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...

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

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

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

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

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

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

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Despite the growing evidence that metastatic lymph node ratio (MLNR) is a valuable predictor for the prognosis of papillary thyroid carcinoma, it has not yet been fully determined which factors give the ratio predictive value independent of the number of metastatic lymph nodes (MLNs).Retrospective cohort study.A comprehensive cancer center.Recurrence and clinicopathologic factors were analyzed in 2409 patients with papillary thyroid carcinoma who underwent total thyroidectomy and central node dissection.Cutoff values of MLNs ≥2 and MLNR ≥28.2% increased the recurrence risk (hazard ratio [95% CI], 9.97 [4.73-21.0] and 11.4 [5.53-23.3], respectively). Younger age, male sex, multifocality, tumor size, lymphatic and vascular invasion, and gross extrathyroidal extension positively correlated with MLN and MLNR (allOur study demonstrates that MLN and MLNR are independently observed prognostic markers for tumor recurrence. However, lymphocytic thyroiditis in female patients seems to have lower MLNR by increasing total lymph node yields. In light of their association, a different cutoff for MLNR needs to be applied according to the presence or absence of underlying lymphocytic thyroiditis in the use of MLNR for predicting the recurrence.4.

Purpose No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults.Materials and Methods We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m2 intravenously on day 1, irinotecan, 50 mg/m2/day intravenously on days 1-5, and temozolomide, 100 mg/m2/day orally on days 1-5.Results A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality.Conclusion The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.

Background The impact of reflux esophagitis on the decline of lung function has been rarely reported. This study was performed to evaluate the association between erosive reflux esophagitis and lung function changes. Methods We included patients with normal lung function who underwent esophagogastroduodenoscopy for health screening from a health screening center. Patients with persistent erosive reflux esophagitis on two discrete endoscopic examinations were designated as the erosive reflux esophagitis group. We also selected patients without erosive reflux esophagitis and matched them 1:4 with patients from the erosive reflux esophagitis group. We estimated annual forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) changes from baseline and compared these estimates by the linear mixed regression model. We also estimated the biannual incidence of chronic obstructive pulmonary disease (COPD). Results In total, 1,050 patients (210 patients with erosive reflux esophagitis, and 840 matched controls) were included. The median follow-up duration for spirometry was six years. In patients with erosive reflux esophagitis, mild reflux esophagitis (A grade) was most common (165 patients, 78.6%). The adjusted annual FEV1 change in patients with erosive reflux esophagitis was −51.8 mL/yr, while it decreased by 46.8 mL/yr in controls (P = 0.270). The adjusted annual FVC decline was similar between the two groups (−55.8 vs. −50.5 mL/yr, P = 0.215). The estimated COPD incidence during the follow-up period was not different between the erosive reflux esophagitis and control groups. Conclusion In patients with normal lung function, the presence of erosive reflux esophagitis did not affect the annual declines in FEV1 or FVC., Graphical Abstract

Background The purpose of the study was to translate and linguistically validate a Korean language version of the PROMIS (K-PROMIS) for the six profile adult domains: Fatigue, Pain Intensity, Pain Interference, Physical Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities. Methods A total of 268 items were translated into Korean according to the Functional Assessment of Chronic Illness Therapy multilingual translation methodology. Participants first completed approximately 27 to 35 items and were then interviewed to evaluate the conceptual equivalence of the translation to the original English language source. The K-PROMIS items that met the a priori threshold of ≥ 20% of respondents with comprehension difficulties in the cognitive interview. Results 54 of the 268 items were identified as difficult items to comprehend for at least 20% of respondents in Round 1. The most frequently identified K-PROMIS domain on difficult items to comprehend was the Physical function (24.5%). Most items with linguistic difficulties were Fatigue and Physical function. Cultural difficulties were only included the Physical function and Ability to Participate in Social Roles and Activities domains. 25 of 54 items were slightly revised, and then these revised items were tested with additional six participants in Round 2, and most participants had no problems to understand modified items. Conclusion The six profile adult domains of K-PROMIS have been linguistically validated. Further psychometric validation of the K-PROMIS items will provide additional information of meaningful outcomes for chronic disease and clinical setting., Graphical Abstract

Purpose Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non–small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification.Materials and Methods Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients’ clinical outcome were retrospectively reviewed.Results A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123).Conclusion Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.

OBJECTIVE: This study aimed to investigate the underlying pathogenesis of acute unilateral vestibulopathy (AUV) using gene expression profiling combined with bioinformatics analysis. METHODS: Total RNA was extracted from the peripheral blood mononuclear cells of ten AUV patients in the acute phase and from ten controls. The differentially expressed genes (DEGs) between these two groups were screened using microarray analysis with the cut-off criteria (|fold changes| > 1.5 and p-value

Background The quarantine process at a country's port of entry has an important role in preventing an influx of coronavirus disease 2019 (COVID-19) cases from abroad and further minimizing the national healthcare burden of COVID-19. However, there has been little published on the process of COVID-19 screening among travelers entering into a country. Identifying the characteristics of COVID-19 infected travelers could help attenuate the further spread of the disease. Methods The authors analyzed epidemiological investigation forms and real-time polymerase chain reaction (PCR) results for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of entrants to Incheon International Airport between March 11 to April 30, 2020. We performed univariate and multivariate logistic regression analysis to determine the odds of positive SARS-CoV-2 result. Results A total of 11,074 entrants underwent reverse-transcription PCR for SARS-CoV-2, resulting 388 confirmed cases of COVID-19 infection. COVID-19 had a strong association with the reported loss of smell or taste and association with self-reported fever, chill, cough, and vomiting. If a traveler reported contact with an individual with either respiratory symptoms or confirmed COVID-19 in the last two weeks directly prior to landing, the probability of a positive result was increased. Conclusion If overseas travelers experience loss of smell or taste in the two weeks prior to arrival, they may require an immediate examination to rule out COVID-19 at a port of entry. As to measure body temperature upon arrival at a port of entry, it is important to screen for any occurrence of fever within the two weeks prior to travel. Also, information with epidemiological relevance, such as recent contact with an individual suffering from any respiratory symptoms or with confirmed COVID-19, should be included in COVID-19 screening questionnaires for international travelers., Graphical Abstract

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

Background Exposure to endocrine disrupting chemicals (EDCs) that influence the hormonal and homeostatic systems is known to be associated with gynecologic health risks in many countries. In this study, we evaluated exposure to EDCs associated with diminished ovarian reserve (DOR) and gynecologic health risks. Methods This cross-sectional study was performed from September 2014 to November 2014 and included 307 Korean reproductive-aged women. Anthropometric measurements, laboratory tests with urine and blood sampling and pelvic ultrasound examinations were performed. Results Urinary bisphenol A (BLA) level was significantly higher in the DOR group with anti-Müllerian hormone lower than 25 percentile (1.89 ± 2.17 ug/g and 1.58 ± 1.08 ug/g, P < 0.05). Urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate and mono-N-butyl phthalate, and substrates of phthalate were evaluated and no significant difference was observed between the DOR group and non-DOR group. Logistic regression analysis suggested an increase in infertility in high BPA exposure group and the odds ratio (OR, 4.248) was statistically significant after adjustment for age, birth control pills, and the age of menarche, parity, and waist circumference. High phthalate exposure was associated with endometrial polyp after adjustment (OR, 2.742). Conclusion BPA exposure might be associated with DOR and infertility. Meanwhile, endometrial polyp is increased in women with high phthalate exposure. Therefore, the risk of exposures to EDCs for reproduction should be a matter of concern in reproductive-aged women., Graphical Abstract

IntroductionDespite the significant disease burden of bronchiectasis in Korea, no large-scale, representative prospective cohort studies have been conducted to evaluate the clinical characteristics of Korean patients with bronchiectasis, indicating an urgent need for cohort studies on bronchiectasis.Methods and analysisThe Korean Multicenter Bronchiectasis Audit and Research Collaboration (KMBARC) is a prospective, non-interventional observational cohort study on bronchiectasis in Korea. The inclusion criteria of this registry are as follows: (1) adult patients (aged ≥18 years) with or without respiratory symptoms (cough, chronic sputum and/or recurrent respiratory infection) and chest computed tomography revealing bronchiectasis affecting one or more lobes and (2) stable status at the time of registration: patients with bronchiectasis who were admitted for a respiratory aetiology can be enrolled at least 4 weeks after hospital discharge. The exclusion criteria are as follows: (1) bronchiectasis due to cystic fibrosis; (2) traction bronchiectasis associated with interstitial lung disease; (3) patients actively being treated for pneumonia, pulmonary tuberculosis or non-tuberculous mycobacterial infection; (4) patients who are unable or unwilling to provide informed consent; and (5) pregnant patients. Although the KMBARC questionnaires for baseline and annual follow-up data are similar to the European Multicentre Bronchiectasis Audit and Research Collaboration questionnaires, KMBARC has distinctive features such as use of Bronchiectasis Health Questionnaires, measurement with fatigue and depression scales, blood tests, use of consensus definition of exacerbations and information on emergency room or hospitalisation.We aim to recruit at least 1200 patients over the study period from more than 26 hospitals in South Korea. Patients will undergo a detailed baseline and yearly assessment for up to 5 years. The study objectives of the KMBARC registry are as follows: (1) uncovering the natural course of bronchiectasis; (2) aiding in establishing evidence-based bronchiectasis guidelines in Korea; and (3) encouraging and facilitating studies on bronchiectasis in Korea.Ethics and disseminationThis study received necessary approval from the Institutional Review Boards of all participating institutions. The Asan Medical Center Institutional Review Board gave overall approval for the study. Results will be disseminated via peer-reviewed publications and conference presentations.Trial registration numberKCT0003088.

Author(s): Park, Ki Yun; Lee, John J; Dierker, Donna; Marple, Laura M; Hacker, Carl D; Roland, Jarod L; Marcus, Daniel S; Milchenko, Mikhail; Miller-Thomas, Michelle M; Benzinger, Tammie L; Shimony, Joshua S; Snyder, Abraham Z; Leuthardt, Eric C | Abstract: BackgroundUse of functional MRI (fMRI) in pre-surgical planning is a non-invasive method for pre-operative functional mapping for patients with brain tumors, especially tumors located near eloquent cortex. Currently, this practice predominantly involves task-based fMRI (T-fMRI). Resting state fMRI (RS-fMRI) offers an alternative with several methodological advantages. Here, we compare group-level analyses of RS-fMRI vs. T-fMRI as methods for language localization.PurposeTo contrast RS-fMRI vs. T-fMRI as techniques for localization of language function.MethodsWe analyzed data obtained in 35 patients who had both T-fMRI and RS-fMRI scans during the course of pre-surgical evaluation. The RS-fMRI data were analyzed using a previously trained resting-state network classifier. The T-fMRI data were analyzed using conventional techniques. Group-level results obtained by both methods were evaluated in terms of two outcome measures: (1) inter-subject variability of response magnitude and (2) sensitivity/specificity analysis of response topography, taking as ground truth previously reported maps of the language system based on intraoperative cortical mapping as well as meta-analytic maps of language task fMRI responses.ResultsBoth fMRI methods localized major components of the language system (areas of Broca and Wernicke) although not with equal inter-subject consistency. Word-stem completion T-fMRI strongly activated Broca's area but also several task-general areas not specific to language. RS-fMRI provided a more specific representation of the language system.ConclusionWe demonstrate several advantages of classifier-based mapping of language representation in the brain. Language T-fMRI activated task-general (i.e., not language-specific) functional systems in addition to areas of Broca and Wernicke. In contrast, classifier-based analysis of RS-fMRI data generated maps confined to language-specific regions of the brain.

Highlights • Decreased FVC (% pred) was associated with increased cerebral small vessel disease burden even in cognitively normal subjects. • This reduced lung function was related to low Mini-Mental Status Examination (MMSE) scores in cognitively normal subjects. • Path analyses showed that white matter hyperintensities partially mediated the positive relationship between FVC (% pred) and MMSE score. • There was no significant association between low FVC (% pred) and cortical thickness in cognitively normal subjects., Background Pulmonary dysfunction is associated with elevated risk of cognitive decline. However, the mechanism underlying this relationship has not been fully investigated. In this study, we investigate the relationships between pulmonary function, cerebral small vessel disease (CSVD) markers, cortical thickness, and the Mini-Mental Status Examination (MMSE) scores in cognitively normal individuals. Methods We used a cross-sectional study design. We identified 1924 patients who underwent pulmonary function testing, three-dimensional brain magnetic resonance imaging (MRI), and the MMSE. Pulmonary function was analyzed according to the quintiles of percentage predicted values (% pred) for forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1). Regarding CSVD markers, we visually rated white matter hyperintensities (WMH) and manually counted lacunes and microbleeds. Cortical thickness was measured by surface-based methods. Results Compared with the highest quintile of FVC, the lowest quintile of FVC (% pred) showed a higher risk of WMH (OR 1.98, 95% CI: 1.21–3.24) and lacunes (OR 1.86, 95% CI: 1.12–3.08). There were no associations between FVC or FEV1 and cortical thickness. Low FVC, but not FEV1, was associated with low MMSE scores. Path analyses showed that WMH partially mediated the positive relationship between FVC (% pred) and MMSE score. Conclusions Our findings suggested that decreased pulmonary function was associated with increased CSVD burdens, which in turn wass associated with decreased cognition, even in cognitively normal subjects.

Background Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are needed across sarcoma types to improve therapeutic strategies. To investigate the molecular characteristics of complex karyotype sarcomas (CKSs) for therapeutic targets, we performed genomic profiling. Results The mutational landscape showed that TP53, ATRX, and PTEN genes were highly mutated. CKS samples were categorized into three groups based on copy number variations that were associated with CDK4 and RB1 signatures. Integrated analysis of genomic and transcriptomic data revealed several pathways related to PDGFR, which could be a strategic target for anti-sarcoma therapy. Conclusions This study provides a detailed molecular classification of CKSs and proposes several therapeutic targets. Targeted or combinational therapies for treating CKS should be considered before chemotherapy. Electronic supplementary material The online version of this article (10.1186/s12881-018-0722-6) contains supplementary material, which is available to authorized users.

ObjectiveTo determine the prevalence of central lesions in persistent geotropic positional nystagmus, and characteristics and anatomical substrates of the nystagmus in cerebellar lesions.MethodsWe prospectively recruited 58 patients with persistent geotropic positional nystagmus at the Dizziness Clinic of Pusan National University Hospital. Seven patients with unilateral cerebellar lesions were subjected to analysis of clinical characteristics, oculographic data, and MRI lesions. For comparison, we studied 37 cases of peripheral persistent geotropic positional nystagmus.ResultsThe prevalence of central lesions in persistent geotropic positional nystagmus was 12% (7/58). Persistent geotropic positional nystagmus in cerebellar lesions was mostly asymmetrical. Horizontal nystagmus changed in direction during the bow-and-lean test with null positions. All patients showed impaired horizontal smooth pursuit bilaterally, and 3 of them also had positional downbeat nystagmus. The peak intensity and asymmetry of persistent geotropic positional nystagmus did not differ between central and peripheral groups (p > 0.05), while there was a difference in the maxima. Lesion overlays revealed that damage to the cerebellar tonsil was responsible for the generation of persistent geotropic positional nystagmus.ConclusionAlthough persistent geotropic positional nystagmus in cerebellar lesions shares the characteristics of nystagmus measures with peripheral cases, accompanying central oculomotor signs can aid in differentiation. In tonsillar lesions, compensatory rotational feedback due to erroneous estimation of the direction of gravity may generate constant horizontal geotropic positional nystagmus.

Background Blood eosinophils have been suggested as a potential biomarker in chronic obstructive pulmonary disease (COPD), and their stability over time has been investigated in a few studies. However, the association between the stability of blood eosinophils and long-term clinical outcomes in COPD patients has yet to be fully elucidated. This study aimed to evaluate the stability of blood eosinophils and its association with clinical outcomes in COPD patients. Methods In total, 299 COPD patients from the Korean Obstructive Lung Disease cohort with at least two blood eosinophil measurements were included. Patients were stratified according to a cut-off of 300 cells/μL, and the association between eosinophil changes and all-cause mortality was analysed. The annual decline in forced expiratory volume in 1 s (FEV1), serial changes in St George’s Respiratory Questionnaire score (SGRQ), and exacerbations during follow-up were compared among eosinophil groups. Results Patients were stratified into three groups according to the blood eosinophil cut-off: persistently

Purpose The purpose of this study was to evaluate the adverse drug reactions (ADRs) and serious adverse events associated with capecitabine use in Korean patients by analyzing data from a comprehensive national database of adverse events. Method Data from all reports concerning capecitabine (Anatomical Therapeutic Chemical code: L01BC06) generated between January 2011 and December 2014 were collected from the Korean Adverse Event Reporting System database (KAERS). Results A total of 676 reports and 1069 capecitabine-related ADRs were identified. Ninety-nine cases (14.6%) were classified as serious adverse events. The most commonly reported capecitabine-related ADRs involved gastrointestinal system disorders (324, 30.3%), including diarrhea, nausea, vomiting, and stomatitis , followed by skin and appendage reactions (220, 20.6%), which included symptoms such as skin discoloration/disorder/dryness, itching, and rash. Conclusions Patients need to be educated about the common ADRs associated with capecitabine intake in a clinical setting. Patient characteristics must be considered when determining the capecitabine dosage and risk of ADRs, and nursing intervention is critical for preventing exacerbation of these ADRs.

To determine the efficacy of prophylactic medications for migraine in reducing associated dizziness and motion sickness.Multicenter prospective observational study.Nationwide 9 Dizziness Clinics in South Korea.One hundred thirty-eight patients who required a preventive medication for migraine accompanied by dizziness and motion sickness.At least one of the prophylactic medications was prescribed among the beta-blockers, calcium channel blockers, tricyclic antidepressants, and antiepileptic drugs.For 3 months from the index visit, the patients had monthly assessments of the headache (frequency and duration), dizziness handicap inventory, University of California Los Angeles dizziness questionnaire, vertigo symptom scale, and motion sickness score.The prophylactic medications significantly improved the headache profiles, all three parameters of dizziness (dizziness handicap inventory, University of California Los Angeles dizziness questionnaire, and vertigo symptom scale), and severity of motion sickness (p 0.001).The prophylactic medication for migraine also improves associated dizziness and motion sickness as well as the headaches.

Various biomarkers have emerged as potential surrogates to represent various subgroups of chronic obstructive pulmonary disease (COPD), which manifest with different phenotypes. However, the biomarkers representing never-smokers with COPD have not yet been well elucidated. The aim of this study was to evaluate the associations of certain serum and radiological biomarkers with the presence of COPD in never-smokers. To explore the associations of serum and radiological biomarkers with the presence of COPD in never-smokers, we conducted a cross-sectional patient cohort study composed of never-smokers from the COPD in Dusty Areas (CODA) cohort, consisting of subjects living in dusty areas near cement plants in South Korea. Of the 131 never-smokers in the cohort, 77 (58.8%) had COPD. There were no significant differences in the number of subjects with high levels of inflammatory biomarkers (>90th percentile of never-smokers without COPD), including white blood cell count, total bilirubin, interleukin (IL)-6, IL-8, and C-reactive protein, or radiologic measurements (including emphysema index and mean wall area percentage) between never-smokers with COPD and those without COPD. However, the number of subjects with high uric acid was significantly higher in never-smokers with COPD than never-smokers without COPD (31.2% (24/77) vs. 11.1% (6/54); p = 0.013). In addition, multivariate analysis revealed that high uric acid was significantly associated with the presence of COPD in never-smokers (adjusted relative risk: 1.63; 95% confidence interval: 1.21, 2.18; p = 0.001). Our study suggests that high serum levels of uric acid might be a potential biomarker for assessing the presence of COPD in never-smokers.

Background/Aims Despite increasing interest in pulmonary thromboembolism (PTE), data on recent trends in PTE incidence are limited. This study evaluated the recent incidence rate of PTE. Methods We performed a retrospective chart review of patients with PTE admitted to Chung-Ang University Hospital during the 10-year period from 2006 to 2015. Age-standardized incidence and mortality rates were calculated by the direct method per 100,000 populations. To analyze the trend of risk factor, we also calculated the proportions of cancer, major operation, and recent major fracture over that time. Results Total crude incidence rate of PTE per 100,000 was 229.36 and the age-sex adjusted standardized incidence rate was 151.28 (95% confidence interval [CI], 127.88 to 177.10). The incidence rate have been significantly increased 1.083 times annually from 2006 (105.96 per 100,000) to 2015 (320.02 per 100,000) (95% CI, 1.049 to 1.118; p < 0.001). These incidences also increased annually in age group of 35 to 54, 55 to 74, and ≥ 75 years, and in both males (odds ratio [OR], 1.071; 95% CI, 1.019 to 1.127; p = 0.007) and females (OR, 1.091; 95% CI, 1.047 to 1.136; p < 0.001). Cancer accounted for most of the increase from 20.0% at 2006 to 2007 to 42.8% at 2014 to 2015 (OR, 1.154; 95% CI, 1.074 to 1.240; p < 0.001), while the proportions of recent fracture and major operation remained constant. Conclusions The incidence of pulmonary embolism has gradually increased over the 10 years. The increase of PTE incidence was mainly due to increased proportion of cancer patients.

Hyun Lee,1,* Byung Woo Jhun,1,* Juhee Cho,2–4 Kwang Ha Yoo,5 Jin Hwa Lee,6 Deog Kyeom Kim,7 Jong Deog Lee,8 Ki-Suck Jung,9 Jung Yeon Lee,10 Hye Yun Park1 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 2Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 4Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea; 6Division of Pulmonary and Critical Care Medicine, School of Medicine, Ewha Womans University, Seoul, South Korea; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, South Korea; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungju Hospital, Konkuk University School of Medicine, Chungju, South Korea *These authors contributed equally to this work Background: Patients with chronic obstructive pulmonary disease (COPD) often have poor health-related quality of life (HRQoL) that is disproportionate to their degree of airflow limitation. This study evaluated the association between St George’s Respiratory Questionnaire for COPD (SGRQ-C) score and forced expiratory volume in one second and investigated the factors responsible for high SGRQ-C score according to severity of airflow limitation.Methods: Data from 1,264 COPD patients were obtained from the Korean COPD Subgroup Study (KOCOSS) cohort. Patients were categorized into two groups according to severity of airflow limitation: mild-to-moderate and severe-to-very severe COPD groups. We evaluated the clinical factors associated with high SGRQ-C score (≥25) in each COPD patient group.Results: Of the 1,264 COPD patients, 902 (71.4%) had mild-to-moderate airflow limitation and 362 (28.6%) had severe-to-very severe airflow limitation. Of the mild-to-moderate COPD patients, 59.2% (534/902) had high SGRQ-C score, while 80.4% (291/362) of the severe-to-very severe COPD patients had high SGRQ-C score. The association between SGRQ-C score and post-bronchodilator forced expiratory volume in one second (% predicted) was very weak in the mild-to-moderate COPD patients (r=–0.103, p=0.002) and weak in the severe-to-very severe COPD patients (r=–0.219, p

Metastasis of a phyllodes tumor to the stomach is an extremely rare condition with important clinical implications. A 44-year-old woman was initially diagnosed with a phyllodes tumor in her right breast in 2008, and subsequently presented to an outpatient clinic with dizziness on December 16, 2013. We found that she had severe anemia (hemoglobin levels, 6.7 g/dL), and we quickly performed esophagogastroduodenoscopy to identify the cause. This procedure revealed large ulcerofungating masses with active bleeding in the stomach. Histopathological examination revealed that the masses were consistent with phyllodes tumor metastases. In patients with a metastatic phyllodes tumor presenting as anemia, gastric metastasis should be considered as one of the differential diagnoses because overlooking the possibility might have dire consequences if cytotoxic chemotherapy were administered.

OBJECTIVE We aimed to estimate the prevalence of prescriptions to long-acting benzodiazepines (BZDs) among elderly outpatients in Korea in 2013 and analyze the factors that led to inappropriate prescription practices. METHODS Using the Korea Health Insurance Review and Assessment Service-National Patients Sample database in 2013, we estimated the pattern of BZD prescription among elderly outpatients. BZDs were categorized as long-acting (half-life (T1/2) ≥ 20 hours) or short-acting (T1/2

Jin Hwa Lee,1 Chin Kook Rhee,2 Kyungjoo Kim,2 Jee-Ae Kim,3 Sang Hyun Kim,4 Kwang Ha Yoo,5 Woo Jin Kim,6 Yong Bum Park,7 Hye Yun Park,8 Ki-Suck Jung9 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, EwhaWomans University, 2Department of Internal Medicine, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, 3Pharmaceutical Policy Evaluation Research Team, Research Institution, Health Insurance Review and Assessment Service, 4Big Data Division, Health Insurance Review and Assessment Service, Wonju, 5Department of Internal Medicine, Konkuk University College of Medicine, Seoul, 6Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Chuncheon, 7Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, 8Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, South Korea Purpose: The purpose of this study was to identify subtypes in patients with mild-to-moderate airflow limitation and to appreciate their clinical and socioeconomic implications.Methods: Subjects who were aged ≥20 years and had forced expiratory volume in 1 second (FEV1) ≥60% predicted and FEV1/forced vital capacity

Vitamins are known to be associated with immunity and nutrition. Moreover, vitamin deficiency can affect host immunity to various infectious diseases, including tuberculosis. Although patients with tuberculosis often have vitamin D deficiency, little is known about the levels of other vitamins. Here, we aimed to investigate the status of vitamins A, BWe performed a case-control study to investigate the serum vitamin concentrations in 152 patients with tuberculosis and 137 control subjects. The concentrations of vitamin A, vitamin D, vitamin E, homocysteine, and methylmalonic acid were measured using high-performance liquid chromatography (HPLC) or HPLC-tandem mass spectrometry. Patient demographic data and other biochemical parameters were also analyzed.The serum concentrations of vitamins A, D, and E were significantly lower in patients with tuberculosis than in control subjects (1.4 vs. 2.0 μmol/L, P 0.001; 10.6 vs. 19.3 ng/mL, P 0.001; and 22.8 vs. 30.6 μmol/L, P 0.001, respectively). In contrast, the methylmalonic acid levels were higher in patients with tuberculosis (134.9 vs. 110.8 nmol/L, P 0.001). The prevalences of vitamin deficiencies were significantly higher in patients with tuberculosis. Moreover, multiple vitamin deficiencies were only observed in patients with tuberculosis (22.4% of all patients with tuberculosis vs. 0% of all control subjects). Positive correlations among vitamin A, D, and E concentrations were observed (vitamins A and D, r = 0.395; vitamins D and E, r = 0.342; and vitamins A and E, r = 0.427, P 0.001). Body mass index, total cholesterol, low-density lipoprotein, iron, and total iron-binding capacity all showed positive correlations with vitamin A, D, and E concentrations.Vitamin deficiencies are common in patients with tuberculosis. Further research investigating the clinical importance of vitamin and nutritional status in patients with tuberculosis is needed.

The histological subtypes by peripheral tumor location remain uncharacterized in COPD patients with emphysema. We investigated histologic subtypes of peripheral lung cancers based on the context of heterogeneous emphysema distribution in patients with airflow limitation and CT-determined emphysema. A retrospective, cross-sectional study was conducted using data from 754 patients with airflow limitation and newly-diagnosed primary lung cancers from February 2013 to February 2015. Of these, 230 patients had emphysema, as determined by computed tomography software designed to quantify emphysema. Among the 230 patients, the most common subtype in central lesions (n=84) was squamous cell carcinoma (SCC) (n=64/84, 76%). Adenocarcinoma (ADC) was more frequently observed in peripheral lesions (n=146) than central lesions (58/146 [40%] vs. 4/84 [5%], p

Purpose Because anthracofibrosis (AF) is associated with tuberculosis (TB), detection of AF is clinically relevant in Korea, a TB endemic region. We thus sought to develop and validate a predictive model for AF using clinical radiographic data. Materials and methods Between January 1, 2008 and March 31, 2014, 3849 adult patients who underwent bronchoscopies were retrospectively included from an observational registry. We dichotomized patients based on the presence (n=167) or absence (n=242) of AF. After analyzing their clinico-radiographic characteristics, a logistic prediction model was developed. An area under the curve (AUC) was drawn using the weighted score in logistic regression model. To evaluate the degree of overfitting of the predictive model, a 5-fold cross-validation procedure was performed. Results In multivariate logistic regression, clinical findings such as age >70 years, female gender, active TB, and computed tomography findings including atelectasis, stenosis, bronchial wall thickening, enlarged and calcified lymph nodes were significant diagnostic predictors for AF. The weighed score had an AUC of 0.939 [95% confidence interval (CI)=0.911-0.960], similar to the AUC obtained from internal validation (AUC=0.926, 95% CI=0.896-0.949). Conclusion The prediction model may be helpful for predicting AF based only on clinical and radiographic findings. However, further external validation is necessary.