Search

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...

We report a miniaturized, minimally invasive high-density neural recording interface that occupies only a 1.53 mm2 footprint for hybrid integration of a flexible probe and a 256-channel integrated circuit chip. To achieve such a compact form factor, we developed a custom flip-chip bonding technique using anisotropic conductive film and analog circuit-under-pad in a tiny pitch of 75 m. To enhance signal-to-noise ratios, we applied a reference-replica topology that can provide the matched input impedance for signal and reference paths in low-noise aimpliers (LNAs). The analog front-end (AFE) consists of LNAs, buffers, programmable gain amplifiers, 10b ADCs, a reference generator, a digital controller, and serial-peripheral interfaces (SPIs). The AFE consumes 51.92 W from 1.2 V and 1.8 V supplies in an area of 0.0161 mm2 per channel, implemented in a 180 nm CMOS process. The AFE shows > 60 dB mid-band CMRR, 6.32 Vrms input-referred noise from 0.5 Hz to 10 kHz, and 48 M input impedance at 1 kHz. The fabricated AFE chip was directly flip-chip bonded with a 256-channel flexible polyimide neural probe and assembled in a tiny head-stage PCB. Full functionalities of the fabricated 256-channel interface were validated in both in vitro and in vivo experiments, demonstrating the presented hybrid neural recording interface is suitable for various neuroscience studies in the quest of large scale, miniaturized recording systems.

Background: Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea.Methods: A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed.Results: We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016).Conclusion: Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

AIM: To characterize the anti-inflammatory and anti-apoptotic effects of N-acetylcysteine (NAC) in streptozotocin (STZ)-induced diabetic rat corneal epithelium and human corneal epithelial cells (HCECs) exposed to a high-glucose environment. METHODS: HCECs were incubated in 0, 5, 50 mmol/L glucose medium, or 50 mmol/L glucose medium with NAC for 24h. Diabetes was induced in rats by intraperitoneal injection of 65 mg/kg STZ and some of these rats were topically administered NAC to corneas with 3 mice per group. We characterized receptor for advanced glycation end-products (RAGE) expression using immunofluorescence, and interleukin (IL)-1β and cleaved caspase-3 (CCAP-3) expression using immunohistochemistry. Circulating tumor necrosis factor (TNF)-α concentration was measured by ELISA and cleaved poly-ADP ribose polymerase (PARP) concentration was quantified by Western blotting. Apoptotic cells were detected using TUNEL assay and annexin V and propidium iodide staining. RESULTS: Diabetic rats had higher expression of RAGE (2.46±0.13 fold), IL-1β, and CCAP-3 in apoptotic cells of their corneas than control rats. The expression of RAGE (1.83±0.11 fold), IL-1β, and CCAP-3, and the number of apoptotic cells, were reduced by topical NAC treatment. HCECs incubated in 50 mmol/L glucose medium showed high concentrations of TNF-α (310±2.00 pg/mL) and cleaved PARP (7.43±0.56 fold), and more extensive apoptosis than cells in 50 mmol/L glucose medium. However, the addition of NAC reduced the concentrations of TNF-α (153.67±2.31 pg/mL) and cleaved PARP (5.55±0.31 fold) and the number of apoptotic cells. CONCLUSION: NAC inhibits inflammation and apoptosis in the corneas of diabetic rats and HCECs maintained in a high-glucose environment.

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.

Background: Depression and anxiety are prevalent and can cause suffering in patients with Parkinson’s disease (PD). The Korean version of the Hospital Anxiety and Depression Scale (K-HADS) has been widely used to assess depression and anxiety symptoms in Korean patient with PD. The present study aimed to assess the reliability and validity of the K-HADS using Rasch measurement analysis.Methods: A total of 106 PD patients (54 males, 52 females) who met the diagnostic criteria of the United Kingdom Brain Bank were recruited. Unidimensionality, the Rasch model fit, response category functioning, patient-item distribution, and the separation reliability of the K-HADS depression (K-HADS-D) and anxiety (K-HADS-A) subscales were statistically evaluated.Results: The mean K-HADS-D and K-HADS-A scores were 8.08±4.69 (mean±standard deviation) and 5.44±4.18, respectively. Cronbach’s α coefficients of the K-HADS-D and K-HADS-A were 0.82 and 0.83. The Rasch analysis revealed that the K-HADS-D and K-HADS-A showed unidimensionality and no disordered functioning was observed in the 4-point polytomous scale. However, both K-HADS-D and K-HADS-A exhibited suboptimal separation reliability, while the K-HADS-A showed inadequate scale targeting with floor effect.Conclusions: The present study comprises the first validation of the K-HADS using the Rasch measurement model, suggesting that the K-HADS-D and K-HADS-A are clinimetrically acceptable and reliable scales for use in Korean patients with PD. However, the moderate person separation indices implicate the relatively low discriminatory ability of the K-HADS in our study patients.

Background: Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea.Methods: A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement).Results: The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers.Conclusion: Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.

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

BACKGROUND: This study aimed to validate the Korean version of the Patient-Reported Outcome Measurement Information System 29 Profile V2.1 (K-PROMIS-29 V2.1) in a sample of patients with chronic pulmonary diseases (CPDs). METHODS: Participants were recruited from the respiratory disease outpatient clinics of Samsung Medical Center in Seoul, South Korea, from September to October 2018. Participants completed a survey questionnaire, including the K-PROMIS-29 V2.1 and Short Form Health Survey version-2.0 (SF-36v2). Modified Medical Research Council (mMRC) and chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) scores were obtained these scores from electronic medical records (EMRs). Exploratory and confirmatory factor analyses (CFA) and Pearson’s correlations were used to evaluate the reliability and validity of the K-PROMIS-29 V2.1. RESULTS: The mean age [standard deviation (SD)] was 62.8 (12.0) years, and 19.2% had less than middle-school education. Disease types included bronchiectasis (n=46, 24.5%), COPD (n=45, 23.9%), nontuberculous mycobacterial lung disease (n=25, 13.3%), interstitial lung disease (n=22, 11.7%), and others (n=50, 26.6%). Cronbach’s alpha coefficients of the 7 subdomains in the K-PROMIS-29 V2.1 ranged from 0.77 to 0.96, indicating satisfactory internal consistency. In CFA, the goodness-of-fit indices were high (comparative fit index =0.90, standardised root mean residual =0.06). Moderate correlations were observed between comparable subscales of the K-PROMIS-29 V2.1 and those of the SF-36v2 (r=0.55–0.70) and CAT (r=−0.80 to 0.70). CONCLUSIONS: The findings of this study suggest that the K-PROMIS-29 V2.1 is a reliable and valid measure for assessing a broad range of health-related quality-of-life domains in patients with CPDs.

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.

BACKGROUND: Prevalence, respiratory symptoms, and quality of life (QoL) in post-tuberculosis (TB) subjects with bronchiectasis are not well elucidated. METHODS: Subjects who participated in the Korea National Health and Nutritional Examination Survey 2007–2009 were enrolled in this cross-sectional study. We evaluated the prevalence of physician-diagnosed bronchiectasis among post-TB subjects. We compared respiratory symptoms, physical activity limitations, and QoL between post-TB subjects with and without bronchiectasis. RESULTS: The prevalence of bronchiectasis was 3.3% among 963 post-TB subjects. Post-TB subjects with bronchiectasis showed a higher rate of asthma (29.6% vs. 4.9%, P

Background: Endobronchial lung cancer (EBLC) and bronchial anthracofibrosis (BAF) share similar symptoms and radiological findings. The aim of this study was to describe clinical and radiological differences between BAF and EBLC, both of which were confirmed by bronchoscopy. Methods: This was a retrospective study of patients with BAF or EBLC from 2008 to 2014. Data were derived from a bronchoscopy registry made since January 1, 2008. Clinical and radiological characteristics of both diseases were analyzed. Results: Among 3,214 patients who underwent bronchoscopy, 167 and 117 patients were enrolled in BAF and EBLC groups, respectively. BAF occurred more predominantly in older non-smoking female patients with a higher chance of tuberculosis (38.3%) than EBLC (6.0%). Cough, sputum, and dyspnea were common symptoms reported for both groups. Bronchoscopic findings revealed that BAF lesions were more common in multiple lobar bronchi (85.0%) or bilateral bronchi (73.7%). Radiologic findings revealed that bronchial stenosis was the most commonly found lesion in both groups (49.1% and 78.6%, respectively). Rates of peribronchial calcification and bronchial wall thickening were higher in the BAF group. The number of patients with lymph node calcification was also higher in the BAF group. Conclusion: Results of this study demonstrated characteristics of clinical and radiologic findings of BAF and EBLC. Increasing the awareness of both diseases may help clinicians differentiate these two diseases from each other, thus avoiding unnecessary invasive diagnostic procedures.

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

Many studies have introduced full-duplex (FD) medium access controls (MAC) in wireless networks that realize the physical FD capability of the latest devices. However, practical experiences with 802.11 wireless LANs (WLANs) have not yet been addressed. This study proposes a novel FD MAC that extends the IEEE 802.11 based on no acknowledgment (NoAck) data transmission. Because ACK is not needed after data transmission, the MAC can be purely asynchronous; there is neither overhead required for synchronizing transmission, such as request-to-send/clear-to-send (RTS/CTS) handshaking, nor wasted time even in asymmetric traffic. The proposed MAC also provides access point (AP) initiated uni-directional full-duplex (AP-initiated UFD) transmission, which has mostly not been supported in practice, by extending the carrier sense condition. An approximated collision avoidance method is also introduced, where a CTS frame without a preceding RTS is transmitted by AP using FD capability to protect the frame being received. A prototype of the proposed MAC is implemented in ns-3 network simulator, and extensive simulation experiments are conducted in various test setups to validate the correct MAC behaviors, performance improvement, and fairness. The results show that performance improvements, more than twice as high under favorable conditions, are possible while maintaining interoperability with legacy devices.

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.

Introductionthe world is currently facing the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The total number of cases of coronavirus disease 2019 (COVID-19) is rising daily and no vaccine has yet been approved. While the pathophysiology behind the virus is still being studied, many possible several risk factors using small sample sizes have been found.Material and methodsWe conducted a pooled analysis using several databases such as Medline, Scopus, Wangfang, Web of Science, Research Square, medrxiv, and Google Scholar to identify studies reporting severe and non-severe groups of COVID-19 patients. The odds ratios as well as the 95% confidence intervals for hypertension, diabetes, and cerebrovascular disease leading to severe COVID-19 were calculated using R-software.ResultsFifty-three articles were used for our analysis and they involved 30,935 confirmed cases of COVID-19 from several countries across the world. The odds ratio for severe COVID-19 in hypertensive patients, diabetics, and patients with a history of cerebrovascular disease was 2.58 (95% confidence interval (CI): 2.16–3.08, from 53 studies), 2.17 (95% CI: 1.72–2.74, from 44 studies), and 2.63 (95% CI: 1.80–3.85, from 25 studies), respectively.ConclusionsOur analysis confirms that patients with hypertension, diabetes, or cerebrovascular disease are at a higher risk of a severe outcome of COVID-19. It is thus vital for physicians to identify the main risk factors for a severe outcome of this disease.

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.

It has been more than a year since the new virus called severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China. The disease it causes was named Coronavirus disease 2019 (COVID-19), and on 11 March 2020 it was declared a pandemic. As the virus continues to spread, the number of patients worldwide has already crossed the 100 million mark with more than 2 million deaths. We sought to provide an update on the progress made in identifying the virus, its pathophysiology, risk factors such as hypertension, diabetes, and smoking, as well as various methods of treatment. Our review also provided an overview of the different vaccines.

Background: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 μg to indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily in COPD patients in Korea. Methods: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 μg once daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity

In Korean women, a westernized lifestyle is associated with an increased risk of breast cancer. Fertility preservation has become an increasingly important issue for women with breast cancer, in accordance with substantial improvements in survival rate after cancer treatment. The methods of controlled ovarian hyperstimulation (COH) for fertility preservation in breast cancer patients have been modified to include aromatase inhibitors to reduce the potential harm associated with increased estradiol levels. Random-start COH and dual ovarian stimulation are feasible options to reduce the total duration of fertility preservation treatment and to efficiently collect oocytes or embryos. Using a gonadotropin-releasing hormone agonist as a trigger may improve cycle outcomes in breast cancer patients undergoing COH for fertility preservation. In young breast cancer patients with BRCA mutations, especially BRCA1 mutations, the possibility of diminished ovarian reserve may be considered, although further studies are necessary. Herein, we review the current literature on the practical issues surrounding COH for fertility preservation in women with breast cancer.

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.

BACKGROUND PfFAD3 transgenic soybean expressing omega‐3 fatty acid desaturase 3 of Physaria produces increased level of α‐linolenic acid in seed. Composition data of non‐transgenic conventional varieties is important in the safety assessment of the genetically‐modified (GM) crops in the context of the natural variation. RESULTS The natural variation was characterized in seed composition of 13 Korean soybean varieties grown in three locations in South Korea for 2 years. Univariate analysis of combined data showed significant differences by variety and cultivation environment for proximates, minerals, anti‐nutrients, and fatty acids. Percent variability analysis demonstrated that genotype, environment and the interaction of environment with genotype contributed to soybean seed compositions. Principal component analysis and orthogonal projections to latent structure discriminant analysis indicated that significant variance in compositions was attributable to location and cultivation year. The composition of three PfFAD3 soybean lines for proximates, minerals, anti‐nutrients, and fatty acids was compared to a non‐transgenic commercial comparator (Kwangankong, KA), and three non‐transgenic commercial varieties grown at two sites in South Korea. Only linoleic and linolenic acids significantly differed in PfFAD3‐1 lines compared to KA, which were expected changes by the introduction of the PfFAD3‐1 trait in KA. CONCLUSION Genotype, environment, and the interaction of environment with genotype contributed to compositional variability in soybean. PfFAD3‐1 soybean is equivalent to the conventional varieties with respect to these components. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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.

Objective This study aimed to demonstrate the use of preoperative magnetic resonance imaging (MRI) findings to select the optimal surgical technique between single-site (SS) and multi-site (MS) robotic myomectomy based on clinical experience, for the preservation of fertility. Methods Ninety-eight patients who underwent SS or MS robotic myomectomy using the da Vinci® Si system after undergoing MRI were evaluated retrospectively. The correlation between preoperative MRI findings and the intraoperative or postoperative findings during robotic myomectomy for the preservation of fertility was analyzed. The reproductive outcome was investigated when the patient wished to conceive. Results The mean age of the patients was 35.68±5.04 years and 80 patients (81.6%) were nulliparous. The total diameter of myomas on MRI was 106.75±54.52 mm. The number of resected myomas was 4.31±4.39 (range, 1–27), and the total weight of resected myomas was 293.11±281.13 (range, 30–1,260) g. Myomas with high signal intensity on MRI required less time for resection. MS robotic myomectomy was performed for an increased number and total diameter of a myoma or a deep-seated myoma. Postoperatively, all patients resumed normal menstruation. Of the 15 patients who wished to conceive, 12 (80%) conceived successfully. Of these, uterine dehiscence occurred in 1 patient and 10 patients underwent an uneventful cesarean section. Conclusion SS or MS robotic myomectomy can be recommended for patients who wish to conserve fertility. However, the optimal surgical technique should be selected based on preoperative MRI findings to predict an effective surgical process and the successful preservation of fertility.

Understanding regional differences in the aetiology of bronchiectasis will be crucial to make a strategy to control the disease burden related to bronchiectasis. In Asia, where the prevalence of bronchiectasis is substantially higher than in Western countries [1], previous tuberculosis (TB) is one of the leading causes of bronchiectasis [2, 3]. Accordingly, the successful national TB control programme may be an effective strategy to reduce the disease burden of bronchiectasis in many Asian countries. However, to date, no data have supported this assumption. In South Korea, the incidence of TB has declined following government-led TB control programmes, which have changed the country's status from a high-TB burden nation to an intermediate-TB burden country [4]. Thus, the relationship between the incidences of TB and bronchiectasis in South Korea probably provides an answer to this research question. In this study, we aimed to investigate whether TB control was associated with a reduced incidence of bronchiectasis in South Korea, with consideration of other potential factors that can influence the incidence of bronchiectasis., In South Korea, the estimated incidences of bronchiectasis were 147–229 cases per 100000 with a decreasing trend. It may follow the concurrent decrease in the TB prevalence and incidence, and favourable personal and socioeconomic conditions. https://bit.ly/32UA8xH

To gain the target functionality of graphene for gas detection, nonfocused and large-scale compatible MeV electron beam irradiation on graphene with Ag patterns is innovatively adopted in air for chemical patterning of graphene. This strategy allows the metal-assisted site-specific oxidation of graphene to realize monolithically integrated graphene-chemically patterned graphene (CPG)-graphene homojunction-based gas sensors. The size-tunable CPG patterns can be mediated by regulating the size of Ag prepatterns. The impacts of highly energetic electron irradiation (HEEI) on graphene are summarized as follows: (i) the selective p-type doping and the defect generation of graphene by the HEEI-induced oxidation, (ii) the resistance of the homojunction devices manipulated by the HEEI dose, (iii) the band gap opening of graphene as well as the lowering of the Fermi level, (iv) the work function values for pristine graphene and CPG corresponding to 4.14 and 4.88 eV, respectively, and (v) graphene-CPG-graphene homojunction for NO2 gas, revealing an 839% enhanced gas response compared with that of the pristine graphene-based gas sensor.

Background While there is an increasing number of early-stage non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), there are no specific clinical guidelines for treating them. This study aims to evaluate different treatment modalities and corresponding clinical outcomes among early-stage NSCLC patients with COPD. Methods We retrospectively reviewed 692 patients with stage I and II NSCLC and COPD from January 2012 to June 2014. Patients were categorized into four groups according to primary treatment modality: surgery only group (n=442), surgery with adjuvant treatment group (n=157), radiotherapy (RT) group (n=48), and supportive care (SC)-only group (n=45). Results Overall, mortality rate was the highest in the SC-only group (35.7 deaths per 100 person-years), followed by RT group (21.5 deaths per 100 person-years), surgery with adjuvant treatment group (8.9 deaths per 100 person-years) and surgery only group (7.2 deaths per 100 person-years). The adjusted hazard ratios (HR) for all-cause mortality compared to the surgery only group were 1.18 (95% CI, 0.84-1.67) in surgery with adjuvant treatment group, 1.61 (95% CI, 1.01-2.57) in RT group and 3.23 (95% CI, 1.99-5.23) in SC-only group. Conclusions Surgical resection should be considered as the first choice for early-stage NSCLC with COPD. Despite poor lung function or general patient condition, RT rather than SC can be an alternative option if surgery is not feasible. A multi-disciplinary approach and active communication between patients and physicians might be helpful for adequate decision-making regarding treatment for patients with early-stage NSCLC and COPD.

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.

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is not differentiated clinically from other respiratory infections, and intensive care units (ICUs) are vulnerable to in-hospital transmission due to interventions inducing respiratory aerosols This study evaluated the effectiveness of universal SARS-CoV-2 screening in ICUs in terms of screened-out cases and reduction in anxiety of healthcare personnel (HCP) Materials and Methods: This prospective single-armed observational study was conducted in 2 ICUs of a single hospital The number of patients diagnosed with SARS-CoV-2 infection by the screening program and healthcare workers in ICUs that visited the SARS-CoV-2 screening clinic or infection clinic were investigated Results: During the 7-week study period, no positive screening case was reported among a total of 142 patients Among 86 HCP in the ICUs, only 2 HCP sought medical consultation for SARS-CoV-2 infection during the initial 2 weeks Conclusion: A universal screening program for SARS-CoV-2 infection in ICUs with the coordination of other countermeasures in the hospital was reasonably effective in preventing in-hospital transmission in a pandemic situation and making clinical practices and HCP stable

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

Background The risk stratification value of the 6-min walk test (6MWT) to decide the feasibility of surgical resection is not well elucidated in patients with non-small cell lung cancer (NSCLC) and moderately decreased lung function. Objective This study aimed to determine the role of the 6MWT in predicting postoperative cardiopulmonary complications in patients with NSCLC who underwent lobectomy and had moderately decreased lung function. Methods The data were obtained from a prospective cohort study called Coordinate Approach to Cancer Patient’s Health for Lung Cancer (CATCH-LUNG). Patients who underwent lobectomy for NSCLC were classified into two groups according to predicted postoperative pulmonary function (low-risk group or moderate-risk group); each group was then further classified into short-distance ( Results The adjusted ORs for any postoperative pulmonary complications, postoperative cardiac complications, and postoperative cardiopulmonary complications in patients with moderate-risk/short-distance relative to those with low-risk/long-distance were 10.26 (95% CI, 2.37-44.36), 5.65 (95% CI, 1.39-22.90), and 7.84 (95% CI, 2.24-27.46), respectively. However, these complications were not different between the patients with moderate-risk/long-term distance and those with low-risk/long-distance. Among patients in the moderate-risk group, those in the short-distance group had a significantly higher risk of postoperative cardiopulmonary complications compared with those in the long-distance group (adjusted OR, 4.95; 95% CI, 1.37-17.93). Conclusions Patients with NSCLC with moderate-risk/short-distance were at greater risk of developing postoperative cardiopulmonary complications; it may be feasible, however, for patients with NSCLC and moderate-risk/long-distance to undergo lobectomy compared with those with low-risk/long-distance. Our study suggests that the 6MWT could provide additional information in identifying optimal candidates for lung resection surgery of NSCLC. Trial Registry ClinicalTrials.gov; No.: NCT03705546 ; URL: www.clinicaltrials.gov .

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.

BackgroundDegree of expression of programmed death-ligand 1 (PD-L1) is related with Immune check point inhibitors (ICIs) response but is not obligate predictive marker and needs sufficient tissue. Therefore, there is unmet need for easily accessible peripheral blood (PB) biomarkers and evaluation of the prognostic value of this marker is needed. We investigated the application of serum peripheral lymphocyte count (PLC) as a predictive PB biomarker for ICI response in patients with NSCLC. MethodsWe conducted a retrospective study and reviewed the medical charts of patients with NSCLC who were treated with ICIs at Seoul National University Hospital. We evaluated the association between PLC and progression-free survival using a Cox proportional hazard model. The PLC before and after 1 month of immunotherapy was collected. The quartile groups of PLC were compared using the Kruskal-Wallis statistical test.ResultsA total of 231 patients were treated with immunotherapy for NSCLC. The median follow-up period was 4.7 months. During the follow-up period, the disease progressed in 138 patients (59.7%). The post-treatment PLC groups Q2-4 showed significantly lower disease progression than group Q1 in our adjusted model (Q4 hazard ratio: 0.41, 95% confidence interval: 0.25–0.68, p < 0.001). The overall survival also showed similar results. An association between adverse events and PLC was not observed in this study. ConclusionWe revealed that an increased post-treatment PLC was associated with favorable progression-free and overall survival with NSCLC patients treated with ICIs. Therefore, PLC could be a surrogate marker for ICI responses in NSCLC.