Protective efficacy of Bacillus Calmette-Guérin (BCG) may be
affected by the methods and routes of vaccine administration. We have studied
the safety and immunogenicity of oral (PO) and/or intradermal (ID)
administration of BCG in healthy human subjects No major safety concerns were
detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although
both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ
production, ID BCG more strongly induced systemic Th1 responses. In contrast,
stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage
T cells) were induced by PO BCG vaccination. To generate preliminary data
comparing the early gene signatures induced by mucosal and systemic BCG
vaccination, CD4+ memory T cells were isolated from subsets of BCG
vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or
stimulated with BCG infected dendritic cells, and then studied by Illumina
BeadArray transcriptomal analysis. Notably, distinct gene expression profiles
were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated
groups by GSEA analysis. Future correlation analyses between specific gene
expression patterns and distinct mucosal and systemic immune responses induced
will be highly informative for TB vaccine development.
The greatest amount of mean epoprostenol deposition resulted with the nebulizer placed at the humidifier inlet or outlet in a ventilator with bias flow.
The fluoroquinolone class, specifically those with adequate activity against respiratory pathogens, represents an important and convenient treatment option for patients with CAP.
Several patient populations have been identified as high risk for extubation failure despite successful completion of a spontaneous breathing trial (SBT). Extubation failure and subsequent need for emergent re-intubation have been associated with increased morbidity and mortality. In this review, we discuss ways to optimize the value and performance of the SBT in a subgroup of high-risk patients (elderly, cardiac, and/or respiratory failure) to reduce the rate of extubation failure. We recommend the use of T-piece mode, longer duration SBT, and measurement of the rapid shallow breathing index (breathing frequency/tidal volume in L) off ventilatory support to increase the predictive value of the SBT. In addition, measurement of changes in central venous oxygen saturation and serum brain natriuretic peptide, and measurements of mitral inflow and annular velocity using bedside transthoracic echocardiography with tissue Doppler imaging may help guide the clinician in determining who and when to extubate and thus minimize the rate of extubation failure. Arterial blood gas analysis performed at the end of the SBT may help determine who will benefit from prophylactic use of noninvasive ventilatory support postextubation.
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