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Background Pirfenidone slows the progression of idiopathic pulmonary fibrosis. We investigated the efficacy and safety of pirfenidone by dose and disease severity in real-world patients with idiopathic pulmonary fibrosis.Methods This multi-centre retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were recorded. Efficacy was analysed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity (DL CO ) of the lungs for carbon monoxide.Results The mean %FVC predicted and %DL COpredicted were 72.6±13.1% and 61.4±17.9%, respectively. Pirfenidone treatment lasted 16.1±9.0 months. In the standard-dose (1800 mg/day) group, the mean %FVC predicted was -6.56% (95% CI -9.26, -3.87) per year pre-pirfenidone treatment, but -4.43% (95% CI -5.87, -3.00) per year post-treatment. In the lower-dose group, the mean %FVC predicted was -4.96% (95% CI -6.82, -3.09) per year pre-pirfenidone treatment, but -1.79% (95% CI -2.75, -0.83) per year post-treatment. The FVC decline rate was significantly reduced regardless of GAP stage. However, the DL CO decline rate was significantly reduced in the GAP stage II–III group, but not stage I group. Adverse events and mortality were similar across dose groups, but were more frequent in the GAP stage II–III group than in the stage I group.Conclusions The effect of pirfenidone on reducing disease progression persisted even with a consistent lower dose of pirfenidone.Trial registration Retrospectively registered

BACKGROUND: Although low-dose computed tomography (LDCT) screening is known to be effective for the detection of lung cancers localized in peripheral lung regions at a curable stage, limited data is available regarding the characteristics and outcomes of central lung cancers diagnosed in a screening cohort. This study aimed to determine whether LDCT screening could effectively detect central lung cancers at an early stage and offer survival benefits. METHODS: We analyzed 52,615 adults who underwent lung cancer screening with LDCT between May 2003 and Dec 2019 at a tertiary center in South Korea. Characteristics and outcomes of those diagnosed with lung cancer, stratified by screen-detection status and cancer location, were evaluated. RESULTS: A total of 352 individuals (281 screen-detected, 71 non-screen-detected) were diagnosed with lung cancer. Compared to screen-detected cancers, non-screen-detected cancers tended to be centrally-located (11.4% vs. 64.8%, P

Background: Although a rapid response system (RRS) can reduce the incidence of cardiopulmonary resuscitation (CPR) in general wards, avoidable CPR cases still occur. This study aimed to investigate the incidence and causes of avoidable CPR. Methods: We retrospectively reviewed the medical records of all adult patients who received CPR between April 2013 and March 2016 (35 months) at a tertiary teaching hospital where a part-time RRS was introduced in October 2012. Four experts reviewed all of the CPR cases and determined whether each event was avoidable. Results: A total of 192 CPR cases were identified, and the incidence of CPR was 0.190 per 1,000 patient admissions. Of these, 56 (29.2%) were considered potentially avoidable, with the most common cause being doctor error (n=32, 57.1%), followed by delayed do-not-resuscitate (DNR) placement (n=12, 21.4%) and procedural complications (n=5, 8.9%). The percentage of avoidable CPR was significantly lower in the RRS operating time group than in the RRS non-operating time group (20.7% vs. 35.5%; P=0.026). Among 44 avoidable CPR events (excluding cases related to DNR issues), the rapid response team intervened in only three cases (6.8%), and most of the avoidable CPR cases (65.9%) occurred during the non-operating time. Conclusions: A significant number of avoidable CPR events occurred with a well-functioning, part-time RRS in place. However, RRS operation does appear to lower the occurrence of avoidable CPR. Thus, it is necessary to extend RRS operation time and modify RRS activation criteria. Moreover, policy and cultural changes are needed prior to implementing a full-time RRS.

Background Current microbiologic criteria for nontuberculous pulmonary disease (NTM-PD) require cultures with two separate sputum specimens or one non-sputum specimen. However, data on NTM-PD prognosis following non-sputum culture-based diagnosis are limited. We compared the prognosis of NTM-PD diagnosed using non-sputum and sputum cultures. Methods We analyzed 1020 patients in whom NTM was isolated; they were divided into the sputum NTM isolation (n=170), sputum NTM-PD (n=688), and non-sputum NTM-PD groups (n=162). Initiation of therapy and radiographic aggravation was compared between groups. Results Overall median observation time was 44.3 months (interquartile range, 28.0–70.2). Fewer non-sputum NTM-PD patients initiated treatment than sputum NTM-PD patients (p

Aims Rifampicin is a key drug for the treatment of tuberculosis (TB). Little is known for the relationship between the rifampicin pharmacokinetics and genetic polymorphisms in the Asian population. We aimed to investigate relationship between genetic polymorphism of SLCO1B1 and rifampicin exposure and its impact on clinical outcomes in Korean patients with active pulmonary TB. Methods From February 2016 to December 2019, patients with active pulmonary TB who were taking rifampicin for >1 week were prospectively enrolled. Serial or 1-time blood sampling was conducted to determine rifampicin concentrations. The genotype of 4 single nucleotide polymorphisms of SLCO1B1 was determined. To estimate the drug clearance and exposure, population pharmacokinetics analysis was conducted. Clinical outcomes such as time to acid-fast bacteria culture conversion, chest radiograph score changes from baseline, and all-cause mortality were also evaluated. The exposure among different SLCO1B1 genotype was compared and relationship between drug exposure and clinical outcomes were explored. Results A total of 105 patients (70 males and 35 females) were included in the final analysis. The mean age of patients was 55.4 years. The mean drug clearance and exposure were 13.6 L/h and 57.9 mg h/L, respectively. The genetic polymorphisms of SLCO1B1 were not related to rifampicin clearance or exposure. As the rifampicin exposure increased, the chest radiographs improved significantly, but the duration of acid-fast bacteria culture conversion was not related to the drug exposure. Conclusion SLCO1B1 gene polymorphisms did not influence rifampicin concentrations and clinical outcomes in Korean patients with active pulmonary TB.

The purpose of this study is to explore the effects of Diplectria barbata (Wall. Ex C.B. Clarke) Franken & Roons (DFR) on wound healing, antioxidant and aging in Normal Human Dermal Fibroblast cell (NHDF) cells and mouse skin models. We investigated the effects of the aging process in vitro and in vivo. DFRtreated NHDF cells showed a concentration-dependent increase in the expression of extracellular matrix (ECM) proteins (Collagen-2.5-fold increase at 50 μg/ml, Elastin-1.5-fold increase at 1μg/ml) as well as an increase in proteins related to cell survival, differentiation, and development, while expression of aging proteins such as matrix metalloproteinase 3 (MMP-3) was decreased (5-fold decrease at 50 μg/ml). DFR treatment also led to enhanced expression of antioxidant proteins such as nuclear factor erythroid 2-related factor 2 (10-fold increase at 50 μg/ml) and heme oxygenase 1 (1.5-fold increase at 25 μg/ml). To further investigate the antioxidative effects of DFR extracts, the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities were also evaluated. DFR extracts improved wound healing and resulted in increased expression of ECM proteins, while enzymes involved in collagen degradation, including MMP-3, were decreased in NHDF cells as well as in a mouse model. This study demonstrates the anti-aging, antioxidant, and wound healing properties of DFR extracts. Therefore, DFR extracts present may facilitate skin protection and care.

Background Cell division is regulated by protein kinase B (PKB)-mediated FCH domain only 1 (FCHO1) phosphorylation. Methods FCHO1560−571, a synthetic water-soluble peptide, was generated from the PKB substrate motif 560PPRRLRSRKVSC571 found in the human FCHO1 protein. Results In this study, we found that in vitro FCHO1560−571 inhibits cell proliferation via PKB/ERK/SMAD4 pathways in KRAS-mutated A549 lung cancer cells. In addition, FCHO1560−571, at effective doses of 15 and 30 mg/kg, significantly suppressed tumor growth and decreased the size and weight of tumors in A549-xenograft mice. Conclusion These results suggest that the FCHO1560−571 peptide could be a potential therapy for lung cancer.

The development of skeletal muscle requires progression of a highly ordered cascade of events comprising myogenic lineage commitment, myoblast proliferation, and terminal differentiation. The process of myogenesis is controlled by several myogenic transcription factors that act as terminal effectors of signaling cascades and produce appropriate developmental stage-specific transcripts. PHD finger protein 20 (PHF20) is a multidomain protein and subunit of a lysine acetyltransferase complex that acetylates histone H4 and p53, but its function is unclear. Notably, it has been reported that PHF20 knockout mice die shortly after birth and display a wide variety of phenotypes within the skeletal and hematopoietic systems. Therefore, the putative role of PHF20 in myogenic differentiation was further investigated. In the present study, we found that protein and mRNA expression levels of PHF20 were decreased during myogenic differentiation in C(2)C(12) cells. At the same time, Yin Yang 1 (YY1) was also decreased during myogenic differentiation. PHF20 overexpression increased YY1 expression during myogenic differentiation, together with a delay in MyoD expression. PHF20 expression enhanced the transcriptional activity of YY1 while shRNA-mediated depletion of PHF20 resulted in the reduction of YY1 promoter activity in C(2)C(12) cells. In addition, PHF20 directly bounds to the YY1 promoter in C(2)C(12) cells. In a similar manner, YY1 expression was elevated while myosin heavy chain expression was decreased in PHF20 transgenic (TG) mice. Histological analysis revealed abnormalities in the shape and length of muscles in PHF20-TG mice. Furthermore, PHF20-TG muscles slowly regenerated after cardiotoxin injection, indicating that PHF20 affected muscle differentiation and regeneration after injury in vivo. Taken together, these results suggested that PHF20 plays an important role in myogenic differentiation by regulating YY1.

Aim The efficacy and safety of pirfenidone have been previously demonstrated in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, the effect of pirfenidone in patients with advanced IPF remains unclear. Here, we investigated the effects of pirfenidone against advanced IPF in a real-world setting. Methods A prospective nationwide post-marketing study was conducted on 258 patients from 10 Korean institutions. Patients with a predicted forced vital capacity (FVC) less than 50% or a diffusing capacity of the lung for carbon monoxide (DLco) less than 35% at baseline were classified as the advanced IPF group. Results Of 219 patients included in the analysis, the majority were male (76.3%); the mean age was 67.3 years, and the advanced group accounted for 17.8% of the patients. The median treatment duration was 298 days. Among the subjects, 86.3% experienced adverse events (AEs), of which a decreased appetite (32.4%) and a photosensitivity reaction (13.7%) were the most frequent. The incidence of AEs was similar between the advanced and non-advanced groups (92.3% vs. 85.0%, respectively; p = 0.229). Although the overall discontinuation rate was higher in the advanced group than in the non-advanced group (74.4% vs. 50.0%, respectively; p = 0.006), the percentages of the patients who discontinued treatment as a result of AEs were similar in both groups (20.5% vs. 23.3%, respectively; p = 0.704). In all patients, the rates of decline in the predicted FVC and DLco over 48 weeks were − 4.3 ± 1.3% and − 4.4 ± 1.7%, respectively. There was no between-group difference in the rate of lung function decline. Conclusions Pirfenidone used for the treatment of patients with IPF in a real-world setting was well tolerated, with an acceptable safety profile and a consistent therapeutic effect, regardless of the disease severity. Trial Registration ClinicalTrials.gov NCT03761082; the trial was retrospectively registered on December 3, 2018. Electronic supplementary material The online version of this article (10.1007/s12325-020-01328-8) contains supplementary material, which is available to authorized users.

Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years, 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration &lt, 50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.

Purpose Impairment of diaphragmatic function is one of the main pathophysiological mechanisms of chronic obstructive pulmonary disease (COPD) and is known to be related to acute exacerbation. Ultrasonography (US) allows for a simple, non-invasive assessment of diaphragm kinetics. The purpose of this study was to investigate the changes in diaphragmatic function during acute exacerbation of COPD, by US. Methods This single-center, prospective study included patients with acute exacerbation of COPD symptoms. US measurements were performed within 72 hrs after exacerbation and after improvement of symptoms. Diaphragmatic excursion and its thickening fraction (TF) were measured as markers of diaphragmatic function. TF was calculated as (thickness at end inspiration - thickness at end expiration)/thickness at end expiration. Results Ten patients were enrolled. All patients were male, and the mean age was 79.8 years. The TF of the right diaphragm showed a significant increase from the initial to the follow-up values (80.1 ± 104.9 mm vs. 159.5 ± 224.6 mm, p = 0.011); however, the diaphragmatic excursion did not vary significantly between the initial and follow-up values (22 ± 6 mm vs 23 ±12 mm). The change in excursion between the stable and exacerbation periods was positively correlated with time to the next exacerbation and negatively correlated with the time taken to recover from the exacerbation. Conclusion These data support the possibility that a defect in diaphragm thickening is related to acute exacerbation of COPD.

1,2-Dichloropropane (1,2-DCP) has been used as an industrial solvent and a chemical intermediate, as well as in soil fumigants. Human exposure may occur during its production and industrial use. The target organs of 1,2-DCP are the eyes, respiratory system, liver, kidneys, central nervous system, and skin. Repeated or prolonged contact may cause skin sensitization. In this study, 1,2-DCP was dissolved in corn oil at 0, 2.73, 5.75, and 8.75 mL/kg. The skin of mice treated with 1,2-DCP was investigated using western blotting, hematoxylin and eosin staining, and immunohistochemistry. 1,2-DCP was applied to the dorsal skin and both ears of C57BL/6J mice. The thickness of ears and the epidermis increased significantly following treatment, and the appearance of blood vessels was observed in the dorsal skin. Additionally, the expression of vascular endothelial growth factor, which is tightly associated with neovascularization, increased significantly. The levels of protein kinase-B (PKB), phosphorylated PKB, mammalian target of rapamycin (mTOR), and phosphorylated mTOR, all of which are key components of the phosphoinositide 3-kinase/PKB/mTOR signaling pathway, were also enhanced. Taken together, 1,2-DCP induced angiogenesis in dermatitis through the PI3K/PKB/mTOR pathway in the skin.

Doxorubicin is a widely used DNA damage-inducing anti-cancer drug. However, its use is limited by its dose-dependent side effects, such as cardiac toxicity. Cholesterol-lowering statin drugs increase the efficacy of some anti-cancer drugs. Cholesterol is important for cell growth and a critical component of lipid rafts, which are plasma membrane microdomains important for cell signaling. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMG-CR) is a critical enzyme in cholesterol synthesis. Here, we show that doxorubicin downregulated HMG-CR protein levels and thus reduced levels of cholesterol and lipid rafts. Cholesterol addition attenuated doxorubicin-induced cell death, and cholesterol depletion enhanced it. Reduction of HMG-CR activity by simvastatin, a statin that acts as an HMG-CR inhibitor, or by siRNA-mediated HMG-CR knockdown enhanced doxorubicin cytotoxicity. Doxorubicin-induced HMG-CR downregulation was associated with inactivation of the EGFR-Src pathway. Furthermore, a high-cholesterol-diet attenuated the anti-cancer activity of doxorubicin in a tumor xenograft mouse model. In a multivulva model of Caenorhabditis elegans expressing an active-EGFR mutant, doxorubicin decreased hyperplasia more efficiently in the absence than in the presence of cholesterol. These data indicate that EGFR/Src/HMG-CR is a new pathway mediating doxorubicin-induced cell death and that cholesterol control could be combined with doxorubicin treatment to enhance efficacy and thus reduce side effects.

The risk of lung cancer is higher in idiopathic pulmonary fibrosis (IPF) because both conditions share common risk factors. However, no standard treatment modality for LC in IPF exists due to rare incidence, poor prognosis, and acute exacerbation (AE) of IPF during treatment. We aimed to determine the efficacy of LC treatments and the prognosis in LC patients with IPF according to the LC stage and GAP (gender [G], age [A], and two physiology variables [P]) stage. From 2003 to 2016, 160 retrospectively enrolled patients were classified according to the LC clinical stage and GAP stage. The average (±standard deviation) patient age was 70.1 ± 8.2 years; the cohort predominantly comprised men (94.4%). In GAP stage I, surgery was significantly associated with better survival outcomes in LC. In contrast, no treatment modality yielded significant clinical improvement in GAP stage II/III. The incidences of AE in IPF and its mortality during treatment were 13.8% and 6.3%, respectively. AE occurred commonly in advanced GAP stage. Active treatment should be considered in GAP stage I. The performance status and LC stage should be considered when deciding about the necessity of surgery for patients in advanced GAP stage.

Introduction. Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer development, and small cell lung cancer (SCLC) comprises 15-20% of lung cancers with IPF. The objective of this study was to investigate survival outcomes and treatment-related complications according to GAP (gender, age, and physiology) stage in patients having SCLC with IPF (SCLC-IPF). Materials and Methods. Retrospectively collected data of SCLC-IPF patients from two tertiary care university hospitals in South Korea were reviewed. A total of 59 SCLC-IPF patients were identified and categorized according to GAP stage, which was proposed by Ley et al. in 2012 to predict the prognosis of IPF. Survival outcomes and treatment-related complications were compared between the two groups. Results. In a total of 59 patients, the median age was 71 years and 58 (98.3%) were male. In a comparison of the median overall survival (OS) according to GAP stage, median OS of the advanced GAP stage group was significantly shorter than median OS of GAP stage I group (7.1 months vs. 16.1 months; p = 0.002). Treatment-related complications occurred more frequently in the advanced GAP stage group; advanced GAP stage was the only predictor that exhibited a significant association with the incidence of acute exacerbation of IPF. Conclusions. Inferior survival outcome and higher incidence of treatment-related pulmonary toxicities were noted in the advanced GAP stage group. Furthermore, advanced GAP stage was the only predictor of treatment-related acute exacerbation of IPF. Physicians should thus consider GAP stage, which reflects the severity of IPF, during treatment of SCLC-IPF.

Introduction The incidence of lung cancer among never-smokers has been increasing rapidly. The U. S. National Lung Screening Trial and the NELSON trial showed that screening using low-dose computerized tomography (LDCT) effectively reduced lung cancer mortality among heavy smokers. However, its effectiveness in never-smokers has not been well investigated. This study investigated the role of LDCT in lung cancer screening among never-smokers. Methods The study was designed as a single-center, retrospective cohort study. We analyzed the data on patients who underwent LDCT screening between May 2003 and June 2016. Nodules detected by computerized tomography were classified according to the Lung Imaging Reporting and Data System criteria. The detection rate and lung cancer outcomes (type of cancer, staging of lung cancer, and mortality) according to smoking history were determined. Results Of the 28,807 enrolled patients, 12,176 were never-smokers; of these patients, 7744 (63.6%) were women and 1218 (10.0%) were found to have lung nodules. Overall, lung cancer was diagnosed in 55 never-smokers (0.45%). In contrast, lung cancer was diagnosed in 143 (0.86%) of the 16,631 ever-smokers. Of the never-smokers with lung cancer, 51 (92.7%) presented with stage I disease, and all patients had adenocarcinomas. Conclusions In the never-smoker population, LDCT screening helped to detect a significant number of lung cancers. Most of these lung cancers were detected at a very early stage. The positive results of the National Lung Screening Trial in the United States and the NELSON trial may have established the value of LDCT screening for heavy smokers, but future research should consider the value of using LDCT screening in the never-smoker population.

Potent P2Y12 blockers are preferred in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). However, the risk of bleeding remains a major concern. We assessed the association of potent P2Y12 blockers with ischemic and bleeding outcomes in patients with NSTEMI.From the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 4927 patients with NSTEMI receiving drug-eluting stents (DES) were divided into potent P2Y12 blocker (ticagrelor or prasugrel, n=901) and clopidogrel (n=3180) groups. Propensity-matched 12-month ischemic and bleeding events were compared. Patients who received anticoagulants or who discontinued P2Y12 blockers or switched between potent P2Y12 blockers and clopidogrel were excluded.In the overall population, patients at higher ischemic and bleeding risks more often received clopidogrel. After propensity matching (n=901 in each group), 12-month rates of major adverse cardiac and cerebrovascular events were lower (7.3% vs. 10.1%, p=0.038), but Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were higher (5.9% vs. 2.2%, p0.001) with potent P2Y12 blockers. Twelve-month rates of death from any cause, MI, stroke, or TIMI major bleeding were not different. On multivariate analysis, 12-month risk of TIMI major or minor bleeding was higher with B2 or C lesion, potent P2Y12 blocker use, body weight60kg, and lower with time to PCI12h and radial artery access.In patients with NSTEMI receiving DES, potent P2Y12 blockers were associated with reduced ischemic but increased bleeding risk with similar net clinical benefits.

Summary Background Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis. Methods We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul–Seongnam, South Korea). Patients, aged 20–80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460. Findings Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI −4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and −1·1% (−11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient. Interpretation Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis. Funding Ministry of Health and Welfare, South Korea.

Background: Laryngeal microsurgery (LMS) causes hemodynamic instability and postoperative agitation, cough, pain, nausea, and vomiting. Moreover, because of a short operation time, it is associated with challenging anesthetic management. The aim of this study was to compare the usefulness of continuous administration of dexmedetomidine and remifentanil in inducing general anesthesia in patients undergoing LMS. Methods: This is a prospective randomized control design. Continuous intravenous infusion of dexmedetomidine (group D) or remifentanil (group R) was administered from 10 minutes before the induction of anesthesia to the end of surgery. In both groups, 1.5 mg/kg propofol and 0.5 mg/kg rocuronium were administered for the induction of anesthesia, and desflurane were titrated during the measurement of the bispectral index. We recorded hemodynamic data, recovery time, grade of cough, pain score, and analgesic requirements during the perioperative period. Results: 61 patients were finally analyzed (30 for group D, 31 for group R). The incidence of moderate to severe postoperative sore throat was higher in group R than in group D (42% vs 10%, P = .008), and the quantity of rescue fentanyl used in post-anesthesia care unit was significantly higher in group R than in group D (23.2 ± 24.7 mg vs 3.3 ± 8.6 mg; P

GATA transcription factors (TFs) are widespread eukaryotic regulators whose DNA-binding domain is a class IV zinc finger motif (CX2CX17–20CX2C) followed by a basic region. We identified 262 GATA genes (389 GATA TFs) from seven Populus genomes using the pipeline of GATA-TFDB. Alternative splicing forms of Populus GATA genes exhibit dynamics of GATA gene structures including partial or full loss of GATA domain and additional domains. Subfamily III of Populus GATA genes display lack CCT and/or TIFY domains. 21 Populus GATA gene clusters (PCs) were defined in the phylogenetic tree of GATA domains, suggesting the possibility of subfunctionalization and neofunctionalization. Expression analysis of Populus GATA genes identified the five PCs displaying tissue-specific expression, providing the clues of their biological functions. Amino acid patterns of Populus GATA motifs display well conserved manner of Populus GATA genes. The five Populus GATA genes were predicted as membrane-bound GATA TFs. Biased chromosomal distributions of GATA genes of three Populus species. Our comparative analysis approaches of the Populus GATA genes will be a cornerstone to understand various plant TF characteristics including evolutionary insights.

Histone deacetylase 6 (HDAC6)-selective inhibitors are potent anticancer agents that are gaining increasing attention and undergoing various developments. These have been approved or are under clinical trials for use with other anticancer agents, such as pomalidomide, anti-programmed death-ligand 1 antibody and paclitaxel, for various types of cancer, including solid tumors. In the present study, a second generation HDAC6-selective inhibitor, ACY-241 (citarinostat), and a novel inhibitor, A452, exhibited synergistic anticancer effects with paclitaxel in AT-rich interaction domain 1A-mutated ovarian cancer in vitro. Co-treatment of paclitaxel and the two HDAC6 inhibitors synergistically decreased cell growth and viability of TOV-21G. Furthermore, the protein expression levels of pro-apoptotic markers, such as poly(ADP-ribose) polymerase, cleaved caspase-3, Bak and Bax, were increased, whereas the expression levels of anti-apoptotic markers, such as Bcl-xL and Bcl-2, were decreased synergistically. Treatment with all drug combinations increased the portion of apoptotic cells in fluorescence-activated cell sorting analysis. These results demonstrated synergy between paclitaxel and HDAC6-selective inhibitors, providing further impetus for clinical trials of combination therapy using HDAC6-selective inhibitors, not only in ovarian cancer but also in other tumors.

Background East Asians treated with potent P2Y12 inhibitors, prasugrel or ticagrelor exhibit more potent platelet inhibition than clopidogrel. Whether half-dose de-escalation strategy would improve optimal platelet reactivity at maintenance in East Asian patients with acute coronary syndrome (ACS) remains uncertain. Method In de-escalation strategy single center study, eligible Korean ACS patients (n=96) were assigned to receive standard-dose ticagrelor (n=33), prasugrel (n=28), followed by half-dose reduction at 1 month for maintenance, and clopidogrel (n=35) as control. Platelet reactivity was measured by VerifyNow, light transmittance aggregometry (LTA) and multiple electrode aggregometry (MEA). The investigators aim to compare optimal platelet reactivity status (OPR, defined as 85–208 P2Y12 reaction unit [PRU] for VerifyNow (VN), 16%–47% for LTA and 19–46 U for MEA) among 3 different platelet function tests at 3 months post PCI. Results At 3 months, ticagrelor achieved significantly lower PRU (17 [6–51] vs. 95 [61–151] vs. 172 [111–204]) than prasugrel and clopidogrel, resulting OPR rate 10% vs. 57.7% vs. 60.0%, respectively. Similar results were observed at LTA method (2% [0–12] in ticagrelor vs. 18% [13–22] in prasugrel vs. 18% [11–30] in clopidogrel), with OPR rate 11.8% vs. 69.2% vs. 50.0%, respectively. However, platelet reactivity was similar by MEA method (16 [13–20] in ticagrelor vs. 17 [13–22] in prasugrel vs. 19 [14–28] in clopidogrel), with OPR rate 33.3% vs. 40.0% vs. 42.0%, respectively (all p>0.005). Among the three tests, resulting higher correlation between VN and LTA (r=0.745), MEA and LTA vs. MEA and VN showed lower correlations (r=0.412 and r=0.303). (Fig.) Conclusion In Korean ACS patients with half-dose de-escalation strategy after 1 month, OPR rate in ticagrelor is still rare during 3-month treatment by VN and LTA methods, however, prasugrel appears comparable to clopidogrel. VN/LTA might overestimate platelet function than MEA or MEA underestimate OPR rate than VN/LTA. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): National Research Foundation of Korea

To determine the accuracy of CT-guided percutaneous transthoracic needle lung biopsy (PTNB) for the diagnosis of malignancy and the associated complication rates in patients with idiopathic pulmonary fibrosis (IPF). This retrospective study included 91 CT-guided PTNBs performed in 80 patients with IPF from April 2003 through December 2016. Data regarding patients, target lesions, procedures, complications, and pathological reports were collected, and the final diagnosis was made. The diagnostic accuracy, sensitivity, specificity, percentage of nondiagnostic results, and complication rates were determined. Multivariable logistic regression analyses were performed to identify risk factors for nondiagnostic results and major complications. Three biopsies (technical failure [n = 2] and undetermined final diagnosis [n = 1]) were excluded from the diagnostic accuracy calculation. The diagnostic accuracy, sensitivity, and specificity were 89% (78/88), 90% (62/69), and 84% (16/19), respectively. The percentage of nondiagnostic results was 34% (30/88). Lesion size ≤ 3 cm (odds ratio [OR], 8.8; 95% confidence interval [CI], 2.5–31.2; p = 0.001) and needle tip placement outside the target lesion (OR, 13.7; 95% CI, 1.4–132.2; p = 0.02) were risk factors for nondiagnostic results. The overall and major complication rates were 51% (46/91) and 12% (11/91), respectively. The presence of honeycombing along the path of the needle (OR, 11.2; 95% CI, 1.4–89.1; p = 0.02) was an independent risk factor for major complications. CT-guided PTNB shows a relatively reasonable accuracy in diagnosing malignancy in patients with IPF. The complication rate may be high, especially when the needle passes through honeycomb lesions. • In patients with idiopathic pulmonary fibrosis (IPF), CT-guided percutaneous transthoracic needle lung biopsy (PTNB) showed a relatively reasonable accuracy for the diagnosis of malignancy. • Target lesion size ≤ 3 cm and biopsy needle tip placement outside the target lesion were risk factors for nondiagnostic results of CT-guided PTNB. • The complication rate may be high, especially in cases where the biopsy needle passes through honeycomb lesions.

It is widely acknowledged that cancer cell energy metabolism relies mainly on anaerobic glycolysis; this phenomenon is described as the Warburg effect. However, whether the Warburg effect is caused by genetic dysregulation in cancer or is the cause of cancer remains unknown. The exact reasons and physiology of this abnormal metabolism are unclear; therefore, many researchers have attempted to reduce malignant cell growth in tumors in preclinical and clinical studies. Anticancer strategies based on the Warburg effect have involved the use of drug compounds and dietary changes. We recently reviewed applications of the Warburg effect to understand the benefits of this unusual cancer-related metabolism. In the current article, we summarize diet strategies for cancer treatment based on the Warburg effect.

The incidence of pulmonary nontuberculous mycobacterial (NTM) infection is high in patients with underlying lung disease such as bronchiectasis. Although previous studies have reported many risk factors contributing to the development of NTM-lung disease (LD), only a few reports on the relationship of the characteristics of patients, such as body mass index (BMI), skeletal mass, and fat mass, with NTM-LD have been published. We aimed to investigate the association between these parameters and NTM-LD in patients with bronchiectasis. A monocentric retrospective study in a university hospital was conducted over 4 years (2013–2016). Parameters including BMI, skeletal mass, and fat mass were measured using bioelectrical impedance analysis in noncystic fibrosis bronchiectasis patients. Patients were grouped by the presence or absence of NTM-LD, and the differences in BMI, skeletal mass, and fat mass between the 2 groups were compared. In the NTM-LD group, the progression of disease was also followed. Two hundred forty-five patients with bronchiectasis were enrolled in the study. One hundred six subjects (48%) had NTM-LD. These patients with NTM-LD were predominantly female, and had a significantly lower body weight (58.20 ± 8.84 vs 54.16 ± 8.99, P

Alpha-Methylacyl-CoA racemase (AMACR), which was initially discovered as a prostate cancer marker, is critical for the chiral inversion mechanism of branched-chain fatty acids. However, the function of AMACR in brain tumors has not been investigated. In this study, AMACR appeared to be involved in glioblastoma. The protein and mRNA levels of AMACR were highly elevated in glioblastoma. Downregulation of AMACR inhibited cell proliferation. Comprehensive analysis of the public REMBRANDT GBM dataset also confirmed that the level of AMACR expression was correlated with the clinical prognosis of glioma patients. In summary, these findings indicate that AMACR expression is increased in a glioblastoma cell line and glioma patients, suggesting that AMACR might be a potential diagnostic marker and therapeutic target for cancer, including glioma.

Lung cancer is the most common cause of cancer-associated death worldwide. Most patients with non-small cell lung cancer die within several years of the initial diagnosis, and new therapies are desperately needed. Transmembrane protein (TMEM) 39AS41, a synthetic peptide, was generated from the protein kinase B substrate motif (34)GLRNRNGSAIGLPVP(48) found in the human TMEM39A protein. Myristic acid was conjugated to the N-terminus of the peptide to confer cell permeability. In this study, we found that in vitro TMEM39AS41 peptide led to cell death via inhibition of inflammation/autophagy pathways in KRAS-mutated cell and tissues. In addition, TMEM39A, at a dose of 30 mg/kg, significantly suppressed tumor growth in KRAS(LA1) non-small cell lung cancer mice. These results suggest that the TMEM39AS41 peptide could have therapeutic potential for lung cancer.

Metabolic syndrome is an important public health issue and is associated with a more affluent lifestyle. Many studies of metabolic syndrome have been reported, but its pathogenesis remains unclear and there is no effective treatment. The ability of natural compounds to ameliorate metabolic syndrome is currently under investigation. Unlike synthetic chemicals, such natural products have proven utility in various fields. Recently, ginsenoside extracted from ginseng and ginseng root are representative examples. For example, ginseng is used in dietary supplements and cosmetics. In addition, various studies have reported the effects of ginsenoside on metabolic syndromes such as obesity, diabetes, and hypertension. In this review, we describe the potential of ginsenoside Rg3, a component of ginseng, in the treatment of metabolic syndrome.

BackgroundPyrazinamide (PZA) is a common drug that causes serious adverse events (SAEs). The aim of this study was to determine the incidence of and risk factors for SAEs due to PZA during first-line anti-tuberculosis treatment.MethodsThe medical records of patients with tuberculosis (TB) treated with PZA-containing regimens including first-line drugs-ethambutol, rifampicin, and isoniazid-from January 2003 to June 2016 were reviewed. SAEs were defined as side effects that led to drug discontinuation. The causative drug was determined based on the disappearance of the SAEs upon drug withdrawal and/or the recurrence of the same SAEs with re-challenge.ResultsOf 2,478 patients with TB, 16.4% experienced SAEs. The incidence of SAEs increased significantly as age increased, except with rifampin. PZA accounted for most SAEs (55.8%). Hepatotoxicity was the most common SAE due to PZA (44.5%), followed by gastrointestinal (GI) intolerance (23.8%). The risk of SAEs due to PZA increased significantly as age increased, when sex and comorbidities were adjusted (odds ratio, 1.013; 95% confidence interval, 1.004-1.023; P = 0.007). In the subgroup analysis, older age was an independent risk factor for GI intolerance but not for hepatotoxicity.ConclusionPZA was the most common drug associated with SAEs among the first-line anti-TB drugs, and old age was an independent factor for SAE occurrence. This study suggests that the early recognition of whether the causative agent is PZA may improve effective treatment compliance, particularly in elderly patients.

BackgroundIdiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, its effect on recurrence after curative surgery remains unclear.ObjectivesThis study aimed to determine the impact of IPF on recurrence-free survival following curative surgical resection of stage I-III non-small cell lung cancer (NSCLC) and investigate the effects of patient and surgical factors on the risk of recurrence.MethodsWe reviewed retrospectively collected data of patients with surgically resected stage I-III NSCLC from two tertiary care hospitals in South Korea. By propensity score matching, patients with IPF (LC with IPF) were matched to those without IPF (LC without IPF).ResultsIn total, 3416 patients underwent surgical resection, and 96 were diagnosed with underlying IPF. In the LC with IPF group, 89.6% patients were men, and the average age was 69.7 years. Sublobar resection was performed more frequently in the LC with IPF group than in the LC without IPF group, while the rate of mediastinal lymph node dissection and dissected node number were lower in the former group. The 5-year recurrence-free survival rate was significantly lower in the LC with IPF group (49.2%) than in the LC without IPF group (69.1%; PConclusionsIPF may increase the risk of recurrence after curative surgical treatment for NSCLC. Close surveillance for recurrence is mandatory for patients with underlying IPF.

Objectives Immune checkpoint inhibitors (ICIs) can cause pneumonitis in lung cancer patients. We aimed to identify the clinical and radiologic characteristics, incidence, and risk factors of ICI-related pneumonitis in patients with non-small cell lung cancer (NSCLC). Materials and Methods Medical records and chest computed tomography scans of NSCLC patients treated with an ICI over a 5-year period at a tertiary hospital were retrospectively analyzed. Clinical characteristics were compared between patients with and without ICI-related pneumonitis to identify risk factors. Results Data from 167 eligible patients were analyzed. The incidences of all-grade and grade 3–4 pneumonitis were 13.2% and 4.2%, respectively. The presence of preexisting interstitial lung disease [odd ratio (OR), 6.03; 95% confidence interval (CI), 1.19–30.45; P = 0.030] was associated with a higher incidence of ICI-related pneumonitis. The presence of extrathoracic metastasis [OR, 0.34; 95% CI, 0.13–0.92; P = 0.034] was associated with a lower incidence of ICI-related pneumonitis. The dominant radiologic pattern (72.7%) of ICI-related pneumonitis was organizing pneumonia. Half of the patients with pneumonitis completely recovered or improved; however, the mortality rate was 18.2%. Conclusion ICIs should be used with caution when treating lung cancer patients who have underlying chronic lung disease, especially interstitial lung disease.

Purpose: To evaluate the efficacy of short-term low-dose quetiapine for delirium prevention in critically ill patients. Methods: In this prospective, a single-center, randomized, double-blind, placebo-controlled trial, adult patients who were admitted from July 2015 to July 2017 to a medical intensive care unit (ICU) of a tertiary teaching hospital affiliated to Seoul National University were included. Quetiapine (12.5 mg or 25 mg oral at night, N = 16) or placebo (N = 21) was administered according to randomization until ICU discharge or the 10th ICU day. The primary endpoint was the incidence of delirium within the first 10 ICU days. Secondary endpoints included the rate of positive Confusion Assessment Method for the ICU (CAM-ICU) (the number of positive CAM-ICU counts/the number of total CAM-ICU counts), delirium duration, successful extubation, and overall mortality. Result: The incidence of delirium during the 10 days after ICU admission was 46.7% (7/15) in the quetiapine group and 55.0% (11/20) in the placebo group (p = 0.442). In the quetiapine group, the rate of positive CAM-ICU was significantly lower than in the placebo group (14.4% vs. 37.4%, p = 0.048), delirium duration during the study period was significantly shorter (0.28 day vs. 1.83 days, p = 0.018), and more patients in the quetiapine than in the placebo group were weaned from mechanical ventilation successfully (84.6% vs. 47.1%, p = 0.040). Conclusions: Our study suggests that prophylactic use of low-dose quetiapine could be helpful for preventing delirium in critically ill patients. A further large-scale prospective study is needed.

The clinical course of idiopathic pulmonary fibrosis (IPF) is difficult to predict, partly owing to its heterogeneity. Composite physiologic index (CPI) and gender-age-physiology (GAP) models are easy-to-use predictors of IPF progression. This study aimed to compare the predictive values of these two models. From 2003 to 2007, the Korean Interstitial Lung Disease (ILD) Study Group surveyed ILD patients using the 2002 ATS/ERS criteria. A total of 832 patients with IPF were enrolled in this study. CPI was calculated as follows: 91.0 − (0.65 × %DLCO) − [0.53 × %FVC + [0.34 × %FEV1. GAP stage was calculated based on gender (0–1 points), age (0–2 points), and two physiologic lung function parameters (0–5 points). The two models had similar significant predictive values for patients with IPF (p

AIMS Although clinical guidelines advocate the use of the highest tolerated dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after acute myocardial infarction (MI), the optimal dosing or the risk-benefit profile of different doses have not been fully identified. METHODS AND RESULTS In this multicentre trial, 495 Korean patients with acute ST segment elevation MI and subnormal left ventricular (LV) ejection fraction (

Autophagy is a biological recycling process via the self-digestion of organelles, proteins, and lipids for energy-consuming differentiation and homeostasis. The Golgi serves as a donor of the double-membraned phagophore for autophagosome assembly. In addition, recent studies have demonstrated that pulmonary and hepatic fibrosis is accompanied by autophagy. However, the relationships among Golgi function, autophagy, and fibrosis are unclear. Here, we show that the deletion of GOLGA2, encoding a cis-Golgi protein, induces autophagy with Golgi disruption. The induction of autophagy leads to fibrosis along with the reduction of subcellular lipid storage (lipid droplets and lamellar bodies) by autophagy in the lung and liver. GOLGA2 knockout mice clearly demonstrated fibrosis features such as autophagy-activated cells, densely packed hepatocytes, increase of alveolar macrophages, and decrease of alveolar surfactant lipids (dipalmitoylphosphatidylcholine). Therefore, we confirmed the associations among Golgi function, fibrosis, and autophagy. Moreover, GOLGA2 knockout mice may be a potentially valuable animal model for studying autophagy-induced fibrosis.

TRIO and F-actin-binding protein (TrioBP), which was initially discovered as a binding partner of Trio and F-actin, is a critical factor associated with hearing loss in humans. However, the function of TrioBP in cancer has not been investigated. In the present study, TrioBP expression was indicated to be highly elevated in U87-MG and U343-MG cells. Furthermore, the TrioBP mRNA expression level was markedly increased in U87-MG and U251-MG cells compared with that in cerebral cortex cells, as determined by deep sequencing. Comprehensive analysis of a public TCGA dataset confirmed that TrioBP expression is elevated in patients with glioblastoma. In summary, the present data indicate that TrioBP expression is increased in glioblastoma cell lines and in patients with glioma, suggesting that TrioBP has potential as a diagnostic marker or therapeutic agent for glioma.

Objectives Therapeutic drug monitoring (TDM) of anti-tuberculosis (TB) drugs is important for proper treatment of TB. Dried blood spots (DBSs) are widely used for TDM because of their several advantages. Rifampicin and pyrazinamide assays with DBSs have already been developed. However, isoniazid (INH) assay for capillary DBSs have not been reported because of INH instability. We developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for measuring INH concentrations in venous and capillary DBSs. Methods Each DBS was analyzed on an UPLC system. INH and internal standard (IS) concentrations were determined by multiple-reaction monitoring in positive ion mode. Analytical performances, including precision, linearity, and comparison of different types of specimens were determined. Further, the stability of INH in venous DBSs was tested. Results INH and IS were clearly separated in the UPLC-MS/MS system without matrix effect. Within-run precision and between-day precision were 2.68–8.02% and 2.54–5.45%, respectively. INH concentrations in venous DBS showed proportional bias compared with those in plasma (Slope: 0.8704) with good correlation. INH concentration in capillary DBS was slightly but not significantly higher than that in venous DBS. Conclusions The findings of our study show that the analytical performance of this novel method for capillary and venous DBSs was clinically acceptable for the TDM of INH.

BACKGROUND The nodular bronchiectatic (NB) form of non-tuberculous mycobacteria (NTM) lung disease usually involves the right middle lobe (RML) and the left upper lobe lingular segment. However, the reason underlying this preference is not known. METHODS Fifty patients with NB NTM lung disease who had both positive NTM culture(s) and NB lesions in the RML or lingular segment on computed tomography (CT) of the chest, and 100 healthy subjects matched for sex, age, height and body weight with normal chest CT, were randomly selected. Using reconstructed curved multiplanar reformation (MPR) images, the lengths, diameters and angles of the RML and lingular bronchi were measured. RESULTS Of the 150 individuals, 64% were female; the mean age was 55 years. The angles of the bronchi were significantly more acute in patients than in healthy subjects, both in the RML (patients, mean 46.75° ± standard deviation 8.87° vs. healthy subjects, mean 51.73° ± 7.76°; P = 0.001) and in the lingular segments (patients, mean 26.94° ± 8.16° vs. healthy subjects, mean 34.65° ± 9.75°; P < 0.001). In addition, the angles of the bronchi in the involved segments were more acute than those in the non-involved segments, both in the RML and the lingular segments. There were no differences in the lengths and bronchi diameters between groups. CONCLUSIONS An acute angle (obtuse slope) of RML/lingular bronchi could be an anatomical risk factor for NB NTM lung disease.

Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive, supervised chemotherapy because second-line anti-TB drugs have a narrower therapeutic range than first-line drugs. This study aimed to develop population pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB, evaluate the recommended dosage regimens and, if necessary, suggest new dosage regimens. A prospective, single-centre PK study was performed on second-line anti-TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p-aminosalicylic acid (PAS), kanamycin and other second-line drugs were administered to the patients. Plasma concentrations were analysed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Population PK models were developed using non-linear mixed effect modelling (NONMEM, Version 7.30; ICON Development Solutions, Ellicott City, MD, USA). Simulations were performed using the calculated PK parameters. The respective absorption rate constant, apparent clearance and apparent volume of distribution values were as follows: 0.305/h, 9.37 L/h and 56.7 L for moxifloxacin; 0.135/h, 1.38 L/h and 10.5 L for cycloserine; 0.510/h, 30.8 L/h and 79.4 L for PAS; and 1.67/h, 3.75 L/h and 15.2 L for kanamycin. The simulations showed that the following dosage regimens were more likely to be within the recommended concentration ranges than the raw data in this study: 200 mg of moxifloxacin once daily (QD) (patient weight50 kg) and 400 mg of moxifloxacin QD (patient weight ≥50 kg), 500-750 mg of cycloserine QD, 4.95-6.6 g of PAS twice daily and 750-1000 mg of intramuscular kanamycin QD. These findings indicate that the recommended doses should be revised to improve the clinical outcomes of MDR-TB treatment.

Background/aims The tuberculin skin test (TST) and interferon γ release assay are currently used as diagnostic tools to detect latent tuberculosis (TB) infection; however, there are inconsistencies about the degree of agreement between the tests. We aimed to evaluate the concordance rate between the two tests in household contacts of a country with intermediate TB burden, where most people were vaccinated. Methods We recruited household contacts who spent > 8 hours daily with patients with microbiologically confirmed active pulmonary TB, and received both TST and T-SPOT.TB (Oxford Immunotec) simultaneously. The degree of agreement was analysed according to TST cutoff and Bacille Calmette-Guerin (BCG) vaccination status. Relevant factors were analysed to establish the association with TST or T-SPOT.TB. Results Among 298 household contacts, 122 (40.9%) were spouses, and 250 (83.9%) had received BCG vaccination. In the contact sources, 117 (39.3%) showed a positive result for acid-fast bacillus (AFB) sputum smear and 109 (36.6%) had cavities. The highest agreement rate of 69.5% and κ value of 0.378 were found with a 10 mm cutoff. Spouse, time interval from TB diagnosis to test, and AFB sputum smear positivity were significantly associated with a positive result for T-SPOT.TB. Sex, BCG vaccination, and cavity on chest computed tomography were related to TST positivity. Conclusions The present study suggested it was not possible for TST and T-SPOT.TB to replace each other because of considerable discrepancy between the two tests in household contacts in a country with intermediate TB prevalence.

Background A number of questionnaires designed for analyzing family members’ inconvenience and demands in intensive care unit (ICU) care have been developed and validated in North America. The family satisfaction in the intensive care Unit-24 (FS-ICU-24) questionnaire is one of the most widely used of these instruments. This study aimed to translate the FS-ICU-24 questionnaire into Korean and validate the Korean version of the questionnaire. Methods The study was conducted in the medical, surgical, and emergency ICUs at three tertiary hospitals. Relatives of all patients hospitalized for at least 48 hours were enrolled for this study participants. The validation process included the measurement of construct validity, internal consistency, and interrater reliability. The questionnaire consists of 24 items divided between two subscales: satisfaction with care (14 items) and satisfaction with decision making (10 items). Results In total, 200 family members of 176 patients from three hospitals completed the FS-ICU-24 questionnaire. Construct validity for the questionnaire was superior to that observed for a visual analog scale (Spearman’s r = 0.84, p < 0.001). Cronbach’s αs were 0.83 and 0.80 for the satisfaction with care and satisfaction with decision making subscales, respectively. The mean (± standard deviation) total FS-ICU-24 score was 75.44 ± 17.70, and participants were most satisfied with consideration of their needs (82.13 ± 21.03) and least satisfied with the atmosphere in the ICU waiting room (35.38 ± 34.84). Conclusions The Korean version of the FS-ICU-24 questionnaire demonstrated good validity and could be a useful instrument with which to measure family members’ satisfaction about ICU care.