Biomarkers of immune capacity, infection and inflammation are associated with poor outcome and mortality after stroke - the PREDICT study.

BACKGROUND: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome. METHODS: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed. RESULTS: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time. CONCLUSIONS: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.

An imaging spectroscopy approach for measurement of oxygen saturation and hematocrit during intravital microscopy.

OBJECTIVE: Oxygen supply and partial pressure are key determinants of tissue metabolic status and are also regulators of vascular function including production of reactive oxygen species, vascular remodeling, and angiogenesis. The objective of this study was to develop an approach for the determination of oxygen saturation and hematocrit for individual microvessels in trans- and epi-illumination intravital microscopy. METHODS: A spectral approach was used, taking advantage of the availability of commercial imaging systems that allow digital recording of intravital images at a number of predetermined wavelengths within a relatively short time. The dependence of validity and precision of saturation measurements on critical experimental variables (reference spectra, number and selection of wavelengths, exposure time, analysis area, analysis model) was evaluated. In addition, a software approach for two-dimensional analysis of images was developed. RESULTS: Exposure times per wavelength of about 200 ms and use of up to 50 wavelengths evenly spaced from 500 to 598 nm allow automatic discrimination of microvessels from tissue background (segmentation) with reliable determination of oxygen saturation (in trans- and epi-illumination) and hematocrit (in transillumination). CONCLUSIONS: The present imaging spectroscopy approach allows detailed assessment of oxygen transport and other functional parameters at the microcirculatory level.