Proinflammatory and Antiinflammatory Cytokine Levels in Complicated and Noncomplicated Parapneumonic Pleural Effusions

Objectives: This study aimed to evaluate a panel of proinflammatory and antiinflammatory cytokines in noncomplicated and complicated parapneumonic pleural effusions and to correlate their levels with pleural fluid biochemical parameters. Methods: Serum and pleural effusion were collected from 60 patients with noncomplicated (n = 26) or complicated (n = 34) parapneumonic effusions and assayed for cytologic, biochemical, and proinflammatory and antiinflammatory cytokines. Student t test was used to compare serum and pleural fluid values, Spearman correlation to analyze the relationship between pleural fluid cytokines and biochemical parameters, and accuracy of pleural fluid cytokine levels to determine the optimal cutoff value for identification of complicated effusions. Corrections for multiple comparisons were applied and a P value < .05 was accepted as significant. Results: Serum and pleural fluid cytokine levels of IL-8, vascular endothelial growth factor (VEGF), IL-10, and tumor necrosis factor (TNF) soluble receptor (sR) II were similar between groups. In contrast, complicated effusions had higher levels of pleural fluid IL-1 beta, IL-1 receptor antagonist (ra), and TNF sRI. Negative correlations were found between pleural fluid glucose with IL-1 beta and TNF sRI and positive correlations between lactic dehydrogenate (LDH) with IL-1 beta, IL-8, and VEGF. Pleural fluid levels of IL-1 beta, IL-1ra, and TNF sRI were more accurate than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. Conclusions: Both proinflammatory and antiinflammatory cytokine levels in pleural fluid are elevated in complicated in comparison with noncomplicated parapneumonic pleural effusions, and they correlate with both pleural fluid glucose and LDH levels. IL-1 beta, IL-1ra, and TNF sRI had higher sensitivity and specificity than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. CHEST 2012; 141( 1):183-189

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.