Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study.

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. FUNDING: Ministry of Health and Welfare of Taiwan.

Levofloxacin degradation under visible-LED photo-catalyzing by a novel ternary Fe-ZnO/WO3 nanocomposite.

As semiconductor photocatalysts showing their efficient redox ability upon illumination, new development of materials to enhance the pollution degradation is gaining popularity, especially on their oxidation ability. In this study, a highly stable ternary Fe-ZnO/WO3 nanocomposite photocatalyst has been synthesized in order to improve charge transfer of photocatalytic oxidation under 30W LED light (425-470 nm) to efficiency degrade the Levofloxacin (LVF) in the solution. This catalyst was characterized and analyzed by XRD, FE-SEM, HR-TEM, X-ray XPS, UPS, PL, TRPL, LSV, EIS, and Photocurrent. Various important factors for the photodegradation were investigated, including Fe content, initial LVF concentration, catalyst dosage, and solution pH. The optimal conditions were Fe 1.0 wt%, LVF 10 mg L-1, Fe-ZnO/WO3 dosage 0.5 g L-1, and pH 7 for LVF photodegradation up to 96% with a kinetic rate constant of 0.0342 min-1 and were stable in photodegradation efficiency (90%) after five test cycles. In the visible LED light, the activation bandgap was estimated to be 2.75 eV with high electron-hole pair separation and charge transfer from Fe-ZnO to WO3 that could enhance the generation of active species of •OH. Moreover, the more effective charge separation of Fe-ZnO/WO3 were confirmed by lower PL intensity and longer charge carrier lifetime. Fe-ZnO/WO3 also demonstrated the excellent electrochemical properties with high photocurrent and small resistance. For the LVF degradation, 3 possible pathways were proposed with 12 intermediate products. This study demonstrated that the synthesized Fe-ZnO/WO3 could serve as a reliable visible-light responsive photocatalysts with the potential for degrading antibiotics in solution.

Association between sugary drinks consumption and dental caries incidence among Taiwanese schoolchildren with mixed dentition.

OBJECTIVES: Dental caries is a multifactorial disease, and a sugary diet can generate an acidic plaque environment that advances its development. However, the specific effect of sugary drinks on the subsequent oral health of schoolchildren with mixed dentition is unclear. In this study, we investigated the association between the consumption of sugary drinks and 1 year incidence rate of caries in permanent teeth among Taiwanese schoolchildren with mixed dentition. METHODS: A longitudinal 1 year follow-up study was conducted among Taiwanese schoolchildren aged 8-9 years. A questionnaire collected information regarding the parents' oral health status and their children's demographic background, oral health-related behaviours and consumption habits of sugary drinks, including handmade drinks (specifically bubble tea and pearl milk tea) and carbonated drinks. Dental caries was recorded through standardized oral examinations. The number of dental services received was retrieved from the Taiwan National Health Insurance Research Database. Multivariate Cox proportional hazards models and zero-inflated negative binomial models were used to estimate the association between the consumption of sugary drinks and the incidence rate of caries in permanent teeth after 1 year. RESULTS: The study involved 494 children. During the 1 year follow-up period, 117 children developed new dental caries in their permanent teeth, yielding a caries incidence rate of 0.183 per person-year. After adjustments for confounding factors, children who preferred having sugar-rich beverages were associated with having a 4.3 times higher (95% confidence interval [CI] = 1.2-15.7) risk of developing caries than did those who preferred nonsugary drinks (P < .05). Additionally, children who often consumed handmade drinks were associated with having a 1.7 times higher (95% CI = 1.1-2.9) risk of developing caries than those who seldom consumed (P < .05). CONCLUSIONS: The findings suggest that the consumption of sugary drinks during the mixed dentition stage might be a major etiological factor for caries in permanent teeth. These findings could be valuable to paediatricians, dentists, nutritionists and policymakers.

Trajectory of smoking behaviour during the first 6 months after diagnosis of lung cancer: A study from Taiwan.

AIMS: To identify different classes of change pattern/ trajectory of tobacco smoking behaviour after diagnosis of lung cancer using multi-wave data and to explore factors associated with the class membership. DESIGN: This is a multi-wave observational study. METHODS: Smoking behaviour data were collected at diagnosis and then every month for 6 months from 133 newly diagnosed people with lung cancer who had recently quit smoking or continued to smoke at diagnosis. These patients were recruited from three medical centres and data were collected from May 2014 to January 2017. Smoking behaviour was assessed based on patients' self-reports on whether they smoked during the last month (yes/no) for a total of seven times. Mixture latent Markov model and logistic regression were used to analyse data. RESULTS: Two latent classes of smoking trajectory were identified among recent quitters or current smokers of people with lung cancer, namely "perseverance for abstinence" and "indecisive for abstinence." Patients who were younger age (OR = 0.95, p = 0.026), exposure to second-hand smoke (OR = 3.35, p = 0.012) and lower self-efficacy for not smoking (OR = 0.96, p = 0.011) were more likely to belong to the class of "indecisive for abstinence." CONCLUSIONS: Heterogeneous classes of smoking trajectory existed in newly diagnosed people with lung cancer. The risk factors associated with a less favourable smoking trajectory can be incorporated into tailored smoking-cessation programs for patients newly diagnosed with lung cancer. IMPACT: The dynamic trajectory of smoking behaviour had not been adequately explored among newly diagnosed people with lung cancer. Two classes of smoking trajectory and the predictors associated with the class membership were identified. These findings suggest that the diagnosis of cancer is a teachable moment for smoking cessation. Patients with younger age, lower self-efficacy of not smoking and exposure to second-hand smoke at home need special attention.

Small Airway Dysfunction by Impulse Oscillometry in Symptomatic Patients with Preserved Pulmonary Function.

BACKGROUND: Asthma and chronic obstructive pulmonary disease are characterized by persistent airway inflammation and airflow limitation. Early detection of these diseases in patients with respiratory symptoms and preserved pulmonary function (PPF) defined by spirometry is difficult. Impulse oscillometry (IOS) may have better sensitivity than effort-dependent forced expiratory flow between 25% and 75% (FEF25%-75%) to detect small airway dysfunction (SAD). OBJECTIVE: To identify SAD in patients with respiratory symptoms and PPF using IOS. METHODS: Medical records of symptomatic patients without acute or known structural lung diseases were evaluated. Patients had bronchodilator testing and IOS in the outpatient clinic between March 1 and July 31, 2017. Correlations between respiratory symptoms, spirometry, and IOS parameters were determined. RESULTS: Among 349 patients enrolled to the study, 255 (73.1%) patients met the criteria of PPF. The IOS parameters-difference in resistance at 5 Hz and resistance at 20 Hz , reactance at 5 Hz, resonant frequency (Fres), and area under reactance curve between 5 Hz and resonant frequency-were significantly correlated with FEF25%-75%. The cutoffs for SAD were difference in resistance at 5 Hz and resistance at 20 Hz greater than 0.07 kPa/(L/s), reactance at 5 Hz less than -0.12 kPa/(L/s), Fres greater than 14.14 Hz, and area under reactance curve between 5 Hz and resonant frequency greater than 0.44 kPa/L. Of the IOS parameters, Fres and reactance at 5 Hz had the highest sensitivity and specificity. When compared with FEF25%-75%, Fres had greater sensitivity to detect SAD in patients with PPF. Patients with IOS-defined SAD had a significantly higher incidence of wheeze or sputum production than did those defined by FEF25%-75%. CONCLUSIONS: Patients with respiratory symptoms and PPF may have SAD, which can be identified with the aid of IOS in addition to spirometry.

Rare Concurrence of Two Congenital Disorders: Miller-Dieker Syndrome and T-Cell Lymphopenia.

Miller-Dieker syndrome (MDS; OMIM 247200) is a rare contiguous gene deletion syndrome associated with lissencephaly and characteristic facial dysmorphism. T-cell lymphopenia is an immunodeficiency disorder which can be early detected by newborn blood screening, and all live vaccines should be avoided. We report a 2.32-Mb microdeletion at chromosome 17p13.3p13.2 and T-cell lymphopenia in a 6-month-old male infant with MDS. This is, to our knowledge, the first description of these 2 conditions co-occurring in the same patient.

Smoking Status Among Patients With Newly Diagnosed Lung Cancer in Taiwan.

BACKGROUND: Continued smoking after receiving a diagnosis of cancer seriously affects disease prognosis and survival. The prevalence and risk factors of continued smoking among patients with newly diagnosed lung cancer are unknown in Taiwan. PURPOSE: The aims of this study were to assess the smoking status of patients with newly diagnosed lung cancer and to identify the characteristics that are associated with different smoking statuses. METHODS: Baseline data of a longitudinal study on smoking behaviors after lung cancer diagnosis were analyzed in this study. Patients were consecutively recruited from three medical centers in northern Taiwan. A structured questionnaire and medical chart reviews were used to collect data. Multinomial logistic regression analysis was used to examine the factors associated with continuing to smoke after being diagnosed with lung cancer. RESULTS: Among the 406 patients with newly diagnosed lung cancer who were recruited, 47.0% were never-smokers and 53.0% were ever-smokers. Among the second group, 38% were former smokers, 18% were recent quitters, and 44% were current smokers. Compared with former smokers, current smokers were more likely to be younger (OR = 1.05), to not exercise regularly (OR = 2.74), to currently live with smokers (OR = 2.48), and to have lower self-efficacy for refusing to smoke (OR = 0.95). Compared with recent quitters, current smokers were more likely to have lower self-efficacy for refusing to smoke. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: A significant proportion of ever-smoker lung cancer patients in Taiwan will continue to smoke after receiving their diagnosis. Variables known to modify the risk factors associated with continued smoking such as regular exercise and better refusal self-efficacy should be considered and incorporated into future smoking cessation programs for patients with lung cancer.

Glycopyrronium bromide inhibits lung inflammation and small airway remodeling induced by subchronic cigarette smoke exposure in mice.

The effects of long-acting muscarinic receptor antagonists (LAMAs) have not been evaluated in a model with simultaneous lung inflammation and small airway remodeling induced by cigarette smoke (CS). We exposed the mice to CS for four weeks with daily treatment with a LAMA (glycopyrronium bromide, NVA237) or its vehicle. Human bronchial epithelial cells (PBECs) and lung fibroblasts were exposed to CS extract (CSE) or acetylcholine with or without NVA237 treatment. We found that NVA237, but not its vehicle, suppressed elevations in inflammatory score, epithelial thickness, and peribronchial collagen deposition in CS-exposed mice. NVA237 alleviated CS-induced increased levels of chemokines, inflammatory cells, and total protein in the bronchoalveolar lavage fluid. NVA237 suppressed acetylcholine- or CSE-induced elevations in IL-8 production in PBECs and elevations in proliferation and collagen production in lung fibroblasts. These phenomena were also prevented by a p44/42 MAPK inhibitor. In conclusion, NVA237 exerted a potent suppressive effect on lung inflammation and small airway remodeling induced by subchronic CS exposure.

Statin Use Is Associated With a Lower Risk of TB.

BACKGROUND: Statins are widely used to lower cholesterol levels and cardiovascular risk. Further, studies have shown that statins may decrease the risks of infectious diseases and infection-related mortality; however, the association between statin use and active TB disease remains unclear. METHODS: Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population-based study. Patients taking statins between 2000 and 2013, without antecedent TB disease, were included. Data from 102,424 statin users and 202,718 age-, sex-, and enrollment date-matched subjects were analyzed. The two cohorts were monitored until December 31, 2013, for incident TB disease. The definition of TB disease was validated using the claims database of Taipei Veterans General Hospital. RESULTS: The statin and matched cohorts were observed for 571,568 and 1,027,385 person-years, respectively. Of the total 305,142 subjects, 1,264 (0.41%) developed subsequent TB disease. Validation study confirmed the accuracy of the definition of TB disease (sensitivity, 96.3%), with excellent interobserver agreement (κ = 1.00). Multivariate analysis revealed a reduced risk of TB disease among the statin cohort (hazard ratio [HR], 0.53; 95% CI, 0.47-0.61; P < .001). Compared with the matched group, statin use showed a dose-response relationship with the incident TB disease risk (<180 cumulative defined daily doses [cDDDs]: HR, 1.06; 95% CI, 0.91-1.24; P = .477; 180 to 365 cDDDs: HR, 0.57; 95% CI, 0.45-0.72; P < .001; >365 cDDDs: HR, 0.27; 95% CI, 0.22-0.33; P < .001). CONCLUSIONS: Statin use associates with a lower risk of incident TB disease.

Differential Expression of VEGFA Isoforms Regulates Metastasis and Response to Anti-VEGFA Therapy in Sarcoma.

Elevated plasma concentrations of soluble VEGFA isoforms are associated with poor prognosis in parallel with improved response to treatment with the anti-VEGFA antibody bevacizumab. To uncover the underlying mechanism to these observations, we administered anti-VEGFA therapy to mice bearing luminescent mouse fibrosarcomas expressing single VEGFA isoforms or their wild-type counterparts expressing all isoforms (fs120, fs164, fs188, or fsWT). Expression of the more soluble isoforms conferred an advantage for lung metastasis from subcutaneous tumors (fs120/164 vs. fs188/WT); fs120 cells also produced more lung colonies than fs188 cells when injected intravenously. Metastasis from subcutaneous fs120 tumors was more sensitive than fs188 to treatment with the anti-VEGFA antibody B20-4.1.1. Despite elevated plasma levels of VEGFA in fs120 tumor-bearing mice and a dependence on VEGF receptor 1 activity for metastasis to the lung, B20-4.1.1 did not affect survival in the lung on intravenous injection. B20-4.1.1 inhibited subcutaneous tumor growth and decreased vascular density in both fs120 and fs188 tumors. However, migration of fs120, but not fs188 cells, in vitro was inhibited by B20-4.1.1. The greater survival of fs120 cells in the lung was associated with VEGFR1-dependent accumulation of CD11b-positive myeloid cells and higher expression of the VEGFR1 ligand, PlGF2, by the fs120 cells in vitro and in the plasma and lungs of fs120 tumor-bearing mice. We conclude that soluble VEGFA isoform expression increases fibrosarcoma metastasis through multiple mechanisms that vary in their sensitivity to anti-VEGF/VEGFR inhibition, with VEGFA-targeted therapy suppressing metastasis through effects on the primary tumor rather than the metastatic site. Cancer Res; 77(10); 2633-46. ©2017 AACR.

Measuring (1,3)-ß-D-glucan in tracheal aspirate, bronchoalveolar lavage fluid, and serum for detection of suspected Candida pneumonia in immunocompromised and critically ill patients: a prospective observational study.

BACKGROUND: While Candida pneumonia is life-threatening, biomarker measurements to early detect suspected Candida pneumonia are lacking. This study compared the diagnostic values of measuring levels of (1, 3)-ß-D-glucan in endotracheal aspirate, bronchoalveolar lavage fluid, and serum to detect suspected Candida pneumonia in immunocompromised and critically ill patients. METHODS: This prospective, observational study enrolled immunocompromised, critically ill, and ventilated patients with suspected fungal pneumonia in mixed intensive care units from November 2010 to October 2011. Patients with D-glucan confounding factors or other fungal infection were excluded. Endotracheal aspirate, bronchoalveolar lavage fluid and serum were collected from each patient to perform a fungal smear, culture, and D-glucan assay. RESULTS: After screening 166 patients, 31 patients completed the study and were categorized into non-Candida pneumonia/non-candidemia (n = 18), suspected Candida pneumonia (n = 9), and non-Candida pneumonia/candidemia groups (n = 4). D-glucan levels in endotracheal aspirate or bronchoalveolar lavage were highest in suspected Candida pneumonia, while the serum D-glucan level was highest in non-Candida pneumonia/candidemia. In all patients, the D-glucan value in endotracheal aspirate was positively correlated with that in bronchoalveolar lavage fluid. For the detection of suspected Candida pneumonia, the predictive performance (sensitivity/specificity/D-glucan cutoff [pg/ml]) of D-glucan in endotracheal aspirate and bronchoalveolar lavage fluid was 67%/82%/120 and 89%/86%/130, respectively, accounting for areas under the receiver operating characteristic curve of 0.833 and 0.939 (both P < 0.05), respectively. Measuring serum D-glucan was of no diagnostic value (area under curve =0.510, P = 0.931) for the detection of suspected Candida pneumonia in the absence of concurrent candidemia. CONCLUSIONS: D-glucan levels in both endotracheal aspirate and bronchoalveolar lavage, but not in serum, provide good diagnostic values to detect suspected Candida pneumonia and to serve as potential biomarkers for early detection in this patient population.

Brain metastasis features and association with tumor epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung.

AIM: Epidermal growth factor receptor (EGFR) mutations are frequent in pulmonary adenocarcinoma patients. The association between tumor EGFR mutation and characteristics of brain metastasis (BM) is still unclear. METHODS: We retrospectively reviewed pulmonary adenocarcinoma patients with and without BMs, and characteristics of BM to analyze the association between tumor EGFR mutation and characteristics of BM. RESULTS: Of 374 cases, 239 had EGFR mutations; 69 had BM at initial diagnosis, and 82 with BMs after treatment. All eligible patients received EGFR-tyrosine kinase inhibitors treatment. Older patients (≥70 years old) were less likely to have BMs than younger patients (25.8% vs 48%, P < 0.001). Patients with higher N stage had higher proportion of BMs (P = 0.006). Patients with exon 19 deletion were more likely to have BMs than those without EGFR mutation (48.1% vs 34.1%, P = 0.021). Patients with exon 19 deletion didn't have significantly higher chance of BMs at initial diagnosis but had higher chance to develop BM after treatment than those without EGFR mutation (35.6% vs 21.2%, P = 0.019). Patients with exon 19 deletion survived longer than those without EGFR mutation (1-year survival rate 95.8% vs 78.7%, P = 0.003). Thus, longer survival may lead to higher proportion of BM occurrence in patients with exon 19 deletion than those without EGFR mutation. CONCLUSIONS: In pulmonary adenocarcinoma, there is no significant difference in frequency of BMs at initial diagnosis between patients with EGFR mutation and wild type. However, after treatment, patients with EGFR mutations are significantly more likely to develop BM.

The Efficacy of Traditional Chinese Herbal Medicine in the Treatment of EGFR Mutated Stage IV Pulmonary Adenocarcinoma Patients Who Received First-Line EGFR-TKI Treatment.

BACKGROUND: Chinese herbal medicine (CHM) has been used for thousands of year in Eastern countries. First-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment is the standard treatment in stage IV pulmonary adenocarcinoma patients who had tumor EGFR mutations. This study was to find the efficacy of CHM on lung cancer treatment. MATERIALS AND METHODS: We retrospectively reviewed chart records of our stage IV EGFR-mutated pulmonary adenocarcinoma patients who received first-line EGFR-TKI treatment from January 2010 to September 2014. RESULTS: Total, 527 patients were studied. Among them, 34 patients received CHM treatment, including 24 patients who received CHM treatment from the beginning of first-line EGFR-TKI treatment and 10 patients who started to receive CHM treatment after their disease had progressed to EGFR-TKI treatment. Median progression-free survival (PFS) of first-line EGFR-TKI treatment was numerically better in patients who also received CHM than those who did not (12.1 months vs 10.5 months, P = .7668). Overall survival of those 24 patient who received CHM treatment together with EGFR-TKI was 30.63 months (95% CI = 11.7 to not reached), compared to 23.67 months in the remaining patients (95% CI = 21.37-26; hazard ratio = 0.75; P = .399). No increase of CHM-related toxicities was found during CHM treatment, compared with EGFR-TKI treatment alone ( P > .05). CONCLUSION: Alternative CHM treatment during first-line EGFR-TKI treatment did no harm to the patients and PFS and overall survival was numerically better, although not significant, than those patients who did not receive CHM treatment.

Induced Pluripotent Stem Cell-conditioned Medium Suppressed Melanoma Tumorigenicity Through the Enhancement of Natural-Killer Cellular Immunity.

Induced pluripotent stem cells (iPSCs) can secrete cytokines that are involved in T-cell development and affect cytotoxic activity. To assess the effect of iPSC-conditioned medium on tumorigenicity, we retrieved splenocytes from B6 mice and cocultured them with or without irradiated B16 melanoma cells, mouse interleukin-2 (mIL-2), or iPSC-conditioned medium. Splenocyte cytotoxicity assays against B16 melanoma cells [as cytotoxic T lymphocyte (CTL) activity] and P815 cells [as natural killer (NK) activity] were performed. IL-10 and interferon-γ concentrations were measured. An in vivo subcutaneous B16 melanoma growth model was performed in B6 mice and treated with iPSC-conditioned medium. The lymphocyte subpopulation depletion test was performed to determine effectors against B16 melanoma cells. We found that unstimulated splenocytes had little cytotoxic activity. Without tumor cells, mIL-2 could augment iPSC-conditioned medium-treated CTL and NK activities (P<0.01). With irradiated tumor cells, mIL-2 treatment of splenocytes could not enhance CTL or NK activity, but iPSC-conditioned medium could enhance CTL and NK activity (P<0.001). Irradiated tumor cells induced mice splenocytes to secrete more IL-10, similar to mIL-2 treatment, but not iPSC-conditioned medium treatment. mIL-2 had better efficacy than conditioned medium in inducing splenocyte interferon-γ production. The CTL and NK cell depletion test showed that the immunostimulating effect of iPSC-conditioned medium on splenocytes was through the enhancement of NK cellular activity (P<0.05). The subcutaneous melanoma growth model showed that B16-bearing mice treated with an iPSC-conditioned medium intraperitoneal injection had a decreased tumor growth rate (P<0.01). Our study suggests that iPSC-conditioned medium had a protective effect against tumor-induced immunosuppression through the enhancement of host NK cellular activity.

Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study.

BACKGROUND: The combined therapy of inhaled corticosteroids and long-acting beta-2 agonists for mechanically ventilated patients with COPD has never been explored. Therefore, the aim of this study was to investigate their dynamic effects on lung mechanics and gas exchange. MATERIALS AND METHODS: Ten mechanically ventilated patients with resolution of the causes of acute exacerbations of COPD were included. Four puffs of salmeterol 25 µg/fluticasone 125 µg combination therapy were administered. Lung mechanics, including maximum resistance of the respiratory system (Rrs), end-inspiratory static compliance, peak inspiratory pressure (PIP), plateau pressure, and mean airway pressure along with gas exchange function were measured and analyzed. RESULTS: Salmeterol/fluticasone produced a significant improvement in Rrs and PIP after 30 minutes. With regard to changes in baseline values, salmeterol/fluticasone inhalation had a greater effect on PIP than Rrs. However, the therapeutic effects seemed to lose significance after 3 hours of inhaled corticosteroid/long-acting beta-2 agonist administration. CONCLUSION: The combination of salmeterol/fluticasone-inhaled therapy in mechanically ventilated patients with COPD had a significant benefit in reducing Rrs and PIP.

Adjuvant Therapy for Thymic Carcinoma--A Decade of Experience in a Taiwan National Teaching Hospital.

BACKGROUND: Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma. METHODS: To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014. RESULTS: Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS) and overall survival (OS) were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003). Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11). Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029). Among 30 patients (with stage I- IV carcinoma) who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months) than 2 patients who received adjuvant chemotherapy (5.9 months) or 4 patients who received concurrent chemoradiotherapy (7.5 months) after surgery (p = 0.003). CONCLUSIONS: Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection.

A prospective study of the use of circulating markers as predictors for epidermal growth factor receptor-tyrosine kinase inhibitor treatment in pulmonary adenocarcinoma.

BACKGROUND: The use of liquid tissue, such as circulating cells, to predict treatment response is attracting more attention. OBJECTIVE: The aim of this study was to evaluate association between circulating markers and treatment response. METHODS: One hundred and twelve advanced pulmonary adenocarcinoma patients who were going to receive epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were included. Tumor tissue and plasma specimens were collected before treatment and analyzed for EGFR mutation and plasma IL-6 and IL-8. Pre-treatment peripheral blood CD146+/CD3- cells (as circulating endothelial cells, CECs), CD34+/CD45- cells (as endothelial progenitor cells, EPCs), and CD133+ cells (as cancer stem cells, CSCs) were measured with flow cytometry. RESULTS: The progression-free survival (PFS) was significantly longer in patients with low CEC, low EPC, and low CSC counts than in those with high cell counts (p < 0.001, 0.041, and 0.001, respectively). Multivariate analysis showed that mutant plasma EGFR (pEGFR) was a poor prognostic factor in EGFR-mutated patients (p = 0.048), and there was a tendency for EGFR mutation-negative patients with high IL-6 level to have worse overall survival (p = 0.051). CONCLUSIONS: CECs, EPCs, CSCs, and mutant pEGFR are useful predictive biomarkers of EGFR-TKI treatment efficacy. IL-6 may predict prognosis in advanced lung cancer.

Assessment of latent tuberculosis infection in psychiatric inpatients: A survey after tuberculosis outbreaks.

BACKGROUND/PURPOSE: To investigate risk factors of latent tuberculosis infection (LTBI) among inpatients of chronic psychiatric wards with tuberculosis (TB) outbreaks. METHODS: In April 2013, inpatients of four all-male wards with TB outbreaks were tested for LTBI using the QuantiFERON-TB Gold in Tube (QFT) method. Based on this investigation, a retrospective study was conducted to assess risk factors for LTBI. Inpatients exposed to cluster-A or cluster-B TB cases were defined as contacts of cluster-A or cluster-B, and others, as nonclustered contacts. RESULTS: Among 355 inpatients with TB exposure, 134 (38%) were QFT-positive for LTBI. Univariate analysis showed that significant predictors for QFT-positivity were age, case-days of exposure to all TB cases (TB-all) and to sputum smear positive cases, number of source cases with cough, and exposure to cluster-A TB cases. Independent risk factors for LTBI were higher age [adjusted odds ratio (OR) 1.03, 95% confidence intervals (CI: 1.01-1.05)], TB-all exposure case-days ≥ 200 [adjusted OR 2.04 (1.06-3.92)] and exposure to cluster-A TB cases [adjusted OR 2.82 (1.30-6.12)] after adjustment for the sputum smear positivity, and cough variables of the source cases. The contacts of cluster-A had a greater risk of LTBI than did those of cluster-B, especially in the younger population (≤50 years) after adjustment [adjusted OR 2.64 (1.03-6.76)]. CONCLUSION: After TB outbreaks, more than one third of inpatients were QFT-positive for LTBI. Our findings suggest that, beside the infectiousness of source cases, intensity of exposure, and age of contacts, exposure to TB cases in potential genotyping clusters may be predictive for LTBI in this male psychiatric population.

Efficacy of chemotherapy in epidermal growth factor receptor (EGFR) mutated metastatic pulmonary adenocarcinoma patients who had acquired resistance to first-line EGFR tyrosine kinase inhibitor (TKI).

INTRODUCTION: Salvage chemotherapy is frequently used when tumour epidermal growth factor receptor (EGFR) mutated patients experience disease progression with first-line EGFR-tyrosine kinase inhibitor (TKI) treatment. However, the efficacy of salvage chemotherapy is still unknown. METHODS: We retrospectively reviewed the chart records of our pulmonary adenocarcinoma patients between 2010 and 2013. RESULTS: Five hundred and six of the 1240 stage IV adenocarcinoma patients had an EGFR mutation and 338 received first-line EGFR-TKI treatment. In all, 169 patients in this group received salvage chemotherapy after failure of EGFR-TKI, and 102 patients were eligible for this study. The chemotherapy response rate of these 102 patients was 24.5%, with a median progression-free survival (PFS) of 4.5?months, and median survival time was 14.6?months. Patients who received pemetrexed-based chemotherapy had longer PFS and overall survival (OS), although the extent was statistically insignificant. Progression-free survival and OS were longer for patients who received combination chemotherapy than single-agent chemotherapy. CONCLUSIONS: Pemetrexed-based combination chemotherapy is preferred before a more efficient treatment strategy is found.

Erlotinib Salvage Therapy in Pulmonary Adenocarcinoma Patients With Disease Progression After Previous EGFR-TKI Treatment.

BACKGROUND: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with promising efficacy in treating pulmonary adenocarcinoma. Treatment choices are few when patients with pulmonary adenocarcinoma have failed both EGFR-TKI and chemotherapy. The purpose of this study was to demonstrate the efficacy of erlotinib as salvage treatment for these nonresponsive patients. METHODS: We retrospectively reviewed the chart records of our stage IV pulmonary adenocarcinoma patients who were diagnosed and treated between July 2004 and June 2013. Clinical data, including type of response to treatment, time to disease progression, duration between the end of first-line EGFR-TKI treatment and starting erlotinib treatment, and overall survival time, were collected. RESULTS: A total of 98 patients were enrolled, and all had been treated with EGFR-TKI, either as a first-line therapy or following platinum-based chemotherapy; of them, 60 patients had a response to initial EGFR-TKI treatment. All received erlotinib as salvage treatment after their disease had progressed following EGFR-TKI treatment. Ninety-three (93.3%) patients had also received previous platinum-based chemotherapy. The median progression-free survival with erlotinib as salvage treatment for patients with and without a response to front-line EGFR-TKI was 4.9 and 3.4 months (P=0.869), respectively. The progression-free survival with erlotinib treatment in the sensitizing EGFR mutation group was 4.3 months, and in the EGFR wild-type group it was 2.6 months (P=0.22). CONCLUSIONS: In pulmonary adenocarcinoma patients who had been heavily treated, erlotinib could still be a choice, regardless of the EGFR mutation status, or whether the patients had responded to previous EGFR-TKI treatment.