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Gamma-aminobutyric acid (GABA) transaminase—also called GABA aminotransferase (GABA-AT)—deficiency is a rare autosomal recessive disorder characterized by a severe neonatal-infantile epileptic encephalopathy with symptoms such as seizures, hypotonia, hyperreflexia, developmental delay, and growth acceleration. GABA transaminase deficiency is caused by mutations in GABA-AT, the enzyme responsible for the catabolism of GABA. Mutations in multiple locations on GABA-AT have been reported and their locations have been shown to influence the onset of the disease and the severity of symptoms. We examined how GABA-AT mutations influence the structural stability of the enzyme and GABA-binding affinity using computational methodologies such as molecular dynamics simulation and binding free energy calculation to understand the underlying mechanism through which GABA-AT mutations cause GABA-AT deficiency. GABA-AT 3D model depiction was carried out together with seven individual mutated models of GABA-AT. The structural stability of all the predicted models was analyzed using several tools and web servers. All models were evaluated based on their phytochemical values. Additionally, 100 ns MD simulation was carried out and the mutated models were evaluated using RMSD, RMSF, Rg, and SASA. gmxMMPBSA free energy calculation was carried out. Moreover, RMSD and free energy calculations were also compared with those obtained using online web servers. Our study demonstrates that P152S, Q296H, and R92Q play a more critical role in the structural instability of GABA-AT compared with the other mutated models: G465R, L211F, L478P, and R220K.

Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX1) is an orphan nuclear receptor encoded by the NR0B1 gene. The functional study showed that DAX1 is a physiologically significant target for EWS/FLI1-mediated oncogenesis, particularly Ewing Sarcoma (ES). In this study, a three-dimensional DAX1 structure was modeled by employing a homology modeling approach. Furthermore, the network analysis of genes involved in Ewing Sarcoma was also carried out to evaluate the association of DAX1 and other genes with ES. Moreover, a molecular docking study was carried out to check the binding profile of screened flavonoid compounds against DAX1. Therefore, 132 flavonoids were docked in the predicted active binding pocket of DAX1. Moreover, the pharmacogenomics analysis was performed for the top ten docked compounds to evaluate the ES-related gene clusters. As a result, the five best flavonoid-docked complexes were selected and further evaluated by Molecular Dynamics (MD) simulation studies at 100 ns. The MD simulation trajectories were evaluated by generating RMSD, hydrogen bond plot analysis, and interaction energy graphs. Our results demonstrate that flavonoids showed interactive profiles in the active region of DAX1 and can be used as potential therapeutic agents against DAX1-mediated augmentation of ES after in-vitro and in-vivo evaluations.

This study aimed to investigate the feasibility of Krebs von den Lungen-6 (KL-6) as potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom serum KL-6 was measured for differentiating between pneumonia and ILD (category 1), diagnosing and assessing the severity of suspicious TR-ILD (category 2), or evaluating baseline levels before cancer treatment (category 3). Among 1297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 194 patients. In lung cancer patients, median KL-6 level was higher in patients with drug-induced ILD than in those without ILD or those with radiation pneumonitis, and it was correlated with the severity of TR-ILD. Elevated serum KL-6 (cutoff: 449.9 U/mL) was an independent risk factor of severe TR-ILD, and elevated serum KL-6 with normal serum procalcitonin was associated with severe TR-ILD rather than non-ILD respiratory disease or non-severe TR-ILD. Patients with high serum KL-6 levels had worse overall survival compared with those with low serum KL-6 levels, regardless of patients’ categories. Therefore, serum KL-6 may be surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspicious ILD events and before lung cancer treatment.

Amaranthus tricolor L. is a cultivated green vegetable, commonly known as amaranth, which is similar to spinach, broccoli, and cabbage. In the present study, we investigated the antioxidant and antimicrobial activities of the methanol extract and various fractions from A. tricolor. Results show that A. tricolor ethyl acetate (EtOAc) extract displayed the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging activity (IC50=16.43±1.53 μg/ml), which was higher than that of the positive control, butyl hydroxy anisd (IC50=19.42±0.91 μg/ml). This extract had a reducing power of 2.743 at 0.5 mg/ml and significantly attenuated production of reactive oxygen species in a dose-dependent manner. Further bioassay-monitored fractionation of the EtOAc extract yielded two flavonoids, kaempferol (1) and quercetin (2), and one phenolic acid, gallic acid (3). We found that the antimicrobial activity of compound 3 (at a dose of 63 μg/mL) was superior to that of the tetracycline control (at a dose of 250 μg/mL) against Escherichia coli. Additionally, compounds 1 and 2 (at a dose of 63 μg/mL each) displayed higher activities against Penicillium oxalicum and Staphylococcus aureus than the control. These results suggest that A. tricolor extract may represent a promising nutraceutical source due to the antioxidant and antimicrobial properties of its phenolic compounds.

Pinosylvin stilbenes are phenolic compounds mainly occurring in the Pinaceae family. We previously reported that the accumulation of two pinosylvin stilbene compounds, dihydropinosylvin methyl ether (DPME) and pinosylvin monomethyl ether (PME), in Pinus strobus trees was highly enhanced by infection with pine wood nematodes (PWNs: Bursaphelenchus xylophilus), and these two compounds showed strong nematicidal activity against PWNs. In this work, we established a system of pinosylvin stilbene (DPME and PME) production via the in vitro culture of P. strobus calli, and we examined the nematicidal activity of callus extracts. Calli were induced from the culture of mature zygotic embryos of P. strobus. Optimized growth of calli was obtained in 1/2 Litvay medium with 1.0 mg/L 2,4-D and 0.5 mg/L BA. DPME and PME accumulation did not occur in nonaged (one-month-old) calli but increased greatly with prolonged callus culture. The concentrations of DPME and PME in three-month-old dark-brown calli were 6.4 mg/g DW and 0.28 mg/g DW, respectively. The effect of methyl jasmonate treatment on the accumulation of DPME and PME was evaluated in cell suspension culture of P. strobus. However, the treatment appeared to show slight increase of DPME accumulation compared to callus browning. A test solution prepared from crude ethanol extracts from aged calli (three months old) containing 120 µg/ml DPME and 5.16 µg/ml PME treated with PWNs resulted in 100% immobilization of the adult PWNs and 66.7% immobilization of the juvenile PWNs within 24 h. However, nonaged callus extracts did not show any nematicidal activity against juvenile PWNs and showed less than 20% nematicidal activity against adult PWNs. These results indicate that pinosylvin stilbenes can be effectively produced by prolonged culture of P. strobus calli, can be isolated using simple ethanolic extraction, and are applicable as beneficial eco-friendly compounds with nematicidal activity against PWNs.

Previously, anti-inflammatory properties of 3,4,5-Trihydroxycinnamic acid (THC) has been reported in lipopolysaccharide (LPS)-induced RAW264.7 murine macrophage cells and in an LPS-induced sepsis BALB/c mice animal model. However, the effect of THC on the anti-allergic effect in mast cells has not been elucidated. The current study aimed to demonstrate the anti-allergic properties of THC and its underlying mechanism. Rat basophilic leukemia (RBL-2H3) cells were treated with phorbol-12-myristate-13-acetate (PMA) and A23187, a calcium ionophore, to be activated. The anti-allergic effect of THC was determined by measuring cytokine and histamine release. Western blotting was conducted to determine mitogen-activated protein kinases (MAPKs) activation and nuclear factor-κB (NF-κB) translocation. THC significantly suppressed PMA/A23187-induced tumor necrosis factor α secretion and THC also significantly attenuated degranulation, releasing β-hexosaminidase and histamine in concentration-dependent manners. Furthermore, THC significantly attenuated PMA/A23187-induced cyclooxygenase 2 expression and nuclear translocation of NF-κB. THC significantly suppressed PMA/A23187-induced increased phosphorylation of p38 mitogen-activated protein kinase, phosphorylated (p-)extracellular signal-regulated kinase 1/2 and p-c-Jun N-terminal kinase in RBL-2H3 cells. Overall, the results demonstrated that THC exhibited anti-allergic action by significantly attenuating degranulation of mast cells through the inhibition of MAPKs/NF-κB signaling pathway in RBL-2H3 cells.

Hyperuricemia is common during tuberculosis (TB) treatment, mainly pyrazinamide (PZA). This study investigated the relationship between major adverse cardiovascular events (MACEs) and hyperuricemia during TB treatment. From January 2010–June 2017, this study retrospectively evaluated TB patients treated in a South Korean tertiary hospital. Hyperuricemia was defined as elevated serum uric acid >7.0 mg/dL (men) and >6.0 mg/dL (women). A total of 1,143 patients were enrolled in this study, and PZA was used in 1081 (94.6%), while hyperuricemia was detected in 941 (84.4%). Eight patients developed MACEs. Multivariate analysis using logistic regression revealed that previous ischemic heart disease was associated with MACE development (OR, 19.071; 95% CI, 4.648–78.249; P < 0.000), while hyperuricemia was not (OR, 1.505; 95% CI, 0.184–12.299; P = 0.703). Among patients without drug-resistant TB, no hyperuricemia was associated with increased deaths (OR, 2.923; 95% CI, 1.119–7.638; P = 0.029), while hyperuricemia was associated with increased favorable outcomes (OR, 3.366; 95% CI, 1.787–6.340; P < 0.001). In conclusions, most patients who received PZA had hyperuricemia; however, it was not associated with MACE development. Hyperuricemia during TB treatment was associated with better outcomes, possibly due to good compliance with TB treatment.

Background Multidrug-resistant tuberculosis (MDR-TB) represents a major public health concern, with an ongoing need for new effective treatments. Bedaquiline is an oral diarylquinoline that has shown encouraging treatment success and culture conversion rates in MDR-TB. Methods A South Korean patient registry was set up across 19 centres between 2016 and 2018 for the prospective collection of data from patients with MDR-TB who received either a bedaquiline-containing or a non-bedaquiline-containing regimen. Treatment was at the physician’s discretion (bedaquiline use requiring approval by special committee) and was based on patient characteristics, disease status, and local treatment guidelines. Results The safety population included 172 patients (88 bedaquiline and 84 non-bedaquiline). The mean (standard deviation, SD) duration of follow-up was 24.3 (9.5) months. Mean (SD) durations of treatment were 5.4 (1.8) months in bedaquiline-treated patients and 15.7 (6.7) months in the non-bedaquiline group. Treatment success (cured and treatment completed according to WHO 2013 treatment outcome definitions) was achieved by 56.3% of bedaquiline-treated and 45.2% of non-bedaquiline-treated patients. Sputum culture conversion rates were 90.4% and 83.7% with and without bedaquiline, respectively. Diarrhoea and nausea were the most frequently reported treatment-emergent adverse events (TEAEs) in the bedaquiline group (27.3% [24/88] and 22.7% [20/88], respectively). The most frequent bedaquiline-related TEAEs were prolonged QT interval (10.2%; 9/88), and diarrhoea and nausea (9.1% each; 8/88). QT interval prolongation was reported in 19.3% (17/88) of bedaquiline-treated and 2.4% (2/84) of non-bedaquiline-treated patients, but bedaquiline was not discontinued for any patient for this reason. There were 13 (14.7%) and three (3.6%) deaths in the bedaquiline-treated and non-bedaquiline groups, respectively. Review of fatal cases revealed no unexpected safety findings, and no deaths were bedaquiline-related. The most common cause of death was worsening cancer (three patients). Patients in the bedaquiline group tended to have poorer baseline risk profiles than non-bedaquiline patients and were more likely to have relapsed or already failed second-line treatment. Interpretation of mortality data was complicated by high rates of loss to follow-up in both groups. Conclusions The South Korean registry findings support previous risk/benefit observations and the continued use of bedaquiline as part of combination therapy in patients with MDR-TB.

Ewing sarcoma (ES) is a highly malignant carcinoma prevalent in children and most frequent in the second decade of life. It mostly occurs due to t(11;22) (q24;q12) translocation. This translocation encodes the oncogenic fusion protein EWS/FLI (Friend leukemia integration 1 transcription factor), which acts as an aberrant transcription factor to deregulate target genes essential for cancer. Traditionally, flavonoids from plants have been investigated against viral and cancerous diseases and have shown some promising results to combat these disorders. In the current study, representative flavonoid compounds from various subclasses are selected and used to disrupt the RNA-binding motif of EWS, which is required for EWS/FLI fusion. By blocking the RNA-binding motif of EWS, it might be possible to combat ES. Therefore, molecular docking experiments validated the binding interaction patterns and structural behaviors of screened flavonoid compounds within the active region of the Ewing sarcoma protein (EWS). Furthermore, pharmacogenomics analysis was used to investigate potential drug interactions with Ewing sarcoma-associated genes. Finally, molecular dynamics simulations were used to investigate the stability of the best selected docked complexes. Taken together, daidzein, kaempferol, and genistein exhibited a result comparable to ifosfamide in the proposed in silico study and can be further analyzed as possible candidate compounds in biological in vitro studies against ES.

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

Plasmodium vivax (P. vivax) is one of the highly prevalent human malaria parasites. Due to the presence of extravascular reservoirs and recurrent infections from latent liver stages, P. vivax is extremely challenging to manage and eradicate. Traditionally, herbs have been widely used to combat various diseases. Flavonoids from plants are investigated against viral and infectious diseases and showed some promising results to combat these disorders. In the present study, in silico approaches are utilized to study the effect of flavonoids against P. vivax to inhibit malarial invasion of human red blood cells (RBC). Duffy binding protein (DBP) is a malarial protein responsible for binding the Duffy antigen receptor for chemokines (DARC) on human red blood cells and causes malarial invasion. The main focus is to block the DBP binding site to restrict the formation of the DBP-DARC complex. A molecular docking study was performed to analyze the interaction of flavonoid molecules with the DARC-binding site of DBP of P. vivax. Furthermore, molecular dynamic simulation studies are carried out to study the stability of top-docked complexes. The results showed the good effectiveness of flavonoids such as daidzein, genistein, kaempferol, and quercetin in the DBP binding site. These flavonoids bind with DBP and blocked its active site. Furthermore, the binding of these four ligands was maintained throughout the 50 ns simulation maintaining stable hydrogen bond formation with the active site residues of DBP. The present study suggests that flavonoids might be good candidates and novel agents against DBP-mediated RBC invasion of P. vivax.

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

Background The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted. Methods This study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited. Discussion This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB. Trial registration ClinicalTrials.gov NCT04485156. Registered on July 24, 2020.

A phytochemical study on the MeOH extract of Lespedeza tomentosa roots led to the discovery of two new pterocarpans (labelled tomentocarpan A and B), along with three known pterocarpans and a flavanone. The structures of the two new compounds were found to be (6aR,11aR)-1-methoxy-8-hydroxy-2′,2′-dimethylpyrano[5′,6′:2,3]-2′′,2′′-dimethylpyrano[6′′,5′′:9,10]pterocarpan (5), and 1-methoxy-8-hydroxy-2′,2′-dimethylpyrano[5′,6′:2,3]-2′′,2′′-dimethylpyrano[6′′,5′′:9,10]pterocarp-6a(11a)-ene (6), based on comprehensive spectral and physical property analyses. Compounds 5 and 6 showed butyrylcholinesterase inhibitory activities with IC50 values of 0.50 and 0.62 mM, respectively.

Plasmodium vivax (P. vivax) is one of the human’s most common malaria parasites. P. vivax is exceedingly difficult to control and eliminate due to the existence of extravascular reservoirs and recurring infections from latent liver stages. Traditionally, licorice compounds have been widely investigated against viral and infectious diseases and exhibit some promising results to combat these diseases. In the present study, computational approaches are utilized to study the effect of licorice compounds against P. vivax Duffy binding protein (DBP) to inhibit the malarial invasion to human red blood cells (RBCs). The main focus is to block the DBP binding site to Duffy antigen receptor chemokines (DARC) of RBC to restrict the formation of the DBP–DARC complex. A molecular docking study was performed to analyze the interaction of licorice compounds with the DARC binding site of DBP. Furthermore, the triplicates of molecular dynamic simulation studies for 100 ns were carried out to study the stability of representative docked complexes. The leading compounds such as licochalcone A, echinatin, and licochalcone B manifest competitive results against DBP. The blockage of the active region of DBP resulting from these compounds was maintained throughout the triplicates of 100 ns molecular dynamic (MD) simulation, maintaining stable hydrogen bond formation with the active site residues of DBP. Therefore, the present study suggests that licorice compounds might be good candidates for novel agents against DBP-mediated RBC invasion of P. vivax.

Background The fractional exhaled nitric oxide (FENO) test is useful in asthma patients. However, a few studies on its usefulness in chronic obstructive pulmonary disease (COPD) patients have been reported. We analyzed the FENO level distribution and clinical characteristics according to the FENO level in COPD patients. Methods From December 2014 to June 2019, COPD patients who underwent pulmonary function and FENO tests at Chonnam National University Hospital were retrospectively evaluated for FENO, comorbidities, asthma history, blood eosinophil, and pulmonary function test. The high FENO group was defined as those with FENO level>25 parts per billion (ppb). Results A total of 849 COPD patients (mean age, 70.3±9.4 years) were included. The mean forced expiratory volume at 1 second was 66.5±21.7% and the mean FENO level was 24.3±20.5 ppb. Patients with FENO ≤25 ppb were 572 (67.4%) and those with FENO >25 ppb were 277 (32.6%). Blood eosinophil percentage was significantly higher (4.2±4.8 vs. 2.7±2.5, p3% (46.9% vs. 34.8%, p=0.001) and asthma history (25.6% vs. 8.6%, p3%, and positive bronchodilator response (BDR) were independent risk factors for the high FENO level (adjusted odds ratio [aOR], 3.85; p

Background The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA). Methods The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected. Conclusion NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.

Background: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA). Methods: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii ; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants’ clinical course will be tracked and their clinical data as well as NTM isolates will be collected. Conclusion: NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.

Objective Pulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study aimed to evaluate the risk factors for cerebral complications in patients with PAVMs. Methods We retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital. Results Fifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16–250.31; P = 0.038). Conclusion Older age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs.

The clinical characteristics of patients with post-tuberculosis (TB) bronchiectasis have not been well evaluated. We enrolled 598 patients with bronchiectasis who participated in the Korean prospective bronchiectasis registry and compared the characteristics of post-TB bronchiectasis (19.7%) with post-infectious (19.6%), idiopathic (40.8%), and other (19.9%) bronchiectasis. The patients with post-TB bronchiectasis had a lower body mass index, higher rate of chronic obstructive pulmonary disease, and lower rate of asthma than those in the other groups. The patients with post-TB bronchiectasis had more upper lobe involvement, more severe radiological extent, and worse lung function than those in the other groups. Long-acting muscarinic antagonist/long-acting ß agonist use and mucolytics were more commonly used in the patients with post-TB bronchiectasis than those in the other groups, while inhaled corticosteroid/long-acting ß agonist was less commonly used. There were no significant intergroup differences in bronchiectasis severity scores except for FACED, the number of exacerbations, and quality of life. Post-TB bronchiectasis is characterised by reduced lung function and higher rates of mucolytic use when compared with other bronchiectasis, thus, adequate bronchodilator use and airway clearance techniques may alleviate symptom burden in this population.

Background Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS

Many factors should be considered when selecting the optimal location to establish a sports facility. This study develops a framework to select a set of optimal rooftop locations for sports facilit...

Background/aims Peripheral eosinophilia during tuberculosis (TB) treatment is common, but has not been fully evaluated. The aim of this study was to determine the prevalence and clinical significance of peripheral blood eosinophilia in patients undergoing anti-TB treatment. Methods We retrospectively reviewed the clinical and laboratory data of patients who received anti-TB treatment and had peripheral blood eosinophilia (> 5% of the total white blood cell count) at the Chonnam National University Hospital between January 2010 and December 2014. Results Of all 2,234 patients with TB who received anti-TB treatment, 397 (17.8%) had peripheral blood eosinophilia. Of the 397 with eosinophilia, we reviewed the data of 262 (66%), and cutaneous adverse drug reactions (CADRs) were observed in 161 (61.5%). Of the 161 with CADRs, itching (47.2%) and skin rash (47.8%) were common. Older age, abnormal liver function, and higher peak blood eosinophil percentage were associated with CADRs in multivariate analysis. There was a significant relationship between increased peak eosinophil counts and the degree of severity of CADRs. Conclusion Peripheral blood eosinophilia is a relatively common occurrence during anti-TB treatment. Peripheral blood eosinophil counts were higher according to the degree of severity of CADRs.

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

Since it is a widely known fact that smoking cessation is beneficial physically and cognitively, efforts should be made to enable smokers to quit smoking through policy. Intensive care smoking cessation camps generally show a high smoking cessation success rate, but research is needed to determine which smokers should be admitted due to costeffectiveness. Although many studies have been conducted to find factors related to smoking cessation success, there is still controversy about the will and success rate of smoking cessation of elderly smokers. We performed this study to determine behavior characteristics and smoking cessation success rates in nonelderly and elderly smokers who participated in an intensive care smoking cessation camp. Heavy smokers participating in an intensive care smoking cessation camp at Chonnam National University Hospital between the August 2015 and December 2017 were classified into elderly (age ≥65 years old) or nonelderly (age65 years old) groups after excluding missing data. Smokers were followed up at 4 weeks, 6 weeks, 12 weeks, and 6 months from the start of abstinence by self-report, measurement of carbon monoxide expiration levels or cotinine testing. A total of 351 smokers were enrolled in the study. At the 6-month follow-up, 56 of 107 (52.3%) elderly smokers and 109 of 244 (44.7%) nonelderly smokers continued to abstain from smoking. Elderly smokers showed a higher smoking cessation rate than that of nonelderly smokers, but it was not statistically significant (OR = 1.36, 95%CI: 0.862, 2.145). The most common causes of cessation failure in both groups were stress and temptation, followed by withdrawal symptoms. Smoking cessation rates in the elderly are comparable to that in the nonelderly after an intensive care smoking cessation camp. Intensive care smoking cessation camps can help both elderly and nonelderly smokers who intend to quit smoking by providing motivation, education and medication. Smoking cessation should be strongly recommended regardless of age.

There are insufficient data regarding the relationship between non-cystic fibrosis bronchiectasis and incident aspergillosis. We performed a population-based, matched cohort study using data from the Korean National Health Insurance database between 2003 and 2013. The incidence of aspergillosis was 50/100,000 person-years in the bronchiectasis cohort and 11/100,000 person-years in the matched cohort (subdistribution hazard ratio, 4.53, 95% confidence interval (CI), 3.25–6.32). Among the bronchiectasis cohort, chronic obstructive pulmonary disease (adjusted HR, 1.95, 95% CI, 1.07–3.57), previous pulmonary tuberculosis (adjusted HR, 3.67, 95% CI, 2.03–6.64), and non-tuberculous mycobacterial pulmonary disease (adjusted HR, 11.25, 95% CI, 1.49–85.18) increased the risk of incident aspergillosis. The incidence of aspergillosis in patients with bronchiectasis was approximately 4.5-fold that in those without bronchiectasis. Comorbid pulmonary diseases—chronic obstructive pulmonary disease, previous pulmonary tuberculosis, and non-tuberculous mycobacterial pulmonary disease—significantly increased the risk of aspergillosis in patients with bronchiectasis. Our study indicates that close monitoring is warranted for aspergillosis in patients with bronchiectasis.

Six new compounds (1−6) were isolated from the leaves of Viburnum erosum along with four known compounds 7−10. The structures were determined by NMR and MS spectroscopic analyses, and their absolute configurations were established by chemical and spectroscopic methods. Compounds 1–6 were α-glucosidic hydroquinone derivatives with different linear monoterpenoid structures. Compounds 1−10 were also evaluated for their tyrosinase inhibitory activities, and 10 showed potent inhibition of tyrosinase enzyme with IC50 of 37.9 μM compared to 47.6 μM of the positive control (β-arbutin).

Objective Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP. Methods We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC). Results The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015–1.153; P = 0.016). Conclusions Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.