Li, Liang, Chari, Suresh T, Feng, Ziding, Fisher, William E, Forsmark, Christopher E, Jeon, Christie Y, Habtezion, Aida, Hart, Phil A, Hughes, Steven J, Othman, Mohamed O, Rinaudo, Jo Ann S, Pandol, Stephen J, Tirkes, Temel, Serrano, Jose, Srivastava, Sudhir, Van Den Eeden, Stephen K, Whitcomb, David C, Topazian, Mark, and Conwell, Darwin L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pancreatic Cancer, Prevention, Digestive Diseases, Rare Diseases, Cancer, Clinical Research, 2.1 Biological and endogenous factors, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Aetiology, Oral and gastrointestinal, Adult, Biomarkers, Blood Specimen Collection, Diabetes Mellitus, Disease Progression, Humans, Longitudinal Studies, Observational Studies as Topic, Outcome Assessment, Health Care, Pancreatic Neoplasms, Pancreatitis, Chronic, Prospective Studies, Research Design, Specimen Handling, Translational Research, Biomedical, United States, pancreas, alcohol, tobacco, genetic, biorepository, cohort, Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer, Gastroenterology & Hepatology, Clinical sciences
Abstract

Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.

Published
2018

20. Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis

Author

Lowe, Mark E, Goodman, Marc T, Coté, Gregory A, Glesby, Marshall J, Haupt, Mark, Schork, Nicholas J, Singh, Vikesh K, Andersen, Dana K, Pandol, Stephen J, Uc, Aliye, and Whitcomb, David C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Cancer, Rare Diseases, Diabetes, Clinical Research, Oral and gastrointestinal, Good Health and Well Being, Acute Disease, Biomedical Research, Clinical Trials as Topic, Drug Development, Humans, National Institute of Diabetes and Digestive and Kidney Diseases (U.S.), Pancreatitis, Pancreatitis, Chronic, Pharmaceutical Preparations, Recurrence, United States, drug trials, pancreatitis, patient-reported outcomes, Gastroenterology & Hepatology, Clinical sciences
Abstract

Recurrent acute pancreatitis (RAP) is a complex clinical syndrome with significant morbidity, unpredictable outcomes, and limited treatment options. The National Institute of Diabetes and Digestive and Kidney Disease sponsored a workshop on July 25, 2018, in Pittsburgh, Pennsylvania, to address research gaps impeding development of effective therapies for pancreatitis. The RAP working group identified challenges to clinical progress using existing definitions, risk assessment, diagnostic and severity criteria, disease trajectories, outcomes, and research methods. Recurrent acute pancreatitis includes all the risk of acute pancreatitis and often progresses to chronic pancreatitis with variable complications of chronic pain, exocrine insufficiency, diabetes, and pancreatic cancer. However, the great variability among individuals with RAP requires better precision in defining the risks, individual episodes, as well as their frequency, pathogenic pathways, and specific outcome measures for each of the systems affected by pancreatic inflammation. Because of disease complexity, few patients are similar enough for traditional studies and methods to conduct clinical trials with small sample sizes are required. The need for genetic testing, biomarker development, and better imaging methods was highlighted. Adaptive and N-of-one study designs, better endpoints, and outcome measures including patient-reported outcomes should considered early in developing future therapeutic trial design and include all stakeholders.

Published
2018

21. Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study

Author

Falconi, Massimo, Zou, Wen-Bin, Engjom, Trond, Ooi, Chee Y., Sutton, Robert, Frulloni, Luca, Neoptolemos, John, Wilcox, Charles, Miroslav, Vujasinovic, Trikudanathan, Guru, Liao, Zhuan, Hauge, Truls, Mössner, Joachim, Hoge, Chantal, Fockens, Paul, Mieog, Sven, Capurso, Gabriele, Cui, Yunfeng, de Madaria, Enrique, Distler, Marius, Aghdassi, Ali, Whitcomb, David C., Russell, Kylie, Beyer, Georg, Kunovsky, Lumír, Kwanten, Wilhelmus, Nava, Andrea Kazemi, Conlon, Kevin, Siriwardena, A.K., Paiella, Salvatore, Alconchel, Felipe, Marino, Marco Vito, de Meijer, Vincent E., Domingo, Carlos, Kleeff, Jorg, Lakshmanan, Aarti, Lie Chu, Michael Jen, Bouwense, Stefan, Nashidengo, Pueya Rashid, Konstantinos, Perivoliotis, Muttillo, Edoardo Maria, Umar, Garzali Ibrahim, Castro Santiago, Maria Jesus, Lopez-Lopez, Victor, Torri, Francesco, Schmelzle, Moritz, Ignatavicius, Povilas, Wicherts, Dennis, Gomes, Antonio, Machairas, Nikolaos A., Dorovinis, Panagiotis I., Serrablo, Alejandro, Soreide, Kjetil, Rahbari, Mohammad, Jie Chu, Michael Jen, Ptasnuka, Margarita, Petrulionis, Marius, Noel, Colin Byron, Castro, Ernest, Di Martino, Marcello, Recordare, Alfonso, Stättner, Stefan, Ausania, Fabio, Hartman, Vera, Roeyen, Geert, Egorov, Viacheslav, Vanagas, Tomas, Ebrahim, Mohamed, Arabadzhieva, Elena, Malleo, Giuseppe, Li, Liang, Adams, David, Oracz, Grzegorz, Nageshwar, Reddy D., Waldthaler, Alexander, Masamune, Atsushi, Drewes, Asbjorn Mohr, Amodio, Antonio, Tirkes, Temel, Srivastava, Anshu, Beilman, Gregory J., Berger, Zoltan, Lindkvist, Bjorn, Cavestro, Giulia Martina, Gariepy, Cheryl, Czakó, Laszlo, Di Leo, Milena, Sharma, Vishal, Lakhtakia, Sundeep, Rana, Surinder Singh, Duggan, Sinaed N., Kwon, Chang-Il, Phillips, Anna Evans, Forsmark, Christopher E., Gleeson, Ferga C., Lehman, Glen A., Greenhalf, William, Costamagna, Guido, Halloran, Christopher M., Friess, Helmut, Rasmussen, Henrik Hojgaard, Ikeura, Tsukasa, Haldorsen, Ingfrid S., Itoi, Takao, Izbicki, Jacob R., Windsor, John, Poulsen, Jakob Lykke, Frokjaer, Jens Brondum, Larino-Noia, Jose, Wang, Dan, Garcia, Julio Iglesias, Kalaitzakis, Evangelos, Wertheim-Tysarowska, Kararzyna, Kubota, Kensuke, Larusch, Jessica, Lerch, Markus M., Hu, Liang-Hao, Erkan, Mert, Machicado, Jorg D., Arvanitakis, Marianna, Buchler, Markus W., Levy, Marlon F., Heyman, Melvin B., Nojgaard, Camilla, Khashab, Mouen A., Delhaye, Myriam, Ogura, Takeshi, Okazaki, Kazuichi, Ghaneh, Paula, Banks, Peter A., Gupta, Pankaj, Papachristou, Georgios I., Michl, Patrick, Levy, Philippe, Pukitis, Aldis, Pezzilli, Raffaele, Baron, Ryan D., Amann, Stephen T., Schwarzenberg, Sarah Jane, Isaji, Shuiji, Olesen, Soren Schou, Novovic, Srdan, Hughes, Steven J., Werlin, Steven L., Gonska, Tanja, Gardner, Timothy B., Topazian, Mark D., Weiss, Frank Ulrich, Akshintala, Venakata S., Morinville, Veronique D., Rebours, Vinciane, Vincze, Aron, Singh, Vikesh K., Cui, Naiqiang, Zhang, Hong, Li, Zhao-shen, de Rijk, Florence E.M., van Veldhuisen, Charlotte L., Besselink, Marc G., van Hooft, Jeanin E., van Santvoort, Hjalmar C., van Geenen, Erwin J.M., Hegyi, Peter, Löhr, J-Matthias, Dominguez-Munoz, Juan E., de Jonge, Pieter Jan F., Bruno, Marco J., and Verdonk, Robert C.

Published
2022
Full Text
View/download PDF

23. Serum biomarkers for chronic pancreatitis pain patterns

Author

Saloman, Jami L., Tang, Gong, Stello, Kimberly M., Hall, Kristen E., Wang, Xianling, AlKaade, Samer, Banks, Peter A., Brand, Randall E., Conwell, Darwin L., Coté, Gregory A., Forsmark, Christopher E., Gardner, Timothy B., Gelrud, Andres, Lewis, Michele D., Sherman, Stuart, Slivka, Adam, Whitcomb, David C., and Yadav, Dhiraj

Published
2021
Full Text
View/download PDF

26. Biomarkers of Chronic Pancreatitis: A systematic literature review

Author

Cruz-Monserrate, Zobeida, Gumpper, Kristyn, Pita, Valentina, Hart, Phil A., Forsmark, Christopher, Whitcomb, David C., Yadav, Dhiraj, Waldron, Richard T., Pandol, Stephen, Steen, Hanno, Anani, Vincent, Kanwar, Natasha, Vege, Santhi Swaroop, Appana, Savi, Li, Liang, Serrano, Jose, Rinaudo, Jo Ann S., Topazian, Mark, and Conwell, Darwin L.

Published
2021
Full Text
View/download PDF

27. 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

Author

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., and Yadav, Dhiraj

Published
2021
Full Text
View/download PDF

28. Response to Han et al.

Author

Greer, Phil, Spangolo, Dan, Ohlsen, Celeste Shelton, Ellison, Mitchell, Breze, Cameron, Haupt, Mark, and Whitcomb, David C.

Published
2022
Full Text
View/download PDF

30. The histopathology of SPINK1-associated chronic pancreatitis

Author

Jones, Terrell E., Bellin, Melena D., Yadav, Dhiraj, Freeman, Martin L., Schwarzenberg, Sarah J., Slivka, Adam, Chennat, Jennifer S., Beilman, Gregory J., Chinnakotla, Srinath, Pruett, Timothy L., Kirchner, Varvara, Humar, Abhinav, Wijkstrom, Martin, Zureikat, Amer H., Nikiforova, Marina N., Wald, Abigail I., Whitcomb, David C., and Singhi, Aatur D.

Published
2020
Full Text
View/download PDF

32. Low serum trypsinogen levels in chronic pancreatitis: Correlation with parenchymal loss, exocrine pancreatic insufficiency, and diabetes but not CT-based cambridge severity scores for fibrosis

Author

Zhan, Wei, Akshintala, Venkata, Greer, Phil J., Greer, Julia B., Alkaade, Samer, Anderson, Michelle A., Muniraj, Thiruvengadam, Papachristou, Georgios I., Sandhu, Bimaljit S., Slivka, Adam, Wilcox, C. Mel, Bellin, Melena D., Singh, Vikesh K., Yadav, Dhiraj, Brand, Randall E., and Whitcomb, David C.

Published
2020
Full Text
View/download PDF

34. International consensus guidelines on interventional endoscopy in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club

Author

Kitano, Masayuki, Gress, Thomas M., Garg, Pramod K., Itoi, Takao, Irisawa, Atsushi, Isayama, Hiroyuki, Kanno, Atsushi, Takase, Kei, Levy, Michael, Yasuda, Ichiro, Lévy, Phillipe, Isaji, Shuiji, Fernandez-Del Castillo, Carlos, Drewes, Asbjørn M., Sheel, Andrea R.G., Neoptolemos, John P., Shimosegawa, Tooru, Boermeester, Marja, Wilcox, C. Mel, and Whitcomb, David C.

Published
2020
Full Text
View/download PDF

35. International consensus guidelines on the role of diagnostic endoscopic ultrasound in the management of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club

Author

Mel Wilcox, C., Gress, Thomas, Boermeester, Marja, Masamune, Atsushi, Lévy, Philippe, Itoi, Takao, Varadarajulu, Shyam, Irisawa, Atsushi, Levy, Michael, Kitano, Masayuki, Garg, Pramod, Isaji, Shuiji, Shimosegawa, Tooru, Sheel, Andrea R.G., Whitcomb, David C., and Neoptolemos, John P.

Published
2020
Full Text
View/download PDF

36. The role of total pancreatectomy with islet autotransplantation in the treatment of chronic pancreatitis: A report from the International Consensus Guidelines in chronic pancreatitis

Author

Abu-El-Haija, Maisam, Anazawa, Takayuki, Beilman, Gregory J., Besselink, Marc G., Del Chiaro, Marco, Demir, Ihsan Ekin, Dennison, Ashley R., Dudeja, Vikas, Freeman, Martin L., Friess, Helmut, Hackert, Thilo, Kleeff, Jorg, Laukkarinen, Johanna, Levy, Marlon F., Nathan, Jaimie D., Werner, Jens, Windsor, John A., Neoptolemos, John P., Sheel, Andrea R.G., Shimosegawa, Tooru, Whitcomb, David C., and Bellin, Melena D.

Published
2020
Full Text
View/download PDF

37. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club

Author

Esposito, Irene, Hruban, Ralph H., Verbeke, Caroline, Terris, Benoit, Zamboni, Giuseppe, Scarpa, Aldo, Morohoshi, Toshio, Suda, Koichi, Luchini, Claudio, Klimstra, David S., Adsay, Volkan, Haeberle, Lena, Saluja, Ashok, Fernandez-del Castillo, Carlos, Sheel, Andrea, Neoptolemos, John P., Isaji, Shuiji, Shimosegawa, Tooru, Whitcomb, David C., and Campbell, Fiona

Published
2020
Full Text
View/download PDF

38. International Consensus Guidelines for Risk Factors in Chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club

Author

Hegyi, Péter, Párniczky, Andrea, Lerch, Markus M., Sheel, Andrea R.G., Rebours, Vinciane, Forsmark, Chris E., Del Chiaro, Marco, Rosendahl, Jonas, de-Madaria, Enrique, Szücs, Ákos, Takaori, Kyoichi, Yadav, Dhiraj, Gheorghe, Cristian, Rakonczay, Zoltán, Jr., Molero, Xavier, Inui, Kazuo, Masamune, Atsushi, Fernandez-Del Castillo, Carlos, Shimosegawa, Tooru, Neoptolemos, John P., Whitcomb, David C., and Sahin-Tóth, Miklós

Published
2020
Full Text
View/download PDF

42. S6 Treatment of Exocrine Pancreatic Insufficiency in Patients with Chronic/Recurrent Acute Pancreatitis Improves Treatment Satisfaction and Decreases Healthcare Utilization: Interim Findings from the PACT-CP Registry

Author

Barkin, Jodie A., primary, Hernandez-Barco, Yasmin G., additional, Al-Kaade, Samer, additional, Pannala, Rahul, additional, Twal, Janine, additional, Pack, Jennifer, additional, Delk, Trudi, additional, Powell, Valerie J., additional, and Whitcomb, David C., additional

Published
2023
Full Text
View/download PDF

43. S34 Experiences of the Patient With Chronic Pancreatitis Including Individuals With Exocrine Pancreatic Insufficiency: Findings From a Patient-Centered Observational Analysis of an Online Community

Author

Hernandez-Barco, Yasmin G., primary, Barkin, Jodie A., additional, Al-Kaade, Samer, additional, Pannala, Rahul, additional, Twal, Janine, additional, Pack, Jennifer, additional, Delk, Trudi, additional, Powell, Valerie J., additional, and Whitcomb, David C., additional

Published
2023
Full Text
View/download PDF

46. Increased expression of anion transporter SLC26A9 delays diabetes onset in cystic fibrosis

Author

Lam, Anh-Thu N., Aksit, Melis A., Vecchio-Pagan, Briana, Shelton, Celeste A., Osorio, Derek L., Anzmann, Arianna F., Goff, Loyal A., Whitcomb, David C., Blackman, Scott M., and Cutting, Garry R.

Subjects
Cystic fibrosis -- Care and treatment -- Development and progression, Genes, Type 2 diabetes -- Care and treatment -- Development and progression, Diabetes therapy, RNA sequencing, DNA binding proteins, RNA, DNA, Fibrosis, Youth, Diseases, Health care industry
Abstract

Diabetes is a common complication of cystic fibrosis (CF) that affects approximately 20% of adolescents and 40%-50% of adults with CF. The age at onset of CF-related diabetes (CFRD) (marked by clinical diagnosis and treatment initiation) is an important measure of the disease process. DNA variants associated with age at onset of CFRD reside in and near SLC26A9. Deep sequencing of the SLC26A9 gene in 762 individuals with CF revealed that 2 common DNA haplotypes formed by the risk variants account for the association with diabetes. Single-cell RNA sequencing (scRNA-Seq) indicated that SLC26A9 is predominantly expressed in pancreatic ductal cells and frequently coexpressed with CF transmembrane conductance regulator (CFTR) along with transcription factors that have binding sites 5' of SLC26A9. These findings were replicated upon reanalysis of scRNA-Seq data from 4 independent studies. DNA fragments derived from the 5' region of SLC26A9-bearing variants from the low-risk haplotype generated 12%-20% higher levels of expression in PANC-1 and CFPAC-1 cells compared with the high-risk haplotype. Taken together, our findings indicate that an increase in SLC26A9 expression in ductal cells of the pancreas delays the age at onset of diabetes, suggesting a CFTR-agnostic treatment for a major complication of CF., Introduction Cystic fibrosis (CF), one of the most common life-limiting autosomal recessive disease in the white European population, is caused by deleterious variants in the CF transmembrane conductance regulator (CFTR) [...]

Published
2020
Full Text
View/download PDF

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

Author

Muniraj, Thiruvengadam, Yadav, Dhiraj, Abberbock, Judah N., Alkaade, Samer, Amann, Stephen T., Anderson, Michelle A., Banks, Peter A., Brand, Randall E., Conwell, Darwin, Cote, Gregory A., Forsmark, Christopher E., Gardner, Timothy B., Gelrud, Andres, Guda, Nalini, Lewis, Michele D., Romagnuolo, Joseph, Sandhu, Bimaljit S., Sherman, Stuart, Singh, Vikesh K., Slivka, Adam, Tang, Gong, Whitcomb, David C., and Wilcox, C. Mel

Published
2019
Full Text
View/download PDF

49. Interventions for Pancreatitis—New Approaches, Knowledge Gaps, and Research Opportunities

Author

Phillips, Anna Evans, Hughes, Steven J., Andersen, Dana K., Bell, Adam, Brand, Randall, Coté, Gregory A., Cowdin, Adriana, Diazgranados, Nancy, Dudeja, Vikas, Duggan, Sinead N., Fogel, Evan, Forsmark, Chris E., Freeman, A. Jay, Gittes, George, Hart, Phil A., Jeon, Christie, Nealon, William, Neoptolemos, John, Palermo, Tonya M., Pandol, Stephen, Roberts, Kristen M., Rosenthal, Martin, Singh, Vikesh K., Yadav, Dhiraj, Whitcomb, David C., and Zyromski, Nicholas

Abstract

There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results