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Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard of care for EGFR mutation-positive non-small cell lung cancer (NSCLC). However, optimal sequence of treatment has yet to be defined. Overall survival (OS) is influenced by the availability/use of subsequent therapy after first-line treatment. Emergence of T790M is the main mechanism of resistance to afatinib and second-line osimertinib could be a treatment option in this instance. Methods In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naive patients with EGFR mutation-positive NSCLC (Del19 or L858R) treated with first-line afatinib and second-line osimertinib in regular clinical practice (n = 191; all T790M-positive). The primary objective was time to treatment failure (TTF). Key secondary objectives were OS and objective response rate (ORR). Results At the start of afatinib treatment, median age (range) was 62 years (34–88). Fifty-five percent of patients were female and 67% were Asian. ECOG PS (0/1/≥2) was 31%/57%/12%. Fourteen percent of patients had brain metastases. At the start of osimertinib treatment, ECOG PS (0/1/≥2) was 25%/61%/14% and 14% had brain metastases (rising to 29% at the end of osimertinib treatment). The source of biopsy material (solid/liquid) was 86%/3% at the start of afatinib and 54%/33% at start of osimertinib. Mutations were mainly detected with PCR methods. Overall, median TTF was 27.7 months (95% CI: 24.0–30.2) and median OS was 36.5 months (95% CI: 32.9–41.8). ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups. Conclusion Sequential afatinib and osimertinib demonstrated encouraging activity in patients with EGFR mutation-positive NSCLC and acquired T790M. Activity was observed across all subgroups, including patients with poor ECOG PS or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib treatment.

Second primary malignancy (SPM) is a well-known cause of death in head and neck cancers. Recently, with reports of many incidences of human papilloma virus (HPV) associated SPM, the disease has been widely investigated. We report a HPV-positive tracheal cancer in a 49-yearold male who had been diagnosed with HPV-positive squamous cell carcinoma of the right tonsil within intervals of two years. In this case, the metachronous tracheal cancer lesion as well as the primary tonsillar cancer showed the same subtype HPV-16.

Background: This study compared the treatment outcomes of patients with multidrug-resistant tuberculosis (MDRTB) before and after the implementation of public-private mix (PPM). Factors affecting treatment success were also investigated. Methods: Data from culture-confirmed pulmonary MDR-TB patients who commenced MDR-TB treatment at Pusan National University Hospital between January 2003 and December 2017 were retrospectively reviewed. Patients were divided into two groups in terms of PPM status: pre-PPM period, patients who commenced MDR-TB treatment between 2003 and 2010; and post-PPM period, patients treated between 2011 and 2017. Results: A total of 176 patients were included (64 and 112 in the pre- and post-PPM periods, respectively). 36.9% of the patients were resistant to a fluoroquinolone or a second-line injectable drug, or both. The overall treatment success rate was 72.7%. The success rate of post-PPM patients was higher than that of pre-PPM patients (79.5% vs. 60.9%, p=0.008). Also, loss to follow-up was lower in the post-PPM period (5.4% vs. 15.6%, p=0.023). In multivariate regression analysis, age ≥65 years, body mass index ≤18.5 kg/m2, previous TB treatment, bilateral lung involvement, and extensively drug-resistant (XDR)- or pre-XDR-TB were associated with poorer treatment outcomes. However, the use of bedaquiline or delamanid for ≥1 month increased the treatment success. Conclusion: The treatment success rate in MDR-TB patients was higher in the post-PPM period than in the pre-PPM period, particularly because of the low rate of loss to follow-up. To ensure comprehensive patient-centered PPM in South Korea, investment and other support must be adequate.

INTRODUCTION Poor sleep quality in patients with chronic obstructive pulmonary disease (COPD) has been associated with poor health outcomes. However, there is a lack of research on factors associated with sleep disturbance in patients with COPD. OBJECTIVES We investigated patterns of sleep disturbance and factors associated with sleep impairment in patients with COPD. METHODS This was a prospective, multicenter cross-sectional study enrolling a sample of 245 COPD subjects. All patients completed the patient-reported measure, the COPD and Asthma Sleep Impact Scale (CASIS) to assess sleep impairment. The St. George's Respiratory Questionnaire (SGRQ), the 36-item Short-Form health survey (SF-36), Hospital Anxiety and Depression Scale (HADS), and the COPD Self-Efficacy Scale (CSES) were utilized to assess health-related quality of life (HRQL), anxiety/depression and self-efficacy, respectively. RESULTS About 35.1% of the patients reported that they had a bad night's sleep. Univariate analysis showed that the CASIS total score was significantly correlated with the modified Medical Research Council dyspnea scale, SGRQ total score, SF-36 PCS, SF-36 MCS, HADS-A, HADS-D and CSES (all P

We aimed to identify the association between sleep deprivation and inflammatory response. Fourteen-week old male Wistar rats were used randomly assigned to a sleep deprivation [sleep deprivation (SD) group, n = 3] or a control [healthy sleep (HS) group, n = 3] group. To induce sleep deprivation, we used a modified multiple platform method. We examined serum interleukin-1beta (IL-1β), corticosterone, the number of inflammatory cells in broncho-alveolar lavage fluid (BALF), and the histopathology of the pulmonary parenchyma (peri-bronchiolar infiltration) between the SD and the HS groups. The SD group showed an increase in serum IL-1β, corticosterone, the number of neutrophil and eosinophil in BALF, and peri-bronchiolar infiltration of eosinophils compared to the HS group. However, serum IL-1β and the number of inflammatory cells in BALF, except for corticosterone and eosinophil in lung parenchyma, were statistically insignificant. We suggest that SD may be associated with worsening of allergic inflammatory response.

Background Disease-specific knowledge is associated with outcomes of patients, but the knowledge level of chronic obstructive pulmonary disease (COPD) patients is known to be low. Objective We measured the level of disease-specific knowledge and defined factors associated with poor disease knowledge in COPD patients. Materials and Methods A cross-sectional survey was performed in five hospitals in South Korea. At enrolment, all patients completed the Bristol COPD Knowledge Questionnaire (BCKQ), Satisfaction with Life Scale (SWLS), Personal Resource Questionnaire (PRQ), St. George's Respiratory Questionnaire (SGRQ), 36-item Short-Form Health Survey (SF-36), and the Hospital Anxiety and Depression Scale (HADS). The data were analyzed via linear regression to identify factors associated with low-level knowledge of COPD. Results A total of 245 COPD patients were enrolled in this study. The mean total BCKQ score was 28.1 (SD, 7.4). The lowest scores were seen for items exploring knowledge of "Oral steroids" and "Inhaled steroids". In univariate analysis, higher level of education (r = 0.17), low income (r = 0.13), the post-bronchodilator FEV1, % predicted (r = -0.24), the post-bronchodilator FEV1/FVC ratio (r = -0.13), SWLS (r = 0.15), PRQ (r = 0.16), SF-36 MCS (r = 0.13), HADS-A (r = -0.17), and HADS-D (r = -0.28) scores correlated with the BCKQ score (all p < 0.05). FEV1 (r = -0.25, p < 0.001) and HADS-D score (r = -0.29, p < 0.001) were significantly associated with the total BCKQ score in multivariate analysis. Conclusion Our Korean patients with COPD lacked knowledge on oral and inhaled steroid treatments. In particular, patients with higher-level lung function and/or depressive symptoms exhibited poorer disease-specific knowledge; such patients may require additional education.

Background/aims Matrix-assisted laser desorption/ionization time-of-f light mass spectrometry (MALDI-TOF MS) is a new diagnostic tool for microorganism identification. The clinical usefulness of this approach has not been widely examined in Korea. This retrospective pre-post-intervention quasi-experimental study examined the effect of MALDI-TOF MS on patients with multidrug-resistant (MDR) bacteremia in the intensive care unit (ICU). Methods All consecutive patients with MDR bacteremia in the ICU of a tertiary care hospital between March 2011 and February 2013 and between March 2014 and February 2016 were enrolled. MALDI-TOF MS was introduced between these periods. In the pre-intervention and intervention groups, microorganisms were identified by conventional means and by MALDI-TOF MS, respectively. The groups were compared in terms of time from venipuncture to microorganism identification and antimicrobial susceptibility test results. Results In total, 187 patients (mean age, 61.0 years; 56.7% male) were enrolled. Of these, 97 and 90 were in the pre-intervention and intervention groups, respectively. The intervention group had a significantly shorter time from venipuncture to microorganism identification and antimicrobial susceptibility test results (82.5 ± 21.6 hours vs. 92.3 ± 40.4 hours, p = 0.038). The antibiotics were adjusted in 52 patients (26 each in the pre-intervention and intervention groups) based on these results. These groups did not differ in terms of time from venipuncture to antibiotic adjustment, and multivariate regression analysis showed that MALDI-TOF MS-based microorganism identification was not associated with 28-day mortality. Conclusion Our study showed that MALDI-TOF MS accelerated microorganism identification in patients with MDR bacteremia, but did not inf luence 28-day mortality.

Background Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissues. Most myelolipomas are found in the adrenal glands, whereas intrathoracic myelolipoma is extremely rare. In particular, bronchial myelolipoma without the involvement of lung parenchyma has never been reported. Case presentation A previously healthy 38-year-old male developed dyspnea and a productive cough. Computed tomography revealed an endobronchial mass at the right bronchus intermedius and subsequent atelectasis of the right middle and lower lobes. Flexible bronchoscopy found a total obstruction of the right bronchus intermedius due to an endobronchial tumor. Using a rigid bronchoscope, the endobronchial tumor was resected and the base of the tumor was additionally ablated with a diode laser to prevent recurrence. The removed endobronchial tumor was a 13 mm × 20 mm-sized oval-shaped mass and was pathologically diagnosed as bronchial myelolipoma. Chest radiographs, obtained on the day following the procedure, showed an improvement of atelectasis, and accompanying symptoms were immediately improved. Follow-up bronchoscopy performed after 12 months evidenced no recurrence of the bronchial myelolipoma. Conclusions We used bronchoscopic intervention in patients with solitary bronchial myelolipoma and there was no evidence of recurrence.

Background The presence of EGFR mutation in patients with advanced non-small cell lung cancer (NSCLC) plays an important role in determining the appropriate treatment, response, and survival. Therefore, this study attempted to predict the prognosis of NSCLC patients using data from quantitative mutation measurements. Methods The data of patients with advanced NSCLC who underwent EGFR mutation testing using the peptide nucleic acid (PNA) mediated clamping method at the Pusan National University Hospital from October 2015 to December 2017 were retrospectively analyzed. The efficiency of PNA clamping was determined by measuring the threshold cycle (Ct ) value. The ΔCt -1 value (standard Ct value minus sample Ct value) was calculated to quantify EGFR mutation. Results During the study period, 71 patients were treated with EGFR-tyrosine kinase inhibitors. The cutoff point for the ΔCt -1 value derived from the receiver operating characteristic curve was 5.32. A survival benefit was observed in the group with an ΔCt -1 value > 5.32 or with a common EGFR mutation type compared to the group with an ΔCt -1 value Conclusion EGFR mutation testing using PNA clamping may predict patient survival, especially in patients with common EGFR mutations, such as exon 19 deletion or L858R. A higher ΔCt -1 value correlates with better survival.

Purpose To reduce lung cancer mortality, lung cancer screening was recommended using low-dose computed tomography (LDCT) to high-risk population. A protocol for multicenter lung cancer screening pilot project was developed to evaluate the effectiveness and feasibility of lung cancer screening to implement National Cancer Screening Program in Korea. Materials and methods Multidisciplinary expert committee was comprised to develop a standardized protocol for Korean Lung Cancer Screening Project (K-LUCAS). K-LUCAS is a population-based single arm trial that targets high-risk population aged 55-74 years with at least 30 pack-year smoking history. LDCT results are reported by Lung-RADS suggested by American Radiology Society. Network-based system using computer-aided detection program is prepared to assist reducing diagnostic errors. Smoking cessation counselling is provided to all currently smoking participants. A small pilot test was conducted to check the feasibility and compliance of the protocols for K-LUCAS. Results In pilot test, 256 were participated. The average age of participants was 63.2 years and only three participants (1.2%) were female. The participants had a smoking history of 40.5 pack-year on average and 53.9% were current smokers. Among them, 86.3% had willing to participate in lung cancer screening again. The average willingness to quit smoking among current smokers was 12.7% higher than before screening. In Lung-RADS reports, 10 (3.9%) were grade 3 and nine (3.5%) were grade 4. One participant was diagnosed as lung cancer. Conclusion The protocol developed by this study is assessed to be feasible to perform K-LUCAS in multicenter nationwide scale.

Objectives Immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor-1 and its ligand have achieved impressive success in treating patients with advanced-stage non-small cell lung cancer (NSCLC) after failed first-line cytotoxic chemotherapy. However, knowledge on clinical biomarkers that could help select patients who will respond well to second-line ICI therapy is limited. Patients and methods Medical records of patients with NSCLC treated with first-line platinum-based chemotherapy and subsequent second-line ICI were collected from 6 medical centers between January 2018 and June 2020. Clinical information, pathologic variables, and radiologic findings of the data collected were reviewed. The patients were followed up until the date of the last visit, the death of any cause, or the end of data recording (December 31, 2020). Results A total of 181 patients with NSCLC were treated with second-line ICI following first-line platinum-based doublet chemotherapy. The median progression-free survival was 2.0 months (interquartile range, 1.0 to 5.5 mo), and the median overall survival was 12.0 months (interquartile range, 6.0 to 20.0 mo). Low body mass index (BMI) was independently associated with progression-free survival (odds ratio [OR], 0.826; 95% confidence interval [CI], 0.723-0.945; P=0.005). Similarly, a low BMI (OR, 0.839; 95% CI, 0.740-0.952; P=0.005) and a high number of metastatic organs (OR, 1.682; 95% CI, 1.156-2.448; P=0.007) were independently associated with the overall survival after second-line ICI therapy. Conclusion BMI and the number of metastatic sites were significantly associated with second-line ICI therapy outcomes in patients with NSCLC receiving first-line platinum-based chemotherapy.

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small-cell lung cancer cell line NCI-H889 cDNA libraries was performed using serum obtained from a small-cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones comprised of 74 different genes, designated KP-SCLC-1 through KP-SCLC-74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis. Three of these antigens, including KP-SCLC-29 (NOL4), KP-SCLC-59 (CCDC83), and KP-SCLC-69 (KIF20B), were CT antigens. RT-PCR and western blot analysis showed that NOL4 was frequently present in small-cell lung cancer cell lines (8/9, 8/9). In addition, NOL4 mRNA was weakly, or at a low frequency, or not detected in various cancer cell lines. Our results reveal that NOL4 was expressed at protein levels in small-cell lung cancer tissues (10/10) but not detected in lung adenocarcinoma and squamous cell carcinoma by immunohistochemical analysis. Serological response to NOL4 was also evaluated by western blot assay using NOL4 recombinant protein. A humoral response against NOL4 proteins was detected in 75% (33/44) of small-cell lung cancer patients and in 65% (13/20) of healthy donors by a serological western blot assay. These data suggest that NOL4 is a specific target that may be useful for diagnosis and immunotherapy in SCLC.

The British Thoracic Society guidelines recommend observation for patients with asymptomatic malignant pleural effusion (MPE). However, asymptomatic MPE can become symptomatic. This study examined the clinical course of asymptomatic MPE in patients with non-small cell lung cancer (NSCLC), including the incidence and timing of symptom development of asymptomatic MPE and the associated factors. Retrospective data of 4822 NSCLC patients between January 2012 and December 2017 were reviewed. Symptom development of asymptomatic MPE was defined as the development of symptoms requiring additional treatment, such as insertion of a chest tube, within 1 year in patients who lacked MPE symptoms at the time of diagnosis. Clinical information, pathological parameters, and radiological characteristics were reviewed. Patient data up to 1 year from the initial diagnosis were reviewed. Of 113 patients with asymptomatic MPE, 46 (41%) became symptomatic within 1 year despite appropriate anticancer treatment. The median time to symptom development was 4 months, and 38 patients (83%) developed symptoms within 6 months. Multivariate logistic regression showed that female sex (odds ratio [OR], 0.256; 95% confidence interval [CI], 0.101–0.649; P = .004) and the depth of pleural effusion on initial computed tomography (CT) (OR, 0.957; 95% CI, 0.932–0.982; P = .001) were independently associated with symptom development of asymptomatic MPE. A fraction of 41% of patients with asymptomatic MPE became symptomatic within 1 year. Female sex and larger MPE on initial CT were independently associated with symptom development of asymptomatic MPE.

Background: Radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) is widely used for diagnosis of peripheral lung lesions (PLLs). To date, there have been no reports regarding the clinical outcomes of RP-EBUS-TBLB for PLLs in patients with idiopathic pulmonary fibrosis (IPF). Objectives: This study was performed between October 2017 and December 2019 to identify the safety and diagnostic performance of RP-EBUS-TBLB in IPF patients. Methods: Patients were divided into the usual interstitial pneumonia (UIP) group (n = 39, 4%), the probable UIP group (n = 12, 1%), and the noninterstitial lung disease (non-ILD) group (n = 903, 95%). Results: The diagnostic yield was significantly lower in the UIP group than in the non-ILD group (62% vs. 76%; p = 0.042), but there were no significant differences between the UIP and probable UIP groups (62% vs. 83%; p = 0.293) or the probable UIP and non-ILD groups (83% vs. 76%; p = 0.741). Multivariate logistic analysis showed that the mean diameter of PLLs, positive bronchus sign on CT, and “within the lesion” status on EBUS were independently associated with success of the procedure. Especially, the presence of the UIP pattern on CT (OR, 0.385; 95% CI: 0.172–0.863; p = 0.020) was independently associated with failed diagnosis. Among patients with UIP, “within the lesion” status on EBUS (OR, 25.432; 95% CI: 2.321–278.666; p = 0.008) was shown to be a factor contributing to a successful diagnosis. Overall, there were no significant differences in complication rates among the 3 study groups. Conclusion: RP-EBUS-TBLB can be performed safely with an acceptable diagnostic yield, even in patients with IPF.

BACKGROUND: Extrapulmonary TB (EPTB) is more difficult to diagnose than pulmonary TB. The delayed management of EPTB can lead to complications and increase the socio-economic burden.METHODS: Patients newly diagnosed with EPTB were retrospectively enrolled from 11 general hospitals in South Korea from January 2017 to December 2018. The basic characteristics of patients were described. Univariable and multivariable analyses were performed between early and delayed diagnosis groups to identify risk factors for delayed diagnosis and treatment in EPTB.RESULTS: In total, 594 patients were enrolled. Lymph node TB (28.3%) was the predominant form, followed by abdominal (18.4%) and disseminated TB (14.5%). Concurrent lung involvement was 17.8%. The positivity of diagnostic tests showed no significant difference between the two groups. Acute clinical manifestations in disseminated, pericardial and meningeal TB, and immunosuppression were associated with early diagnosis. Delayed diagnosis was associated with outpatient clinic visits, delayed sample acquisition and diagnostic departments other than infection or pulmonology.CONCLUSION: The delay in diagnosis and treatment of EPTB was not related to differences in microbiological characteristics of Mycobacterium tuberculosis itself; rather, it was due to the indolent clinical manifestations that cause referral to non-TB-specialised departments in the outpatient clinic and delay the suspicion of TB and diagnostic testing.

Meniscus allograft transplantation (MAT) can be performed to treat symptomatic patients with meniscus-deficient knees. However, the current epidemiologic status of MAT is unknown in many countries, including Korea. This study aimed to investigate the national trends of MAT in Korea which covers MAT procedures by the Korean national health insurance system. Information from the national database was acquired through the Korean Health Insurance Review and Assessment Service (HIRA) from 2010 to 2017. All patients encoded as MAT were included. The total number of MATs and their incidence per 100,000 persons were determined, and the results were stratified by age and sex. The total number of MATs and their incidence per 100,000 persons per year were 369 and 0.77, respectively, in 2010, which increased to 826 and 1.72, respectively, in 2017. The number of MATs increased by 124% over 8 years. The peaks for the total number of MATs and their incidence were seen in patients in their 20 s in 2010, but in 2017, the peaks were observed in patients who were in their 40 s. MAT was performed more frequently in males (61%) than in females (39%) over the study period. The total number of MATs and their incidence had increased by 124% between 2010 and 2017. The peak treatment age range for MAT changed from 20 years of age in 2010 to 40 years of age in 2017, and MAT was performed more frequently in males than in females. IV

Blunt airway trauma is rare but life threatening. Injuries to other vital organs accompany this type of injury in most cases; therefore, conservative treatment may be considered first. In cases of delayed fibrotic airway stenosis after conservative treatment, surgical treatment or bronchoscopic intervention are therapeutic options. We herein report a case of delayed airway stenosis after a blunt traumatic airway injury that was successfully managed by silicone stenting.

Purpose To evaluate the efficacy of combined vitamin C, hydrocortisone, and thiamine in patients with severe pneumonia. Materials and methods All consecutive patients with severe pneumonia who were treated with the vitamin C protocol (6 g of vitamin C per day) in June 2017-January 2018 (n = 53) were compared to all consecutive patients with severe pneumonia who were treated in June 2016-January 2017 (n = 46). Propensity score analysis was used to adjust for potential baseline differences between the groups. Results In the propensity-matched cohort (n = 36/group), the treated patients had significantly less hospital mortality than the control group (17% vs. 39%; P = 0.04). The vitamin C protocol associated independently with decreased mortality in propensity score-adjusted analysis (adjusted odds ratio = 0.15, 95% confidence interval = 0.04-0.56, P = 0.005). Relative to the control group, the treatment group had a significantly higher median improvement in the radiologic score at day 7 compared with baseline (4 vs. 2; P = 0.045). The vitamin C protocol did not increase the rates of acute kidney injury or superinfection. Conclusions Combined vitamin C, hydrocortisone, and thiamine therapy may benefit patients with severe pneumonia.

Introduction HER2 mutations are found in 2% to 4% of non–small-cell lung cancer cases and are usually mutually exclusive with other genetic alterations. We screened a large cohort of patients from multiple institutions in Korea, described the characteristics of HER2-mutant cases, and reported on several patients who were treated with pan-HER inhibitors. Patients and Methods The study population consisted of 360 patients diagnosed with adenocarcinoma from 4 institutions in Korea from June 2015 to September 2016. Tissue specimens from all participants were screened by direct sequencing, and next-generation sequencing was conducted only on specimens that were positive in direct sequencing. HER2-targeted therapy, either poziotinib or afatinib, was orally administrated. Results Next-generation sequencing was conducted in 129 patients, and finally 29 (8.1%) patients with HER2 mutation were identified. Most patients were female (58.6%), had never smoked (70.0%), and had stage IV non–small-cell lung cancer (55.2%). For all patients, the histologic type was adenocarcinoma, with no coexisting EGFR or ALK alterations. The most common type of HER2 mutation (48.3%) was c.2326_2327insTGT in exon 20. A partial response was observed in 2 patients who received poziotinib and 1 patient who received afatinib. The main toxicities of the pan-HER inhibitors were nausea, diarrhea, and mucositis. Conclusion HER2 mutation was estimated at a frequency of approximately 8.1% in Korean patients with adenocarcinoma in the absence of known driver mutations. Because some of the HER2-mutant cases responded to poziotinib or afatinib, further studies are warranted.

Background The diagnostic yields and safety profiles of transbronchial lung biopsy have not been evaluated in inexperienced physicians using the combined modality of radial probe endobronchial ultrasound and a guide sheath (EBUS-GS). This study assessed the utility and safety of EBUS-GS during the learning phase by referring to a database of performed EBUS-GS procedures. Methods From December 2015 to January 2017, all of the consecutive patients who underwent EBUS-GS were registered. During the study period, two physicians with no previous experience performed the procedure. To assess the diagnostic yields, learning curve, and safety profile of EBUS-GS performed by these inexperienced physicians, the first 100 consecutive EBUS-GS procedures were included in the evaluation. Results The overall diagnostic yield of EBUS-GS performed by two physicans in 200 patients with a peripheral lung lesion was 73.0%. Learning curve analyses showed that the diagnostic yields were stable, even when the procedure was performed by beginners. Complications related to EBUS-GS occurred in three patients (1.5%): pneumothorax developed in two patients (1%) and resolved spontaneously without chest tube drainage; another patient (0.5%) developed a pulmonary infection after EBUS-GS. There were no cases of pneumothorax requiring chest tube drainage, severe hemorrhage, respiratory failure, premature termination of the procedure, or procedure-related mortality. Conclusions EBUS-GS is a safe and stable procedure with an acceptable diagnostic yield, even when performed by physicians with no previous experience. Electronic supplementary material The online version of this article (10.1186/s12890-018-0704-7) contains supplementary material, which is available to authorized users.

BACKGROUND Studies on antioxidant enzyme activity and apoptosis related protein expression associated with diabetes are mainly limited to aerobic exercise. Since the effectiveness and efficiency of the resistance to diabetes has recently emerged, it is necessary to investigate the effects of regular resistance exercise on these factors. OBJECTIVE The purpose of this study was to investigate the effects of resistance exercise on antioxidant enzymes activities and apoptosis related protein expression in hippocampus of diabetic rats. METHODS Twenty-one male rats were divided into 3 groups: LETO (control group), OLETF (diabetes group) and OLETF + EX (OLETF with resistance exercise group). Resistance exercise consisted of ladder climbing every 5 days for 30 minutes for 8 weeks. The exercise group was trained to climb a 180-cm vertical ladder with weights secured to their tails. Antioxidant enzyme activities, apoptosis related protein expression, and HOMA-IR level were measured. RESULTS The lipid peroxide and superoxide dismutase (SOD) activity were significantly increased in OLETF + EX compared to OLETF (p< 0.001). Glutathione peroxidase (GPx) activity was significantly lower in OLETF + EX than OLETF (p< 0.001). Caspase-3 expression of hippocampus was significantly decreased in OLETF + EX compared to OLETF (p< 0.05). Bax protein expression was significantly lower in OLETF + EX than OLETF (p< 0.05) whereas Bcl-2 expression was significantly higher in OLETF + EX than OLETF (p< 0.05). HOMA-IR level was significantly decreased in OLETF + EX compared to OLETF (p< 0.05). CONCLUSIONS Regular resistance exercise intervention can decrease oxidative stress by enhancing antioxidant enzyme activity and this may lead to attenuate apoptosis related protein such as caspase-3, bax and bcl-2 expression in hippocampus of diabetic population.

PURPOSE This study was to investigate the effects of 5 weeks combined exercise on blood lipid profile and health-related quality of life in obese military recruits. METHODS Twenty-eight obese recruits were randomly assigned for exercise (n=14) and control (n=14) group. All groups performed a basic military training for 5 weeks. Additionally, exercise group conducted combined exercise consisting of twice a day, in the morning and afternoon, 3 days per week for 5 weeks. RESULTS The results of this study was following; The body weight and BMI were significantly decreased in all groups, in which rate of change showed higher in exercise group than control group (p

BACKGROUND Low-dose computed tomography can identify smaller nodules more often than chest radiography in lung screening. However, complications from invasive diagnostic procedures performed to detect nodules are common. Exosomes contain a diverse array of biomolecules that reflect the biological state of the cell from which they are released. The aim of this study was to investigate the diagnostic value of bronchoalveolar lavage (BAL) fluid exosomal microRNAs (miRNAs) for early-stage lung adenocarcinoma. METHODS We evaluated miRNAs (miR-7, miR-21, miR-126, Let-7a, miR-17, and miR-19) known to have diagnostic value for lung adenocarcinoma. Exosomes were isolated from the BAL fluid of control subjects (n = 15) and patients with lung adenocarcinoma (n = 13). Exosomal miRNA was analyzed using a commercial kit containing probes targeting six selected miRNAs. Results were validated via quantitative PCR. RESULTS The presence of miRNAs was confirmed in exosomes from BAL fluid of both lung adenocarcinoma patients and control subjects. miR-126 (P < 0.001) and Let-7a (P = 0.015) levels were significantly higher in the BAL fluid of lung adenocarcinoma patients than in control subjects. The BAL fluid miRNA signature was confirmed using an independent set of paired adenocarcinoma and normal tissue samples (n = 4). Lung adenocarcinoma tissues showed increased expression of miR-126 (P = 0.039) compared to normal tissue samples. CONCLUSION We identified a close correlation between BAL fluid exosomal miRNAs and tumor miRNAs. BAL fluid exosomal miRNAs obtained through noninvasive methods could serve as diagnostic biomarkers in early-stage lung adenocarcinoma.

PURPOSE This study was to investigate the effects of combined exercise training on isokinetic muscular function and nerve conduction velocity and pain in the obesity women with carpal tunnel syndrome. METHODS The participants were divided into two groups: Exercise group (n=10) and Control group (n=10). The combined exercise training program for 12 weeks. RESULTS The results of this study were as follows: First, As for the isokinetic muscular function abilities, there were significantly increased in extensors, flexors of Left, Right in the exercise group. Second, As for the nerve conduction velocity, there were significantly increased in distal motor latency (DML), distal sensory latency (DSL), sensory conduction velocity (SCV), distal motor amplitude (DMA), distal sensory amplitude (DSA) in the exercise group. and as for the pain, there were significantly increased in the exercise group. CONCLUSIONS As conclusions, this study confirmed that the combined exercise training could improve the isokinetic muscular function and nerve conduction velocity and pain of obesity women with carpal tunnel syndrome.

To evaluate the performance of the Prognosis for Prolonged Ventilation (ProVent) 14 score in patients requiring prolonged mechanical ventilation (PMV).Data were obtained from 366 patients receiving at least 14days of MV between January 2011 and December 2015 at a university-affiliated tertiary care hospital in Korea. ProVent 14 scores were assessed using the six standard variables. Model discrimination was assessed with the area under the receiver operating characteristic curve. Kaplan-Meier estimates were stratified according to the ProVent 14 score to predict 1-year survival.The median age of the study group was 62years (range, 50-72years); 65% were male, and medical patients comprised 66% of the group. Overall mortality at 1year was 43%. For ProVent 14 scores ranging from 0 to ≥4, 1-year mortality rates were 7%, 22%, 41%, 52%, and 75%, respectively (log-rank test, P0.001). The area under the receiver operating characteristic curve of the ProVent 14 score predicting 1-year mortality was 0.74 (95% confidence interval, 0.69-0.78).The ProVent 14 score accurately identified patients receiving PMV with a high 1-year mortality risk. Further validation in a larger sample is required.

Background/Aims: In patients with chronic obstructive pulmonary disease (COPD), the extent of physical activity (PA) is correlated with disease severity and prognosis. However, factors associated with low-level PA in elderly COPD patients are not known. We assessed the levels of PA and clinical factors associated with low-level of PA in elderly COPD patients. Methods: This was a secondary analysis of a multicenter, prospective study of 245 patients with COPD. Among them, 160 patients with 65 years or more were included. Three PA groups were defined with respect to daily activity time (low, moderate, and high). Health related quality of life (HRQL) was measured using St. George’s respiratory questionnaire (SGRQ) and 36-item short-form health survey. Anxiety and depression status were assessed employing the hospital anxiety and depression scale (HADS). Multivariate logistic regression was performed to iden tify independent predictors of low-level PA in elderly COPD patients. Results: Of all the 160 patients, 103 (64.4%) engaged in low-level PA. Upon uni variate analysis, a decreased exercise capacity (6-minute walk test < 250 m), an increased dyspnea (the modified medical research council [MMRC] dyspnea scale ≥ 2), a decreased HRQL (total SGRQ score), and a presence of depression (HADS-D ≥ 8) were significantly associated with low-level PA. Upon multivariate analysis, an MMRC grade ≥ 2 (hazard ratio [HR], 2.550; p = 0.034), and HADS-D ≥ 8 (HR, 2.076; p = 0.045) were independently associated with low-level PA in elderly COPD patients. Conclusions: Two-thirds of elderly patients with COPD reported low-level of PA. More severe dyspnea and a presence of depression were independently associated with low-level PA in elderly COPD patients.

Background: Talc poudrage during thoracoscopy is considered the standard procedure for patients with symptomatic malignant pleural effusion (MPE). Until now, no alternative technique other than talc poudrage for pleurodesis during medical thoracoscopy has been proposed. Liquid sclerosants, such as mistletoe extract, have been sprayed evenly into the pleural cavity during semirigid pleuroscopy for chemical pleurodesis. Objective: We conducted a retrospective study using the database of semirigid pleuroscopy to identify the usefulness of pleurodesis using a mistletoe extract delivered via a spray catheter during semirigid pleuroscopy for symptomatic MPE. Methods: All consecutive patients with symptomatic MPE who underwent semirigid pleuroscopy from October 2015 to September 2016 were registered. The responses were evaluated using chest X- ray or computed tomography 4 weeks after pleurodesis. Results: The study included 43 patients who underwent pleurodesis with mistletoe extract via a spray catheter during semirigid pleuroscopy. Complete and partial responses were seen in 21 (49%) and 19 (44%) patients, respectively. The median duration of chest tube placement after pleurod­esis was 7 days (range 6–8 days) in the 40 patients with complete or partial responses. No cases of severe hemorrhage, empyema formation, respiratory failure, or procedure-related mortality were observed in the subjects at 4 weeks after semirigid pleuroscopy. Conclusion: Pleurodesis with mistletoe extract delivered via a spray catheter during semirigid pleuroscopy is a safe and effective procedure for managing symptomatic MPE.

PURPOSE This study was to investigate the effects of resistance exercise on serum inflammatory markers and CatSper 1-4 expression in testis of OLETF rats. METHODS Male OLETF rats were divided into two groups; control group (n=12), resistance exercise group (n=12). The exercise group performed a total of 8 weeks of moderate intensity resistance exercise on a 1.35 m vertical ladder with weights secured to their tails. RESULTS The results of this study was following; The exercise group showed a significant decreased in the inflammatory (IL-1β, IL-6, TNF-α) levels as compared to the control group. But CRP was no significant difference between control and exercise groups. Also, CatSper 1 and 2 were significantly increased in the exercise group compared to the control group, whereas CatSper 3, 4 were no significant difference between both groups. CONCLUSIONS This study suggests that resistance exercise training can contribute to reduce pro-inflammatory responses in whole body and it affects male reproductive function by improve sperm quality and CatSper protein expression.

Introduction To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non–small-cell lung cancer. Materials and Methods A total of 148 chemotherapy-naive patients lacking driver mutations were randomized into 21-day regimens of cisplatin 70 mg/m 2 with either docetaxel 60 mg/m 2 (n = 71) or pemetrexed 500 mg/m 2 (n = 77) for ≤ 4 cycles. The primary objective was to assess the noninferiority of progression-free survival (PFS) for patients receiving the Doc-Cis regimen. The secondary endpoints were the response rates, overall survival, and toxicity profiles. Results Partial remission was observed in 24 (31.2%) and 24 (33.8%) patients in the Pem-Cis and Doc-Cis groups, respectively. The median PFS was 4.7 months (95% confidence interval [CI], 4.4-5.0) in the Pem-Cis arm and 4.4 months (95% CI, 3.7-5.1) in the Doc-Cis arm ( P > .05). The median overall survival was longer in the Doc-Cis arm (13.3 months; 95% CI, 8.1-18.5) than in the Pem-Cis arm (11.7 months; 95% CI, 8.6-14.8; P > .05). Between the 2 arms, no significant difference was found in the subsequent treatments after failure of first-line treatment. The rate of grade 3 or 4 neutropenia and febrile neutropenia was greater in the Doc-Cis arm than in the Pem-Cis arm. Conclusion In nonsquamous non–small-cell lung cancer patients lacking driver mutations, the PFS and response rates were similar between the 2 arms, and toxicity was tolerable, although adverse events and more severe toxicities were observed more frequently in the Doc-Cis arm.

BACKGROUND This multicenter study was performed to develop a prognosis-prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non-small cell lung cancer (NSCLC) patients. METHODS A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression. RESULTS Among the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis-prediction model, we categorized patients into low, intermediate, and high-risk groups, which had greater accuracy in predictive ability (log-rank statistics = 54.66) than the conventional tumor node metastasis staging (log-rank statistics = 39.56). Next, we generated a prognosis-prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high-risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy. CONCLUSIONS This prognosis-prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.

Background Generally, structural destruction of lung parenchyma, such as pulmonary emphysema, is considered to be related to the low diagnostic yields and high complication rates of lung biopsies of peripheral lung lesions. Currently, little is known about the clinical outcomes of using endobronchial ultrasound with a guide sheath (EBUS-GS) to diagnose peripheral lesions in patients with emphysema. Methods This retrospective study was performed to identify the clinical outcomes of EBUS-GS in patients with pulmonary emphysema. This study included 393 consecutive patients who received EBUS-GS between February 2017 and April 2018. The patients were classified according to the severity of their emphysema, and factors possibly contributing to a successful EBUS-GS procedure were evaluated. Results The overall diagnostic yield of EBUS-GS in patients with no or mild emphysema was significantly higher than in those with moderate or severe pulmonary emphysema (78% vs. 61%, P = 0.007). There were no procedure-related complications. The presence of a bronchus sign on CT (P

INTRODUCTION Although sleep problems have an important impact on daily life and health outcome measures in patients with chronic obstructive pulmonary disease (COPD), patterns of sleep disturbance in patients with mild-moderate COPD remain unknown. OBJECTIVE The aim of this study was to investigate patterns of sleep disturbance and factors associated with sleep impairment in patients with mild-moderate COPD. METHODS This prospective cross-sectional study enrolled 148 male patients with COPD. At enrolment, all patients completed a disease-specific sleep measure, the COPD and Asthma Sleep Impact Scale (CASIS) to assess sleep impairment. Health-related quality of life (HRQL) was measured using the St. George's Respiratory Questionnaire (SGRQ) and the 36-item Short-Form health survey (SF-36). Anxiety and depression status were assessed using the Hospital Anxiety and Depression Scale (HADS). Self-efficacy was measured by the COPD Self-Efficacy Scale (CSES). RESULTS The mean age of the subjects was 67 years [standard deviation (SD) = 8.11]. The proportion of patients who indicated that they had a bad night's sleep was 33.1%. Univariated analysis showed that CASIS score was significantly correlated with the modified Medical Research Council (mMRC) dyspnea scale, SGRQ, SF-36 Physical Component Summary, SF-36 Mental Component Summary, HADS-anxiety, HADS-depression and CSES scores (all P

BackgroundRadial probe endobronchial ultrasound using a guide sheath (EBUS-GS) is used to diagnose peripheral lung cancer. The aim was to identify the accuracy of molecular analysis that were performed with EBUS-GS specimens in patients with non-small cell lung cancer (NSCLC).MethodFrom December 2015 to September 2017, we retrospectively studied 91 patients with peripheral NSCLC who underwent surgery after EBUS-GS. Epidermal growth factor receptor (EGFR) mutational and anaplastic lymphoma kinase (ALK) translocation status obtained from surgical specimens served as the references.ResultsCompared to the reference data, EGFR mutational testing of EBUS-GS specimens was in 97% agreement, and the κ coefficient was 0.931 (P< 0.001). In addition, on ALK translocation testing, the results of all 91 patients were in agreement with the reference data (concordance rate of 100%, κ coefficient 1.000; P< 0.001).ConclusionWe found that EBUS-GS could be used for molecular diagnosis, such as EGFR mutational and ALK translocation status, in patients with peripheral NSCLC.

Introduction: BRAF mutation is present in about 8% of all cancer. Oncogenic activity of BRAF V600E mutation was established in lung cancers. Dabrafenib and trametinib combination therapy is preferred first line therapy for advanced or metastatic lung cancer with BRAF V600E mutation. However, there is only little basic knowledge of BRAF mutational status among Korean population. In this study, BRAF mutation, particularly BRAF V600E mutational status was explored among Korean non-small cell lung cancer patients. The clinical and pathologic characteristics of BRAF V600E mutation in non-small cell lung cancers were also investigated. Materials and Methods: The final cohort was 378 cases of primary non-small cell lung cancers. Fromalin-fixed paraffin embedded (FFPE) tissue blocks were used. PNA-mediated clamping PCR for BRAF V600, BRAF V600E real-time PCR and immunohistochemistry for mutation specific monoclonal antibody of Ventana VE1 were performed on all 378 cases of non-small cell lung cancers. For positive cases, direct sequencing was performed for validation. Results: BRAF V600 mutation was detected in five cases using PNA clamping method among 378 non-small cell carcinoma cases. By using BRAF real-time PCR, a BRAF V600E mutation was detected in 3 patients among total 378 cohort. There were 2 discordant cases between PNA clamping and real-time PCR. On immunohistochemistry, 3 patients showed positive staining for tumor cytoplasm and all positive cases also had positive results in real-time PCR. Direct Sanger sequencing was done in 5 cases that had any positive results for 3 methods. The results of Sanger sequencing was the same with those of real-time PCR and immunohistochemistry. Direct sequencing using PAN PCR product was performed on 2 negative cases for validation. On sequencing using PNA clamping PCR product, all cases showed mutation for BRAF gene other than V600E genotype. Finally, there were 3 cases (0.8%) of BRAF V600E mutation and 2 cases of BRAF mutation (0.5%) other than V600E genotype. Among BRAF mutated patients, there were 2 never smokers and 3 ever smokers. All patients harboring BRAF mutation had no concomitant EGFR or ALK aberrations. Conclusion: BRAF mutation incidence is relatively lower than that of Western data set and similar to that of Japanese report. Immunohistochemistry for Ventana VE1 antibody can be a useful screening method to detect BRAF V600E mutation. Citation Format: Ahrong Kim, Hyo Yeong Ahn, Chang Hun Lee, Young Dae Kim, Min Ki Lee, Yeon Joo Jeong, So Jeong Lee. The incidence of BRAF mutation in non-small cell lung cancers is low in Korean patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2343.

We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC. Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated. Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64–0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71–0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (Ptrend = 0.02) in tumor tissues. These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.

Background and Objective: Radial probe endobronchial ultrasound combined with guide sheath (EBUS-GS) is used for the diagnosis of peripheral lung cancer. However, the accuracy of molecular analysis using EBUS-GS specimen is unknown in patients with non-small cell lung cancer (NSCLC). Methods: From December 2015 to September 2017, a retrospective study was conducted with 91 patients with peripheral NSCLC, who underwent surgery after EBUS-GS. Epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase (ALK) gene rearrangement results using surgical specimens were considered as reference standard value. Results: Compared with the reference standard value, EGFR mutation test using EBUS-GS specimen showed a concordance rate of 97%, and the κ coefficient was 0.931 (P < 0.001). Also, in the ALK gene rearrangement study, the results of all 91 patients were consistent, showing the concordance rate of 100%, and the κ coefficient was 1.000 (P < 0.001). Conclusion: The current study results showed that EBUS-GS is a useful method for the molecular diagnosis, such as EGFR mutation and ALK gene rearrangement analysis, in patients with peripheral NSCLC. Reference: 1. Steinfort DP et al. The European respiratory journal. 2011;37(4):902-910. 2. Vanderlaan PA et al. Lung Cancer. 2014;84(1):39-44.

Objectives: In the LUX-Lung clinical trials of afatinib in EGFR mutation-positive NSCLC, tolerability-guided dose adjustment reduced the incidence and severity of adverse events while maintaining efficacy. The RealGiDo study evaluated the impact of afatinib dose adjustment in a real-world setting. Materials and methods: This non-interventional, observational study used medical records of EGFR mutation-positive NSCLC patients treated with first-line afatinib. Primary outcomes were adverse drug reaction (ADR) incidence and severity, time to treatment failure (TIT), and time to progression (TTP), relative to LUX-Lung 3 (LL3). Results: 228 patients were enrolled from 13 countries. Baseline characteristics were in line with LL3 but with more Del19 patients (78.1% vs. 49.0%) and fewer Asian patients (43.9% vs. 72.2%); 11.8% had ECOG performance status 2-3. A total of 71 (31.1%) received a modified starting dose of = grade 3 ADRs (28.4% vs. 48.9%) and serious adverse events (5.2% vs. 14.0%) than in LL3. Median TTF and TTP were 18.7 and 20.8 months, respectively, and were not impacted by reduced starting dose or dose modification. Conclusion. Real-world data show that afatinib dose adjustments reduced the frequency and intensity of ADRs without compromising effectiveness, highlighting the benefit of tailoring afatinib dose to optimise treatment outcomes and supporting clinical decision-making. The study is registered at clinicaltrials.gov (NCT02751879).