Lung Injury Induces Alveolar Type 2 Cell Hypertrophy and Polyploidy with Implications for Repair and Regeneration.

Epithelial polyploidization after injury is a conserved phenomenon recently shown to improve barrier restoration during wound healing. Whether lung injury can induce alveolar epithelial polyploidy is not known. We show that bleomycin injury induces alveolar type 2 cell (AT2) hypertrophy and polyploidy. AT2 polyploidization is also seen in short term ex vivo cultures, where AT2-to-AT1 transdifferentiation is associated with substantial binucleation due to failed cytokinesis. Both hypertrophic and polyploid features of AT2 cells can be attenuated by inhibiting the integrated stress response using the small molecule ISRIB. These data suggest that AT2 hypertrophic growth and polyploidization may be a feature of alveolar epithelial injury. Because AT2 cells serve as facultative progenitors for the distal lung epithelium, a propensity for injury-induced binucleation has implications for AT2 self-renewal and regenerative potential upon reinjury, which may benefit from targeting the integrated stress response.

Prediction of Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: An Enhanced Model of BARD Score.

BACKGROUND/AIMS: The BARD score is a model to detect advanced liver fibrosis in nonalcoholic fatty liver disease (NAFLD) patients. The aims of this study were to identify additional factors and then to build an enhanced version of the BARD score. METHODS: One hundred seven patients with biopsy-proven NAFLD were enrolled retrospectively. Logistic regressions were performed to identify independent risk factors for advanced liver fibrosis (stage 3 or 4). An enhanced model of the BARD score (BARDI score) was built and evaluated with a receiver operating characteristic (ROC) curve. RESULTS: In multivariate analysis, age (odds ratio [OR], 0.89; p=0.04), aspartate aminotransferase/alanine aminotransferase ratio (OR, 1.73; p<0.01), and international normalized ratio (INR) (OR, 8.85; p<0.01) were independently significant factors. The BARDI score was created by adding the INR to the BARD. The area under the ROC curve of the BARDI score was significantly larger than that of the BARD score (0.881 vs 0.808, p<0.01). A BARDI score of 3 or more showed a positive predictive value (PPV) of 51.0% and a negative predictive value (NPV) of 96.0%. CONCLUSIONS: The BARDI score had an improved PPV over the BARD score and maintained an excellent NPV. Further study is warranted for its external validation and comparison with other models.