Plasma glycomics predict cardiovascular disease in patients with ART-controlled HIV infections.

Despite effective control of HIV infection with antiretroviral drugs, individuals with HIV have high incidences of secondary diseases. These sequelae, such as cardiovascular disease (CVD), are poorly understood and represent a major health burden. To date, predictive biomarkers of HIV-associated secondary disease have been elusive, making preventative clinical management essentially impossible. Here, we applied a newly developed and easy to deploy, multitarget, and high-throughput glycomic analysis to banked HIV+ human plasma samples to determine whether the glycome may include biomarkers that predict future HIV-associated cardiovascular events or CVD diagnoses. Using 324 patient samples, we identified a glycomic fingerprint that was predictive of future CVD events but independent of CD4 counts, diabetes, age, and birth sex, suggesting that the plasma glycome may serve as a biomarker for specific HIV-associated sequelae. Our findings constitute the discovery of novel glycan biomarkers that could classify patients with HIV with elevated risk for CVD and reveal the untapped prognostic potential of the plasma glycome in human disease.-Oswald, D. M., Sim, E. S., Baker, C., Farhan, O., Debanne, S. M., Morris, N. J., Rodriguez, B. G., Jones, M. B., Cobb, B. A. Plasma glycomics predict cardiovascular disease in patients with ART-controlled HIV infections.

Adjunctive Pharmacotherapies in Children With Asthma Exacerbations Requiring Continuous Albuterol Therapy: Findings From The Ohio Pediatric Asthma Repository.

OBJECTIVES: To identify associations between use of ipratropium and/or intravenous magnesium and outcomes of children hospitalized with acute asthma exacerbations and treated with continuous albuterol. METHODS: Secondary analysis of data from children prospectively enrolled in the multicenter Ohio Pediatric Asthma Repository restricted to only children who were treated with continuous albuterol in their initial inpatient location. Children were treated with adjunctive therapies per the clinical team. RESULTS: Among 242 children who received continuous albuterol, 94 (39%) received ipratropium only, 13 (5%) received magnesium alone, 42 (17%) received both, and 93 (38%) received neither. The median duration of continuous albuterol was 7.0 (interquartile range [IQR]: 2.8-12.0) hours. Ipratropium use was associated with a shorter duration of continuous albuterol (4.9 [IQR: 2.0-10.0] hours) compared with dual therapy (11.0 [IQR: 5.6-28.6] hours; P = .001), but magnesium use was not (7.5 [IQR: 2.5-16.0] hours; P = .542). In Cox proportional models (adjusted for hospital, demographics, treatment location, and respiratory failure), magnesium was associated with longer durations of continuous albuterol (hazard ratio, 0.54 [95% confidence interval: 0.37-0.77]; P < .001) and hospitalization (hazard ratio, 0.41 [95% confidence interval: 0.28-0.60]; P < .001), but ipratropium was not. CONCLUSIONS: Ipratropium and magnesium were both often used in children with severe asthma hospitalizations that required continuous albuterol therapy. Magnesium use was associated with unfavorable outcomes, possibly reflecting preferential treatment to patients with more severe cases and differing practices between centers. Given the high prevalence of asthma, wide variations in practice, and the potential to improve outcomes and costs, prospective trials of these adjunctive therapies are needed.

A retrospective evaluation of the age-adjusted D-dimer versus the conventional D-dimer for pulmonary embolism.

: The conventional D-dimer cut-off value of at least 500 µg FEU/l has good sensitivity but poor specificity for identifying pulmonary embolism. An elevated age-adjusted D-dimer value (age in years × 10 µg FEU/l) for patients at least 50 years old has been recommended as a better cut-off with adequate sensitivity and improved specificity for identifying pulmonary embolism compared with the conventional value. We retrospectively reviewed 3117 patient encounters in which a D-dimer was ordered. The D-dimer value, age of the patient, and the computed tomography radiology report was evaluated. The sensitivity and specificity of the age-adjusted D-dimer was calculated using bootstrapping. With an assumed 99% sensitivity for the conventional D-dimer cut-off the specificity was 39.2% [95% confidence interval (CI): 37.5-41.0%]. The sensitivity of the age-adjusted D-dimer was 91.8% (95% CI: 83.8-97.2%) with a specificity of 51.0% (95% CI: 49.1-53.1%). The sensitivity of the age-adjusted D-dimer was unacceptably low compared with the conventional D-dimer cut-off.

Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation.

Disruption of microvascular blood flow is a common cause of tissue hypoxia in disease, yet no therapies are available that directly target the microvasculature to improve tissue oxygenation. Red blood cells (RBCs) autoregulate blood flow through S-nitroso-hemoglobin (SNO-Hb)-mediated export of nitric oxide (NO) bioactivity. We therefore tested the idea that pharmacological enhancement of RBCs using the S-nitrosylating agent ethyl nitrite (ENO) may provide a novel approach to improve tissue oxygenation. Serial ENO dosing was carried out in sheep (1-400 ppm) and humans (1-100 ppm) at normoxia and at reduced fraction of inspired oxygen (FiO2 ). ENO increased RBC SNO-Hb levels, corrected hypoxia-induced deficits in tissue oxygenation, and improved measures of oxygen utilization in both species. No adverse effects or safety concerns were identified. Inasmuch as impaired oxygenation is a major cause of morbidity and mortality, ENO may have widespread therapeutic utility, providing a first-in-class agent targeting the microvasculature.