Longitudinal Assessment of Cytokine Expression and Plasminogen Activation in Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction in End-Stage Disease

Simons, Peter C.; Guo, Yan; Bondu, Virginie; Tigert, Susan L; Harkins, Michelle; Goodfellow, Samuel M; Tompkins, Cana; Chabot‐Richards, Devon; Yang, Xuexian O.; Bosc, Laura V. González; Bradfute, Steven B.; Lawrence, Daniel A.; Buranda, Tione

doi:10.3390/v13081597

Cited by 4 publications

(2 citation statements)

References 88 publications

(131 reference statements)

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“…We next used Principal Component Analysis (PCA) 38 to determine the relationship between the relative expression of different types of significant leukocyte groups: lymphocytes (L), monocytes (M), and neutrophils (N) and their immune function represented by Rac1•GTP measured in PBMCs and PMNs from patients with confirmed bloodstream infection compared to uninfected controls. ( Fig.…”

Section: Resultsmentioning

confidence: 99%

G-Trap Assay II: Characterization of blood Leukocyte Functionality differentiates immune activation and immune suppression in bacteremia patient samples

Simons

Shevy

Bondu

et al. 2022

Preprint

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Sepsis is a severe organ dysfunction syndrome caused by a dysregulation of the immune system’s response to infection. Unfortunately, most infection-causing pathogens aren’t routinely detectable in real-time to enable targeted and lifesaving treatment. Thus, clinicians frequently have limited data on which to base treatment decisions. A complete blood count with differential is available within 24 h, and positive culture is only available in ∼30% of cases. Furthermore, a blood culture, the traditional gold standard for accurate diagnosis of bacteremia, may take up to five days for results, long after a clinical decision for sepsis management is required. Circulating leukocytes can sense chemotactic signals released by bloodborne pathogens or focal infections not in the bloodstream. Our earlier study showed that pathogen and host immune factors released in the bloodstream stimulated GTP binding of Ras homology (Rho) GTPases such as Rac1 in quiescent endothelial and human leukocytes after exposure to blood plasma from infected patients.1 In this study, we measured Rac1•GTP as a biomarker of immune functionality of peripheral blood monocytes and polymorphonuclear cells extracted from blood samples drawn for diagnostic use in blood culture assays; from 120 non-infected control patients and serial blood test samples from 28 patients with a confirmed diagnosis of bloodstream infection. 18 cases presented with Rac1•GTP elevation of ≥3 fold above that of control samples. Ten patients with normal or below-normal GTPase activity, accompanied by neutrophilia or pancytopenia. We used Principal Component Analysis to differentiate the 2D spatial distribution of infected patients and negative controls. Measuring differential leukocyte functionality in infected and control patients’ blood samples with the G-Trap assay may provide an innovative process for a real-time distinction between infection and non-infectious etiologies.

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Section: Resultsmentioning

confidence: 99%

G-Trap Assay II: Characterization of blood Leukocyte Functionality differentiates immune activation and immune suppression in bacteremia patient samples

Simons

Shevy

Bondu

et al. 2022

Preprint

Self Cite

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“…Thrombolytic (clot‐busting) drugs dissolve blood clots within blood vessels and are used in medical devices to prevent damage to components from clot formation. In particular, tPA, [ 78 ] rtPA, [ 79 ] urokinase plasminogen activator (uPA), [ 80 ] and streptokinase are commonly used thrombolytic drugs in ECMO. These drugs activate plasminogen, which degrades fibrin, the main component of blood clots.…”

Section: Toward Drug‐loaded Liposomes For Thrombosis Prevention In Me...mentioning

confidence: 99%

Shear‐Responsive Drug Delivery Systems in Medical Devices: Focus on Thrombosis and Bleeding

Shirejini

Carberry

Alt

et al. 2023

Adv Funct Materials

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Cardiovascular disease is the leading cause of death worldwide. Blood‐contacting medical devices provide critical support for patients with severe respiratory and/or cardiac failure. High shear stress zones and non‐biocompatible circuit can increase the risk of thrombus formation in patients. These thrombi restrict blood flow through the circuits and travel to the lungs and brain, creating significant consequences. Antithrombotic drugs are used to lower this risk, but they also raise the incidence of bleeding problems. This article explores the delicate balance between thrombosis and bleeding in medical devices by examining platelet activation and thrombosis formation under shear stress. The feasibility of a shear‐responsive nanomedicine‐based drug delivery system has been explored as a potential approach for targeted administration of antithrombotic medications to lower systemic drug levels and reduce the bleeding risk. Furthermore, the lack of in vitro platforms to investigate the biological behavior of antithrombotic nanoparticles is impeding their clinical translation. As a result, microfluidic technology offers a platform for investigating nanoparticle behavior in vitro and linking it to their performance in vivo. Finally, the challenges and factors that affect the functionality, stability, and circulation time of liposomal drugs are investigated to improve their efficacy for targeted drug administration in medical devices.

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Hantavirus Pulmonary Syndrome: 1993–2018

Thorp¹,

Fullerton²,

Whitesell

et al. 2023

Pediatrics

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OBJECTIVES: From 1993 to 2018, hantavirus infections were reported in 39 states, with hantavirus pulmonary syndrome (HPS) as the most common and fatal manifestation. To identify differences in the presentation of HPS between children and adults, we hypothesized that children with HPS would be diagnosed later in their illness course given the nonspecific clinical features of HPS. METHODS: This was an evaluation of the clinical and demographic characteristics of national HPS cases from 1993 to 2018. Data were from the Centers for Disease Control and Prevention database and 1 state department of health, comprising 97% of US cases. We compared children (0 to 12 years), adolescents (13 to 18 years), and adults using nonparametric and parametric analyses, with additional exploratory analyses to identify clinical variables associated with mortality. RESULTS: Among 719 HPS patients, 22 (3.0%) were aged ≤12 years, 47 (6.5%) were 13 to 18 years old, and the remaining 650 (90.4%) were adults. Overall mortality was 35.4% and did not differ between age groups (P = .8). The time between symptom onset and death differed by age group, with children living a median of 2 days (interquartile range [IQR] 2 to 3), adolescents 4 days (IQR 3 to 5), and adults 5 days (IQR 4 to 8; P = .001). The mean highest hematocrit and median highest creatinine level were significantly associated with mortality in those 0 to 18 years old but not adults. CONCLUSIONS: In our dataset representing the largest study of HPS in the United States, we found that children with HPS died more quickly than adults and that highest hematocrit and creatinine levels were associated with death only among those <19 years old.

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Longitudinal Assessment of Cytokine Expression and Plasminogen Activation in Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction in End-Stage Disease

Cited by 4 publications

References 88 publications

G-Trap Assay II: Characterization of blood Leukocyte Functionality differentiates immune activation and immune suppression in bacteremia patient samples

G-Trap Assay II: Characterization of blood Leukocyte Functionality differentiates immune activation and immune suppression in bacteremia patient samples

Shear‐Responsive Drug Delivery Systems in Medical Devices: Focus on Thrombosis and Bleeding

Hantavirus Pulmonary Syndrome: 1993–2018

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