Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.

Objective This phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a cannabinoid type 2 receptor agonist, in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods A multinational double‐blind study was conducted in 365 dcSSc patients who were randomized and dosed 1:1:1 with lenabasum 20 mg, lenabasum 5 mg, or placebo, each twice daily and added to background treatments, including immunosuppressive therapies (IST). Results The primary end point, the American College of Rheumatology combined response index in dcSSc (CRISS) at week 52 for lenabasum 20 mg twice a day versus placebo, was not met, with CRISS score of 0.888 versus 0.887 ( P = 0.4972, using mixed models repeated measures [MMRM]). The change in the modified Rodnan skin thickness score (MRSS) at week 52 for lenabasum 20 mg twice a day versus placebo was −6.7 versus −8.1 ( P = 0.1183, using MMRM). Prespecified analyses showed higher CRISS scores, greater improvement in MRSS, and lower decline in forced vital capacity in patients on background mycophenolate and those who were taking IST for ≤1 year. No deaths or excess in serious or severe adverse events related to lenabasum were observed. Conclusion A benefit of lenabasum in dcSSc was not demonstrated. Most patients were treated with background IST, and treatment with mycophenolate mofetil in particular was associated with better outcomes. These findings support the use of IST in the treatment of dcSSc and highlight the challenge of demonstrating a treatment effect when investigational treatment is added to standard of care IST. These findings have relevance to trial design in SSc, as well as to clinical care.

Introduction: Coronavirus disease 2019 (COVID-19) still has a high mortality rate when it is severe. Regdanvimab (CT-P59), a neutralizing monoclonal antibody that has been proven effective against mild to moderate COVID-19, may be effective against severe COVID-19. This study was conducted to determine the effectiveness of the combined use of remdesivir and regdanvimab in patients with severe COVID-19. Methods: From March to early May 2021, 124 patients with severe COVID-19 were admitted to Ulsan University Hospital (Ulsan, Korea) and received oxygen therapy and remdesivir. Among them, 25 were also administered regdanvimab before remdesivir. We retrospectively compared the clinical outcomes between the remdesivir alone group [n = 99 (79.8%)] and the regdanvimab/remdesivir group [n = 25 (20.2%)]. Results: The oxygen-free days on day 28 (primary outcome) were significantly higher in the regdanvimab/remdesivir group [mean ± SD: 19.36 ± 7.87 vs. 22.72 ± 3.66, p = 0.003]. The oxygen-free days was also independently associated with use of regdanvimab in the multivariate analysis, after adjusting for initial pulse oximetric saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio (severity index). Further, in the regdanvimab/remdesivir group, the lowest SpO2/FiO2 ratio during treatment was significantly higher (mean ± SD: 237.05 ± 89.68 vs. 295.63 ± 72.74, p = 0.003), and the Kaplan-Meier estimates of oxygen supplementation days in surviving patients (on day 28) were significantly shorter [mean ± SD: 8.24 ± 7.43 vs. 5.28 ± 3.66, p = 0.024]. Conclusions: In patients with severe COVID-19, clinical outcomes can be improved by administering regdanvimab, in addition to remdesivir.

Background/Aims To assess the efficacy and safety of intra-articular sacroiliac glucocorticoid injection in ankylosing spondylitis (AS). Methods Patients with AS undergoing fluoroscopy-guided intra-articular sacroiliac glucocorticoid injection were enrolled between 2012 and 2018. Efficacy was assessed by numeric pain rating scale, acute phase reactants, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index, and Ankylosing Spondylitis Disease Activity Score (ASDAS). Patients who started biologics within 3 months despite the intervention were compared with those not starting biologics, hence: the nonbiologic group. Results A total of 96 patients were treated, with a total of 107 injections. After intervention, there were significant decreases in numeric pain rating scale (7.8 +/- 1.8 vs. 3.3 +/- 2.2, p < 0.001) and acute phase reactants level (erythrocyte sedimentation rate [ESR] 23.0 mm/h [10.0-47.0 mm/h] vs. 13.0 mm/h [4.0-27.0 mm/h], p < 0.001; C-reactive protein [CRP] 1.0 mg/dL [0.2-2.7 mg/dL] vs. 0.2 mg/dL [0.2-0.9 mg/dL], p < 0.001). Disease activity scores also decreased for BASDAI (6.2 +/- 1.8 vs. 4.5 +/- 2.5, p = 0.001), Bath Ankylosing Spondylitis Functional Index (5.5 [4.1-7.0] vs. 1.8 [0.5-4.1], p = 0.001), ASDAS-CRP (2.9 +/- 1.0 vs. 2.3 +/- 1.3, p = 0.046), and ASDAS-ESR (3.7 +/- 1.1 vs. 2.4 +/- 1.3, p < 0.001). However, 12 patients (12.5%) started biologics within 3 months. These patients showed higher ESR (91.0 mm/h [IQR 21.0-113.0 mm/h] vs. 21.5 mm/h [IQR 9.5-43.0 mm/h], p = 0.010), CRP (8.0 mg/dL [IQR 1.11-17.1 mg/dL] vs. 0.8 mg/dL [IQR 0.2-1.8 mg/dL], p = 0.002), BASDAI (7.4 +/- 1.2 vs. 5.9 +/- 1.8, p = 0.027), and ASDAS-CRP (4.0 +/- 0.5 vs. 2.8 +/- 1.0, p = 0.004) than the nonbiologic group. There was no serious adverse event. Conclusions Intra-articular sacroiliac glucocorticoid injection can be a safe and effective treatment option for active sacroiliitis in AS.

Background MUC5B variant rs35705950 is the common and most significant risk variant for rheumatoid arthritis-interstitial lung disease (RA-ILD) in Western populations. However, little is known about its significant association with RA-ILD in Asian populations. We here investigate the association of rs35705950 with Korean patients with RA-ILD. Methods In this cross-sectional study, we genotyped rs35705950 in 2444 patients with RA. Among them, 683 patients with RA who have chest CT were divided into RA-ILD and RA-noILD. RA-ILD was classified as usual interstitial pneumonia (UIP) and other than UIP. The associations of rs35705950 with RA-ILD and its subtype were analysed using multivariable regression adjusted for age at RA diagnosis. Meta-analysis of a previously reported Japanese dataset and Korean dataset obtained for this study was conducted. Results The minor allele (T) frequency of rs35705950 was 0.37%, 1.43% and 2.38% in 2444 patients with RA, 105 patients with RA-ILD and 63 patients with UIP, respectively. Genotypic association of rs35705950 with RA-ILD was insignificant (OR 2.49, 95% CI 0.64 to 9.69, p=0.187), but showed significant association with UIP (OR 4.90, 95% CI 1.23 to 19.59, p=0.024) compared with RA-noILD. In meta-analysis (123 UIP and 878 RA-noILD) combining our data with previously reported Japanese data, this variant was found to be significantly associated with UIP (OR 3.51, 95% CI 1.19 to 10.37, p=0.023). Conclusion MUC5B variant rs35705950 is a rare but significant risk factor for Asian patients with RA-ILD with UIP, suggesting a sharing of the genetic background between Asian and Western populations.

Background: Hyperuricemia in patients with gout is associated with a low risk of neurodegenerative diseases, including dementia. However, the prevalence of dementia in patients with gout has not yet been reported. Objective: To analyze the prevalence of dementia among patients diagnosed with gout by utilizing the Health Insurance and Review Assessment database, a nationwide registry of the South Korean population. Methods: Data from the Health Insurance and Review Assessment database of patients diagnosed with gout between 2011 and 2018 were extracted. The annual prevalence of dementia according to age and sex was analyzed. We investigated whether there was an association between comorbidities and gout medication in patients with both gout and dementia and in patients with only gout. Results: Between 2011 and 2018, the age-adjusted prevalence of dementia per 100,000 persons ranged from 54.0 (95% confidence interval: 47.7-60.2) to 69.9 (95% confidence interval: 65.3-74.5). Compared to previous studies, the prevalence of dementia was lower in patients with gout than in the general population. Patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related drugs, including allopurinol, febuxostat, nonsteroidal anti-inflammatory drugs, and steroids than patients with gout without dementia. Conclusions: This study demonstrated a relatively low prevalence of dementia in patients with gout. Gout, characterized by hyperuricemia, might be associated with a reduced risk of dementia.

BACKGROUND:This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19.METHODS:This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021.RESULTS:A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2.CONCLUSION:At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

Background YouTube has become an increasingly popular educational tool and an important source of healthcare information. We investigated the reliability and quality of the information in Korean-language YouTube videos about gout. Methods We performed a comprehensive electronic search on April 2, 2021, using the following keywords—“gout,” “acute gout,” “gouty arthritis,” “gout treatment,” and “gout attack”—and identified 140 videos in the Korean language. Two rheumatologists then categorized the videos into three groups: “useful,” “misleading,” and “personal experience.” Reliability was determined using a five-item questionnaire modified from the DISCERN validation tool, and overall quality scores were based on the Global Quality Scale (GQS). Results Among the 140 videos identified, 105 (75.0%), 29 (20.7%), and 6 (4.3%) were categorized as “useful,” “misleading,” and “personal experience,” respectively. Most videos in the “useful” group were created by rheumatologists (70.5%). The mean DISCERN and GQS scores in the “useful” group (3.3 ± 1.0 and 3.8 ± 0.7) were higher than those in the “misleading” (0.9 ± 1.0 and 1.9 ± 0.6) and “personal experience” groups (0.8 ± 1.2 and 2.0 ± 0.8) (P < 0.001 for both the DISCERN and GQS tools). Conclusion Approximately 75% of YouTube videos that contain educational material regarding gout were useful; however, we observed some inaccuracies in the medical information provided. Healthcare professionals should closely monitor media content and actively participate in the development of videos that provide accurate medical information.

Background There have been many studies on the clinical characteristics of neutrophilic, lymphocytic, and/or eosinophilic pleural effusion. While caring for patients with pleural effusion, we found that histiocytic pleural effusion (HisPE) was not uncommon. However, few studies have explored HisPE. The purpose of the present study was to determine the clinical characteristics and etiologies of HisPE. Methods In this retrospective study, HisPE was defined as pleural fluid white blood cells comprised of ≥ 50% histiocytes. Using a clinical data warehouse, patients with HisPE among all patients aged >18 years who underwent thoracentesis and pleural fluid analysis between January 2010 and December 2019 at Ulsan University Hospital were enrolled. A total of 295 (9.0%) of 3279 patients who underwent thoracentesis were identified as HisPE patients. Among them, 201 with exudative HisPE were included. Clinical characteristics and etiologies were extracted from medical records and analyzed. Results Among the 201 patients with exudative HisPE, the major causes were malignant pleural effusion ( n = 102 [50.7%]), parapneumonic effusion ( n = 9 [4.5%]), and tuberculous pleurisy ( n = 9 [4.5%]). In the 102 patients with malignant pleural effusion, the main types of cancer were lung ( n = 42 [41.2%]), breast ( n = 16 [15.7%]), and stomach cancer ( n = 11 [10.8%]). Among lung cancers, adenocarcinoma ( n = 34 [81.0%]) was the most common histology. Conclusions The leading cause of exudative HisPE was malignancy, particularly lung cancer. Physicians should consider the possibility of malignant disease if histiocytes are predominantly present in pleural effusion.

Background: Lenabasum is an oral CB2 agonist that attenuates inflammation and fibrosis in SSc animal models and showed clinical benefit with acceptable safety in a Phase 2 trial in dcSSc. Objectives: Test efficacy and safety of lenabasum in a Phase 3 trial in dcSSc. Methods: Subjects ≥18 years old with disease duration ≤ 6 years were randomized 1:1:1 to lenabasum 5 mg, 20 mg, or placebo (PBO), all BID, with stable background immunosuppressant therapy (IST) allowed. The primary efficacy endpoint was ACR CRISS score, and secondary endpoints were ΔmRSS, ΔHAQ-DI, and ΔFVC, all at Week 52 for lenabasum 20 mg vs PBO. Results: 363 adults were dosed; 37 (10%) stopped study drug early, with only 1 subject (PBO cohort) stopping due to adverse event (AE). Baseline demographics were similar among groups. Disease duration was ≤ 3 years in 60% and 66%, mean mRSS score was 22.0 and 23.3, and background IST was used by 89% and 84% of lenabasum 20 mg and PBO groups, respectively. Safety results showed serious AEs and severe AEs occurred in 9.2% and 5.8% vs 14.6% and 13.0%, respectively, of lenabasum 20 mg and PBO groups. Efficacy results (Table) demonstrated: Table 1. Primary and secondary efficacy endpoints and post-hoc analyses, Week 52 Group, by IST treatment Cohort N ΔmRSS, mean (SD ) ΔFVC% mean (SD ) ΔFVC, mL mean (SD ) ΔHAQ-DI mean (SD ) ACR CRISS median mITT population, MMRM primary analysis method All Placebo 123 -8.1 (7.72) -1.0 (8.68) -51 (317) -0.13 (0.468) 0.887 Lenabasum 20 mg 120 -6.7 (6.59) -1.6 (6.91) -78 (265) -0.13 (0.436) 0.888 Placebo subjects, per protocol completers, LOCF No IST Placebo 16 -2.3 (9.4) -2.8 (7.4) -97 (244) 0.12 (0.34) 0.417 All IST Placebo 97 -8.9 (7.07) -1.0 (9.2) -43 (330) -0.17 (0.474) 0.936 MMF, no other IST Placebo 29 -10.7 (8.1) -0.58 (7.1) -37 (235) -0.12 (0.456) 0.935 MMF ≤ 2 years, no other IST Placebo 23 -11.7 (8.1) -0.3 (6.0) -41 (197) -0.13 (0.495) 0.935 Non-MMF ≤ 2 years Placebo 24 -6.7 (6.2) -1.4 (7.87) -52 (281) -0.15 (0.357) 0.931 Post-hoc comparisons, per protocol completers, LOCF No IST Placebo 16 -2.3 (9.4) -2.8 (7.4) -97 (244) 0.12 (0.34) 0.417 Lenabasum 20 mg 10 -6.3 (6.02) -2.3 (5.58) -99 (209) -0.06 (0.498) 0.811 Established IST1 Placebo 26 -6.1 (5.35) -4.6 (10.11) -170 (350) -0.17 (0.445) 0.619 Lenabasum 20 mg 38 -7.4 (5.08) - 0.4 (5.70) 2 -21 (233) 3 -0.07 (0.357) 0.941 Established IST, subjects with ILD Placebo 22 -5.9 (5.28) -3.7 (5.43) -133 (206) -0.10 (0.372) 0.553 Lenabasum 20 mg 33 -7.2 (5.70) -1.0 (10.5) -47 (365) -0.06 (0.391) 0.819 2 P = 0.0386 two-sample t-test; 3 P = 0.0481 two-sample t-test; other comparisons were not significant • No significant differences were seen in primary and secondary efficacy endpoints. Primary MMRM analyses with treatment-by-time-by-subgroup interactions showed that background mycophenolate (MMF) significantly influenced the outcome •oSubjects on no IST with disease duration ≤3 years were only 7% of PBO subjects and showed little improvement on PBO, in line with other dcSSc trials in which IST was restricted. Post-hoc subgroup analyses of these subjects on no IST suggested improvement in ΔmRSS and ΔHAQ-DI, for lenabasum 20 mg vs PBO •uUnexpectedly high improvement occurred in PBO subjects receiving IST, notably those on MMF started within 2 years of baseline •nPost-hoc analyses of subjects on established IST (MMF or, if no MMF, ≥ 1 non-MMF IST started > 2 years before baseline) suggested improvement in ΔFVC% (nominal P = 0.0386) and ΔFVC mL (nominal P = 0.0481) for lenabasum 20 mg vs PBO. Improvement in FVC was also seen in subjects on established IST who had ILD at baseline, lenabasum 20 mg vs PBO •mACR CRISS score demonstrated a ceiling effect and correlated most highly with ΔmRSS (r = -0.739) and moderately with MDGA (-0.432), HAQ-DI (-0.362), FVC% (0.366), and PtGA (-0.288) Conclusion: Lenabasum was safely used in this study. Unexpectedly high improvement on background IST, especially MMF, has not been previously reported at this level. The primary endpoint was not met. Post-hoc analyses showed greater improvement in lenabasum- vs PBO-treated subjects who were not on background IST and those on established IST, including subjects with ILD. Disclosure of Interests: Robert Spiera Consultant of: Abbvie, Roche-Genetech, GSK, CSL Behring, Sanofi, Janssen, Chemocentryx, Formation Biologics, Mitsubishi Tanabe, Grant/research support from: Roche-Genetech, GSK, Boehringer Ingelheim, Chemocentryx, Corbus, Formation Biologics, Sanofi, Inflarx, Astra Zeneca, Kadmon, Masataka Kuwana Speakers bureau: Boehringer-Ingelheim, Chugai, Janssen, Consultant of: Boehringer-Ingelheim, Chugai, Corbus, Grant/research support from: Boehringer-Ingelheim, Chugai, MBL, Ono Pharmaceuticals, Tanabe-Mitsubishi, Dinesh Khanna Shareholder of: Eicos Sciences, Inc (less than 5%). Leadership/Equity position – Chief Medical Officer, CiviBioPharma/Eicos Sciences, Inc, Consultant of: Acceleron, Actelion, Abbvie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead, Galapagos, Genentech/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis, and United Therapeutics, Grant/research support from: NIH, Immune Tolerance Network, Bayer, BMS, Horizon, Pfizer, Laura Hummers Consultant of: CSL Behring, Boehringer Ingelheim, Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals. Corbus, Boehringer Ingelheim, Medpace, Kadmon, Cumberland, CSL Behring, Tracy Frech Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals, Wendy Stevens Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals, Jessica Gordon Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals. Research funding for EICOS Pharmaceuticals and Cumberland Pharmaceuticals., Suzanne Kafaja Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals, Marco Matucci-Cerinic Consultant of: Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals, Oliver Distler Consultant of: Consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB., Eun Bong Lee Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals, Yair Levy Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals, Jae-Bum Jun Consultant of: Consultant to Boehringer Ingelheim Korea, Jeil Pharma, Dae Woong Pharma, Kwangdong Pharma, and Sama Pharma., Grant/research support from: Investigator for study sponsored by Corbus Pharmaceuticals, Scott Constantine Employee of: Employee of Corbus Pharmaceuticals, Nancy Dgetluck Employee of: Employee of Corbus Pharmaceuticals, Barbara White Employee of: Employee and stockholder of Corbus Pharmaceuticals, Daniel Furst Consultant of: Corbus, Galapagos, Pfizer, CSL Behring, Mitsubishi Tanabi, Actelion, Amgen, Novartis, Roche/Genentech, Gilead, Talaris, and Boehringer Ingelheim., Grant/research support from: grants from Corbus, Galapagos, GSK, Pfizer, Talaris, CSL Behring, Mitsubishi Tanabi, Christopher Denton Consultant of: Consultancy fees and/or honoraria from Corbus, Actelion, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Inventiva, Boehringer Ingelheim, Roche, CSL Behring, Acceleron, Horizon, Arxx Therapeutics

Copyright © 2021 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. pISSN 1226-3303 eISSN 2005-6648 http://www.kjim.org Departments of 1Rheumatology and 2Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul; 3Department of Pathology, National Police Hospital, Seoul, Korea

Background: Active tuberculosis (TB) develops in approximately 10% of people with a latent tuberculosis infection (LTBI). TB guidelines recommend that LTBI screening and treatments target high-risk patients. Malignancies are not universally considered a high-risk factor for active TB. This study aimed to determine the degrees to which active TB risk was associated with various cancers in a Korean population. Methods: This study involved patients aged >= 20 years who were diagnosed with cancer at Ulsan University Hospital (UUH) from January 2000 to December 2014 and individuals who visited UUEI for health screening and were age- and sex-matched randomly with cases in a 1:2 ratio. Using retrospective cohort study, the development of bacteriologically con firmed TB (BCTB) within 3 years after enrollment was investigated. The relative risks of BCTB were estimated using incidence rate ratios (IRRs) and a Poisson regression analysis. Results: During the study period, 380 of 34,783 cancer patients and 79 of 69,566 control subjects developed BCTB, yielding respective incidence rates of 535 and 37/100,000 person-years, respectively. In all cancer cases, the IRR of BCTB was 14.30, and especially high rates were associated with the following cancers: esophageal cancer (74.72), multiple myeloma (70.76), lung cancer (50.35), pancreatic cancer (46.04), leukemia (40.45), head and neck cancer (24.60), and lymphoma (22.67). Conclusions: The incidence of active TB was higher in cancer patients than in control subjects. In particular, lung cancer, esophageal cancer, pancreatic cancer, hematologic malignancy and head and neck cancer were identified as high-risk factors for active TB, as indicated by IRRs of 20-75. These findings suggest that patients with high-risk cancers should be targeted for LTBI screening and treatment.

Objective. This study aimed to evaluate the relationship between serum immunoglobulin G4 (IgG4) levels and the presence and disease activity of rheumatoid arthritis (RA). Methods. The study enrolled 128 participants (RA, 96; healthy controls, 17; osteoarthritis, 11; and IgG4-related disease, 4) between March 2014 and July 2017. Blood samples were collected prior to the commencement of treatment, and serum IgG4 levels were determined using a nephelometric assay (levels >= 135 mg/dL were considered elevated). The levels of serum IgG4 and the ratio of IgG4/total IgG in patients with RA were compared with those in healthy controls, patients with osteoarthritis, and patients with IgG4-related disease. Furthermore, the relationship between serum IgG4 levels and RA disease activity was evaluated. Results. Among the 96 patients with RA, the mean (+/- standard deviation) serum IgG4 level was 48.0 +/- 45.4 mg/dL; 6 (6.3%) patients had elevated serum IgG4 levels. However, none of the healthy controls or patients with osteoarthritis had elevated serum IgG4 levels. The mean serum IgG4/IgG ratio in patients with RA was 3.5%+/- 2.8% (range, 0.2%similar to 16.9%). Using Spearman's correlation coefficient analysis, a significant correlation was found between serum IgG4 levels and the Disease Activity Score-28 with erythrocyte sedimentation rate (r, 0.245; p=0.016). Conclusion. There was an increased frequency of elevated serum IgG4 levels in patients with RA, and the levels were correlated with RA disease activity.

Objective. We investigated Asian mitochondrial DNA (mtDNA) haplogroups associated with knee osteoarthritis (OA) progression in a prospective community-based cohort comprised of Koreans. Methods. Epidemiologic data and Kellgren-Lawrence (K/L) scores of knee radiographs were obtained from the second (2005 similar to 2006) and sixth (2013 similar to 2014) follow-up, and patient DNA was analyzed. The mtDNA haplogroup frequencies (M, G, D, D4, D5, M7, M8, M9, M10, N, A, N9, R, F, and B) were compared between the progression (K/L score change on either knee >= 2 or arthroplasty) and non-progression (K/L score change on both knee <= 1) groups at the sixth follow-up. Multiple logistic regression was performed to determine relative risk (RRs) of mtDNA haplogroups for OA. Results. In total, 1,115 participants were included, 405 of whom had early OA (higher K/L score on both knees of 1 or 2). Among them, 143 and 166 patients were classified in non-progression and progression groups, respectively, at the sixth follow-up. The most frequent haplogroups, B and D4, in Koreans also showed a high frequency in our study. There were no significantly different haplogroups between the non-progression and progression groups. However, the frequency of haplogroup D4 was likely higher in the non-progression group than in the progression group, although not significantly (13.3% vs. 7.2%, RR=0.51, p=0.081 in the unadjusted model and RR=0.56, p=0.149 in the adjusted model). Conclusion. No significant haplogroups are related to OA progression. Large-scaled studies are needed to reveal the association between mtDNA haplogroups and OA.

Background: Digital ulcer (DU) is a common clinical manifestation in patients with systemic sclerosis (SSc). About 70% of patients with SSc experience DUs during the first 10 years, which limit daily activities and may result in digital gangrene or amputation. Several vasoactive/vasodilating agents have been suggested for treatment, but few studies have compared the efficacy of those drugs. Objectives: The objective of our study was to compare the efficacy of medical treatment for SSc related-DUs, focusing on on endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitors (PDE5inh). Methods: In this prospective observational cohort study, we recruited patients who had one or more active SSc-related DUs and newly started or changed a medical treatment for SSc-related DUs from 13 medical centers in South Korea. The primary outcome was to compare the time to resolution of cardinal DU (CU) according to the treatments. The secondary outcomes included changes in the size or number of CU and changes in the number of DUs. CU was defined as the most clinically significant DU chosen by the investigators. Patients were followed up at every 4 weeks after enrollment until 12 weeks and finally at 24 weeks. Results: Seventy-one patients were enrolled. Seven patients were excluded due to follow-up loss or withdrawal of consent. A total of 64 patients were analyzed. Seventy-eight percent (n=50) were female. The mean age at enrollment was 49.6 ± 11.6 year-old, and the mean disease duration was 7.1 ± 5.9 years. Twenty-eights pateitns (43.8%) were limited SSc. Forty-nine patients (n=76.6%) started ERA treatment (bosentan=49). Eleven patients (17.2%) started PDE5inh treatment (n=9 for sildenafil, n=1 for udenafil, and n=1 for tadalafil). Four patients who started medication other than ERA or PDE5inh classified as other treatment groups. Seventeen patients (26.6%) were on background calcium channel blockers (CCBs). CU healed in 25 patients (39.1%) at 12 weeks and 43 patients (67.2%) at 24 weeks. The mean time to heal CUs were 54.4 ± 22.7 days at 12 weeks and 91.6 ± 49.2 days at 24 weeks. Time to heal CU was comparable among patients on ERA, PDE5inh, and others (p=0.53, figure 1). The CU area was comparable among the three groups at baseline, 12, and 24 weeks. The mean area of CU in patients on ERA at baseline at 12, and 24 weeks was 21.3±19.4 mm 2 , 8.2±14.6 mm 2 , and 4.6±7.7 mm 2 , respectively. The mean area of CU in patients with PDE5inh at baseline at 12, and 24 weeks was 26.2±28.1 mm 2 , 3.5±3.6 mm 2 , and 1.3±4.3 mm 2 . New DUs developed in 4 patients (8.3%) in ERA, whereas 4 patients (40.0%) in PDE5inh at 4 weeks. The use of ERA was significantly associated with less new DUs development than the use of PDE5inh at 4 weeks follow-up (RR for developing new DU patients on ERA, 0.21; 95% CI 0.06-0.70; p=0.02) At 24 weeks follow-up, none of the patients on CCB developed new DUs. Conclusion: The time to heal CU for ERA and PDEinh users was comparable in the current study. ERA treatment was associated with reduced new DU occurrence compared with PDE5inh treatment. None of the patients with CCB treatment developed new DU development at 24 weeks. Acknowledgments: This study was supported by Handok Pharmaceutical Inc., Seoul, Republic of Korea. Disclosure of Interests: Sung Hae Chang: None declared, Jae-Bum Jun Grant/research support from: Clinical trials; Corbus, JW Pharmaceutical, Speakers bureau: SK Chemical, Yun Jong Lee: None declared, Tae Young Kang: None declared, Yongbeom Park: None declared, Seung-Geun Lee: None declared, Shin-Seok Lee: None declared, Eun Bong Lee: None declared Figure 1

Objectives: To investigate the association of hyperuricemia with pulmonary hypertension (PH) in term of subsequent development, severity, and prognosis of PH. Methods: The authors systematically reviewed articles from databases and conducted meta-analyses as follows: (1) association of serum uric acid (UA) levels with the presence of PH; (2) association between serum UA levels and subsequent development of PH, in terms of odds ratio of the development of PH; and (3) association of serum UA levels with severity and prognosis of PH, in terms of pulmonary arterial pressure and hazard ratio of death. Results: Twenty-six studies published between 1999 and 2017 were included. The level of serum UA was higher in subjects with PH than subjects without PH and this finding was observed regardless of status of diuretics use or renal function. The odds ratio of the development of PH was 2.32 (95% CI, 1.05-5.15) in subjects with hyperuricemia. Pulmonary arterial pressure among subjects with PH was also higher in subjects with hyperuricemia than subjects with normouricemia. There was a 19% increased hazard ratio of death (95% CI, 1.06-1.33) among patients with PH who had hyperuricemia. Conclusion: Hyperuricemia is associated with the subsequent development, worse severity and poor prognosis of PH.

“의료 윤리”가 의사들이 이수해야 할 필수 과목이 된 시대를 살고 있다. 본 지면에서는 우선 대한내과학회에 윤리위원회가 설치된 배경과 그 과정을 정리하고, 내과 의사 윤리 선언의 제정과 내용에 대하여 살펴본 후, 내과 의사가 되고자하는 내과 전공의들에 대한 윤리 교육의 현재와 앞으로의 방향에 대하여 기술해보고자 한다.