Browsing by Subject "Platelet activation"

Now showing 1 - 3 of 3
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    Cytomegalovirus reactivation and acute and chronic complications in children with cerebral malaria: a prospective cohort study
    (Springer Nature, 2025-02-17) Mayhew, Jonathan A.; Witten, Andrew J.; Bond, Caitlin A.; Opoka, Robert O.; Bangirana, Paul; Conroy, Andrea L.; Hernandez‑Alvarado, Nelmary; Schleiss, Mark R.; John, Chandy C.; Pediatrics, School of Medicine
    Background: Virus co-infection or reactivation may modify the host response during cerebral malaria. Cytomegalovirus (CMV) DNAemia has been associated with increased morbidity and mortality in adults with sepsis; however, the impact of CMV DNAemia on adverse outcomes in children with cerebral malaria is unknown. Methods: Clinical, physiological, and neurocognitive outcomes were compared in children aged 18 months to 12 years with cerebral malaria (N = 242) based on the presence or absence of CMV DNAemia 24 h after admission. The primary study outcome was subsequent in-hospital mortality. Secondary outcomes included the presence of acute kidney injury, neurocognitive impairment over a 2-year follow-up, and chronic kidney disease at the 1-year follow-up. Markers of platelet and endothelial cell activation and oxidative and nitrosative stress were measured to characterize the mechanisms by which CMV DNAemia might contribute to pathogenesis. Results: CMV DNAemia was present in 33 children with cerebral malaria (13.6%) 24 h after admission. CMV DNAemia was not significantly associated with mortality in this study. Children with CMV-DNAemia had a higher prevalence of acute kidney injury than those without CMV-DNAemia (59.4% vs. 38.6%, p = 0.03). There was no difference in the prevalence of chronic kidney disease or long-term neurocognitive impairment based on the presence of DNAemia. CMV DNAemia was associated with elevated plasma levels of P-selectin, angiopoietin-1, asymmetric dimethylarginine, and platelet counts. Conclusions: In children with cerebral malaria, CMV DNAemia is associated with acute kidney injury but not in-hospital mortality, chronic kidney disease, or long-term neurocognitive impairment.
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    Effect of Modernized Collaborative Care for Depression on Depressive Symptoms and Cardiovascular Disease Risk Biomarkers: eIMPACT Randomized Controlled Trial
    (Elsevier, 2023) Stewart, Jesse C.; Patel, Jay S.; Polanka, Brittanny M.; Gao, Sujuan; Nurnberger, John I., Jr.; MacDonald, Krysha L.; Gupta, Samir K.; Considine, Robert V.; Kovacs, Richard J.; Vrany, Elizabeth A.; Berntson, Jessica; Hsueh, Loretta; Shell, Aubrey L.; Rollman, Bruce L.; Callahan, Christopher M.; Psychology, School of Science
    Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression. We conducted a single-center, parallel-group, assessor-blinded randomized controlled trial. Primary care patients with depression and elevated CVD risk from a safety net healthcare system (N = 216, Mage = 59 years, 78% female, 50% Black, 46% with income <$10,000/year) were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Outcomes were depressive symptoms and CVD risk biomarkers at 12 months. Intervention participants, versus usual care participants, exhibited moderate-to-large (Hedges' g = -0.65, p < 0.01) improvements in depressive symptoms. Clinical response data yielded similar results - 43% of intervention participants, versus 17% of usual care participants, had a ≥ 50% reduction in depressive symptoms (OR = 3.73, 95% CI: 1.93-7.21, p < 0.01). However, no treatment group differences were observed for the CVD risk biomarkers - i.e., brachial flow-mediated dilation, high-frequency heart rate variability, interleukin-6, high-sensitivity C-reactive protein, β-thromboglobulin, and platelet factor 4 (Hedges' gs = -0.23 to 0.02, ps ≥ 0.09). Our modernized collaborative care intervention - which harnessed technology to maximize access and minimize resources - produced clinically meaningful improvements in depressive symptoms. However, successful depression treatment did not lower CVD risk biomarkers. Our findings indicate that depression treatment alone may not be sufficient to reduce the excess CVD risk of people with depression and that alternative approaches are needed. In addition, our effective intervention highlights the utility of eHealth interventions and centralized, remote treatment delivery in safety net clinical settings and could inform contemporary integrated care approaches.
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    Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism
    (Elsevier, 2020-03-01) Kline, Jeffrey A.; Puskarich, Michael A.; Pike, Jonathan; Zagorski, John; Alves, Nathan J.; Emergency Medicine, School of Medicine
    Background: We test if inhaled nitric oxide (NO) attenuates platelet functional and metabolic hyper-reactivity in subjects with submassive pulmonary embolism (PE). Methods: Participants with PE were randomized to either 50 ppm NO + O2 or O2 only for 24 h with blood sampling at enrollment and after treatment; results were compared with healthy controls. Platelet metabolic activity was assessed by oxygen consumption (basal and uncoupled) and reactivity was assessed with agonist-stimulated thromboelastography (TEG) and fluorometric measurement of agonist-stimulated cytosolic [Ca++] without and with pharmacological soluble guanylate (sGC) modulation. Results: Participants (N = 38 per group) were well-matched at enrollment for PE severity, comorbidities as well as TEG parameters and platelet O2 consumption. NO treatment doubled the mean plasma [NO3-] (P < 0.001) indicating successful delivery, but placebo treatment produced no change. After 24 h, neither TEG nor O2 consumption parameters differed significantly between treatment groups. Platelet cytosolic [Ca++] was elevated with PE versus controls, and was decreased by treatment with cinaciguat (an sGC activator), but not riociguat (an sGC stimulator). Stimulated platelet lysate sGC activity was increased with PE compared with controls. Conclusions: In patients with acute submassive PE, despite evidence of adequate drug delivery, inhaled NO had no major effect on platelet O2 consumption or agonist-stimulated parameters on TEG. Pharmacological activation, but not stimulation, of sGC effectively decreased platelet cytosolic [Ca++], and platelet sGC activity was increased with PE, confirming the viability of sGC as a therapeutic target.