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Background Peer-support programs are a useful social support strategy for populations trying to quit smoking who are willing to maintain smoking abstinence. This study is a protocol for a systematic review and meta-analysis to assess the effectiveness of peer support for smoking cessation. Methods This protocol will be conducted in accordance with the Cochrane Handbook of Systematic Reviews of Interventions 6.2. We will conduct a comprehensive search in the Cochrane Central Register of Controlled Trials, ovidEmbase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, ovidMEDLINE, Google Scholar, and Open Grey, as well as the Trials Register of Promoting Health Interventions in EPPI-Centre, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and reference lists of included papers. The review will include randomized controlled trials of peer support interventions aimed to stop smoking in any population. Two reviewers will independently screen and select relevant studies. Version 2 of the Cochrane tool that assesses risk of bias in randomized trials will be used to assess the risk of bias in the included studies. The primary outcomes will be defined as the tobacco abstinence rate and adverse events. If a quantitative synthesis is not appropriate, a synthesis without meta-analysis will be undertaken. Discussion This review will provide the best available evidence regarding the effects of peer support interventions to quit smoking. The results from this study will help to inform healthcare providers on the optimal peer support intervention modalities such as intensity, delivery methods, type of support provider, and duration of the intervention. Systematic review registration PROSPERO CRD42020196288

Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs.

Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. We enrolled patients with lung cancer (n = 144) and healthy volunteers as the controls (n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using enzyme-linked immunosorbent assay. Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC) and 19 had small cell lung cancer. The area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80–0.89) for differentiating lung cancer patients from controls. The levels of all the markers were significantly higher in NSCLC patients with stage IV than in those with stages I–III. A Kaplan-Meier survival analysis showed that NSCLC cancer patients with higher levels of all markers showed poorer survival than those with lower levels. In Cox multivariate analysis of patients with NSCLC, independent prognostic factors for overall survival were CXCL9 and CXCL11. CXCL9 was the only independent prognostic factor for cancer-specific survival. Serum IFN-γ-inducible chemokines may be useful as clinical markers of metastasis and prognosis in NSCLC, and CXCL9 levels showed the most significant results.

The diagnosis of tuberculous lymphadenitis (TB-LAP) is challenging. We evaluated the role of blood CXC chemokine receptor 3 (CXCR3) ligands in its diagnosis. A total of 65 lymphadenopathy patients were enrolled and lymph node sampling was performed. We also recruited 113 control subjects, consisting of 27 with positive results and 86 with negative results, in the interferon (IFN)-γ release assay (IGRA). In all study subjects, whole-blood samples were collected using the IGRA methodology. After incubation, plasma levels of IFN-γ and two CXCR3 ligands, IFN-inducible T-cell a chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG), were measured using immunoassay. Fifty-three TB-LAP patients were enrolled. TB antigen-stimulated IFN-γ, I-TAC, and MIG levels were all significantly higher in the TB-LAP patients than in the controls and non-TB-LAP patients. The levels of I-TAC and MIG, but not IFN-γ, showed significant differences between the TB-LAP patients and IGRA-positive controls. Area under the receiver operating characteristic curves (AUROCs) of IFN-γ, I-TAC, and MIG were 0.955, 0.958, and 0.959, respectively, for differentiating TB-LAP from control group, and were 0.912, 0.956, and 0.936, respectively, for differentiating TB-LAP from non-TB-LAP. In conclusion, the TB antigen-stimulated MIG and I-TAC could be useful biomarkers in the diagnosis of TB-LAP.

Objectives Radon, a natural radiation, is the leading environmental cause of lung cancer in never-smokers. However, the radon exposure impact on the mutational landscape and tumor mutation burden (TMB) of lung cancer in never-smokers has not been explored. The aim of this study was to investigate the mutational landscape of lung adenocarcinoma in never-smokers who were exposed to various degrees of residential radon. Materials and methods To investigate the effect of indoor radon exposure, we estimated the cumulative exposure to indoor radon in each house of patients with lung cancer with a never-smoking history. Patients with at least 2 year-duration of residence before the diagnosis of lung adenocarcinoma were included. Patients were subgrouped based on the median radon exposure level (48 Bq/m3): radon-high vs. radon-low and targeted sequencing of tumor and matched blood were performed in all patients. Results Among 41 patients with lung adenocarcinoma, the TMB was significantly higher in the radon-high group than it was in the radon-low group (mean 4.94 vs. 2.6 mutations/Mb, P = 0.01). The recurrence rates between radon-high and radon-low group did not differ significantly. Mutational signatures of radon-high tumors showed features associated with inactivity of the base excision repair and DNA replication machineries. The analysis of tumor evolutionary trajectories also suggested a series of mutagenesis induced by radon exposure. In addition, radon-high tumors revealed a significant protein-protein interaction of genes involved in DNA damage and repair (P Conclusions Indoor radon exposure increased the TMB in never-smoker patients with lung adenocarcinoma and their mutational signature was associated with defective DNA mismatch repair.

Background Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. Methods This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. Results With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. Conclusions Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.

Background: COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove the hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. Methods: This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 16,757 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. This cohort enrolled six arms consisting of never-smokers without COPD (N=313,553), former smokers without COPD (N=41,359), smokers without COPD (N=112,627), never-smokers with COPD (N=7,789), former smokers with COPD (N=1,085), and smokers with COPD (N=2,677). Results: Incident rate of lung cancer per 100,000 person-year was higher according to smoking and COPD (216 in non-COPD and 757 in COPD among never-smokers, 271 in non-COPD and 1266 in COPD among former smokers, 394 in non-COPD and 1560 in COPD among former smokers, p

BACKGROUND: Lead exposure is a resurgent environmental issue globally. Smoking can be a source of lead exposure, although the majority of lead poisonings originate from workplace exposures. However, no study has been undertaken concerning the blood lead levels based on the chronic obstructive pulmonary disease (COPD), smoking status, and other risk factors of COPD. This cross-sectional study was conducted to investigate the blood lead levels according to COPD and clinical variables associated with COPD. METHODS: Data (total number =53,829) were collected from the Korean National Health and Nutrition Examination Survey (IV in 2008 and 2009, V in 2010–2012, and VI in 2013). Multivariable linear regression analyses were performed to determine variables associated with elevated blood lead levels. RESULTS: Univariate regression analysis showed that male sex, older age, smoking, occupation level, income level, education level, and presence of COPD were related to higher blood lead levels, whereas the other co-morbidities including diabetes, hypertension, cerebral stroke, osteoporosis, asthma, and depression were not related (P

Background COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove the hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. Methods This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 16,757 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. This cohort enrolled six arms consisting of never-smokers without COPD (N = 313,553), former smokers without COPD (N = 41,359), smokers without COPD (N = 112,627), never-smokers with COPD (N = 7789), former smokers with COPD (N = 1085), and smokers with COPD (N = 2677). Results Incident rate of lung cancer per 100,000 person-year was higher according to smoking and COPD (216 in non-COPD and 757 in COPD among never-smokers, 271 in non-COPD and 1266 in COPD among former smokers, 394 in non-COPD and 1560 in COPD among smokers, p p p Conclusion Our data suggested that COPD was an independent risk factor for the development of lung cancer, and colorectal cancer and liver cancer among other major cancers in the Korean population, regardless of smoking status.

Residential radon exposure and cigarette smoking are the two most important risk factors for lung cancer. The combined effects thereof were evaluated in a multi-center matched case-control study in South Korea. A total of 1038 participants were included, comprising 519 non-small cell lung cancer cases and 519 age- and sex- matched community-based controls. Residential radon levels were measured for all participants. Multivariate logistic regression was used to calculate odds ratios (OR) for lung cancer according to radon exposure (high &ge, 100 Bq/m3 vs. low &lt, 100 Bq/m3), smoking status, and combinations of the two after adjusting for age, sex, indoor hours, and other housing information. The median age of the participants was 64 years, and 51.3% were women. The adjusted ORs (95% confidence intervals [CIs]) for high radon and cigarette smoking were 1.56 (1.03&ndash, 2.37) and 2.53 (1.60&ndash, 3.99), respectively. When stratified according to combinations of radon exposure and smoking status, the adjusted ORs (95% CIs) for lung cancer in high-radon non-smokers, low-radon smokers, and high-radon smokers were 1.40 (0.81&ndash, 2.43), 2.42 (1.49&ndash, 3.92), and 4.27 (2.14&ndash, 8.52), respectively, with reference to low-radon non-smokers. Both residential radon and cigarette smoking were associated with increased odds for lung cancer, and the difference in ORs according to radon exposure was much greater in smokers than in non-smokers.

Exposure-response and clinical outcome (CO) model for inhaled budesonide/formoterol was developed to quantify the relationship among pharmacokinetics (PK), pharmacodynamics (PD) and CO of the drugs and evaluate the covariate effect on model parameters. Sputum eosinophils cationic proteins (ECP) and forced expiratory volume (FEV1) were selected as PD markers and asthma control score was used as a clinical outcome. One- and two-compartment models were used to describe the PK of budesonide and formoterol, respectively. The indirect response model (IDR) was used to describe the PD effect for ECP and FEV1. In addition, the symptomatic effect on the disease progression model for CO was connected with IDR on each PD response. The slope for the effect of ECP and FEV1 to disease progression were estimated as 0.00008 and 0.644, respectively. Total five covariates (ex. ADRB2 genotype etc.) were searched using a stepwise covariate modeling method, however, there was no significant covariate effect. The results from the simulation study were showed that a 1 puff b.i.d. had a comparable effect of asthma control with a 2 puff b.i.d. As a result, the 1 puff b.i.d. of combination drug could be suggested as a standardized dose to minimize the side effects and obtain desired control of disease compared to the 2 puff b.i.d.

Background Although combination chemotherapy (CC) is generally recommended in recurrent or primary metastatic gastric cancer (RPMGC), the results of randomized trials are conflicting. Methods A retrospective review was conducted on 687 RPMGC patients who received palliative chemotherapy. We compared the overall survival (OS) between CC and single-agent chemotherapy (SC) among these patients, and we analyzed the clinicopathological characteristics affecting outcome including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Results Although 521 patients (75.8%) underwent CC, SC was more frequently performed in elderly patients (57.6%) and ECOG performance status (PS) 2 or 3 (65.8%) patients (p p p = 0.583), poor PS (p = 0.810), signet ring cell (p = 0.347), palliative surgical resection (p = 0.307), and high PLR (p = 0.120), with a significant interaction between age and type of regimen (p = 0.012). Moreover, there was no difference in OS between CC and SC after propensity score matching (p = 0.322). Multivariate analysis revealed that palliative resection and ≥ second-line chemotherapy were independently associated with favorable OS (p p = 0.004), signet ring cell (p p = 0.04), high NLR (p = 0.001), and high PLR (p = 0.033) were independent prognostic factors of poor OS. Conclusions Although CC is the standard of care in RPMGC, SC can be considered a reasonable option in certain subgroups, such as elderly patients.

Exon 19 deletion and L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are both common mutations that predict a good response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the existence of clinically significant difference in sensitivity to EGFR tyrosine kinase inhibitors among different EGFR mutation subtypes is still a matter of debate.The outcome of 60 EGFR mutation-positive advanced NSCLC patients who received first-line gefitinib therapy (250 mg/d) was retrospectively analyzed according to EGFR mutation subtypes.The median progression-free survival (PFS) and overall survival (OS) after the initiation of gefitinib therapy for all patients was 11 and 26 months, respectively. Univariate analysis showed that patients with exon 19 deletion (n=28) had significantly longer median PFS (20 vs. 8 mo, P=0.004) and OS (36 vs. 22 mo, P=0.001) compared with those with L858R mutation (n=25) and uncommon or dual mutations (n=7). Multivariate analysis revealed that exon 19 deletion (P=0.007) was an independent prognostic factor of favorable PFS, with an independent association with poor PFS of male sex (P=0.049). Exon 19 deletion was also independently associated with favorable OS (P0.0001), whereas male sex (P=0.004) and primary metastatic disease (P=0.032) were independent prognostic factors of poor OS.The EGFR exon 19 deletion was associated with favorable PFS and OS in patients receiving first-line gefitinib treatment. The EGFR mutation subtype should be considered when making treatment decision or designing clinical trials for chemotherapy-naive, EGFR mutation-positive advanced NSCLC patients.

OBJECTIVES: We aimed to determine the characteristics of the deceased victims of deaths caused by exposure to humidifier disinfectants, and present the distribution of the victims’ data submitted for damage application, demographic characteristics, imaging findings, characteristics of humidifier disinfectant exposure, and distribution of the causes of death.METHODS: An integrated database of victims was established using the medical records data of 1,413 victims submitted during the application for death damage caused by exposure to humidifier disinfectants, and the demographic characteristics, medical records, imaging findings, exposure characteristics, and cause of death were examined.RESULTS: The average numbers of data submissions of each applicant for death damage were 3.0 medical use records. A total of 608 (43.0%) victims had more than one finding of acute, subacute, or chronic interstitial lung diseases. The average daily and cumulative use times of the victims were 14.40 and 24,645.81 hours, respectively, indicating greater exposure in this group than in the survivors. The humidifier disinfectants’ components comprised polyhexamethylene guanidine (72.8%), chloromethylisothiazolinone/methylisothiazolinone (10.5%), other components (15.0%), and oligo-[2-(2-ethoxy)-ethoxyethyl] guanidine chloride (1.5%). The components’ distribution was 67.8% for single-component use, which was higher than that in the survivors (59.8%). The distribution of the causes of death were: respiratory diseases (54.4%), neoplasms (16.8%), and circulatory diseases (6.3%). Other interstitial lung diseases (65.5%) were the most common cause of death among those who died due to respiratory diseases.CONCLUSIONS: Careful discussions of appropriate remedies should be conducted based on a comprehensive understanding of the characteristics of the deceased victims, considering their specificities and limitations.

Background Presence of purulent sputum during an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is considered sufficient indication for starting empirical antibiotics. We investigated the relationship between detection of potentially pathogenic bacteria (PPB) using sputum culture or polymerase chain reaction (PCR) and clinical response and sought the risk factors for PPB growth. Methods In 342 outpatients with AECOPD, we compared detection rates of H. influenzae (HI) and S. pneumoniae (SP) using conventional sputum culture versus PCR. The utility of either technique to predict clinical cure or failure after effective antibiotics was assessed. The factors predicting positive sputum cultures were evaluated using logistic regression. Results Using sputum culture, 132 PPB were detected. The predominant bacteria were HI (40.9%) and SP (19.7%). Detection of HI or SP in sputum was higher using PCR than culture growth (60.8% vs 18.6%; P

Background: Lead exposure is a resurgent environmental issue globally. Smoking can be a source of lead exposure although the majority of lead poisonings originate from workplace exposures. We attempted to investigate the blood lead levels based on COPD and smoking status and the independent association between elevated blood lead levels and clinical variables. Methods: Our data were collected from Korean National Health and Nutrition Examination Survey (KNHANES) IV (n= 9744 in 2008, n= 10533 in 2009), V (n = 8518 in 2011), and VI (n = 8018 in 2013). Blood lead levels were analyzed based on clinical variables. Multivariate linear regression analyses were done to find variables associated with elevated blood lead levels. Results: Blood lead levels were higher in males, older age group, smokers, COPD, lower education group, and lower income group (p Conclusion: Smoking status and education level along with old age and male gender were independently associated with higher blood lead levels, however COPD was not, suggesting higher blood lead level in COPD should be attributed to other correlated clinical factors.

BACKGROUND Mobile health (mHealth) is used to strengthen patients’ self-care management, facilitate communication between patients and service providers, provide information to improve health behaviors and decision making, prevent health-related complications, and improve health-related quality of life. Among the chronic diseases, type 2 diabetes is a critical health problem with increasing incidence, prevalence, and complications worldwide. OBJECTIVE This scoping review of systematic reviews and meta-analyses concerning mHealth interventions aimed to examine service platforms, program types, outcomes of interest, current status of research activities, and effectiveness for type 2 diabetes self-care management among community-dwelling adults, and identify research gaps. METHODS This scoping review adopted the method developed by Arksey and O’Malley. The databases searched were Ovid Medline and Ovid EMBASE, and the period was from inception until April 2018. Two reviewers independently screened, selected, and charted studies using a piloted charting form. Discrepancies were resolved by consensus, after which the results were collated, summarized, and thematically analyzed. RESULTS The final sample (N=81) included systematic reviews or meta-analyses reporting the clinical effectiveness of mHealth interventions (n=64), behavioral outcomes related to mHealth interventions (n=47), and the usability of mHealth interventions (n=14). The most common sub-types of mHealth interventions for type 2 diabetes care were patient monitoring (32.5%), treatment adherence (30.7%), and diabetes-related advice and education (20.9%). Mobile devices were most often used to provide such mHealth services (40%), followed by the internet (28.9%). The mHealth intervention strategy that was effective for controlling blood glucose in patients with type 2 diabetes was a multimodal intervention consisting of treatment advice and education, treatment adherence/reminder methods, and patient monitoring. The intervention strategy that showed behavioral effects was the one consisting of treatment adherence/reminder methods and/or patient monitoring. The usability of mHealth interventions was controversial. CONCLUSIONS This scoping review outlined the clinical effects, behavioral effects, and usability of mHealth interventions in literature focused on diabetes self-care management via mHealth technologies. In order to improve clinical and behavioral outcomes, the process of applying mHealth interventions should include strategies for improving interaction between patients and health care service providers. Systematic reviews of mHealth interventions using comprehensive mobile apps, containing at least three major components of treatment advice, reminders, patient monitoring, and social networking services are needed. In addition, systematic reviews on the effectiveness of mHealth interventions in pre-diabetics are needed. CLINICALTRIAL none

The role of palliative surgical resection in recurrent or metastatic gastric cancer is still controversial. A retrospective review was conducted on 689 patients who received palliative chemotherapy for recurrent (n = 307) or primary metastatic (n = 382) gastric cancer. Among 131 patients (89 primary metastatic and 42 recurrent) with surgical resection before chemotherpay, 75 underwent gastrectomy, 42 metastasectomy, and 14 gastrectomy with metastasectomy. The median overall survival (OS) of patients who underwent surgical resection was significantly longer than that of patients who received chemotherapy alone (18 vs. 9 months, p p p p pensity score matching. In addition, the median OS of patients who underwent gross complete resection (n = 54) was significantly longer than that of patients who underwent incomplete resection (n = 77) (30 vs. 15 months, p = 0.002). The present study suggests that judicious use of surgical resection before chemotherapy in recurrent or metastatic gastric cancer patients may result in a favorable outcome, especially when complete resection is achievable.

In preparation for the surge of coronavirus disease 2019 (COVID-19), it is crucial to allocate medical resources efficiently for distinguishing people who remain asymptomatic until the end of the disease. Between January 27, 2020, and April 21, 2020, 517 COVID-19 cases from 13 healthcare facilities in Gyeonggi province, Korea, were identified out of which the epidemiologic and clinical information of 66 asymptomatic patients at the time of diagnosis were analyzed retrospectively. An exposure-diagnosis interval within 7 days and abnormal aspartate aminotransferase levels were identified as characteristic symptom development in asymptomatic COVID-19 patients. If asymptomatic patients without these characteristics at the time of diagnosis could be differentiated early, more medical resources could be secured for mild or moderate cases in this COVID-19 surge.

Body fat distribution is closely related to cardiovascular diseases. We aimed to evaluate the relationship between truncal fat distribution and the extent of coronary atherosclerosis.Total body fat and regional body fat distributions were measured using dual-energy X-ray absorptiometry (DXA) in 746 Korean patients who underwent coronary angiography. The ratios of truncal fat mass to total body fat mass (FMtrunk/FMtotal), truncal fat mass to fat mass in both legs (FMtrunk/FMleg) and truncal fat mass to fat mass in both arms (FMtrunk/FMarm) were calculated as representative parameters for truncal fat accumulation. The extent of coronary atherosclerosis was assessed using the Gensini score.The mean Gensini score of the patients was 21.3 ± 24.4. FMtrunk/FMtotal, FMtrunk/FMleg and FMtrunk/FMarm revealed positive correlations with the Gensini score (r = 0.242, p 0.001; r = 0.219, p 0.001; r = 0.133, p 0.001, respectively). In contrast, body mass index (BMI) and total body fat mass did not correlate with the Gensini score. On multiple regression analysis, FMtrunk/FMtotal was associated with the Gensini score independently of age, gender, BMI and major risk factors of coronary heart disease (B = 0.039, p 0.001).Truncal fat distribution is associated with the extent of coronary atherosclerosis and more clinically relevant to that compared with total body fat or BMI in Korean patients.

Background: Vitamin D is suggested to play a role in airway and systemic inflammation in chronic obstructive pulmonary disease (COPD). Low serum 25-hydroxyvitamin D (25-OHD) levels have been suggested to be associated with lower lung function and poorer exercise capacity in COPD. Objectives: The main purpose of this study was to investigate the effects of vitamin D deficiency on the change in exercise capacity in male COPD patients. Methods: A total of 156 male subjects were selected from the Korean Obstructive Lung Disease cohort. Vitamin D deficiency was subdivided into three subgroups: mild, moderate, and severe deficiency groups. Rapid decline was defined as an annual rate of change in exercise capacity ≥17 m. Exercise capacity was assessed by 6-minute walk distance (6MWD). Results: Significant differences were observed in the serum levels of 25-OHD, the number of patients with vitamin D sufficiency, and moderate-to-severe deficiency between rapid decliners (n = 40) and non-rapid decliners (n = 116). No differences were found between the groups for age, smoking status, lung function, and 6MWD. Multivariate analysis showed that vitamin D deficiency was independently related to rapid decline in exercise capacity (p = 0.028). A statistically significant difference was observed among the subgroups of vitamin D deficiency in terms of the change in exercise capacity (p < 0.001). The annual decline in exercise capacity was prominent in the severe deficiency group (23.1 m/year). Conclusion: This study shows that vitamin D deficiency is associated with rapid decline in exercise capacity in male patients with COPD.

The prognostic significance of Bcl-2, Bcl-6, p53, topoisomerase II, and β-tubulin expression was evaluated in diffuse large B-cell lymphoma (DLBCL) patients treated with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab. Eight-year progression-free survival (PFS, P = 0.006) and overall survival (OS, P = 0.001) of patients with high Bcl-2 expression were significantly inferior to those of patients with low expression without prognostic significance of Bcl-6, p53, topoisomerase II, and β-tubulin expression. High expression of Bcl-2 was associated with poor PFS (P = 0.045) and OS (P = 0.004) only in patients with low international prognostic index (IPI). In multivariate analysis, high expression of Bcl-2 was a significant independent prognostic factor of poor PFS (P = 0.026) and OS (P = 0.007) along with high IPI. In conclusion, the expression of Bcl-2 may be a useful prognostic factor, especially in DLBCL patients with low IPI.

SETTING: A tertiary care academic medical centre.OBJECTIVE: To evaluate the clinical usefulness of C-X-C motif chemokine receptor 3 (CXCR3) ligands in tuberculous pleural effusion (TPE).DESIGN: We recruited 336 patients with pleural effusion due to various causes. Concentrations of interferon-gamma (IFN-γ) and the CXCR3 ligands CXCL9 and CXCL11 were determined using enzyme immunoassays; adenosine deaminase (ADA) activity was measured in pleural fluid and serum.RESULTS: TPE was diagnosed in 106 patients. Non-TB conditions included lung cancer (n = 95), para-pneumonic effusion (n = 52), non-lung malignancy (n = 30), other exudate (n = 24) and transudate (n = 29) disorders. All marker levels in serum samples and pleural fluid were significantly higher in the TPE group. Analyses of receiver operating characteristic curves for differentiating TPE from non-TB effusions produced the following results for the area under the curve (AUC) for CXCL9, CXCL11, IFN-γ and ADA, respectively: 0.982, 0.952, 0.982, and 0.952. Marker AUCs in lymphocytic exudates were also high. Combining the levels of CXCL9, IFN-γ and ADA in pleural fluid improved the diagnostic performance. Serum levels of CXCL9 had the highest AUC (0.848) for diagnosing TPE.CONCLUSION: Levels of CXR3 ligands in pleural effusion are useful for diagnosing TPE.

Background and objective The distribution of body fat is closely related to cardiovascular disease and outcomes, although its impact on patient prognosis after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) has not been evaluated. We investigated the impact of truncal fat distribution on long-term clinical outcomes after DES treatment. Methods In 441 DES-treated patients, dual energy X-ray absorptiometry was performed to assess total and regional body fat distribution after index PCI. The ratio of truncal fat to total body fat mass (%FMtrunk/FMtotal) was calculated as a representative parameter for truncal fat distribution. The primary endpoint was major adverse cardiac events (MACE), a composite of ischemia-driven target vessel revascularization (TVR), non-procedural myocardial infarction, cardiac death at 5 years. Results During the median follow-up duration of 1780 days, MACE occurred in 22.0% of patients, with the highest-quartile group of %FMtrunk/FMtotal having a higher rate than the lowest quartile group (27.8% vs. 15.3%; log rank p = 0.026). The difference was driven by a higher rate of ischemia-driven TVR (25.9% vs. 9.9%; log rank p = 0.008). In multivariable Cox regression analyses, %FMtrunk/FMtotal was independently associated with MACE (hazard ratio: 1.075; 95% CI: 1.022-1.131; p = 0.005), but body mass index (BMI) was not. Conclusions In DES-treated patients, truncal fat distribution is associated with unfavorable clinical outcomes and is more clinically relevant than BMI.

Background: Cardiovascular disease is the most common cause of death in chronic obstructive pulmonary disease (COPD). However, the impact of cardiovascular comorbidities on the prognosis of COPD is not well known. Objectives: This study was performed to investigate the effects of cardiovascular comorbidities on the prognosis of COPD. Methods: We enlisted 229 patients with COPD who underwent comprehensive cardiac evaluations including coronary angiography and echocardiography at Ajou University Hospital between January 2000 and December 2012. Survival analyses were performed in this retrospective cohort. Results: Kaplan-Meier analyses showed that COPD patients without left heart failure (mean survival = 12.5 ± 0.7 years) survived longer than COPD patients with left heart failure (mean survival = 6.7 ± 1.4 years; p = 0.003), and the survival period of nonanemic COPD patients (mean survival = 13.8 ± 0.8 years) was longer than that of anemic COPD patients (mean survival = 8.3 ± 0.8 years; p < 0.001). The survival period in COPD with coronary artery disease (CAD; mean survival = 11.37 ± 0.64 years) was not different from that in COPD without CAD (mean survival = 11.98 ± 0.98 years; p = 0.703). According to a multivariate Cox regression model, a lower hemoglobin level, a lower left ventricular ejection fraction, and the forced expiratory volume in 1 s (FEV1) were independently associated with higher mortality in the total COPD group (p < 0.05). Conclusions: Hemoglobin levels and left ventricular ejection fraction along with a lower FEV1 were identified as independent risk factors for mortality in COPD patients who underwent comprehensive cardiac evaluations, suggesting that multidisciplinary approaches are required in the care of COPD.

SETTING Frequent exacerbation is an important phenotype in chronic obstructive pulmonary disease (COPD), while emphysema is associated with many comorbidities and lung function decline. OBJECTIVE To investigate unique features of frequent exacerbators and test the hypothesis that emphysematous phenotype is associated with frequent exacerbations of COPD. METHODS A total of 380 COPD patients were recruited from 16 hospitals in Korea from June 2005 to April 2012 for analysis. We searched for independent predictors of frequent exacerbators in comparison with non-exacerbators. RESULTS As the severity of emphysema increased, forced expiratory volume in 1 s (FEV₁), and FEV₁/FVC (forced volume capacity) worsened; hyperinflationary features characterised by higher total lung capacity (TLC) were observed (P < 0.05). Frequent exacerbators had lower body mass index (BMI), higher St George's Respiratory Questionnaire (SGRQ) scores, higher residual volume (RV)/TLC, more severe airflow limitation (lower FEV₁ and FEV₁/FVC), lower carbon monoxide diffusion capacity, lower serum protein levels and a higher emphysema index than non-exacerbators (P < 0.05). In multivariate analysis, frequent exacerbators were independently associated with a higher emphysema index, lower serum protein levels and higher RV/TLC (P < 0.05). CONCLUSION Our data show that the severity of emphysema, severe static hyperinflation and serum lower protein levels are independent predictors of frequent exacerbations in COPD patients.

Aims: Cardiovascular disease is one of the main causes of mortality for COPD and atherosclerosis is a root cause of cardiac co-morbidities in COPD. However, it is not clear whether airflow limitation is associated with atherosclerosis irrespective of smoking. Therefore, we attempted to investigate whether airflow limitation is independently associated with peripheral atherosclerosis. Methods: We enrolled 22,466 participants (male = 69.7 %, non-smoker = 44.5 %) who underwent spirometry and brachial-ankle pulse wave velocity (baPWV) for health screening at Ajou University Hospital from January 2010 to December 2015. We defined peripheral atherosclerosis as baPWV≥1400 cm/s and airflow limitation as pre-bronchodilator ratio of FEV1 to FVC Results: Mean baPWV was higher in airflow limitation group than in control group (1477.6 ± 330.7 vs. 1350.7 ± 222.1 cm/s, p Conclusion: FEV1/FVC was an independent predictor of peripheral atherosclerosis both in smokers and non-smokers, suggesting airflow limitation is linked with atherosclerosis irrespective of smoking.

Significantly lower endogenous expression of B-cell translocation gene 2 (BTG2) was observed in human muscle-invasive bladder cancers (MIBC) than matched normal tissues and non-muscle invasive bladder cancers (NMIBC). BTG2 expression was inversely correlated with increased expression of the DNA methyltransferases DNMT1 and DNMT3a in MIBC, but not NMIBC, suggesting a potential role for BTG2 expression in muscle invasion of bladder cancer. Over 90% of tumor tissues revealed strong methylation at CpG islands of the BTG2 gene, compared with no methylation in the normal tissues, implying epigenetic regulation of BTG2 expression in bladder carcinogenesis. By using EJ bladder cancer cells and the demethylating agent decitabine, transcription of BTG2 was shown to be up-regulated by inhibiting DNMT1 expression via modification at CpG islands. DNMT1 binding to the BTG2 gene further regulated BTG2 expression by chromatin remodeling, such as H3K9 dimethylation and H3K4 trimethylation, and Sp1 activation. Induced BTG2 expression significantly reduced EJ cell tumorigenesis and invasiveness together with induction of G2 /M arrest. These results demonstrate an important role for the BTG2(/TIS21/PC3) gene in the progression of bladder cancers, and suggest that BTG2(/TIS21/PC3) is a promising epigenetic target for prevention of muscle invasion in human bladder cancers.

Background: The incidence rate of thyroid cancer has been increasing worldwide in recent years, and it is also the most prevalent cancer when it comes to the number of patients among Korean women. With it, ultrasonographic screening test has also become very common. However, there is still controversy over the performance of this screening test. Therefore, the National Evidence-based Healthcare Collaborating Agency (NECA) organized a Round-table Conference on the issues regarding ultrasonographic screening for thyroid cancer in Korea. The objective of the conference was mainly about delivering worthwhile information reflecting social value for the current situation, which was based on evidence surrounding thyroid cancer screening that relevant experts investigated and agreed on. The significance of this Round-table Conference lies in the fact that we reviewed the current evidence, and we were able to discuss the social value and future direction for ultrasonographic screening in Korea.

Supplemental Digital Content is available in the text, Although concern regarding the increased risk for new-onset diabetes mellitus (NODM) after statin treatment has been raised, there has been a lack of evidence in real-world clinical practice, particularly in East Asians. We investigated whether statin use is associated with risk for NODM in Koreans. We conducted a retrospective cohort study using the clinical research database from electronic health records. The study cohort consisted of 8265 statin-exposed and 33,060 matched nonexposed patients between January 1996 and August 2013. Matching at a 1:4 ratio was performed using a propensity score based on age, gender, baseline glucose levels (mg/dL), and hypertension. The comparative risks for NODM with various statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) were estimated by both statin exposure versus matched nonexposed and within-class comparisons. The incidence of NODM among the statin-exposed group (6.000 per 1000 patient-years [PY]) was higher than that of the nonexposed group (3.244 per 1000 PY). The hazard ratio (HR) of NODM after statin exposure was 1.872 (95% confidence interval [CI], 1.432–2.445). Male gender (HR, 1.944; 95% CI, 1.497–2.523), baseline glucose per mg/dL (HR, 1.014; 95% CI, 1.013–1.016), hypertension (HR, 2.232; 95% CI, 1.515–3.288), and thiazide use (HR, 1.337; 95% CI, 1.081–1.655) showed an increased risk for NODM, while angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker showed a decreased risk (HR, 0.774; 95% CI, 0.668–0.897). Atorvastatin-exposed patients showed a higher risk for NODM than their matched nonexposed counterparts (HR, 1.939; 95% CI, 1.278–2.943). However, the risk for NODM was not significantly different among statins in within-class comparisons. In conclusion, an increased risk for NODM was observed among statin users in a practical healthcare setting in Korea.

Background: To date, no clinical parameter has been associated with the decline in lung function other than emphysema severity in COPD. Objectives: The main purpose of this study was to explore whether the rate of lung function decline differs between COPD patients with and without exertional desaturation. Methods: A total of 224 subjects were selected from the Korean Obstructive Lung Disease cohort. Exertional desaturation was assessed using the 6-min walk test (6MWT), and defined as a post-exercise oxygen saturation (SpO2) of Results: There was a significant difference between the desaturator and non-desaturator groups in terms of the change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) over a 3-year period of follow-up (p = 0.006). The mean rate of decline in FEV1 was greater in the desaturator group (33.8 ml/year) than in the non-desaturator group (11.6 ml/year). A statistically significant difference was also observed between the two groups in terms of the change in the St. George's Respiratory Questionnaire (SGRQ) total score over 3 years (p = 0.001). Conclusions: This study suggests, for the first time, that exertional desaturation may be a predictor of rapid decline in lung function in patients with COPD. The 6MWT may be a useful test to predict a rapid lung function decline in COPD.

Background: In COPD, coronary artery disease (CAD) is a frequent co-morbidity and cardiovascular disease is the most common cause of death. When coronary angiography was performed, the Gensini score is used for the assessment of CAD severity. This study was performed to evaluate the clinical impact of Gensini score in COPD. Methods: We retrospectively reviewed 191 patients with COPD (male 90.1%, mean age 68.5 ± 8.9 years, smoker 86.2%) who had undergone coronary angiography in Ajou University Hospital from Jan 2000 to Dec 2012. The extent of CAD in the entire coronary arterial tree was assessed by Gensini score. Comparative analyses between high Gensini group (≥4 points; median value or more) and low Gensini group ( Results: High Gensini group was more frequently associated with triple vessel CAD (37.2% vs. 1.0%, p 1 (66.4 ± 16.9 vs 64. 9 ± 19.0, p=0.583) and prevalence of hypertension (59.6% vs. 57.7%, p=0.796) did not differ between two groups. High Gensini group was independently related to triple vessel CAD (OR 3.51, 95% CI 1.77 – 6.94) and myocardial infarction (OR 5.38, 95% CI 1.83 – 15.82). Conclusion: Our data suggest that high Gensini score in COPD was independently associated with cardiac co-morbidities such as triple vessel CAD and myocardial infarction.

OBJECTIVES As of November 2011, the Korean government recalled and banned humidifier disinfectants (HDs) from the market, because four case-control studies and one retrospective epidemiological study proved the association between HDs and lung injury of unknown cause. The report reviewed the causal role of HDs in lung injury based on scientific evidences. METHODS A careful examination on the association between the HDs and lung injury was based on the criteria of causality inference by Hill and the US Surgeon General Expert Committee. RESULTS We found that all the evidences on the causality fulfilled the criteria (strength of association, consistency, specificity, temporality, biologic gradient, plausibility, coherence, experiment, analogy, consideration of alternative explanations, and cessation of exposure), which proved the unknown cause lung injury reported in 2011 was caused by the HDs. In particular, there was no single reported case of lung injury since the ban in selling HDs in November 2011 as well as before the HDs were sold in markets. CONCLUSIONS Although only a few epidemiological studies in Korea have evaluated the association between lung injury and the use of HDs, those studies contributed to proving the strong association between the use of the HDs and lung injury, based on scientific evidence.

BACKGROUND The functional significance of an intermediate coronary lesion is crucial for determining the treatment strategy, but age-related changes in cardiovascular function could affect the functional significance of an epicardial stenosis. The aim of this study was therefore to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease (CAD). METHODS AND RESULTS Intracoronary pressure measurements and intravascular ultrasound (IVUS) were performed in 178 left anterior descending coronary arteries with intermediate stenosis. The morphological characteristics and FFR of 91 lesions in patients

Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB. We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into “fast” and “slow” based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as “significant.” In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P

Papillary thyroid carcinoma is the most common type of thyroid malignancy, and CD56, a neural cell adhesion molecule, is typically down-regulated in almost all cases of papillary thyroid carcinoma. Homeobox B9 is a transcription factor, belongs to the products of the homeobox transcription factor gene family, and has been known to regulate transcription of CD56 and to promote tumorigenicity and metastasis in some malignancies. In this study, we investigated the expression and relation of homeobox B9 to reduced expression of CD56 in papillary thyroid carcinomas and also a relationship between their expression and clinicopathologic parameters. Therefore, we performed CD56 and homeobox B9 immunohistochemical staining on 72 papillary thyroid carcinomas and Western blotting on 31 papillary thyroid carcinomas. CD56 protein staining revealed that it was reduced or absent in 65 papillary thyroid carcinomas (90.3%) and was related to silencing of homeobox B9 (77.8%) (P = .003). The loss of homeobox B9 expression was associated with extrathyroidal extension (P = .002), pathologic stage of tumor (P = .01), and age older than 45 years (P = .032). However, the CD56 staining did not reveal any significant relationship with clinicopathologic features (P > .05). In conclusion, reduced expression of CD56 is associated with homeobox B9 in papillary thyroid carcinomas. Furthermore, silencing of homeobox B9 is more common in older age and is linked to extrathyroidal extension and advanced pathologic stage of papillary thyroid carcinoma.