Positive outcome of first-line therapy for a SMARCA4-deficient thoracic sarcomatoid tumor.

SMARCA4-deficient thoracic sarcomatoid tumor is a rare malignancy indicating some characteristics of a smoking-related disease. The purpose of this report is to describe a case of aggressive thoracic tumor with loss of immunochemical SMARCA4 expression and detail the results of our treatment regimen. The patient was a 58-year-old male and clinicopathologically diagnosed with a SMARCA4-deficient thoracic sarcomatoid tumor. Pembrolizumab plus carboplatin and pemetrexed resulted in significant response. This combination therapy showed potential for first-line systemic treatment of SMARCA4-deficient thoracic sarcomatoid tumors.

Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells.

Both pro- and anti-oncogenic roles of miR-221 and miR-222 microRNAs are reported in several types of human cancers. A previous study suggested their oncogenic role in invasiveness in lung cancer, albeit only one cell line (H460) was used. To further evaluate involvement of miR-221 and miR-222 in lung cancer, we investigated the effects of miR-221 and miR-222 overexpression on six lung cancer cell lines, including H460, as well as one immortalized normal human bronchial epithelial cell line, HBEC4. miR-221 and miR-222 induced epithelial-to-mesenchymal transition (EMT)-like changes in a minority of HBEC4 cells but, unexpectedly, both the microRNAs rather suppressed their invasiveness. Consistent with the prior report, miR-221 and miR-222 promoted growth in H460; however, miR-221 suppressed growth in four other cell lines with no effects in one, and miR-222 suppressed growth in three cell lines but promoted growth in two. These are the first results to show tumor-suppressive effects of miR-221 and miR-222 in lung cancer cells, and we focused on clarifying the mechanisms. Cell cycle and apoptosis analyses revealed that growth suppression by miR-221 and miR-222 occurred through intra-S-phase arrest and/or apoptosis. Finally, lung cancer cell lines transfected with miR-221 or miR-222 became more sensitive to the S-phase targeting drugs, possibly due to an increased S-phase population. In conclusion, our data are the first to show tumor-suppressive effects of miR-221 and miR-222 on lung cancer, warranting testing their potential as therapeutics for the disease.

Health-care-associated pneumonia among hospitalized patients in a Japanese community hospital.

BACKGROUND: Health-care-associated pneumonia (HCAP) is a relatively new concept. Epidemiologic studies are limited, and initial empirical antibiotic treatment is still under discussion. This study aimed to reveal the differences in mortality and pathogens between HCAP and community-acquired pneumonia (CAP) in each severity class, and to clarify the strategy for the treatment of HCAP. METHODS: We conducted a retrospective observational study of patients with HCAP and CAP who were hospitalized between November 2005 and January 2007, and compared baseline characteristics, severity, pathogen distribution, antibiotic regimens, and outcomes. In each severity class (mild, moderate, and severe) assessed using the A-DROP scoring system (ie, age, dehydration, respiratory failure, orientation disturbance, and low BP), we investigated the in-hospital mortality and occurrence of potentially drug-resistant (PDR) pathogens. RESULTS: A total of 371 patients (141 HCAP patients, 230 CAP patients) were evaluated. The proportion of patients in the severe class was higher in the HCAP patients than in CAP patients. In the moderate class, the in-hospital mortality proportion of HCAP patients was significantly higher than that of CAP patients (11.1% vs 1.9%, respectively; p = 0.008). In moderate-class patients in whom pathogens were identified, PDR pathogens were isolated more frequently from HCAP patients than from CAP patients (22.2% vs 1.9%, respectively; p = 0.002). The occurrence of PDR pathogens was associated with initial treatment failure and inappropriate initial antibiotic treatment. CONCLUSIONS: The present study provides additional evidence that HCAP should be distinguished from CAP, and suggests that the therapeutic strategy for HCAP in the moderate class holds the key to improving mortality. Physicians may need to consider PDR pathogens in selecting the initial empirical antibiotic treatment of HCAP.

Implication of clinical pathway care for community-acquired pneumonia in a community hospital: early switch from an intravenous beta-lactam plus a macrolide to an oral respiratory fluoroquinolone.

OBJECTIVE: The effect of clinical pathway (CP) care and early switch from intravenous to oral antibiotics therapy on community-acquired pneumonia (CAP) has been well documented. However, limited studies have evaluated the effects of CP on reducing time taken for attaining clinical stability and duration of antibiotics prescriptions. This study was aimed to investigate the use of a CP and its implication for CAP in a community hospital. METHODS: We conducted a retrospective cohort study of CAP patients hospitalized between November 2005 and January 2007. The patients were divided into two groups, those for whom CP was adopted and those for whom CP was not adopted on admission. We compared the outcomes of three risk classes assessed using the severity scoring system (A-DROP). CP included switching from an intravenous beta-lactam plus a macrolide to an oral respiratory fluoroquinolone, when the patients exhibited risk factors for drug-resistant pneumococci. RESULTS: One hundred thirty-five patients were evaluated, and sixty received CP care. Patients in the CP group had a lower A-DROP score. Although clinical cure proportions were similar, the CP group in the mild and moderate classes (A-DROP score,

Comparison of severity scoring systems A-DROP and CURB-65 for community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: The initial assessment of the severity of community-acquired pneumonia (CAP) is important for patient management. The Japanese Respiratory Society (JRS) has proposed a 6-point scale (0-5) to assess the clinical severity of CAP. The A-DROP scoring system assesses the following parameters: (i) Age (male >or= 70 years, female >or= 75 years); (ii) Dehydration (blood urea nitrogen (BUN) >or= 210 mg/L); (iii) Respiratory failure (SaO(2) 7 mmol/L (200 mg/L), respiratory rate >or= 30/min, low blood pressure (diastolic or= 65 years) proposed by the British Thoracic Society. However, validation of A-DROP has not been attempted nor has it been compared with CURB-65. The aim of this study was to confirm that A-DROP is equivalent to CURB-65 for predicting severity of CAP. METHODS: A retrospective observational study was conducted of patients with CAP hospitalized at a single centre between November 2005 and January 2007. The 30-day mortality after admission was compared following assessment of severity using the A-DROP and CURB-65 scoring systems. RESULTS: Three-hundred and twenty-nine patients were evaluated. The areas under the receiver operating characteristic curves were 0.846 (95% confidence interval (CI): 0.790-0.903) and 0.835 (95% CI: 0.763-0.908) for A-DROP and CURB-65, respectively. CONCLUSION: The JRS A-DROP can be used to assess severity of CAP, and gives similar results to CURB-65.

[Case of polymer fume fever with interstitial pneumonia caused by inhalation of polytetrafluoroethylene (Teflon)].

A 30-year old man was admitted to our hospital with cough, slight fever, and dyspnea that he had developed several hours after inhaling the fumes produced from a Teflon-coated pan, after evaporation of the water in the pan. Chest radiography revealed diffuse infiltrations, and a computed tomography (CT) scan revealed patchy interstitial shadows in both lungs. In pulmonary function tests, the diffusing capacity of the lungs showed a moderate decrease. Leukocytosis and slight hypoxemia were observed. The patient recovered clinically in a few days without any specific treatment. We speculated that the pulmonary problems in this patient may have been induced by the products of thermal degradation of Teflon that were present in the fumes. When Teflon is heated, the fumes generated cause an influenza like syndrome (polymer fume fever) or cause severe toxic effects such as pulmonary edema, pneumonitis, and death in the exposed individual.