Rationale: Current clinical prediction scores for acute lung injury (ALI) have limited positive predictive value. No studies have evaluated predictive plasma biomarkers in a broad population of critically ill patients or as an adjunct to clinical prediction scores. Objectives: To determine whether plasma angiopoietin-2 (Ang-2), von Willebrand factor (vWF), interleukin-8 (IL-8), and/or receptor for advanced glycation end products (sRAGE) predict ALI in critically ill patients. Methods: Plasma samples were drawn from critically ill patients (n ¼ 230) identified in the emergency department. Patients who had ALI at baseline or in the subsequent 6 hours were excluded, and the remaining patients were followed for development of ALI. Measurements and Main Results: Nineteen patients developed ALI at least 6 hours after the sample draw. Higher levels of Ang-2 and IL-8 were significantly associated with increased development of ALI (P ¼ 0.0008, 0.004, respectively). The association between Ang-2 and subsequent development of ALI was robust to adjustment for sepsis and vasopressor use. Ang-2 and the Lung Injury Prediction Score each independently discriminated well between those who developed ALI and those who did not (area under the receiver operating characteristic curve, 0.74 for each), and using the two together improved the area under the curve to 0.84 (vs. 0.74, P ¼ 0.05). In contrast, plasma levels of sRAGE and vWF were not predictive of ALI. Conclusions: Plasma biomarkers such as Ang-2 can improve clinical prediction scores and identify patients at high risk for ALI. In addition, the early rise of Ang-2 emphasizes the importance of endothelial injury in the early pathogenesis of ALI.

Background. Cognitive impairment persists despite suppression of plasma human immunodeficiency virus (HIV) RNA. Monocyte-related immune activation is a likely mechanism. We examined immune activation and cognition in a cohort of HIVinfected and uninfected women from the Women's Interagency HIV Study (WIHS).Methods. Blood levels of activation markers, soluble CD163 (sCD163), soluble CD14 (sCD14), CRP, IL-6, and a gut microbial translocation marker (intestinal fatty acid binding protein (I-FABP)) were measured in 253 women (73% HIV-infected). Markers were compared to concurrent (within ± one semiannual visit) neuropsychological testing performance.Results. Higher sCD163 levels were associated with worse overall performance and worse verbal learning, verbal memory, executive function, psychomotor speed, and fine motor skills (P < .05 for all comparisons). Higher sCD14 levels were associated with worse verbal learning, verbal memory, executive function, and psychomotor speed (P < .05 for all comparisons). Among women with virological suppression, sCD163 remained associated with overall performance, verbal memory, psychomotor speed, and fine motor skills, and sCD164 remained associated with executive function (P < .05 for all comparisons). CRP, IL-6, and I-FABP were not associated with worse cognitive performance.Conclusions. Monocyte activation was associated with worse cognitive performance, and associations persisted despite viral suppression. Persistent inflammatory mechanisms related to monocytes correlate to clinically pertinent brain outcomes.Keywords. CD163; CD14; women; HIV infection; cognition disorders; intesticial fatty acid-binding protein (1-19).Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is a debilitating condition that affects up to 50% of people living with HIV, despite access to combination antiretroviral therapy (cART) [1]. Understanding the cellular and molecular mechanisms leading to HAND is of clinical importance, particularly among those adherent to treatment, as HAND is associated with loss of employment [2], decreased ability to multitask [3], impaired medication self-management [4], and shorter time to virologic failure.[5] These factors influence health and quality of life [6]. Chronic immune activation is a common theme in describing potential mechanisms underlying persistence of HAND despite suppression of plasma viremia [7]. Two postulated sources of this immune activation are intracellular HIV DNA in tissues and circulating cells (eg, monocytes, lymph nodes, and, potentially, the brain) and gut microbial translocation [8,9]. However, published work describing HAND is frequently based on the evaluation of study participants who have a mixture of suppressed or unsuppressed plasma HIV RNA levels, a factor that limits our understanding of persistent impairment despite suppressive therapy [10].Circulation of activated CD14 + /CD16 + monocytes containing HIV contribute to chronic immune activation. These monocytes are theorized to carry HIV into the brain [7]....

Staphylococcus aureus is a leading cause of bacteremia (1, 2). Even when an individual is appropriately treated, the risk of mortality from S. aureus bacteremia (SAB) is 20 to 40% per episode (3-8). Furthermore, the morbidity from SAB is striking, with 10 to 15% of episodes being complicated by endocarditis or a risk of metastatic disease elsewhere in the body (9, 10). The financial consequences of SAB are also significant, with health care costs ranging from $12,078 to $25,573 per episode of SAB (11-13). Typically, SAB is treated with narrow-spectrum beta-lactam antibiotics for methicillin-susceptible S. aureus (MSSA) isolates and the glycopeptide antibiotic vancomycin for methicillin-resistant S. aureus (MRSA) isolates (14-17). Isolates with vancomycin MICs of Յ2 g/ml are considered susceptible, those with MICs of 4 to 8 g/ml are considered intermediately resistant, and those with MICs of Ͼ8 g/ml are designated resistant (18). The question of whether infection by S. aureus strains with vancomycin MICs of 2 g/ml is associated with worse outcomes has been a topic of much research, although a consensus has not been reached. Compared with research methods such as Epsilometer testing (Etest) or broth microdilution (BMD), automated MIC measurements can be off by 1 dilution in either direction (e.g., a value of 2 g/ml could mean 1 or 4 g/ml if repeated) (19,20), which adds to the deliberation over interpreting study results, although consistency between BMD and Etest results can also vary. In addition, most studies have focused on MRSA, but the role of vancomycin MIC in MSSA infection has not been fully evaluated. A number of studies, including systematic reviews and meta-analyses, have demonstrated increased mortality in the setting of SAB with vancomycin MICs of Ն2.0 g/ml (21-28). Conversely, others have shown an increased risk of mortality in individuals with MICs of Ͻ2.0 g/ml (29-32). In spite of these data, the majority of studies have failed to show any significant increase in the risk of mortality attributable to vancomycin MIC (5,26,. A recent rigorous meta-analysis failed to demonstrate increased 30-day or in-hospital mortality attributable to vancomycin MIC, irrespective of the MIC cutoff that was chosen (1.5, 2.0, 4.0, or 8.0 g/ml) (5). Although valuable, meta-analyses are lim-