Nomogram for predicting in-hospital mortality of nonagenarians with community-acquired pneumonia.

AIM: Nonagenarians with community-acquired pneumonia (CAP) have a high mortality rate; however, appropriate tools for reliable severity assessment in this population are lacking. The current study aimed to evaluate the risk factors and establish a nomogram to predict in-hospital mortality of nonagenarians with CAP. METHODS: In total, 304 patients aged ≥90 years who were admitted with CAP to Jiangsu Provincial People's Hospital and Jiangsu Provincial Hospital of Chinese Medicine between 2014 and 2020 were retrospectively analyzed. Clinical information, laboratory imaging results and pathogen detection were retrieved. Significant variables independently associated with CAP were identified by a logistic regression model, and a nomogram prediction model was constructed. The nomogram was compared with the widely used assessments: CURB-65, PSI and National Early Warning Score (NEWS) scores. RESULTS: Univariate and multivariate logistic regression analyses identified gender, blood urea nitrogen, C-reactive protein-to-albumin ratio, Charlson Comorbidity Index and systemic immune inflammation index as independent factors that affect the prognosis. We created a nomogram for CAP based on these risk factors. The nomogram had a bootstrapped concordance index of 0.796 and was well-calibrated in the decision analysis curve range of 0.1-0.98. The area under the curve was 0.796 (95% CI: 0.74-0.85), significantly higher than for CURB-65, PSI and NEWS scores (P < 0.05). CONCLUSIONS: Our nomogram model can predict the outcome of hospitalized nonagenarians with CAP and guide clinicians to provide better treatment, leading to improved prognosis and reduced mortality. Geriatr Gerontol Int 2022; 22: 635-641.

Interleukin-19 Aggravates Pulmonary Fibrosis via Activating Fibroblast through TGF-ß/Smad Pathway.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia disease with no cure. Communication between injured cells is triggered and maintained by a complicated network of cytokines and their receptors. IL-19 is supported by increasing evidences for a deleterious role in respiratory diseases. However, its potential role in lung fibrosis has never been explored. Methods: Bioinformatic, immunohistochemistry and western blot analysis were used to assess the expression of IL-19 in human and mouse fibrosis lung tissues. CCK-8, transwell and flow cytometry assay were utilized to analyze the effect of IL-19 on biological behaviors of lung fibroblasts. Histopathology was used to elucidate profibrotic effect of IL-19 in vivo. Results: IL-19 was upregulated in fibrosis lung tissues. IL-19 promoted lung fibroblasts proliferation and invasion, inhibited cell apoptosis, and induced differentiation of fibroblasts to the myofibroblast phenotype, which could be revised by LY2109761, a TGF-ß/Smad signaling pathway inhibitor. Furthermore, we found that IL-19 aggravated lung fibrosis in murine bleomycin-induced lung fibrosis. Conclusions: Our results imply the profibrotic role for IL-19 through direct effects on lung fibroblasts and the potential of targeting IL-19 for therapeutic intervention in pulmonary fibrosis.

Efficacy of YAP1-gene Knockdown to Inhibit Alveolar-Epithelial-Cell Senescence and Alleviate Idiopathic Pulmonary Fibrosis (IPF).

BACKGROUND/AIM: The prevalence of idiopathic pulmonary fibrosis (IPF) increases with age and is associated with senescence of alveolar epithelial cells (AECs). AEC senescence in pulmonary cells mediates IPF. We herein aimed to determine if YAP1 gene knockdown, a member of the Hippo/YAP signal pathway, in the bleomycin (BLM)-induced mouse model of IPF, inhibits onset of senescence of AECs and alleviates IPF. MATERIALS AND METHODS: Adeno-associated viruses (AAVs) expressing Yes-associated protein 1 (YAP1) short hairpin RNA (shRNA) were delivered into the lung of BLM-induced IPF mice via intratracheal injection, to knockdown the YAP1 gene in AECs. The mice were assigned to 4 groups: G1: control (normal mice); G2: IPF mice; G3: IPF + AAV/YAP1; G4: IPF + AAV/scramble. After 28 days, AECs were examined for senescence using H&E staining, Masson's trichrome Staining, senescence-associated ß-galactosidase (SA-ß-gal) staining, western blotting and co-immunofluorescence staining, to determine the expression of YAP1, Smad-3 and p21, in order to determine the induction of senescence of ACEs. RESULTS: The severity of IPF determined by H&E staining, Masson's staining and immunofluorescence (IF) staining was positively correlated with the senescence of AECs. Down-regulation of YAP1 expression of the Hippo-signaling pathway, determined by western blotting in AECs, alleviated pulmonary fibrosis as determined by Masson's staining. Down regulation of YAP1 expression reduced the senescence of AECs as determined by ß-galactosidase (SA-ß-gal) staining, which alleviated the clinical symptoms of IPF mice, as determined by body weight and lung index. CONCLUSION: Down-regulation of YAP1 expression in AECs inhibited AEC senescence which is thought to be the cause of IPF. Therefore, future studies can focus on inhibiting YAP1 to effectively treat IPF.