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Mammalian auditory hair cells transduce sound-evoked traveling waves in the cochlea into nerve stimuli, which are essential for hearing function. Pillar cells located between the inner and outer hair cells are involved in the formation of the tunnel of Corti, which incorporates outer-hair-cell-driven fluid oscillation and basilar membrane movement, leading to the fine-tuned frequency-specific perception of sounds by the inner hair cells. However, the detailed molecular mechanism underlying the development and maintenance of pillar cells remains to be elucidated. In this study, we examined the expression and function of brain-specific angiogenesis inhibitor 3 (Bai3), an adhesion G-protein-coupled receptor, in the cochlea. We found that Bai3 was expressed in hair cells in neonatal mice and pillar cells in adult mice, and, interestingly, Bai3 knockout mice revealed the abnormal formation of pillar cells, with the elevation of the hearing threshold in a frequency-dependent manner. Furthermore, old Bai3 knockout mice showed the degeneration of hair cells and spiral ganglion neurons in the basal turn. The results suggest that Bai3 plays a crucial role in the development and/or maintenance of pillar cells, which, in turn, are necessary for normal hearing function. Our results may contribute to understanding the mechanisms of hearing loss in human patients. [ABSTRACT FROM AUTHOR]

Anti-PL-7 is an anti-tRNA synthetase antibody, and interstitial lung disease (ILD) is the most frequent complication of anti-PL-7-associated antisynthetase syndrome. However, the features of ILD have not been fully elucidated. The present study retrospectively compares 7 and 15 patients who were positive for anti-PL-7 and anti-Jo-1 antibodies, respectively. The features of ILD did not significantly differ between the two groups, but the ratio of lymphocytes in bronchoalveolar lavage fluid was higher in the Jo-1 than in the PL-7 group. High-resolution computed tomography revealed nonspecific interstitial pneumonia in all patients in the PL-7 group and organizing pneumonia in four of the 15 patients in the Jo-1 group. These findings suggest that pulmonary complications slightly differ between patients expressing anti-PL-7 and anti-Jo-1 antibodies. Further studies are required to clarify the features of ILD associated with PL-7., Author(s): Masaomi Tomonaga[sup.1] , Noriho Sakamoto[sup.1] , Yuji Ishimatsu[sup.1] , Tomoyuki Kakugawa[sup.1] , Tatsuhiko Harada[sup.1] , Shota Nakashima[sup.1] , Atsuko Hara[sup.1] , Shintaro Hara[sup.1] , Yoshihiro Horai[sup.2] , Atsushi Kawakami[sup.2] [...]

The association between gut microbiota and the lung immune system has been attracting increasing interest. Here, we report a case of pancreatic cancer in which the dipeptidyl peptidase‐4 inhibitor vildagliptin induced unusual manifestations of interstitial pneumonia, possibly under the influence of Lactobacillus paraplantarum probiotic supplementation. Chest computed tomography and positron emission tomography showed multiple ground‐glass nodules (GGNs) mimicking metastatic lung cancer. Transbronchial biopsy specimens showed mild fibrosis and infiltration of lymphocytes consisting of more CD4+ than CD8+ cells. The CD4+ cells did not include FOXP3+ regulatory T cells. Bronchoalveolar lavage confirmed lymphocytosis with a markedly increased CD4+/CD8+ ratio of 7.4. The nodules disappeared shortly after vildagliptin and probiotics were withheld. If unusual interstitial pneumonia is observed in some cancer patients, physicians should pay careful attention to their medication history, including probiotic supplements. [ABSTRACT FROM AUTHOR]

The circulating tumor DNA (ctDNA) assay has recently been approved for the selection of EGFR-tyrosine kinase inhibitors as first-line treatment in lung cancer. However, it remains to be determined whether this assay can detect all complex EGFR mutations within a single tumor. We report a case of an elderly woman with stage IV lung adenocarcinoma, in which EGFR mutation assays detected L858R and pretreatment T790M from a tissue biopsy. In contrast, the circulating tumor DNA assay detected L858R, but not pretreatment T790M in the plasma, regardless of the fact that similar amounts of each mutation were present in the biopsy specimen. Treatment with afatinib was not effective, but subsequent treatment with osimertinib remarkably regressed the tumor. Our findings indicate that physicians should accurately evaluate EGFR-tyrosine kinase inhibitor-insensitive mutations using tissue samples in the first-line setting, even when L858R and exon 19 deletions are detected in the plasma. [ABSTRACT FROM AUTHOR]

Pulmonary pleomorphic carcinoma has been shown to respond remarkably to PD-1 inhibitors; however, the biomarkers for this therapy have not been fully proven. We report a case of pulmonary pleomorphic carcinoma with overexpressed PD-L1, in which a complete response to nivolumab was sustained for >14 months. Immunohistochemical analysis revealed few PD-1+ immune cells and regulatory T cells in the tumor, in addition to predominant infiltration of CD8+ cells and macrophages. Our findings suggest that the presence of a small number of PD-1+ immune cells and regulatory T cells should be investigated as candidate therapeutic biomarkers. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbations of idiopathic pulmonary fibrosis are major causes of morbidity and mortality among patients with idiopathic pulmonary fibrosis. However, acute exacerbations remain unpredictable. The aim of this study was to investigate risk factors for acute exacerbations of idiopathic pulmonary fibrosis.Methods: We performed a retrospective cohort study of patients with idiopathic pulmonary fibrosis who visited our institutions from January 1999 to September 2014. We investigated risk factors for acute exacerbations in patients with idiopathic pulmonary fibrosis diagnosed retrospectively based on the official 2011 idiopathic pulmonary fibrosis ATS/ERS/JRS/ALAT Update Statement.Results: The idiopathic pulmonary fibrosis study cohort included 65 subjects. The median follow-up period was 2.6 years. During follow-up, 24 patients (36.9 %) experienced acute exacerbations. A Kaplan-Meier curve demonstrated that the 1-year, 2-year, and 3-year incidences of acute exacerbation were 9.6, 19.2 and 31.0 %, respectively. Acute exacerbation exerted a significant impact on overall survival among those with the disease. A log-rank test showed that baseline cardiovascular diseases, higher GAP (gender, age, physiology) stage (≥II), higher serum lactate dehydrogenase level (≥180 U/L), higher serum surfactant protein-D level (≥194.7 ng/mL), higher neutrophil (≥1.77 %) and eosinophil (≥3.21 %) percentages in bronchoalveolar lavage fluid samples, and treatment with an immunosuppressive agent after diagnosis were associated with poor acute exacerbation-free probability. In the Cox analysis adjusted for treatment with an immunosuppressive agent, baseline cardiovascular diseases, higher GAP stage (≥II), and higher eosinophil percentage (≥3.21 %) in bronchoalveolar lavage fluid samples were predictors of an acute exacerbation of idiopathic pulmonary fibrosis.Conclusions: This study demonstrated that baseline cardiovascular diseases, higher GAP stage (≥II), and higher eosinophil percentage (≥3.21 %) in bronchoalveolar lavage fluid samples were associated with the onset of an acute exacerbation of idiopathic pulmonary fibrosis. [ABSTRACT FROM AUTHOR]