Search

Jungsang Kim,1,2,* Ju-Hyun Lee,3,* Dongbin Jeong,4 Taekyung Lim,4 Sangwoo Jung,4 Kwongil Paeng,4 Sangyoup Lee,4 Hyunki Cho,4 Seungyoup Lee,4 Ikdu Kim,4 Byungsoo Kang,5,6 Jae Hyo Kim,7 Hongmin Chu,8 Museok Hong4 1Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Daeat Korean Medicine Clinic, Suwon, Kyunggi-do, Republic of Korea; 3Department of Medical Support, Imsil-Gun Medical Center, Imsil, Jeollabuk-do, Republic of Korea; 4Rodam Korean Medical Clinic Network, Seoul, Republic of Korea; 5Daeat Korean Medicine Hospital, Seoul, Republic of Korea; 6Gachon University, Seongnam-si, Gyeonggi-do, Republic of Korea; 7Department of Meridian & Acupoint, College of Korean Medicine, Wonkwang University, Iksan-si, Jeollabuk-do, Republic of Korea; 8Korean Medicine Convergence Research Information Center for Stroke, College of Korean Medicine, Wonkwang University, Gwangju, Republic of Korea*These authors contributed equally to this workCorrespondence: Hongmin Chu, Korean Medicine Convergence Research Information Center for Stroke, College of Korean Medicine, Wonkwang University, Hoejaero 1140-23, Republic of Korea, Email hongminchu2@gmail.com Museok Hong, Department of Korean Internal Medicine, College of Korean Medicine, Wonkwang University, 460, Iksan-daero, Iksan-si, Jeollabuk-do, Republic of Korea, Email hongbar21@hanmail.netPurpose: This study is a retrospective, multicenter research designed to report the efficacy of Korean medicine subcision therapies in scar treatment.Patients and Methods: Charts and photographs of 29 patients who received subcision treatment between May 2016 and June 2020 in four scar treatment network clinics were analyzed. The Qualitative Global Acne Scarring Grade System (QGASC) and the Stony Brook Scar Evaluation Scale (SBSES) were used to objectively measure scar scores.Results: Except for 4 patients whose GASGS and SBSES scores remained unchanged, most patients’ scars showed improvement from Visit 2 to about Visit 8. Furthermore, the degree of change for both scales was found to be statistically significant.Conclusion: Subcision therapy using acupuncture has been found to be an effective treatment for scar, with statistically significant improvements in patients’ SBSES and QGASC scores.Keywords: scar, Korean medicine, subcision, acupuncture

Sangmin Lee,1 Jae-Hun Kim,2 Wan Song,1 Hyun Hwan Sung,1 Hwang Gyun Jeon,1 Byong Chang Jeong,1 Seong Il Seo,1 Seong Soo Jeon,1 Se Hoon Park,3 Ji Hyun Lee,2 Jiwoong Yu,1,* Minyong Kang1,4,5,* 1Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea; 5Samsung Genome Institute, Samsung Medical Center, Seoul, Korea*These authors contributed equally to this workCorrespondence: Minyong Kang; Jiwoong Yu, Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea, Tel +82-2-3410-1138 ; +82-2-3410-3559, Fax +82-2-3410-6992 ; +82-2-3410-6990, Email dr.minyong.kang@gmail.com; darwin082smart@gmail.comPurpose: We investigated the relationship between body mass index (BMI), radiological body composition, and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) underwent first-line immune checkpoint inhibitor (ICI)-based therapy.Methods: Analyzing data from 102 patients treated between November 2019 and March 2023, pre-treatment computed tomography (CT) scans assessed fat and muscle areas. BMI and body composition indices were examined, including skeletal muscle index, subcutaneous fat index (SFI), visceral fat index, and total fat index. Kaplan–Meier curves and Log rank tests compared progression-free survival (PFS) and overall survival (OS), while multivariable Cox proportional regression analysis was performed to identify the variables significantly associated with survival outcomes.Results: 54 patients (52.9%) experienced disease progression, and 26 (25.5%) died during a median follow-up of 17.4 months. High SFI was significantly associated with improved OS (p = 0.018) but not PFS (p = 0.090). Multivariable analysis confirmed the positive impact of high SFI on OS (adjusted HR: 0.37, p = 0.029) and suggested a trend towards improved PFS (adjusted HR: 0.61, p = 0.088). Notably, in the ipilimumab + nivolumab subgroup, high SFI significantly correlated with both PFS and OS (p = 0.047 and p = 0.012, respectively).Conclusion: High SFI predicts favorable OS in patients with mRCC receiving first-line ICI-based therapy, especially patients treated with ipilimumab + nivolumab displayed a significant association between high SFI and favorable PFS and OS.Keywords: immunotherapy, renal cell carcinoma, body composition, prognosis

Enkyu Noh,1,&ast; Hyungmin Jeong,1,&ast; In-So Cho,2 Min-Seok Chang,2 Iseul Yu,2 Sunmin Park,2 Ji-Ho Lee,2 Seok Jeong Lee,2 Won-Yeon Lee,2 Suk Joong Yong,2 Sang-Ha Kim2 1Yonsei University Wonju College of Medicine, Wonju, 26426, Korea; 2Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea&ast;These authors contributed equally to this workCorrespondence: Sang-Ha Kim, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea, 20 Ilsanro, Wonju, 26426, Korea, Tel +82-33-741-0926, Fax +82-33-746-4667, Email sanghakim@yonsei.ac.krPurpose: Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea.Patients and Methods: This population-based cohort study enrolled adults aged ≥ 40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan–Meier curves.Results: Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P < 0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P < 0.001).Conclusion: The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.Keywords: cardiovascular event, chronic obstructive pulmonary disease, metabolic syndrome

En-Yi Lin,1,2 Shao-Xi Hsu,1 Bing-Hua Wu,1 Yu-Chen Deng,1,3 Wei Wuli,1 Yuan-Sheng Li,3 Jui-Hao Lee,3 Shinn-Zong Lin,2,4 Horng-Jyh Harn,2,5 Tzyy-Wen Chiou1 1Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan; 2Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; 3Everfront Biotech Inc, Taipei, Taiwan; 4Department of Neurosurgery, Hualien Tzu Chi Hospital, Hualien, Taiwan; 5Department of Pathology, Hualien Tzu Chi Hospital, Hualien, TaiwanCorrespondence: Tzyy-Wen Chiou, Department of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Road, Shou-Feng, Hualien, Taiwan, Tel +886-3-890-3638, Email twchiou@gms.ndhu.edu.tw Horng-Jyh Harn, Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan, Tel +886-3-856-1825, Email arthewduke@gmail.comPurpose: Exosomes are membrane vesicles secreted by various cells and play a crucial role in intercellular communication. They can be excellent delivery vehicles for oligonucleotide drugs, such as microRNAs, due to their high biocompatibility. MicroRNAs have been shown to be more stable when incorporated into exosomes; however, the lack of targeting and immune evasion is still the obstacle to the use of these microRNA-containing nanocarriers in clinical settings. Our goal was to produce functional exosomes loaded with target ligands, immune evasion ligand, and oligonucleotide drug through genetic engineering in order to achieve more precise medical effects.Methods: To address the problem, we designed engineered exosomes with exogenous cholecystokinin (CCK) or somatostatin (SST) as the targeting ligand to direct the exosomes to the brain, as well as transduced CD47 proteins to reduce the elimination or phagocytosis of the targeted exosomes. MicroRNA-29b-2 was the tested oligonucleotide drug for delivery because our previous research showed that this type of microRNA was capable of reducing presenilin 1 (PSEN1) gene expression and decreasing the β-amyloid accumulation for Alzheimer’s disease (AD) in vitro and in vivo.Results: The engineered exosomes, containing miR29b-2 and expressing SST and CD47, were produced by gene-modified dendritic cells and used in the subsequent experiments. In comparison with CD47-CCK exosomes, CD47-SST exosomes showed a more significant increase in delivery efficiency. In addition, CD47-SST exosomes led to a higher delivery level of exosomes to the brains of nude mice when administered intravenously. Moreover, it was found that the miR29b-2-loaded CD47-SST exosomes could effectively reduce PSEN1 in translational levels, which resulted in an inhibition of beta-amyloid oligomers production both in the cell model and in the 3xTg-AD animal model.Conclusion: Our results demonstrated the feasibility of the designed engineered exosomes. The application of this exosomal nanocarrier platform can be extended to the delivery of other oligonucleotide drugs to specific tissues for the treatment of diseases while evading the immune system.Keywords: oligonucleotide drug, functional nanocarriers, hippocampus, SH-SY5Y, 3xTG-AD

Young Woo Um,1 Inwon Park,1 Jae Hyuk Lee,1 Hee Eun Kim,1 Dongkwan Han,1 Seung Hyun Kang,1 Seonghye Kim,1 You Hwan Jo1– 3 1Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea; 2Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea; 3Disaster Medicine Research Center, Seoul National University Medical Research Center, Seoul, KoreaCorrespondence: Jae Hyuk Lee, Department of Emergency Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Korea, Tel +82-31-787-7579, Fax +82-31-787-4055, Email hyukmd@gmail.comPurpose: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis.Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility.Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028).Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.Keywords: anti-bacterial agents, biomarkers, drug resistance, sepsis, triggering receptor expressed on myeloid cells-1

Seunghee Bae,1 Sowon Bae,1 Hee Su Kim,1 Ye Jin Lim,1 Gyeongmi Kim,2 In-Chul Park,2 Kyeong A So,3 Tae Jin Kim,3 Jae Ho Lee1 1Department of Cosmetics Engineering, Konkuk University, Seoul, 05029, Republic of Korea; 2Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Republic of Korea; 3Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, 05030, Republic of KoreaCorrespondence: Jae Ho Lee, Department of Cosmetics Engineering, Konkuk University, Seoul, 05029, Republic of Korea, Email jaeho390@konkuk.ac.krBackground: Ovarian cancer is one of women’s malignancies with the highest mortality among gynecological cancers. Paclitaxel is used in first-line ovarian cancer chemotherapy. Research on paclitaxel-resistant ovarian cancer holds significant clinical importance.Methods: Cell viability and flow cytometric assays were conducted at different time and concentration points of deguelin and paclitaxel treatment. Immunoblotting was performed to assess the activation status of key signaling molecules important for cell survival and proliferation following treatment with deguelin and paclitaxel. The fluo-3 acetoxymethyl assay for P-glycoprotein transport activity assay and cell viability assay in the presence of N-acetyl-L-cysteine were also conducted.Results: Cell viability and flow cytometric assays demonstrated that deguelin resensitized paclitaxel in a dose- and time-dependent manner. Cotreatment with deguelin and paclitaxel inhibited EGFR and its downstream signaling molecules, including AKT, ERK, STAT3, and p38 MAPK, in SKOV3-TR cells. Interestingly, cotreatment with deguelin and paclitaxel suppressed the expression level of EGFR via the lysosomal degradation pathway. Cotreatment did not affect the expression and function of P-glycoprotein. N-acetyl-L-cysteine failed to restore cell cytotoxicity when used in combination with deguelin and paclitaxel in SKOV3-TR cells. The expression of BCL-2, MCL-1, and the phosphorylation of the S155 residue of BAD were downregulated. Moreover, inhibition of paclitaxel resistance by deguelin was also observed in HeyA8-MDR cells.Conclusion: Our research showed that deguelin effectively suppresses paclitaxel resistance in SKOV3-TR ovarian cancer cells by downregulating the EGFR and its downstream signaling pathway and modulating the BCL-2 family proteins. Furthermore, deguelin exhibits inhibitory effects on paclitaxel resistance in HeyA8-MDR ovarian cancer cells, suggesting a potential mechanism for paclitaxel resensitization that may not be cell-specific. These findings suggest that deguelin holds promise as an anticancer therapeutic agent for overcoming chemoresistance in ovarian cancer. Keywords: ovarian cancer, paclitaxel-resistance, deguelin, EGFR, AKT

Dongjin Shin,1,&ast; Juhyun Kim,1,&ast; Jang Ho Lee,2,&ast; Jong-Il Kim,1,3– 5 Yeon-Mok Oh2 1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea; 4Genomic Medicine Institute, Seoul National University, Seoul, Republic of Korea; 5Seoul National University Cancer Research Institute, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jong-Il Kim, Department of Biomedical Sciences, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Tel +82-2-740-8246, Email jongil@snu.ac.kr Yeon-Mok Oh, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-3136, Fax +82-2-3010-6968, Email ymoh55@amc.seoul.krPurpose: The aim of the study was to use RNA sequencing (RNA-seq) data of lung from chronic obstructive pulmonary disease (COPD) patients to identify the bacteria that are most commonly detected. Additionally, the study sought to investigate the differences in these infections between normal lung tissues and those affected by COPD.Patients and Methods: We re-analyzed RNA-seq data of lung from 99 COPD patients and 93 non-COPD smokers to determine the extent to which the metagenomes differed between the two groups and to assess the reliability of the metagenomes. We used unmapped reads in the RNA-seq data that were not aligned to the human reference genome to identify more common infections in COPD patients.Results: We identified 18 bacteria that exhibited significant differences between the COPD and non-COPD smoker groups. Among these, Yersinia enterocolitica was found to be more than 30% more abundant in COPD. Additionally, we observed difference in detection rate based on smoking history. To ensure the accuracy of our findings and distinguish them from false positives, we double-check the metagenomic profile using Basic Local Alignment Search Tool (BLAST). We were able to identify and remove specific species that might have been misclassified as other species in Kraken2 but were actually Staphylococcus aureus, as identified by BLAST analysis.Conclusion: This study highlighted the method of using unmapped reads, which were not typically used in sequencing data, to identify microorganisms present in patients with lung diseases such as COPD. This method expanded our understanding of the microbial landscape in COPD and provided insights into the potential role of microorganisms in disease development and progression.Keywords: chronic obstructive pulmonary disease, next-generation sequencing, microbiome, metagenomics

Jang Ho Lee,1 Sehee Kim,2 Ye-Jee Kim,2 Sei Won Lee,1 Jae Seung Lee,1 Yeon-Mok Oh1 1Department of Pulmonary and Critical Care Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2Department of Clinical Epidemiology and Biostatistics, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of KoreaCorrespondence: Yeon-Mok Oh, Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Centre, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-3136, Fax +82-2-3010-6968, Email ymoh55@amc.seoul.krPurpose: To identify the risk factors for chronic obstructive pulmonary disease (COPD) in view of potential etiotypes in a general population and referred COPD patients.Patients and Methods: We performed a cross-sectional observational study utilizing two distinct datasets: a dataset of a general population including 2430 subjects with COPD from the Korea National Health and Nutrition Examination Survey (KNHANES) and another dataset of referral clinics including 579 patients with COPD from the Korean Obstructive Lung Disease (KOLD).Results: The mean age of both groups was 67 years, and 71.2% and 93.8% were male in the COPD subjects from the KNHANES and the KOLD, respectively. The mean forced expiratory volume in 1 second of predicted value was 79.1% (KNHANES) and 55.4% (KOLD). The frequency of risk factors of cigarette smoking (C), infection (I), pollution (P), and asthma (A) was 54.6%, 9.4%, 10.7%, and 7.9%, respectively, in the KNHANES COPD subjects, and 88.4%, 26.6%, 41.6%, and 35.2%, respectively, in the KOLD COPD subjects. Risk factors were unidentified in 32.6% (KNHANES) and 3.1% (KOLD) of COPD subjects. Additionally, 14.1% and 66.2% of subjects with COPD had two or more risk factors in the KNHANES and KOLD, respectively.Conclusion: The profiles of risk factors C, I, P, and A were identified and appeared to be different among the two COPD groups from a general population or referral clinics. In some of the COPD subjects, risk factors were not identified, so we should endeavour to find out unidentified COPD risk factors, especially in the general population.Keywords: chronic obstructive pulmonary disease, etiotype, smoking, tuberculosis, asthma, pollutants

Breda Cushen,1,&ast; Mariko Siyue Koh,2,&ast; Trung N Tran,3 Neil Martin,3,4 Ruth Murray,5 Thendral Uthaman,6 Celine Yun Yi Goh,5,6 Rebecca Vella,7 Neva Eleangovan,5,6 Lakmini Bulathsinhala,5,6 Jorge F Maspero,8,9 Matthew J Peters,10 Florence Schleich,11 Paulo Pitrez,12 George Christoff,13 Mohsen Sadatsafavi,14 Carlos A Torres-Duque,15,16 Celeste Porsbjerg,17 Alan Altraja,18 Lauri Lehtimäki,19 Arnaud Bourdin,20 Christian Taube,21 Nikolaos G Papadopoulos,22,23 Csoma Zsuzsanna,24 Unnur Björnsdóttir,25 Sundeep Salvi,26 Enrico Heffler,27 Takashi Iwanaga,28 Mona al-Ahmad,29 Désirée Larenas-Linnemann,30 Job FM van Boven,31 Bernt Bøgvald Aarli,32,33 Piotr Kuna,34 Cláudia Chaves Loureiro,35,36 Riyad Al-lehebi,37 Jae Ha Lee,38 Nuria Marina,39 Leif Bjermer,40 Chau-Chyun Sheu,41,42 Bassam Mahboub,43 John Busby,44 Andrew Menzies-Gow,45 Eileen Wang,46 David B Price5,6,47 On behalf of ISAR Inventory Study Group1Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland; 2Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 3AstraZeneca, Gaithersburg, MD, USA; 4Department of Respiratory Medicine, University of Leicester, Leicester, UK; 5Optimum Patient Care Global, Cambridge, UK; 6Observational Pragmatic Research Institute, Singapore, Singapore; 7Optimum Patient Care, Brisbane, Queensland, Australia; 8Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 9University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 10Department of Thoracic Medicine, Concord Hospital, Sydney, Australia; 11CHU Sart-Tilman, GIGA I3, University of Liege, Liège, Wallonia, Belgium; 12Pulmonology Division, Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil; 13Faculty of Public Health, Medical University, Sofia, Bulgaria; 14Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada; 15CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 16Universidad de La Sabana, Chia, Colombia; 17Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark; 18Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 19Allergy Centre, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 20PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 21Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 22Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 23Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 24Asthma Outpatient Clinic, National Koranyi Institute for Pulmonology, Budapest, Hungary; 25Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland; 26Pulmocare Research and Education Foundation, Pune, India; 27Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 28Kindai University Hospital, Osakasayama, Japan; 29Microbiology Department, College of Medicine, Kuwait University, Kuwait, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 30Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 31University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Department of Clinical Pharmacy & Pharmacology, Groningen, the Netherlands; 32Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway; 33Department of Clinical Science, University of Bergen, Bergen, Norway; 34Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland; 35Pneumology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 36Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 37Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia, Alfaisal University, Riyadh, Saudi Arabia; 38Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 39Pneumology Service, Biocruces, Cruces University Hospital, Barakaldo, Spain; 40Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; 41Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 42Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 43Rashid Hospital, Dubai Health Authority (DHA), Dubai, United Arab Emirates; 44Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland, UK; 45Lung Division, Royal Brompton & Harefield Hospital, London, UK; 46Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health and University of Colorado School of Medicine, Denver and Aurora, CO, USA; 47Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK&ast;These authors contributed equally to this workCorrespondence: David B Price, Observational and Pragmatic Research Institute (OPRI) Pte Ltd, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgAim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests.Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR’s Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised.Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting > 90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases.Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.Keywords: Asia-Pacific, biologics, COVID-19, Europe, ISAR, International Severe Asthma Registry, oral corticosteroids, Registry, Middle East, Severe Asthma, Latin America, USA

Tou-Yuan Tsai,1– 3,&ast; Jen-Feng Lin,4,&ast; Yu-Kang Tu,3 Jian-Heng Lee,4 Yu-Ting Hsiao,4 Sheng-Feng Sung,5 Ming-Jen Tsai4 1Department of Emergency Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, Taiwan; 3Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 4Department of Emergency Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan; 5Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan&ast;These authors contributed equally to this workCorrespondence: Sheng-Feng Sung, Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan, Tel +886 5 276 5041 Ext 7283, Fax +886 5 278 4257, Email sfusng@cych.org.tw; richard.sfsung@gmail.com Ming-Jen Tsai, Department of Emergency Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan, Tel +886 5 276 5041 Ext 1909, Fax +886 5 277 4511, Email tshi33@gmail.comPurpose: Distinguishing ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) is crucial in acute myocardial infarction (AMI) research due to their distinct characteristics. However, the accuracy of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for STEMI and NSTEMI in Taiwan’s National Health Insurance (NHI) database remains unvalidated. Therefore, we developed and validated case definition algorithms for STEMI and NSTEMI using ICD-10-CM and NHI billing codes.Patients and Methods: We obtained claims data and medical records of inpatient visits from 2016 to 2021 from the hospital’s research-based database. Potential STEMI and NSTEMI cases were identified using diagnostic codes, keywords, and procedure codes associated with AMI. Chart reviews were then conducted to confirm the cases. The performance of the developed algorithms for STEMI and NSTEMI was assessed and subsequently externally validated.Results: The algorithm that defined STEMI as any STEMI ICD code in the first three diagnosis fields had the highest performance, with a sensitivity of 93.6% (95% confidence interval [CI], 91.7– 95.2%), a positive predictive value (PPV) of 89.4% (95% CI, 87.1– 91.4%), and a kappa of 0.914 (95% CI, 0.900– 0.928). The algorithm that used the NSTEMI ICD code listed in any diagnosis field performed best in identifying NSTEMI, with a sensitivity of 82.6% (95% CI, 80.7– 84.4%), a PPV of 96.5% (95% CI, 95.4– 97.4), and a kappa of 0.889 (95% CI, 0.878– 0.901). The algorithm that included either STEMI or NSTEMI ICD codes listed in any diagnosis field showed excellent performance in defining AMI, with a sensitivity of 89.4% (95% CI, 88.2– 90.6%), a PPV of 95.6% (95% CI, 94.7– 96.4%), and a kappa of 0.923 (95% CI, 0.915– 0.931). External validation confirmed these algorithms’ efficacy.Conclusion: Our results provide valuable reference algorithms for identifying STEMI and NSTEMI cases in Taiwan’s NHI database.Keywords: administrative claims data, acute myocardial infarction, diagnosis, ICD-10-CM, non-ST-elevation myocardial infarction, ST-elevation myocardial infarction

Yune-Young Shin,1,&ast; Sojung Park,1,&ast; Kyung Joo Kim,2 Chin Kook Rhee,2 Kwang Ha Yoo,3 Ki-Suck Jung,4 Jin Hwa Lee1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 4Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Gyeonggi-do, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jin Hwa Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, 25 Magokdong-ro 2-gil Gangseo-gu, Seoul, 07804, Republic of Korea, Tel +82 2 6986 1631, Fax +82 2-2655-2076, Email jinhwalee@ewha.ac.krPurpose: To investigate the clinical characteristics and medical utilization of smokers with preserved ratio impaired spirometry (PRISm).Patients and Methods: We used data from the Korean National Health and Nutrition Examination Survey between 2007 and 2012, linked to the Health Insurance Review and Assessment Service. Clinical characteristics and medical utilization, including inpatient admission, emergency department visit, prescribed medication, and medical cost, were retrospectively compared among three groups: normal spirometry, PRISm, and chronic obstructive pulmonary disease (COPD).Results: A total of 7115 smokers were included (4743 normal spirometry, 689 PRISm, and 1683 COPD subjects). The mean age was the highest in the COPD group, followed by the PRISm and normal groups, and the proportion of women was the highest in the PRISm group. The tobacco exposure, socioeconomic status (SES), and schooling level of the PRISm group were at levels between those of the normal and COPD groups. However, the PRISm group had the highest proportion of current smokers, highest body mass index (BMI), and lowest mean FEV1 and FVC % predicted. During the study period, the medical utilization of 92 smokers (13.4%) in the PRISm group and 436 smokers (25.9%) in the COPD group was related to respiratory diseases. Emergency department visit or hospitalization and overall medical cost of the PRISm group were comparable to those of the COPD group, except for outpatient clinic visit. Old age, women, low BMI, low SES, low schooling level, high amount of tobacco exposure, wheezing, and decreased FEV1 and FVC % predicted were factors associated with medical utilization in PRISm.Conclusion: Medical utilization was comparable between the PRISm and COPD groups. Smokers with PRISm who were older, women, or heavy smokers with low BMI, low SES and schooling level, wheezing, or low FEV1 and FVC might need close observation and early treatment.Keywords: emergency department, hospitalization, lung function, restrictive lung disease, wheezing

Min-Cheol Park,1,2,&ast; Ju-Hyun Lee,3,&ast; Eun-Jin Seong,4 Dong-Sung Lee,5 Eun-Heui Jo2,6 1Department of Korean Medicine Ophthalmology and Otolaryngology and Dermatology, Wonkwang University Korean Medicine Hospital, Iksan, Jeollabuk-do, 54538, Republic of Korea; 2Research Center of Traditional Korean Medicine, Wonkwang University, Iksan, Jeollabuk-do, 54538, Republic of Korea; 3Department of Medical Support, Imsil-Gun Medical Center, Imsil, Jeollabuk-do, 55927, Republic of Korea; 4Seoul Clinic, Hanam, Gyeonggi-do, 12945, Republic of Korea; 5College of Pharmacy, Chosun University, Gwangju, Jeollanam-do, 61452, Republic of Korea; 6Department of Acupuncture and Moxibustion, Wonkwang University Korean Medicine Hospital, Jeonju, Jeollabuk-do, 54887, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Dong-Sung Lee, College of Pharmacy, Chosun University, 309, Pilmundae-ro, Dong-gu, Gwangju, Jeollanam-do, 61452, Republic of Korea, Tel +82-62-230-6386, Fax +82-62-232-8834, Email dslee2771@chosun.ac.kr Eun-Heui Jo, Department of Acupuncture and Moxibustion, Wonkwang University Korean Medicine Hospital, 99, Garyeonsan-ro, Deokjin-gu, Jeonju, Jeollabuk-do, 54887, Republic of Korea, Tel +82-63-270-1022, Fax +82-63-270-1199, Email freezo@wonkwang.ac.krPurpose: This study is to report a case of chronic atopic dermatitis (AD) with eosinophilia, which did not respond to conventional therapy and was improved by Daesiho-tang (DSHT).Patients and Methods: The patient visited our clinic with symptoms of atopic dermatitis including skin lesions and pruritus. Based on her symptoms, DSHT was prescribed. At each visit, the Scoring Atopic Dermatitis (SCORAD), Dermatology Life Quality Index (DLQI), and accompanying systemic symptoms (ASS) were measured. Multiple Allergen Simultaneous Test (MAST) was initially performed for 108 allergens and analyzed by Western blotting using an Alternate Scoring Method (ASM) according to the specific IgE concentration. Also, peripheral blood laboratory (Lab) tests were performed three times during the patient’s visit.Results: After taking DSHT, the total SCORAD score improved from 62.9 to 23.5, while the patient’s ASS also improved. The DLQI score improved from 19 to 5. The total number of eosinophils in the peripheral blood, which showed a mild increase, recovered from 17.2% (0.98 x103/μL) to 4.5% (0.24 x103/μL). The total IgE slightly decreased, while AST and ALT were also restored to normal ranges.Conclusion: Based on this case, DSHT is considered a potential alternative treatment for AD.Graphical Abstract: Keywords: case report, atopic dermatitis, eosinophilia, Daesiho-tang

Jieun Shin,1 Ji-Hoon Lee,1 Nam-Yi Kim2 1Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea; 2Department of Nursing, Konyang University, Daejeon, Republic of KoreaCorrespondence: Nam-Yi Kim, Department of Nursing, Konyang University, Daejeon, 35365, Republic of Korea, Tel +82-42-600-8586, Fax +82-42-600-8555, Email namyi00@konyang.ac.kr; namyi8213@gmail.comPurpose: To address the increasing number of patient safety incidents, their scope and extent should be assessed and the situations in which they occur determined. This study employed a decision tree analysis based on patient safety incident cases to identify groups at high risk for adverse patient safety incidents and provide data to develop prevention strategies for minimizing their occurrence or recurrence.Methods: In total, 8934 patient safety incidents were analyzed using the “ 2021 Patient Safety Report Data”, which were systematically collected by the Korea Institute for Healthcare Accreditation. A decision tree analysis (Chi-square Automatic Interaction Detection) was employed to identify the characteristics associated with the degree of risk for patient safety incidents.Results: The groups most vulnerable to adverse events were those who experienced healthcare-associated infections (HAI) in long-term care facilities, followed by those experiencing HAI in tertiary hospitals, general hospitals, or clinics, and those experiencing fall-related events in neuropsychiatry departments of tertiary hospitals, general hospitals, or clinics.Conclusion: The most important factor in the degree of harm in patient safety accidents was the type of accident, followed by the type of medical institution, and then the treatment department. Particularly, HAI and falls are the most important factors determining the degree of harm in patient safety accidents.Keywords: decision tree, infection, incident, patient safety, prevention

Jung Hwan Lee,1 Jun Ho Lee,2 Min Cheol Chang3 1Namdarun Rehabilitation Clinic, Yongin-City, Gyeonggi-Do, South Korea; 2Department of Neurosurgery, Kyung Hee University Medical Center, Seoul, 02447, South Korea; 3Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Daegu, 705-717, Republic of KoreaCorrespondence: Min Cheol Chang, Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, 317-1, Daemyungdong, Namku, Daegu, 705-717, Republic of Korea, Tel +82-53-620-4862, Email wheel633@gmail.comPurpose: This study aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) in patients with lumbosacral disc herniation by comparing its effect between those diagnosed by clinical evaluation and plain radiography only (X-ray group) and those by additional magnetic resonance imaging (MRI) (MRI group). Additionally, we investigated the accuracy of the preliminary clinical assumption in the X-ray group using confirmative post-injection MRI.Patients and Methods: We retrospectively recruited 367 patients with back and radicular pain due to lumbosacral disc herniation from a single pain clinic. Among them, 201 and 166 patients were categorized into the X-ray and MRI groups, respectively. In the X-ray group, the pathological level assumed initially by clinical evaluation and plain radiography concurred with that confirmed later on post-injection MRI in 139 patients (corresponding group); the remaining 62 patients lacked this concurrence (non-corresponding group). The NRS scores and Macnab criteria results were compared between the X-ray and MRI groups as well as the corresponding and non-corresponding groups.Results: Both the X-ray and MRI groups showed significant reductions in the NRS scores at 2 and 10 weeks post-injection when compared with the pretreatment scores. However, no significant difference was noted between the groups in terms of the magnitude of clinical improvement assessed by successful reduction in the NRS or Macnab scores. Furthermore, similar results were obtained in the comparison between the corresponding and non-corresponding groups of the X-ray group.Conclusion: TFESI guarantees favorable clinical outcomes even in the absence of confirmative MRI in patients with back and radicular pain. The preemptive application of this procedure could be prioritized and justified in patients suspected of lumbosacral disc herniation based on clinical evaluation and plain radiography only without the preceding MRI verification.Keywords: lumbosacral disc herniation, epidural injection, transforaminal, numeric rating scale, plain radiography

Hyocheong Chae,1,2,&ast; Hongmin Chu,1,3,&ast; Junghun Lee,1 Hagdong Kim,1 Dongha Kim,1 Sebong Park,1 Kwanghwan Lim,1 Minsu Jeong,1 Kyungho Kang,1 Gyeongchan Kim,1 Joo Hyun Lee,1 Sehun Jung,1 Jaehyo Kim,4 Yongjoo Kim,5 Myungseok Ryu1,6 On behalf of Korean Medical Society of Acupotomology KM Doctors Group1Departmental Research Committee, Korean Medical Society of Acupotomology, Seoul, Republic of Korea; 2Sunyujae Korean Medicine Clinic, Yongin, Republic of Korea; 3Department of Korean Internal Medicine, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea; 4Department of Meridian & Acupoint, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea; 5College of Korean Medicine, Sangji University, Wonju, Republic of Korea; 6Clinic Department, Daemyeong Korean Medicine Clinic, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Myungseok Ryu, Clinic Department of Daemyung Korean Medicine Clinic, Wonwoo b/d 3rd fl, Yangpyeong-ro, Yeongdeungpo-gu, Seoul, 07208, Republic of Korea, Tel +82-2-2671-7191, Fax +82-2-2676-1297, Email yeonbu16@gmail.comObjective: Shoulder pain is a common complaint in outpatient clinics and can result in an inability to work or perform household activities, leading to significant socioeconomic burden. Acupotomy, as one kind acupuncture that has flat knife-shaped tip, has been widely used for treating shoulder pain. However, despite the widespread use of acupotomy in primary medical institutions, large sample size clinical trials have not sufficiently been performed. In this respect, this multi-center retrospective study aimed to investigate the effectiveness and safety of acupotomy in reducing shoulder pain and disability using data from multi-center primary care clinics.Methods: This study was conducted in 25 Korean medicine clinics affiliated with the Korean Medical Society of Acupotomology, Republic of Korea, from August 2021 to December 2021. The medical records of patients who visited the clinics complaining of shoulder pain were gathered, and among them were those of patients who underwent acupotomy treatment and those who received acupuncture combined therapy. The Numeric Rating Scale (NRS), SPADI (Shoulder Pain and Disability Index), Range of Motion (ROM) and adverse event were evaluated at each visit. A linear mixed-effects models and paired t-test were used to identify the effectiveness of the treatment.Results: Overall analysis showed that the NRS score of patients decreased from 4.95 ± 1.97 before treatment to 3.78 ± 2.03 after treatment (n = 332, difference in NRS score, 1.17; 95% CI: 0.96– 1.38, t = 10.89 p < 0.001). SPADI score decreased from 19.05 ± 20.44 at baseline before treatment to 12.12 ± 17.26 after the last visit, which was statistically significant (n = 332, mean difference in SPADI score, 6.93; 95% CI: 4.71– 9.15, t = 6.150, p < 0.001). No serious adverse event was reported in both groups.Conclusion: This study showed the effectiveness of acupotomy therapy for shoulder pain, and as the treatment sessions increased, the effect of pain reduction and shoulder function improvement were also increased.Keywords: acupotomy, shoulder pain, retrospective study, multicenter study

Eun Kyung Jun,1,&ast; Sunghwan Lim,2,&ast; Joonho Seo,3 Kae Hong Lee,1 Jae Hee Lee,1 Deukhee Lee,2 Jae Chul Koh1 1Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, Seoul, Korea; 2Center for Healthcare Robotics, Artificial Intelligence and Robotics Institute, Korea Institute of Science and Technology, Seoul, Korea; 3Department of Medical Assistant Robot, Korea Institute of Machinery and Materials, Daegu, Korea&ast;These authors contributed equally to this workCorrespondence: Deukhee Lee, Center for Bionics, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 136-791, Republic of Korea, Tel +82-2-958-5633, Fax +82-2-920-2275, Email dkylee@kist.re.kr Jae Chul Koh, Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, 73, Goryeodae-ro, Seongbukgu, Seoul, 02841, Korea, Tel +82-2-920-5632, Fax +82-2-920-2275, Email jaykoh@korea.ac.krPurpose: Multiple studies have attempted to demonstrate the benefits of augmented reality (AR)-assisted navigation systems in surgery. Lumbosacral transforaminal epidural injection is an effective treatment commonly used in patients with radiculopathy due to spinal degenerative pathologies. However, few studies have applied AR-assisted navigation systems to this procedure. The study aimed to investigate the safety and effectiveness of an AR-assisted navigation system for transforaminal epidural injection.Patients and Methods: Through a real-time tracking system and a wireless network to the head-mounted display, computed tomography images of the spine and the path of a spinal needle to the target were visualized on a torso phantom with respiration movements installed. From L1/L2 to L5/S1, needle insertions were performed using an AR-assisted system on the left side of the phantom, and the conventional method was performed on the right side.Results: The procedure duration was approximately three times shorter, and the number of radiographs required was reduced in the experimental group compared to the control group. The distance from the needle tips to the target areas in the plan showed no significant difference between the two groups. (AR group 1.7 ± 2.3mm, control group 3.2 ± 2.8mm, P value 0.067).Conclusion: An AR-assisted navigation system may be used to reduce the time required for spinal interventions and ensure the safety of patients and physicians in view of radiation exposure. Further studies are essential to apply AR-assisted navigation systems to spine interventions.Keywords: interventional procedure, epidural injection, augmented reality, navigation system, radiation exposure

Jung Hee Lee,1,&ast; Hyun-Jong Lee,1,&ast; Sang Ha Woo,1 Yu-Kyeong Park,1 Ji Hoon Han,1 Ga-Young Choi,1 Eun Sil Heo,1 Jae Soo Kim,1 Chung A Park,2 Woo Dong Lee,3 Chang Sop Yang,4 Ae-Ran Kim,5 Chang-Hyun Han4,6 1Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 2Department of Diagnostics, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 3Pre-Major of Cosmetics and Pharmaceutics, College of Herbal Bio-Industry, Daegu Haany University, Daegu, Republic of Korea; 4KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 5Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 6Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chang-Hyun Han, KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea, Tel +82 42 868 9498, Fax +82 42 869 2775, Email chhan@kiom.re.krPurpose: In Korea, complex treatments such as acupotomy, acupuncture, and physical therapy are performed for lumbar spinal stenosis (LSS). Although there are reports of acupotomy as monotherapy or acupuncture treatment for LSS, pragmatic studies are lacking. Therefore, this study aimed to determine the effectiveness and safety of acupotomy for LSS to provide baseline evidence for a large-scale study.Materials and Methods: This pragmatic randomized controlled pilot study enrolled 34 participants and randomly assigned them to two groups (n=17/group). The intervention was conducted for 8 weeks. Acupotomy plus and usual care groups received acupuncture (17 acupoints) and interferential current therapy (ICT) twice weekly; however, the acupotomy plus group received an additional acupotomy (7 acupoints) for treatment of the usual care group. The primary outcome was measured using visual analog scales (VAS), and secondary outcomes were assessed using the self-rated walking distance, short-form McGill Pain Questionnaire (SF-MPQ), and the Oswestry Disability Index (ODI). Outcome measurements were conducted at baseline and 4, 8, and 12 weeks after the commencement of the intervention. Adverse events were assessed at each visit. Hematological and biochemical examinations were performed at screening and week 8.Results: Overall, 33 of the 34 participants completed the study, and one participant in the usual care group dropped out. In both groups, VAS scores at weeks 4, 8, and 12 significantly improved compared to baseline. Also, self-rated walking distance, SF-MPQ, and ODI scores were significantly improved at weeks 4, 8, and 12 than at baseline. However, there were no significant differences in the time-dependent and group-to-time interactions between the two groups. In addition, no severe adverse reactions were reported, and there were no significant differences in hematological and biochemical results.Conclusion: This study provides baseline data for large-scale studies on the effectiveness and safety of acupotomy in LSS.Clinical Trial Number: KCT0006234.Keywords: complementary therapy, pragmatic clinical trial, low back pain, acupuncture therapy

Jang Ho Lee,1,&ast; Sehee Kim,2,&ast; Yeon-Mok Oh1 1Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2Department of Clinical Epidemiology and Biostatistics, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Yeon-Mok Oh, Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-3136, Fax +82-2-3010-6968, Email ymoh55@amc.seoul.krPurpose: The aims of this study were to develop a scoring model that predicts the effects of withdrawing inhaled corticosteroids (ICSs) from triple therapy and to examine its adaptability when applied to assess the effect of adding ICSs to dual bronchodilators patients with chronic obstructive pulmonary disease (COPD).Patients and Methods: A scoring model was developed using the IMPACT study dataset, consisting of 2389 COPD patients treated with triple therapy before enrollment (ICS withdrawal dataset). The developed model consisted of COPD duration, Acute exacerbation history, Sex, Pulmonary function tests, blood Eosinophil count, and Race (CASPER) and was used to predict composite events of moderate-to-severe exacerbation, all-cause mortality, and pneumonia. Treatment heterogeneity was assessed using Cox interaction analyses. The CASPER model was applied to 540 COPD patients treated with dual bronchodilator before enrollment (ICS addition dataset). Validity was assessed using Harrell’s C-index, time-dependent receiver operating characteristic curves, and calibration plots.Results: The cumulative incidence of the composite event was 60.1% over 12 months in the ICS withdrawal dataset. Cox interaction analyses revealed that ICS was different according to race and blood eosinophil counts. The hazard ratios (HRs) for dual bronchodilator compared with triple therapy were 1.318 (95% confidence interval (CI)=1.170– 1.485; P-value < 0.001) in whites and 0.922 (95% CI = 0.712– 1.195; P-value=0.541) in other races. The treatment effect was different in the eosinophil count ≥ 0.3 group (HR = 1.586; 95% CI = 1.274– 1.975) and in the eosinophil count = 0.1– 0.3 group (HR = 1.211; 95% CI = 1.041– 1.408), but it was same in the eosinophil count < 0.1 (HR = 1.009; P-value=0.940). The CASPER model performed well with good discrimination and calibration, which were superior to the prediction based on exacerbation history and blood eosinophil count.Conclusion: The presented CASPER model might be able to predict and compare the risk of composite events when dual bronchodilator or triple therapy is administered to COPD patients.Keywords: chronic obstructive pulmonary disease, inhaled corticosteroid, exacerbation, mortality, pneumonia

Sung-Soo Kim,1,&ast; Sojung Won,2,&ast; Ha Eun Lee,2 Seung Hyun Ryu,2 Dong Joon Choi,2 Sung Ig Cho,2 Byoung Joo Gwag,2 Hwa-Young Youn,3 Jin Hwan Lee2 1VIP Animal Medical Center KR, Seoul, 02830, Republic of Korea; 2GNT Pharma, Yongin, Gyeonggi, 17096, Republic of Korea; 3Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jin Hwan Lee, GNT Animal Health Business Unit, Yongin, Gyeonggi, 17096, Republic of Korea, Tel +82 10 8878 0456, Fax +82 31 8005 9931, Email jhlee@gntpharma.comPurpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 selective inhibitors are the most widely used drugs to treat pain. Conventional NSAIDs and COX-2 selective inhibitors, however, cause several side effects such as gastric damage, kidney damage, and cardiovascular problems. Our previous study showed that 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid ie, flusalazine (also known as ND-07), which exerts dual actions by serving both as an anti-inflammatory agent and a free radical scavenger, is an effective and safe treatment for severe inflammatory diseases in mice. The goal of the present study was to examine the potential analgesic action and safety of flusalazine in mice models of pain.Methods and Results: Flusalazine showed a significant analgesic effect in an acetic acid-induced abdominal constriction model. Likewise, total paw licking was reduced significantly in neurogenic (early stage) and inflammatory (late stage) pain induced by formalin in flusalazine-treated mice. In the tail immersion test, flusalazine significantly increased tail withdrawal time at 2 h after its administration. Also, the formation of paw edema in the flusalazine-treated group was significantly inhibited in a carrageenan-induced inflammatory pain model. Gastric damage was not induced by flusalazine even up to 1000 mg/kg, while aspirin and indomethacin caused critical gastric bleeding.Conclusion: These findings suggest that flusalazine’s safety profile and analgesic effects have high translational potential for the clinical treatment of patients experiencing pain.Keywords: analgesic effect, aspirin, flusalazine, indomethacin, NSAIDs

Hyung Joon Yim,1,&ast; Ji Hoon Kim,2,&ast; Yong Kyun Cho,3 Young Oh Kweon,4 Hyun Chin Cho,5 Jae Seok Hwang,6 Changhyeong Lee,7 Moon Soo Koh,8 Yang-Hyun Baek,9 Young-Min Park,10 Jeong-Hoon Lee,11 Seung Up Kim,12 Min-Kyu Kang,13 Neung Hwa Park,14 June Sung Lee,15 Young Eun Chon,16 Gab Jin Cheon,17 Hee Bok Chae,18 Joo Hyun Sohn,19 Young-Suk Lim20 1Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Korea; 2Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; 3Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea; 5Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea; 6Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea; 7Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea; 8Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Dongguk University, Goyang, Korea; 9Department of Gastroenterology, DongA University College of Medicine, Busan, Korea; 10Department of Internal Medicine, Bundang Jesaeng General Hospital, Seongnam, Korea and Hepatology Center, Bundang Jesaeng General Hospital, Seongnam, Korea; 11Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea; 12Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, and Yonsei Liver Center, Severance Hospital, Seoul, Korea; 13Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea; 14Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea; 15Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea; 16Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 17Department of Medicine, GangNeung Asan Hospital, Ulsan University College of Medicine, Gangwon-do, Korea; 18Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea; 19Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea, and Hanyang University Guri Hospital, Guri, Korea; 20Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Young-Suk Lim, Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 43-Gil 88, Olympic-Ro, Songpa-Gu, Seoul, Korea, Tel +82-2-3010-3190, Fax +82-2-485-5782, Email limys@amc.seoul.krPurpose: Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet’s size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB).Patients and Methods: CHB patients with HBV-DNA < 69 IU/mL after ≥ 24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA < 69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities.Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was − 2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; − 0.8 ± 9.8 versus − 2.4 ± 12.8 mL/min, respectively (P=0.017).Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.Keywords: viral DNA, bone density, antiviral agents, viral suppression

Hye Jung Park,1 Soyoung Jeon,2 Hye Sun Lee,2 Bo Yeon Kim,3 Yu Jin Chae,3 Gui Ok Kim,3 Jung-Won Park,4,5 Jae-Hyun Lee4,5 1Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Healthcare Insurance Review & Assessment Service, Wonju, Republic of Korea; 4Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Institute of Allergy, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Jae-Hyun Lee, Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea, Tel +82-2-2228-1977, Fax +82-2-393-6884, Email jhleemd@yuhs.acBackground: Although a wide variety of asthma medications have been developed and are used in clinical practice, there is limited evidence of their comparative effects on asthma exacerbations.Methods: We used claims data provided by the Health Insurance Review and Assessment Service. We selected subjects commencing asthma treatment between July 1, 2017 and June 30, 2018, with no change in drug regimen. The primary outcome was asthma exacerbation requiring systemic corticosteroids. Cox regression analysis was used to assess outcomes considering the exacerbation-free period.Results: Of the 254,951 asthma subjects, 107,694 subjects (42.2%) experienced asthma exacerbation. Inhaled corticosteroids (ICSs) (hazard ratio [HR], 0.378– 0.508), ICS-long-acting β2-agonist (LABAs) (HR, 0.284– 0.479), long-acting muscarine antagonists (LAMAs) (HR, 0.432– 0.572), leukotriene receptor antagonists (LTRAs) (HR, 0.371– 0.419), and xanthines (HR, 0.326– 0.482) significantly reduced the rate of first and second exacerbation of asthma (all P-values, < 0.001). The clinical effectiveness of asthma medications varied according to the active ingredient (HR 0.164– 0.670) and was significant for all active ingredients (all P-values, < 0.001). The effectiveness of combination treatment using ICS-LABA and LTRA varied (HR, 0.159– 0.670); however, all combination treatment options evaluated were effective in preventing asthma exacerbations (all P-values, < 0.001). Long-term use of ICS-LABA (HR, 0.278– 0.653), LTRA (HR, 0.259– 0.628), and xanthines (HR, 0.351– 0.783) showed consistent effectiveness (all P-values, < 0.001).Conclusion: This real-world study showed that the effectiveness of asthma medications varied according to drug type, active ingredient, combination, and period of use, although effectiveness was significant in all cases studied.Keywords: asthma, medication, exacerbation, real-world data, drug, combination

Jisoo Park,1 Eun-Kyung Kim,1 Se Hee Lee,1 Mi-Ae Kim,1 Jung-Hyun Kim,1 Sang Min Lee,2,3 Jae Seung Lee,4,5 Yeon-Mok Oh,4,5 Sang-Do Lee,4,5 Ji-Hyun Lee1 On behalf of the KOLD Study Group1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea; 2Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 5Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of KoreaCorrespondence: Ji-Hyun Lee, Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, 59, Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13496, Republic of Korea, Tel +82-31-780-5205, Fax +82-31-780-2992, Email plmjhlee@cha.ac.krPurpose: We explored the differences in clinical manifestations of COPD patients regarding emphysema distribution along with evidence of airway involvement in chest computed tomography (CT) scans.Patients and Methods: The patients were divided into three groups according to the emphysema distribution: the upper dominant (UD), lower dominant (LD), and homogeneous (HD) groups. Airway wall thickness was quantitatively measured and the presence of bronchiectasis and/or bronchial wall thickening (BE/BWT) was visually assessed. Baseline characteristics including the evidence of airway involvement and long-term outcomes were compared among the three groups. Non-severe patients of each group were first treated with 3 months of ICS/LABA combination after 2 weeks of wash-out period and lung functions before and after the treatment were compared.Results: Of the 425 patients, 141 were in the UD, 107 in LD, and 177 in HD. The LD had more severe airway obstruction with lower emphysema index (EI) than the UD (LD vs UD; FEV1, 49.5– 14.9 vs 54.6– 16.5; EI, 21.0 [IQR: 14.0– 33.1] vs 26.3 [IQR: 15.8– 39.0]). The LD showed thicker airways (higher WA% and Pi10) and more severe air trapping (higher RV and RV/TLC) than UD. A larger proportion of patients in LD had BE/BWT (35.5% in LD vs 11.3% in UD). In LD, more patients experienced acute exacerbations and the time to first exacerbation was shorter than UD. Non-severe patients in LD treated with 3 months of ICS/LABA combined inhalers showed a notable reduction of RV than UD (LD vs UD; − 531.1– 936.5 vs − 86.5– 623.5).Conclusion: The LD showed a more prominent airway involvement than UD, which may cause more frequent exacerbations and a marked reduction of RV after the ICS/LABA combination treatment in LD. Phenotyping of the COPD patients using quantitatively measured emphysema distribution would be useful for predicting treatment response and exacerbation.Keywords: pulmonary disease, chronic obstructive, computed tomography, emphysema

Hye Soon Kim,1 Jae Myung Yu,2 Hak Chul Jang,3 Eui Kwang Choi,4 Jeong Hyun Park,5 Ho Sang Shon,6 Choon Hee Chung,7 Keun-Gyu Park,8 Jae Hyoung Cho,9 Won Kim,10 Kyoung Hwa Lee,10 Jee Hyun Lee,10 Soon Jib Yoo11 1Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea; 2Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 4Department of Internal Medicine, Naedang Dr. Choi’s Clinic, Seoul, Republic of Korea; 5Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; 6Department of Internal Medicine, Catholic University of Daegu, School of Medicine, Daegu, Republic of Korea; 7Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; 8Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea; 9Department of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 10Medical Department Sanofi-Aventis Korea, Seoul, Republic of Korea; 11Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of KoreaCorrespondence: Soon Jib Yoo, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, 14647, Republic of Korea, Tel +82-32-340-7011, Fax +82-32-340-2039, Email sjyoomt@gmail.comPurpose: Although rapid-acting insulins (RAIs) are used frequently in Korean clinical settings, evidence on their use is limited. This study explores the pattern and clinical effectiveness of the use of RAIs in Korean patients with type 2 diabetes mellitus (T2DM).Patients and Methods: This non-interventional, observational study enrolled patients (aged > 18 years) with T2DM who were prescribed RAIs. The pattern of use and effectiveness of RAI analogs were evaluated over 6 months.Results: A total of 299/451 patients were analyzed. Approximately 90% (n/N=270/299) of the patients received insulin glulisine, which significantly reduced their levels of glycated hemoglobin (HbA1c: n=270, mean± standard deviation [SD]; − 1.16± 6.02%, p=0.0017), fasting plasma glucose (n=40; mean±SD: − 54.9± 90.89 mg/dl, p=0.0005), and post prandial blood glucose (n=35, mean±SD: − 89.46± 105.68 mg/dl, p< 0.0001) at 6 months, with a corresponding increase in body weight (BW) (n=197, mean±SD:1.45± 3.64 kg, p< 0.0001). At 6 months, more patients receiving an intensive regimen (basal insulin+≥ 2 RAI injections/day) had HbA1c < 7% than those receiving a non-intensive regimen (basal insulin+1 RAI injection/day) (20.69% vs 7.46%; p=0.0333); the corresponding reduction in HbA1c was also higher in patients receiving the intensive regimen (p< 0.0001). About one-fourth patients (n/N=22/95) were switched to the intensive regimen (from 1 to ≥ 2 RAI injections/day), and only 4.41% (n/N=9/204) of the patients were switched to 1 RAI injection/day. The patients receiving the intensive regimen showed higher levels of HbA1c reductions (mean±SD: − 1.27± 1.96%) compared with the maintenance group-1 RAI injection/day (mean±SD: − 0.72± 1.66%) (p=0.0459), without a significant increase in BW and body mass index.Conclusion: The insulin glulisine intensification regimen showed glycemic target achievement and can be considered a therapeutic tool in the management of T2DM patients.Keywords: glycated hemoglobin, insulin glulisine, intensification, RAI analogs

Hyewon Seo,1 Yun Su Sim,2 Kyung Hoon Min,3 Jae Ha Lee,4 Byung-Keun Kim,5 Yeon Mok Oh,6 Seung Won Ra,7 Tae-Hyung Kim,8 Yong Il Hwang,9 Jeong-Woong Park10 1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Kangnam Sacred Heart Hospital, Seoul, Republic of Korea; 3Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 4Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 5Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 6Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 7Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea; 9Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 10Department of Allergy, Pulmonary and Critical Care Medicine, Gachon University Gil Medical Center, Incheon, Republic of KoreaCorrespondence: Jeong-Woong Park, Department of Allergy, Pulmonary and Critical Care Medicine, Gachon University Gil Medical Center, Namdong-daero 774 beon-gil, Namdong, Incheon, 21565, Republic of Korea, Tel +82-10-5574-0164, Fax +82-32-469-4320, Email jwpark@gilhospital.comPurpose: Data regarding the relationship between microbiologic features and comorbidities in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are limited. The aim of this study was to correlate microbiologic findings with comorbidities in patients with moderate to severe AECOPD.Patients and Methods: This multicenter observational study included patients with AECOPD seen at 28 hospitals in South Korea between January 2015 and December 2018, and the data were retrospectively collected. Pathogens were examined in patients with either pulmonary or extrapulmonary comorbidities, and compared to those of patients without comorbidities. The relationship between pathogen type and the number of comorbidities was also evaluated.Results: Bacterial infections (178 [37.2%] vs 203 [28.7%], p = 0.002) and co-infections with bacteria and viruses (65 [13.6%] vs 57 [8.1%], p = 0.002) were more prevalent in patients with pulmonary comorbidities. Bacterial pathogens (280 [34.7%] vs 101 [26.7%], p=0.006) were detected at a higher rate in patients with extrapulmonary comorbidities. Previous pulmonary tuberculosis (PTB), bronchiectasis, and diabetes mellitus were risk factors for bacterial infection, and congestive heart failure was a risk factor for bacterial and viral co-infection. As the number of comorbidities increased, the risk of bacterial infection increased considerably. Pseudomonas aeruginosa was more frequently identified in patients with previous PTB (57 [15.3%] vs 59 [7.4%], p < 0.001) and bronchiectasis (33 [19.6%] vs 83 [8.3%], p < 0.001).Conclusion: AECOPD patients with comorbidities were more likely to experience infection-related exacerbations compared to those without comorbidities. As the overall number of comorbidities increased, the risk of bacterial infection increased significantly.Keywords: chronic obstructive pulmonary disease, acute exacerbation, comorbidity, bacteria, virus

Minseok Albert Kim,1 Heejoon Jang,1 Na Ryung Choi,1 Joon Yeul Nam,1 Yun Bin Lee,1 Eun Ju Cho,1 Jeong-Hoon Lee,1 Su Jong Yu,1 Hyo-Cheol Kim,2 Jin Wook Chung,2 Jung-Hwan Yoon,1 Yoon Jun Kim1 1Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea; 2Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South KoreaCorrespondence: Yoon Jun KimDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South KoreaTel +82-2-2072-3081Fax +82-2-743-6701Email yoonjun@snu.ac.krBackground: Both trans-arterial radioembolization (TARE) and conventional trans-arterial chemoembolization (TACE) can effectively control hepatocellular carcinoma (HCC) in patients who are not suitable for curative resection. This study compared the effectiveness of TARE and conventional TACE as the initial trans-arterial treatment for hepatocellular carcinoma (HCC) assessed by tumor response and clinical outcomes.Material and Methods: Data were retrospectively analyzed the propensity score-matched cohort for overall survival (OS), progression-free survival (PFS), and intrahepatic PFS in patients who have received TARE or TACE as the first HCC treatment from March 2012 to December 2017.Results: A total of 138 patients initially treated with TARE (n = 54) or TACE (n = 84) was included in this study. Of 138 patients, median age was 59 years and the mean follow-up period was 27.6 months. TARE showed better OS (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.31– 0.92, log-rank P = 0.02), better PFS (HR = 0.51, 95% CI = 0.36– 0.97, log-rank P = 0.04), and better intrahepatic PFS (HR = 0.51, 95% CI = 0.30– 0.88, log-rank P = 0.01) compared with TACE. TARE was an independent prognostic factor for OS (adjusted HR [aHR] = 0.52, 95% CI = 0.30– 0.90, P = 0.02), PFS (aHR = 0.57, 95% CI = 0.35– 0.94, P = 0.03), and intrahepatic PFS (aHR = 0.49, 95% CI = 0.28– 0.84, P = 0.01).Conclusion: TARE as initial trans-arterial treatment is associated with better clinical outcomes such as longer OS compared with TACE in patients with HCC.Keywords: liver neoplasms, brachytherapy, yttrium radioisotopes, embolization

Eun Kyung Kim,1 Mi-Ae Kim,1 Jae Seung Lee,2 Sang Min Lee,3 Soyeoun Lim,4 Jisoo Park,1 Jung-Hyun Kim,1 Yeon-Mok Oh,2 Sang-Do Lee,2 Se Hee Lee,1 Ji-Hyun Lee1 On behalf of the KOLD Study Group1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of KoreaCorrespondence: Ji-Hyun LeeDepartment of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of KoreaTel +82-31-780-5205Fax +82-31-780-2992Email plmjhlee@cha.ac.krPurpose: Bronchiectasis (BE) is a poor prognostic factor in COPD. However, it is not clear whether the poor prognosis is a result of BE alone or accompanying chronic bronchitis symptoms. Therefore, we investigated the effect of chronic bronchitis symptoms on clinical outcomes in COPD patients with BE.Patients and Methods: We analyzed data of COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. The presence of BE was verified by chest computed tomography. Chronic bronchitis symptoms were determined using items in the symptomatic domain of the SGRQ, which is also used as an alternative definition of chronic bronchitis (CB). Patients were divided into four groups according to the presence of BE and CB symptoms: BE/CB, BE-only, CB-only, and no BE/CB. Demographic features and clinical outcomes were compared among these groups.Results: In total, 389 COPD patients were included in the analysis. BE was present in 148 (38%) patients and CB symptoms were found in 123 patients (33.2%). The patients were divided according to BE and CB symptoms, and the numbers and percentages of each group were as follows: BE/CB, 52 (13.4%); BE-only, 96 (24.7%); CB-only, 77 (19.8%); no BE/CB, 164 (42.2%). No significant differences were observed in baseline characteristics of lung function, radiological findings, and inflammatory markers among the four groups. The proportion of annual exacerbators was higher in the BE/CB and CB-only groups than the other two groups. After adjusting other parameters, the BE/CB group was significantly associated with acute exacerbation of COPD (AE-COPD) (OR = 2.110, p = 0.045).Conclusion: BE accompanying CB symptoms is associated with AE-COPD, while BE alone was not significantly associated. This finding suggests that it is more important to examine chronic bronchitis symptoms of BE to predict acute exacerbation than simply to identify BE in COPD patients.Keywords: COPD, bronchiectasis, chronic bronchitis, exacerbation

Jae-Hwa Choi,1,&ast; Keun-Bae Jeong,1,&ast; You Hyun Park,2 Iseul Yu,1 Seok Jeong Lee,1 Myoung Kyu Lee,1 Sang-Ha Kim,1 Won-Yeon Lee,1 Suk Joong Yong,1 Ji-Ho Lee1 1Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea; 2Department of Biostatistics, Yonsei University, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Ji-Ho LeeDepartment of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 26426, KoreaTel +82-33-741-0926Fax +82-33-741-0928Email airwayleejh@yonsei.ac.krIntroduction: Inhaled corticosteroids (ICSs) play an important role in lowering the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD). However, ICSs are known to increase the risk of pneumonia. Moreover, previous studies have shown that the incidence rate of pneumonia varies depending on the type of ICS. In this study, the risk of pneumonia according to the type of ICS was investigated in a population-based cohort.Methods: A retrospective cohort study was conducted using claims data of the entire population from the Korean National Health Insurance Service. Patients who were newly diagnosed with COPD and prescribed fluticasone propionate or budesonide were enrolled as study subjects. Cumulative doses of ICSs were classified into categorical variables to analyze the risk of pneumonia within identical ICS doses.Results: A total of 47,473 subjects were identified and allocated as 14,518 fluticasone propionate and 14,518 budesonide users through 1:1 propensity score matching. Fluticasone propionate users were more likely to develop pneumonia than budesonide users (14.22% vs 10.66%, p< 0.0001). The incidence rate per 100,000 person-years was 2,914.77 for fluticasone propionate users and 2,102.90 for budesonide users. The hazard ratio (HR) of pneumonia in fluticasone propionate compared to budesonide was 1.34 (95% CI 1.26– 1.43, p< 0.0001). The risk of pneumonia for fluticasone propionate compared to budesonide increased with higher ICS cumulative doses: 1.06 (0.93– 1.21), 1.41 (1.19– 1.66), 1.41 (1.23– 1.63), and 1.49 (1.33– 1.66) from the lowest to highest quartiles, respectively.Conclusion: ICS types and doses need to be carefully considered during treatment with ICSs in patients with COPD.Keywords: inhaled corticosteroid, chronic obstructive pulmonary disease, pneumonia, fluticasone propionate, budesonide

Ji Eun Park,1,&ast; Mi Jeong Hong,2,3,&ast; Shin Yup Lee,1,4 Jang Hyuck Lee,2,4 Jin Eun Choi,2,3 Hyo-Gyoung Kang,2,3 Sook Kyung Do,2,3 Ji Yun Jeong,5 Kyung Min Shin,6 Won Kee Lee,7 Sun Ha Choi,1 Yong Hoon Lee,1 Hye won Seo,1 Seung Soo Yoo,1 Jaehee Lee,1 Seung Ick Cha,1 Chang Ho Kim,1 Jae Yong Park1,2 1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 3Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 4BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea; 5Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 6Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 7Department of Medical Informatics, School of Medicine, Kyungpook National University, Daegu, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Shin Yup Lee; Jae Yong ParkDepartment of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of KoreaTel +82-53-200-2632Fax +82-53-200-2027Email shinyup@knu.ac.kr; jaeyong@knu.ac.krIntroduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have represented the prototype of targeted therapy in NSCLC. Patients with EGFR-mutant lung adenocarcinoma extract an extraordinary clinical benefit from EGFR-TKIs. However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual’s response to TKIs. We investigated whether genetic variants in miRNA binding sites are associated with the clinical outcome of EGFR-TKIs in lung adenocarcinoma patients.Methods: One hundred SNPs at miRNA binding sites in cancer-related genes were selected for the analysis using the crosslinking, ligation and sequencing of hybrids (CLASH) and CancerGenes database. qRT-PCR and luciferase assays were conducted to evaluate the functional relevance of the SNPs.Results: NUP62 rs9523A>G were significantly associated with worse response to EGFR-TKIs, overall survival (OS), and progression-free survival (PFS). The other three SNPs (DVL2 rs2074216G>A, ARF1 rs11541557G>T, and UHRF1 rs2261988C>A) were significantly associated with worse OS and PFS. The rs9523A>G was significantly associated with decreased NUP62 expression in tumor tissues. In addition, a significantly decreased luciferase activity was noted in NUP62 rs9523 G allele compared to A allele.Conclusion: Genetic variants in miRNA binding sites, especially NUP62 rs9523A>G, may be useful in predicting the clinical outcomes of EGFR-mutant lung adenocarcinoma patients treated with EGFR-TKIs.Keywords: lung adenocarcinoma, EGFR-TKI, clinical outcome, miRNA binding site, polymorphism

Mihir Gandhi,1– 4 Wen-Huan Ling,5 Chien-Hung Chen,6 Joon Hyeok Lee,7 Masatoshi Kudo,8 Rawisak Chanwat,9 Simone I Strasser,10 Zhu Xu,11 Soh-Han Lai,5 Pierce Kah-Hoe Chow12,13 1Biostatistics, Singapore Clinical Research Institute, Singapore; 2Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore; 3Lien Centre for Palliative Care, Duke-NUS Medical School, Singapore; 4Tampere Center for Child, Adolescent, and Maternal Health Research, Tampere University, Tampere, Finland; 5Programme in Translational and Clinical Liver Research, National Cancer Centre Singapore, Singapore; 6Department of Internal Medicine, National Taiwan University Hospital, Douliu City, Yunlin, Taiwan; 7Division of Gastroenterology, Sungkyunkwan University School of Medicine, Samsung Medical Centre, Seoul, Korea; 8Department of Gastroenterology and Hepatology, Kindai University Hospital, Osaka, Japan; 9Department of Surgery, National Cancer Institute, Bangkok, Thailand; 10AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 11Department of Interventional Therapy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, People’s Republic of China; 12Department of Hepatopancreatobiliary and Transplant Surgery, National Cancer Centre Singapore and Singapore General Hospital, Singapore; 13Surgery Academic Clinical Programme, Duke-NUS Medical School, SingaporeCorrespondence: Pierce Kah-Hoe ChowDivision of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, 169610, SingaporeTel +65 6576 2151Email pierce.chow.k.h@singhealth.com.sgPurpose: The COVID-19 pandemic has altered healthcare priorities which may adversely impact cancer management. We aimed to evaluate the impact of the pandemic on the diagnosis, treatment, and consultation methods for patients with hepatocellular carcinoma (HCC).Patients and Methods: We conducted a survey among 27 hospitals from 14 Asia-Pacific countries, collecting hospital-level information on the number of newly diagnosed HCC cases during a pre-pandemic period (February to May 2019) and for the same period during the pandemic (February to May 2020). Information was also collected on delays in diagnosis and treatment, changes in treatment modalities and complication rates, changes in patient enrollment in clinical trials, and modes of patient consultation. The information was stratified by the Barcelona Clinic Liver Cancer (BCLC) stage.Results: The survey included cohorts of 2789 and 2045 patients newly diagnosed with HCC during the pre- and pandemic period, respectively. A decline of 26.7% in new HCC cases was reported during the pandemic compared to the pre-pandemic. A sizable proportion of institutions reported delays in diagnosis (48.2% in BCLC 0/A/B and 51.9% in BCLC C), delays in treatment (66.7% in BCLC 0/A/B and 63.0% in BCLC C), changes in treatment modality (33.3% in BCLC 0/A/B and 18.5% in BCLC C), an increase in treatment complications (about 15% across all BCLC stages), and no growth in clinical trial enrollments during the pandemic. Furthermore, there was a decline of 27.3% in face-to-face patient consultations and an increase of 18.3% in video/telephonic consultations during the pandemic. A considerable variation in changes in HCC management was observed among countries.Conclusion: The COVID-19 pandemic has significantly impacted the management of HCC among Asia-Pacific countries. The impact varies according to the disease stage and country. Well thought-through long-term strategies are required to ameliorate the negative impact of the pandemic on HCC patients.Keywords: hepatocellular carcinoma, liver cancer, COVID-19, Asia-Pacific

Jung Hyun Kim,1 Jae-Hoon Lee,2 Hye Sun Lee,3 Su-Jin Shin,4 Eun Jung Park,1 Eun-Suk Cho,5 Seung Hyuk Baik,1 Kang Young Lee,6 Jeonghyun Kang1 1Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea; 4Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 6Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Jeonghyun KangDepartment of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Republic of KoreaTel +82-2-2019-3372Fax +82-2-3462-5994Email ravic@naver.comBackground: Recent data suggest that alterations in the neutrophil-to-lymphocyte ratio (NLR) in the perioperative periods can serve as prognostic factors. However, research on the clinical impact has been limited and even discordant in patients with colorectal cancer (CRC).Patients and Methods: The optimal cut-off value of preoperative NLR (NLR-pre), postoperative NLR (NLR-post), and its change (NLR-delta) were determined to maximize differences in overall survival (OS) between groups. Patients were categorized into four groups (NLR-trend) as follows: G1, low NLR-pre and NLR-post; G2, low NLR-pre and high NLR-post; G3, high NLR-pre and low NLR-post; and G4, high NLR-pre and NLR-post. Discriminatory performance was compared using integrated AUC (iAUC) between all indicators.Results: A total of 576 patients diagnosed with stage I–IV CRC were included. The cut-off points were determined as 2.33 for NLR-pre, 2.06 for NLR-post, and − 1.08 for NLR-delta. Subgroup dichotomization using NLR-pre, NLR-post, NLR-delta and NLR-trend were all identified as significant prognostic factors by univariate analysis. However, NLR-trend was only remained as an independent prognostic factor in the multivariate analysis. The iAUC of the NLR-trend was superior to that of NLR-pre (bootstrap iAUC mean difference=0.036; 95% CI 0.013– 0.073), NLR-post (bootstrap iAUC mean difference=0.045; 95% CI 0.019– 0.081) and NLR-delta (bootstrap iAUC mean difference=0.061; 95% CI 0.025– 0.104).Conclusion: Risk stratification and combining of preoperative and postoperative NLR (NLR-trend) can improve prognostic discrimination compared with single measurements or simple changes in NLR in patients with CRC.Keywords: NLR, colorectal cancer, survival, iAUC

Su-Jeong Kim,1,&ast; Jae-Ho Lee,2,&ast; Woo-Jae Park,1 Shin Kim3– 5 1Department of Biochemistry, College of Medicine, Gachon University, Yeonsu-gu, Incheon, 21999, Republic of Korea; 2Department of Anatomy, School of Medicine, Keimyung University, Dalseo-gu, Daegu, 42601, Republic of Korea; 3Department of Immunology, School of Medicine, Keimyung University, Dalseo-gu, Daegu, 42601, Republic of Korea; 4Institute of Medical Science, Keimyung University, Dalseo-gu, Daegu, 42601, Republic of Korea; 5Institute for Cancer Research, Keimyung University Dongsan Medical Center, Dalseo-gu, Daegu, 42601, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Shin Kim Email god98005@dsmc.or.krIntroduction: Sphingolipid metabolism is a highly controlled process that is involved in regulating bioactive lipid signaling pathways and serves important roles in several cellular processes in breast cancer. Invasive ductal carcinoma (IDC), which is characterized by the malignant proliferation of the ductal epithelium and stromal invasion, is the most common type of breast cancer. Recent advances in genetic research have accelerated the discovery of novel prognostic factors and therapeutic targets for the disease. The aim of the present study was to investigate the expression and prognostic significance of sphingolipid metabolism-related genes in female IDC.Methods: The present study used gene expression RNAseq data obtained from The Cancer Genome Atlas breast invasive carcinoma (TCGA BRCA) datasets.Results: Sphingolipid metabolism-related genes exhibited dysregulated mRNA expression levels in IDC. The Student’s t-test revealed that SMPDL3B, B4GALNT1, LPAR2, and LASS2 were significantly upregulated, while LASS3, LPAR1, B4GALT6, GAL3ST1, HPGD, ST8SIA1, UGT8, and S1PR1 were significantly downregulated in female IDC tissues compared with normal solid tissues. Kaplan–Meier survival analyses revealed that high SMPDL3B mRNA expression levels were associated with good prognosis in female IDC, suggesting that SMPDL3B plays a tumor suppressor role. To the best of our knowledge, the present study was the first to report that dysregulated expressions of SMPDL3B are significantly associated with age, estrogen receptor status, progesterone receptor status, and histological subtype.Conclusion: Taken together, our study indicated that SMPDL3B may have a pathophysiological role and serve as a novel prognostic biomarker in IDC.Keywords: SMPDL3B, sphingolipid metabolism, invasive ductal carcinoma, TCGA

Soyeon Jang,1 Soyoung Jang,1 Si-Yong Kim,1 Jiwon Ko,1 Eungyung Kim,2 Ji Yeong Park,1 Hyejin Hyung,1 Jin Hong Lee,1 Su-Geun Lim,3 Sijun Park,3 Junkoo Yi,4 Heon-Jin Lee,5 Myoung Ok Kim,2 Hyun-Shik Lee,1 Zae Young Ryoo1 1School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea; 2Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea; 3School of Life Science, Kyungpook National University, Daegu, Korea; 4Gyeongsangbukdo Livestock Research Institute, Yeongju, Korea; 5Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, 41940, KoreaCorrespondence: Zae Young Ryoo; Hyun-Shik LeeSchool of Life Science, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, KoreaTel +82-53-950-7361; +82-53-950-7367Fax +82-53-943-6925; +82-53-943-2762Email jaewoong64@knu.ac.kr; leeh@knu.ac.krPurpose: Psoriasis is a common and well-studied autoimmune skin disease, which is characterized by plaques. The formation of psoriasis plaques occurs through the hyperproliferation and abnormal differentiation of keratinocytes, infiltration of numerous immune cells into the dermis, increased subepidermal angiogenesis, and various autoimmune-associated cytokines and chemokines. According to previous research, Lin28 regulates the let-7 family, and let-7b is associated with psoriasis. However, the link between Lin28 and psoriasis is unclear. In this study, an association was identified between Lin28a and psoriasis progression, which promoted the pathological characteristic of psoriasis in epidermal keratinocytes.Patients and Methods: This study aims to investigate the role of Lin28a and its underlying mechanism in psoriasis through in vivo and in vitro models, which include the Lin28a-overexpressing transgenic (TG) mice and Lin28a-overexpressing human keratinocyte (HaCaT) cell lines, respectively.Results: In vivo and in vitro results revealed that overexpression of Lin28a downregulated microRNA let-7 expression levels and caused hyperproliferation and abnormal differentiation in keratinocytes. In imiquimod (IMQ)-induced psoriasis-like inflammation, Lin28a overexpressing transgenic (TG) mice exhibited more severe symptoms of psoriasis.Conclusion: Mechanistically, Lin28a exacerbated psoriasis-like inflammation through the activation of the extracellular-signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 signaling (STAT 3) by targeting proinflammatory cytokine interleukin-6 (IL-6).Keywords: psoriasis, keratinocyte, Lin28a, let-7

This study aimed to investigate the technical feasibility of a percutaneous endoscopic limited-dorsal laminectomy (PELDL) and to evaluate if the decompression and examination of the lumbosacral vertebral canals could be achieved using an endoscope in small dogs. A total of eight fresh canine cadavers were used for the study. Following the injection of a barium and agarose mixture (BA-gel), which simulates intervertebral disc herniation, a PELDL was performed over L7-S1 in these animals. Computed tomography (CT) scans were obtained pre- and postoperatively to evaluate the surgical outcomes. All the procedures were completed with a clear visualisation of the spinal cord and removal of the BA-gel. The mean surgery time for the PELDL was 30.00 ± 12.01 minutes. In two dogs, iatrogenic nerve root injuries were caused by the surgical instruments during the operation. The CT scans showed that the amount of BA-gel removed was sufficient for a spinal-cord decompression. A PELDL could be used for the BA-gel removal to decompress the spinal cord and provide a clear view of the spinal canal. Therefore, it could be used as an alternative surgical option to treat lumbosacral disc disease in dogs.

Sung Won Chung,1,* Min Kyung Park,1,* Young Youn Cho,1,2,* Youngsu Park,1 Cheol-Hyung Lee,1 Hyunwoo Oh,1 Heejoon Jang,1 Minseok Albert Kim,1 Sun Woong Kim,1 Joon Yeul Nam,1 Yun Bin Lee,1 Eun Ju Cho,1 Su Jong Yu,1 Hyo-Cheol Kim,3 Yoon Jun Kim,1 Jin Wook Chung,3 Jung-Hwan Yoon,1 Jeong-Hoon Lee1 1Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea; 2Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea; 3Department of Radiology, Seoul National University College of Medicine, Seoul, Korea*These authors contributed equally to this workCorrespondence: Jeong-Hoon LeeDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, KoreaTel +82-2-2072-2228Fax +82-2-743-6701Email pindra@empal.comBackground: Still in real-world practice, advanced hepatocellular carcinoma (HCC) patients are treated with transarterial chemoembolization (TACE). This study compared the therapeutic effectiveness of initial TACE treatment and initial sorafenib treatment in advanced HCC patients.Patient and Methods: Advanced HCC patients initially treated with sorafenib or TACE were included in this study. Treatment crossover due to an unfavorable response to initial treatment was allowed. Propensity score (PS) matching was applied for balancing baseline characteristics. The primary outcome was overall survival (OS) and the secondary outcomes included tumor response.Results: A total of 554 patients were included in this study: 85 were initially treated with sorafenib (the sorafenib-first group) and 469 with TACE (the TACE-first group). In the entire cohort, the TACE-first group was associated with lower risk of death [adjusted hazard ratio (HR)=0.75, P=0.04]. In the PS-matched cohort (85 patients per group), the TACE-first group showed longer OS than the sorafenib-first group in both univariable (HR=0.68, P=0.02) and multivariable analyses (adjusted HR=0.58, P=0.002). Specifically, within both the entire and the PS-matched cohorts, the TACE-first group showed longer OS in subgroups with major portal vein tumor thrombosis (HR=0.72, P=0.048; HR=0.52, P=0.003) or infiltrative HCC (HR=0.42, P< 0.001; HR=0.30, P=0.004, respectively). The objective response rate was higher in the TACE-first group (29.3% vs 14.7%, P=0.03) within the PS-matched cohort.Conclusion: For advanced HCC, initial TACE leads to longer OS with a more favorable tumor response than initial sorafenib treatment. Intrahepatic tumor control with initial locoregional therapy may be a potent strategy for advanced HCC.Keywords: liver cancer, transarterial therapy, locoregional therapy, tyrosine kinase inhibitor

A one-and-a-half-year-old male Wire Fox Terrier weighing 3 kg presented with continuous drooling and vomiting. Its body condition score was 3/9, and severe atrophy of the temporal/masticatory muscle, trismus, and enophthalmos was observed on physical examination. The radiographic examination and fluoroscopic oesophagography revealed a type 1 hiatal hernia with gastroesophageal reflux. The serology tests revealed increased muscle enzyme activities. The antibody tests for acetylcholine receptor, type 2M fibre, and infectious agents were negative. A conventional surgical treatment was performed, and a thickened, stretched, and flaccid diaphragmatic muscle and an extended inelastic oesophageal hiatus were observed. On the histological examination of the diaphragmatic muscle, a diffuse histiocytic myositis was confirmed. Although the postoperative gastroesophageal reflux totally disappeared, the oesophageal motility and clinical signs did not improve significantly. Medical treatment with immunosuppressive agents was attempted and was effective in alleviating the clinical signs and abnormal oesophageal motility. The health condition of the dog was adequately maintained in the 12-month monitoring period. These findings suggest that, although the medical and surgical treatment have different therapeutic effects, they should be considered simultaneously for the management of a hiatal hernia associated with polymyopathy in dogs.

Jeong-Won Choi, Gi-Eun Lee, Jang-Han Lee Department of Psychology, Chung-Ang University, Seoul, KoreaCorrespondence: Jang-Han LeeDepartment of Psychology, Chung-Ang University, Seoul 06974, KoreaTel +82 2 820 5751Fax +82 2 816 5124Email clipsy@cau.ac.krPurpose: The aim of the present study was to examine the effects of emotional state on time perception in patients with depression and to investigate if time perception in patients with depression could be changed by induced emotional state.Patients and Methods: A clinically-depressed (CD, n=19) and non-depressed (ND, n=22) group viewed four video clips of different levels of valence and arousal (ie, positive-high arousal, positive-low arousal, negative-high arousal, negative-low arousal). After inducing emotion state, all participants performed a time perception task to measure differences in the perception of time.Results: The results showed that the CD group perceived time passing more slowly than the ND group at baseline and in all conditions, especially in the negative-low arousal condition. The ND group perceived time passed more quickly in the positive-high arousal condition compared to the CD group. These results indicate that emotional state with combined valence and arousal factors could change time perception in patients with depression.Conclusion: Based on these results, it is suggested that changing the emotional state of the depressive patient by considering valence as well as arousal is important to improve the distortion on time perception.Keywords: depression, time perception, valence, arousal, internal clock model

Jae Ik Kim,1,* Chang-Hyun Han,2,3,* Ju Hyun Jeon,1 Jin Youp Kim,4 Ojin Kwon,2 So-Young Jung,2 Jun-Hwan Lee,2,3 Changsop Yang,2 Eunseok Kim,1 Young Il Kim1 1Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea; 2Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 3Korean Medicine Life Science, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 4Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Young Il KimDepartment of Acupuncture & Moxibustion Medicine, Daejeon University Daejeon Korean Medicine Hospital, 75, Daedeok-daero 176, Seo-gu, Daejeon, Republic of KoreaTel +82-42-470-9137Fax +82-42-477-9005Email omdkim01@dju.krEunseok KimDepartment of Acupuncture & Moxibustion Medicine, Daejeon University Seoul Korean Medicine Hospital, 32, Beobwon-ro 11, Songpa-gu, Seoul, Republic of KoreaTel +82-2-2222-8103Fax +82-2-2222-8111Email mybestcando@naver.comBackground: Thread embedding acupuncture (TEA) has recently been used as a conservative treatment method for non-specific chronic neck pain (CNP). The objective of this study was to evaluate the effectiveness and safety of TEA compared to physical therapy (PT) for treating patients with CNP.Methods: A total of 128 patients diagnosed with CNP were randomly assigned to a TEA group and a PT group at a 1:1 ratio. The TEA group received four sessions of TEA, while the PT group received eight sessions of PT over 4 weeks. Outcomes were assessed using Neck Pain and Disability Scale (NPDS), clinically important difference (CID), cervical spinal angle, Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), Patient Global Impression of Change (PGIC), and EuroQol Five-Dimension (EQ-5D) at baseline and 5, 9, and 13 weeks.Results: The TEA group showed significant improvement in NPDS compared to the PT group at 5, 9, and 13 weeks. Proportions of patients with decreased NPDS scores of more than 11.5 points (minimal CID) were significantly higher in the TEA group at 5, 9, and 13 weeks. There were significant differences between the two groups at 5, 9, and 13 weeks for BDI-II, and at 5 and 9 weeks for BAI. For EQ-5D, the TEA group showed significant improvement at 5, 9, and 13 weeks. There was no significant difference in cervical spinal angle between the two groups. For PGIC, better improvement was observed at 9 and 13 weeks in the TEA group. Adverse events associated with interventions were mostly temporary and mild.Conclusion: For patients with CNP, TEA treatment was found to be more effective than PT treatment for improving their pain and dysfunction, quality of life, and psychological distress. Despite some post-treatment discomfort, TEA treatment can be considered as a useful treatment method for patients with CNP.Trial Registration: This trial has been registered 5 April 2019 in Clinical Research Information Service of South Korea (CRIS- KCT0003720).Keywords: thread embedding acupuncture, physical therapy, non-specific chronic neck pain, randomized controlled trial

Jonathan W Revels,1 Sherry S Wang,2 Kiran Gangadhar,3 Arafat Ali,4 Al-Amin Ali,5 Jean H Lee3 1Department of Radiology, University of New Mexico, Albuquerque, NM, USA; 2Department of Radiology and Imaging Sciences, University of Utah, Salt Lake, UT, USA; 3Department of Radiology, University of Washington Medical Center, Seattle, WA, USA; 4Department of Radiology, University of Cincinnati Medical Center, Cincinnati, OH, USA; 5Department of Literature, Science, and Arts, University of Michigan, Ann Arbor, MI, USACorrespondence: Jonathan W Revels Email revels.do@gmail.comAbstract: With an overall 5-year survival rate > 95%, patients with testicular cancer have a great prognosis. Although initial diagnosis is based on clinical examination, imaging does play a significant role in the diagnosis and prognosis of testicular cancer, which are dependent on tumor burden and staging. Successful treatment requires appropriate disease assessment throughout a patient’s treatment: evaluating treatment response, restaging, and monitoring for disease recurrence after treatment completion. Ultrasound is usually the initial screening modality for painless testicular masses, and computedtomography (CT) the most commonly used for staging and restaging. However, with regard to seminomas, positron-emission tomography (PET) combined with CT is slowly taking priority. With regard to nonseminomatous germ-cell tumors, PET-CT has not proven to be completely effective, due to a high number of false-negative results. The purpose of this paper is to provide radiologists with a pictorial review of testicular carcinoma from initial staging through posttreatment follow-up.Keywords: testicular, oncology, computed tomography, positron-emission tomography

Ji-Ho Lee,1,* You Hyun Park,2,* Dae Ryong Kang,3 Seok Jeong Lee,1 Myoung Kyu Lee,1 Sang-Ha Kim,1 Suk Joong Yong,1 Won-Yeon Lee1 1Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea; 2Department of Biostatistics, Yonsei University, Seoul, Korea; 3Department of Precision Medicine & Biostatistics, Yonsei University Wonju College of Medicine, Wonju, Korea*These authors contributed equally to this workCorrespondence: Won-Yeon LeeDepartment of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-Ro, Wonju 26426, KoreaTel +82-33-741-0926Fax +82-33-741-0928Email wonylee@yonsei.ac.krIntroduction: Inhaled corticosteroids (ICSs) are recommended for patients with frequent exacerbation of chronic obstructive pulmonary disease (COPD). However, accumulating evidence has indicated the risk of pneumonia from the use of ICS. This study aimed to investigate the association between ICS and pneumonia in the real-world clinical setting.Methods: A retrospective cohort study was performed using nationwide population data from the Korea National Health Insurance Service. Subjects who had a new diagnosis of COPD and who received inhaled bronchodilators without a diagnosis of pneumonia before the initiation of bronchodilators were identified. Subjects were followed up until their first diagnosis of pneumonia. The risk of pneumonia in ICS users was compared to that in non-ICS users.Results: A total of 87,594 subjects were identified and 1:1 matched to 22,161 ICS users and non-ICS users. More ICS users were diagnosed with pneumonia compared to non-ICS users (33.73% versus 24.51%, P< 0.0001). The incidence rate per 100,000 person-years was 8904.98 for ICS users and 6206.79 for non-ICS users. The hazard ratio (HR) of pneumonia for ICS users was 1.62 (95% CI 1.54– 1.70). The HR of subjects prescribed with the lowest ICS cumulative dose was 1.35 (1.27– 1.43). The HR increased to 1.51 (1.42– 1.60), 1.96 (1.85– 2.09), and 2.03 (1.89– 2.18) as the cumulative dose increased. Pneumonia was strongly associated with fluticasone propionate (1.79 (1.70– 1.89)) and fluticasone furoate (1.80 (1.61– 2.01)) use, compared to the use of other types of ICS.Conclusion: ICS increases the risk of pneumonia in patients with COPD. Hence, ICS should be carefully prescribed in patients with risk factors for pneumonia while considering the cumulative doses and subtypes of ICS.Keywords: inhaled corticosteroid, chronic obstructive pulmonary disease, pneumonia, fluticasone

Boram Lee,1 Bo-Kyung Kim,2 Hyeong-Jun Kim,3 In Chul Jung,4 Ae-Ran Kim,1 Hyo-Ju Park,1 O-Jin Kwon,1 Jun-Hwan Lee,1,5 Joo-Hee Kim6,7 1Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 2Department of Neuropsychiatry, School of Korean Medicine, Pusan National University, Yangsan-si, Gyeongsangnam-do, Republic of Korea; 3Department of Oriental Gynecology, Jecheon Oriental Hospital of Semyung University, Jecheon, Republic of Korea; 4Department of Neuropsychiatry, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea; 5Korean Medicine Life Science, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 6Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University, Wonju-si, Gangwon-do, Republic of Korea; 7Research Institute of Korean Medicine, Sangji University, Wonju-si, Gangwon-do 26339, Republic of KoreaCorrespondence: Joo-Hee KimDepartment of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University, 83, Sangjidae-gil, Wonju-si, Gangwon-do, Republic of KoreaTel +82 33 741 9268Fax +82 33 741 9141Email jhkim714v@gmail.comPurpose: To evaluate the efficacy and safety of electroacupuncture in treating insomnia.Patients and Methods: In a multicenter, randomized, assessor-blinded, controlled trial, 150 patients with DSM-5-diagnosed insomnia with Insomnia Severity Index (ISI) scores ≥ 15 were randomly assigned to three different groups that underwent 10 sessions of electroacupuncture, sham-electroacupuncture, or usual care for 4 weeks from October 2015 to June 2016 at four Korean medicine hospitals, Republic of Korea. The primary outcome included the ISI score at Week 4; the secondary outcomes included evaluations of Pittsburgh Sleep Quality Index (PSQI), sleep diary, Hospital Anxiety and Depression Scale (HADS), EuroQoL five dimension (EQ-5D), Patient Global Impression of Change (PGIC), and salivary melatonin and cortisol levels. Assessments were performed at baseline (Week 0) and at Weeks 2, 4, 8, and 12.Results: Compared with the usual care group, electroacupuncture group showed a greater improvement in ISI, PSQI, sleep diary-derived variables and HADS and EQ-5D scores at Week 4. The effects mostly persisted until Week 12. There were no significant differences between electroacupuncture and sham-electroacupuncture groups at Week 4 in all outcome measures, except sleep diary-derived sleep efficiency. However, the ISI score showed a significant difference between these groups at Weeks 8 and 12. Treatment success as per PGIC was significantly and borderline higher for electroacupuncture compared with usual care and sham-electroacupuncture, respectively. No significant changes in salivary melatonin and cortisol levels before and after treatment were observed in all groups. No serious adverse events were reported. Blinding was maintained in the sham-electroacupuncture group.Conclusion: Ten sessions of electroacupuncture can improve the sleep quality of patients with insomnia without serious adverse effects. Thus, it can be recommended as an effective, safe, and well-tolerated intervention.Keywords: electroacupuncture, insomnia, sleep initiation and maintenance disorders, randomized controlled trial

Joon Young Choi,1,* Shin Young Kim,2,* Jae Ha Lee,3 Yong Bum Park,4 Yee Hyung Kim,5 Soo-Jung Um,6 Ki Suck Jung,7 Kwang Ha Yoo,8 Seoung Ju Park,9 Hyoung Kyu Yoon10 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonology, Department of Internal Medicine, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea; 4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul 134-701, Republic of Korea; 5Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 6Division of Respiratory Medicine, Department of Internal Medicine, Dong-A University College of Medicine, Dong-A University Medical Center, Busan, Republic of Korea; 7Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Republic of Korea; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea*These authors contributed equally to this work.Correspondence: Hyoung Kyu YoonDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, #62 Youido-Dong Yeongdeungpo-Gu, Seoul, Republic of KoreaTel +82 2 3779 2213Fax +82 2 780 3132Email cmcyhg@gmail.comPurpose: The prevalence of chronic obstructive pulmonary disease (COPD) in females has increased, changing the concept of COPD as a disease mostly limited to males. In this study, the clinical characteristics of COPD in females were investigated.Patients and Methods: The study was based on a multicenter cohort of COPD patients recruited from 54 medical centers in South Korea. Sex-based differences in general characteristics, exposure risk factors, depression scores, results of pulmonary function tests, COPD exacerbation, symptom scores, and radiologic findings were evaluated. Sex-related differences in the annual FEV1 change over 5 years were analyzed in a linear mixed model.Results: Of the 2515 patients enrolled in this study, 8.1% were female. Female patients who had a higher BMI and a lower level of education were less likely to be smokers, were more exposed to passive smoking/biomass, and were more depressed compared to males. The rates of bronchiectasis, previous childhood respiratory infection, and asthma were higher in females. Female patients also had more symptoms and a poorer exercise capacity than males, but no significant differences were observed in terms of exacerbations. Radiologic findings revealed that male patients had worse emphysema, and female patients had worse bronchiectasis, as determined based on chest X-ray and computed tomography findings. On pulmonary function tests, female patients had less obstruction and less annual FEV1 loss over 5 years.Conclusion: This study revealed differences in the clinical parameters between male and female patients with COPD, including general characteristics, disease characteristics, and clinical outcomes.Keywords: COPD, gender difference, KOCOSS database, cohort study

Jang Ho Lee, Hyang Yi Lee, Youngwon Jang, Jae Seung Lee, Yeon-Mok Oh, Sang-Do Lee, Sei Won Lee Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of KoreaCorrespondence: Sei Won Lee Department of Pulmonary and Critical Care Medicine, Asan Medical CenterUniversity of Ulsan College of Medicine, Songpa-Gu, Seoul 05505, Republic of KoreaEmail iseiwon@gmail.comPurpose: Pulmonary rehabilitation (PR) is a well-established treatment for chronic obstructive pulmonary disease (COPD). The standard protocol for PR requires frequent hospital visits, which can be difficult for patients. We performed this study to assess whether unsupervised home-based PR (HBPR) is effective for patients with COPD.Patients and Methods: After assessing the outcome data, including the results of a COPD assessment test (CAT); the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index; a spirometry; the modified Medical Research Council (mMRC) dyspnea scale; and the 6-min walking test (6MWT), specialists imparted 1-hour education to patients regarding unsupervised HBPR at the baseline visit. This included methods for breathing, inhaler use, stretching, and exercise. On reviewing diaries after 8 weeks from the first visit, patients who exercised at least thrice per week were classified as the compliant group and the others were categorized as the noncompliant group. Changes in the outcomes were compared between the compliant and noncompliant groups.Results: A total of 41 patients were enrolled in this study; for 8 weeks of unsupervised HBPR, there were significant improvements in CAT scores (− 4.62± 4.61 vs 2.40± 6.73; P=0.002), BODE index (− 1.00± 1.06 vs − 0.20± 0.56; P=0.01), and forced expiratory volume in 1 s (0.05± 0.19 vs − 0.09± 0.16; P=0.02) among patients in the compliant group, compared with the noncompliant group. Moreover, their CAT (16.46± 7.80 vs 11.85± 7.23; P=0.03) and mMRC scores (2.54± 0.76 vs 1.81± 0.63; P=0.001) improved significantly after 8 weeks, compared with those at baseline. On the other hand, patients in the noncompliant group showed no significant improvement in any of the outcomes.Conclusion: In this study, compliant patients with unsupervised HBPR achieved favorable outcomes in 8 weeks. Thus, we recommend unsupervised HBPR for patients with COPD, even when regular hospital visits for PR are not possible.Trial Registration: NCT03754881.Keywords: chronic obstructive lung disease, chronic obstructive lung disease assessment test, home-based pulmonary rehabilitation, modified Medical Research Council, pulmonary rehabilitation

Anthony K Ma,1 Jun Hui Lee,1 Joshua L Warren,2 Christopher C Teng3 1Yale School of Medicine, New Haven, CT, USA; 2Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA; 3Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT, USACorrespondence: Christopher C TengDepartment of Ophthalmology and Visual Science, Yale School of Medicine, 40 Temple Street, Suite 1B, New Haven, CT, USATel +1 203-785-3366Fax +1 203-785-6220Email christopher.teng@yale.eduPurpose: To understand the distribution of trabeculectomies, glaucoma drainage implants (GDI) and micro-invasive glaucoma surgeries (MIGS) performed in the United States through geospatial mapping.Methods: We performed an observational cohort study to evaluate glaucoma surgeries in patients age ≥ 65. The most recently released data from Centers for Medicare Part B Carrier Summary Files were queried to determine the number of glaucoma surgeries performed per state during the year of 2017. We created choropleth maps, titled “GlaucoMap”, to characterize the rates of various surgeries performed across the United States, defined as the number of procedures performed per 10,000 individuals. A chi-squared analysis was further used to evaluate differences in surgical preferences across geographic region. Standardized residuals (SR) were calculated to determine regional influences on surgical distribution.Results: There were 174,788 glaucoma surgeries performed: 22,862 trabeculectomies (13.1%), 19,991 GDI (11.4%) and 131,935 (75.5%) MIGS. The Northeast had the highest trabeculectomy rate, GDI was highest in the Southeast and MIGS were highest in the Southwest. There was a statistically significant difference in proportional use of conventional surgeries versus MIGS across various regions in the United States (p < 0.0001). Given the high trabeculectomy and GDI rates and relatively low MIGS adoption in the Southeast, we observed a +7.03 SR for conventional surgeries and − 4.01 SR for MIGS. The Southwest and Western states had the highest MIGS rate and contributed +3.29 and +3.24 SR toward disproportional MIGS preference, respectively. The preference for conventional surgeries in the Northeast (SR = +2.93) and MIGS in the Midwest (SR = +0.99) also contribute to the overall differences in glaucoma surgeries across the United States.Conclusion: GlaucoMap is useful for visualizing the distribution of glaucoma surgeries in the United States. The heterogeneity in surgical preferences points to regional differences in glaucoma management.Keywords: glaucoma, MIGS, trabeculectomies, GDI, heatmaps

Koung Mi Kang,1 Chul-Ho Sohn,2 Min Soo Byun,3 Jun Ho Lee,4 Dahyun Yi,3 Younghwa Lee,4 Jun-Young Lee,5 Yu Kyeong Kim,6 Bo Kyung Sohn,7 Roh-Eul Yoo,1 Tae Jin Yun,1 Seung Hong Choi,2 Ji-hoon Kim,1 Dong Young Lee8 On behalf of the KBASE Research Group1Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Medical Research Center Seoul National University, Institute of Human Behavioral Medicine, Seoul, Republic of Korea; 4Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; 5Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea; 6Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea; 7Department of Psychiatry, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea; 8Department of Neuropsychiatry, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of KoreaCorrespondence: Chul-Ho SohnDepartment of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul 03080, Republic of KoreaTel +82-2-207203972Fax +82-2-747-7418Email neurorad63@gmail.comDong Young LeeDepartment of Neuropsychiatry, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul 03080, Republic of KoreaTel +82-2-2072-2205Fax +82-2-744-7241Email selfpsy@snu.ac.krObjective: To assess the predictive ability of regional volume information provided by fully automated brain segmentation software for cerebral amyloid positivity in mild cognitive impairment (MCI).Methods: This study included 130 subjects with amnestic MCI who participated in the Korean brain aging study of early diagnosis and prediction of Alzheimer’s disease, an ongoing prospective cohort. All participants underwent comprehensive clinical assessment as well as 11C-labeled Pittsburgh compound PET/MRI scans. The predictive ability of volumetric results provided by automated brain segmentation software was evaluated using binary logistic regression and receiver operating characteristic curve analysis.Results: Subjects were divided into two groups: one with Aβ deposition (58 subjects) and one without Aβ deposition (72 subjects). Among the varied volumetric information provided, the hippocampal volume percentage of intracranial volume (%HC/ICV), normative percentiles of hippocampal volume (HCnorm), and gray matter volume were associated with amyloid-β (Aβ) positivity (all P < 0.01). Multivariate analyses revealed that both %HC/ICV and HCnorm were independent significant predictors of Aβ positivity (all P < 0.001). In addition, prediction scores derived from %HC/ICV with age and HCnorm showed moderate accuracy in predicting Aβ positivity in MCI subjects (the areas under the curve: 0.739 and 0.723, respectively).Conclusion: Relative hippocampal volume measures provided by automated brain segmentation software can be useful for screening cerebral Aβ positivity in clinical practice for patients with amnestic MCI. The information may also help clinicians interpret structural MRI to predict outcomes and determine early intervention for delaying the progression to Alzheimer’s disease dementia.Keywords: amyloid, brain segmentation, magnetic resonance imaging, cognitive impairment

Jeong Kyo Jeong,1,* Eunseok Kim,1,* Kwang Sik Yoon,2 Ju Hyun Jeon,1 Young Il Kim,1 Hyun Lee,2 Ojin Kwon,3 So-Young Jung,3 Jun-Hwan Lee,3,4 Changsop Yang,3 Jae Hui Kang,2 Chang-Hyun Han3,4 1Department of Acupuncture and Moxibustion Medicine, Daejeon University Dunsan Korean Medicine Hospital, Daejeon, Republic of Korea; 2Department of Acupuncture and Moxibustion Medicine, Daejeon University Cheonan Korean Medicine Hospital, Cheonan, Republic of Korea; 3Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea; 4Korean Medicine Life Science, University of Science and Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea*These authors contributed equally to this workCorrespondence: Chang-Hyun HanClinical Medicine Division, Korea Institute of Oriental Medicine, 1672, Yuseongdaero, Daejeon 34054, Republic of KoreaTel +82 42 868 9498Fax +82 42 869 2775Email rkd12@hanmail.netJae Hui KangDepartment of Acupuncture and Moxibustion Medicine, Daejeon University Cheonan Korean Medicine Hospital, 4, Notaesan-ro, Cheonan 31099, Republic of KoreaTel +82 41 521 7579Fax +82 41 521 7007Email chhan@kiom.re.krBackground: Acupotomy, which involves the addition of a scalpel function to the conventional acupuncture treatment, has recently been applied as a conservative treatment method for lumbar disc herniation (LDH). This study investigated the effectiveness and safety of acupotomy, compared to manual acupuncture, for the treatment of patients with LDH.Methods: A total of 146 patients diagnosed with LDH were randomly assigned to either the acupotomy group or the manual acupuncture group at a 1:1 ratio. Participants in both groups received four sessions of each intervention over 2 weeks. Outcome assessments based on the visual analog scale (VAS), Roland Morris Disability Questionnaire (RMDQ), Modified-Modified Schober Test (MMST), EuroQol Five Dimensions (EQ-5D), clinically important difference (CID), and patient global impression of change (PGIC) were conducted at baseline and at 2, 4, and 6 weeks post-randomization.Results: The acupotomy group showed significant improvement in VAS and MMST at 2, 4, and 6 weeks than did the manual acupuncture group. RMDQ was significantly different between the two groups at 2 and 6 weeks. In EQ-5D, there was no significant difference between the two groups. The proportion of patients with ≥ 15 mm decrease on the VAS (minimal CID) was significantly higher in the acupotomy group at weeks 2 and 4. Better improvement in the PGIC at week 4 was also observed in the acupotomy group. Post-intervention muscle pain was reported, but there was no serious adverse event related to interventions.Conclusion: In this study, four sessions of acupotomy treatment were found to be effective in improving the pain intensity and range of motion of the lumbar region in patients with LDH. Despite post-treatment muscle pain, acupotomy treatment can be considered a preferred treatment method over manual acupuncture.Trial Registration: This trial has been registered 24 April 2018 in Clinical Research Information Service of South Korea (CRIS-KCT0002824).Keywords: acupotomy, manual acupuncture, lumbar disc herniation, pain intensity, range of motion

Subong Kim,1 Inyong Choi,1,2 Adam T Schwalje,2 KyooSang Kim,3 Jae Hee Lee4 1Department of Communication Sciences and Disorders, University of Iowa, Iowa City, IA 52242, USA; 2Department of Otolaryngology – Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA; 3Department of Occupational Environmental Medicine, Seoul Medical Centerr, Seoul 02053, South Korea; 4Department of Audiology and Speech-Language Pathology, HUGS Center for Hearing and Speech Research, Hallym University of Graduate Studies, Seoul 06197, South KoreaCorrespondence: Jae Hee LeeDepartment of Audiology and Speech-Language Pathology, HUGS Center for Hearing and Speech Research, Hallym University of Graduate Studies, Seoul 06197, South KoreaTel +82-2-3453-9333Fax +82-2-3453-6618Email leejaehee@hallym.ac.krIntroduction: Older listeners have difficulty understanding speech in unfavorable listening conditions. To compensate for acoustic degradation, cognitive processing skills, such as working memory, need to be engaged. Despite prior findings on the association between working memory and speech recognition in various listening conditions, it is not yet clear whether the modality of stimuli presentation for working memory tasks should be auditory or visual. Given the modality-specific characteristics of working memory, we hypothesized that auditory working memory capacity could predict speech recognition performance in adverse listening conditions for older listeners and that the contribution of auditory working memory to speech recognition would depend on the task and listening condition.Methods: Seventy-six older listeners and twenty younger listeners completed four kinds of auditory working memory tasks, including digit and speech span tasks, and sentence recognition tasks in four different listening conditions having multi-talker noise and time-compression. For older listeners, cognitive function was screened using the Mini-Mental Status Examination, and audibility was assured.Results: Auditory working memory, as measured by listening span, significantly predicted speech recognition performance in adverse listening conditions for older listeners. A linear regression model showed speech recognition performance for older listeners could be explained by auditory working memory whilst controlling for the impact of age and hearing sensitivity.Discussion: Measuring working memory in the auditory modality facilitated explaining the variance in speech recognition in adverse listening conditions for older listeners. The linguistic features and the complexity of the auditory stimuli may affect the association between working memory and speech recognition performance.Conclusion: We demonstrated the contribution of auditory working memory to speech recognition in unfavorable listening conditions in older populations. Taking the modality-specific characteristics of working memory into account may be a key to better understand the difficulty in speech recognition in daily listening conditions for older listeners.Keywords: auditory working memory, age, hearing loss, speech recognition

Kyung Hun Kim,1,2 Seo Hyun Lim,2 Cho Rok Shim,2 Junsung Park,2 Woo Heon Song,2 Min Chang Kwon,2 Jong Hyuk Lee,3 Jun Sang Park,2 Han-Gon Choi1 1College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea; 2GL PharmTech Corp, Seongnam, Republic of Korea; 3Department of Pharmaceutical Engineering, College of Life and Health Sciences, Hoseo University, Asan, Republic of KoreaCorrespondence: Jun Sang ParkGL PharmTech Corp, #714, Jungang Induspia V, 137 #714, Jungang Induspia V, 137, Seongnam-Si, Gyeonggi-Do 13202, South KoreaTel +82-31-739-5220Fax +82-31-739-5224Email jspark@glpt.co.krHan-Gon ChoiCollege of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of KoreaEmail hangon@hanyang.ac.krBackground: Novel three-layered (TL) tablet systems were compared with both monolithic matrix (MM) formulations and a commercial immediate-release (IR) capsule to develop once-a-day (OAD) pregabalin tablets.Methods: The physical properties of the TL tablets, including dissolution and swelling rates, were compared with those of the MM tablets and the pharmacokinetic parameters of the TL tablet were compared with those of an IR capsule in beagles and humans.Results: Our results indicated that the same amount of a hydrophilic polymer in the formulations had similar dissolution profiles at 12 h, regardless of the tablet geometry. However, the degree of tablet swelling differed, with larger amounts of polymer in the tablets showing a greater degree of swelling. In addition, TL tablets swelled more rapidly compared with MM tablets. For the pharmacokinetic study of the TL tablet, the beagles demonstrated absorption results similar to those of an IR capsule, whereas the humans demonstrated low total absorption compared with an IR capsule. The time of the peak plasma concentration at 6 h in the fed state of humans coincided with the results of the study on beagles.Conclusion: The novel TL tablet system of pregabalin may prove to be helpful in developing improved formulations with better continuous drug absorption for OAD administration.Keywords: controlled-release, three-layered tablet, polyethylene oxide, high swellable, once-a-day

Jeong Uk Lim,1 Eun Kyung Kim,2 Seong Yong Lim,3 Jin Hwa Lee,4 Jae Seung Lee,5 Sang-Do Lee,5 Yeon-Mok Oh,5 Chin Kook Rhee1 On behalf of the KOLD Study Group1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, South Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, South Korea; 5Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaCorrespondence: Chin Kook RheeDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero Seocho-gu, Seoul 06591, Republic of KoreaTel +82-2-2258-6067Fax +82-2-599-3589Email chinkook77@gmail.comObjective: The presence of both emphysema and airway wall thickening determined via volumetric computed tomography (CT) is defined as mixed phenotype. The long-term clinical course of this phenotype has not been studied in depth. This study compared the mixed phenotype to other phenotypes of chronic obstructive pulmonary disease (COPD) patients.Methods: COPD patients enrolled in the Korean Obstructive Lung Disease (KOLD) study from June 2005 to October 2015 were evaluated. The emphysema index and the percentage of bronchial mean wall area were calculated from volumetric CT scans. Patients with COPD were classified into four phenotypes using two cutoffs: emphysema index of 15% and median value of mean wall area (MWA%).Results: Of 435 patients with COPD, 99 (22.8%) were defined as CT-normal type, 119 (27.4%) as emphysema-dominant type, 113 (26.0%) as airway-dominant type, and 104 (23.9%) as mixed type. The mixed phenotype showed the highest baseline total COPD Assessment Test (CAT) and St. George’s Respiratory Questionnaire (SGRQ) scores. Moreover, it had the highest proportion of patients experiencing exacerbation of COPD (50.0%), and had the lowest baseline FEV1. Lower BMI, GOLD stages III–IV, and mixed phenotype were significant factors associated with severe exacerbation frequency in univariate analyses. Multivariate analyses showed that lower BMI and CT phenotype were significant factors associated with severe exacerbation frequency. Compared to the CT-normal phenotype, the mixed phenotype was significantly associated with more frequent severe exacerbation (IRR 4.134, 95% CI: 1.135–15.057, P=0.031).Conclusion: Patients with mixed phenotype are more symptomatic, have poorer pulmonary function, and are associated with more frequent severe exacerbation.Keywords: COPD, emphysema, computed tomography, mixed phenotype

Jung-Kyu Lee,1 Chin Kook Rhee,2 Kyungjoo Kim,2 Seung Won Ra,3 Jae Ha Lee,4 Ki-Suck Jung,5 Kwang Ha Yoo,6 Yoo-Il Kim,7 Deog Kyeom Kim1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea; 3Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 4Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 7Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of KoreaCorrespondence: Deog Kyeom KimDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, #395 Shindaebang-2-Dong, Dongjak-Gu, Seoul 156-707, Republic of KoreaTel +82-2-870-2228Fax +82-2-831-0714Email kimdkmd@snu.ac.krBackground: Methylxanthines and leukotriene receptor antagonists (LTRA) are not a first-line medical treatment for chronic obstructive pulmonary disease (COPD) but are frequently prescribed despite limited evidence. We aimed to elucidate the real prescribing status and clinical impacts of these agents in early COPD patients.Methods: Patients with mild-to-moderate COPD (FEV1>50%) were selected from the Korean National Health and Nutrition Examination Survey data between 2007 and 2012. Besides analyzing the prescription status of methylxanthines and LTRA and the contributing factors to the prescription, we evaluated the clinical impacts of these drugs on the exacerbation, hospitalization, and medical costs.Results: Of 2269 patients with mild-to-moderate COPD, 378 patients (16.7%) were under medical treatments, and the users of methylxanthines and/or LTRA were 279 patients (12.3%); however, only 139 patients (6.1%) were inhaler users. The contributing factors for the prescription of methylxanthines were a comorbidity of asthma or allergic disease, poor lung function, low quality of life, prescribing doctor from the specialty of internal medicine, and an institution type of private hospital. The prescription of LTRA was associated with the comorbidity of allergic disease. The methylxanthine and/or LTRA users had more hospital utilization but did not have significant differences in acute exacerbations and medical cost for hospital utilization, compared with the non-users.Conclusion: Methylxanthines and LTRA were used in a significant proportion of patients with mild-to-moderate COPD in real fields without favorable impacts on the exacerbations, hospitalizations, or medical costs. The use of more effective inhaled medications should be encouraged.Keywords: pulmonary disease, chronic obstructive, methylxanthine, leukotriene antagonists, drug prescriptions

Sung Yoon Lim,1 Gajin Lim,2 Yeon Joo Lee,1 Young Jae Cho,1 Jong Sun Park,1 Ho Il Yoon,1,2 Jae Ho Lee,1,2 Choon-Taek Lee1,3 1Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 2Division of Pulmonology Medicine, Department of Internal Medicine, Cheongju Hana Hospital, Cheongju-si, Korea; 3Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, KoreaCorrespondence: Choon-Taek LeeDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, Seongnam, Seoul, South KoreaTel +82 31 787 7002Fax +82 31 787 4052Email ctlee@snubh.orgPurpose: 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.Keywords: ultrasonography, diaphragmatic excursion, diaphragmatic thickening, exacerbation, chronic obstructive pulmonary disease