Objectives: We sought to determine if interleukin (IL)-1β and prostaglandin E2 (PGE2) (inflammatory mediators in pancreatic fluid) together with serum carbohydrate antigen (CA) 19-9 could better predict intraductal papillary mucinous neoplasm (IPMN) dysplasia than individual biomarkers alone.
Methods: Pancreatic cyst fluid (n = 92) collected via endoscopy or surgery (2003-2016) was analyzed for PGE2 and IL-1β (enzyme-linked immunosorbent assay). Patients had surgical pathology-proven IPMN. Threshold values (PGE2 [>1100 pg/mL], IL-1β [>20 pg/mL], and serum CA 19-9 [>36 U/mL]) were determined.
Results: Levels of IL-1β were higher in high-grade dysplasia (HGD)/invasive-IPMN (n = 42) compared with low/moderate IPMN (n = 37) (median [range], 54.6 [0-2671] vs 5.9 [0-797] pg/mL; P < 0.001; area under curve [AUC], 0.766). Similarly, PGE2 was higher in HGD/invasive IPMN (n = 45) compared with low/moderate IPMN (n = 47) (median [range], 1790 [20-15,180] vs. 140 [10-14,630] pg/mL; P < 0.001; AUC, 0.748). Presence of elevated PGE2 and IL-1β (AUC, 0.789) provided 89% specificity and 82% positive predictive value (PPV) for HGD/invasive IPMN. Elevated levels of all 3 provided 100% specificity and PPV for HGD/invasive IPMN.
Conclusions: Cyst fluid PGE2, IL-1β, and serum CA 19-9 in combination optimize specificity and PPV for HGD/invasive IPMN and may help build a panel of markers to predict IPMN dysplasia.
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http://dx.doi.org/10.1097/MPA.0000000000001377 | DOI Listing |
Alzheimers Dement
December 2024
Pacific Brain Health Center, Pacific Neuroscience Institute Foundation, Santa Monica, CA, USA.
Background: Brain accumulation of amyloid-ß (Aß) in plaques and neurons is the cause of AD neuropathology that is opposed by autologous monocyte/macrophages (MMs) in health but this defense fails in AD.
Method: RNAseq, immunochemistry of the brain, immunofluorescence, and confocal microscopy of macrophages.
Result: In the AD brain, MMs shuttle Aß from parenchyma to vessels, which develop vasculitis, causing amyloid-related imaging abnormalities (ARIAs).
Alzheimers Dement
December 2024
University of Southern California, Los Angeles, CA, USA.
Background: Synaptic loss predicts cognitive decline in Alzheimer's disease (AD). However, the critical disease modifying molecular mechanisms of synaptic failure remain elusive. Animal studies implicate the increased activation of cytosolic phospholipase (cPLA2) activation in synaptic loss and neuroinflammation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Background: Multiple AD risk genes are implicated in lipid metabolism, and plasma and brain lipid levels are altered in AD. Astrocytes are enriched in key lipid-related factors and are likely contributors to altered lipid homeostasis in AD. We hypothesize that APP/Aβ-related pathology and neuroimmune factors modulate astrocytic gene transcription that promote maladaptive changes in lipid pathways, including aberrant astrocytic production and release of lipids that could affect Aβ pathology and neuronal deficits.
View Article and Find Full Text PDFShock
December 2024
Department of Pathology and Pathophysiology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China.
Background: Sepsis-associated encephalopathy (SAE) represents a severe complication of sepsis, substantially elevating both mortality and healthcare costs for patients. Gastrodin (GAS), a principal bioactive constituent of Gastrodia elata Blume, is neuroprotective in various neurological disorders, including ischemic stroke, epilepsy, Alzheimer's disease, and neuropathic pain. In this study, we sought to investigate whether GAS could serve as a protective agent against SAE.
View Article and Find Full Text PDFMucosal Immunol
December 2024
Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Electronic address:
Inflammatory bowel diseases (IBDs) are characterized by unrestrained innate and adaptive immune responses and compromised intestinal epithelial barrier integrity. Regulatory T (T) cells are crucial for maintaining self-tolerance and immune homeostasis in intestinal tissues. Prostaglandin E (PGE), a bioactive lipid compound derived from arachidonic acid, can modulate T cell functions in a receptor subtype-specific manner.
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