Inaccurate point-of-care blood glucose measurement in a dog with secondary erythrocytosis.

BACKGROUND: Point-of-care (POC) portable blood glucose meters (PBGMs) are convenient and inexpensive tools for assessing patient blood glucose concentrations. They are often used to quickly diagnose hypoglycemia or collect serial glucose readings in diabetic patients. However, POC meters have been previously identified in human and veterinary literature to be inaccurate when utilized in patients with abnormal HCT. This problem may not be reflected in manufacturer guidelines referenced by practitioners in the POC setting. KEY FINDINGS: A 1.5-year-old dog, previously diagnosed with multiple congenital cardiac malformations, right-to-left cardiac shunting and secondary erythrocytosis, presented to a veterinary emergency center minimally responsive and without detectable pulses. PBGM measurement identified hypoglycemia. Following stabilization of the dog, serial glucose assessments showed discordant results between PBGMs and the reference laboratory biochemistry analyzer. A pathological cause for hypoglycemia was not identified and PBGM readings were determined to be erroneously low due to the dog's abnormally high HCT. SIGNIFICANCE: This case demonstrates the limitations of using PBGMs to assess blood glucose in a dog with secondary erythrocytosis. The report emphasizes the need for judicious use of PBGMs in critically ill patients and that these glucometers may not be reliable in patients with abnormal HCT values.

Interleukin 1/Toll-like receptor-induced autophosphorylation activates interleukin 1 receptor-associated kinase 4 and controls cytokine induction in a cell type-specific manner.

IRAK4 is a central kinase in innate immunity, but the role of its kinase activity is controversial. The mechanism of activation for IRAK4 is currently unknown, and little is known about the role of IRAK4 kinase in cytokine production, particularly in different human cell types. We show IRAK4 autophosphorylation occurs by an intermolecular reaction and that autophosphorylation is required for full catalytic activity of the kinase. Phosphorylation of any two of the residues Thr-342, Thr-345, and Ser-346 is required for full activity, and the death domain regulates the activation of IRAK4. Using antibodies against activated IRAK4, we demonstrate that IRAK4 becomes phosphorylated in human cells following stimulation by IL-1R and Toll-like receptor agonists, which can be blocked pharmacologically by a dual inhibitor of IRAK4 and IRAK1. Interestingly, in dermal fibroblasts, although complete inhibition of IRAK4 kinase activity does not inhibit IL-1-induced IL-6 production, NF-κB, or MAPK activation, there is complete ablation of these processes in IRAK4-deficient cells. In contrast, the inhibition of IRAK kinase activity in primary human monocytes reduces R848-induced IL-6 production with minimal effect on NF-κB or MAPK activation. Taken together, these studies define the mechanism of IRAK4 activation and highlight the differential role of IRAK4 kinase activity in different human cell types as well as the distinct roles IRAK4 scaffolding and kinase functions play.