SCI 발표논문

1. 38082022

   제1저자 이현정 · 교신저자 김형관, 이상철

   Lee HJ, Kim J, Chang SA, Kim YJ, Kim HK^*, Lee SC^*

   Major Clinical Issues in Hypertrophic Cardiomyopathy.

   Korean Circ J. 2022;52(8):563-575.

   Abstract

   Hypertrophic cardiomyopathy (HCM) is one of the most common inheritable cardiomyopathies. Contemporary management strategies, including the advent of implantable cardioverter-defibrillators and effective anticoagulation, have substantially improved the clinical course of HCM patients; however, the disease burden of HCM is still high in Korea. Sudden cardiac death (SCD), atrial fibrillation and thromboembolic risk, dynamic left ventricular outflow tract (LVOT) obstruction, and heart failure (HF) progression remain important issues in HCM. SCD in HCM can be effectively prevented with implantable cardioverter-defibrillators. However, appropriate patient selection is important for primary prevention, and the 5-year SCD risk score and the presence of major SCD risk factors should be considered. Anticoagulation should be initiated in all HCM patients with atrial fibrillation regardless of the CHA₂DS₂-VASc score, and non-vitamin K antagonist oral anticoagulants are the first option. Symptomatic dynamic LVOT obstruction is first treated medically with negative inotropes, and if symptoms persist, septal reduction therapy is considered. The recently approved myosin inhibitor mavacamten is promising. HF in HCM is usually related to diastolic dysfunction, while about 5% of HCM patients show reduced left ventricular ejection fraction <50%, also referred to as "end-stage" HCM. Myocardial fibrosis plays an important role in the progression to advanced HF in patients with HCM. Patients who do not respond to guideline-directed medical therapy can be considered for heart transplantation. The development of imaging techniques, such as myocardial deformation on echocardiography and late gadolinium enhancement on cardiac magnetic resonance, can provide better risk evaluation and decision-making for management strategies in HCM.

   PubMed IF 3.4 순환기내과
2. 38072022

   제1저자 장희준, 이윤빈, 문혜미 · 교신저자 이윤빈, 이준영

   Jang H, Lee YB, Moon H, Chung JW, Nam JY, Cho EJ, Lee JH, Yu SJ, Kim YJ, Lee J, Yoon JH

   Aspirin use and risk of hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis.

   Hepatology. 2022;76(2):492-501.

   Abstract

   BACKGROUND AND AIMS Studies on differential effect of aspirin therapy on HCC risk across the spectrum of liver diseases are lacking. We investigated the association between aspirin use and risks of HCC, liver-associated death, and major bleeding in chronic hepatitis B (CHB) patients with or without cirrhosis.

   APPROACH AND RESULTS We identified 329,635 eligible adults with CHB from 2007 through 2017, using the Korean National Health Insurance Service database, including patients who received aspirin for ≥90 consecutive days (n = 20,200) and patients who never received antiplatelet therapy (n = 309,435). Risks of HCC, liver-associated mortality, and major bleeding were estimated in a propensity-score-matched cohort (19,003 pairs), accounting for competing risks. With a median follow-up of 6.7 years, 10-year cumulative incidence of HCC was 9.5% in the aspirin-treated group and 11.3% in the untreated group (adjusted subdistribution hazard ratio [aSHR], 0.85; 95% CI, 0.78-0.92). However, among patients with cirrhosis (2479 pairs), an association of aspirin use with HCC risk was not evident (aSHR, 1.00; 95% CI, 0.85-1.18). Cirrhosis status had a significant effect on the association between aspirin use and HCC risk (p_interaction , n = 0.04). Aspirin use was also associated with lower liver-associated mortality (aSHR, 0.80; 95% CI, 0.71-0.90). Moreover, aspirin use was not associated with major bleeding risk (aSHR, 1.09; 95% CI, 0.99-1.21).

   CONCLUSIONS Aspirin use was associated with reduced risks of HCC and liver-associated mortality in adults with CHB. Cirrhosis status had a substantial effect on the association between aspirin use and HCC risk.

   PubMed IF 18 소화기내과
3. 38062022

   제1저자 이소령, 안효정 · 교신저자 최의근

   Ahn HJ, Lee SR, Choi EK, Han KD, Rhee TM, Kwon S, Kim S, Oh S, Lip GYH

   Associations between obesity parameters and the risk of incident atrial fibrillation and ischaemic stroke in the different age groups.

   Front Cardiovasc Med. 2022;9:906844.

   Abstract

   OBJECTIVE Obesity and aging are important predisposing factors to atrial fibrillation (AF) and ischaemic stroke (IS). However, limited data comprehensively evaluated the relationships between obesity measurements and AF and IS in different ages.

   METHODS A total of 9,432,332 adults from the Korean National Health Insurance Service Database were included. The study population was categorized into the six age subgroups by an increase every decade from the twenties. We evaluated AF and IS risk according to body mass index (BMI) and waist circumference (WC) in the different age groups.

   RESULTS During a mean follow-up of 8.2 ± 1.0 years, BMI-AF presented a J-shaped association across ages. The highest hazard ratio (HR) of the BMI ≥ 30 kg/m² group was observed in subjects aged 30-39 years [HR 1.80, 95% CI 1.63-1.98, p < 0.001]. Underweight adults over 60 years also presented an increased AF risk. Incident IS risk increased in those with BMI over the normal range in early and midlife, but the association became obscured in adults aged > 60 years. Among the BMI ≥ 30 kg/m² groups, subjects aged 20-29 years presented the highest risk of IS [HR 3.00, 95% CI (2.34-3.84), p < 0.001]. Overall, WC-AF and WC-IS showed positive linear correlations, but the WC-IS association was weak in subjects aged ≥ 40 years.

   CONCLUSION The higher risks of AF and IS according to an increment of BMI and WC were most apparent among the young ages. The association between obesity measurements and IS was not significantly above the midlife. Weight management in the young and integrated risk factor management in the elderly are warranted.

   PubMed IF 3 순환기내과
4. 38052022

   제1저자 정석송, 최슬기 · 교신저자 강병주, 이은영

   Jeong S^*, Choi S^*, Park SM, Kim J, Ghang B, Lee EY

   Incident and recurrent herpes zoster for first-line bDMARD and tsDMARD users in seropositive rheumatoid arthritis patients: a nationwide cohort study.

   Arthritis Res Ther. 2022;24(1):180.

   Abstract

   BACKGROUND There is limited information regarding disease-modifying antirheumatic drug (DMARD)-dependent risks of overall, incident, and recurrent herpes zoster (HZ) during first-line biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) treatment among patients with seropositive rheumatoid arthritis (RA) in terms of HZ risk.

   METHODS A total of 11,720 patients with seropositive RA who were prescribed bDMARD or tofacitinib between January 2011 and January 2019 from the Korean Health Insurance Review & Assessment Service database were studied. A multivariate Cox proportional hazards regression model was adopted to evaluate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the risk of HZ dependent on the choice of first-line bDMARDs or tsDMARD, including etanercept, infliximab, adalimumab, golimumab, tocilizumab, rituximab, tofacitinib, and abatacept.

   RESULTS During the 34,702 person-years of follow-up, 1686 cases (14.4%) of HZ were identified, including 1372 (11.7%) incident and 314 (2.7%) recurrent HZs. Compared with that of the abatacept group, tofacitinib increased the overall risk (aHR, 2.46; 95% CI, 1.61-3.76; P<0.001), incidence (aHR, 1.99; 95% CI, 1.18-3.37; P=0.011), and recurrence (aHR, 3.69; 95% CI, 1.77-7.69; P<0.001) of HZ. Infliximab (aHR, 1.36; 95% CI, 1.06-1.74; P=0.017) and adalimumab (aHR, 1.29; 95% CI, 1.02-1.64; P=0.032) also increased the overall HZ risk. Moreover, a history of HZ was found to be an independent risk factor for HZ (aHR, 1.54; 95% CI, 1.33-1.78; P<0.001).

   CONCLUSIONS HZ risk is significantly increased in RA patients with a history of HZ after the initiation of bDMARDs or tsDMARD. The risk of incident and recurrent HZ was higher after tofacitinib treatment in patients with RA than that after treatment with bDMARDs. Individualized characteristics and history of HZ should be considered when selecting bDMARDs or tsDMARD for RA patients considering HZ risks.

   PubMed IF 5.4 류마티스내과
5. 38042022

   제1저자 정성민, 정재형, 노지윤 · 교신저자 송경호, 송준영, 신의철

   Jung S, Jung JH, Noh JY, Kim WJ, Yoon SY, Jung J, Kim ES, Kim HB, Cheong HJ, Kim WJ, Park SH, Song KH, Song JY, Shin EC

   The generation of stem cell-like memory cells early after BNT162b2 vaccination is associated with durability of memory CD8+ T cell responses.

   Cell Rep. 2022;40(4):111138.

   Abstract

   COVID-19 vaccines elicit humoral and cellular immune responses. Durable maintenance of vaccine-induced immunity is required for long-term protection of the host. Here, we examine activation and differentiation of vaccine-induced CD8⁺ T cells using MHC class I (MHC-I) multimers and correlations between early differentiation and the durability of CD8⁺ T cell responses among healthcare workers immunized with two doses of BNT162b2. The frequency of MHC-I multimer⁺ cells is robustly increased by BNT162b2 but decreases 6 months post-second vaccination to 2.4%-65.6% (23.0% on average) of the peak. MHC-I multimer⁺ cells dominantly exhibit phenotypes of activated effector cells 1-2 weeks post-second vaccination and gradually acquire phenotypes of long-term memory cells, including stem cell-like memory T (T_SCM) cells. Importantly, the frequency of T_SCM cells 1-2 weeks post-second vaccination significantly correlates with the 6-month durability of CD8⁺ T cells, indicating that early generation of T_SCM cells determines the longevity of vaccine-induced memory CD8⁺ T cell responses.

   PubMed IF 7.7 감염내과
6. 38032022

   제1저자 오상민 · 교신저자 함신영, 박상원

   Oh SM^*, Ham SY^*, Suh HJ, Lee E, Park SW

   Clinical Characteristics of COVID-19: Use of Steroids in Mostly Unvaccinated COVID-19 Patients Before the Omicron Variant.

   J Korean Med Sci. 2022;37(29):e228.

   Abstract

   BACKGROUND Glucocorticoids are one of the current standard agents for moderate to severe coronavirus disease 2019 (COVID-19) treatment based on the RECOVERY trial. Data on the real clinical application of steroids for COVID-19 are scarce and will help guide the optimal use of steroids. We described the current prescription pattern of steroids for COVID-19 and investigated the factors related to specific practices.

   METHODS All adults aged ≥ 19 years who were diagnosed with COVID-19 by real-time reverse transcription-polymerase chain reaction and admitted to one of 3 study hospitals from 8 December 2020 to 30 June 2021 were enrolled. Demographic and clinical data, including medications and oxygen therapy, were retrospectively collected from electronic medical records. The severity of comorbidities and COVID-19 were measured. The subjects were divided into steroid and nonsteroid groups, and the steroid group was then subdivided into standard and higher/longer groups.

   RESULTS Among a total of 805 patients, 217 (27.0%) were treated with steroids. The steroid group showed a higher rate of oxygen therapy (81.1% vs. 2.7%), more concomitant use of remdesivir (77.4% vs. 1.4%) or antibiotics (79.3% vs. 4.3%), and a higher proportion of high risk according to National Early Warning Score-2 score (30.0% vs. 0.9%) or severe risk according to National Institute of Allergy and Infectious Disease Ordinal Scale score (81.1% vs. 2.7%) than the nonsteroid group. The mortality of the steroid group was 4.6%. In the steroid group, 82.5% received a standard or lower dose of steroids within ten days, and 17.5% (38/217) received a higher or longer dose of steroids. Multivariate analysis showed that initial lymphopenia (adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.89-0.99) and high level of lactate dehydrogenase (LDH) (aOR, 1.00; 95% CI, 1.00-1.01) were independent risk factors for higher doses or longer steroid use.

   CONCLUSION The dose and duration of steroids were in line with current guidelines in 82.5% of COVID-19 patients, but the outliers may need tailored therapy according to surrogate markers, such as initial lymphopenia or high level of LDH.

   PubMed IF 3.2 감염내과
7. 38022022

   제1저자 박도현 · 교신저자 최평균

   Park DH, Lee CM, Chang E, Kang CK, Park WB, Kim NJ, Choe PG, Oh MD

   Clinical Impact of Empirical Antibiotic Therapy in Patients With Coronavirus Disease 2019 Requiring Oxygen Therapy.

   J Korean Med Sci. 2022;37(29):e238.

   Abstract

   Despite the low prevalence of secondary bacterial infection in coronavirus disease 2019 (COVID-19) patients, most of them were administered antibiotic therapy empirically. However, the prognostic impact of empirical antibiotic therapy has not been evaluated. We conducted retrospective propensity score-matched case-control study of 233 COVID-19 patients with moderate to severe illnesses who required oxygen therapy and evaluated whether empirical antibiotic therapy could improve clinical outcomes. Empirical antibiotic therapy did not improve clinical outcomes including length of stay, days with oxygen requirement, the proportion of patients with increased oxygen demand, the proportion of patients who required mechanical ventilation, and overall mortality. This finding implies that routine administration of antibiotics for the treatment of COVID-19 is not essential and should be restricted.

   PubMed IF 3.2 감염내과
8. 38012022

   제1저자 장상미, 최광현 · 교신저자 정숙향

   Jang S, Choi GH, Chang W, Jang ES, Kim JW, Jeong SH

   Elevated alpha-fetoprotein in asymptomatic adults: Clinical features, outcome, and association with body composition.

   PLoS One. 2022;17(7):e0271407.

   Abstract

   BACKGROUND AND AIM Apparently healthy individuals with elevated serum alpha-fetoprotein (AFP) levels (>7 ng/mL) for unknown causes visit clinics. We investigated their clinical characteristics, outcomes, and relationship with body fat deposition and muscle mass.

   METHODS The case group included asymptomatic 137 individuals with "elevated AFP level" (R772) diagnostic code from 2009 to 2018 in a tertiary hospital. The control group enrolled 274 age- and sex-matched patients with <5 cm hepatic hemangiomas. Hepatic, visceral, and psoas muscle adiposity and psoas muscle index (PMI) were measured in the subgroups of 45 cases and 90 controls with pre-contrast computed tomography (CT) images.

   RESULTS The case group (mean age 47.5 years, male 35.8%) showed higher AFP levels (10.3 vs 2.5 ng/mL, p<0.001) and total bilirubin (0.8 vs 0.7 mg/dL, p<0.001), but a lower body mass index (22.2 vs 23.3 kg/m2, p = 0.011) and alanine aminotransferase levels (17.0 vs 19.0 IU/L, p = 0.047) than the controls. During 13 months of median follow-up, there was no cancer or liver disease development. The AFP levels were stable. In the subgroups with CT images, cases showed a lower proportion of hepatic steatosis (4.4% vs 18.9%, p = 0.023), higher psoas muscle attenuation (48.2 vs 43.8 Hounsfield units, p<0.001) and higher PMI (5.7 vs 4.2 cm2/m2, p<0.001) than the controls.

   CONCLUSION Elevated AFP levels in asymptomatic individuals may play a role in expressing a protective phenotype against hepatic steatosis, myosteatosis, and sarcopenia. AFP levels in patients with elevated AFP were stable during follow-up without liver injury or cancer development. Interaction between AFP expression and steatosis warrants further study.

   PubMed IF 2.8 소화기내과
9. 38002022

   제1저자 이현정 · 교신저자 김형관, 이상철

   Lee HJ, Kim HK, Lee SC, Kim J, Park JB, Hwang IC, Choi YJ, Lee SP, Chang SA, Lee W, Park EA, Cho GY, Kim YJ

   Supplementary role of left ventricular global longitudinal strain for predicting sudden cardiac death in hypertrophic cardiomyopathy.

   Eur Heart J Cardiovasc Imaging. 2022;23(8):1108-1116.

   Abstract

   AIMS We investigated the prognostic role of left ventricular global longitudinal strain (LV-GLS) and its incremental value to established risk models for predicting sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM).

   METHODS AND RESULTS LV-GLS was measured with vendor-independent software at a core laboratory in a cohort of 835 patients with HCM (aged 56.3 ± 12.2 years) followed-up for a median of 6.4 years. The primary endpoint was SCD events, including appropriate defibrillator therapy, within 5 years after the initial evaluation. The secondary endpoint was a composite of SCD events, heart failure admission, heart transplantation, and all-cause mortality. Twenty (2.4%) and 85 (10.2%) patients experienced the primary and secondary endpoints, respectively. Lower absolute LV-GLS quartiles, especially those worse than the median (-15.0%), were associated with progressively higher SCD event rates (P = 0.004). LV-GLS was associated with an increased risk for the primary endpoint, independent of the LV ejection fraction, apical aneurysm, and 2014 European Society of Cardiology (ESC) risk score [adjusted hazard ratio (aHR) 1.14, 95% confidence interval (CI) 1.02-1.28] or 2011 American College of Cardiology/American Heart Association (ACC/AHA) risk factors (aHR 1.18, 95% CI 1.05-1.32). LV-GLS was also associated with a higher risk for the composite secondary endpoint (aHR 1.06, 95% CI 1.01-1.12). The addition of LV-GLS enhanced the performance of the ESC risk score (C-statistic 0.756 vs. 0.842, P = 0.007) and the 2011 ACC/AHA risk factor strategy (C-statistic 0.743 vs. 0.814, P = 0.007) for predicting SCD.

   CONCLUSION LV-GLS is an important prognosticator in patients with HCM and provides additional information to established risk stratification strategies for predicting SCD.

   PubMed IF 6.1 순환기내과
10. 37992022

    제1저자 이지형, 김혜령 · 교신저자 이상협, 구자록

    Lee JH, Kim H, Lee SH, Ku JL, Chun JW, Seo HY, Kim SC, Paik WH, Ryu JK, Lee SK, Lowy AM, Kim YT

    Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies.

    Gut Liver. 2022;16(4):625-636.

    Abstract

    BACKGROUND/AIMS Three-dimensional cultures of human pancreatic cancer tissue also known as "organoids" have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research.

    METHODS Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays.

    RESULTS Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy.

    CONCLUSIONS The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research.

    PubMed IF 4.1 소화기내과
11. 37982022

    제1저자 정석송 · 교신저자 박상민, 김원

    Jeong S, Oh YH, Choi S, Chang J, Kim SM, Son JS, Lee G, Kim W, Park SM

    Metabolic Dysfunction-Associated Fatty Liver Disease Better Predicts Incident Cardiovascular Disease.

    Gut Liver. 2022;16(4):589-598.

    Abstract

    BACKGROUND/AIMS Metabolic dysfunction (MD)-associated fatty liver disease is a new positive diagnostic criterion based on hepatic steatosis and MD. However, a comprehensive evaluation on the association of MD and hepatic steatosis with incident cardiovascular disease (CVD) has yet to be performed.

    METHODS This retrospective cohort study included 333,389 participants from the Korean National Health Insurance Service database who received a health examination between 2009 and 2010. Hepatic steatosis was defined using the Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease scoring system. Cox proportional hazards regression was adopted to determine the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for CVD according to the presence of hepatic steatosis and MD, as well as the composite term.

    RESULTS This study included 179,437 men and 153,952 women with a median age of 57 years. Hepatic steatosis with MD (aHR, 2.00; 95% CI, 1.89 to 2.13) and without MD (aHR, 1.30; 95% CI, 1.10 to 1.54) significantly increased the risk of CVD compared to no steatosis without MD (reference). However, steatosis revealed no significant difference in the risk of CVD compared to no steatosis among participants with one MD (aHR, 1.09; 95% CI, 0.91 to 1.30). In participants with steatosis, the presence of one and ≥2 MDs had aHR values of 1.25 (95% CI, 0.87 to 1.79) and 1.71 (95% CI, 1.22 to 2.41), respectively, compared to no MD.

    CONCLUSIONS Combined consideration of hepatic steatosis and MD was significantly associated with increased CVD risk and showed better predictive performance for CVD than hepatic steatosis or MD alone.

    PubMed IF 4.1 소화기내과
12. 37972022

    제1저자 모요셉, 강한빛 · 교신저자 강혜련

    Mo Y^*, Kang H^*, Bang JY, Shin JW, Kim HY, Cho SH, Kang HR

    Intratracheal administration of mesenchymal stem cells modulates lung macrophage polarization and exerts anti-asthmatic effects.

    Sci Rep. 2022;12(1):11728.

    Abstract

    Mesenchymal stem cells (MSCs) possess immunomodulatory properties that have therapeutic potential for the treatment of inflammatory diseases. This study investigates the effects of direct MSC administration on asthmatic airways. Umbilical cord MSCs (ucMSCs) were intratracheally administered to six-week-old female BALB/c mice sensitized and challenged with ovalbumin; airway hyperresponsiveness (AHR), analyses of airway inflammatory cells, lung histology, flow cytometry, and quantitative real-time PCR were performed. Furthermore, ex vivo and in vitro experiments were performed to assess the effects of ucMSC on M2 activation. Intratracheally administered ucMSCs decreased degree of airway resistance and the number of inflammatory cells such as T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), and macrophages in the murine asthma model. Particularly, MHCII and CD86 expression diminished in dendritic cells and alveolar macrophages (AMs) following ucMSC treatment. SiglecF⁺CD11c⁺CD11b^- AMs show a negative correlation with type II inflammatory cells including Th2 cells, ILC2, and eosinophils in asthmatic mice and were restored following intratracheal ucMSCs treatment. In addition, ucMSCs decreased the macrophage polarization to M2, particularly M2a. The expression levels of markers associated with M2 polarization and Th2 inflammation were also decreased. ucMSC reduced Il-12 and Tnfa expression as well as that of M2 markers such as Cd206 and Retnla ex vivo. Furthermore, the in vitro study using IL-4 treated macrophages confirmed that both direct and indirect MSC treatment significantly reduced the expression of Il-5 and Il-13. In conclusion, ucMSCs appear to suppress type II inflammation by regulating lung macrophages via soluble mediators.

    PubMed IF 4.9 알레르기내과
13. 37962022

    제1저자 이학승, 김웅 · 교신저자 Goran Stankovic, 구본권

    Lee HS, Kim U, Yang S, Murasato Y, Louvard Y, Song YB, Kubo T, Johnson TW, Hong SJ, Omori H, Pan M, Doh JH, Kinoshita Y, Banning AP, Nam CW, Shite J, Lefèvre T, Gwon HC, Hikichi Y, Chatzizisis YS, Lassen JF, Stankovic G, Koo BK

    Physiological Approach for Coronary Artery Bifurcation Disease: Position Statement by Korean, Japanese, and European Bifurcation Clubs.

    JACC Cardiovasc Interv. 2022;15(13):1297-1309.

    Abstract

    Coronary artery bifurcation lesions are frequently encountered in cardiac catheterization laboratories and are associated with more complex procedures and worse clinical outcomes than nonbifurcation lesions. Therefore, anatomical and physiological assessment of bifurcation lesions before, during, and after percutaneous coronary intervention is of paramount clinical importance. Physiological assessment can help interventionalists appreciate the hemodynamic significance of coronary artery disease and guide ischemia-directed revascularization. However, it is important to understand that the physiological approach for bifurcation disease is more important than simply using physiological indexes for its assessment. This joint consensus document by the Korean, Japanese, and European bifurcation clubs presents the concept of a physiological approach for coronary bifurcation lesions, as well as current knowledge, practical tips, pitfalls, and future directions of applying physiological indexes in bifurcation percutaneous coronary intervention. This document aims to guide interventionalists in performing appropriate physiology-based assessments and treatment decisions for coronary bifurcation lesions.

    PubMed IF 12.7 순환기내과
14. 37952022

    제1저자 김효진 · 교신저자 오국환

    Kim HJ, Kim Y, Kang M, Kim S, Park SK, Sung S, Hyun YY, Jung JY, Ahn C, Oh KH

    Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD.

    Front Med (Lausanne). 2022;9:904963.

    Abstract

    BACKGROUND We aimed to evaluate soluble Klotho and circulating fibroblast growth factor 23 (FGF23) ratio as a risk factor for renal progression, cardiovascular (CV) events, and mortality in chronic kidney disease (CKD).

    METHODS We analyzed 2,099 subjects from a CKD cohort whose soluble Klotho and C-terminal FGF23 levels were measured at enrollment. The Klotho to FGF23 ratio was calculated as Klotho values divided by FGF23 values + 1 (hereinafter called the Klotho/FGF23 ratio). Participants were categorized into quartiles according to Klotho/FGF23 ratio. The primary outcome was renal events, defined as the doubling of serum creatinine, 50% reduction of estimated glomerular filtration rate from the baseline values, or development of end-stage kidney disease. The secondary outcomes consisted of CV events and death. Changes in CV parameters at the time of enrollment and during follow-up according to the Klotho/FGF23 ratio were also examined.

    RESULTS During the follow-up period of 64.0 ± 28.2 months, 735 (35.1%) and 273 (13.0%) subjects developed renal events and composite outcomes of CV events and death, respectively. After adjustment, the first (HR: 1.36; 95% CI: 1.08-1.72, P = 0.010) and second (HR: 1.45; 95% CI: 1.15-1.83, P = 0.002) quartiles with regard to the Klotho/FGF23 ratio showed elevated risk of renal events as compared to the fourth quartile group. There was no significant association between Klotho/FGF23 ratio and the composite outcome of CV events and death. The prevalence of left ventricular hypertrophy and vascular calcification was higher in the low Klotho/FGF23 ratio quartiles at baseline and at the fourth-year follow-up.

    CONCLUSIONS Low Klotho/FGF23 ratio was significantly associated with increased renal events in the cohort of Korean predialysis CKD patients.

    PubMed IF 3.6 신장내과
15. 37942022

    제1저자 권유욱, 채정환 · 교신저자 권유욱, 김효수

    Kwon YW, Chae CW, Lee H, Shin D, Yoo H, Lee CS, Lee Y, Seong KM, Kim HS

    A subset of macrophages and monocytes in the mouse bone marrow express atypical chemokine receptor 1.

    Cell Stem Cell. 2022;29(7):1016-1017.

    Abstract

    Duffy antigen receptor for chemokines (DARC)/CD234, also known as atypical chemokine receptor 1 (ACKR1), is a seven-transmembrane domain protein expressed on erythrocytes, vascular endothelium, and a subset of epithelial cells (Peiper et al., 1995). Previously, we reported that ACKR1 was expressed in bone marrow macrophages. ACKR1 interacts with CD82 on long-term repopulating hematopoietic stem cells (LT-HSCs) to maintain the dormancy of LT-HSCs during homeostasis (Hur et al., 2016). We also demonstrated that ACKR1 interacts with CD82 in HSCs from human umbilical cord blood (hUCB). These findings demonstrated that CD82 is a functional surface marker of LT-HSCs and this molecule maintains LT-HSC quiescence by interactions with ACKR1-expressing macrophages in mice and humans.

    PubMed IF 23.3 순환기내과
16. 37932022

    제1저자 강은정, 이성우 · 교신저자 오국환

    Kang E, Lee SW, Ryu H, Kang M, Kim S, Park SK, Jung JY, Lee KB, Han SH, Ahn C, Oh KH

    Left Ventricular Diastolic Dysfunction and Progression of Chronic Kidney Disease: Analysis of KNOW-CKD Data.

    J Am Heart Assoc. 2022;11(13):e025554.

    Abstract

    Background Few studies have examined the association between the early diastolic mitral inflow velocity/early diastolic mitral annulus velocity ratio (E/e') and chronic kidney disease progression. Methods and Results We reviewed data from 2238 patients with nondialysis chronic kidney disease from the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease); data from 163 patients were excluded because of missing content. A >50% decrease in estimated glomerular filtration rate from baseline, doubling of serum creatinine, or dialysis initiation and/or kidney transplantation were considered renal events. At baseline, median (interquartile range) ejection fraction and E/e' were 64.0% (60.0%-68.0%) and 9.1 (7.4-11.9), respectively. Proportions of ejection fraction <50% and E/e' ≥15 were 1.3% and 9.6%, respectively. More than one quarter of patients (27.2%) had an estimated glomerular filtration rate <30 mL/min per 1.73 m². During the mean 59.1-month follow-up period, 724 patients (34.9%) experienced renal events. In multivariable Cox proportional hazard regression analysis, the hazard ratio with 95% CI per 1-unit increase in E/e' was 1.027 (1.005-1.050; P=0.016). Penalized spline curve analysis yielded a suggested threshold of E/e' for renal events of 12; in our data set, the proportion of E/e' ≥12 was 4.1%. Conclusions Increased E/e' was associated with an increased hazard of renal events, suggesting that diastolic heart dysfunction is a novel risk factor for chronic kidney disease progression.

    PubMed IF 6 신장내과
17. 37922022

    제1저자 이소령 · 교신저자 최의근

    Lee SR, Choi EK, Park SH, Lee SW, Han KD, Oh S, Lip GYH

    Clustering of Unhealthy Lifestyle and the Risk of Adverse Events in Patients With Atrial Fibrillation.

    Front Cardiovasc Med. 2022;9:885016.

    Abstract

    BACKGROUND Little is known regarding the risk of clinical outcomes depending on the clustering of lifestyle behaviors after atrial fibrillation (AF) diagnosis. This study evaluated the association between a cluster of healthy lifestyle behaviors and the risk of adverse outcomes in patients with AF.

    METHODS Using the Korean National Insurance Service database, patients who were newly diagnosed with AF between 2009 and 2016 were included. A healthy lifestyle behavior score (HLS) was calculated by assigning 1 point each for non-current smoking, for non-drinking, and for performing regular exercise from the self-reported questionnaire in health examinations. The primary outcome was defined as major adverse cardiovascular event (MACE), including ischemic stroke, myocardial infarction, and hospitalization for heart failure.

    RESULTS A total of 208,662 patients were included; 7.1% in HLS 0, 22.7% in HLS 1, 58.6% in HLS 2, and 11.6% in HLS 3 groups. Patients with HLS 1, 2, and 3 were associated with a lower risk of MACE than those with HLS 0 (adjusted hazard ratio [95% confidence interval (CI)]: 0.788 [0.762-0.855], 0.654 [0.604-0.708], and 0.579 [0.527-0.636], respectively). After propensity score weighting, consistent results were observed. The risk reduction of healthy lifestyle combinations was consistently observed in various subgroups, regardless of the CHA₂DS₂-VASc score and oral anticoagulant use.

    CONCLUSION Increased number of healthy lifestyle behaviors was significantly associated with lower MACE risk in patients with new-onset AF. These findings support the promotion of a healthy lifestyle to reduce the risk of adverse events in patients with AF.

    PubMed IF 3 순환기내과
18. 37912022

    제1저자 강창경 · 교신저자 박완범

    Kang CK, Chang E, Jung J, Lee E, Song KH, Choe PG, Bang JH, Kim ES, Park SW, Kim HB, Kim NJ, Park WB, Oh MD

    Different levels of humoral and cellular immunity to varicella-zoster virus in seropositive healthcare workers.

    J Infect Public Health. 2022;15(7):734-738.

    Abstract

    BACKGROUND There have been occasional reports on varicella infection among healthcare workers (HCWs) despite varicella-zoster virus (VZV) seropositivity. We compared the levels of humoral and cellular immunity to VZV in seropositive HCWs who had acquired immunity by natural infection or vaccination.

    METHODS Seropositive healthy HCWs with an apparent history of varicella or VZV vaccination once or twice were recruited. Their samples were assessed for anti-VZV IgG levels, the relative avidity index (RAI), and the frequencies of VZV-specific cytokine-producing or polyfunctional CD4⁺ or CD8⁺ T cells.

    RESULTS A total of 75 seropositive HCWs (29 with a history of varicella, 25 vaccinated once, and 21 vaccinated twice) were assessed for humoral immunity. Cellular responses could be analyzed in 59 (28, 21, and 10 in the respective groups). The anti-VZV IgG level, RAI, and memory CD4⁺ T cell responses were significantly higher in the past infection group than in the vaccinated once group. The RAI levels were significantly higher in the past infection group than in the vaccinated twice group.

    CONCLUSION Seropositive HCWs without a varicella history, especially those who received the vaccine only once, had significantly lower levels of immune responses to VZV. Such HCWs might need to comply with airborne precautions.

    PubMed IF 4.8 감염내과
19. 37902022

    제1저자 강승경, 박미래 · 교신저자 조수정

    Kang S^*, Park M^*, Cho JY, Ahn SJ, Yoon C, Kim SG, Cho SJ

    Tumorigenic mechanisms of estrogen and Helicobacter pylori cytotoxin-associated gene A in estrogen receptor α-positive diffuse-type gastric adenocarcinoma.

    Gastric Cancer. 2022;25(4):678-696.

    Abstract

    BACKGROUND Diffuse-type gastric cancer (DGC), for which Helicobacter pylori infection is a causal factor, is associated with poor prognosis among young women, possibly due to female hormones such as estrogen. We aimed to identify the carcinogenesis induced by estrogen and H. pylori in DGC.

    METHODS We screened and selected estrogen receptor alpha (ERα)-positive (MKN45) and ERα-negative (SNU5) DGC cell lines. H. pylori strain 60190 and its isogenic mutant strain lacking cytotoxin-associated gene A (60190ΔCagA) were used to infect MKN45 cells. And the cytotoxin-related gene A (CagA) cDNA which was cloned into pSP65-SR-HA (cagA-pSP65SRa) vector was used to transfect MKN45 cells. Tumor samples were used for DGC organoid culture.

    RESULTS In MKN45 cells, we found that estradiol promotes epithelial-mesenchymal transition (EMT) and stemness phenotypes via HOTAIR expression. These effects were further enhanced by the addition of CagA secreted by H. pylori but were reversed by co-treatment with fulvestrant (ICI 182,780), a selective ER degrader. We also validated the effect of estrogen on DGC organoids. ERα expression was associated with tumor invasion and HOTAIR expression in DGC patients with overt H. pylori infection.

    CONCLUSIONS These findings may explain the rapid DGC progression in young women with physiologically high levels of estrogen and suggest that fulvestrant with ovarian function suppression could serve as a tumor-suppressive agent in premenopausal patients with DGC.

    PubMed IF 6.1 소화기내과
20. 37892022

    제1저자 정석송 · 교신저자 김원, 박상민

    Jeong S, Oh YH, Choi S, Chang J, Kim SM, Son JS, Lee G, Ahn JC, Lee DH, Koo BK, Kim W, Park SM

    Association of non-alcoholic fatty liver disease with incident dementia later in life among elder adults.

    Clin Mol Hepatol. 2022;28(3):510-521.

    Abstract

    BACKGROUND/AIMS Accumulating evidence suggests a link between non-alcoholic fatty liver disease (NAFLD) and brain health. However, population-based evidence on the association between NAFLD and dementia remains unclear. This study was conducted to determine the association between NAFLD and incident dementia.

    METHODS The study population included 608,994 adults aged ≥60 years who underwent health examinations between 2009 and 2010. Data were collected from the Korean National Health Insurance Service database. NAFLD was assessed using the fatty liver index (FLI). A Cox proportional hazards regression model was used to determine the association between NAFLD and dementia.

    RESULTS During the 6,495,352 person-years of follow-up, 48,538 participants (8.0%) developed incident dementia. The participants were classified into low (FLI <30), intermediate (FLI ≥30 and <60), and high (FLI ≥60) groups. In the overall study population, the FLI groups were associated with a risk of dementia (P for trend <0.001). After propensity score matching, a low FLI was associated with a reduced risk of dementia (adjusted hazard ration [aHR], 0.96; 95% confidence interval [CI], 0.93-0.98; P=0.002), whereas a high FLI (NAFLD) was associated with an increased risk of dementia (aHR, 1.05; 95% CI, 1.02-1.08; P=0.001). A higher risk of dementia in the high FLI group than in the intermediate FLI group was attributed to Alzheimer's disease (aHR, 1.04; 95% CI, 1.01-1.07; P=0.004) rather than vascular dementia (aHR, 0.94; 95% CI, 0.75-1.18; P=0.602).

    CONCLUSION NAFLD was associated with an increased risk of dementia, which was attributed to an increased risk of Alzheimer's disease.

    PubMed IF 21.7 소화기내과
21. 37882022

    제1저자 황보율, 최준영 · 교신저자 이은경, 문재훈

    Hwangbo Y, Choi JY, Lee EK, Ryu CH, Cho SW, Chung EJ, Hah JH, Jeong WJ, Park SK, Jung YS, Kim JH, Kim MJ, Kim SJ, Kim YK, Lee CY, Lee JY, Lee YJ, Yu HW, Park DJ, Ryu J, Park YJ, Lee KE, Moon JH

    A Cross-Sectional Survey of Patient Treatment Choice in a Multicenter Prospective Cohort Study on Active Surveillance of Papillary Thyroid Microcarcinoma (MAeSTro).

    Thyroid. 2022;32(7):772-780.

    Abstract

    Background: Active surveillance (AS) is offered as a choice to patients with low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to identify patient and physician factors associated with the choice of AS. Methods: We conducted a cross-sectional survey of patients with low-risk PTMC who were enrolled in a prospective study comparing outcomes following AS and surgery. Patients completed a questionnaire to assess their prior knowledge of the disease, considerations in the decision-making process, and reasons for choosing the treatment. We also surveyed 19 physician investigators about their disease management preferences. Variables affecting the patients' choice of AS, including patients' characteristics and their decision-making process, were analyzed in a multivariable analysis. Results: The response rate of the patient survey was 72.8% (857/1177). Among the patients who responded to the survey, 554 patients (128 male; mean age 49.4 ± 11.6 years; response rate 73.4%) with low-risk PTMC chose AS (AS group), whereas 303 patients (55 male; 46.6 ± 10.7 years; 71.8%) chose immediate surgery (iOP group). In the AS group, 424 patients (76.5%) used a decision aid, and 144 (47.5%) used it in the iOP group. The choice of AS was associated with the following variables: patient age >50 years (odds ratio 1.713 [confidence interval, CI 1.090-2.690], p = 0.020), primary tumor size ≤5 mm (odds ratio 1.960 [CI 1.137-3.379], p = 0.015), and consulting an endocrinologist (odds ratio 114.960 [CI 48.756-271.057], p < 0.001), and use of a decision aid (odds ratio 2.469 [CI 1.320-4.616], p = 0.005). The proportion of patients who were aware of AS before their initial consultation for treatment decision was higher in the AS group than in the iOP group (64.6% vs. 56.8%). Family members were reported to have influenced the treatment decisions more in the iOP group (p = 0.025), whereas the AS group was more influenced by information from the media (p = 0.017). Physicians' attitudes regarding AS of low-risk PTMC tended to be more favorable among endocrinologists than surgeons and all became more favorable as the study progressed. Conclusions: Emerging evidence suggests that physicians' attitudes and communication tools influence the treatment decision of low-risk PTMC patients. Support is needed for patient-centered decision making. (Clinical trial No: NCT02938702).

    PubMed IF 6.6 내분비대사내과
22. 37872022

    제1저자 박혜인조 · 교신저자 오윤규

    Park HC, Hong Y, Yeon JH, Ryu H, Kim YC, Lee J, Kim YH, Chae DW, Chung W, Ahn C, Oh KH, Oh YK

    Mayo imaging classification is a good predictor of rapid progress among Korean patients with autosomal dominant polycystic kidney disease: results from the KNOW-CKD study.

    Kidney Res Clin Pract. 2022;41(4):432-441.

    Abstract

    BACKGROUND Mayo imaging classification (MIC) is a useful biomarker to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). This study was performed to validate MIC in the prediction of renal outcome in a prospective Korean ADPKD cohort and evaluate clinical parameters associated with rapid disease progression.

    METHODS A total of 178 ADPKD patients were enrolled and prospectively observed for an average duration of 6.2 ± 1.9 years. Rapid progressor was defined as MIC 1C through 1E while slow progressor was defined as 1A through 1B. Renal composite outcome (doubling of serum creatinine, 50% decline of estimated glomerular filtration rate [eGFR], or initiation of renal replacement therapy) as well as the annual percent change of height-adjusted total kidney volume (mHTKV-α), and eGFR decline (mGFR-α) were compared between groups.

    RESULTS A total of 110 patients (61.8%) were classified as rapid progressors. These patients were younger and showed a higher proportion of male patients. Rapid progressor was an independent predictor for renal outcome (hazard ratio, 4.09; 95% confidence interval, 1.23-13.54; p = 0.02). The mGFR-α was greater in rapid progressors (-3.58 mL/min per year in 1C, -3.7 in 1D, and -4.52 in 1E) compared with that in slow progressors (-1.54 in 1A and -2.06 in 1B). The mHTKV-α was faster in rapid progressors (5.3% per year in 1C, 9.4% in 1D, and 11.7% in 1E) compared with that in slow progressors (1.2% in 1A and 3.8% in 1B).

    CONCLUSION MIC is a good predictive tool to define rapid progressors in Korean ADPKD patients.

    PubMed IF 3.5 신장내과
23. 37862022

    제1저자 Mariam T. Nawas, 이정옥 · 교신저자 Roni Tamari

    Nawas MT^*, Lee JO^*, Flynn J, Maloy M, Jakubowski AA, Papadopoulos EB, Cho C, Ponce DM, Sauter CS, Perales MA, Devlin S, Giralt SA, Castro-Malaspina HR, Tamari R

    CD34+ -selected hematopoietic stem cell transplant conditioned with a myeloablative regimen in patients with advanced myelofibrosis.

    Bone Marrow Transplant. 2022;57(7):1101-1107.

    Abstract

    Allogeneic hematopoietic stem cell transplantation (Allo-HCT) remains the only curative treatment for myelofibrosis (MF). Transplantation in patients with MF is mostly done using a reduced intensity conditioning regimen with calcineurin inhibitors for graft versus host disease (GVHD) prophylaxis. Here we sought to evaluate outcomes of patients who underwent an ex vivo CD34+ -selected allo-HCT using myeloablative conditioning (MAC). Twenty-seven patients were included in this retrospective analysis. All patients were conditioned with busulfan, melphalan and fludarabine and antithymocyte globulin to prevent graft rejection. G-CSF mobilized peripheral blood stem cell grafts were depleted of T-cells using immunomagnetic CD34+ selection by CliniMACS device. Median follow-up among survivors was 50.6 months. The estimated 3-year overall survival, relapse free survival and the combined endpoint of GVHD/relapse free survival were 88% (95% CI, 75-100%), 80% (95% CI, 66-98%) and 74% (95% CI, 59-93%), respectively. The cumulative incidence of grade II-IV acute GVHD at day 100 was 33.3% (95% CI 16.4-51.3%), and two patients suffered chronic GVHD. There were no cases of primary graft failure. However, delayed graft failure occurred in two patients. We conclude that CD34+ selected allo-HCT with a MAC resulted in high survival rates in this cohort of patients with MF.

    PubMed IF 5.1 혈액종양내과
24. 37852022

    제1저자 김정한, 김택수 · 교신저자 박완범, 김인호

    Kim JH, Kim TS, Chang E, Kang CK, Choe PG, Kim NJ, Oh MD, Park WB, Kim I

    Effectiveness of antimicrobial stewardship programmes based on rapid antibiotic susceptibility testing of haematological patients having high-risk factors for bacteraemia-related mortality: a post-hoc analysis of a randomised controlled trial.

    Int J Antimicrob Agents. 2022;60(1):106604.

    Abstract

    A randomised controlled trial showed that rapid phenotypic antibiotic susceptibility testing (AST) with antimicrobial stewardship programme (ASP) increases the proportion of haematological patients with bacteraemia receiving optimal targeted therapy within 72 h of blood culture collection. This post-hoc analysis aimed to evaluate the effects of rapid phenotypic AST intervention in haematological patients at high risk of a poor outcome from bacteraemia. Haematological patients with bacteraemia (n = 116) were assigned randomly to a conventional AST group or a rapid AST group. The two outcome measures were the proportion of patients receiving optimal targeted therapy at 72 h post blood culture collection and the time to optimal targeted therapy; subgroup analysis was conducted based on baseline demographics (age, sex) and prognostic (Charlson comorbidity index, haematological treatment intensity, Pitt bacteraemia score, appropriateness of empirical antibiotic therapy and multidrug-resistant organism) indicators. The interaction effect between the intervention and subgroup factors was examined using regression model analysis. Age, sex, Charlson comorbidity index, haematological treatment intensity, Pitt bacteraemia score and appropriateness of empirical antibiotic therapy had no significant interaction effects on the proportion of patients receiving optimal targeted therapy (P = 0.129-0.826). However, infection by a multidrug-resistant organism did have a significant interaction effect (P = 0.042). Regarding time to optimal targeted therapy, there were no significant interaction effects between the intervention and subgroup factors (P = 0.156-0.848). In conclusion, rapid phenotypic AST with ASP intervention may accelerate early optimal targeted antimicrobial treatment of haematological patients, even those in high-risk subgroups with bacteraemia.

    PubMed IF 5 감염내과
25. 37842022

    제1저자 최유정 · 교신저자 이승표

    Choi YJ, Koh Y, Lee HJ, Hwang IC, Park JB, Yoon YE, Kim HL, Kim HK, Kim YJ, Cho GY, Sohn DW, Paeng JC, Lee SP

    Independent Prognostic Utility of 11C-Pittsburgh Compound B PET in Patients with Light-Chain Cardiac Amyloidosis.

    J Nucl Med. 2022;63(7):1064-1069.

    Abstract

    ¹¹C-Pittsburgh compound B (PiB) PET/CT visualizes the amount of myocardial amyloid deposit and can be used to prognosticate patients with amyloid light-chain (AL) cardiac amyloidosis (CA). However, whether ¹¹C-PiB PET/CT has any independent additional prognostic value beyond the commonly used biomarkers remains unknown. Methods: This prospective study was on a cohort of 58 consecutive patients with AL CA who underwent ¹¹C-PiB PET/CT. The patients were stratified into 2 groups on the basis of a visual assessment of whether there was myocardial ¹¹C-PiB uptake on PET/CT. The primary endpoint was 1-y overall mortality. The independent prognostic utility of ¹¹C-PiB PET/CT was analyzed using net reclassification improvement and integrated discrimination improvement. Results: Among the 58 patients enrolled, 35 were positive for myocardial ¹¹C-PiB uptake on PET/CT. Patients with myocardial ¹¹C-PiB PET uptake had a worse 1-y overall survival rate than those without (81.8% vs. 45.5%, P = 0.003 by log-rank test). In the multivariate analysis, positivity for myocardial ¹¹C-PiB uptake on PET/CT was an independent predictor of 1-y mortality (adjusted hazard ratio, 3.382; 95% CI, 1.011-11.316; P = 0.048). In analysis of 3 subgroups of patients-those with a troponin I level of at least 0.1 ng/mL, those with an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of at least 1,800 pg/mL, and those with a difference of at least 180 mg/L between free light chains (the 3 commonly used biomarkers and their thresholds for staging in AL amyloidosis)-Kaplan-Meier curves showed for all 3 subgroups that patients positive for myocardial ¹¹C-PiB uptake on PET/CT had a worse prognosis than those who were negative. Additionally, when the results of ¹¹C-PiB PET/CT were added to these 3 biomarkers, the performance of 1-y mortality prediction significantly improved by net reclassification improvement (troponin I, 0.861; NT-proBNP, 0.914; difference between free light chains, 0.987) and by integrated discrimination improvement (0.200, 0.156, and 0.108, respectively). Conclusion:¹¹C-PiB PET/CT is a strong independent predictor of 1-y overall mortality and provides incremental prognostic benefits beyond the 3 commonly used biomarkers of AL amyloidosis staging. Considering the recent development of numerous amyloid-targeting molecular imaging agents, further investigations are warranted on whether PET/CT should be included in risk stratification for patients with AL CA.

    PubMed IF 9.6 순환기내과
26. 37832022

    제1저자 황영재, 최용훈 · 교신저자 김나영

    Hwang YJ^*, Choi Y^*, Kim N, Lee HS, Yoon H, Shin CM, Park YS, Lee DH

    The Difference of Endoscopic and Histologic Improvements of Atrophic Gastritis and Intestinal Metaplasia After Helicobacter pylori Eradication.

    Dig Dis Sci. 2022;67(7):3055-3066.

    Abstract

    BACKGROUND/AIMS Helicobacter pylori (H. pylori) is an important risk factor of atrophic gastritis (AG), intestinal metaplasia (IM), and gastric cancer (GC). However, no report to date has described the endoscopic improvement of AG and IM after H. pylori eradication. Thus, the aim of this study was to evaluate the improvement of AG and IM after H. pylori eradication using endoscopic and histologic analyses.

    METHODS A total of 380 subjects were prospectively enrolled for up to 12 years and grouped by their H. pylori infection status: negative, non-eradicated, and eradicated. Endoscopic and histologic analyses of AG and IM were performed in the antrum and the corpus, by annual follow-up endoscopy.

    RESULTS Endoscopic AG and IM in the antrum and corpus in the eradicated group improved compared to that in the non-eradicated group (AG, P = 0.002 and P = 0.005; IM, P = 0.038 and P = 0.048, respectively). Histologic AG and IM in the antrum and corpus in the eradicated group also improved compared to that in the non-eradicated group (all P < 0.001). Time taken to the endoscopic improvement of AG and IM after H. pylori eradication was significantly longer than time taken to the histologic improvement in the antrum and corpus (AG in antrum: 3.47 ± 2.60 vs. 2.34 ± 1.71 years, P = 0.004; AG in corpus: 3.19 ± 2.30 vs. 1.87 ± 1.48 years, P = 0.002; IM in antrum: 4.40 ± 2.38 vs. 3.62 ± 2.35 years, P = 0.043; and IM in corpus: 4.82 ± 1.08 vs. 3.61 ± 2.22 years, P = 0.007, respectively).

    CONCLUSIONS Both endoscopic and histologic improvements of AG and IM were observed after H. pylori eradication, while endoscopic improvement took significantly longer time than histologic improvement.

    PubMed IF 2.8 소화기내과
27. 37822022

    제1저자 신동훈 · 교신저자 김홍빈

    Shin DH, Kim HS, Heo E, Shin MJ, Kim NH, Lee H, Park JS, Park KU, Jung J, Song KH, Kang M, Jung J, Kim ES, Kim HB

    Stepwise Expansion of Antimicrobial Stewardship Programs and Its Impact on Antibiotic Use and Resistance Rates at a Tertiary Care Hospital in Korea.

    Microbiol Spectr. 2022;10(3):e0033522.

    Abstract

    To optimize antibiotic use, the US CDC has outlined core elements of antimicrobial stewardship programs (ASP). However, they are difficult to implement in limited-resource settings. We report on the successful implementation of a series of ASP with insufficient number of infectious diseases specialists. We retrospectively collected data regarding antibiotic administration and culture results of all patients admitted to a tertiary care teaching hospital, Seoul National University Bundang Hospital (SNUBH), from January 2010 to December 2019. Trends of antibiotic use and antibiotic resistance rates were compared with those from Korean national data. Trend analyses were performed using nonparametric, two-sided, correlated seasonal Mann-Kendall tests. Total antibiotic agent usage has significantly decreased with ASP implementation at SNUBH since 2010. National claim data from tertiary care hospitals have revealed an increase in the use of all broad-spectrum antibiotics except for third-generation cephalosporins (3GC). In contrast, at SNUBH, glycopeptide and fluoroquinolone use gradually decreased, and 3GC and carbapenem use did not significantly change. Furthermore, the rate of colonization with methicillin-resistant Staphylococcus aureus showed a consistently decreasing trend, while that with 3GC- and fluoroquinolone-resistant Escherichia coli significantly increased. Unlike the national rate, the rate of colonization with antibiotic resistant-Klebsiella pneumoniae did not increase and that of 3GC- and fluoroquinolone-resistant Pseudomonas aeruginosa significantly decreased. Stepwise implementation of core ASP elements was effective in reducing antibiotic use despite a lack of sufficient manpower. Long-term multidisciplinary teamwork is necessary for successful and sustainable ASP implementation. IMPORTANCE Antimicrobial stewardship programs aimed to optimize antibiotic use are difficult to implement in limited-resource settings. Our study indicates that stepwise implementation of core antimicrobial stewardship program elements was effective in reducing antibiotic use in a tertiary care hospital despite the lack of sufficient manpower.

    PubMed IF 4.1 감염내과
28. 37812022

    제1저자 이희선 · 교신저자 김형관

    Lee H, Kim HK, Kim B, Han K, Park JB, Hwang IC, Yoon YE, Park HE, Choi SY, Kim YJ, Cho GY

    Augmented risk of dementia in hypertrophic cardiomyopathy: A propensity score matching analysis using the nationwide cohort.

    PLoS One. 2022;17(6):e0269911.

    Abstract

    BACKGROUND Dementia is a big medical and socioeconomic problem on aging society, and cardiac diseases have already shown a significant contribution to developing dementia. However, the risk of dementia related to hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has never been evaluated.

    METHODS In a large-scale longitudinal cohort using National Health Insurance database, 4,645 subjects with HCM aged ≥50 years between 2010 and 2016 were collected and matched with 13,935 controls, based on propensity scores (1:3). We investigated the incidence and risk of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) between groups.

    RESULTS During follow-up (median 3.9 years after 1-year lag), incident dementia occurred in 739 subjects (4.0%): 78.2% for AD and 13.0% for VaD. The incidence of dementia, AD, and VaD were 23.0, 18.0, and 2.9/1,000 person-years, respectively, and was generally more prevalent in HCM. HCM group had a 50% increased risk of dementia, particularly AD, whereas there was no difference in the risk of VaD. The impact of HCM on AD (HR 1.52, 95% CI 1.26-1.84, p<0.001) was comparable with that of diabetes mellitus and smoking. Increased risk of AD in relation to HCM was consistent in various subgroups including younger healthier population.

    CONCLUSIONS This is the first to demonstrate the increased risk of dementia, mainly AD rather than VaD, in subjects with HCM. Early surveillance and active prevention for cognitive impairment could help for a better quality of life in an era that HCM is considered a chronic manageable disease with low mortality.

    PubMed IF 2.8 순환기내과
29. 37802022

    제1저자 김민주 · 교신저자 조선욱

    Kim MJ, Cho SW, Kim YA, Choi HS, Park YJ, Park DJ, Cho BY

    Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves' Disease.

    Endocrinol Metab (Seoul). 2022;37(3):524-532.

    Abstract

    BACKGRUOUND Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves' disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves' disease.

    METHODS Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy.

    RESULTS The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months.

    CONCLUSION Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

    PubMed IF 5.1 내분비대사내과
30. 37792022

    제1저자 김율담, 방지영 · 교신저자 강혜련

    Kim RL^*, Bang JY^*, Kim J, Mo Y, Kim Y, Lee CG, Elias JA, Kim HY, Kang HR

    Mesenchymal stem cells exert their anti-asthmatic effects through macrophage modulation in a murine chronic asthma model.

    Sci Rep. 2022;12(1):9811.

    Abstract

    Despite numerous previous studies, the full action mechanism of the pathogenesis of asthma remains undiscovered, and the need for further investigation is increasing in order to identify more effective target molecules. Recent attempts to develop more efficacious treatments for asthma have incorporated mesenchymal stem cell (MSC)-based cell therapies. This study aimed to evaluate the anti-asthmatic effects of MSCs primed with Liproxstatin-1, a potent ferroptosis inhibitor. In addition, we sought to examine the changes within macrophage populations and their characteristics in asthmatic conditions. Seven-week-old transgenic mice, constitutively overexpressing lung-specific interleukin (IL)-13, were used to simulate chronic asthma. Human umbilical cord-derived MSCs (hUC-MSCs) primed with Liproxstatin-1 were intratracheally administered four days prior to sampling. IL-13 transgenic mice demonstrated phenotypes of chronic asthma, including severe inflammation, goblet cell hyperplasia, and subepithelial fibrosis. Ly6C⁺M2 macrophages, found within the pro-inflammatory CD11c⁺CD11b⁺ macrophages, were upregulated and showed a strong correlation with lung eosinophil counts. Liproxstatin-1-primed hUC-MSCs showed enhanced ability to downregulate the activation of T helper type 2 cells compared to naïve MSCs in vitro and reduced airway inflammation, particularly Ly6C⁺M2 macrophages population, and fibrosis in vivo. In conclusion, intratracheal administration is an effective method of MSC delivery, and macrophages hold great potential as an additional therapeutic target for asthma.

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