Healthcare utilization of lung cancer patients associated with exposure to fine particulate matter: A Korean cohort study.

BACKGROUND: Higher concentrations of particulate matter (PM) have been shown to cause deterioration of the symptoms of respiratory and cardiovascular disease in several regional studies. Here, we aimed to investigate the healthcare utilization of lung cancer patients associated with short-term exposure to PM at the national level in Korea. METHODS: We extracted the data of 210 558 subjects over a period of 3 years (2015-2017), who were diagnosed with lung cancer before 2015 and benefited from the National Health Insurance Sharing Service. We performed the interpolation method using the geographic information system to calculate the estimated mean PM2.5 and PM10 concentrations by regions and classified three groups as high (upper 10%), intermediate (10%-90%), and low (bottom 10%) based on the mean PM mass concentrations of the month. RESULTS: The monthly average number of outpatient visits was significantly increased in high PM2.5 urban areas (46.296 vs. 50.646, p = 0.015). In high PM2.5 nationwide regions, the monthly average number of emergency admission was significantly increased (0.528 vs. 0.785, p = 0.001). The outpatient visits tended to change with PM2.5 concentration and correlated with PM10 /PM2.5 concentrations in urban and nationwide areas. In high PM2.5 urban regions, there was a significant increase in bronchodilator prescriptions (3.102 vs. 3.758, p = 0.008). Concerning high PM2.5 nationwide regions, there were significantly increased prescriptions of antibiotics, steroids, bronchodilators, antihistamines, and mucolytics. CONCLUSIONS: This study suggests that exposure to PM2.5 is significantly associated with hospital utilization and drug prescription in lung cancer patients.

Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation-Positive Non-Small Cell Lung Cancer.

PURPOSE: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation-positive non-small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. MATERIALS AND METHODS: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. RESULTS: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. CONCLUSION: Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation-positive in Korean patients with no new safety signals.

Multi-Omic Analyses Reveal Habitat Adaptation of Marine Cyanobacterium Synechocystis sp. PCC 7338.

Cyanobacteria are considered as promising microbial cell factories producing a wide array of bio-products. Among them, Synechocystis sp. PCC 7338 has the advantage of growing in seawater, rather than requiring arable land or freshwater. Nonetheless, how this marine cyanobacterium grows under the high salt stress condition remains unknown. Here, we determined its complete genome sequence with the embedded regulatory elements and analyzed the transcriptional changes in response to a high-salt environment. Complete genome sequencing revealed a 3.70 mega base pair genome and three plasmids with a total of 3,589 genes annotated. Differential RNA-seq and Term-seq data aligned to the complete genome provided genome-wide information on genetic regulatory elements, including promoters, ribosome-binding sites, 5'- and 3'-untranslated regions, and terminators. Comparison with freshwater Synechocystis species revealed Synechocystis sp. PCC 7338 genome encodes additional genes, whose functions are related to ion channels to facilitate the adaptation to high salt and high osmotic pressure. Furthermore, a ferric uptake regulator binding motif was found in regulatory regions of various genes including SigF and the genes involved in energy metabolism, suggesting the iron-regulatory network is connected to not only the iron acquisition, but also response to high salt stress and photosynthesis. In addition, the transcriptomics analysis demonstrated a cyclic electron transport through photosystem I was actively used by the strain to satisfy the demand for ATP under high-salt environment. Our comprehensive analyses provide pivotal information to elucidate the genomic functions and regulations in Synechocystis sp. PCC 7338.

Schwannoma arising in mediastinal lymph node diagnosed by endobronchial ultrasound.

Schwannoma is a peripheral nerve sheath tumour that largely originates from the posterior mediastinum. Schwannoma arising in mediastinal lymph node is extremely rare. A 53-year-old female was referred to our hospital for the evaluation of enlarged mediastinal lymph node. Computed tomography scan revealed a non-enhancing soft tissue mass at Rt. paratracheal area. Endobronchial ultrasound showed a well-defined round-shaped lymph node and transbronchial needle aspiration was performed from this lymph node. Pathologic findings revealed spindle cells with strong S100 positivity. Complete surgical excision was done. We report a rare case of schwannoma arising in mediastinal lymph node diagnosed by endobronchial ultrasound.

Potential and limitation of fluorescence-based membrane integrity monitoring (FMIM) for reverse osmosis membranes.

In wastewater recycle for potable purposes, virus removal is the most critical issue from the public health stand point. Therefore, the regulatory agency sets minimum virus removal efficiencies that must be met by combining multiple treatment processes. In most potable reuse processes, reverse osmosis (RO) plays a critical role by removing salts, viruses, dissolved organic matters, etc. It has been reported that RO removes viruses at over 6 log efficiencies, but it receives no more than 2 log credits from regulatory agencies due to the lack of sensitive integrity monitoring technologies better than conductivity-based technologies. In recent years, fluorescence-based membrane integrity monitoring (FMIM) has drawn special attention because of its simplicity, capability of continuous monitoring, and the high resolution. Lab and field studies have shown FMIM can provide around 4 log resolution for commercially available RO membranes. In this study, potential and limitation of current FMIM technology are reviewed. Further, ideas to improve the resolution beyond 4 log are suggested.

Variability in the anti-tumor effect of tegafur-uracil depending on histologic types of lung cancer.

BACKGROUND: Tegafur-uracil (UFT) is an anticancer agent that inhibits thymidylate synthase (TS). The degree of TS expression in primary lung cancer (LC) is different according to histologic cell type. In this study, we examined the variability of the anti-tumor efficacy of UFT monotherapy depending on histological subtypes of LC. METHODS: In the current single-institution, retrospective study, we assigned the patients with LC to three histologic groups [the squamous (Sq) non-small cell lung cancer (NSCLC)] group, the non-Sq NSCLC group and the SCLC group] and then compared the clinical response to UFT monotherapy between the three groups. RESULTS: Our clinical series of 149 patients include 54 cases of Sq NSCLC, 67 cases of non-Sq NSCLC and 28 cases of SCLC. For Sq NSCLC, non-Sq NSCLC and SCLC group, the overall response rates (ORRs) were 1%, 1% and 0% (P=0.522), respectively. The disease control rates (DCRs) were 38.9%, 31.3% and 10.7% (P=0.012), respectively. The median progression-free survivals (PFSs) were 2.68, 2.25 and 1.46 months (P=0.004 for three groups and P=0.773 for two groups except for the SCLC group at the log-rank test), respectively. There was no significant difference between the groups in median overall survival (OS). CONCLUSIONS: Our results indicate that the degree of the anti-tumor effect of UFT was higher in patients with NSCLC as compared with SCLC. But it showed no significant difference between the patients with Sq NSCLC and those with non-Sq NSCLC.

Peptide Nucleic Acid Clamping Versus Direct Sequencing for the Detection of EGFR Gene Mutation in Patients with Non-small Cell Lung Cancer.

PURPOSE: Direct sequencing (DS) is the standard method for detection of epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC); however, low detection sensitivity is a problem. The aim of this study is to demonstrate higher detection rate of EGFR gene mutation with peptide nucleic acid (PNA) clamping compared with DS. MATERIALS AND METHODS: This is a single arm, prospective study for patients with stage IIIB/IV or relapsed NSCLC. Using tumor DNA from 138 patients, both DS and PNA clamping for EGFR gene in exon 18, 19, 20, and 21 were performed. Discrepant results between the two methods were verified using Cobas and a mutant enrichment based next generation sequencing (NGS). Patients with activating mutations were treated with EGFR tyrosine kinase inhibitor (EGFR-TKI, gefitinib, or erlotinib) as first line treatment. RESULTS: Of 138 paired test sets, 24 (17.4%) and 45 (32.6%) cases with activating mutations were detected by DS and PNA clamping, respectively. The difference of detection rate between the two methods was 15.2% (95% confidence interval, 8.7% to 17.8%; p < 0.001). Between the two methods, 25 cases showed discrepant results (n=23, PNA+/DS-; n=2, PNA-/DS+). Mutations were confirmed by Cobas or NGS in 22 of 23 PNA+/DS- cases. The response rates to EGFR-TKI were 72.2% in the PNA+/DS+ group and 85.0% in the PNA+/DS- group. CONCLUSION: PNA clamping showed a significantly higher detection rate of EGFR gene mutation compared with DS. Higher sensitivity of PNA clamping was not compromised by the loss of predictive power of response to EGFR-TKI.

Corticosteroid therapy against treatment-related pulmonary toxicities in patients with lung cancer.

BACKGROUND: With the recent increased use of new anti-neoplastic agents, molecular-targeted drugs and radiation in patients with lung cancer, there has been an increase in the occurrence drug-induced or radiation-induced pulmonary toxicities. We conducted this study to evaluate the clinical characteristics of patients with lung cancer who presented with treatment-related pulmonary toxicities and to analyze the dosage pattern of corticosteroid therapy against them. METHODS: To collect the baseline data from the patients with lung cancer who developed treatment-related pulmonary toxicities, we initially selected those who were prescribed corticosteroids between January 1, 2008 and December 31, 2012. Depending on clinical and radiological diagnoses, we classified pulmonary toxicities into drug-induced interstitial lung disease (DILD), radiation pneumonitis, acute exacerbation of chronic obstructive pulmonary disease (AE COPD) and others. RESULTS: We divided total patients (n=398) into four groups, and these include 88 cases (22%) of DILD, 189 cases (47%) of radiation pneumonitis, 47 cases (12%) of AE COPD and 74 cases (19%) of others. The prescribed rate of pulse or high-dose steroid was measured as 73%, 20%, 40% and 38%, respectively (P<0.001). In DILD radiologic findings, the 2-month mortality was significantly higher in the patients with the diffuse alveolar damage (DAD) pattern (100%) as compared with those with the non-specific interstitial pneumonia (NSIP) or bronchiolitis obliterans with organizing pneumonia (BOOP) one (62% or 42%, respectively) (P=0.032). CONCLUSIONS: This study showed that the natural course of DILD had more unfavorable outcome requiring higher dose steroid therapy as compared with those with radiation pneumonitis or AE COPD. According to a subgroup analysis of the patients with DILD, BOOP and NSIP radiographic patterns showed more favorable outcomes.

Prevalence of chronic sputum and associated factors in Korean adults.

Chronic sputum is a troublesome symptom in many respiratory diseases. The prevalence of chronic sputum varies from 1.2% to 13% according to the country. The purpose of this study was to estimate the prevalence of chronic sputum and to find its associated factors in a general Korean population. We analyzed the data of the Korea National Health and Nutrition Examination Survey 2010 and 2011. A total number of 6,783 subjects aged 40 yr or more were enrolled in this study with 3,002 men and 3,781 women. As a result, the prevalence of chronic sputum was 6.3% (n=430). Significant risk factors for chronic sputum by multivariate analysis were: age (≥ 70 yr) (odds ratio [OR], 1.954; 95% confidence interval [CI], 1.308-2.917), current smoking (OR, 4.496; 95% CI, 3.001-6.734), chronic obstructive pulmonary disease (COPD) (OR, 1.483; 95% CI, 1.090-2.018), and tuberculosis (OR, 1.959; 95% CI, 1.307-2.938). In conclusion, the prevalence of chronic sputum in Korea was in the intermediate range compared with other countries. Smoking is a preventable risk factor identified in this study, and major respiratory diseases, such as COPD and tuberculosis, should be considered in subjects with chronic sputum.

Efficacy and safety of docetaxel plus oxaliplatin as a first-line chemotherapy in patients with advanced or metastatic non-small cell lung cancer.

BACKGROUND: Platinum doublets are standard first-line treatment for stage IV non-small cell lung cancer (NSCLC) without targetable driver mutations. Oxaliplatin is more potent than cisplatin, requiring fewer DNA adducts to provide equivalent cytotoxicity. The objective of this study was to evaluate the efficacy and safety of oxaliplatin combined with docetaxel as a first-line treatment for stage IV NSCLC. METHODS: This was a prospective, single-center, phase II trial. Patients with chemotherapy-naive NSCLC received 60 mg/m(2) docetaxel (day 1) and 70 mg/m(2) oxaliplatin (day 2) every three weeks for up to six cycles. The primary endpoint was objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Treatment response was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Thirty-three patients were enrolled and a response evaluation was available in 31 patients. There were 11 patients with a partial response, 15 with stable disease, and five with progressive disease. Two patients ceased further treatment after the first cycle of chemotherapy. Thus, the ORR was 33.3% in the 33 patients of the intention-to-treat population. Median PFS was 3.6 months (95% confidence interval [CI], 2.8-4.5), and median OS was 10.9 months (95% CI, 8.2-13.6). The most common hematologic toxicity was neutropenia. Grade 3-4 neutropenia occurred in 51.5% of patients. CONCLUSION: The results suggest that the combination of oxaliplatin and docetaxel is effective in patients with NSCLC with reasonable toxicity.

Removal of micropollutants and NOM in carbon nanotube-UF membrane system from seawater.

One of the main problems for seawater reverse osmosis desalination is membrane fouling associated with natural organic matter. Bisphenol-A (BPA) and 17alpha-ethinylestradiol (EE2) are well-known endocrine-disrupting compounds that have been detected in wastewater and seawater. In this study, the contribution of carbon nanotubes (CNTs, single-walled carbon nanotubes) to membrane fouling control and the potential adsorption mechanisms of BPA and EE2 were investigated using artificial seawater (ASW) in a bench scale ultrafiltration (UF) membrane coupled with CNTs. For high ionic strength ASW, UVA254 nm is a good alternative for highly aromatic dissolved organic carbon (DOC) determination, with a very strong linear relationship (R2 > or = 0.99) with increasing DOC concentrations. Approximately 80% of DOC in ASW was rejected by the CNT-UF system where 31% of DOC was removed due to adsorption by CNTs. The presence of CNTs shows a 20% increase in membrane flux in ASW. A strong linear correlation between retention and adsorption of BPA and EE2 was obtained. The percentage of adsorption/retention of BPA and EE2 in UF-CNTs follows the order: 94.0/96.6 (DI + CNTs, EE2) > 86.2/90.0 (ASW + CNTs, EE2) > 73.6/78.9 (DI + CNTS, BPA) > or = 74.1/77.3 (ASW + CNTS, BPA) > 29.8/29.8 (ASW, EE2) approximately equal to 27.3/27.3 (ASW, BPA) > or = 25.3/25.3 (DI, EE2) approximately equal to 24.8/24.8 (DI, BPA). This indicates that retention by the UF-CNT system is mainly due to adsorption. Overall, EE2 adsorption was greater than BPA during the UF-CNT experiments, presumably due to the higher hydrophobicity of EE2 than BPA.

Critical operational parameters for zero sludge production in biological wastewater treatment processes combined with sludge disintegration.

Mathematical models were developed to elucidate the relationships among process control parameters and the effect of these parameters on the performance of anoxic/oxic biological wastewater processes combined with sludge disintegrators (A/O-SD). The model equations were also applied for analyses of activated sludge processes hybrid with sludge disintegrators (AS-SD). Solubilization ratio of sludge in the sludge disintegrator, alpha, hardly affected sludge reduction efficiencies if the biomass was completely destructed to smaller particulates. On the other hand, conversion efficiency of non-biodegradable particulates to biodegradable particulates, beta, significantly affected sludge reduction efficiencies because beta was directly related to the accumulation of non-biodegradable particulates in bioreactors. When 30% of sludge in the oxic tank was disintegrated everyday and beta was 0.5, sludge reduction was expected to be 78% and 69% for the A/O-SD and AS-SD processes, respectively. Under this condition, the sludge disintegration number (SDN), which is the amount of sludge disintegrated divided by the reduced sludge, was calculated to be around 4. Due to the sludge disintegration, live biomass concentration decreased while other non-biodegradable particulates concentration increased. As a consequence, the real F/M ratio was expected to be much higher than the apparent F/M. The effluent COD was maintained almost constant for the range of sludge disintegration rate considered in this study. Nitrogen removal efficiencies of the A/O-SD process was hardly affected by the sludge disintegration until daily sludge disintegration reaches 40% of sludge in the oxic tank. Above this level of sludge disintegration, autotrophic biomass concentration decreases overly and TKN in the effluent increases abruptly in both the A/O-SD and AS-SD processes. Overall, the trends of sludge reduction and effluent quality according to operation parameters matched well with experimental results found in literatures.

The optimum operational condition of membrane bioreactor (MBR): cost estimation of aeration and sludge treatment.

A methodology to obtain the most economical operational condition of membrane bioreactor (MBR) is developed. In order to achieve the optimum design parameters of MBR with which operational costs are minimized, aeration and sludge treatment costs were estimated for various operational conditions. Generally sludge treatment cost and aeration cost were inversely proportional to each other, which means sludge treatment cost is minimized when aeration cost is maximized and vice versa. Therefore, there might exist an optimum point between the two extreme cases. However, sludge treatment cost turned out to overwhelm the aeration cost over the reasonable operational conditions. Therefore, sludge minimization was considered to be a key for the economical operation of MBR. In the case of typical municipal wastewater of which COD was 400mgL(-1), steady-state MLSS was expected to increase from 11,000 to 15,000mg/L without sludge removal when HRT was decreasing from 16 to 12h. For the range of operational conditions considered in this study, economically optimum HRT and target MLSS were turned out to be 16h and 11,000mg/L, respectively. Under this condition, aeration for the biodegradation of organic matters would be 13.3m(3) air/min when influent was 1000m(3)/day.

Important operational parameters of membrane bioreactor-sludge disintegration (MBR-SD) system for zero excess sludge production.

In order to prevent excess sludge production during wastewater treatment, a membrane bioreactor-sludge disintegration (MBR-SD) system has been introduced, where the disintegrated sludge is recycled to the bioreactor as a feed solution. In this study, a mathematical model was developed by incorporating a sludge disintegration term into the conventional activated sludge model and the relationships among the operational parameters were investigated. A new definition of F/M ratio for the MBR-SD system was suggested to evaluate the actual organic loading rate. The actual F/M ratio was expected to be much higher than the apparent F/M ratio in MBR-SD. The kinetic parameters concerning the biodegradability of organics hardly affect the system performance. Instead, sludge solubilization ratio (alpha) in the SD process and particulate hydrolysis rate constant (k(h)) in biological reaction determine the sludge disintegration number (SDN), which is related with the overall economics of the MBR-SD system. Under reasonable alpha and k(h) values, SDN would range between 3 and 5 which means the amount of sludge required to be disintegrated would be 3-5 times higher for preventing a particular amount of sludge production. Finally, normalized sludge disintegration rate (q/V) which is needed to maintain a certain level of MLSS in the MBR-SD system was calculated as a function of F/V ratio.

Effect of acidity consumption/production on the pH of aeration tank during the biodegradation of acetic acid/epichlorohydrin.

In order to elucidate the biologically driven pH fluctuation phenomena in industrial wastewater treatment, the contrary effects of acetic acid (AA) and epichlorohydrin (ECH) on the pH of aeration tank were investigated. Two simple equations were derived to estimate optimum neutralization pHs for the biological AA/ECH wastewater treatment, and the calculated optimum neutralization pHs were compared with experimental results. The pH in aeration tank was expected to fluctuate sharply with the smallest deviation of neutralization pH from the optimum value. However experimental results showed that real pH fluctuation is smaller than the theoretical one. It was considered that carbonate buffer in aqueous system relieves the pH fluctuation. The deviation between experimental and theoretical optimum neutralization pH could be mainly caused by volatility of AA and ECH. The deviation was larger with ECH wastewater of which volatility is larger than AA. Finally, this theory was successfully applied to the real petrochemical wastewater treatment. The pH of aeration tank was properly maintained when acidified wastewater (pH 3.4) was supplied.

Comparison of the filtration characteristics of organic and inorganic membranes in a membrane-coupled anaerobic bioreactor.

Comparison of filtration characteristics of organic and inorganic membranes was made in terms of physicochemical properties of the membrane materials, cake layer formation, backflushing and backfeeding effects in a membrane-coupled anaerobic bioreactor. For the inorganic membrane, struvite (MgNH4PO4 x 6H2O) was found to have accumulated inside the membrane pore and plays a key role in flux decline. For the organic, however, a thick cake layer composed of biomass and struvite formed on the membrane surface, thus causing a major hydraulic resistance. In order to mitigate flux decline for both membranes, backflushing and backfeeding modes were examined. With acidic (pH 2.0) backflushing, the flux was approximately doubled for the organic membrane. However, unexpectedly a negative effect was observed for the inorganic membrane. An alkaline backflushing instead of acidic backflushing gave rise to a flux improvement by a factor of two without any negative effect, even for the inorganic membrane. The backfeeding mode gave rise to a much higher flux compared with the normal mode in both types of membrane, although the flux returned to the same level as that with the normal mode after 6 days for the inorganic membrane. The differences between the two types of membranes were explained by membrane morphology, a ligand exchange reaction as well as a surface charge effect.