BackgroundCigarette smoking-induced oxidative stress is known to be a key mechanism in COPD pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a central transcription factor that regulates the antioxidant defense system. The aim of this study was to compare Nrf2 expression in COPD subjects and control subjects, and to determine the role of Nrf2 in protecting against oxidative stress-induced apoptosis.MethodsWe enrolled 8 COPD subjects and 7 control subjects in this study. We performed bronchial brushing by bronchoscopy and obtained bronchial epithelial cells from the airways. Nrf2 expression in bronchial epithelial cells was evaluated by real-time PCR and Western blotting. We examined the effect of 10 or 15 % cigarette smoke extract (CSE) induced A549 cells apoptosis using a time-lapse cell imaging assay with caspase-3/7 activation detecting reagent and performed Terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling assay for confirming A549 cells apoptosis. We also examined the effects of Nrf2 knockdown and, 0.1, 0.5, and 1.0 mM N-acetyl cysteine on CSE-induced apoptosis. Statistical analyses were performed using t-test, paired t-test or an analysis of variance followed by the Tukey-Kramer method.ResultsNrf2 mRNA expression in COPD subjects was significantly lower than that in control subjects and Nrf2 mRNA were negatively correlated with pack year. Nrf2 protein in COPD subjects was significantly lower than that in control subjects. CSE-induced A549 cells apoptosis was increased in a time-, concentration-dependent manner, and was significantly increased by Nrf2 knockdown. N-acetyl cysteine significantly ameliorated CSE-induced apoptosis.ConclusionsNrf2 expression was lower in COPD patients than in control subjects. Nrf2 might have a protective role against apoptosis caused by CSE-induced oxidative stress. These results suggest an involvement of Nrf2 in COPD and administration of antioxidants to patients with COPD might be a basic therapeutic option.

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Objective Hemorrhagic pneumonia due to Stenotrophomonas maltophilia (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. Methods This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. Patients All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. Results The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p= 0.02). Conclusion Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation.

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Background: In this study, we analyzed the usefulness of adjuvant chemotherapy for non-small cell lung cancer based on the histoculture drug response assay (HDRA). Methods: From September 2001 to December 2008, 65 patients with pathologic stage II or higher non-small cell lung cancer who underwent surgery received two-cycle HDRA-based adjuvant chemotherapy. Chemosensitivity to cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and irinotecan was examined by the HDRA. All patients were classified according to the number of administered HDRA-positive drugs: the prediction-sensitive group (PSG) (n ϭ 31) comprised patients treated with two HDRA-positive drugs and the prediction-nonsensitive group (PNSG) (n ϭ 34) comprised those treated with a combination of one HDRA-positive and one HDRAnegative drug or two HDRA-negative drugs. The clinical outcomes of the two groups were analyzed. Results: The overall 5-year survival rate of the PSG was 82.4%. On the other hand, that of the PNSG was 40.1%. There were significant differences between the two groups (p ϭ 0.03). The 5-year diseasefree survival rate was more favorable in the PSG than in the PNSG (PSG: 56.5%, PNSG: 30.1%, p ϭ 0.05). Multivariate analysis showed that chemotherapy based on the HDRA was a significant prognostic factor (p ϭ 0.03). Conclusions:The prognosis of patients treated with two HDRApositive drugs was significantly better than that of those treated with one HDRA-positive drug or HDRA-negative drugs. Adjuvant chemotherapy based on the in vitro HDRA may be useful to improve survival in patients who have undergone surgery.

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Background: Secondary pneumothorax with interstitial lung disease (ILD) is often difficult to treat in comparison to primary pneumothorax. The purpose of this study was to analyze the actual management and outcome, and to find the most effective treatment.Methods: Among 180 patients with pneumothorax caused by ILD, who were managed between January 2000 and April 2021, 129 patients were included. Fifty-one patients with observation only were excluded. In the present study, a patient was considered to be cured if their chest tube could be removed. Results:The managements included chest tube drainage alone (n=41), pleurodesis (n=67), bronchoscopic treatment (n=14), and surgery (include overlapping cases) (n=25). The mean number of pleurodesis treatments was 2.4 (range, 1-9), and the most frequently used agent was blood-patch. All patients who received bronchoscopic treatment underwent bronchial occlusion with silicon spigots. The surgical procedures included bullectomy (n=20), lung cyst ligation (n=3), pleural covering with oxidized cellulose sheet (n=1), and spraying of fibrin glue alone (n=1). One hundred patients (77.5%) were curatively treated, 27 patients (20.9%) died, and 2 patients were transferred without chest tube removal. Among 25 patients who received surgery [including 6 patients with performance status (PS) ≥2], 24 patients (96.0%) were cured, and 1 patient died due to an acute exacerbation of ILD after surgery. The univariate analysis revealed that PS ≥2 and >3 pleurodesis treatments were significant non-curative factors, while steroid treatment before the development of pneumothorax was not. Conclusions:The outcomes of surgery for pneumothorax in patients with ILD were good, and it is desirable to consider the surgical indications.

IntroductionMicronodular thymoma with lymphoid stroma is a rare subtype of thymoma. Here we report a case of micronodular thymoma with lymphoid stroma that was completely resected after incomplete resection 10 years earlier.Case presentationA 70-year-old Japanese woman who had undergone resection for a thymic cyst 10 years earlier was found to have a solid nodule with a multilocular lesion at the site of the previous operation. We suspected that the tumor was a malignant tumor and performed trans-sternal radical thymectomy and diagnosed the lesion as micronodular thymoma with lymphoid stroma pathologically. When we reassessed the thymic cyst that had been resected 10 years earlier, a few lesions of micronodular thymoma with lymphoid stroma were found in the cyst wall. Based on these findings, we concluded that only the cystic component of micronodular thymoma with lymphoid stroma had been removed, and that the residual lesion grew locally over the next 10 years before being completely resected by reoperation.ConclusionWe experienced an unusual case of micronodular thymoma with lymphoid stroma, which is a rare subtype of thymoma. Greater care should be taken to exclude a thymoma with a cystic lesion, even if a thymic cyst is strongly suspected on computed tomography and magnetic resonance imaging.