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The field study was undertaken to examine the potential for adverse effects of transgenic soybean expressing bioactive human epidermal growth factor (with tolerance to the herbicide glufosinate, PPT) on the abundance and diversity of plant-dwelling arthropods by comparing with those of a non-GM parental cultivar, Gwangan soybean. Field surveys of soybean fields were carried out over two consecutive years, 2016 and 2017 at Ochang and Jeonju, Korea. The number of captured individuals associated with either of EGF and Gwangan soybean plants increased in 2017 compared with 2016 in both Ochang and Jeonju. During the survey period, the diversity and richness of the occurred insects and arachnids increased, dominance decreased, and the evenness of the insects remained static. The insects of Hymenoptera Order occurred most often comprised 25.4% of total captured insect pests. On the contrary, natural enemy from Hymenoptera Order and other insects from Diptera Order occurred more frequently (29.9% and 19.0%, respectively) in both the survey regions during the study periods. The score from PROXSCAL multidimensional scaling using combined data showed that the occurrence of insects and arachnids were separated due to their cultivation regions and years, irrespective of soybean cultivars. Consequently, the results indicated that there happened no notable change in the composition of arthropod communities in soybean agroecosystem due to GM event in soybean expressing EGF.

Rationale: While the history of pulmonary tuberculosis (PTB) is a risk factor for developing both chronic obstructive pulmonary disease (COPD) and lung cancer, it remains unclear whether the histor...

Background/Aims: We assessed the diagnostic yield of chest computed tomography (CT) as an initial diagnostic method for patients with a tuberculosis (TB) infection detected by mass screening in a country with an intermediate TB burden.Methods: A retrospective study was conducted on patients with TB infection detected by mass screening performed between January 2015 and March 2018. The patients were classified according to whether they had a chest X-ray (CXR) or CT scan as an initial diagnostic test to exclude active TB.Results: Of 542 patients with TB infection detected by mass screening, 222 and 320 were initially examined by CXR and CT, respectively; the two modalities showed no significant difference in rate of detection of patients with active TB (0.9% and 2.5%, respectively; p = 0.110). However, chest CT was associated with further invasive tests using bronchoscopy and respiratory specimens, and significantly increased the frequency of hospital visits.Conclusions: Chest CT was not supported as an initial diagnostic method to rule out active TB in patients with a TB infection detected by mass screening in a country with an intermediate TB burden.

AIM To report our initial experience with robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system and to evaluate the feasibility of the procedure. MATERIAL AND METHODS This prospective observational study was performed at a university teaching hospital from January 2019 to December 2019. Sixty-one women with symptomatic fibroids received RSPM. RESULTS Based on seven resected fibroids and a maximal diameter of resected fibroids

Risk factors for postoperative pulmonary complication (PPC) have not been determined according to preoperative respiratory spirometry. Thus, we aimed to find contributors for PPC in patients with restrictive or normal spirometric pattern. We analyzed 654 patients (379 with normal and 275 with restrictive spirometric pattern). PPCs comprised respiratory failure, pleural effusion, atelectasis, respiratory infection, and bronchospasm. We analyzed the association between perioperative factors and PPC using binary logistic regression. In particular, we conducted subgroup analysis on the patients stratified according to preoperative spirometry. Of 654 patients, 27/379 patients (7.1%) with normal spirometric pattern and 33/275 patients (12.0%) with restrictive spirometric pattern developed PPCs. Multivariable analysis demonstrated that high driving pressure was the only intraoperative modifiable factor increasing PPC risk (OR = 1.13 [1.02–1.25], p = 0.025). In the subgroup of patients with restrictive spirometric pattern, intraoperative driving pressure was significantly associated with PPC (OR = 1.21 [1.05–1.39], p = 0.009), whereas driving pressure was not associated with PPC in patients with normal spirometric pattern (OR = 1.04 [0.89–1.21], p = 0.639). In patients with restrictive spirometric pattern, greater intraoperative driving pressure is significantly associated with increased PPC risk. In contrast, intraoperative driving pressure is not associated with PPC in patients with normal spirometric pattern.

Limited data are available in COVID-19 patients on the prediction of treatment response to systemic corticosteroid therapy based on systemic inflammatory markers. There is a concern whether the response to systemic corticosteroid is different according to white blood cell (WBC) counts in COVID-19 patients. We aimed to assess whether WBC count is related with the clinical outcomes after treatment with systemic corticosteroids in severe COVID-19.We conducted a retrospective cohort study and analysed the patients hospitalised for severe COVID-19 and received systemic corticosteroids between July 2020 and June 2021. The primary endpoint was to compare the composite poor outcome of mechanical ventilation, extracorporeal membrane oxygenation, and mortality among the patients with different WBC counts.Of the 585 COVID-19 patients who required oxygen supplementation and systemic corticosteroids, 145 (24.8%) belonged to the leukopoenia group, 375 (64.1%) belonged to the normal WBC group, and 65 (11.1%) belonged to the leukocytosis group. In Kaplan-Meier curve, the composite poor outcome was significantly reduced in leukopoenia group compared to leukocytosis group (log-rankLeukopoenia may be related with a better response to systemic corticosteroid therapy in COVID-19 patients requiring oxygen supplementation.KEY MESSAGESIn severe COVID-19 treated with systemic corticosteroids, patients with leukopoenia showed a lower hazard for composite poor outcome compared to patients with normal white blood cell counts or leukocytosis.Leukopoenia may be a potential biomarker for better response to systemic corticosteroid therapy in COVID-19 pneumonia.

Background Next‐generation sequencing has mostly been used for genotyping cell‐free DNA (cfDNA) in plasma. However, this assay has several clinical limitations. We evaluated the clinical utility of a novel polymerase chain reaction–free nanowire (NW)‐based plasma cfDNA assay for detecting ALK fusion and mutations. Patients, Materials, and Methods We consecutively enrolled 99 patients with advanced non‐small cell lung cancer undergoing a fluorescence in situ hybridization (FISH) test for ALK fusion; ALK‐positive (n = 36). The NW‐based assay was performed using 50–100 μL of plasma collected at pretreatment and every 8 weeks during ALK inhibitor treatment. Results There was high concordance between the NW‐based assay and the FISH test for identification of ALK fusion (94.9% with a kappa coefficient value of 0.892, 95% confidence interval [CI], 0.799–0.984). There was no difference in the response rate to the first anaplastic lymphoma kinase inhibitor between the ALK‐positive patients identified by the NW‐based assay and by the FISH test (73.5% vs. 72.2%, p = .931). In the ALK variant analysis, variants 1 and 3 subgroups were detected in 27 (75.0%) and 8 (22.2%) patients, respectively. Among 24 patients treated with crizotinib, variant 3 subgroup was associated with worse median overall survival than variant 1 subgroup (36.5 months; 95% CI, 0.09–87.6 vs. 19.8 months; 95% CI, 9.9–not reached, p = .004]. A serial assessment identified that ALK L1196M resistance mutation emerged before radiologic progression during crizotinib treatment. Conclusion The newly developed simple NW‐based cfDNA assay may be clinically applicable for rapid diagnosis of ALK fusion with its variant forms and early detection of resistance. Implications for Practice The authors developed a novel one‐step polymerase chain reaction–free nanowire (NW)‐based plasma cell‐free DNA (cfDNA) assay. This study evaluated the clinical utility of this novel method for the diagnosis of EML4‐ALK fusion in advanced non‐small cell lung cancer (NSCLC). The NW‐based assay and FISH test showed high concordance rate in 99 patients with advanced NSCLC. Serial cfDNA assessment demonstrated this method provided early detection of resistance before radiologic progression during crizotinib treatment. Taken together, plasma cfDNA genotyping by the NW‐based cfDNA assay may be useful for the rapid diagnosis of ALK fusion, classifying variants, and early detection of resistance., This article describes a novel one‐step polymerase chain reaction–free nanowire‐based plasma cell‐free DNA assay and evaluates the clinical utility of this novel method for the diagnosis of EML4‐ALK fusion in advanced non‐small cell lung cancer.

Forced expiratory volume in 1 second (FEVWe evaluated individuals aged 40-69 years who underwent baseline and biannual follow-up spirometric assessments for up to 18 years, excluding those with airflow limitations at baseline. Based on the quartiles of the annual FEVThe annual FEVThe annual FEV

Background: Continuous glucose monitoring (CGM)-derived metrics, including time in range (TIR), are attracting attention as new indicators, beyond hemoglobin A1c, of glycemic control and diabetes c...

Hyun-Il Gil,1,* Sungmin Zo,2,* Paul W Jones,3,4 Bo-Guen Kim,2 Noeul Kang,2 Yeonseok Choi,5 Hyun Kyu Cho,6 Danbee Kang,7 Juhee Cho,7 Hye Yun Park,2 Sun Hye Shin2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 3Institute For Infection and Immunity, St George’s University of London, London, UK; 4Value Evidence and Outcomes, Global Medical R&D, GlaxoSmithKline, Uxbridge, UK; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea; 7Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Sun Hye Shin; Hye Yun ParkDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaTel +82-2-3410-3429Fax +82-2-3410-3849Email freshsunhye@gmail.com; hyeyunpark@skku.eduPurpose: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is widely used to assess the impact of COPD symptoms on health status. Whilst the CAT consists of eight different items, details on the distribution of each item are limited. This study aimed to investigate the distribution and clinical implication of each CAT item, stratified by CAT severity group, in stable COPD patients.Patients and Methods: This was a cross-sectional study at a single referral hospital in South Korea. Spirometry confirmed COPD patients with CAT measured at the first clinical visit were retrospectively identified. Patients were categorized into three groups: low (0 ≤ CAT < 10), medium (10 ≤ CAT < 20), and high (20 ≤ CAT ≤ 40) impact group. For the purpose of this analysis, the first four items (cough, sputum, chest tightness, and dyspnea) and the remaining four items (activities, confidence, sleep and energy) were also grouped as “pulmonary” and “extra-pulmonary”, respectively.Results: A total of 815 patients were included, and mean (SD) forced expiratory volume in 1 s (FEV1) was 62.8 (17.4) % pred. Among them, 300 patients (36.8%) were in the high impact group and had a greater exacerbation history and lower lung function. The proportion of “extra-pulmonary” items score was greater in patients with higher total CAT scores, with the activity and confidence items showing higher scores.Conclusion: In our study, in addition to dyspnea, activity limitation is a particular problem in individual patients with higher CAT total scores, for which physicians need to pay more attention. Our study suggests that whilst CAT total score captures the overall impact of COPD, each item of the CAT contains potentially useful information in understanding the patient’s symptom burden.Keywords: COPD, COPD assessment test, patient reported outcome, symptom

Background Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated. Methods This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group. Results Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity. Conclusion Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.

Objective Whether hormonal changes during menopausal transition postmenopause stages influence pulmonary function is not clearly understood. We evaluated the association between each stage of menopause and the prevalence of abnormal lung function in healthy middle-aged women. We hypothesized that the prevalence of abnormal lung function would increase from the late menopausal transition stage during menopausal transition postmenopause stages. Methods The study population included women 40 to 65 years of age who underwent comprehensive health screening examination at the Kangbuk Samsung Hospital Total Healthcare Centers from January 2015 to December 2017. Stages of menopause (premenopausal, early menopausal transition, late menopausal transition, and postmenopausal) were defined using the 2011 Stages of Reproductive Aging Workshop (STRAW + 10) criteria. Abnormal lung function was defined based on spirometry as forced expiratory volume in 1 second/forced vital capacity less than70% or forced vital capacity less than 80% predicted. Prevalence ratios (PRs) for abnormal lung function by stages of menopause were estimated from logistic regression models adjusted for age, anthropometric measurements, lifestyle factors, medical history, lipid and inflammatory biomarkers, and reproductive factors. Results Among 43,822 participants, there were 4,615 participants (10.5%) with restrictive ventilatory disorder and 653 participants (1.5%) with obstructive ventilatory disorder. The fully adjusted PRs (95% confidence interval) for abnormal ventilatory disorder comparing early menopausal transition, late menopausal transition, and postmenopausal stage to premenopausal stage were 1.01 (0.94-1.08), 1.13 (1.03-1.22), and 1.10 (0.98-1.22), respectively. The fully adjusted PRs for restrictive ventilatory disorder comparing early menopausal transition, late menopausal transition, and postmenopausal stages to premenopausal stage were 1.02 (0.94-1.11), 1.18 (1.06-1.30), and 1.15 (1.00-1.31), respectively. There was, however, no clear association between stages of menopause and obstructive ventilatory disorder. Conclusions In this large study of middle-aged women, the fully adjusted prevalence of abnormal lung function, particularly that of restrictive ventilatory disorder, was higher in women in late menopausal transition and menopausal stages compared to women in premenopausal stage.

Background The presence and progression of interstitial lung abnormalities (ILAs) is known to be associated with a decline of lung function and increased risk of mortality. Research Question We aimed to elucidate the clinical course according to ILAs in patients with COPD. Study Design and Methods A retrospective study was conducted between January 2013 and December 2018 of COPD patients who underwent chest CT imaging and longitudinal pulmonary function tests. We evaluated radiologic findings, history of acute exacerbations of COPD, and lung function changes during the longitudinal follow-up. Results Of 363 patients with COPD, 44 and 103 patients had equivocal and definite ILAs, respectively. Patients with ILAs were significantly older and had lower FEV1 and FVC than patients without ILAs. During the mean follow-up period of 5.2 years, ILAs were associated significantly with the annual incidence of moderate to severe acute exacerbation of COPD (β ± SD, 0.38 ± 0.12; P = .002) and with the risk of frequent exacerbation (adjusted OR, 2.03; P = .045). Patients with progressive ILAs showed a significantly higher rate of annual decline in FEV1 and FVC than those showing no change in, or improved, ILAs. Interpretation ILAs were associated significantly with moderate to severe acute exacerbation in patients with COPD, and the progression of ILAs was associated with an accelerated decline in lung function.

The objective of this study was to examine the dependence of the pressure level in the wound area on the height of the syringe needle from the wound, the gauge of the needle, and the flow rate using the Bernoulli equation. This study was the control-volume analysis using the Bernoulli equation. At a given height of the syringe needle from the wound, the gauge of the syringe needle was fixed, and the pressure in the wound area, which depended on the flow rate of the irrigation solution discharged from the tip of the needle, was calculated according to the Bernoulli equation and the definition of the flow rate. At a constant flow rate of the irrigation solution, the velocity of the irrigation solution discharged through the syringe needle decreased (7.80 → 0.80) with an increase in the diameter of the needle (18G → 14G). At a constant inner diameter of the needle, the velocity of the irrigation solution increased with a reduction in the flow rate of the solution. As the velocity of the irrigation solution increased, the pressure in the wound area increased. As the height of the syringe needle from the wound area increased, the pressure in the wound area increased. In order to maintain the pressure of 8–15 psi when nurses perform syringe-based irrigation, it is necessary to set the flow rate of the cleaning solution from 3.5 cc/s to less than 4.8 cc/s for 19G. In addition, 20G maintains the flow rate of the solution at 2.6 cc/s or more and less than 3.5 cc/s, 22G maintains the flow rate of solution at 1.3 cc/s or more and less than 1.8 cc/s, and 25G maintains the flow rate of solution at 0.5 cc/s. This study provides nurses with a reference for the flow rate at which syringe-based irrigation can be performed while maintaining the appropriate pressure based on fluid dynamics, which can be used as the basis for wound nursing standards.

The aim of our study was to investigate the incidence of and risk factors for coronavirus disease 2019 (COVID-19) in patients with non-tuberculous mycobacterial-pulmonary disease (NTM-PD). A total of 3,866 patients with NTM-PD were retrospectively identified from a single center. Compared to the general population of Korea, patients with NTM-PD had a substantially increased age-standardized incidence of COVID-19 from January 2020 to February 2021 (2.1% vs. 0.2%). The odds of being infected with COVID-19 was particularly higher in patients who received treatment for NTM-PD than in those who did not receive treatment for NTM-PD (adjusted odd ratio = 1.99, 95% confidence interval = 1.09-3.64

OBJECTIVE: Localization of focal epilepsy is critical for surgical treatment of refractory seizures. There remains a great need for noninvasive techniques to localize seizures for surgical decision-making. We investigate the use of deep learning using resting state functional magnetic resonance imaging (RS-fMRI) to identify the hemisphere of seizure onset in temporal lobe epilepsy (TLE) patients. METHODS: A total of 2132 healthy controls and 32 preoperative TLE patients were studied. All participants underwent structural MRI and RS-fMRI. Healthy control data were used to generate training samples for a three-dimensional convolutional neural network (3DCNN). RS-fMRI was synthetically altered in randomly lateralized regions in the healthy control participants. The model was then trained to classify the hemisphere containing synthetic noise. Finally, the model was tested on TLE patients to assess its performance for detecting biological seizure onset zones, and gradient-weighted class activation mapping (Grad-CAM) identified the strongest predictive regions. RESULTS: The 3DCNN classified healthy control hemispheres known to contain synthetic noise with 96% accuracy, and TLE hemispheres clinically identified to be seizure onset zones with 90.6% accuracy. Grad-CAM identified a range of temporal, frontal, parietal, and subcortical regions that were strong anatomical predictors of the seizure onset zone, and the resting state networks that colocalized with Grad-CAM results included default mode, medial temporal, and dorsal attention networks. Lastly, in an analysis of a subset of patients with postsurgical outcomes, the 3DCNN leveraged a more focal set of regions to achieve classification in patients with Engel Class >I compared to Engel Class I. SIGNIFICANCE: Noninvasive techniques capable of localizing the seizure onset zone could improve presurgical planning in patients with intractable epilepsy. We have demonstrated the ability of deep learning to identify the correct hemisphere of the seizure onset zone in TLE patients using RS-fMRI with high accuracy. This approach represents a novel technique of seizure lateralization that could improve preoperative surgical planning.

Background We examined the actionable genomic alterations in ovarian cancer by analysing the nationwide registry of next-generation sequencing (NGS) data. Methods From March 2017 to December 2018, 16,458 patients with cancer underwent NGS testing under the interim coverage programme for NGS provided by the National Health Insurance of Korea. Among these patients, 779 patients had advanced ovarian cancer. Fifty-eight mutations were reported as pathogenic variants, which included likely pathogenic variants, and 55 theoretically actionable genes were analysed. Results The prevalence of pathogenic mutations in the population was 81.5%, whereas 11.6% of the population had neither a pathogenic mutation nor a variant of unknown significance. Common pathogenic mutations shared by at least 3% of the study population were mutations in TP53 (61.5%), BRCA1 (12.2%), PIK3CA (10.4%), KRAS (10.3%), BRCA2 (9.6%) and PTEN (3.7%). BRCA1/2 pathogenic mutations were found in 14.0% (42 of 300, 95% confidence interval = 10–18%) of the patients with TP53 wild-type tumours, comprising approximately one-quarter (25.9%) of the total observed BRCA1/2 pathogen mutations. At least one pathogenic mutation in a theoretically actionable gene was found in 49.2% of patients. Among patients without a BRCA1/2 pathogenic mutation, mutations were frequently observed in KRAS (12.2%), PIK3CA (10.4%) and PTEN (4.2%). PTCH1 mutations were correlated with ATM, NF1, ERBB2 and MTOR mutations (adjusted p = 0.0054, p = 0.0035, p = 0.0010 and p = 0.0003, respectively). Conclusions Almost half of patients with ovarian cancer could be estimated as theoretical candidates for genomic medicine. Substantial BRCA1/2 pathogenic mutations were observed in patients not harbouring a TP53 mutation.

PurposeImmune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis. Materials and MethodsIn this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated. ResultsPneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031).ConclusionSequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.

Ceritinib is a potent selective ALK inhibitor with a manageable safety profile. In anecdotal reports, ceritinib was associated with organizing pneumonia (OP), which could be confused with disease progression. We aimed to delineate the characteristics of OP that occurs during treatment with ceritinib, and evaluate its clinical implications. We retrospectively analyzed 44 lung cancer patients whose tumors harbored ALK or ROS1 fusions and who had received ceritinib. OP diagnosis was based on radiographic and clinical features. Four OP cases were pathologically confirmed. Among 44 patients, 22 OP events occurred in 16 (36.4%) patients. The median time to the first event was 17.2 weeks (range 6.7–68.7 weeks). All events were grade 1 or 2. Radiographic features were categorized into four patterns: nodular (54.6%), consolidation (27.3%), parenchymal band (4.5%), and ground-glass opacity (GGO) (13.6%). OP improved in 20 events with drug interruption or corticosteroids. The median duration of OP was 11.3 weeks (range 2–24 weeks). Tumor response rate was 75% in OP-positive and 42.9% in OP-negative groups. The median progression-free survival was 16.7 months [95% confidence interval (CI) 10.1–not applicable (NA)] in OP-positive and 5.4 months (95% CI 3.6–8.4) in OP-negative patients (P = 0.004). The median overall survival was 46.2 months (95% CI 38.1–NA) in OP-positive and 10.5 months (95% CI 6.2–18.9) in OP-negative patients (P

Tight junction protein 1 (TJP1) is a membrane-associated cytosolic protein important for cell-cell communication in intercellular barriers in epithelial and non-epithelial cells. Here, we explored the functional involvement of TJP1 in non-epithelial tumors such as soft tissue sarcoma, especially in leiomyosarcoma (LMS). TJP1 expression in soft tissue sarcoma was analyzed in normal and tumor tissues as well as from public datasets such as the TCGA provisional dataset, in which TJP1 expression was compared with other subtypes such as undifferentiated sarcomas, and myxofibrosarcomas. SK-LMS-1 cell lines with reduced TJP1 expression showed attenuated anchorage-independent colony formation as well as reduced intercellular aggregation on non-coated culture plates compared with control as well as parental SK-LMS-1 cells. Transcriptome profiling following TJP1 knockdown in SK-LMS-1 cells suggested the involvement of several signaling pathways, including NF-κB pathway and growth factor receptor signaling. In addition, TJP1 downregulation induced enhanced response against anti-cancer agents, doxorubicin and gefitinib. Taken together, these results suggest that TJP1 contributes to sarcoma genesis and might be useful therapeutic target. KEY MESSAGES: • TJP1 expression at RNA level higher in tumor than in normal tissues of sarcoma. • Targeting TJP1 attenuates cell-cell aggregation and anchorage-independent growth. • Targeting TJP1 is beneficial in anti-cancer therapy in LMS.

Background/Aims Although acute pulmonary embolism (PE) adversely impacts survival and should be treated regardless of cancer, the treatment rate of cancer-related PE is relatively low. We aimed to compare clinical characteristics and long term prognosis of PE in patients with or without cancer. Methods From March 2010 to December 2013, patients with newly diagnosed PE were analyzed. Baseline demographics, comorbidities, cancer status and clinical manifestations of PE were recorded. We defined primary composite outcome as recurrent venous thromboembolism (VTE) and death from PE. Results Among a total of 976 patients with PE, the 703 (72.0%) had cancer-related PE. Cancer-related PE group was more frequently asymptomatic (54.5% vs. 13.2%, p < 0.001), less extensive (involvement of bilateral pulmonary arteries: 42.8% vs. 51.3%, p = 0.017; lung infarction: 5.3% vs. 10.3%, p = 0.005) and less likely to accompany right ventricular dysfunction (10.3% vs. 27.2%, p < 0.001) compared with the non-cancer PE group. Anticoagulation was less frequently underwent in patients with cancer-related PE than those without cancer (62.0% vs. 81.7%, p < 0.001). A composite of recurrent VTE and death from PE was significantly higher in the cancer-related PE group (14.4% vs. 6.6%, p = 0.001). Conclusions Although PE in cancer patients were seem to be less aggressive initially, compared to those without cancer, they had significantly poor prognosis. Given a high rate of recurrent VTE and relatively similar risk of anticoagulation associated bleeding events in cancer patients, more active treatment of PE is warranted in cancer patients.

As cancer chemotherapy transitions from inpatient care to outpatient care, the number of patients who receive a central venous catheter (CVC) and the interest in CVCs as a safe intravenous administration route have increased recently in South Korea. The purpose of this study was to investigate the discomforts and satisfaction that cancer patients with a CVC may experience in daily activities as an outpatient and to provide rationale for nursing interventions. Data collection was conducted between April 11, 2011, and August 31, 2011. Forty-three questionnaires were collected, and a total of 41 questionnaires were used for the final analysis. The mean age of patients was 45.1 years (SD = 11.1 years; range, 18-64 years). The average score of experience of the CVC insertion procedure, daily life experiences of patients with a CVC, the satisfaction and fear of using a CVC, and the acceptance of CVCs were 2.48 ± 0.56, 2.18 ± 0.50, 2.56 ± 0.49, and 2.35 ± 0.39, respectively. The results showed that more detailed information on CVCs, as well as sufficient emotional support, should be provided to the patient to minimize discomfort during CVC insertion. Patient-centered education helps empower patients to master CVC self-management, as well as an understanding of the cultural aspect of South Korean patients who practice the traditional Confucian ethics of "unaltering one's body" and are therefore reluctant to have CVCs inserted into their bodies.

Evolution of vestibular function requires further elucidation in spinocerebellar ataxia (SCA). This study aimed to determine temporal evolution in the findings of head impulse tests (HITs) in SCA type 6 (SCA6). We serially evaluated HITs in 12 patients with SCA6 using video-oculography for 3 months to 5 years [median = 12 months, interquartile range (IQR) = 9-50] at two university hospitals in South Korea. Patients (8/12, 67%) usually showed abnormal responses at least for one semicircular canal during video-HITs. The gains of the vestibulo-ocular reflex (VOR) for the anterior canals (ACs) were larger than those for the posterior canals (PCs, p = 0.005) at initial presentation. During the follow-up, the VOR gains decreased for the horizontal canals (HCs, p = 0.008) and ACs (p = 0.021), but those for the PCs remained unchanged (p = 0.212). Perverted HITs were observed in seven patients (7/12, 58%). The differences in the head impulse VOR gains were larger between the ACs and PCs (ΔACs - PCs) in those with perverted HITs than in those without (p = 0.003). The gains for each semicircular canal showed a negative correlation with the Scale for the Assessment and Rating of Ataxia (HCs, Spearman's coefficient = - 0.675, p = 0.003; ACs, - 0.637, p = 0.006; PCs, - 0.605, p = 0.010). The head impulse gain of the VOR may serve a marker for clinical decline in SCA6. The dissociation in the temporal evolution of the VOR gain indicates dissimilar cerebellar modulation of the vestibular signals from each semicircular canal.

Background and objective This study aims to evaluate the impact of diffusing capacity of the lung for carbon monoxide (DLco) before and after neoadjuvant concurrent chemoradiotherapy (CCRT) on postoperative pulmonary complication (PPC) among stage IIIA/N2 non-small-cell lung cancer (NSCLC) patients. Methods We retrospectively studied 324 patients with stage IIIA/N2 NSCLC between 2009 and 2016. Patients were classified into 4 groups according to DLco before and after neoadjuvant CCRT; normal-to-normal (NN), normal-to-low (NL), low-to-low (LL), and low-to-very low (LVL). Low DLco and very low DLco were defined as DLco Results On average, DLco was decreased by 12.3% (±10.5) after CCRT. In multivariable-adjusted analyses, the incidence rate ratio (IRR) for any PPC comparing patients with low DLco to those with normal DLco before CCRT was 2.14 (95% confidence interval (CI) = 1.36–3.36). Moreover, the IRR for any PPC was 3.78 (95% CI = 1.68–8.49) in LVL group compared to NN group. The significant change of DLco after neoadjuvant CCRT had an additional impact on PPC, particularly after bilobectomy or pneumonectomy with low baseline DLco. Conclusions The DLco before CCRT was significantly associated with risk of PPC, and repeated test of DLco after CCRT would be helpful for risk assessment, particularly in patients with low DLco before neoadjuvant CCRT.

Chai Young Lee,1,&ast; Sun Hye Shin,1,&ast; Hye Sook Choi,2 Yunjoo Im,1 Bo-Guen Kim,1 Ju Yeun Song,1 Daegeun Lee,1 Hye Yun Park,1 Jun Hyeok Lim3 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 3Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hye Yun Park, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Tel +82-2-3410-3429, Fax +82-2-3410-3849, Email hyeyunpark@skku.edu Jun Hyeok Lim, Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea, Tel +82-32-890-1038, Fax +82-32-890-3099, Email jhl@Inha.ac.krPurpose: Vitamin D insufficiency or deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD). However, the association between vitamin D levels and respiratory symptoms in patients with stable COPD has not been fully investigated. This study evaluated the association between vitamin D levels and respiratory symptoms in patients with stable COPD.Patients and Methods: Patients with COPD who had their serum 25-hydroxyvitamin D (25-OH vitamin D) level measured within 6 months of spirometry between January 2016 and April 2020 were retrospectively included. Respiratory symptoms were assessed using the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT) score.Results: Of the 329 included patients, 193, 88, and 48 were categorized as having vitamin D deficiency (< 20 ng/mL), insufficiency (20– 29 ng/mL), and sufficiency (≥ 30 ng/mL), respectively. The mean serum 25-OH vitamin D level of each group was 13.45 ng/mL, 24.61 ng/mL, and 38.90 ng/mL, respectively. Patients with vitamin D insufficiency/deficiency showed higher CAT scores than those with vitamin D sufficiency (p = 0.004). In multivariable adjusted models, vitamin D insufficiency/deficiency was significantly associated with a CAT score of 10 or more (adjusted odds ratio [aOR] = 2.41, 95% confidence interval [CI] = 1.20– 4.82, p = 0.013) and mMRC ≥ 2 (aOR = 2.39, 95% CI = 1.08– 5.32, p = 0.032). Among CAT items, the amount of phlegm (p = 0.008), chest tightness (p = 0.030), breathlessness walking upstairs (p < 0.001), home activity limitations (p = 0.002), and lack of energy (p = 0.003) were significantly associated with vitamin D insufficiency/deficiency after adjustment for age, sex, body mass index, smoking history, Charlson comorbidity index, post-bronchodilator forced expiratory volume in 1 second, and season of blood draw.Conclusion: Vitamin D insufficiency/deficiency were associated with worse respiratory symptoms in patients with stable COPD.Keywords: chronic obstructive pulmonary disease, vitamin D, respiratory symptoms, COPD assessment test, modified Medical Research Council

Background and objective Chronic obstructive pulmonary disease (COPD) patients with a body mass index (BMI) 2 are prone to develop adverse event of pharmacological treatment for frequent exacerbation. As chronic bronchitis (CB) is one of the strong risk factors of exacerbation, we investigated the associations between BMI and COPD exacerbations in patients with CB. Methods Patients with COPD were included from the Korean COPD Subgroup Study (KOCOSS), a multicenter observational cohort study. CB was defined using the St. George’s Respiratory Questionnaire and the participants were categorized according to BMI cut-off of 25 kg/m2. Exacerbations during a 1-year follow-up were compared among four groups: non-CB with BMI ≥ 25 kg/m2, non-CB with BMI 2, CB with BMI ≥ 25 kg/m2, and CB with BMI 2. Results Among the 1264 patients with COPD, 451 (35.7%) had CB and 353 (27.9%) had both CB and BMI 2. The COPD exacerbation risk increased across the non-CB with BMI 2, CB with BMI ≥ 25 kg/m2, and CB with BMI 2 groups (adjusted incidence rate ratio [95% confidence interval] 1.21 [0.89–1.62], 1.20 [0.77–1.88], and 1.41 [1.02–1.91], respectively, compared to the non-CB with BMI ≥ 25 kg/m2 group). Conclusions COPD patients having both CB and a BMI 2 are at higher risk of exacerbations. Considering that a BMI 2 often limits treatment options preventing exacerbations, modified guidelines might be needed for non-obese CB patients in Asia.

Background Surgery is the mainstay of treatment for non-small cell lung cancer, but the decline in pulmonary function after surgery is noticeable and requires attention. This study aimed to evaluate longitudinal changes in pulmonary function and integrated patient-reported outcomes (PROs) after lung cancer surgery. Methods Data were obtained from a prospective cohort study, the Coordinate Approach to Cancer Patients’ Health for Lung Cancer. Changes in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) at 2 weeks, 6 months, and 1 year after surgery, and the corresponding modified Medical Research Council (mMRC) dyspnea scale and chronic obstructive lung disease assessment test (CAT) scores were evaluated. Mixed effects model was used to investigate changes in pulmonary function and PROs. Results Among 620 patients, 477 (76.9%) underwent lobectomy, whereas 120 (19.4%) and 23 (3.7%) were treated with wedge resection/segmentectomy and bilobectomy/pneumonectomy, respectively. Both FVC and FEV1 markedly decreased 2 weeks after surgery and improved thereafter; however, they did not recover to baseline values. The corresponding mMRC dyspnea scale and CAT scores worsened immediately after surgery. The dyspnea scale of the mMRC was still higher, while CAT scores returned to baseline one year after surgery, although breathlessness and lack of energy persisted. Compared to the changes from baseline of FVC and FEV1 in patients who underwent lobectomy, patients who underwent bilobectomy/pneumonectomy showed a greater decrease in FVC and FEV1, while wedge resection/segmentectomy patients had smaller decreases in FVC and FEV1 at 2 weeks, 6 months, and 1 year after surgery. Bilobectomy/pneumonectomy patients had the highest mMRC dyspnea grade among the three groups, but the difference was not statistically significant one year after surgery. Conclusions After lung cancer surgery, pulmonary function and PROs noticeably decreased in the immediate post-operative period and improved thereafter, except for dyspnea and lack of energy. Proper information on the timeline of changes in lung function and symptoms following lung cancer surgery could guide patient care approaches after surgery. Trial registration: ClinicalTrials.gov; No.: NCT03705546; URL: www.clinicaltrials.gov

Mitochondria are one of organelles that undergo significant changes associated with senescence. An increase in mitochondrial size is observed in senescent cells, and this increase is ascribed to the accumulation of dysfunctional mitochondria that generate excessive reactive oxygen species (ROS). Such dysfunctional mitochondria are prime targets for ROS-induced damage, which leads to the deterioration of oxidative phosphorylation and increased dependence on glycolysis as an energy source. Based on findings indicating that senescent cells exhibit mitochondrial metabolic alterations, a strategy to induce mitochondrial metabolic reprogramming has been proposed to treat aging and age-related diseases. In this review, we discuss senescence-related mitochondrial changes and consequent mitochondrial metabolic alterations. We assess the significance of mitochondrial metabolic reprogramming for senescence regulation and propose the appropriate control of mitochondrial metabolism to ameliorate senescence. Learning how to regulate mitochondrial metabolism will provide knowledge for the control of aging and age-related pathologies. Further research focusing on mitochondrial metabolic reprogramming will be an important guide for the development of anti-aging therapies, and will provide novel strategies for anti-aging interventions.

Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosomal pathway (ALP). Here, we cloned a novel splicing variant of TFEB, comprising 281 amino acids (hereafter referred to as small TFEB), and lacking the helix-loop-helix (HLH) and leucine zipper (LZ) motifs present in the full-length TFEB (TFEB-L). The TFEB variant is widely expressed in several tissues, including the brain, although its expression level is considerably lower than that of TFEB-L. Intriguingly, in cells stably expressing small TFEB, the expression profile of genes was inverted compared to that in cells ectopically expressing TFEB-L. In addition, fisetin-induced luciferase activity of promoter containing either coordinated lysosomal expression and regulation (CLEAR) element or antioxidant response element (ARE) was significantly repressed by co-transfection with small TFEB. Moreover, fisetin-mediated clearance of phosphorylated tau or α-synuclein was attenuated in the presence of small TFEB. Taken together, the results suggest that small TFEB is a novel splicing variant of TFEB that might act as a negative regulator of TFEB-L, thus fine tuning the activity of ALP during cellular stress.

The importance of dying with dignity in the intensive care unit (ICU) has been emphasized. The South Korean government implemented the "well-dying law" in 2018, which enables patients to refuse futile life-sustaining treatment (LST) after being determined as terminally ill. We aimed to study whether the well-dying law is associated with a significant change in the quality of death in the ICU.The Quality of Dying and Death (QODD) questionnaires were prospectively collected from the doctors and nurses of deceased patients of four South Korean medical ICUs after the law was passed (January 2019 to May 2020). Results were compared with those of our previous study, which used the same metric before the law was passed (June 2016 to May 2017). We compared baseline characteristics of the deceased patients, enrolled staff, QODD scores, and staff opinions about withdrawing LST from before to after the law was passed.After the well-dying law was passed, deceased patients (N = 252) were slightly older (68.6 vs. 66.6, p = 0.03) and fewer patients were admitted to the ICU for post-resuscitation care (10.3% vs. 20%, p = 0.003). The mean total QODD score significantly increased after the law was passed (36.9 vs. 31.3, p = 0.001). The law had a positive independent association with the increased QODD score in a multiple regression analysis.Our study is the first to show that implementing the well-dying law is associated with quality of death in the ICU, although the quality of death in South Korea remains relatively low and should be further improved.

Emerging immune profiling data suggest a higher sensitivity to immune checkpoint inhibitors (ICIs) in nonsmall cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), compared to those without COPD. This study aimed to investigate the clinical impact of COPD on the treatment response to ICIs in a large number of patients with NSCLC. In total, 133 patients with spirometry test results were retrospectively identified among those who received palliative pembrolizumab for NSCLC. COPD was defined as pre-bronchodilator forced expiratory volume in 1 s/forced vital capacity

Transcriptional factor EB (TFEB) and nuclear factor E2-related factor 2 (Nrf2) play crucial roles in the biological response against cellular stressors; however, their relationship has not yet been investigated. Here, we constructed human neuroglioma cell lines stably expressing TFEB. The expression of Nrf2-response genes, including heme oxygenase (HO)-1, glutathione-s-transferase-mu1 (GSTM1), and p62, was induced in the cell line, independent of oxidative stress. Of note, the protein level of Nrf2 was significantly increased, and its ubiquitinated fraction was reduced in stable cells compared to that in the control cells. Among E3 ubiquitin ligases known to be involved in the ubiquitination of Nrf2, DDB1 and Cullin4 associated factor 11 (DCAF11) was down-regulated at both protein and mRNA levels in stable cells, indicating that the repression of DCAF11 by TFEB may be mainly involved in the stabilization of Nrf2. In addition, the level of phosphorylated p62 at S349 was highly increased in stable cells compared to that in control cells, which could allow it to interfere with the association of Keap1 and Nrf2, thus stabilizing Nrf2. We suggest for the first time that TFEB could activate Nrf2 by increasing its stability under conditions devoid of oxidative stress.

Objectives: The histologic response to chemotherapy is an important prognostic factor in osteosarcoma. Thus, we attempted to develop an effective neoadjuvant regimen to achieve an improvement in histologic response. Methods: Twenty-nine patients with a high-grade osteosarcoma received 2 courses of neoadjuvant chemotherapy non-randomly with either the MAP regimen (methotrexate 12 g/m2, cisplatin 120 mg/m2, and doxorubicin 75 mg/m2) or MAPI regimen (MAP plus ifosfamide 9 g/m2). We applied interval compression to MAPI by shortening the preoperative period to be aligned with that of MAP. Adjuvant chemotherapy was tailored according to the necrosis rate of resected tumor specimens. Necrosis rate, toxicity, and survival outcome were compared retrospectively between the 2 groups. Results: The median interval between the beginning of neoadjuvant chemotherapy and surgery was 97.0 days in the MAPI group (17 patients) and 90.5 days in the MAP group (12 patients; p = 0.19). The good histologic response (>90% of necrosis) was observed in 71% of MAPI and in 42% of MAP (p = 0.12). Major toxicities of grade 3 or worse were not different between the 2 groups. The probability of 5-year progression-free survival and overall survival of the MAPI group were 74 and 83%, and those in the MAP group were 50 and 75%, showing no difference. Conclusions: Interval-compressed MAPI therapy given in a similar duration of the preoperative phase to that of conventional MAP therapy showed a marginal trend toward a better histologic response without a significant increase in major toxicities. Regarding the proportion of good histologic response, 71% is one of the highest values ever reported in the literature. The results warrant further testing in a prospective way in a larger cohort.

BACKGROUND AND OBJECTIVE The global burden of chronic obstructive pulmonary disease (COPD) is increasing and COPD patients are at higher risk for all-cause mortality. We aimed to evaluate the impact of COPD on specific-cause mortality using national data. METHODS This was nationwide retrospective cohort study of 340, 767 adults aged 40-84 years who lacked COPD diagnosis at baseline between 1 January 2003 and 31 December 2013. Incident COPD was defined by reference to COPD claim codes and prescription of COPD medication at least twice annually. Cox proportional hazard ratio (HR) for each cause of death in the COPD group was compared to that of the non-COPD group, with other causes of death accounted as the competing risk. RESULTS All-cause mortality was higher in the COPD (2,978 per 100, 000 person-years) than the non-COPD group (629 per 100, 000 person-years) and adjusted HR was 1.41 (95% CI = 1.32, 1.50). The association was particularly strong for chronic lower airway disease (adjusted sub-HR = 9.67; 95% CI = 7.21, 12.96) and lung cancer (adjusted sub-HR = 3.16; 95% CI = 2.68, 3.71), and the association was stronger in those aged

Supplemental Digital Content is available in the text, Background: Differential diagnosis of idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) is challenging since they share clinical features with parkinsonism and autonomic dysfunction. To distinguish MSA-P from IPD when the symptoms are relatively mild, we investigated the usefulness of the quantitative fractionalized autonomic indexes and evaluated the correlations of autonomic test indexes and functional status. Methods: Thirty-six patients with parkinsonism (22 with IPD and 14 with MSA-P) in Soonchunhyang University Bucheon Hospital from February 2014 to June 2015 were prospectively enrolled in the study. We compared fractionalized autonomic indexes and composite autonomic scoring scale between patients with IPD and MSA-P with Hoehn and Yahr (H&Y) score ≤3. Parasympathetic indexes included expiratory/inspiratory ratio during deep breathing, Valsalva ratio (VR), and regression slope of systolic blood pressure (BP) in early phase II (vagal baroreflex sensitivity) during Valsalva maneuver. Sympathetic adrenergic indexes were pressure recovery time (PRT) and adrenergic baroreflex sensitivity (BRSa) (BP decrement associated with phase 3 divided by the PRT), sympathetic index 1, sympathetic index 3, early phase II mean BP drop, and pulse pressure reduction rate. Additionally, we compared the unified multiple system atrophy rating scale (UMSARS) and H&Y scores and the autonomic indexes in all patients. Results: PRT was significantly different between the IPD and MSA-P groups (P = 0.004) despite the similar BP drop during tilt. Cut-off value of PRT was 5.5 s (sensitivity, 71.4%; specificity, 72.7%). VR (r = −0.455, P = 0.009) and BRSa (r = −0.356, P = 0.036) demonstrated a significant correlation with UMSARS and H&Y scores. Conclusions: Among the cardiovascular autonomic indexes, PRT can be a useful parameter in differentiating the early stage of MSA-P from that of IPD. Moreover, VR, and BRSa may be the optimal indexes in determining functional symptom severity.

Background Peripheral high-density lipoprotein cholesterol (HDL-C) has been known to influx into the brain and be inversely associated with the risk of Alzheimer’s disease (AD). However, recent prospective studies of the association between HDL-C and AD have yielded inconsistent results. Here, we examined the association between the endothelial lipase (EL), which is known to be major determinant of HDL-C levels, and cognitive function. Method We compared plasma from 20 patients with Alzheimer’s disease (AD), 38 persons with mild cognitive impairment, and 51 cognitively normal controls. Plasma EL levels were measured using the enzyme-linked immunosorbent assay. Results EL levels were inversely correlated with HDL-C, as previously reported; however, there were no mean differences in plasma EL between the diagnostic groups. An analysis by classification of dementia severity according to clinical dementia rating (CDR) showed that the EL levels were significantly higher in the CDR1 group (mild dementia), as compared to CDR0 (no dementia), CDR0.5 (very mild), and CDR2 (moderate) groups. Prior to moderate dementia stage, trends analysis showed that EL levels tended to increase with increasing severity (p for trend = 0.013). Consistently, elevated EL levels were significantly correlated with the mini-mental state examination (MMSE) score (r = − 0.29, p = 0.003). Logistic regression for association between plasma EL and cognitive impairment (MMSE score ≤ 25) showed that participants with EL levels in the upper range (> 31.6 ng/ml) have a higher adjusted odds ratio of cognitive impairment than those within the lower EL range. Conclusion Findings from the present study reflect the association of EL and cognition, suggesting that the individuals with elevated plasma EL concentration are at an increased risk of cognitive impairment. Electronic supplementary material The online version of this article (10.1186/s12888-019-2174-8) contains supplementary material, which is available to authorized users.

Background Risk of exacerbations in chronic obstructive pulmonary disease (COPD) associated with biomass smoke has not been well addressed, although biomass smoke is similar in composition to tobacco smoke. Methods To investigate whether the risk of exacerbations in COPD associated with biomass smoke differs from that in COPD associated with tobacco smoke, we recruited patients with COPD from two Korean multicenter prospective cohorts. In a multiple linear regression model, the standardized regression coefficient (β) of biomass smoke exposure ≥25 years was most similar to that (β′) of tobacco smoke exposure ≥10 pack-years (β = − 0.13 and β′ = − 0.14). We grouped patients with COPD into four categories based on the above cut-offs: Less Tobacco-Less Biomass, Less Tobacco-More Biomass, More Tobacco-Less Biomass, and More Tobacco-More Biomass. The main outcome was the incidence of moderate or severe exacerbations. Results Among 1033 patients with COPD, 107 were included in Less Tobacco-Less Biomass (mean age: 67 years, men: 67%), 40 in Less Tobacco-More Biomass (mean age: 70 years, men: 35%), 631 in More Tobacco-Less Biomass (mean age: 68 years, men: 98%), and 255 in More Tobacco-More Biomass (mean age: 69 years, men: 97%). The incidence rates of exacerbations were not significantly different between Less Tobacco-More Biomass and More Tobacco-Less Biomass (adjusted incidence rate ratio, 1.03; 95% confidence interval, 0.56–1.89; P = 0.921). No interaction between sex and tobacco and biomass smoke was observed. When propensity score matching with available covariates including age and sex was applied, a similar result was observed. Conclusions Patients with COPD associated with biomass smoke and those with COPD associated with tobacco smoke had a similar risk of exacerbations. This suggests that patients with COPD associated with biomass smoke should be treated actively. Electronic supplementary material The online version of this article (10.1186/s12890-019-0833-7) contains supplementary material, which is available to authorized users.

BACKGROUND: Inhaler usability and deposition differ between devices. Change of device may therefore have an impact on clinical and economic outcomes.OBJECTIVE: To characterize clinical and economic asthma outcomes surrounding the change from a dry powder inhaler (DPI) to a pressurized metered-dose inhaler (pMDI) for fixed-dose combination inhaled corticosteroid/long-acting β agonist (FDC ICS/LABA) treatment.METHODS: Three retrospective cohort substudies using 2010 to 2015 data from the Korean Health Insurance and Review Assessment Service database were performed. Patients with asthma who received an FDC ICS/LABA pMDI for the first time after initially being on FDC ICS/LABA DPI were included. The following outcomes were assessed: (1) persistence of change to pMDI over 6 months, (2) clinical outcomes during the year after the change compared with the baseline year; and (3) noninferiority comparison of costs and effectiveness between patients changing to a pMDI and matched patients who continued their DPI.RESULTS: Patients who change inhalers seem to represent a more severe subpopulation. Fifty-eight percent of patients (95% CI, 56-60) persisted with the change. After the change in therapy, an increased proportion of patients (58.3%) remained free from severe exacerbations compared with the year before (47.4%; P < .001). Patients who changed to pMDIs had significantly less severe exacerbations, acute respiratory events, and lower short-acting β agonist inhaler average daily dose, but higher average ICS daily dose (all P < .05), compared with matched patients remaining on a DPI. Total costs were similar between patients who changed to pMDI therapy compared with those remaining on a DPI.CONCLUSION: Changing from a DPI to a pMDI for FDC ICS/LABA asthma treatment can be as effective and cost-effective as remaining on a DPI.

Background This cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines. Methods A total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed. Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/μl, or ≥ 2 exacerbations in the year prior to enrollment. Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal. Results ICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead. Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period. The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs. 0.53, p

We categorized patients with amnestic mild cognitive impairment (aMCI) based on cortical atrophy patterns and evaluated whether the prognosis differed across the subtypes. Furthermore, we developed a classifier that learns the cortical atrophy pattern and predicts subtypes at an individual level. A total of 662 patients with aMCI were clustered into 3 subtypes based on cortical atrophy patterns. Of these, 467 patients were followed up for more than 12 months, and the median follow-up duration was 43 months. To predict individual-level subtype, we used a machine learning–based classifier with a 10-fold cross-validation scheme. Patients with aMCI were clustered into 3 subtypes: medial temporal atrophy, minimal atrophy (Min), and parietotemporal atrophy (PT) subtypes. The PT subtype had higher prevalence of APOE e4 carriers, amyloid PET positivity, and greater risk of dementia conversion than the Min subtype. The accuracy for binary classification was 89.3% (MT vs. Rest), 92.6% (PT vs. Rest), and 86.6% (Min vs. Rest). When we used ensemble model of 3 binary classifiers, the accuracy for predicting the aMCI subtype at an individual level was 89.6%. Patients with aMCI with the PT subtype were more likely to have underlying Alzheimer's disease pathology and showed the worst prognosis. Our classifier may be useful for predicting the prognosis of individual aMCI patients.

Background: Infantile nystagmus syndrome (INS) is a genetically heterogeneous disorder. Identifying genetic causes of INS would help clinicians to facilitate clinical diagnosis and provide appropriate treatment. The aim of this study was to determine the diagnostic utility of targeted next-generation sequencing (NGS) for INS. Materials and methods: We recruited 37 patients who were referred to the Neuro-ophthalmology clinics for evaluations of INS. NGS was performed using a targeted panel that included 98 candidate genes associated with INS. We identified pathogenic variants according to guidelines of the American College of Medical Genetics and Genomics. We also calculated the sensitivity and specificity of each clinical sign to assess the diagnostic yield of our gene panel. Results: After variant filtering, annotation, and interpretation, the potential pathogenic variants were detected in 13 of the 37 patients, achieving a molecular diagnostic rate of 35%. The identified genes were PAX6 (n = 4), FRMD7 (n = 4), GPR143 (n = 2), CACNA1F (n = 1), CNGA3 (n = 1) and GUCY2D (n = 1). In approximately 30% (n = 4) of the patients, the initial clinical diagnosis was revised after a molecular diagnosis was performed. The presence of a family history had the highest predictive power for a molecular diagnosis (sensitivity = 61.5%, specificity = 91.7%), and the sensitivity increased when the family history was considered together with one of two clinical signs such as pendular nystagmus waveforms or anterior segment dysgenesis. Conclusions: Our study shows that targeted NGS can be useful to determine a molecular diagnosis for patients with INS. Targeted NGS also helps to confirm a clinical diagnosis in atypical phenotypes or unresolved cases.

Background and Purpose: The recognition of clinical features of transient vestibular symptoms (TVSs) preceding posterior circulation stroke (PCOS) would be informative to discriminate dizziness/vertigo due to vertebrobasilar transient ischemic attack from the acute transient vestibular syndrome. We sought to determine the prevalence and characteristics of TVSs preceding PCOS. Methods: We performed a prospective multicenter observational study that had recruited 447 patients with PCOS from referral-based 4 university hospitals in Korea. We investigated the timing, pattern, frequency, duration, and accompanying neurological symptoms of TVSs during the 3 months preceding PCOS. Results: The prevalence of TVSs preceding PCOS was 12% (55/447) during the previous 3 months. The TVSs preceding PCOS occurred within 1 week (33%), between 1 week and 1 month (16%), or between 1 and 3 months (51%). The TVSs were mostly dizziness/vertigo with (36%) or without (60%) imbalance, while the remaining 4% had an isolated imbalance. The dizziness/vertigo was spinning in 38% and was aggravated during head position in 45%. The duration of TVSs was mostly a few seconds (55%) or minutes (38%). Approximately 72% of the patients with PCOS had TVSs 1 to 5 times, while 16% had >10 times. Accompanying neurological symptoms, including headache, tinnitus, limb weakness, sensory change, dysarthria, visual field defect, and diplopia, were reported in 11%. Conclusions: Preceding TVSs can occur in 12% of PCOS during the previous 3 months. Isolated dizziness/vertigo of unknown cause needs to be considered as a vertebrobasilar transient ischemic attack symptom, especially in patients with vascular risk factors. The characteristics of isolated vestibular symptom in vertebrobasilar transient ischemic attacks is highly variable and atypical compared with other transient ischemic symptoms.

Background and purpose The microenvironment of lymphomas is known to be highly variable and closely associated with treatment resistance and survival. We tried to develop a physiologic MR imaging-based spatial habitat analysis to identify regions associated with treatment resistance to facilitate the prediction of tumor response after initial chemotherapy in patients with primary central nervous system lymphoma. Materials and methods Eighty-one patients with pathologically confirmed primary central nervous system lymphoma were enrolled. Pretreatment physiologic MR imaging was performed, and K-means clustering was used to separate voxels into 3 spatial habitats according to ADC and CBV values. Associations of spatial habitats and clinical and conventional imaging predictors with time to progression were analyzed using Cox proportional hazards modeling. The performance of statistically significant predictors for time to progression was assessed using the concordance probability index. Results The 3 spatial habitats of hypervascular cellular tumor, hypovascular cellular tumor, and hypovascular hypocellular tumor were identified. A large hypovascular cellular habitat was most significantly associated with short time to progression (hazard ratio, 2.83; P = . 017). The presence of an atypical finding (hazard ratio, 4.41; P = . 016), high performance score (hazard ratio, 5.82; P = . 04), and high serum lactate dehydrogenase level (hazard ratio, 1.01; P = .013) was significantly associated with time to progression. A predictive model constructed using the habitat score and other imaging parameters showed a concordance probability index for prediction of time to progression of 0.70 (95% CI, 0.54-0.87). Conclusions A hypovascular cellular tumor habitat is associated with treatment resistance in primary central nervous system lymphoma, and its assessment may refine prechemotherapy imaging-based response prediction for patients with primary central nervous system lymphoma.

Chronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV1) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV1 (adjusted mean difference in FEV1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; − 161.1 mL [− 240.2, − 82.0], − 179.2 mL [− 252.1, − 106.3], − 128.8 mL [− 193.2, − 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC.

Yeonseok Choi,1,* Sun Hye Shin,1,* Hyun Lee,2 Hyun Kyu Cho,1 Yunjoo Im,1 Noeul Kang,1 Hye Sook Choi,3 Hye Yun Park1 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 2Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea; 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, South Korea*These authors contributed equally to this workCorrespondence: Hye Yun ParkDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South KoreaTel +82-2-3410-3429Fax +82-2-3410-3849Email hyeyunpark@skku.eduPurpose: Long-term macrolide treatment is recommended for patients with chronic obstructive pulmonary disease (COPD) with frequent exacerbations. Bronchiectasis is a common comorbid condition in patients with COPD, for which long-term azithromycin is effective in preventing exacerbation. This study aimed to compare the effect of long-term azithromycin between bronchiectasis patients with chronic airflow obstruction (CAO) and COPD patients without bronchiectasis.Patients and Methods: Patients with CAO who received azithromycin for more than 12 weeks were retrospectively identified at a single referral hospital. CAO was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7, and bronchiectasis was determined using computed tomography. The development of exacerbation and symptom improvement were compared between bronchiectasis patients with CAO and COPD patients without bronchiectasis.Results: A total of 59 patients (43 in bronchiectasis with CAO group vs 16 in COPD without bronchiectasis group) were included in this study. Compared to COPD patients without bronchiectasis, those in bronchiectasis with CAO group were younger, more likely to be female, and never smokers. There was no difference in the previous exacerbation history or FEV1 between the two groups. The median duration of azithromycin treatment was 15 months (interquartile range, 8– 25 months). At the 12-month follow-up, the development of ≥ 2 moderate or ≥ 1 severe exacerbations was significantly lower in bronchiectasis with CAO group than in COPD without bronchiectasis group (46.5% vs 87.5%, P = 0.005). The proportion of patients with symptom improvement determined by the COPD assessment test score was also significantly higher in bronchiectasis with CAO group than COPD without bronchiectasis group at the 12-month follow-up (68.2% vs 16.7%, P = 0.004).Conclusion: Bronchiectasis patients with CAO could benefit more from long-term azithromycin treatment than COPD patients without bronchiectasis.Keywords: COPD, bronchiectasis, azithromycin, exacerbation

Aims Berteroin (5-methylthiopentyl isothiocyanate) is a naturally occurring sulforaphane analog containing a non-oxidized sulfur atom in cruciferous vegetables. The objectives of the present study were to determine the effects of berteroin on lipid metabolism in hepatocytes and adipocytes and to elucidate the mechanisms involved. Main methods The effect of berteroin on lipid metabolism were evaluated in liver X receptor α agonist-stimulated HepG2 cells and adipocyte differentiation-induced 3T3-L1 cells using MTT assay, western blot, real time polymerase chain reaction, oil red O staining, and triglyceride assay. Key findings T0901317 treatment increased the expression of sterol regulatory element binding protein (SREBP)-1c, a major transcription factor that mediates lipogenesis, and berteroin pretreatment significantly inhibited the expressions of T0901317-induced SREBP-1c and lipogenic genes. Especially, berteroin had a greater inhibitory effect on T0901317-induced SREBP-1c activation than sulforaphane, AICAR, or metformin. Berteroin also markedly suppressed lipid droplet formations and triglyceride accumulations caused by both T0901317 stimulation in HepG2 hepatocytes and differentiation induction in 3T3-L1 preadipocytes. However, berteroin significantly increased the expression of mitochondrial fatty acid oxidation-related genes (carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptor gamma coactivator-1α) and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in HepG2 cells. Interestingly, effects of berteroin on the expressions of SREBP-1c protein and CPT-1 mRNA were remarkably prevented by compound C (an AMPK inhibitor). Significance Our results suggest berteroin-inhibited hepatic lipid accumulation and adipocyte differentiation might be mediated by AMPK activation and that berteroin might be useful for the prevention, amelioration, and treatment of metabolic diseases, including hepatic steatosis.