Browsing by Subject "NSAID"

Now showing 1 - 4 of 4
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    Development and Validation of a Machine Learning-based, Point-of-Care Risk Calculator for Post-ERCP Pancreatitis and Prophylaxis Selection
    (Elsevier, 2024) Brenner, Todd; Kuo, Albert; Sperna Weiland, Christina J.; Kamal, Ayesha; Elmunzer, B. Joseph; Luo, Hui; Buxbaum, James; Gardner, Timothy B.; Mok, Shaffer S.; Fogel, Evan S.; Phillip, Veit; Choi, Jun-Ho; Lua, Guan W.; Lin, Ching-Chung; Reddy, D. Nageshwar; Lakhtakia, Sundeep; Goenka, Mahesh K.; Kochhar, Rakesh; Khashab, Mouen A.; van Geenen, Erwin J. M.; Singh, Vikesh K.; Tomasetti, Cristian; Akshintala, Venkata S.; Medicine, School of Medicine
    Background and Aims A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning–based tool for PEP risk prediction to aid in clinical decision making related to periprocedural prophylaxis selection and postprocedural monitoring. Methods Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk, and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a 1-month period. Results A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on 20 PEP risk factors and 5 prophylactic interventions (rectal nonsteroidal anti-inflammatory drugs [NSAIDs], aggressive hydration, combined rectal NSAIDs and aggressive hydration, pancreatic duct stenting, and combined rectal NSAIDs and pancreatic duct stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, and 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. Conclusions This study demonstrates the feasibility and utility of a novel machine learning–based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended postprocedure monitoring.
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    Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2
    (Springer Nature, 2013) Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Chitteti, Brahmananda Reddy; Speth, Jennifer M.; Hu, Peirong; Poteat, Bradley A.; Stilger, Kayla N.; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Farag, Sherif S.; Czader, Magdalena; Milne, Ginger L.; Breyer, Richard M.; Serezani, Carlos H.; Scadden, David T.; Guise, Theresa; Srour, Edward F.; Pelus, Louis M.; Medicine, School of Medicine
    To maintain lifelong production of blood cells, haematopoietic stem cells (HSCs) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSCs reside in several, perhaps overlapping, niches that produce regulatory molecules and signals necessary for homeostasis and for increased output after stress or injury. Despite considerable advances in the specific cellular or molecular mechanisms governing HSC-niche interactions, little is known about the regulatory function in the intact mammalian haematopoietic niche. Recently, we and others described a positive regulatory role for prostaglandin E2 (PGE2) on HSC function ex vivo. Here we show that inhibition of endogenous PGE2 by non-steroidal anti-inflammatory drug (NSAID) treatment in mice results in modest HSC egress from the bone marrow. Surprisingly, this was independent of the SDF-1-CXCR4 axis implicated in stem-cell migration. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin. Haematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in other species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced E-prostanoid 4 (EP4) receptor signalling. These results not only uncover unique regulatory roles for EP4 signalling in HSC retention in the niche, but also define a rapidly translatable strategy to enhance transplantation therapeutically.
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    Integrated single-cell sequencing and histopathological analyses reveal diverse injury and repair responses in a participant with acute kidney injury: a clinical-molecular-pathologic correlation
    (Elsevier, 2022) Menon, Rajasree; Bomback, Andrew S.; Lake, Blue B.; Stutzke, Christy; Grewenow, Stephanie M.; Menez, Steven; D’Agati, Vivette D.; Jain, Sanjay; Kidney Precision Medicine Project; Medicine, School of Medicine
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    Recovery from Hematopoietic Injury by Modulating Prostaglandin E2 Signaling Post-Irradiation
    (Elsevier, 2013) Hoggatt, Jonathan; Singh, Pratibha; Stilger, Kayla N.; Plett, P. Artur; Sampson, Carol H.; Chua, Hui Lin; Orschell, Christie M.; Pelus, Louis M.; Microbiology and Immunology, School of Medicine
    While high dose total body irradiation (TBI) is used therapeutically, the proliferation of nuclear weapons, increasing use of nuclear power, and worldwide radical terrorism underscore the need to develop countermeasures to a radiological mass casualty event. The hematopoietic syndrome of the acute radiation syndrome (HS-ARS) results from severe compromise to the hematopoietic system, including lymphocytopenia, neutropenia, thrombocytopenia, and possible death from infection and/or hemorrhage. Given adequate time to recover, expand, and appropriately differentiate, bone marrow hematopoietic stem cells (HSC) and progenitor cells (HPC) may overcome HS-ARS and restore homeostasis of the hematopoietic system. Prostaglandin E(2) (PGE(2)) has been shown to have pleiotropic effects on hematopoiesis, acting to inhibit apoptosis and promote self-renewal of HSC, while inhibiting HPC proliferation. We assessed the radio-mitigating potential of modulating PGE(2) signaling in a mouse model of HS-ARS. Treatment with the PGE(2) analog 16,16 dimethyl PGE(2) (dmPGE(2)) 6h post-irradiation or inhibition of PGE(2) synthesis via delayed administration of the non-steroidal anti-inflammatory drug (NSAID) Meloxicam resulted in increased survival of lethally irradiated mice. Both early dmPGE(2) and delayed Meloxicam treatment were associated with increased HPC activity 35days following irradiation, demonstrating enhanced recovery of hematopoiesis. Our results define two different treatment modalities that are highly effective and safe to administer, and can be readily available.