The Association of Prehospital Intravenous Fluids and Mortality in Patients with Penetrating Trauma.

BACKGROUND: The optimal approach to prehospital care of trauma patients is controversial, and thought to require balancing advanced field interventions with rapid transport to definitive care. OBJECTIVE: We sought principally to examine any association between the amount of prehospital IV fluid (IVF) administered and mortality. METHODS: We conducted a retrospective cohort analysis of trauma registry data patients who sustained penetrating trauma between January 2008 and February 2011, as identified in the Pennsylvania Trauma Systems Foundation registry with corresponding prehospital records from the Philadelphia Fire Department. Analyses were conducted with logistic regression models and instrumental variable analysis, adjusted for injury severity using scene vital signs before the intervention was delivered. RESULTS: There were 1966 patients identified. Overall mortality was 22.60%. Approximately two-thirds received fluids and one-third did not. Both cohorts had similar Trauma and Injury Severity Score-predicted mortality. Mortality was similar in those who received IVF (23.43%) and those who did not (21.30%) (p = 0.212). Patients who received IVF had longer mean scene times (10.82 min) than those who did not (9.18 min) (p < 0.0001), although call times were similar in those who received IVF (24.14 min) and those who did not (23.83 min) (p = 0.637). Adjusted analysis of 1722 patients demonstrated no benefit or harm associated with prehospital fluid (odds ratio [OR] 0.905, 95% confidence interval [CI] 0.47-1.75). Instrumental variable analysis utilizing variations in use of IVF across different Emergency Medical Services (EMS) units also found no association between the unit's percentage of patients that were provided fluids and mortality (OR 1.02, 95% CI 0.96-1.08). CONCLUSIONS: We found no significant difference in mortality or EMS call time between patients who did or did not receive prehospital IVF after penetrating trauma.

Notch signaling promotes airway mucous metaplasia and inhibits alveolar development.

The airways are conduits that transport atmospheric oxygen to the distal alveolus. Normally, airway mucous cells are rare. However, diseases of the airway are often characterized by mucous metaplasia, in which there are dramatic increases in mucous cell numbers. As the Notch pathway is known to regulate cell fate in many contexts, we misexpressed the active intracellular domain of the mouse Notch1 receptor in lung epithelium. Notch misexpression resulted in an increase in mucous cells and a decrease in ciliated cells in the airway. Similarly, mouse embryonic tracheal explants and adult human airway epithelium treated with Notch agonists displayed increased mucous cell numbers and decreased ciliated cell numbers. Notch antagonists had the opposite effect. Notably, Notch antagonists blocked IL13-induced mucous metaplasia. IL13 has a well-established role as an inflammatory mediator of mucous metaplasia and functions through Stat6-mediated gene transcription. We found that Notch ligands, however, are able to cause mucous metaplasia in Stat6-null cultured trachea, thus identifying a novel pathway that stimulates mucous metaplasia. Notch signaling may therefore play an important role in airway disease and, by extension, Notch antagonists may have therapeutic value. Conversely, in the distal lung, Notch misexpression prevented the differentiation of alveolar cell types. Instead, the distal lung formed cysts composed of cells that were devoid of alveolar markers but that expressed some, but not all, markers of proximal airway epithelium. Occasional distal cystic cells appeared to differentiate into normal proximal airway cells, suggesting that ectopic Notch signaling arrests the normal differentiation of distal lung progenitors before they initiate an alveolar program.

Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme.

The effects of Wnt7b on lung development were examined using a conditional Wnt7b-null mouse. Wnt7b-null lungs are markedly hypoplastic, yet display largely normal patterning and cell differentiation. In contrast to findings in prior hypomorphic Wnt7b models, we find decreased replication of both developing epithelium and mesenchyme, without abnormalities of vascular smooth muscle development. We further demonstrate that Wnt7b signals to neighboring cells to activate both autocrine and paracrine canonical Wnt signaling cascades. In contrast to results from hypomorphic models, we show that Wnt7b modulates several important signaling pathways in the lung. Together, these cascades result in the coordinated proliferation of adjacent epithelial and mesenchymal cells to stimulate organ growth with few alterations in differentiation and patterning.