In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in group IIIB-IV TNM stage lung cancer and is associated with poor prognosis, as shown by decreased survival among subjects with early stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with IIIB-IV stage disease. In addition, this lower airway microbiota signature was associated with upregulation of IL-17, PI3K, MAPK and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL-17 inflammatory phenotype and activation of checkpoint inhibitor markers.
Statement of Significance (50 word limit)Multiple lines of investigations have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here we support that the local airway microbiota modulates the host immune tone in lung cancer affecting tumor progression and prognosis.Research.
In novice critical care fellows, simulation-based extracorporeal membrane oxygenation training is superior to traditional training. Benefits transfer to novel scenarios and are maintained over the long term. Further studies evaluating the utility of simulation in other learner groups and for maintenance of proficiency are required.
Background-S-Adenosylmethionine (AdoMet) is a major methyl donor for transmethylation reactions and propylamine donor for the biosynthesis of polyamines in biological systems, and therefore may play a role in lung cancer development. We hypothesized that AdoMet levels were elevated in patients with lung cancer and may prove useful as a biomarker for early lung cancer.
Implementation of a rapid-response system was associated with an increase in do-not-resuscitate order placement. As a sentinel event, medical emergency team activation and transfer to a critical care unit foster consideration of goals of care and frequently results in a transition to a palliative care strategy.
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