SCI 발표논문

1. 34182021

   제1저자 김기표, 양현식 · 교신저자 김세중

   Kim K^*, Yang H^*, Yi J, Son HE, Ryu JY, Kim YC, Jeong JC, Chin HJ, Na KY, Chae DW, Han SS, Kim S

   Real-Time Clinical Decision Support Based on Recurrent Neural Networks for In-Hospital Acute Kidney Injury: External Validation and Model Interpretation.

   J Med Internet Res. 2021;23(4):e24120.

   Abstract

   BACKGROUND Acute kidney injury (AKI) is commonly encountered in clinical practice and is associated with poor patient outcomes and increased health care costs. Despite it posing significant challenges for clinicians, effective measures for AKI prediction and prevention are lacking. Previously published AKI prediction models mostly have a simple design without external validation. Furthermore, little is known about the process of linking model output and clinical decisions due to the black-box nature of neural network models.

   OBJECTIVE We aimed to present an externally validated recurrent neural network (RNN)-based continuous prediction model for in-hospital AKI and show applicable model interpretations in relation to clinical decision support.

   METHODS Study populations were all patients aged 18 years or older who were hospitalized for more than 48 hours between 2013 and 2017 in 2 tertiary hospitals in Korea (Seoul National University Bundang Hospital and Seoul National University Hospital). All demographic data, laboratory values, vital signs, and clinical conditions of patients were obtained from electronic health records of each hospital. We developed 2-stage hierarchical prediction models (model 1 and model 2) using RNN algorithms. The outcome variable for model 1 was the occurrence of AKI within 7 days from the present. Model 2 predicted the future trajectory of creatinine values up to 72 hours. The performance of each developed model was evaluated using the internal and external validation data sets. For the explainability of our models, different model-agnostic interpretation methods were used, including Shapley Additive Explanations, partial dependence plots, individual conditional expectation, and accumulated local effects plots.

   RESULTS We included 69,081 patients in the training, 7675 in the internal validation, and 72,352 in the external validation cohorts for model development after excluding cases with missing data and those with an estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or end-stage kidney disease. Model 1 predicted any AKI development with an area under the receiver operating characteristic curve (AUC) of 0.88 (internal validation) and 0.84 (external validation), and stage 2 or higher AKI development with an AUC of 0.93 (internal validation) and 0.90 (external validation). Model 2 predicted the future creatinine values within 3 days with mean-squared errors of 0.04-0.09 for patients with higher risks of AKI and 0.03-0.08 for those with lower risks. Based on the developed models, we showed AKI probability according to feature values in total patients and each individual with partial dependence, accumulated local effects, and individual conditional expectation plots. We also estimated the effects of feature modifications such as nephrotoxic drug discontinuation on future creatinine levels.

   CONCLUSIONS We developed and externally validated a continuous AKI prediction model using RNN algorithms. Our model could provide real-time assessment of future AKI occurrences and individualized risk factors for AKI in general inpatient cohorts; thus, we suggest approaches to support clinical decisions based on prediction models for in-hospital AKI.

   PubMed IF 8.2 신장내과
2. 34172021

   제1저자 최유정 · 교신저자 박준빈

   Choi YJ, Park JB, Park CS, Hwang I, Yoon YE, Lee SP, Kim HK, Kim YJ, Cho GY, Sohn DW

   Prognostic implications of left ventricular mass-geometry in patients with no or nonobstructive coronary artery disease.

   BMC Cardiovasc Disord. 2021;21(1):187.

   Abstract

   BACKGROUND Coronary computed tomography angiography (CCTA) is widely used as a first-line noninvasive modality that frequently exhibits no or nonobstructive coronary artery disease (CAD) in clinical practice, along with abnormal left ventricular (LV) geometry on echocardiography. However, the combined prognostic value of these findings has not been well elucidated. Therefore, we aimed to evaluate the prognostic implications of abnormal LV geometry in individuals with no or nonobstructive CAD.

   METHODS A total of 5806 subjects with no CAD or nonobstructive CAD (luminal narrowing < 50%) on CCTA were included in the study. The major exclusion criteria were structural heart disease and a history of myocardial infarction or coronary revascularization. Abnormal LV geometry on echocardiography was defined as LV mass index > 95 g/m² in women and > 115 g/m² in men, and/or relative wall thickness > 0.42. The primary outcome was all-cause mortality.

   RESULTS A total of 5803 subjects without significant obstructive CAD (age, 56.6 ± 8.87 years; men, 3884 [66.9%]). Of them, 4045 (69.7%) subjects had normal LV geometry and 1758 (30.3%) had abnormal LV geometry respectively. During a mean follow-up of 6.2 ± 1.48 years, 84 (1.44%) subjects died in the study population. Of these, 56 subjects were from the normal LV geometry group (1.24%) and 28 were from the abnormal LV geometry group (2.32%). Subjects with abnormal LV geometry had significantly worse survival rates (log-rank, p < 0.001). After adjustment for confounding factors, abnormal LV geometry was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.64; 95% confidence interval, 1.04-2.58; p = 0.034). Moreover, abnormal LV geometry was significantly worse in survival when classified as those with no CAD (log-rank, p = 0.024) and nonobstructive CAD (Log-rank, p < 0.001).

   CONCLUSIONS Abnormal LV geometry portends a worse prognosis in subjects with no or nonobstructive CAD. These findings suggest that LV geometry assessment can help improve the stratification of individuals with these CCTA findings.

   PubMed IF 3.1 순환기내과
3. 34162021

   제1저자 이은영, 송경호 · 교신저자 진범식, 박진균

   Lee EE^*, Song KH^*, Hwang W, Ham SY, Jeong H, Kim JH, Oh HS, Kang YM, Lee EB, Kim NJ, Chin BS, Park JK

   Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis.

   Sci Rep. 2021;11(1):8080.

   Abstract

   The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

   PubMed IF 4.9 류마티스내과
4. 34152021

   제1저자 이춘수 · 교신저자 김효수

   Lee CS, Cho HJ, Lee JW, Son H, Chai J, Kim HS

   Adhesion GPCR Latrophilin-2 Specifies Cardiac Lineage Commitment through CDK5, Src, and P38MAPK.

   Stem Cell Reports. 2021;16(4):868-882.

   Abstract

   Identifying lineage-specific markers is pivotal for understanding developmental processes and developing cell therapies. Here, we investigated the functioning of a cardiomyogenic cell-surface marker, latrophilin-2 (LPHN2), an adhesion G-protein-coupled receptor, in cardiac differentiation. LPHN2 was selectively expressed in cardiac progenitor cells (CPCs) and cardiomyocytes (CMCs) during mouse and human pluripotent stem cell (PSC) differentiation; cell sorting with an anti-LPHN2 antibody promoted the isolation of populations highly enriched in CPCs and CMCs. Lphn2 knockdown or knockout PSCs did not express cardiac genes. We used the Phospho Explorer Antibody Array, which encompasses nearly all known signaling pathways, to assess molecular mechanisms underlying LPHN2-induced cardiac differentiation. LPHN2-dependent phosphorylation was the strongest for cyclin-dependent kinase 5 (CDK5) at Tyr15. We identified CDK5, Src, and P38MAPK as key downstream molecules of LPHN2 signaling. These findings provide a valuable strategy for isolating CPCs and CMCs from PSCs and insights into the still-unknown cardiac differentiation mechanisms.

   PubMed IF 5.6 순환기내과
5. 34142021

   제1저자 오상민 · 교신저자 김남중

   Oh SM, Jeong H, Chang E, Choe PG, Kang CK, Park WB, Kim TS, Kwon WY, Oh MD, Kim NJ

   Clinical Application of the Standard Q COVID-19 Ag Test for the Detection of SARS-CoV-2 Infection.

   J Korean Med Sci. 2021;36(14):e101.

   Abstract

   We evaluated the Standard Q COVID-19 Ag test for the diagnosis of coronavirus disease 2019 (COVID-19) compared to the reverse transcription-polymerase chain reaction (RT-PCR) test. We applied both tests to patients who were about to be hospitalized, had visited an emergency room, or had been admitted due to COVID-19 confirmed by RT-PCR. Two nasopharyngeal swabs were obtained; one was tested by RT-PCR and the other by the Standard Q COVID-19 Ag test. A total of 118 pairs of tests from 98 patients were performed between January 5 and 11, 2021. The overall sensitivity and specificity for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the Standard Q COVID-19 Ag test compared to RT-PCR were 17.5% (95% confidence interval [CI], 8.8-32.0%) and 100% (95% CI, 95.3-100.0%). Analysis of the results using RT-PCR cycle thresholds of ≤ 30 or ≤ 25 increased the sensitivity to 26.9% (95% CI, 13.7-46.1%), and 41.1% (95% CI, 21.6-64.0%), respectively.

   PubMed IF 3.2 감염내과
6. 34132021

   제1저자 조성우, 김동영 · 교신저자 강혜련, 이하나

   Cho SW, Kim DY, Choi S, Won S, Kang HR, Yi H

   Microbiome profiling of uncinate tissue and nasal polyps in patients with chronic rhinosinusitis using swab and tissue biopsy.

   PLoS One. 2021;16(4):e0249688.

   Abstract

   Chronic rhinosinusitis (CRS) is characterized according to the presence or absence of nasal polyps (NPs) and displays nasal microbiota dysbiosis. However, optimal sampling methods of the nasal microbiome in CRS have not been identified. We aimed to assess the microbial composition in patients with CRS, comparing different sampling methods (swab and tissue biopsy), tissue types (uncinate tissue and NP), and disease subtypes. Samples were obtained by swabbing the middle meatus and taking a biopsy of uncinate tissue (UT) in patients with CRS with (CRSwNP, N = 8) or without NP (CRSsNP, N = 6) and controls (N = 8). NPs were also harvested in CRSwNP. DNAs were extracted from fifty-two samples and analyzed by 16S rRNA gene amplicon sequencing. As a result, a great interpersonal variance was observed in nasal swabs, while UT samples presented distinct microbiome with low inter-personal differences. Moreover, the UT microbiomes were further differentiated into three clusters which are associated with disease status (control, CRSsNP, and CRSwNP). Compared to UT, NP revealed a unique microbiome profile with significantly less bacterial diversity. Prevotella was the genus whose abundance was negatively correlated with disease severity in NP. In conclusion, tissue samples are better specimens than nasal swabs for assessing the microbiomes of CRS patients. Several bacteria in UT and NP tissues revealed an association with clinical severity of CRSwNP.

   PubMed IF 2.8 알레르기내과
7. 34122021

   제1저자 최정연, 김진각 · 교신저자 김광일

   Choi JY^*, Kim JK^*, Kim KI, Lee YK, Koo KH, Kim CH

   How does the multidimensional frailty score compare with grip strength for predicting outcomes after hip fracture surgery in older patients? A retrospective cohort study.

   BMC Geriatr. 2021;21(1):234.

   Abstract

   BACKGROUND Frailty and low handgrip strength (HGS) are associated with adverse outcomes after hip fracture (HF) surgery. We aimed to compare the predictive role of frailty and HGS for adverse outcome in HF patients.

   METHODS We included older patients (age ≥ 65 years) who underwent HF surgery to compare the predictive role of HGS and hip-multidimensional frailty score (Hip-MFS) for postoperative complications and mortality. The Hip-MFS was calculated based on comprehensive geriatric assessment (CGA), and HGS was measured with a hand dynamometer. The primary outcome was a composite of postoperative complications (e.g., pneumonia, urinary tract infection, delirium, acute pulmonary thromboembolism, and unplanned intensive care unit admission). The secondary outcomes were 6-month mortality and mortality at the end of follow-up.

   RESULTS The median observation time was 620.5 days (interquartile range: 367.0-784.8 days). Among the 242 patients (mean age: 81.5 ± 6.7 years, 73.1% women), 106 (43.8%) experienced postoperative complications. The 6-month mortality and mortality at the end of follow-up were 7.4% (n = 18) and 20.7% (n = 50), respectively. The Hip-MFS (odds ratio [OR], 1.250; 95% confidence interval [CI], 1.092-1.432) and HGS (OR, 1.147; 95% CI, 1.082-1.215) could predict postoperative complications. The Hip-MFS could predict both 6-month mortality (hazard ratio [HR], 1.403; 95% CI, 1.027-1.917) and mortality at the end of follow-up (HR, 1.493; 95% CI, 1.249-1.769) after adjustment, while HGS was only associated with mortality at the end of follow-up (HR, 1.080; 95% CI, 1.024-1.139). For mortality at the end of follow-up, predictive models with the Hip-MFS were superior to those with HGS in the time-dependent receiver-operating curve analysis after adjustment (p = 0.017). Furthermore, the addition of Hip-MFS or HGS to the American Society of Anesthesiologists (ASA) classification improved its prognostic ability.

   CONCLUSIONS Both the Hip-MFS and HGS could predict postoperative complications and improve prognostic utility when combined with the ASA classification. The Hip-MFS was a stronger predictor of mortality than HGS after HF surgery. HGS could be a useful pre-screening tool to identify patients at a high risk of postoperative complications and those who may benefit from further CGA.

   PubMed IF 4.5 노인병내과
8. 34112021

   제1저자 박세훈 · 교신저자 김동기

   Park S, Lee S, Kim Y, Lee Y, Kang MW, Kim K, Kim YC, Han SS, Lee H, Lee JP, Joo KW, Lim CS, Kim YS, Kim DK

   Causal effects of relative fat, protein, and carbohydrate intake on chronic kidney disease: a Mendelian randomization study.

   Am J Clin Nutr. 2021;113(4):1023-1031.

   Abstract

   BACKGROUND The effects of specific macronutrients on kidney function independent of total calorie intake have rarely been studied, although the composition of macronutrient intake has been reported to affect health outcomes.

   OBJECTIVES We aimed to investigate the effects of macronutrient intake ratios on the risk of chronic kidney disease (CKD) by Mendelian randomization (MR) analysis.

   METHODS The study was an observational cohort study mainly based on the UK Biobank and including MR analysis. First, we evaluated the relative baseline macronutrient composition-that is, the number of calories from each macronutrient divided by total calorie intake-of the diets of UK Biobank participants, and we used Cox regression to assess the incidence of end-stage kidney disease (ESKD) in 65,164 participants with normal kidney function [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2]. We implemented a genetic instrument for relative fat, protein, and carbohydrate intake developed by a previous genome-wide association study (GWAS) and performed MR analysis. Two-sample MR was performed with the summary statistics from independent CKDGen GWAS for kidney function traits (n = 567,460), including CKD (eGFR <60 mL/min/1.73 m2) and log-transformed eGFR.

   RESULTS The median relative macronutrient intake composition at baseline was 35% fats, 15% protein, and 50% carbohydrates. Higher relative protein intake in subjects with normal kidney function was significantly associated with a lower risk of incident ESKD (HR: 0.54; 95% CI: 0.30, 0.95) in the observational investigation. Two-sample MR indicated that increased relative fat intake causally increased the risk of kidney function impairment [CKD (OR: 1.94; 95% CI: 1.39, 2.71); log eGFR (β: -0.036; 95% CI: -0.048, -0.024)] and that higher relative protein intake was causally linked to a lower CKD risk [CKD (OR: 0.50; 95% CI: 0.35, 0.72); log eGFR (β: 0.044; 95% CI: 0.030, 0.058)].

   CONCLUSIONS A desirable macronutrient composition, including high relative protein intake and low relative fat intake, may causally reduce the risk of CKD in the general population.

   PubMed IF 6.9 신장내과
9. 34102021

   제1저자 공성혜 · 교신저자 신찬수

   Kong SH, Kim JH, Kim SW, Shin CS

   Radioactive Parathyroid Adenomas on Sestamibi Scans: Low Parathyroid Hormone Secretory Potential and Large Volume.

   Endocrinol Metab (Seoul). 2021;36(2):351-358.

   Abstract

   BACKGROUND We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.

   METHODS The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.

   RESULTS Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [-] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (-) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (-) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.

   CONCLUSION Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.

   PubMed IF 5.1 내분비대사내과
10. 34092021

    제1저자 이은영 · 교신저자 윤성수

    Lee E, Koh Y, Hong J, Eom HS, Yoon SS

    Recent Clinical Update of Acute Myeloid Leukemia: Focus on Epigenetic Therapies.

    J Korean Med Sci. 2021;36(13):e85.

    Abstract

    Acute myeloid leukemia (AML) is a complicated disease characterized by genetic heterogeneity and simultaneous alterations in multiple genes. For decades, its only curative method has been intensive induction chemotherapy with or without allogeneic hematopoietic stem cell transplantation, and this approach cannot be applied to elderly patients, who make up more than 50% of AML patients. Recent advances in genomics facilitated the elucidation of various mutations related to AML, and the most frequent mutations were discovered in epigenetic regulators. Alterations to epigenetic modifications that are essential for normal cell biology, including DNA methylation and histone acetylation, have been identified. As epigenetic dysregulation is an important carcinogenic mechanism and some epigenetic changes are reversible, these epigenetic alterations have become targets for novel drug development against AML. This review summarizes the recent advances in epigenetic therapies for AML and discusses future research directions.

    PubMed IF 3.2 혈액종양내과
11. 34082021

    제1저자 박지석, 정진형 · 교신저자 최의근

    Park J, Jung JH, Choi EK, Lee SW, Kwon S, Lee SR, Kang J, Han KD, Park KW, Oh S, Lip GYH

    Longitudinal Patterns in Antithrombotic Therapy in Patients with Atrial Fibrillation after Percutaneous Coronary Intervention in the Non-Vitamin K Oral Anticoagulant Era: A Nationwide Population-Based Study.

    J Clin Med. 2021;10(7):jcm10071505.

    Abstract

    We investigated whether longitudinal patterns in antithrombotic therapy have changed after the introduction of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI). Using a claims database of the Korean AF population who underwent PCI between 2012 and 2016 (n = 18,691), we analyzed prescription records of oral anticoagulants (OACs) and antiplatelets at 3-month intervals over 2 years after PCI. The study population was stratified (pre-NOAC, transition, and NOAC era) using time-periods of NOAC introduction in Korea and an expansion of reimbursement for NOAC in AF as indicators. The overall rates of OAC were low at baseline (24.9%, 26.9%, and 35.2% in pre-NOAC, transition, and NOAC era, respectively), contrary to high rates of dual antiplatelet therapy (DAPT) (73.3%, 71.4%, and 63.6%). However, OAC prescription rates were increased at 1-year (18.5%, 22.5%, and 31.6%), and 2-year follow-up (17.8%, 24.2%, and 31.8%) from pre-NOAC to NOAC era. In NOAC era, 63.5% of baseline OAC prescriptions comprised NOAC, of which 96.4% included triple therapy with DAPT. Over 2 years, we observed increasing rates of double therapy with a single antiplatelet (18.3% and 20.0% at 1- and 2-year follow-up) and OAC monotherapy (2.7% and 8.9% at 1- and 2-year follow-up).

    PubMed IF 3.3 순환기내과
12. 34072021

    제1저자 장영, 유정주 · 교신저자 신동욱, 유수종

    Chang Y^*, Yoo JJ^*, Cho EJ, Han K, Kim D, Kim BY, Chung GE, Cho Y, Shin DW^*, Yu SJ^*

    Weight fluctuation and risk of hepatocellular carcinoma: a nationwide population-based 8-million-subject study.

    Hepatol Int. 2021;15(2):482-492.

    Abstract

    BACKGROUND/AIM The importance of hepatocellular carcinoma (HCC) caused by obesity has been emphasized. Many studies have shown that weight fluctuations as well as high BMI are associated with various adverse outcomes. In this study, we investigated the relationship between weight fluctuation and HCC in general populations drawn from a nationwide population-based cohort.

    METHOD A population-based cohort study including 8,001,829 subjects participating in more than three health examinations within 5 years from the index year were followed until the end of 2017. The degree of weight fluctuation and incidence of HCC during the period were evaluated.

    RESULTS When we classified groups according to baseline body mass index (BMI) level, the highest risk for HCC was observed in subjects with BMI of 30 or greater (adjusted hazard ratio [aHR] 1.40, 95% confidence interval [CI] 1.27-1.54). Also, increasing trends for the relationship between weight fluctuation and HCC were observed in multivariable Cox proportional analyses. The risk of HCC increased by 16% (aHR 1.16, 95% CI 1.12-1.20) for the highest quartile of weight fluctuation relative to the lowest quartile. These findings were consistent regardless of the baseline BMI or other metabolic factors. However, these effects of weight fluctuation on HCC were not observed in liver cirrhosis or viral hepatitis subgroups.

    CONCLUSION Weight fluctuation is an independent predictor of HCC. In the absence of liver cirrhosis or chronic hepatitis, the impact of weight fluctuation on HCC is further emphasized. These results suggest maintaining steady weight is recommended to reduce the risk of HCC.

    PubMed IF 7.8 소화기내과
13. 34062021

    제1저자 이동호, 조은주 · 교신저자 이재영

    Lee DH, Cho EJ, Bae JS, Lee JY, Yu SJ, Kim H, Lee KB, Han JK, Choi BI

    Accuracy of Two-Dimensional Shear Wave Elastography and Attenuation Imaging for Evaluation of Patients With Nonalcoholic Steatohepatitis.

    Clin Gastroenterol Hepatol. 2021;19(4):797-805.e7.

    Abstract

    BACKGROUND & AIMS We evaluated the accuracy of a multiparametric approach using attenuation imaging and 2-dimensional shear wave elastography (2D-SWE) for the detection of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

    METHODS We studied 102 patients with increased levels of liver enzymes or suspicion of NAFLD, examined by attenuation imaging and 2D-SWE, immediately before biopsy collection and analysis (reference standard), from January 2018 to July 2019. We collected data on the attenuation coefficient (dB/cm/MHz) from attenuation imaging, liver stiffness measurements, and shear wave dispersion slope (SWDS, [m/s]/kHz) from 2D-SWE. Multivariate linear regression analysis was performed to identify factors associated with each parameter. Diagnostic performance was determined from area under the receiver operating curve (AUROC) values.

    RESULTS The attenuation coefficient was associated with steatosis grade (P < .01) and identified patients with steatosis grades S1 or higher, S2 or higher, and S3 or higher, with AUROC values of 0.93, 0.88, and 0.83, respectively. Liver stiffness associated with fibrosis stage (P < .01) and lobular inflammatory activity was the only factor associated with SWDS (P < .01). SWDS detected inflammation grades I1 or higher, I2 or higher, and I3 or higher with AUROC values of 0.89, 0.85, and 0.78, respectively. We developed a risk scoring system to detect steatohepatitis based on the attenuation coefficient (score of 1 for 0.64 < attenuation coefficient ≤ 0.70; score of 2 for 0.70 < attenuation coefficient ≤ 0.73; and score of 3 for attenuation coefficient >0.73) and SWDS (score of 2 for 10.5 [m/s]/kHz < SWDS ≤ 11.7 [m/s]/kHz; and score of 3 for SWDS >11.7 [m/s]/kHz), using an unweighted sum of each score. Based on histopathology analysis, 55 patients had steatohepatitis. Risk scores correlated with NAFLD activity score (rho = 0.73; P < .01). Our scoring system identified patients with steatohepatitis with an AUROC of 0.93-this value was significantly higher than that of other parameters (P < .05), except SWDS (AUROC, 0.89; P = .18).

    CONCLUSIONS In the evaluation of patients with suspected NAFLD, the attenuation coefficient can identify patients with steatosis and liver stiffness can detect fibrosis accurately. SWDS was associated significantly with lobular inflammation. We developed a risk scoring system based on the attenuation coefficient and SWDS that might be used to detect steatohepatitis.

    PubMed IF 16.2 소화기내과
14. 34052021

    제1저자 이진호 · 교신저자 오국환

    Lee J, Ju KD, Kim HJ, Tsogbadrakh B, Ryu H, Kang E, Kang M, Yang J, Kang HG, Ahn C, Oh KH

    Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously.

    Am J Physiol Renal Physiol. 2021;320(4):F559-F568.

    Abstract

    Hypercalciuria is one of the early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal Ca²⁺ reabsorption. Soluble klotho has been previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose, where sialic acid is located, on TRPV5, rather than cleave it. Here, we report that soluble klotho tethers TRPV5 on the membrane by binding both TRPV5 and galectin-1, thereby protecting membrane TRPV5 from diabetes-induced endocytosis. In the present study, we injected recombinant soluble α-klotho protein (rKL) into db/db and db/m mice for 8 wk and collected urine and kidneys. We administered rKL, AZD4547 [fibroblast growth factor (FGF) receptor type 1 inhibitor], and OTX008 (galectin-1 inhibitor) to cultured mouse distal tubular cells with or without 30 mM high-glucose (HG) exposure. db/db mice showed increased renal Ca²⁺ excretion and decreased renal TRPV5 expression. rKL treatment reversed this change. In vitro, TRPV5 expression in distal tubular cells decreased under HG conditions, and rKL successfully upregulated TRPV5 with or without FGF23. Also, immunofluorescence showed colocalization of klotho, TRPV5, and galectin-1 in distal tubule cells, suggesting that klotho binds to both TRPV5 and galectin-1. Moreover, when both FGF receptor type 1 and galectin-1 were inhibited, rKL failed to increase TRPV5 under HG conditions. Our results indicate that soluble klotho prevents TRPV5 from degradation and subsequent diabetes-induced endocytosis by anchoring TRPV5 through binding with both TRPV5 and galectin-1.NEW & NOTEWORTHY Soluble α-klotho anchors transient receptor potential vanilloid type 5 (TRPV5) on the apical membrane of the distal tubule by binding both TRPV5 and a membrane-abundant protein, galectin-1. This newly discovered mechanism works even when fibroblast growth factor (FGF)23 signaling is inhibited by treatment with FGF receptor type 1 inhibitor. Therefore, we identified how soluble α-klotho increases TRPV5 without FGF23. We confirmed this mechanism by observing that soluble α-klotho fails to enhance TRPV5 when both FGF receptor type 1 and galectin-1 are inhibited.

    PubMed IF 3.6 신장내과
15. 34042021

    제1저자 김민주 · 교신저자 박영주, 오병철

    Kim MJ, Kim HH, Song YS, Kim OH, Choi K, Kim S, Oh BC, Park YJ

    DEHP Down-Regulates Tshr Gene Expression in Rat Thyroid Tissues and FRTL-5 Rat Thyrocytes: A Potential Mechanism of Thyroid Disruption.

    Endocrinol Metab (Seoul). 2021;36(2):447-454.

    Abstract

    BACKGROUND Di-2-ethylhexyl phthalate (DEHP) is known to disrupt thyroid hormonal status. However, the underlying molecular mechanism of this disruption is unclear. Therefore, we investigated the direct effects of DEHP on the thyroid gland.

    METHODS DEHP (vehicle, 50 mg/kg, and 500 mg/kg) was administered to Sprague-Dawley rats for 2 weeks. The expression of the thyroid hormone synthesis pathway in rat thyroid tissues was analyzed through RNA sequencing analysis, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemical (IHC) staining. DEHP was treated to FRTL-5 rat thyroid cells, and an RT-PCR analysis was performed. A reporter gene assay containing the promoter of thyroid stimulating hormone receptor (TSHR) in Nthy-ori 3-1 human thyroid cells was constructed, and luciferase activity was determined.

    RESULTS After DEHP treatment, the free thyroxine (T4) and total T4 levels in rats significantly decreased. RNA sequencing analysis of rat thyroid tissues showed little difference between vehicle and DEHP groups. In the RT-PCR analysis, Tshr expression was significantly lower in both DEHP groups (50 and 500 mg/kg) compared to that in the vehicle group, and IHC staining showed that TSHR expression in the 50 mg/kg DEHP group significantly decreased. DEHP treatment to FRTL-5 cells significantly down-regulated Tshr expression. DEHP treatment also reduced luciferase activity in a reporter gene assay for TSHR.

    CONCLUSION Although overall genetic changes in the thyroid hormone synthesis pathway are not clear, DEHP exposure could significantly down-regulate Tshr expression in thyroid glands. Down-regulation of Tshr gene appears to be one of potential mechanisms of thyroid disruption by DEHP exposure.

    PubMed IF 5.1 내분비대사내과
16. 34032021

    제1저자 이승훈 · 교신저자 김정희

    Lee SH, Kim JW, Yoon HK, Koh JM, Shin CS, Kim SW, Kim JH

    Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age.

    Endocrinol Metab (Seoul). 2021;36(2):401-412.

    Abstract

    BACKGROUND Guidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients <35 years old with marked primary aldosteronism (PA) (hypokalemia and elevated plasma aldosterone concentration [PAC]) and a unilateral lesion on computed tomography (CT) are based on limited number of studies. We aimed to determine the accuracy of CT in PA patients according to age.

    METHODS In this retrospective study, we investigated the concordance between CT and AVS in 466 PA patients from two tertiary centers who successfully underwent AVS.

    RESULTS CT had an overall accuracy of 64.4% (300/466). In the group with unilateral lesion, patients with hypokalemia had higher concordance than those without hypokalemia (85.0% vs. 43.6%, P<0.001). In the group with marked PA (hypokalemia and PAC >15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged <35 years; 100.0% (20/20), aged 35 to 39 years; 89.4% (59/66), aged 40 to 49 years; and 79.8% (79/99), aged ≥50 years. Cut-off age and PAC for concordance was <50 years and >29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the <50-year age group and ≥50-year age group (90.9% vs. 79.8%, P=0.044) disappeared in 139 of 198 patients with PAC > 30.0 ng/dL (91.9% vs. 87.7%, P=0.590).

    CONCLUSION Patients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.

    PubMed IF 5.1 내분비대사내과
17. 34022021

    제1저자 박정하, 김주영 · 교신저자 임수

    Park JH^*, Kim JY^*, Choi JH, Park HS, Shin HY, Lee JM, Kim JW, Ko HJ, Chon S, Kim BK, Kim CS, Lim S

    Effectiveness of liraglutide 3 mg for the treatment of obesity in a real-world setting without intensive lifestyle intervention.

    Int J Obes (Lond). 2021;45(4):776-786.

    Abstract

    OBJECTIVE We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea.

    METHODS People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values.

    RESULTS The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m², and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment: -2.94 kg and -1.08 kg/m² at 2 months; -4.23 kg and -1.55 kg/m² at 4 months, and -5.14 kg and -1.89 kg/m² at 6 months (all P < 0.001). In the 6-month cohort, 52.5% and 18.3% of subjects lost ≥5% and ≥10% of body weight, respectively. After 6 months, systolic and diastolic blood pressure decreased significantly by 3.90 and 1.93 mmHg, respectively. In those with diabetes mellitus, HbA1c and fasting glucose levels decreased significantly by 1.14% and 27.8 mg/dl, respectively. Among all participants, 27.6% experienced adverse effects, including nausea (20.8%), vomiting (5.2%), diarrhoea (2.5%), and skin rash (3.6%). Documented reasons for discontinuation of treatment were lack of effect (4.4%), adverse events (4.3%), and high cost (3.1%).

    CONCLUSIONS In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.

    PubMed IF 5.4 내분비대사내과
18. 34012021

    제1저자 조의현, 이진용 · 교신저자 고성준, 박현선

    Jo UH, Lee JY, Lee H, Kim DY, Kang S, Koh SJ, Park H

    Various skin manifestations related to inflammatory bowel disease: A nationwide cross-sectional study on the Korean population.

    J Dermatol. 2021;48(4):431-438.

    Abstract

    Inflammatory bowel disease (IBD) presents with various extraintestinal manifestations. As part of them, various skin diseases are suggested to be related to IBD. We aimed to identify the epidemiology and risk of developing skin manifestations in patients with IBD. We used Korean insurance claims data and selected patients with IBD and age/sex-matched non-IBD subjects between 2013 and 2017 using the diagnosis code and prescription records of IBD-specific medications. The prevalence and risk of concurrent skin diseases were estimated. We identified 64 837 patients with IBD. Reactive skin eruptions including pyoderma gangrenosum and erythema nodosum were associated with IBD with highest odds ratios among three categories of reactive, inflammatory, and autoimmune skin diseases. Inflammatory skin diseases including rosacea, psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne conglobata were significantly associated with IBD, but the association was less marked compared to reactive skin eruptions. The patients with IBD also had a higher risk of autoimmune skin diseases including vitiligo and alopecia areata than non-IBD subjects. We determined that IBD was related to various skin diseases including reactive, inflammatory, and autoimmune skin diseases. Considering these relationships can allow better management of patients with IBD and comorbid skin diseases.

    PubMed IF 2.3 소화기내과
19. 34002021

    제1저자 윤지선 · 교신저자 오도연

    Yoon J, Kang SY, Lee KH, Cheon GJ, Oh DY

    Targeting Hypoxia Using Evofosfamide and Companion Hypoxia Imaging of FMISO-PET in Advanced Biliary Tract Cancer.

    Cancer Res Treat. 2021;53(2):471-479.

    Abstract

    PURPOSE Hypoxia is widely known as one of the mechanisms of chemoresistance and as an environmental condition which triggers invasion and metastasis of cancer. Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard conjugated with 2-nitroimidazole. Biliary tract cancer (BTC) is known to contain large hypoxic area. This study evaluated the efficacy and safety of evofosfamide as a second-line treatment of advanced BTC.

    MATERIALS AND METHODS Patients received evofosfamide at a dose of 340 mg/m2 on days 1, 8, and 15 of every 28-day cycle. Primary end-point was progression-free survival (PFS) rate at 4-months (4m-PFSR). Secondary end-points included overall survival (OS), PFS, disease control rate (DCR), metabolic response by 18F-fluorodeoxyglucose positron emission tomography (PET), hypoxic parameters evaluated by 18F-fluoromisonidazole (FMISO) PET and toxicity.

    RESULTS Twenty patients were treated with evofosfamide, with 16 response-evaluable patients. There was no objective response; stable disease was observed in nine patients, with a DCR of 56.25%. 4m-PFSR was 40.6%. Median PFS was 3.60 months (95% confidence interval [CI], 1.68 to 5.52). Median OS was 6.37 months (95% CI, 3.94 to 8.79). Reduction of tumor metabolic activity was observed in eight of 15 patients (53.3%). High baseline hypoxic parameters were associated with poor PFS. Change of hypoxic parameters between pretreatment and post-treatment reflected hypoxic-activated drug response. There was no treatment-related death.

    CONCLUSION Evofosfamide as second-line treatment of advanced BTC showed acceptable safety and comparable efficacy to other agents. Changes in volumetric parameters measured with FMISO PET, showing the degree of tumor hypoxia, reflected the response to evofosfamide based on the mode of action.

    PubMed IF 4.2 혈액종양내과
20. 33992021

    제1저자 조유리, 조은주 · 교신저자 신동욱, 유수종

    Cho Y, Cho EJ, Yoo JJ, Chang Y, Chung GE, Jeong SM, Park SH, Han K, Shin DW, Yu SJ

    Association between Lipid Profiles and the Incidence of Hepatocellular Carcinoma: A Nationwide Population-Based Study.

    Cancers (Basel). 2021;13(7):cancers13071599.

    Abstract

    BACKGROUND AND AIMS Altered lipid metabolism has been implicated in the development of hepatocellular carcinoma (HCC). This study investigated the relationships between lipid profiles and HCC development.

    METHODS Data were obtained from the Korean National Health Insurance Service from 2009 to 2017. Cox regression analysis was used to examine the hazard ratios of HCC in 8,528,790 individuals who had undergone health check-ups in 2009.

    RESULTS During a median of 7.3 years follow-up, 26,891 incidents of HCCs were identified. The incidence of HCC (per 100,000 person-years) gradually decreased according to the increase in total-cholesterol and LDL-cholesterol; the incidence of HCC was 69.2, 44.0, 33.9, and 25.8 in quartile-1 (Q1), Q2, Q3, and Q4 population of total-cholesterol, and 63.6, 44.5, 37.2, and 28.3 in Q1, Q2, Q3, and Q4 population of LDL-cholesterol, respectively. Compared to Q1 of total-cholesterol, subjects in higher total-cholesterol levels were associated with a lower incidence of HCC (multiple covariates-adjusted hazard ratio (aHR): Q2 0.61; Q3 0.46; Q4 0.36). These associations were consistently observed in stratified subgroup analysis by the presence of liver cirrhosis or viral hepatitis.

    CONCLUSIONS Low serum lipid levels were significantly associated with the increased risk of developing HCC. A low lipid profile might be an independent risk factor and preclinical marker for HCC.

    PubMed IF 4.8 소화기내과
21. 33982021

    제1저자 손민지 · 교신저자 임수

    Sohn M, Lee JE, Ahn M, Park Y, Lim S

    Correlation of dynamic membrane fluctuations in red blood cells with diabetes mellitus and cardiovascular risks.

    Sci Rep. 2021;11(1):7007.

    Abstract

    The rheological and physiological properties of red blood cells (RBCs) are affected by many factors in the vascular environment. Among them, membrane fluctuations (MFs), particularly dynamic fluctuations in RBC cell membrane thickness (RBC-MFs), are likely to be altered by the level of glycation of haemoglobin in patients with diabetes mellitus (DM). We investigated the associations of RBC-MFs with physiological variables associated with DM and cardiovascular diseases (CVDs). Forty-one healthy control subjects and 59 patients with DM were enrolled. Five-microliter samples of blood were collected and diluted 400 times. To measure the RBC-MFs, holotomography was used, which non-invasively and precisely analyses the optical characteristics of RBCs. Associations between the RBC-MFs and biochemical parameters related to glucose homeostasis and lipid profiles were investigated. Independent associations of the RBC-MFs with the presence of CVDs were also analysed. RBC-MFs were lower in patients with DM than in healthy participants (61.64 ± 7.49 nm vs 70.65 ± 6.65 nm, P = 1.4 × 10^-8). RBC-MFs correlated modestly with glycated haemoglobin level (ρ = - 0.47) and weakly with age (ρ = - 0.36), duration of diabetes (ρ = - 0.36), fasting plasma glucose level (ρ = - 0.37), and the 10-year Framingham risk score (ρ = - 0.38) (all P < 0.05). Low RBC-MFs were independently associated with the presence of CVDs after adjusting for CVD risk factors. The weak but significant associations of RBC-MFs with cardiometabolic risk factors and CVDs suggest that such deformity of circulating RBCs may be a useful marker of vascular complications of DM.

    PubMed IF 4.9 내분비대사내과
22. 33972021

    제1저자 김광일 · 교신저자 김철호

    Kim KI, Ji E, Choi JY, Kim SW, Ahn S, Kim CH

    Ten-year trends of hypertension treatment and control rate in Korea.

    Sci Rep. 2021;11(1):6966.

    Abstract

    We analyzed the Korean National Health and Nutrition Examination Survey (KNHANES) database to determine the trends of hypertension treatment and control rate in Korea over the past 10 years. In addition, we tried to investigate the effect of chronic medical conditions on hypertension management. We investigated the hypertension prevalence, awareness, treatment, and control rate from 2008 to 2017. KNHANES, which uses a stratified multistage sampling design, is a cross-sectional, nationally representative survey conducted by the Korean government. A total of 59,282 adults (≥ 20 years) were included, which was representative of the total population of around 40 million Koreans per year. The mean age was 50.7 ± 16.4 years and 42.6% were male. The prevalence of hypertension, hypercholesterolemia, diabetes mellitus, and obesity significantly increased over the 10 years. During this period, the hypertension treatment and control rate significantly improved. Hypertension treatment rate was significantly lower in the younger age group compared to the older age group, but the control rate among the treated patients was not significantly different between age groups. The treatment and control rates of hypertension were higher in patients with multimorbidity, which implies that it has a favorable effect on the treatment and control of hypertension. Hypertension treatment and control rate have improved over the past 10 years. The higher treatment and control rate in patients with multimorbidity suggest that the more aggressive surveillance might be associated with the improvement of hypertension treatment and control rate in Korea.

    PubMed IF 4.9 노인병내과
23. 33962021

    제1저자 윤연이 · 교신저자 윤연이

    Yoon YE, Yun B, Kim KM, Suh JW

    Breast Arterial Calcification: A Potential Biomarker for Atherosclerotic Cardiovascular Disease Risk?

    Curr Atheroscler Rep. 2021;23(5):21.

    Abstract

    PURPOSE OF REVIEW We aimed to summarize the current evidence regarding the association between breast arterial calcification (BAC) and atherosclerotic cardiovascular disease (ASCVD) in women and discuss the potential role of BAC in the risk stratification and preventive approaches for ASCVD.

    RECENT FINDINGS BAC has emerged as a potential women-specific risk marker for ASCVD. Although BAC presents as a medial calcification of the arteries, notably different from the intimal atherosclerotic process, current evidence supports a correlation between BAC and ASCVD risk factors or subclinical and clinical ASCVD, such as coronary artery disease or stroke. As millions of women undergo mammograms each year, the potential clinical application of BAC in enhanced ASCVD risk estimation, with no additional cost or radiation, has tremendous appeal. Although further research regarding optimal risk assessment and management in women with BAC is required, the presence of BAC should prompt healthy cardiovascular lifestyle modifications.

    PubMed IF 6.6 순환기내과
24. 33952021

    제1저자 박진주 · 교신저자 박진주

    Park JJ

    Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes.

    Diabetes Metab J. 2021;45(2):146-157.

    Abstract

    The cardiovascular disease continuum begins with risk factors such as diabetes mellitus (DM), progresses to vasculopathy and myocardial dysfunction, and finally ends with cardiovascular death. Diabetes is associated with a 2- to 4-fold increased risk for heart failure (HF). Moreover, HF patients with DM have a worse prognosis than those without DM. Diabetes can cause myocardial ischemia via micro- and macrovasculopathy and can directly exert deleterious effects on the myocardium. Hyperglycemia, hyperinsulinemia, and insulin resistance can cause alterations in vascular homeostasis. Then, reduced nitric oxide and increased reactive oxygen species levels favor inflammation leading to atherothrombotic progression and myocardial dysfunction. The classification, diagnosis, and treatment of HF for a patient with and without DM remain the same. Until now, drugs targeting neurohumoral and metabolic pathways improved mortality and morbidity in HF with reduced ejection fraction (HFrEF). Therefore, all HFrEF patients should receive guideline-directed medical therapy. By contrast, drugs modulating neurohumoral activity did not improve survival in HF with preserved ejection fraction (HFpEF) patients. Trials investigating whether sodium-glucose cotransporter-2 inhibitors are effective in HFpEF are on-going. This review will summarize the epidemiology, pathophysiology, and treatment of HF in diabetes.

    PubMed IF 8.2 순환기내과
25. 33942021

    제1저자 김민주, 김선미 · 교신저자 박정임, 천기정

    Kim MJ, Kim S, Choi S, Lee I, Moon MK, Choi K, Park YJ, Cho YH, Kwon YM, Yoo J, Cheon GJ, Park J

    Association of exposure to polycyclic aromatic hydrocarbons and heavy metals with thyroid hormones in general adult population and potential mechanisms.

    Sci Total Environ. 2021;762:144227.

    Abstract

    Air pollution and fuel emissions are the common sources of human exposure to polycyclic aromatic hydrocarbons (PAHs) and heavy metals. Several studies have suggested potential associations between PAHs/heavy metals and thyroid hormones, however, reports have been inconsistent. In this study, we employed a subpopulation of the adults (n = 1254) who participated in the Korean National Environmental Health Survey 2015-2017, and investigated the association of PAHs and major heavy metals with thyroid hormones, and explored the underlying mechanisms of thyroid disruption. Four PAH metabolites and three heavy metals of lead (Pb), mercury (Hg), and cadmium (Cd) were measured either in urine or in total blood. In addition, thyroid hormones (T3 and T4), TSH, thyroxine-binding globulin (TBG), and thyroid autoantibodies were measured, and peripheral deiodinase activity (G_D) and thyroid's secretory capacity (G_T) were calculated. Urinary Hg was negatively associated with total T3 in both males and females, while it was positively associated with total T4 among females only. Urinary Hg was related to decreased G_D and increased G_T in both sexes. In contrast, urinary Cd was positively associated with total T3 and G_D in both male and female populations. Urinary Cd also showed a positive association with thyroid autoantibodies, but only in males. A multi-factor model considering co-exposure to multiple chemicals also resulted in similar associations. Among the measured PAH metabolites, only urinary 1-hydroxypyrene showed a negative association with total T3 in males. However, this association was marginal, and disappeared in a multi-chemical model. The present observations are suggestive that exposures to Hg and Cd might disrupt thyroid hormones, possibly through an alteration of deiodinase activity. Association of PAH exposure with thyroid hormone appears to be insignificant.

    PubMed IF 8 내분비대사내과
26. 33932021

    제1저자 황인창 · 교신저자 이승표

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

    Time trajectory of cardiac function and its relation with survival in patients with light-chain cardiac amyloidosis.

    Eur Heart J Cardiovasc Imaging. 2021;22(4):459-469.

    Abstract

    AIMS We aimed to analyse the time-serial change of cardiac function in light-chain (AL) cardiac amyloidosis patients undergoing active chemotherapy and its relationship with patient outcome.

    METHODS AND RESULTS Seventy-two patients with AL cardiac amyloidosis undergoing active chemotherapy who had two or more echocardiographic examinations were identified from a prospective observational cohort (n = 34) and a retrospective cohort (n = 38). Echocardiographic parameters were obtained immediately prior to 1-3, 3-6, 6-12, and 12-24 months after the first chemotherapy. Study endpoint was a composite of death or heart transplantation (HT). During a median of 32 months (interquartile range 8-51) follow-up, 33 patients (45.8%) died and 4 patients (5.6%) underwent HT. Echocardiograms immediately prior to the first chemotherapy did not show differences between the patients with adverse events vs. those without. Significant increase in mitral E/e' ratio and decline in left ventricular global longitudinal strain (LV-GLS) was observed, starting at 3-6 months after the first chemotherapy only in those who experienced adverse events on follow-up, which was also evident in those who responded to chemotherapy. Multivariate analysis demonstrated that B-natriuretic peptide >500 pg/mL and troponin I >0.15 ng/dL at initial diagnosis, hospitalization for heart failure, E/e' >15, and LV-GLS <10% during follow-up were independent predictors of outcome.

    CONCLUSIONS In AL cardiac amyloidosis patients undergoing active chemotherapy, the deterioration of LV function may occur, starting even at 3-6 months after the first chemotherapy. Serial echocardiography may help identify those who experience a clinical event in the near future despite active chemotherapy.

    PubMed IF 6.1 순환기내과
27. 33922021

    제1저자 공민규 · 교신저자 한정규

    Kong MG, Han JK, Kang JH, Zheng C, Yang HM, Park KW, Kang HJ, Koo BK, Chae IH, Kim HS, Collaborators

    Clinical outcomes of long stenting in the drug-eluting stent era: patient-level pooled analysis from the GRAND-DES registry.

    EuroIntervention. 2021;16(16):1318-1325.

    Abstract

    AIMS We aimed to understand the association between stent length and clinical outcomes after percutaneous coronary intervention (PCI) using newer-generation drug-eluting stents (DES).

    METHODS AND RESULTS We analysed 9,217 patients who underwent stenting for a single lesion from the GRAND-DES registry, a patient-level pooled registry including five Korean multicentre DES registries. The median follow-up duration was 730 days (interquartile range 708 to 752 days). A total of 8,035 patients were classified into the short stenting group (≤40 mm), and 1,182 into the long stenting group (>40 mm). The primary endpoint was target lesion failure (TLF). Long stenting (>40 mm) was significantly associated with higher TLF (IPTW adjusted HR 1.88, 95% CI: 1.67-2.13; p<0.001), and definite or probable stent thrombosis (IPTW adjusted HR 2.20, 95% CI: 1.51-3.20; p<0.001). In the landmark analysis, the incidence of TLF was significantly higher with long stenting during the first 30 days after PCI (log-rank p=0.001) and also after 30 days (log-rank p<0.001). Long stenting was associated with a higher risk of early stent thrombosis (log-rank p=0.001), but not with that of late stent thrombosis (log-rank p=0.887).

    CONCLUSIONS In the contemporary second-generation DES era, stenting longer than 40 mm continues to be associated with less favourable clinical outcomes such as TLF and stent thrombosis.

    PubMed IF 9.2 순환기내과
28. 33912021

    제1저자 김수환 · 교신저자 정지봉

    Kim SH, Jeong JB, Kang J, Ahn DW, Kim JW, Kim BG, Lee KL, Oh S, Yoon SH, Park SJ, Lee DH

    Association between sarcopenia level and metabolic syndrome.

    PLoS One. 2021;16(3):e0248856.

    Abstract

    AIMS Metabolic syndrome (MetS) increases the risk of diabetes mellitus (DM), cardiovascular disease (CVD), cancer, and mortality. Sarcopenia has been reported as a risk factor for MetS, non-alcoholic fatty liver disease, and CVD. To date, the association between sarcopenia and MetS has been investigated. However, there have been few studies on the dose-response relationship between sarcopenia and MetS. We investigated the association between sarcopenia and the prevalence of MetS. We also aimed to analyze the dose-response relationship between skeletal muscle mass and the prevalence of MetS.

    METHODS We enrolled 13,620 participants from October 2014 to December 2019. Skeletal muscle mass was measured using bioelectrical impedance analysis (BIA). Appendicular skeletal muscle mass (ASM) was divided by body weight (kg) and was expressed as a percentage (ASM x 100/Weight, ASM%). The quartiles of ASM% were calculated for each gender, with Q1 and Q4 being the lowest and highest quartiles of ASM%, respectively. The quartiles of ASM% were calculated for each gender, with Q1 and Q4 being the lowest and highest quartiles of ASM%, respectively. Linear regression and logistic regression analyses were used to compare the clinical parameters according to ASM%, adjusted for age, sex, obesity, hypertension (HT), DM, dyslipidemia (DL), smoking, alcohol intake, and C-reactive protein (CRP). Multiple logistic regression analysis was performed to determine the risk of MetS in each group.

    RESULTS A dose-response relationship was identified between ASM% and MetS. Sarcopenia was associated with an increased prevalence of MetS. After adjustment for age, sex, obesity, HT, DM, DL, smoking, alcohol intake, and CRP, sarcopenia remained significantly associated with MetS. For each 1 quartile increment in ASM%, the risk of MetS decreased by 56% (P< 0.001). After adjusting for age, sex, obesity, HT, DM, DL, smoking, alcohol intake, and CRP, the risk of MetS decreased by 25% per 1Q increment in ASM% (P < 0.001).

    CONCLUSIONS Sarcopenia by BIA is independently associated with the risk of MetS and has a dose-response relationship.

    PubMed IF 2.8 소화기내과
29. 33902021

    제1저자 김병근 · 교신저자 박흥우

    Kim BK, Lee HS, Lee SY, Park HW

    Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma.

    Front Med (Lausanne). 2021;8:652824.

    Abstract

    Gene regulatory networks address how transcription factors (TFs) and their regulatory roles in gene expression determine the responsiveness to anti-asthma therapy. The purpose of this study was to assess gene regulatory networks of adult patients with asthma who showed good or poor lung function improvements in response to inhaled corticosteroids (ICSs). A total of 47 patients with asthma were recruited and classified as good responders (GRs) and poor responders (PRs) based on their responses to ICSs. Genome-wide gene expression was measured using peripheral blood mononuclear cells obtained in a stable state. We used Passing Attributes between Networks for Data Assimilations to construct the gene regulatory networks associated with GRs and PRs to ICSs. We identified the top-10 TFs that showed large differences in high-confidence edges between the GR and PR aggregate networks. These top-10 TFs and their differentially-connected genes in the PR and GR aggregate networks were significantly enriched in distinct biological pathways, such as TGF-β signaling, cell cycle, and IL-4 and IL-13 signaling pathways. We identified multiple TFs and related biological pathways influencing ICS responses in asthma. Our results provide potential targets to overcome insensitivity to corticosteroids in patients with asthma.

    PubMed IF 3.6 알레르기내과
30. 33892021

    제1저자 차명진 · 교신저자 오세일, 장지현

    Cha MJ, Seo JW, Kim HJ, Kim MK, Yoon HS, Jo SW, Oh S, Chang JH

    Early Changes in Rat Heart After High-Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation.

    J Am Heart Assoc. 2021;10(6):e019072.

    Abstract

    Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early-period antiarrhythmic effects induced by high-dose irradiation are unknown. This study investigated dose-responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild-type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks' postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high-dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose-responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell-related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high-dose irradiation. ECG indicated intracardiac conduction delay with prominent ST-segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.

    PubMed IF 6 순환기내과

서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.