We report here the role of the CXC chemokine, epithelial neutrophil activating peptide (ENA-78), as an angiogenic factor in human non-small cell lung cancer (NSCLC). In freshly isolated human specimens of NSCLC, elevated levels of ENA-78 were found that strongly correlated with the vascularity of the tumors.
Primary nosocomial bloodstream infection (BSI) is a common occurrence in the intensive care unit (ICU) and is associated with a crude mortality of 31.5 to 82.4%. However, an accurate estimate of the attributable mortality has been limited because of confounding by severity of illness. We undertook this study to assess the attributable mortality and costs associated with an episode of BSI. Infected patients were defined as those who had an episode of BSI during the study period. Uninfected control subjects were matched to the infected patients based upon a number of factors, including predicted mortality on the day prior to infection. The main outcome measures were crude ICU mortality, length of stay, and costs. We found no difference in the crude mortality for the infected and the uninfected patients (35.3 and 30.9%, respectively, p = 0.51). However, among survivors, the patients with nosocomial bloodstream infections did have excess length of stay (mean, 10 d; median, 5 d; p = 0.007) and increased direct costs (mean difference, $34,508; p = 0.008). After matching for severity of illness, we could not detect an association between primary nosocomial bloodstream infections and increased ICU mortality. We did find that primary nosocomial bloodstream infections increased ICU length of stay and costs.
Objective To determine the effect of early enteral feeding on the outcome of critically ill medical patients whose hemodynamic condition is unstable. Methods Prospectively collected data in a multi-institutional medical intensive care unit database were analyzed retrospectively. A total of 1174 patients were identified who required mechanical ventilation for more than 2 days and were treated with vasopressor agents to support blood pressure. The patients were divided into 2 groups: those who received enteral nutrition (n = 707) within 48 hours of the start of mechanical ventilation, termed the early enteral nutrition group, and those who did not (n = 467), termed the late enteral nutrition group. The primary end points were overall intensive care unit and hospital mortality. Subgroup analyses were used to evaluate potential confounding variables. The data were also analyzed after adjustments for confounding by matching for propensity score. Results Intensive care unit and hospital mortality were lower in the early enteral nutrition group than in the late enteral group: 22.5% vs 28.3%; P = 03; and 34.0% vs 44.0%; P < .001, respectively. The beneficial effect of early feeding was more evident in the sickest patients, that is, those treated with multiple vasopressors (odds ratio, 0.36; 95% confidence interval, 0.15-0.85) and those without early improvement (odds ratio, 0.59; 95% confidence interval, 0.39-0.90). When adjustments were made for confounding by matching for propensity score, early feeding was associated with decreased hospital mortality. Conclusion Early enteral nutrition may be associated with reduced intensive care unit and hospital mortality in patients whose hemodynamic condition is unstable.
Bronchogenic carcinoma is the leading cause of malignancy-related mortality in the United States, with an overall 5-year survival rate of less than 15%. This aggressive behavior reflects, among other traits, the capacity of the tumor to evade normal host immune defenses, and to induce a pro-angiogenic environment. A central feature of any immune response toward tumors is the recruitment of specific immune cell populations. In the present study we investigated the infiltration of monocytes in human specimens of non-small-cell lung cancer (NSCLC). The presence of macrophages in NSCLC tumors was documented by immunohistochemistry. In vitro chemotaxis assays demonstrated higher monocyte chemotactic activity in NSCLC tumor homogenates than in normal lung tissue. We next investigated the expression of CC chemokines within specimens of NSCLC tumors. Levels of the CC chemokines were higher in NSCLC tumor tissue than in normal lung tissue. Immunolocalization showed that the cells associated with antigenic CC chemokines were the malignant tumor cells, as well as occasional stromal cells. Maximal inhibition of monocyte chemotaxis induced by NSCLC in vitro occurred in the presence of neutralizing antibodies to MCP-1 and MIP-1beta. On follow-up of 15 patients in whom we quantified macrophage infiltration, we found that those with recurrence of disease had higher levels of macrophage infiltration in their initial tumors. However, the functional significance of CC-chemokine-mediated macrophage infiltration into NSCLC remains to be determined.
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