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Item Assay of insulin antibodies and insulin release from the pancreas(1965) Rivera-Calimlim, LeonorItem Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health(Elsevier, 2023) Yadav, Dhiraj; Askew, Robert L.; Palermo, Tonya; Li, Liang; Andersen, Dana K.; Chen, Minxing; Fisher, William E.; Fogel, Evan L.; Forsmark, Christopher E.; Hart, Phil A.; Othman, Mohamed O.; Pandol, Stephen J.; Park, Walter G.; Topazian, Mark D.; Van Den Eeden, Stephen K.; Swaroop Vege, Santhi; Yang, Yunlong; Serrano, Jose; Conwell, Darwin L.; Consortium for the Study of Chronic Pancreatitis; Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of MedicineBackground and aims: Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities. Methods: We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile, which captures 7 symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database. Results: Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes, 2.54-7.03) and had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes, 4.08-10.37) and clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, 2.80-5.38). Conclusions: Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP.Item Association of Pancreatic Steatosis With Chronic Pancreatitis, Obesity, and Type 2 Diabetes Mellitus(Lippincott, Williams & Wilkins, 2019-03) Tirkes, Temel; Jeon, Christie Y.; Li, Liang; Joon, Aron Y.; Seltman, Ted A.; Sankar, Meghana; Persohn, Scott A.; Territo, Paul R.; Radiology and Imaging Sciences, School of MedicineObjective: The aim of this study was to determine the association of the pancreatic steatosis with obesity, chronic pancreatitis (CP), and type 2 diabetes mellitus. Methods: Patients (n = 118) were retrospectively identified and categorized into no CP (n = 60), mild (n = 21), moderate (n = 27), and severe CP (n = 10) groups based on clinical history and magnetic resonance cholangiopancreatography using the Cambridge classification as the diagnostic standard. Visceral and subcutaneous compartments were manually segmented, and fat tissue was quantitatively measured on axial magnetic resonance imaging. Results: Pancreatic fat fraction showed a direct correlation with fat within the visceral compartment (r = 0.54). Patients with CP showed higher visceral fat (P = 0.01) and pancreatic fat fraction (P < 0.001): mild, 24%; moderate, 23%; severe CP, 21%; no CP group, 15%. Patients with type 2 diabetes mellitus showed higher pancreatic steatosis (P = 0.03) and higher visceral (P = 0.007) and subcutaneous fat (P = 0.004). Interobserver variability of measuring fat by magnetic resonance imaging was excellent (r ≥ 0.90–0.99). Conclusions: Increased visceral adipose tissue has a moderate direct correlation with pancreatic fat fraction. Chronic pancreatitis is associated with higher pancreatic fat fraction and visceral fat. Type 2 diabetes mellitus is associated with higher pancreatic fat fraction and visceral and subcutaneous adiposity.Item Carcinosarcoma, a Rare Malignant Neoplasm of the Pancreas(MDPI, 2021-12-12) Khan, Jaffar; Cheng, Liang; House, Michael G.; Guo, Shunhua; Pathology and Laboratory Medicine, School of MedicineCarcinosarcoma of the pancreas is a rare entity with poor prognosis. Here, we report a case of pancreatic carcinosarcoma in a 68-year-old male patient who underwent a pancreatoduodenectomy for a unilocular cystic mass in the head of the pancreas. Histologically, the lesion showed a biphasic tumor with a carcinoma component and a spindle cell sarcomatous component, which were intimately intermingled. Most of the carcinoma components are well-differentiated ductal adenocarcinoma with small areas of moderately to poorly differentiated ductal adenocarcinoma. The sarcomatous component is a high-grade highly cellular spindle cell tumor with frequent mitosis and apoptosis. Immunohistochemical studies demonstrated that the carcinomatous component was positive for epithelial markers and cyclin D1, and the sarcomatous component was negative for these markers while positive for vimentin, p16, and DOG1 with patchy positivity for S100. Other markers, including SOX10, CD117, Melan A, HMB45, actin, desmin, myogenin, beta-catenin, TLE1, and p53, were negative in both components. Molecular studies demonstrated that the tumor was microsatellite stable. Whole exome next generation sequencing analysis was performed and no pathogenic alterations in the genes were identified.Item Chronic Pancreatitis: What the Clinician Wants to Know from MR Imaging(Elsevier, 2018-08) Tirkes, Temel; Radiology and Imaging Sciences, School of MedicineDiagnosis of chronic pancreatitis requires a complete medical history and clinical investigations, including imaging technologies and function tests. MR imaging/magnetic resonance cholangiopancreatography is the preferred diagnostic tool for detection of ductal and parenchymal changes in patients with chronic pancreatitis. Ductal changes may not be present in the initial phase of chronic pancreatitis. Therefore, early diagnosis remains challenging.Item Cilia Signaling and Obesity(Elsevier, 2021) Engle, Staci E.; Bansal, Ruchi; Antonellis, Patrick J.; Berbari, Nicolas F.; Biology, School of ScienceAn emerging number of rare genetic disorders termed ciliopathies are associated with pediatric obesity. It is becoming clear that the mechanisms associated with cilia dysfunction and obesity in these syndromes are complex. In addition to ciliopathic syndromic forms of obesity, several cilia-associated signaling gene mutations also lead to morbid obesity. While cilia have critical and diverse functions in energy homeostasis including their roles in centrally mediated food intake as well as in peripheral tissues, many questions remain. Here, we briefly discuss the syndromic ciliopathies and monoallelic cilia signaling gene mutations associated with obesity. We also describe potential ways cilia may be involved in common obesity. We discuss how neuronal cilia impact food intake potentially through leptin signaling and changes in ciliary G protein-coupled receptor (GPCR) signaling. We highlight several recent studies that have implicated the potential for cilia in peripheral tissues such as adipose and the pancreas to contribute to metabolic dysfunction. Then we discuss the potential for cilia to impact energy homeostasis through their roles in both development and adult tissue homeostasis. The studies discussed in this review highlight how a comprehensive understanding of the requirement of cilia for the regulation of diverse biological functions will contribute to our understanding of common forms of obesity.Item Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study(Wolters Kluwer, 2020-07) Dike, Chinenye R.; Zimmerman, Bridget; Zheng, Yuhua; Wilschanski, Michael; Werlin, Steven L.; Troendle, David; Shah, Uzma; Schwarzenberg, Sarah Jane; Pohl, John; Perito, Emily R.; Ooi, Chee Y.; Nathan, Jaimie D.; Morinville, Veronique D.; McFerron, Brian; Mascarenhas, Maria; Maqbool, Asim; Liu, Quin; Lin, Tom K.; Husain, Sohail Z.; Heyman, Melvin B.; Gonska, Tanja; Giefer, Matthew J.; Gariepy, Cheryl E.; Fishman, Douglas S.; Bellin, Melena; Barth, Bradley; Abu-El-Haija, Maisam; Lowe, Mark E.; Uc, Aliye; Pediatrics, School of MedicineObjective: The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites. Study design: Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test. Results: Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001). Conclusions: This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored.Item Cloning human pancreatic a-amylase cDNA: nucleotide sequence and evolutionary comparisons(1985) Wise, Robert JosephItem Congenital anatomic variations in a pancreas allograft: Is this consistent with safe transplant?(Elsevier, 2022) Walia, Sonal; Powelson, John A.; Lutz, Andrew J.; Fridell, Jonathan A.; Surgery, School of MedicineItem Deciphering the Role of Eukaryotic Initiation Factor 5A in Pancreatic Organogenesis(2024-08) Rutan, Caleb D.; Mastracci, Teresa L.; Berbari, Nicolas F.; Balakrishnan, Lata N.; Roh, Hyun CheolThe pancreas is composed of a variety of cell types such as acinar, endocrine, and ductal cells, as well as endothelial cells and adipocytes. Whereas we understand the distinct functions of each, there remains an incomplete understanding of the molecular pathways and communications that exist between these cells that may influence development, growth, and function. Given that diabetes is characterized by the destruction or dysfunction of the insulin-producing pancreatic beta cell, a better understanding of the mechanisms that influence cell growth and maintenance in the pancreas is of therapeutic interest. Genome-wide association studies identified eukaryotic initiation factor 5A (eIF5A) to be within a type 1 diabetes susceptibility locus, which also suggests this translation factor may play a role in maintaining beta cell health. EIF5A is active once post-translationally modified by the rate-limiting enzyme deoxyhypusine synthase (DHPS) in a process known as hypusination, producing hypusinated eIF5A (eIF5AHYP). The functional loss of eIF5AHYP via pancreas-specific genetic deletion of Dhps or Eif5a within multipotent pancreatic progenitor cells (MPPCs) results in an mRNA translation defect detectable at E14.5 causing the decreased expression of many proteins required for exocrine growth and function. Moreover, DHPSΔPANC mice die by 6 weeks-of-age; however, eIF5AΔPANC mice survive up to 2 years-of-age. The postnatal phenotype of the eIF5AΔPANC model was investigated in this thesis.