Extensive thin-section CT abnormalities indicative of fibroproliferative changes were independently predictive of poor prognosis in patients with a clinically early stage of ARDS.

ObjectivesTo examine whether the extent of fibroproliferative changes on high-resolution CT (HRCT) scan influences prognosis, ventilator dependency and the associated outcomes in patients with early acute respiratory distress syndrome (ARDS).DesignA prospective observational cohort study.SettingIntensive care unit in a teaching hospital.Participants85 patients with ARDS who met American-European Consensus Conference Criteria and eligible criteria.InterventionsHRCT scans were performed and prospectively evaluated by two independent observers on the day of diagnosis and graded into six findings according to the extent of fibroproliferation. An overall HRCT score was obtained by previously published method.Primary and secondary outcomesThe primary outcome was 60-day mortality. Secondary outcomes included the number of ventilator-free days, organ failure-free days, the incidence of barotraumas and the occurrence of ventilator-associated pneumonia.ResultsHigher HRCT scores were associated with statistically significant decreases in organ failure-free days as well as ventilator-free days. Multivariate Cox proportional hazards model showed that the HRCT score remained an independent risk factor for mortality (HR 1.20; 95% CI 1.06 to 1.36; p=0.005). Multivariate analysis also revealed that the CT score had predictive value for ventilator weaning within 28 days (OR 0.63; 95% CI 0.48 to 0.82; p=0.0006) as well as for an incidence of barotraumas (OR 1.61; 95% CI 1.08 to 2.38; p=0.018) and for an occurrence of ventilator-associated pneumonia (OR 1.46; 95% CI 1.13 to 1.89; p=0.004). A HRCT score <210 enabled prediction of 60-day survival with 71% sensitivity and 72% specificity and of ventilator-weaning within 28 days with 75% sensitivity and 76% specificity.ConclusionsPulmonary fibroproliferation assessed by HRCT in patients with early ARDS predicts increased mortality with an increased susceptibility to multiple organ failure, including ventilator dependency and its associated outcomes.

Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is used for treating chronic lower respiratory tract infections. It has been shown that free radicals, such as the superoxide anion and nitric oxide (NO), are pathogenic molecules in viral disease. Much attention has been given to a critical role of NO in the pathologic events of various inflammatory diseases. In the present study, we evaluated the effects of EM on influenza-virus-induced pneumonia in mice infected with a lethal dose of influenza virus A/Kumamoto/Y5/67 (H2N2). The administration of EM at a dose of 3.3 mg/kg/d (intraperitoneally, from Days 1 to 6 after infection), significantly improved the survival rate of mice infected with influenza virus, and the survival rate of the virus-infected mice at Day 20 after infection increased in a dose-dependent fashion with EM administered to the animals, from 14% among controls to 42% among animals given EM at 1.0 mg/kg/d and 57% among those given EM at 3.3 mg/kg/d. The induction of interferon-gamma (IFN-gamma) in the mouse lung was inhibited by EM treatment on Day 6 after infection. Simultaneously, the number of inflammatory cells recovered in lung lavage fluid 6 d after virus infection was significantly reduced by the treatment with EM. The EM treatment resulted in a dose-dependent decrease in the level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase (NOS)-inducting potential in the lungs of the virus-infected mice. These results indicate that EM may have substantial therapeutic value for various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing NO overproduction in the lung.

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Objective: To determine how cortical compensation occurs in higher cognitive systems during the recovery phase of diffuse axonal injury (DAI). Design: 12 right-handed patients with a magnetic resonance imaging (MRI) lesion pattern compatible with pure DAI were identified. Pure DAI was defined as finding of traumatic microbleeds on T2*-weighted gradient-echo images in the absence of otherwise traumatic or non-traumatic MRI abnormalities. 12 matched healthy controls were also enrolled. Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory test (Paced Visual Serial Attention Test (PVSAT)). Results: No significant group differences were observed in reaction times for the PVSAT. Although patients with pure DAI committed a few errors during the PVSAT, controls respond correctly to each probe. Controls showed activations in the left frontal gyrus, left parietal gyrus and right inferior parietal gyrus. Patients with pure DAI showed activations in the left inferior frontal gyrus, right inferior frontal gyrus and right middle frontal gyrus. Between-group analysis of the PVSAT task showed significantly greater activation of the right inferior frontal gyrus (BA 45) and right middle frontal gyrus (BA 9) in patient with pure DAI versus controls. Conclusions: Patients with pure DAI require compensatory activation of the contralateral (right) prefrontal region to carry out activities similar to healthy controls. These findings provide further evidence for the adaptive capacity of neuronal systems and brain plasticity during the recovery stages of DAI.