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Background: Endobronchial masses obstruct the central airway, and cryotechnology is reportedly a feasible means of managing such masses. However, few reports have explored the role of cryotechnology in diagnosing endobronchial masses. Methods: All endobronchial masses were sampled for pathologic diagnosis by forceps biopsy and cryotechnology, performed during flexible bronchoscopy. The diagnostic accuracy of forceps biopsy and that of cryotherapy were compared by the χ2 test, and the obtained specimen sizes were compared by the t test. Results: Between 2007 and 2011, 75 patients with a median age of 64 years (interquartile range [IQR], 49–76; 48 men; 27 women; and 52 smokers [69.3%]) were diagnosed with endobronchial masses. The sites of these masses included the trachea (n = 17), left main bronchus (n = 16), right main bronchus (n = 11), right upper lobe bronchus (n = 11), right intermediate bronchus (n = 8), right lower lobe bronchus (n = 4), left upper lobe bronchus (n = 3), left lower lobe bronchus (n = 3), and right middle lobe bronchus (n = 2). Fifty-nine lesions were malignant, and 16 were benign. Lung squamous cell carcinoma (n = 23) was the leading cause of malignancy, and endobronchial tuberculosis (n = 9) was the most common benign disease. The diagnostic accuracy of cryotechnology was significantly higher than that of forceps biopsy (100% vs 69.3%, p < 0.0001). The specimen size obtained by cryotechnology was also significantly larger than that obtained by forceps biopsy (13.8 ± vs 1.9 ± 0.6 mm, p < 0.0001). Conclusions: The current study supports the view that cryotechnology is a good tool for diagnosing endobronchial masses. Cryotechnology also provides a better diagnostic specimen and has greater diagnostic accuracy than traditional forceps biopsy. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of the study was to investigate the risk factors of developing early-onset delirium in mechanically ventilated patients and determine the subsequent clinical outcomes. Methods: Confusion assessment method for the intensive care unit (ICU) was used to assess the enrolled mechanically ventilated patients for delirium. The risk factors of developing delirium and clinical outcomes were determined in these subjects. Results: Delirium was present in 31 (21.7%) of 143 patients in the first 5 days. In multivariable analysis, hypoalbuminemia (odds ratio, 5.94; 95% confidence interval, 1.23-28.77) and sepsis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9) increased the risk of developing delirium in mechanically ventilated patients. The patients with delirium had a higher in-hospital mortality (67.7% vs 33.9%, respectively; P = .001) and longer duration of mechanical ventilation (19.5 ± 15.8 vs 9.3 ± 8.8 days, respectively; P = .003) than patients without delirium. The incidence of nosocomial pneumonia was increased in delirious patients (64.5% vs 38.4%, P = .01) compared with nondelirious patients, whereas the lengths of ICU or hospital stay were similar between both groups. Conclusions: Mechanically ventilated patients with sepsis or hypoalbuminemia were more vulnerable to develop delirium in their early stay in the ICU. Early-onset delirium is associated with prolonged duration of mechanical ventilation and higher incidence of nosocomial pneumonia, leading to a higher mortality. [Copyright &y& Elsevier]

Summary: Mutational analysis was performed in the kinase domain (exons 18–21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p =0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p =0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness. [Copyright &y& Elsevier]

Differences in the clinical phenotypes and outcomes of fungus-associated asthma remain unclear. We aimed to investigate the presentation of asthmatics with fungal sensitization and/or positive fungal isolates. Clinical characteristics, pulmonary function, microbiological data, allergy test reports, emergency department (ED) visits and hospitalizations were retrieved from the Chang Gung Research Database between 2010 and 2018; the largest electronic medical record-based database in Taiwan. Follow-up care was provided to each patient for 3 years. A total of 30,754 asthmatics were enrolled, and 7976 were eligible for analysis after applying the exclusion criteria. Of these patients, 694 had sputum examinations for fungi. The patients were divided into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n = 386); group 2, positive fungal sensitization (n = 58); group 3, positive fungal isolates (n = 217); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n = 33). Asthmatic patients with fungal sensitization (groups 2 and 4) demonstrated significantly higher IgE levels compared with those without (groups 1 and 3). Group 4 patients had a higher frequency of hospitalization. Amongst patients under Global Initiative for Asthma (GINA) step 4–5 therapies, group 4 asthmatics possessed significantly higher incidence of respiratory failure. The prevalence of fungal sensitization and fungal isolates from sputum were even across asthmatic severities, but the clinical impact of fungi may be more significant among patients with more severe disease. [ABSTRACT FROM AUTHOR]

Summary: Epidermal growth factor receptor (EGFR) initiates a signaling cascade that leads to DNA synthesis and cell proliferation, but its role in regulating DNA replication licensing is unclear. Here, we show that activated EGFR phosphorylates the p56 isoform of Lyn, p56Lyn, at Y32, which then phosphorylates MCM7, a licensing factor critical for DNA replication, at Y600 to increase its association with other minichromosome maintenance complex proteins, thereby promoting DNA synthesis complex assembly and cell proliferation. Both p56Lyn Y32 and MCM7 Y600 phosphorylation are enhanced in proliferating cells and correlated with poor survival of breast cancer patients. These results establish a signaling cascade in which EGFR enhances MCM7 phosphorylation and DNA replication through Lyn phosphorylation in human cancer cells. [Copyright &y& Elsevier]

Summary: To evaluate the association of epidermal growth factor receptor (EGFR) gene copy number with EGFR and k-ras mutation status and tyrosine kinase inhibitor (TKI) sensitivity in non-small cell lung cancer (NSCLC), EGFR gene copy number of 182 NSCLC tumor specimens were analyzed by chromogenic in situ hybridization (CISH). EGFR and k-ras mutation analyses were also performed for, respectively, 176 and 157 of the 182 patients. Additionally, 36 patients in this study had received TKI monotherapy. The tumor was considered to be CISH positive if the gene copy number was ≥5 signals per nucleus in ≥40% of tumor cells. CISH-positive tumors were strongly associated with adenocarcinoma (56.8%) compared with squamous cell carcinoma (15.9%) (p <0.0001). The CISH-positive tumors were also strongly associated with EGFR mutations (78%) compared with wild type (20.2%) (p <0.0001). Only six tumors had k-ras mutations. None had EGFR mutation and only one was CISH positive. In the patients treated with TKI, EGFR mutation was strongly associated with TKI responsiveness (22/25 responders) (p <0.0001), but the CISH-positive tumors were only marginally significant (18/25 responders) (p =0.0665). Patients with EGFR mutations or CISH-positive tumors were all associated with longer median survival, although not statistically significant. Our results suggest Increased EGFR copy number was highly correlated with EGFR mutation in adenocarcinoma. Although it is less correlated with TKI responsiveness when compared with EGFR mutations, it still could be a good alternative molecular predictive marker for TKI responsiveness, since CISH can be done on paraffin section and is much quicker than DNA sequencing. [Copyright &y& Elsevier]