Browsing by Author "Vege, Santhi S."

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    Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain
    (Mary Ann Liebert, 2025) Goodman, Marc T.; Lombardi, Christina; Torrens, Alexa; Bresee, Catherine; Saloman, Jami L.; Li, Liang; Yang, Yunlong; Fisher, William E.; Fogel, Evan L.; Forsmark, Christopher E.; Conwell, Darwin L.; Hart, Phil A.; Park, Walter G.; Topazian, Mark; Vege, Santhi S.; Van Den Eeden, Stephen K.; Bellin, Melena D.; Andersen, Dana K.; Serrano, Jose; Yadav, Dhiraj; Pandol, Stephen J.; Piomelli, Daniele; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of Medicine
    Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (N = 22), acute pancreatitis (N = 33), recurrent acute pancreatitis (N = 57), and definite CP (N = 63). Results: Circulating AEA concentrations were higher in women than in men (p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (p = 0.003). Asymptomatic controls with no pancreatic disease had significantly (p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.
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    Circulating immune signatures across clinical stages of chronic pancreatitis: a pilot study
    (Wolters Kluwer, 2024) Hagn-Meincke, Rasmus; Hart, Phil A.; Andersen, Dana K.; Vege, Santhi S.; Fogel, Evan L.; Serrano, Jose; Bellin, Melena D.; Topazian, Mark D.; Conwell, Darwin L.; Li, Liang; Van Den Eeden, Stephen K.; Drewes, Asbjørn M.; Pandol, Stephen J.; Forsmark, Chris E.; Fisher, William E.; Yadav, Dhiraj; Olesen, Søren S.; Park, Walter G.; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of Medicine
    Objective: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP). Methods: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to characterise immune signatures across CP subgroups. Results: A total of 135 CP subjects (evenly distributed between clinical stages) and 50 controls were studied. Interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble intercellular adhesion molecule 1 (sICAM-1) were significantly elevated in CP subjects compared to controls. The levels of IL-6 and IL-8 increased with advancing disease stages, with the highest levels observed in CP with diabetes and EPD (clinical stage 3). Furthermore, hepatocyte growth factor and macrophage-derived chemokine were significantly increased in clinical stage 3 compared to controls. Conclusion: Our study reveals a progressive elevation in pro-inflammatory cytokines and chemokines with advancing clinical stages of CP. These findings indicate potential targets for the development of disease-modifying interventions.
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    Quantitative MRI of chronic pancreatitis: results from a multi-institutional prospective study, magnetic resonance imaging as a non-invasive method for assessment of pancreatic fibrosis (MINIMAP)
    (Springer Nature, 2022) Tirkes, Temel; Yadav, Dhiraj; Conwell, Darwin L.; Territo, Paul R.; Zhao, Xuandong; Persohn, Scott A.; Dasyam, Anil K.; Shah, Zarine K.; Venkatesh, Sudhakar K.; Takahashi, Naoki; Wachsman, Ashley; Li, Liang; Li, Yan; Pandol, Stephen J.; Park, Walter G.; Vege, Santhi S.; Hart, Phil A.; Topazian, Mark; Andersen, Dana K.; Fogel, Evan L.; Consortium for the Study of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (CPDPC); Radiology and Imaging Sciences, School of Medicine
    Purpose: To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study. Methods: This study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n = 50) and CP (n = 51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI). Results: There was significantly higher T1 relaxation time; mean 669 ms (± 171) vs. 593 ms (± 82) (p = 0.006), ECV fraction; 40.2% (± 14.7) vs. 30.3% (± 11.9) (p < 0.001), and pancreatic fat signal fraction; 12.2% (± 5.5) vs. 8.2% (± 4.4) (p < 0.001) in the CP group compared to controls. The ADC was similar between groups (p = 0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76). Conclusion: Quantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups.