The concept of using metformin as a chemopreventive agent to control head and neck carcinogenesis is promising. Further work is warranted to elucidate largely unexplored mechanisms of metformin uptake and pharmacologic action that may ultimately influence the selection of the most suitable patients who can benefit from metformin in head and neck cancer chemoprevention.

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We previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.

BACKGROUND: Survivors of prolonged ICU admissions are bedridden and immobilized for an extended period of time. These patients often are discharged to long-term acute care hospitals (LTACHs) for continued medical care and rehabilitation. Early ambulation has been associated with improved functional outcomes and lower readmission rates in hospitalized patients. The aim of this study was to determine the association between ambulatory status and discharge disposition in survivors of prolonged ICU stays who were admitted to an LTACH. METHODS: We performed a retrospective cohort study of 285 survivors of prolonged ICU stays who were admitted to a university-affiliated LTACH facility from 2010 to 2013. Outcomes of interest included comparing the relationship between ambulatory status and disposition status (ie, home vs acute rehabilitation facility, nursing home, readmission to an ICU, or death). RESULTS: The mean age of our cohort was 59.0 6 15.3 y, with 129 (45%) males, 148 (52%) African-American, 123 (43%) white, and 14 (5%) of subjects other races. Most of these subjects were transferred from a medical ICU (68%). The median ICU and LTACH lengths of stay were 25.5 (13-38.8) d and 34.0 (14-64) d, respectively. Thirty-eight (13.3%) subjects were discharged home, 25 (8.7%) to an acute rehabilitation facility, 70 (24.6%) to a nursing home, 139 (48.8%) were readmitted to an ICU, and 13 (4.6%) died. Of 285 total subjects, 74 (26%) ambulated during physical therapy, while 211 (74%) subjects never ambulated. Of those who ambulated, 24 (32.4%) went home, whereas 14 of 211 (6.6%) subjects who did not ambulate went home (P < .001). CONCLUSIONS: The ability to ambulate was associated with a greater likelihood of being discharged home in survivors of prolonged ICU stays who were admitted to an LTACH. These results suggest that mobility training for survivors of prolonged ICU stays in LTACH facilities should be strongly emphasized to improve their likelihood of being discharged home.