Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study.

CONTEXT: Reducing aspiration of gastric contents by placing mechanically ventilated patients in a semirecumbent position has been associated with lower incidences of ventilator-associated pneumonia (VAP). The feasibility and efficacy of this intervention in a larger patient population, however, are unknown. OBJECTIVE: Assessment of the feasibility of the semirecumbent position for intensive care unit patients and its influence on development of VAP. DESIGN: In a prospective multicentered trial, critically ill patients undergoing mechanical ventilation were randomly assigned to the semirecumbent position, with a target backrest elevation of 45 degrees , or standard care (i.e., supine position) with a backrest elevation of 10 degrees . MAIN OUTCOME MEASURES: Backrest elevation was measured continuously during the first week of ventilation with a monitor-linked device. A deviation of position was defined as a change of the randomized position >5 degrees . Diagnosis of VAP was made by quantitative cultures of samples obtained by bronchoscopic techniques. RESULTS: One hundred nine patients were assigned to the supine group and 112 to the semirecumbent group. Baseline characteristics were comparable for both groups. Average elevations were 9.8 degrees and 16.1 degrees at day 1 and day 7, respectively, for the supine group and 28.1 degrees and 22.6 degrees at day 1 and day 7, respectively, for the semirecumbent group (p < .001). The target semirecumbent position of 45 degrees was not achieved for 85% of the study time, and these patients more frequently changed position than supine-positioned patients. VAP was diagnosed in eight patients (6.5%) in the supine group and in 13 (10.7%) in the semirecumbent group (NS), after a mean of 6 (range, 3-9) and 7 (range, 3-12) days, respectively. There were no differences in numbers of patients undergoing enteral feeding, receiving stress ulcer prophylaxis, or developing pressure sores or in mortality rates or duration of ventilation and intensive care unit stay between the groups. CONCLUSIONS: The targeted backrest elevation of 45 degrees for semirecumbent positioning was not reached in the conditions of the present randomized study. The achieved difference in treatment position (28 degrees vs. 10 degrees ) did not prevent the development of VAP.

Mycobacteria target DC-SIGN to suppress dendritic cell function.

Mycobacterium tuberculosis represents a world-wide health risk and immunosuppression is a particular problem in M. tuberculosis infections. Although macrophages are primarily infected, dendritic cells (DCs) are important in inducing cellular immune responses against M. tuberculosis. We hypothesized that DCs represent a target for M. tuberculosis and that the observed immuno-suppression results from modulation of DC functions. We demonstrate that the DC-specific C-type lectin DC-SIGN is an important receptor on DCs that captures and internalizes intact Mycobacterium bovis bacillus Calmette-Guérin (BCG) through the mycobacterial cell wall component ManLAM. Antibodies against DC-SIGN block M. bovis BCG infection of DCs. ManLAM is also secreted by M. tuberculosis-infected macrophages and has been implicated as a virulence factor. Strikingly, ManLAM binding to DC-SIGN prevents mycobacteria- or LPS-induced DC maturation. Both mycobacteria and LPS induce DC maturation through Toll-like receptor (TLR) signaling, suggesting that DC-SIGN, upon binding of ManLAM, interferes with TLR-mediated signals. Blocking antibodies against DC-SIGN reverse the ManLAM-mediated immunosuppressive effects. Our results suggest that M. tuberculosis targets DC-SIGN both to infect DCs and to down-regulate DC-mediated immune responses. Moreover, we demonstrate that DC-SIGN has a broader pathogen recognition profile than previously shown, suggesting that DC-SIGN may represent a molecular target for clinical intervention in infections other than HIV-1.