Search

Youlim Kim,1,&ast; Hyun Lee,2,&ast; Sung Jun Chung,2,&ast; Yoomi Yeo,2 Tai Sun Park,2 Dong Won Park,2 Kyung Hoon Min,3 Sang-Heon Kim,2 Tae-Hyung Kim,2 Jang Won Sohn,2 Ji-Yong Moon,2 Ho Joo Yoon2 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Hospital, School of Medicine, Konkuk University, Seoul, Korea; 2Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea; 3Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Medical Center, Guro Hospital, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Ji-Yong MoonDepartment of Internal Medicine, Hanyang University Guri Hospital, Gyeongchun-ro 153, Guri-si, Gyeonggi-do, 11923, KoreaTel +82-31-560-2224Fax +82-31-553-7369Email respiry@gmail.comHo Joo YoonDivision of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, KoreaTel +82-2-2290-8336Fax +82-2-2298-9183Email hjyoon@hanyang.ac.krBackground and Objective: Despite the usefulness of airway hyperresponsiveness (AHR) testing in diagnosing and monitoring asthma, it is challenging to perform in a real-world setting. Forced expiratory flow between 25% and 75% of vital capacity (FEF25– 75), a pulmonary measurement that can be obtained easily during routine spirometry, represents the status of medium-sized and small airways. However, the performance of FEF25– 75 in predicting AHR has not been well elucidated. Therefore, we investigated whether FEF25– 75 can predict AHR to mannitol.Methods: We performed a retrospective cohort study of 428 patients who visited a single clinic due to cough, wheezing, or dyspnea. All patients underwent spirometry with a mannitol provocation test. We compared the area under the curve (AUC) of the percentage of the predicted values of FEF25– 75 (FEF25– 75 %pred) with that of forced expiratory volume in 1 second (FEV1%pred), FEV1/forced vital capacity (FVC), and FEF25– 75/ FVC for predicting AHR.Results: The rate of AHR to mannitol was 20.3%. In the overall study population, the AUC of FEF25– 75 %pred for predicting AHR (0.772; 95% confidence interval [CI], 0.729– 0.811) was significantly higher than that of FEV1%pred (0.666; 95% CI, 0.619– 0.710; p < 0.001), FEV1/FVC (0.741; 95% CI, 0.697– 0.782; p = 0.047), and FEF25– 75/FVC (0.741, 95% CI = 0.696– 0.782, p = 0.046). The sensitivity, specificity, positive predictive value, and negative predictive value of FEF25– 75 %pred < 81% for predicting AHR in the overall study population were 77.0% (95% CI = 66.8– 85.4%), 63.9% (95% CI = 58.6– 69.0), 35.3%, and 91.6%, respectively. When we restricted the study group to subjects with normal lung function, the results were similar.Conclusion: Our results indicate that FEF25– 75 %pred can be used as a surrogate for predicting AHR in patients with respiratory symptoms.Keywords: forced expiratory flow between 25% and 75% of vital capacity, mannitol, bronchial hyperresponsiveness

Abhishek Dubey,1,* Dae Won Park,2,* Jung Eun Kwon,2 Yong Joon Jeong,2 Taegeun Kim,1 Inhye Kim,3 Se Chan Kang,2 Ki-Whan Chi1 1Department of Chemistry, University of Ulsan, Ulsan, 2Department of Life Science, Gachon University, Seongnam, 3Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, Republic of Korea *These authors contributed equally to this work Abstract: Three new large hexanuclear metalla-prisms 9–11 incorporating 1,3,5-tris(pyridin-4-ylethynyl)benzene (tpeb) 4 and one of the dinuclear arene ruthenium clips [Ru2(p-iPrC6H4Me)2(OO∩OO)][CF3SO3]2 (OO∩OO =2,5-dioxydo-1,4-benzoquinonato [dobq] 1, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 2, and 6,11-dihydroxy-5,12-naphthacenedionato [dotq] 3), which encapsulate the guest molecule ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 5) were prepared. All complexes were isolated as triflate salts in good yields and were fully characterized by 1H NMR spectroscopy and electrospray ionization mass spectrometry. The photophysical properties of these metalla-prisms were also investigated. Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30±0.020). Ellagic acid (5) and compound 11 showed weaker activity than that of Trolox. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the metalla-prism compounds exhibit anticancer properties in vitro. Compound 10 inhibited the growth of all cancer cell lines at micromolar concentrations, with the highest cytotoxicity observed against A549 human lung cancer cells (IC50 =25.9 µM). However, these compounds had a lower anti-cancer activity than that of doxorubicin. In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not. While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line. Our results show that ellagic acid encapsulated in metalla-prisms inhibited cancer cells via the modulation of mRNA induction and protein expression levels of the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein in macrophages. Keywords: metalla-prism, antioxidant, tumoricidal assay, G-CSF, Rantes

High mobility group box 1 (HMGB1) protein is a danger-signaling molecule, known to activate an inflammatory response via TLR4 and RAGE. HMGB1 can be either actively secreted or passively released from damaged alveolar epithelial cells. Previous studies hav

Objectives: The purpose of this study was to determine whether cilostazol reduces intimal hyperplasia in patients undergoing long zotarolimus-eluting stent implantation (stent length: ≥ 30 mm) for native long coronary lesions (length: ≥ 25 mm). Background: Restenosis after drug-eluting stent implantation remains a significant clinical problem in long coronary lesions. Methods: Patients (n = 499) were assigned randomly to triple (aspirin, clopidogrel, and cilostazol, triple group: n = 250) or dual antiplatelet therapy (aspirin and clopidogrel and placebo, dual group: n = 249) for 8 months after long zotarolimus-eluting stent implantation. The primary end point was in-stent late loss at the 8-month angiography according to the intention-to-treat principle. Results: The 2 groups had similar baseline characteristics. The in-stent (0.56 ± 0.55 mm vs. 0.68 ± 0.59 mm, p = 0.045) and in-segment (0.32 ± 0.54 mm vs. 0.47 ± 0.54 mm, p = 0.006) late loss were significantly lower in the triple versus dual group, as were 8-month in-stent restenosis (10.8% vs. 19.1%, p = 0.016), in-segment restenosis (12.2% vs. 20.0%, p = 0.028), and 12-month ischemic-driven target lesion revascularization (5.2% vs. 10.0%, p = 0.042) rates. At 12 months, major adverse cardiac events including death, myocardial infarction, and ischemic-driven target lesion revascularization tended to be lower in the triple group than the dual group (7.2% vs. 12.0%, p = 0.07). Percent intimal hyperplasia volume by volumetric intravascular ultrasound analysis was reduced from 27.1 ± 13.2% for the dual group to 22.1 ± 9.9% for the triple group (p = 0.017). Conclusions: Patients receiving triple antiplatelet therapy after long zotarolimus-eluting stent implantation had decreased extent of late luminal loss, percent intimal hyperplasia volume, and angiographic restenosis, resulting in a reduced risk of 12-month target lesion revascularization compared with patients receiving dual antiplatelet therapy. (Triple Versus Dual Antiplatelet Therapy after ABT578-Eluting Stent; NCT00589927). [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the hemodynamic and anatomic factors associated with sinus thrombosis following transcatheter aortic valve replacement (TAVR), integrating in vivo patient data analysis and in vitro experiments., Methods and Results: Postprocedural, 4-dimensional, multiphase computed tomography data from 211 patients enrolled in the ADAPT-TAVR (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement) study were analyzed. The prevalence of native sinus thrombosis was examined in relation to valve type, implant depth, and anatomic features. In vitro experiments used particle image velocimetry to observe changes in sinus flow based on the transcatheter heart valves (23-mm SAPIEN3, Edwards Lifesciences; and 29-mm CoreValve, Medtronic) height and coronary artery flow. Native sinus thrombosis was more common in self-expanding valves (39.1% versus 14.9%, P =0.004). In per-cusp analysis of in vivo patient data, adjusted transcatheter heart valve implant depth (odds ratio, 1.2 [95% CI, 1.1-1.3]; P <0.001), noncoronary sinus of Valsalva (odds ratio, 4.0 [95% CI, 2.0-7.8]; P <0.001), sinus inflow diameter (odds ratio, 0.8 [95% CI, 0.6-0.9]; P =0.008), and implanted valve size (odds ratio, 0.8 [95% CI, 0.7-1.0]; P =0.025) were significant factors associated with native sinus thrombosis. In the in vitro experiments, CoreValve showed noticeable flow stasis compared with SAPIEN3. High-positioned SAPIEN3 was linked to reduced velocity within the native sinus of Valsalva. Coronary artery flow led to higher sinus velocity and improved particle washout, reducing sinus thrombosis risk., Conclusions: This study provides insights into the relationship between transcatheter heart valve deployment and native sinus thrombosis, emphasizing the role of anatomic factors in relation to the risk of sinus thrombosis.

Background: Lipoprotein(a) (Lp[a]) is associated with the development of aortic valve calcification., Objectives: The aim of this study was to evaluate the association between the serum level of Lp(a) and the development of severe degenerative aortic stenosis (AS) and subsequent aortic valve replacement (AVR)., Methods: A total of 44,742 patients with Lp(a) measurements and echocardiography at baseline evaluation between 2000 and 2020 were included from a single tertiary heart center. The primary outcome was the development of severe degenerative AS, defined as a transaortic maximal velocity of ≥4.0 m/s., Results: During a median follow-up period of 6.8 years (Q1-Q3: 2.3-12.4 years), severe degenerative AS was diagnosed in 472 patients (1.1%), and subsequent AVR was performed in 387 patients (0.9%). Lp(a) levels were associated with risk for severe degenerative AS, with levels of 30 to 50, 50 to 100, and >100 mg/dL demonstrating adjusted HRs of 1.02 (95% CI: 0.78-1.34; P  = 0.88), 1.18 (95% CI: 0.91-1.53; P  = 0.22), and 1.96 (95% CI: 1.31-2.94; P  = 0.001) compared to <30 mg/dL. Similarly, the risk for AVR due to severe degenerative AS was significantly associated with higher levels of Lp(a) (>100 mg/dL) (adjusted HR: 2.05; 95% CI: 1.31-3.19; P  = 0.002). Such associations were not observed in the development of severe bicuspid ( P  = 0.63) or rheumatic ( P  = 0.96) AS., Conclusions: Lp(a) levels >100 mg/dL were significantly associated with risk for severe degenerative AS and subsequent AVR, regardless of the baseline severity of AS. Such associations were not observed in other etiologies of severe AS., Competing Interests: This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant HC19C0022). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: The interaction between COVID-19 and tuberculosis (TB) is not yet fully understood, and large-scale research on the mortality outcome of such dual infection has been limited. This study aimed to investigate the impact of PTB on mortality among patients with COVID-19 within a Korean population by conducting an extensive analysis of a nationwide large dataset., Method: We investigated the mortality and disease severity among COVID-19 patients who had PTB in South Korea. This study analyzed 462,444 out of 566,494 COVID-19 patients identified between January 2020 and December 2021., Result: A total of 203 COVID-19 with PTB patients and 812 matched COVID-19 without PTB were analyzed using 1:4 propensity score matching. COVID-19 patients with PTB exhibited higher in-hospital mortality (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.45-6.27, p -value = 0.003) and were at increased risk of requiring conventional oxygen therapy (OR 1.57, 95% CI 1.10-2.25, p -value = 0.013) as well as high flow nasal cannula (HFNC) or noninvasive ventilation (NIV) oxygen therapy (OR 1.91, 95 CI 1.10-3.32, p -value = 0.022) compared to those without PTB. Compared to matched COVID-19 without PTB, co-infected patients showed increased mortality rates across various timeframes, including during hospitalization, and at 30 day and 90 day intervals. In-hospital mortality rates were particularly elevated among women, individuals with malignancy, and those with lower incomes. Furthermore, the increased in-hospital mortality among PTB patients persisted irrespective of the timing of TB diagnosis or vaccination status against COVID-19., Conclusion: We suggest that physicians be aware of the risk of mortality and severity among COVID-19 patients with PTB; coinfection with COVID-19 is a critical situation that remains to be further explored and needs more attention in countries with an intermediate to high PTB burden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Kim, Oh, Kang, Yoo, Ko, Lim, Kim, Lee, Kim, Sohn, Yoon, Choi, Cho and Park.)

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease caused by a complex hypersensitivity reaction to colonization of the airways with various fungi. ABPA caused by Alternaria alternata, other than Aspergillus spp., is named Allergic bronchopulmonary mycosis (ABPM)., Objective: To describe the first case of ABPM caused by Alternaria alternata in East Asia., Methods: Case report., Results: A 58-year-old female visited our hospital due to an abnormal chest x-ray, following chest computed tomography (CT) revealed consolidation in the left lower lobe. On laboratory finding, eosinophil count and total IgE level were high. The skin prick test and specific IgE for Alternaria alternata were positive. After diagnosis of ABPM, the patient was treated with prednisolone without antifungal agents, and her chest image was much improved., Conclusions: Aspergillus is most common etiology of allergic pulmonary disease, however, Alternaria should be considered even though positive culture of Aspergillus spp.

In recent years, a wealth of clinical data has emerged regarding intravascular imaging involving either intravascular ultrasound or optical coherence tomography. This surge in data has propelled the adoption of intravascular imaging-guided percutaneous coronary intervention (PCI) in daily clinical practice. The findings of current randomized clinical trials regarding imaging guidance have lent strong support to the benefits of intravascular imaging-guided PCI. This holds especially true for the diagnosis and treatment of complex lesions, such as left main disease, diffuse long lesions, chronic total occlusion, severely calcified lesions, bifurcations, and in-stent restenosis, as well as in high-risk patients such as those with acute myocardial infarction or chronic kidney disease. During intravascular imaging-guided PCI, operators attempt to achieve stent optimization for maximized benefits of imaging guidance. This paper provides a comprehensive review on the updated clinical data of intravascular imaging-guided PCI and intravascular ultrasound/optical coherence tomography-derived stent optimization criteria., Competing Interests: This work was supported by the Imaging and Physiology with Cardiovascular Disease (IPOP) and the Korean Society of Interventional Cardiology (KSIC). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: We evaluated the radiologic, pulmonary functional, and antibody statuses of coronavirus disease 2019 (COVID-19) patients 6 and 18 months after discharge, comparing changes in status and focusing on risk factors for residual computed tomography (CT) abnormalities., Methods: This prospective cohort study was conducted on COVID-19 patients discharged between April 2020 and January 2021. Chest CT, pulmonary function testing (PFT), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements were performed 6 and 18 months after discharge. We evaluated factors associated with residual CT abnormalities and the correlation between lesion volume in CT (lesion volume ), PFT, and IgG levels., Results: This study included 68 and 42 participants evaluated 6 and 18 months, respectively, after hospitalizations for COVID-19. CT abnormalities were noted in 22 participants (32.4%) at 6 months and 13 participants (31.0%) at 18 months. Lesion volume was significantly lower at 18 months than 6 months ( P < 0.001). Patients with CT abnormalities at 6 months showed lower forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC), and patients with CT abnormalities at 18 months exhibited lower FVC. FVC significantly improved between 6 and 18 months of follow-up (all P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with CT abnormalities at 6 and 18 months ( P < 0.001). At 18-month follow-up assessments, age was associated with CT abnormalities (odds ratio, 1.17; 95% confidence interval, 1.03-1.32; P = 0.01), and lesion volume showed a positive correlation with IgG level ( r = 0.643, P < 0.001)., Conclusion: At 18-month follow-up assessments, 31.0% of participants exhibited residual CT abnormalities. Age and higher SARS-CoV-2 IgG levels were significant predictors, and FVC was related to abnormal CT findings at 18 months. Lesion volume and FVC improved between 6 and 18 months., Trial Registration: Clinical Research Information Service Identifier: KCT0008573., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Purpose: We aimed to investigate the response to balloon pulmonary angioplasty (BPA) in chronic thromboembolic pulmonary hypertension (CTEPH) using semi-quantitative analysis of lung perfusion SPECT/CT., Methods: This is a single-center retrospective study of patients with CTEPH who underwent BPA and pre- and post-BPA lung perfusion SPECT/CT between 2015 and 2022. Segmental defects on SPECT/CT were visually assessed and semi-quantitatively scored as 1 (large defect) or 0.5 (moderate defect) in accordance with modified PIOPED II criteria. The perfusion defect score was defined as (Σ segmental defect scores/18) × 100 (%). Associations between perfusion defect score and hemodynamic or functional parameters including WHO functional class, six-minute walking distance (6MWD), serum B-type natriuretic peptide (BNP), mean arterial pulmonary pressure (mPAP), pulmonary vascular resistance (PVR), and tricuspid regurgitation pressure gradient (TRPG) on echocardiography were statistically analyzed., Results: A total of 24 consecutive patients were included. The perfusion defect score significantly improved after BPA (median 58.3% vs. 47.2%, P  < 0.001), in conjunction with the WHO functional class, 6MWD, serum BNP, mPAP, and TRPG. Perfusion defect scores were significantly correlated with 6MWD ( rho  = - 0.583, P  < 0.001), serum BNP ( rho  = 0.514, P  < 0.001), mPAP ( rho  = 0.583, P  < 0.001), and PVR ( rho  = 0.575, P  < 0.001). The improvement in the perfusion defect score was significantly associated with improvement in mPAP ( rho  = 0.844, P  < 0.001)., Conclusion: Our results suggest that semi-quantitative analysis of lung perfusion SPECT/CT can provide a potential imaging biomarker for monitoring the efficacy of BPA., Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-024-00858-1., Competing Interests: Conflict of InterestShin Ae Han, Sangwon Han, Jinho Lee, Do-Yoon Kang, Jae Seung Lee, Dae-Hee Kim, Duk-Woo Park, Jong-Min Song, Jin-Sook Ryu, Dae-Hyuk Moon declare that they have no conflicts of interest., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

To determine contamination sources and pathways, the use of multiple isotopes, including metal isotopes, can increase the reliability of environmental forensic techniques. This study differentiated contamination sources in groundwater of a mine area and elucidated geochemical processes using Cu, Zn, S-O, and O-H isotopes. Sulfate reduction and sulfide precipitation were elucidated using concentrations of dissolved sulfides, δ 34 S SO4 , δ 18 O SO4 , and δ 66 Zn. The overlying contaminated soil was possibly responsible for the contamination of groundwater at <5 mbgl, which was suggested by low δ 65 Cu values (0.419-1.120‰) reflecting those of soil (0.279-1.115‰). The existence of dissolved Cu as Cu(I) may prevent the increase in δ 65 Cu during leaching of contaminated soil in the sulfate-reducing environment. In contrast, the groundwater at >5 mbgl seemed to be highly affected by the contamination plume from the adit water, which was suggested by high SO 4 2- concentrations (407-447 mg L -1 ) and δ 65 Cu (0.252-2.275‰) and δ 66 Zn (-0.105‰-0.362‰) values at a multilevel sampler approaching those of the adit seepages. Additionally, the O-H isotopic ratios were distinguished between <5 mbgl and >5 mbgl. Using δ 65 Cu and δ 66 Zn to support the determination of groundwater contamination sources may be encouraged, particularly where the isotopic signatures are distinct for each source., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050., Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades., Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population)., Interpretation: This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor., Funding: This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01)., Competing Interests: S.T has received research grant support from Janssen, Merck, American Heart Association (USA) and the National Medical Research Council (Singapore). She has received speaker and/or consulting fees from AstraZeneca, Eli Lilly, Boehringer-Ingelheim, Merck, Novo Nordisk, Abbott, Medtronic, Dexcom, MIMS, Janssen, Novartis and Sanofi. She is also a shareholder of a health technology company (NOVI Health). D.J.H. has received consultant fees from Faraday Pharmaceuticals Inc. and Boehringer Ingelheim International GmbH, honoraria from Servier, and research funding from Astra Zeneca, Merck Sharp & Dohme Corp and Novonordisk. DJH is supported by the Duke-NUS Signature Research Programme funded by the Ministry of Health, Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research Investigator Award (MOH-STaR21jun-0003), Centre Grant scheme (NMRC CG21APR1006), and Collaborative Centre Grant scheme (NMRC/CG21APRC006). L.B. was supported by the National Medical Research Council (NMRC) of Singapore Centre Grant (Program for Transforming and Evaluating Outcomes in Cardiometabolic disease [PROTECT], Grant number: CG21APR1006), the National Medical Research Counsil (NMRC) of Singapore Transitional Award Grant (Improving Obstructive Coronary Artery Disease and Cardiovascular Risk Prediction Using Deep Learning Analysis on Coronary Artery Calcium Imaging, Grant number: TA21nov-0001), and the National Medical Research Council (NMRC) of Singapore Collaborative Centre Grant (CCG) (IMplementing a PArtnership for Cardiovacular Trials-2 [IMPACT-2] Program, Grant number: NMRC/CG2/001a/2021-NHCS). L.Z is supported by National Medical Research Council under its Clinician-Innovator Award Senior Investigator (CIASI24jan-0001) and Health Service Research Award (MOH-000358), SingHealth Duke-NUS Academic Medical Centre AM strategic fund award (07 FY2023 HTP P2 15-A2) and Industry Alignment Fund Pre-Positioning (IAFPP award) (H20c6a0035). S.L.L. is supported by the National Medical Research Council Transitional Award; she has received research grants from National University Health System, National Kidney Foundation of Singapore and Singapore Heart Foundation. She is an Associate Editor of Resuscitation and Guest Editor of Resuscitation Plus. M.Y.C. receives speaker's fees and research grants from Astra Zeneca, Abbott Technologies and Boston Scientific. N.W.S.C has received research grant support from NUHS Seed Fund (NUHSRO/2022/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, and the NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS)., (© 2024 The Author(s).)

This study showed a significantly lower incidence of ILD among COVID-19 vaccinated individuals compared to unvaccinated, suggesting that the risk of COVID-19 vaccine-related ILD is not as high as previously reported https://bit.ly/3TWzzxP., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: The impact of long-term chronic periodontal conditions on the risk of lung cancer could not be accurately evaluated. Our aim was to provide more evidence on the connection between chronic periodontitis (CP) and lung cancer using a nationwide dataset., Methods: This study used data from the Korean National Health Insurance Service National Sample Cohort. We enrolled 72,658 individuals with CP (CP cohort) between 2005 and 2019 and 1:1 age- and sex-matched controls without CP (non-CP cohort)., Results: During the median follow-up period of 5.1 (interquartile range, 2.8-8.0) years, 0.56% (n = 405/72,658) of the CP cohort and 0.29% (n = 212/72,658) of the matched non-CP cohort developed lung cancer, with incidence rates of 8.3 and 4.5 per 10,000 person-years. The risk of incident lung cancer was significantly higher in the CP cohort than in the matched non-CP cohort (adjusted hazard ratio = 2.27, 95% confidence interval = 1.94-2.65). The risk of incident lung cancer was 2.45-fold and 2.10-fold higher in mild and moderate-to-severe CP cohorts than in the matched non-CP control. The risk of incident lung cancer was especially higher in the 40-59 age group, females, and never-smokers than their counterparts., Conclusion: We demonstrate that the risk of incident lung cancer is higher in individuals with CP than in those without. The risk of lung cancer was especially high in individuals with more severe CP, females, never-smokers, and obese populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Lee, Lee, Paik, Yun, Park, Yeo, Park, Moon, Kim, Sohn, Kim, Yoon and Park.)

Comprehensive analyses of the association between a family history of lung cancer and lung cancer risk are limited, especially in the Korean population. We used baseline data from the Korean Genome and Epidemiology Study, conducted between 2001 and 2013. This study enrolled 198,980 individuals. Lung cancer diagnoses and family histories were determined using questionnaires. Multivariable logistic regression analysis was performed to evaluate the effect of family history on the risk of lung cancer. Of 198,980 individuals, 6296 (3.2%) and 140 (0.1%) had a family history of lung cancer and lung cancer, respectively. Individuals with a family history of lung cancer in first-degree relatives (FDRs) had a higher risk of lung cancer development than those without (adjusted odds ratio [aOR] = 2.28, 95% confidence interval [CI] = 1.11-4.66). This was more pronounced in young individuals (<60 years) who had affected relatives diagnosed with lung cancer before the age of 60 years (aOR = 3.77, 95% CI = 1.19-11.88). In subgroup analyses, this association was more evident in women, never smokers, and young individuals. A family history of lung cancer, especially in FDRs, is a significant risk factor for lung cancer development in Korea.

Acute coronary syndromes (ACS) often result from the rupture or erosion of high-risk coronary atherosclerotic plaques (ie, vulnerable plaques). Advances in intracoronary imaging such as intravascular ultrasound, optical coherence tomography, or near-infrared spectroscopy have improved the identification of vulnerable plaques, characterized by large plaque burden, small minimal luminal area, thin fibrous cap, and large lipid content. Although pharmacology, including lipid-lowering agents, and intensive risk-factor control are pivotal for management of vulnerable plaques and secondary prevention, recurrent events tend to accrue despite intensive pharmacotherapy. Therefore, it has been hypothesized that local preventive percutaneous coronary intervention may passivate these vulnerable plaques, preventing the occurrence of plaque-related ACS. However, solid evidence is lacking on its use for treatment of non-flow-limiting vulnerable plaques. As such, the optimal management of vulnerable plaques has not been established. Herein, we have reviewed the diagnosis and management of vulnerable plaques, focusing on systematic pharmacology and focal treatments., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Elaeocarpus sylvestris var. ellipticus (ES), which our research group had confirmed inhibits influenza A and SARS-CoV-2 viruses, was investigated to identify new potent and selective inhibitors of herpes simplex virus-1 (HSV-1) replication. To clarify the optimal condition for ES extract (ESE), ES was extracted at different concentrations of 0, 30, 50, 70, and 100%, to screen for its anti-HSV-1 effect. Among these ESE samples, ESE50 (50% concentration) exhibited the strongest inhibition of HSV-1 replication (EC 50 23.2 μg/mL) while showing low cytotoxicity on host cells (IC 50 342.8 μg/mL). The treatment of ESE50 clearly demonstrated a decrease in the expression of ICP0 in the lungs of HSV-1-infected BALB/c nude mice, compared to the MOCK group. Geraniin, which was isolated from ESE50 and analyzed using ESI-MS and 1D-( 1 H- and 13 C-) and 2D-NMR, showed greater potency in inhibiting HSV-1 replication, as determined by the plaque reduction assay (EC 50 8.3 μg/mL) and luciferase inhibition (EC 50 36.9 μg/mL). The results demonstrate that ESE50 and geraniin show great potential as candidates for new drug discovery in the treatment of HSV-1 and related diseases.

The aim of the study was to investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing definite chemo-radiotherapy (CRT). We included 87 patients with LS-SCLC from South Korea, treated between 2005 and 2019 with definite CRT. ALI was calculated using body mass index, serum albumin, and neutrophil-lymphocyte ratio. We categorized 38 patients into the high ALI group (ALI ≥ 44.3) and 48 into the low ALI group (ALI < 44.3). Patients in the high ALI group exhibited longer overall survival (OS) than patients in the low ALI group. In multivariate analysis, prophylactic cranial irradiation (hazard ratio [HR] = 0.366, 95% confidence interval [CI] 0.20-0.66, P = 0.0008), and high ALI (HR = 0.475, 95% CI 0.27-0.84, P = 0.0103) were identified as independent prognostic factors for predicting better OS. Notably, a high ALI score was particularly indicative of longer survival in patients treated with the combination of etoposide and cisplatin. In conclusion, this study demonstrated that a high pretreatment ALI was significantly associated with better OS in patients with LS-SCLC undergoing definite CRT. This suggests that ALI could be a useful tool for predicting prognosis and guiding chemotherapy regimen selections in clinical practice for LS-SCLC., (© 2024. The Author(s).)

Current literature primarily delves into the relationship between bronchiectasis and severe asthma, and only a few studies have evaluated the impact of bronchiectasis in patients with non-severe asthma. Therefore, this study investigated the clinical impact of bronchiectasis in patients with non-severe asthma. A prospective observational study of 140 non-severe asthmatic patients with (bronchiectasis group) and without bronchiectasis (control group) was conducted between September 2012 and February 2022. The bronchiectasis and control groups were compared in terms of demographics, lung function, asthma control test (ACT) results, exacerbation history, and respiratory medications. Among 140 non-severe asthmatic subjects, approximately 15.7% (n = 22) had bronchiectasis. The most common type of bronchiectasis was cylindrical type (90.7%). The left lingular division was the most frequently involved lung lobe (20.4%). There were no significant differences in the demographics (age, sex, body mass index, smoking history, and comorbidities) or ACT results between the 2 groups. The bronchiectasis group used inhaled corticosteroids/long-acting β2-agonists ( P = 0.074) and mucolytics ( P < 0.001) more frequently than the control group. Compared to the control group, the bronchiectasis group had lower forced expiratory volume in 1 second (FEV1) (L) (1.9 ± 0.7 L vs. 2.3 ± 0.9 L, P = 0.039) and FEV1%predicted (67.2 ± 22.2%predicted vs. 77.1 ± 20.0%predicted, P = 0.038). The rate of hospital admission to a general ward in the preceding year was significantly higher in the bronchiectasis group compared to those of the control group (23.8% vs. 3.5%, P = 0.005) with an adjusted odds ratio of 6.308 (95% confidence interval, 1.401-28.392). Patients with non-severe asthma and bronchiectasis had lower lung function and more frequent exacerbations requiring hospitalization than those without bronchiectasis. More attention is needed for asthmatic patients with bronchiectasis, even if the asthma is not severe., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Biomarkers are playing an increasingly important role in antimicrobial stewardship. Their applications have included use in algorithms that evaluate suspected bacterial infections or provide guidance on when to start or stop antibiotic therapy, or when therapy should be repeated over a short period (6-12 h). Diseases in which biomarkers are used as complementary tools to determine the initiation of antibiotics include sepsis, lower respiratory tract infection (LRTI), COVID-19, acute heart failure, infectious endocarditis, acute coronary syndrome, and acute pancreatitis. In addition, cut-off values of biomarkers have been used to inform the decision to discontinue antibiotics for diseases such as sepsis, LRTI, and febrile neutropenia. The biomarkers used in antimicrobial stewardship include procalcitonin (PCT), C-reactive protein (CRP), presepsin, and interleukin (IL)-1β/IL-8. The cut-off values vary depending on the disease and study, with a range of 0.25-1.0 ng/mL for PCT and 8-50 mg/L for CRP. Biomarkers can complement clinical diagnosis, but further studies of microbiological biomarkers are needed to ensure appropriate antibiotic selection.

Background: Since the emergence of hypervirulent strains of Clostridioides difficile , the incidence of C. difficile infections (CDI) has increased significantly., Methods: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020., Results: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively., Conclusion: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Purpose: To unravel the mechanism regulating the phosphorylation of glycogen synthase kinase 3 (GSK3) and the correlation between the inhibitory phosphorylation of GSK3α and sperm motility in human., Materials and Methods: The phosphorylation and priming phosphorylated substrate-specific kinase activity of GSK3 were examined in human spermatozoa with various motility conditions., Results: In human spermatozoa, GSK3α/β was localized in the head, midpiece, and principal piece of tail and p-GSK3α(Ser21) was enriched in the midpiece. The ratio of p-GSK3α(Ser21)/GSK3α was positively coupled with normal sperm motility criteria of World Health Organization. In high-motility spermatozoa, p-GSK3α(Ser21) phosphotyrosine (p-Tyr) proteins but p-GSK3α(Tyr279) markedly increased together with decreased kinase activity of GSK3 after incubation in Ca 2+ containing medium. In high-motility spermatozoa, p-GSK3α(Ser21) levels were negatively coupled with kinase activity of GSK3, and which was deregulated in low-motility spermatozoa. In high-motility spermatozoa, 6-bromo-indirubin-3'-oxime, an inhibitor of kinase activity of GSK3 increased p-GSK3α(Ser21) and p-Tyr proteins. p-GSK3α(Ser21) and p-Tyr protein levels were decreased by inhibition of PKA and Akt. Calyculin A, a protein phosphatase-1/2A inhibitor, markedly increased the p-GSK3α(Ser21) and p-Tyr proteins, and significantly increased the motility of low-motility human spermatozoa., Conclusions: Down regulation of kinase activity of GSK3α by inhibitory phosphorylation was positively coupled with human sperm motility, and which was regulated by Ca 2+ , PKA, Akt, and PP1. Small-molecule inhibitors of GSK3 and PP1 can be considered to potentiate human sperm motility., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Background: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls., Methods: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls., Results: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92)., Conclusion: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants., Methods: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status., Results: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients., Conclusions: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.

Although major countries, such as South Korea, have developed and disseminated national smoking cessation guidelines, these efforts have been limited to developing individual societies or specialized institution-based recommendations. Therefore, evidence-based clinical guidelines are essential for developing smoking cessation interventions and promoting effective smoking cessation treatments. This guideline targets frontline clinical practitioners involved in a smoking cessation treatment support program implemented in 2015 with the support of the National Health Insurance Service. The Guideline Development Group of 10 multidisciplinary smoking cessation experts employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to review recent domestic and international research and guidelines and to determine evidence levels using the GRADE methodology. The guideline panel formulated six strong recommendations and one conditional recommendation regarding pharmacotherapy choices among general and special populations (mental disorders and chronic obstructive lung disease [COPD]). Strong recommendations favor varenicline rather than a nicotine patch or bupropion, using varenicline even if they are not ready to quit, using extended pharmacotherapy (>12 weeks) rather than standard treatment (8-12 weeks), or using pharmacotherapy for individuals with mental disorders or COPD. The conditional recommendation suggests combining varenicline with a nicotine patch instead of using varenicline alone. Aligned with the Korean Society of Medicine's clinical guideline development process, this is South Korea's first domestic smoking cessation treatment guideline that follows standardized guidelines. Primarily focusing on pharmacotherapy, it can serve as a foundation for comprehensive future smoking cessation clinical guidelines, encompassing broader treatment topics beyond medications.

Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5-13.2], P = 7.2 × 10 -6 ). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5-1423], P = 7.5 × 10 -6 ). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility. Yoon et al. showed that individuals who carry NAT2 UAs and ATP7B 832R/R genotypes are at increased risk of developing isoniazid hepatotoxicity, primarily due to the increased synergistic toxicity between isoniazid and copper, which exacerbates mitochondrial dysfunction-related apoptosis., (© 2024. The Author(s).)

Background: Adjuvant chemotherapy has reduced the risk of recurrence and death in stage IB non-small cell lung cancer (NSCLC) with high-risk factors; however, the impact of visceral pleural invasion (VPI) on outcomes in stage IB NSCLC treated with adjuvant chemotherapy remains controversial. The aim of this study was to explore the clinical and prognostic significance of adjuvant chemotherapy for stage IB (1-4 cm) NSCLC with VPI., Methods: This retrospective study included 251 patients admitted between January 2008 and May 2018 from four hospitals who underwent complete resection for Tumor-Node-Metastasis (TNM) 8th edition stage IB NSCLC with VPI. The relationship between adjuvant chemotherapy and overall survival (OS) or recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards model., Results: Of 251 patients with stage IB NSCLC with VPI, 122 (48.6%) received adjuvant chemotherapy after surgical resection and 129 (51.4%) were placed under observation. Multivariable analysis showed that adjuvant chemotherapy was an independent predictor of RFS [adjusted hazard ratio (aHR), 0.57; 95% confidence interval (CI): 0.33-0.96; P=0.036]. A micropapillary pattern (aHR, 2.46; 95% CI: 1.33-4.55; P=0.004) and lymphovascular invasion (aHR, 2.86; 95% CI: 1.49-5.48; P=0.002) were associated with a higher risk of recurrence. Multivariable analysis also showed that adjuvant chemotherapy was an independent predictor of OS (aHR, 0.22; 95% CI: 0.09-0.58; P=0.002). In a subgroup analysis of patients with a tumor size of 1-3 cm, adjuvant chemotherapy was associated with improved RFS and OS, and this association was maintained even when patients with VPI had additional risk factors., Conclusions: Our study shows that adjuvant chemotherapy is appropriate for patients with stage IB (1-4 cm) NSCLC with VPI, and even those with smaller tumors (1-3 cm)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-936/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)