Faculty Bibliography

BACKGROUND: Age and duration of mechanical ventilation (MV) are strongly associated with mortality and hospital discharge disposition. METHODS: Electronic administrative records from a 425-bed community teaching hospital were obtained for 9,912 patients who were admitted to hospital ICUs between 2003 and 2008. Risk estimates of age and duration of MV for in-hospital mortality and discharge to home vs extended-care facilities (ECFs) also were obtained. RESULTS: Of 9,912 patients, 37 were discharged to hospice care, and 668 were < 18 years of age. Of the remaining 9,207 patients, 4,238 received invasive MV. Mortality or hospital discharge to ECFs increased consistently for each decade of age > 65 years and as the duration of MV increased. Although only 11.7% of patients < 65 years age who received MV for 1 or 2 days died during hospitalization, the mortality rate increased to 72.1% for patients > 85 years of age who had received MV for > 7 days. For patients requiring MV for >or= 7 days, < 10% of the >or= 65 years of age and < 5% of patients >or= 85 years of age survived to be discharged home from the hospital. Multivariate logistic regression analyses showed that age > 65 years and duration of MV remained significantly associated with outcomes, even after adjustment for hospital discharge diagnoses (Charlson scores). CONCLUSIONS: This study suggests that age and duration of MV are strongly associated with mortality and posthospital disposition. If confirmed, the simple combination of age and duration of MV provides prognostic information that could be used with trajectory of illness and in the context of patients' values to inform end-of-life discussions with patients or their surrogates during a trial of critical care.

Phosphorylation of tyrosine residues on platelet-endothelial cell adhesion molecule-1 (PECAM-1), followed by signal transduction events, has been described in endothelial cells following exposure to hyperosmotic and fluid shear stress. However, it is unclear whether PECAM-1 functions as a primary mechanosensor in this process. Utilizing a PECAM-1-null EC-like cell line, we examined the importance of cellular localization and the extracellular and transmembrane domains in PECAM-1 phosphorylation responses to mechanical stress. Tyrosine phosphorylation of PECAM-1 was stimulated in response to mechanical stress in null cells transfected either with full length PECAM-1 or with PECAM-1 mutants that do not localize to the lateral cell-cell adhesion site and that do not support homophilic binding between PECAM-1 molecules. Furthermore, null cells transfected with a construct that contains the intact cytoplasmic domain of PECAM-1 fused to the extracellular and transmembrane domains of the interleukin-2 receptor also underwent mechanical stress-induced PECAM-1 tyrosine phosphorylation. These findings suggest that mechanosensitive PECAM-1 may lie downstream of a primary mechanosensor that activates a tyrosine kinase.