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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: 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.

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.

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

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.

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 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

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.

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 .

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.

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.

Tuberculosis (TB) survivors experience post-TB lung damage and ventilatory function disorders. However, the proportions of obstructive and restrictive ventilatory disorders as well as normal ventilation among subjects with prior TB are unknown. In addition, the impacts of ventilatory disorder and its severity on respiratory symptoms, physical activity limitations, and the quality of life in subjects with prior TB remain unclear. Subjects who participated in the Korean National Health and Nutritional Examination Survey 2007–2016 were enrolled in this study. We evaluated the impact of each ventilatory disorder and its severity on respiratory symptoms, physical activity limitations, and quality of life (measured by the EuroQoL five dimensions questionnaire [EQ-5D] index values) in subjects with prior TB. Among 1466 subjects with prior TB, 29% and 16% had obstructive ventilatory disorders and restrictive ventilatory disorders, respectively. Mild and moderate obstructive ventilatory disorders were not associated with respiratory symptoms, physical activity limitations, or EQ-5D index value compared with normal ventilation, however, severe obstructive ventilatory disorders were associated with more respiratory symptoms (adjusted odds ratio [aOR] = 13.62, 95% confidence interval [CI] = 4.64–39.99), more physical activity limitation (aOR = 218.58, 95% CI = 26.82–1781.12), and decreased EQ-5D index (adjusted coefficient = −0.06, 95% CI = (−0.12–−0.10) compared with normal ventilation. Mild restrictive ventilatory disorders were associated with more respiratory symptoms (aOR = 2.10, 95% CI = 1.07–4.14) compared with normal ventilation, while moderate (aOR = 5.71, 95% CI = 1.14–28.62) and severe restrictive ventilatory disorders (aOR = 9.17, 95% CI = 1.02–82.22) were associated with physical activity limitation compared with normal ventilation. In conclusion, among subjects with prior TB, 29% and 16% developed obstructive and restrictive ventilatory disorders, respectively. Severe obstructive ventilatory disorder was associated with more respiratory symptoms, more physical activity limitation, and poorer quality of life, while severe restrictive ventilatory disorder was associated with more physical activity limitations.

Objectives: Uterine sarcoma is a rare malignant tumor, which is usually diagnosed in postmenopausal women. These sarcomas are occasionally misdiagnosed as uterine fibroids, thereby leading to delayed diagnosis in the advanced stages. We analyzed the sonographic and clinical characteristics of unexpected uterine sarcomas detected after surgery in women in the late reproductive age. Methods: The medical records of 61 patients preoperatively diagnosed with uterine leiomyomas through sonography but confirmed as uterine sarcomas after surgery from January 2005 to December 2018 at Asan Medical Center were retrospectively analyzed. We evaluated the clinical symptoms, sonographic findings, and Doppler indexes, and investigated whether there were any significant characteristics that could clearly differentiate uterine sarcoma from fibroids. Results: The most common clinical finding was increased mass size (15 patients, 24.6%), while 9 patients (14.8%) showed no symptoms. Ultrasonography showed that the maximum diameter of most fibroids was > 5 cm (49 patients, 80.3%), and the average diameter was 75.6 ± 36.3 mm. All the patients showed heterogeneous echogenicity in sonographic imaging. Secondary degeneration of the myomas was reported in 36 patients (59%), and approximately 90% (32/36, 88.9%) showed cystic changes. Of the 40 patients who underwent the evaluation of vascularity, 35 showed increased vascularity of the mass. Conclusions: In this study, sarcomas misdiagnosed as leiomyomas were usually > 5 cm, and ultrasonography showed heterogeneous echogenicity and irregular cystic degeneration. No definite clinical symptoms were helpful; a thorough evaluation is necessary to rule out uterine sarcomas in women having uterine mass with these characteristics.

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

Purpose Current guidelines recommend definitive radiotherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC). However, the impact of underlying pulmonary diseases on survival in those patients remains unclear. Methods We retrospectively reviewed the medical records of 234 patients with stage I-II NSCLC treated with definitive radiotherapy alone at Samsung Medical Center between January 2010 and October 2017. We compared survival outcomes according to the presence of underlying pulmonary diseases, including chronic obstructive pulmonary disease (COPD), combined pulmonary fibrosis and emphysema (CPFE), and idiopathic pulmonary fibrosis (IPF). The control group in this study was stage I-II NSCLC patients who were non-COPD, non-CPFE, and non-IPF. Results The median follow-up duration was 17 (range, 1-92) months. The median survival times of the control, COPD, CPFE, and IPF groups were 32, 49, 17, and 12 months, respectively (P Conclusion Definitive radiotherapy may be a tolerable treatment for early-stage NSCLC with COPD. However, poor survival in early-stage NSCLC patients with IPF or CPFE requires further study to identify and develop patient selection criteria as well as an optimal radiotherapy modality.

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.

Purpose: Rhabdomyolysis (RB) is a syndrome characterized by the decomposition of striated muscles and leakage of their contents into the bloodstream. Acute kidney injury (AKI) is the most significant and serious complication of RB and is a major cause of mortality in patients with RB. Severe RB (creatine kinase [CK] ≥5,000) has been associated with AKI. However, early prediction is difficult because CK can reach peak levels 1-3 days after the trauma. Hence, the aim of our study was to identify predictors of severe RB using initial patient information and parameters. Methods: We retrospectively analyzed 1,023 blunt trauma patients admitted to a single tertiary hospital between August 2011 and March 2018. Patients with previously diagnosed chronic kidney disease were excluded from the study. RB and severe RB were defined as a CK level ≥1,000 U/L and ≥5,000 U/L, respectively. The diagnosis of AKI was based on RIFLE criteria. Results: The overall incidence of RB and severe RB was 31.3% (n=320) and 6.2% (n=63), respectively. On multivariable analysis, male sex (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.43 to 10.00), initial base excess (OR 0.85, 95% CI 0.80 to 0.90), initial CK (OR 2.07, 95% CI 1.67 to 2.57), and extremity abbreviated injury scale score (OR 1.78, 95% CI 1.39 to 2.29) were found to predict severe RB. The results of receiver operating characteristic analysis showed that the best cutoff value for the initial serum CK level predictive of severe RB was 1,494 U/L. Conclusions: Male patients with severe extremity injuries, low base excess, and initial CK level >1,500 U/L should receive vigorous fluid resuscitation.

Purpose: We investigated how prehospital, emergency room (ER), and delta shock indices (SI) correlate with outcomes including mortality in patients with polytrauma. Methods: We retrospectively reviewed the medical records of 1,275 patients who visited the emergency department from January 2015 to April 2018. A total of 628 patients were enrolled in the study. Patients were divided into survivor and non-survivor groups, and logistic regression analysis was used to investigate independent risk factors for death. Pearson coefficient analysis and chi-square test were used to examine the significant relationship between SI and clinical progression markers. Results: Of 628 enrolled patients, 608 survived and 27 died. Multivariate logistic regression analysis reveals “age” (p 0.9” (p 0.9) were associated with poor clinical progression. Conclusions: SI and delta SI are significant predictors of mortality in patients with polytrauma. Moreover, both prehospital and ER SIs can be used as predictive markers of clinical progression in these patients.

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: Transmission electron microscopy (TEM) is one of diagnostic tests for primary ciliary dyskinesia (PCD). The mucosal samples obtained for cilia examination are generally procured from the nasal turbinate, but these specimens often yield inadequate results. The bronchial mucosa is recognized as an alternative sample, but no study has examined the additional utility of bronchial mucosa compared with nasal mucosa in the diagnosis of PCD. Methods: The medical records of 96 patients who underwent TEM for suspected PCD between April 1997 and June 2017 were reviewed. Patients were divided into three groups based on the site of mucosal biopsy: nasal biopsy (NB) group with nasal mucosal biopsy only; bronchial biopsy (BB) group with bronchial mucosal biopsy only; and nasal and bronchial biopsy (NBB) group with a combination of nasal and bronchial mucosal biopsies. Results: The rate of PCD diagnosis was 28.8% (17/59) in the NB group, 41.2% (7/17) in the BB group, and 60.0% (12/20) in the NBB group. The yield of PCD diagnosis significantly increased in the NBB group compared with the NB group (P=0.012). In the NBB group, 25.0% (5/20) of patients were diagnosed with PCD by nasal mucosal biopsy, and 35.0% (7/20) of patients were additionally diagnosed by bronchial mucosal biopsy. The presence of sinusitis or bronchiectasis was not associated with prediction of PCD diagnosis from nasal or bronchial mucosal biopsy. Conclusions: The combination of nasal and bronchial mucosal biopsy for TEM showed higher yields of PCD diagnosis than nasal mucosal biopsy alone.

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.

BackgroundTuberculosis (TB) survivors experience post-TB lung damage and ventilatory function disorders. However, the proportions of obstructive and restrictive ventilatory disorders as well as normal ventilation among post-TB subjects are unknown. In addition, the impacts of ventilatory disorder and its severity on respiratory symptoms, physical activity limitations, and the quality of life in post-TB subjects remain unclear.MethodsSubjects who participated in the Korean National Health and Nutritional Examination Survey 2007–2016 were enrolled in this study. We evaluated the impact of each ventilatory disorder and its severity on respiratory symptoms, physical activity limitations, and quality of life (measured by the EuroQoL five dimensions questionnaire [EQ-5D] index values) in post-TB subjects.Results Among 1,466 post-TB subjects, 29% and 16% had obstructive ventilatory disorders and restrictive ventilatory disorders, respectively. Mild and moderate obstructive ventilatory disorders were not associated with respiratory symptoms, physical activity limitation, or EQ-5D index value compared with normal ventilation; however, severe obstructive ventilatory disorders were associated with more respiratory symptoms (adjusted odds ratio [aOR] = 5.82, 95% confidence interval [CI] = 2.80–12.10), more physical activity limitation (aOR = 92.20, 95% CI = 16.33–520.62), and decreased EQ-5D index (adjusted coefficient = -0.055, 95% CI = -0.096 – -0.013) compared with normal ventilation. Mild restrictive ventilatory disorders were associated with more respiratory symptoms (aOR = 1.95, 95% CI = 1.07–3.56) compared with normal ventilation, while moderate (aOR = 9.17, 95% CI = 1.02–82.22) and severe restrictive symptoms (aOR = 9.17, 95% CI = 1.02–82.22) were associated with physical activity limitation compared with normal ventilation.ConclusionAmong post-TB subjects, 29% and 16% developed obstructive and restrictive ventilatory disorders, respectively. Severe obstructive ventilatory disorder was associated with more respiratory symptoms, more physical activity limitation, and poorer quality of life, while severe restrictive ventilatory disorder was associated with more physical activity limitations.

We aimed to evaluate the long-term use or effects of domiciliary non-invasive positive pressure ventilation (NIPPV) used to treat patients with chronic obstructive pulmonary disease (COPD). Databases were searched to identify randomized controlled trials (RCTs) of COPD with NIPPV for longer than 1 year. The primary outcome as mortality rates were accessed in this meta-analysis. The eight trials included in this study comprised data from 913 patients. The mortality rates for the NIPPV and control groups were 29% (118/414) and 36% (151/419); this difference was statistically significant (risk ratio (RR): 0.79, 95% confidence interval (CI): 0.65-0.95). Mortality rates were reduced with NIPPV in four trials that included stable COPD patients. There was no difference in admission, acute exacerbation and quality of life (QOL) between the NIPPV and control groups. There was no significant difference in withdrawal rates between the two groups (RR 0.99, 95% CI 0.72-1.36, p = 0.94). Maintaining long-term nocturnal NIPPV for more than 1 year in COPD patients, especially stable status COPD patients, leads to a decrease in the mortality rate, and the withdrawal rate is not high compared to long term oxygen treatments.

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.