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Browsing by Author "Warren, Cirle A."

Now showing 1 - 4 of 4
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    Alanyl-glutamine Supplementation for Clostridioides difficile Infection Treatment (ACT): A double-blind randomized controlled trial
    Warren, Cirle A.; Shin, Jae Hyun; Bansal, Ekta N.; Costa, Deiziane V. D. S.; Wang, Xin Qun; Wu, Martin; Swann, Jonathan R.; Behm, Brian W.; Targonski, Paul V.; Archbald-Pannone, Laurie (BMJ Journals, 2023-07-19)
    Introduction: Clostridioides difficile is the leading cause of healthcare-associated infections in the USA, with an estimated 1 billion dollars in excess cost to the healthcare system annually. C. difficile infection (CDI) has high recurrence rate, up to 25% after first episode and up to 60% for succeeding episodes. Preliminary in vitro and in vivo studies indicate that alanyl-glutamine (AQ) may be beneficial in treating CDI by its effect on restoring intestinal integrity in the epithelial barrier, ameliorating inflammation and decreasing relapse. Methods and analysis: This study is a randomised, placebo-controlled, double-blind, phase II clinical trial. The trial is designed to determine optimal dose and safety of oral AQ at 4, 24 and 44 g doses administered daily for 10 days concurrent with standard treatment of non-severe or severe uncomplicated CDI in persons age 18 and older. The primary outcome of interest is CDI recurrence during 60 days post-treatment follow-up, with the secondary outcome of mortality during 60 days post-treatment follow-up. Exploratory analysis will be done to determine the impact of AQ supplementation on intestinal and systemic inflammation, as well as intestinal microbial and metabolic profiles. Ethics and dissemination: The study has received University of Virginia Institutional Review Board approval (HSR200046, Protocol v9, April 2023). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications. Trial registration number NCT04305769.
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    Functional and cognitive status in Clostridium difficile infection in the hospitalized elderly: A Retrospective Study of Two Sites
    Fernandez-Cotarelo, Maria-Jose; Nagy-Agren, Stephanie E.; Smolkin, Mark E.; Jiminez-Diez-Canseco, Leticia; Perez-Pomata, Maria-Teresa; Shenal, Brian V.; Warren, Cirle A. (Springer, 2019-03-20)
    Advanced age is a risk factor for Clostridium difficile infection (CDI), and older patients have more severe CDI and worse outcome [1-3]. We investigated whether CDI in the elderly is associated with functional and cognitive decline, and mortality.
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    Interaction of Clostridioides difficile infection with frailty and cognition in the elderly: A narrative review
    Fernandez-Cotarelo, Maria-Jose; Jackson-Akers, Jasmine Y.; Nagy-Agren, Stephanie E.; Warren, Cirle A. (2023-10-17)
    Purpose: Clostridioides difficile infection (CDI) is the leading cause of antibiotic-related diarrhea and healthcare-associated infections, affecting in particular elderly patients and their global health. This review updates the understanding of this infection, with focus on cognitive impairment and frailty as both risk factors and consequence of CDI, summarizing recent knowledge and potential mechanisms to this interplay. Methods: A literature search was conducted including terms that would incorporate cognitive and functional impairment, aging, quality of life, morbidity and mortality with CDI, microbiome and the gut–brain axis. Results: Advanced age remains a critical risk for severe disease, recurrence, and mortality in CDI. Observational and quality of life studies show evidence of functional loss in older people after acute CDI. In turn, frailty and cognitive impairment are independent predictors of death following CDI. CDI has long-term impact in the elderly, leading to increased risk of readmissions and mortality even months after the acute event. Immune senescence and the aging microbiota are key in susceptibility to CDI, with factors including inflammation and exposure to luminal microbial products playing a role in the gut–brain axis. Conclusions: Frailty and poor health status are risk factors for CDI in the elderly. CDI affects quality of life, cognition and functionality, contributing to a decline in patient health over time and leading to early and late mortality. Narrative synthesis of the evidence suggests a framework for viewing the cycle of functional and cognitive decline in the elderly with CDI, impacting the gut–brain and gut–muscle axes.
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    Modeling the Role of Peroxisome Proliferator-Activated Receptor c and MicroRNA-146 in Mucosal Immune Responses to Clostridium difficile
    Viladomiu, Monica; Hontecillas, Raquel; Pedragosa, Mireia; Carbo, Adria; Hoops, Stefan; Michalak, Pawel; Michalak, Katarzyna; Guerrant, Richard L.; Roche, James K.; Warren, Cirle A.; Bassaganya-Riera, Josep (Public Library of Science, 2012-10-11)
    Clostridium difficile is an anaerobic bacterium that has re-emerged as a facultative pathogen and can cause nosocomial diarrhea, colitis or even death. Peroxisome proliferator-activated receptor (PPAR) c has been implicated in the prevention of inflammation in autoimmune and infectious diseases; however, its role in the immunoregulatory mechanisms modulating host responses to C. difficile and its toxins remains largely unknown. To characterize the role of PPARc in C. difficileassociated disease (CDAD), immunity and gut pathology, we used a mouse model of C. difficile infection in wild-type and T cell-specific PPARc null mice. The loss of PPARc in T cells increased disease activity and colonic inflammatory lesions following C. difficile infection. Colonic expression of IL-17 was upregulated and IL-10 downregulated in colons of T cellspecific PPARc null mice. Also, both the loss of PPARc in T cells and C. difficile infection favored Th17 responses in spleen and colonic lamina propria of mice with CDAD. MicroRNA (miRNA)-sequencing analysis and RT-PCR validation indicated that miR-146b was significantly overexpressed and nuclear receptor co-activator 4 (NCOA4) suppressed in colons of C. difficile infected mice. We next developed a computational model that predicts the upregulation of miR-146b, downregulation of the PPARc co-activator NCOA4, and PPARc, leading to upregulation of IL-17. Oral treatment of C. difficile-infected mice with the PPARc agonist pioglitazone ameliorated colitis and suppressed pro-inflammatory gene expression. In conclusion, our data indicates that miRNA-146b and PPARc activation may be implicated in the regulation of Th17 responses and colitis in C. difficile-infected mice.