Browsing by Author "Prasad, Nagendra K."

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    Biomarkers of Delirium Duration and Delirium Severity in the ICU
    (Wolters Kluwer, 2020-03) Khan, Babar A.; Perkins, Anthony J.; Prasad, Nagendra K.; Shekhar, Anantha; Campbell, Noll L.; Gao, Sujuan; Wang, Sophia; Khan, Sikandar H.; Marcantonio, Edward R.; Twigg, Homer L., III.; Boustani, Malaz A.; Medicine, School of Medicine
    Objectives: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality. Design: Observational study. Setting: Three Indianapolis hospitals. Patients: Three-hundred twenty-one critically ill delirious patients. Interventions: None. Measurements and main results: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100β lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100β levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality. Conclusions: Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.
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    A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination With Ofatumumab After Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma
    (Wolters Kluwer, 2018-04) Robertson, Michael J.; Stamatkin, Christopher W.; Pelloso, David; Weisenbach, Jill; Prasad, Nagendra K.; Safa, Ahmad R.; Medicine, School of Medicine
    Interleukin-18 (IL-18) is an immunostimulatory cytokine that augments antibody-dependent cellular cytotoxicity mediated by human natural killer cells against antibody-coated lymphoma cells in vitro and that has antitumor activity in animal models. Ofatumumab is a CD20 monoclonal antibody with activity against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20 lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Cohorts of 3 patients were given intravenous infusions of ofatumumab 1000 mg weekly for 4 weeks with escalating doses of rhIL-18 as a intravenous infusion weekly for 8 consecutive weeks. Nine male patients with CD20 lymphomas were given ofatumumab in combination with rhIL-18 at doses of 3, 10, and 30 μg/kg. No unexpected or dose-limiting toxicities were observed. The mean reduction from predose levels in the number of peripheral blood natural killer cells after the first rhIL-18 infusion was 91%, 96%, and 97% for the 3, 10, and 30 μg/kg cohorts, respectively. Serum concentrations of interferon-γ and chemokines transiently increased following IL-18 dosing. rhIL-18 can be given in biologically active doses by weekly infusions in combination with ofatumumab after peripheral blood stem cell transplantation to patients with lymphoma. A maximum tolerated dose of rhIL-18 plus ofatumumab was not determined. Further studies of rhIL-18 and CD20 monoclonal antibodies in B-cell malignancies are warranted.
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    S100 calcium binding protein B as a biomarker of delirium duration in the intensive care unit – an exploratory analysis
    (Dove Press, 2013-12-02) Khan, Babar A.; Farber, Mark O.; Campbell, Noll; Perkins, Anthony; Prasad, Nagendra K.; Hui, Siu L.; Miller, Douglas K.; Calvo-Ayala, Enrique; Buckley, John D.; Ionescu, Ruxandra; Shekhar, Anantha; Ely, E. Wesley; Boustani, Malaz A.; Medicine, School of Medicine
    Background: Currently, there are no valid and reliable biomarkers to identify delirious patients predisposed to longer delirium duration. We investigated the hypothesis that elevated S100 calcium binding protein B (S100β) levels will be associated with longer delirium duration in critically ill patients. Methods: A prospective observational cohort study was performed in the medical, surgical, and progressive intensive care units (ICUs) of a tertiary care, university affiliated, and urban hospital. Sixty-three delirious patients were selected for the analysis, with two samples of S100β collected on days 1 and 8 of enrollment. The main outcome measure was delirium duration. Using the cutoff of <0.1 ng/mL and ≥0.1 ng/mL as normal and abnormal levels of S100β, respectively, on day 1 and day 8, four exposure groups were created: Group A, normal S100β levels on day 1 and day 8; Group B, normal S100β level on day 1 and abnormal S100β level on day 8; Group C, abnormal S100β level on day 1 and normal on day 8; and Group D, abnormal S100β levels on both day 1 and day 8. Results: Patients with abnormal levels of S100β showed a trend towards higher delirium duration (P=0.076); Group B (standard deviation) (7.0 [3.2] days), Group C (5.5 [6.3] days), and Group D (5.3 [6.0] days), compared to patients in Group A (3.5 [5.4] days). Conclusion: This preliminary investigation identified a potentially novel role for S100β as a biomarker for delirium duration in critically ill patients. This finding may have important implications for refining future delirium management strategies in ICU patients.