Patients with the acute respiratory distress syndrome (ARDS) have elevated levels of cell-free hemoglobin (CFH) in the air space, but the contribution of CFH to the pathogenesis of acute lung injury is unknown. In the present study, we demonstrate that levels of CFH in the air space correlate with measures of alveolar-capillary barrier dysfunction in humans with ARDS (r = 0.89, P < 0.001) and in mice with ventilator-induced acute lung injury (r = 0.89, P < 0.001). To investigate the specific contribution of CFH to ARDS, we studied the impact of purified CFH in the mouse lung and on cultured mouse lung epithelial (MLE-12) cells. Intratracheal delivery of CFH in mice causes acute lung injury with air space inflammation and alveolar-capillary barrier disruption. Similarly, in MLE-12 cells, CFH increases proinflammatory cytokine expression and increases paracellular permeability as measured by electrical cell-substrate impedance sensing. Next, to determine whether these effects are mediated by the iron-containing heme moiety of CFH, we treated mice with intratracheal hemin, the chloride salt of heme, and found that hemin was sufficient to increase alveolar permeability but failed to induce proinflammatory cytokine expression or epithelial cell injury. Together, these data identify CFH in the air space as a previously unrecognized driver of lung epithelial injury in human and experimental ARDS and suggest that CFH and hemin may contribute to ARDS through different mechanisms. Interventions targeting CFH and heme in the air space could provide a new therapeutic approach for ARDS.

Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography.

Study objective Induction doses of etomidate during rapid sequence intubation (RSI) cause transient adrenal dysfunction, but its clinical significance on trauma patients is uncertain. Ketamine has emerged as an alternative for RSI induction. Among adult trauma patients emergently intubated, we compared clinical outcomes among those induced with etomidate and ketamine. Methods The study entailed a retrospective evaluation of a four-year (January 2011–December 2014) period spanning an institutional protocol switch from etomidate to ketamine as the standard induction agent for adult trauma patients undergoing RSI in the ED of an academic Level I trauma center. The primary outcome was hospital mortality evaluated with multivariable logistic regression adjusted for age, vital signs, and injury severity and mechanism. Secondary outcomes included intensive care unit (ICU)-free days and ventilator-free days (VFD) evaluated with multivariable ordered logistic regression using the same covariates. Results The analysis included 968 patients, including 526 with etomidate and 442 with ketamine. Hospital mortality was 20.4% among patients induced with ketamine compared to 17.3% among those induced with etomidate (aOR: 1.41; 95% CI: 0.92, 2.16). Patients induced with ketamine had similar ICU-free-days (aOR: 0.80; 95% CI: 0.63, 1.00) and VFDs (aOR: 0.96; 95% CI: 0.76, 1.20) as compared to patients induced with etomidate. Conclusion In this analysis spanning an institutional protocol switch from etomidate to ketamine as the standard RSI induction agent for adult trauma patients, patient-centered outcomes were similar for patients who received etomidate and ketamine.

Lysosomes are dynamic organelles that undergo cycles of fusion and fission with themselves and with other organelles. Following fusion with late endosomes to form hybrid organelles, lysosomes are reformed as discrete organelles. This lysosome reformation or formation is a poorly understood process that has not been systematically analyzed and that lacks known regulators. In this study, we quantitatively define the multiple steps of lysosome formation and identify the first regulator of this process.

Even with the CDC Heads-Up campaign on concussion education, there is still need to improve appropriateness of discharge instructions for youth SRCs. There have been dramatic increases in referrals to sports concussion specialists and centers after 2010.