Leukocyte extracellular vesicle concentration is inversely associated with liver fibrosis severity in NAFLD.

The enhanced liver fibrosis (LFS) score and the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) are algorithmic-derived scores for diagnosing severe (F3/F4) liver fibrosis. In a pilot, substudy of the Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy (WELCOME) trial, we tested whether measurements of plasma platelet-, endothelial-, and leukocyte-derived extracellular vesicles (EVs) counts are (a) associated with, and predict, F3/F4 fibrosis and (b) able to improve risk prediction of F3/F4 fibrosis in NAFLD, building upon LFS or NFS algorithms. Twenty-six individuals with NAFLD had liver fibrosis severity determined by Kleiner scoring after liver biopsy. Plasma samples stained with CD41a, CD42b, CD31, CD105, CD14, CD16, and CD284 antibodies were analyzed using flow cytometry to measure platelet-, endothelial-, and leukocyte-derived EVs counts. The independence of associations between EVs and F3/F4 fibrosis were tested using logistic regression. Receiver operator characteristic (ROC) curves were used to evaluate F3/F4 fibrosis prediction models. LFS was more strongly associated with F3/F4 fibrosis than NFS (χ2= 15.403, P < 0.0001, and χ2= 6.300, P = 0.012, respectively). The association between LFS and F3/F4 fibrosis was further improved by addition of CD14+ EVs (χ2=20.847,P = 0.016 vs. χ2=12.803,P = 0.015, respectively) or CD16+ EVs (χ2=22.205,P = 0.009 vs. χ2=17.559,P = 0.001, respectively), and the area under the ROC for LFS (AUC = 0.915, se = 0.055, P = 0.001) was increased by the addition of CD14+ or CD16+ EVs (AUC = 0.948, se = 0.042, and P < 0.001 and AUC = 0.967, se = 0.055, P < 0.001, respectively) as predictor variables. In this small preliminary study, CD14+ and CD16+ EV counts show potential to predict liver fibrosis severity with either marker improving the ability of the LFS to identify F3/F4 fibrosis in this small preliminary cohort study.

IL-6 is a predictive biomarker for stroke associated infection and future mortality in the elderly after an ischemic stroke.

BACKGROUND AND PURPOSE: Stroke associated infection (within the first seven days) occurs in approximately half of stroke patients and is associated with a worse prognosis, especially in the elderly. It is uncertain what factors predict stroke associated infection, yet identification of a suitable biomarker for infection may allow early and appropriate intervention with antibiotics. The aims of this study were to: a) identify independent risk factors for stroke associated infection, and b) test relationships between these risk factors and mortality at 2 years. METHODS: Eight-two elderly patients were assessed within 72 h of stroke. Data on stroke severity (Barthel Index), stroke associated infection and mortality at 2 years were collected. Inflammatory biomarkers at baseline and 6 months were measured by ELISA. Logistic regression was used to identify risk factors for stroke associated infection and death. RESULTS: Patients with stroke associated infection, especially pneumonia, had increased IL-6, more severe strokes, and higher mortality. IL-6 was independently associated with stroke associated infection (OR = 19.2, [95%CI 3.68, 100], p < 0.001), after adjustment for other risk factors and cytokines. IL-6 was also independently associated with 2 year mortality (OR = 9.2, [1.0, 85.1], p = 0.031). CONCLUSIONS: These data suggest that IL-6 may be a key biomarker for predicting stroke associated infection and mortality in the first two years post stroke.

Aspirin resistance is more common in lacunar strokes than embolic strokes and is related to stroke severity.

The aim of this study was to investigate the relationship between aspirin resistance, ischaemic stroke subtype, stroke severity, and inflammatory cytokines. Aspirin resistance was assessed by thrombelastography in 45 people with ischaemic stroke and 25 controls. Plasma interleukin (IL)-6 was measured. Stroke severity was assessed using the modified Rankin scale and National Institute of Health Stroke Score within 72 h of stroke. Aspirin resistance was more common in the stroke than the control group (67% versus 40%, P=0.028), and within the stroke group the aspirin-resistant group had a higher Rankin score (4.0 versus 2.0, P=0.013). Aspirin resistance was greater in lacunar than embolic strokes (platelet activation 79% versus 59%, P=0.020). The stroke aspirin-resistant group had higher levels of IL-6 than the stroke aspirin-sensitive group (2.4+/-1 versus 1.8+/-0.9 ng/mL, P=0.037). Using multivariate analysis, we examined the interrelationships between aspirin resistance, IL-6, and stroke severity. These analyses showed that IL-6 was independently associated with stroke severity as the outcome (B=3.738, P=0.036), and aspirin resistance was independently associated with IL-6 (B=0.765, P=0.005) as the outcome. In conclusion, aspirin resistance is related to stroke severity and aspirin resistance is more common in lacunar strokes than embolic strokes.