SCI 발표논문

1. 35082021

   제1저자 주이진, 곽민선 · 교신저자 윤순호

   Joo I, Kwak MS, Park DH, Yoon SH

   Fully automated waist circumference measurement on abdominal CT: Comparison with manual measurements and potential value for identifying overweight and obesity as an adjunct output of CT scan.

   PLoS One. 2021;16(7):e0254704.

   Abstract

   OBJECTIVE Waist circumference (WC) is a widely accepted anthropometric parameter of central obesity. We investigated a fully automated body segmentation algorithm for measuring WC on abdominal computed tomography (CT) in comparison to manual WC measurements (WC-manual) and evaluated the performance of CT-measured WC for identifying overweight/obesity.

   MATERIALS AND METHODS This retrospective study included consecutive adults who underwent both abdominal CT scans and manual WC measurements at a health check-up between January 2013 and November 2019. Mid-waist WCs were automatically measured on noncontrast axial CT images using a deep learning-based body segmentation algorithm. The associations between CT-measured WC and WC-manual was assessed by Pearson correlation analysis and their agreement was assessed through Bland-Altman analysis. The performance of these WC measurements for identifying overweight/obesity (i.e., body mass index [BMI] ≥25 kg/m2) was evaluated using receiver operating characteristics (ROC) curve analysis.

   RESULTS Among 763 subjects whose abdominal CT scans were analyzed using a fully automated body segmentation algorithm, CT-measured WCs were successfully obtained in 757 adults (326 women; mean age, 54.3 years; 64 women and 182 men with overweight/obesity). CT-measured WC was strongly correlated with WC-manual (r = 0.919, p < 0.001), and showed a mean difference of 6.1 cm with limits of agreement between -1.8 cm and 14.0 cm in comparison to WC-manual. For identifying overweight/obesity, CT-measured WC showed excellent performance, with areas under the ROC curve (AUCs) of 0.960 (95% CI, 0.933-0.979) in women and 0.909 (95% CI, 0.878-0.935) in men, which were comparable to WC-manual (AUCs of 0.965 [95% CI, 0.938-0.982] and 0.916 [95% CI, 0.886-0.941]; p = 0.735 and 0.437, respectively).

   CONCLUSION CT-measured WC using a fully automated body segmentation algorithm was closely correlated with manually-measured WC. While radiation issue may limit its general use, it can serve as an adjunctive output of abdominal CT scans to identify overweight/obesity.

   PubMed IF 2.8 소화기내과
2. 35072021

   제1저자 임재현, 이소령 · 교신저자 최의근

   Lim J, Lee SR, Choi EK, Han KD, Jung JH, Ahn HJ, Yun JP, Kwon S, Oh S, Lip GYH

   Exercise and the Risk of Dementia in Patients with Newly Diagnosed Atrial Fibrillation: A Nationwide Population-Based Study.

   J Clin Med. 2021;10(14):jcm10143126.

   Abstract

   BACKGROUND It is unclear whether exercise would reduce dementia in patients with a new diagnosis of atrial fibrillation (AF). Therefore, we aimed to evaluate the association between the change in physical activity (PA) before and after new-onset AF and the risk of incident dementia.

   METHODS Using the Korean National Health Insurance Service database, we enrolled a total of 126,555 patients with newly diagnosed AF between 2010 and 2016, who underwent health examinations within two years before and after their diagnosis of AF. The patients were divided into four groups: persistent non-exercisers, exercise starters, exercise quitters, and exercise maintainers.

   RESULTS Based on a total of 396,503 person-years of follow-up, 5943 patients were diagnosed with dementia. Compared to persistent non-exercisers, exercise starters (adjusted hazard ratio (aHR) 0.87; 95% confidence interval (CI) 0.81-0.94), and exercise maintainers (aHR 0.66; 95% CI 0.61-0.72) showed a lower risk of incident dementia; however, the risk was similar in exercise quitters (aHR 0.98; 95% CI 0.92-1.05) (p-trend < 0.001). There was a J-shaped relationship between the dose of exercise and the risk of dementia, with the risk reduction maximized at 5-6 times per week of moderate-to-vigorous PA among exercise starters.

   CONCLUSION Patients who initiated or continued regular exercise after diagnosis of AF were associated with a lower risk of dementia than persistent non-exercisers, with no risk reduction associated with exercise cessation. Our findings may provide evidence for the benefit of exercise prescription to patients with new-onset AF to prevent incident dementia regardless of their current exercise status.

   PubMed IF 3.3 순환기내과
3. 35062021

   제1저자 신동우 · 교신저자 황진혁

   Shin DW, Kim MA, Lee JC, Kim J, Hwang JH

   Maintenance of skeletal muscle mass during FOLFIRINOX is a favorable prognostic factor in pancreatic cancer patients.

   BMC Res Notes. 2021;14(1):272.

   Abstract

   OBJECTIVE The study aimed to investigate the effect of body composition changes during chemotherapy on clinical outcomes in patients with pancreatic cancer.

   RESULTS In patients with locally advanced pancreatic cancer (LAPC), the cross-sectional area of skeletal muscle (SM) and adipose tissue (AT) at the level of third lumbar vertebra was measured. The SM and AT ratios indicated the changes during chemotherapy. The patients were classified into three groups based on these ratios: group 1, ≥ 1.00; group 2, 0.85-0.99; group 3, < 0.85. The overall survival (OS) and surgical resection rates were estimated. Fifty-eight patients with LAPC who received first-line FOLFIRINOX were analyzed. Fifteen (25.9%) patients who underwent resection showed maintained BMI, SM, and AT as compared to the patients who did not undergo resection. As the SM ratio decreased, the risk for death increased significantly. Further, the resection rate was significantly higher in patients with maintained SM compared to those with low SM ratio. On the contrary, the change in AT ratio was not associated with OS and resection rate; however, significant decrease in AT more than 15% showed poor clinical outcomes. Maintenance of SM during chemotherapy is a reliable prognostic factor indicating longer OS and higher resection rate.

   PubMed IF 1.7 소화기내과
4. 35052021

   제1저자 강창희, 송진희 · 교신저자 김나영

   Kang C, Song CH, Kim N, Nam RH, Choi SI, Yu JE, Nho H, Choi JA, Kim JW, Na HY, Lee HN, Surh YJ

   The Enhanced Inhibitory Effect of Estrogen on PD-L1 Expression Following Nrf2 Deficiency in the AOM/DSS Model of Colitis-Associated Cancer.

   Front Oncol. 2021;11:679324.

   Abstract

   Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a dual role in carcinogenesis. We previously reported that Nrf2 deficiency enhances the anti-tumorigenic effect of 17β-estradiol (E2) in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated cancer (CAC). Herein, we aimed to determine a possible explanation for our recent work and investigated the immune microenvironment represented by programmed death-ligand 1 (PD-L1) expression. One week after the AOM injection, mice were administered with DSS in drinking water for seven days; daily E2 injections were intraperitoneally administered during this period. The mice were sacrificed 16 weeks after AOM injection and analyzed for PD-L1 expression in the distal colon tissues using Western blotting and immunohistochemistry (IHC). Based on Western blotting results, PD-L1 expression was reduced in Nrf2 knockout (KO) female and E2-treated male mice when compared with their wild-type counterparts, following AOM/DSS treatment; this supports the association of PD-L1 expression with tumor progression. Additionally, this finding was in good agreement with the IHC results for PD-L1. Furthermore, we observed that PD-L1 is predominantly expressed in stromal cells rather than on epithelial cells in the colon. Western blotting revealed that PD-L1 expression in the colon positively correlates with expressions of inducible nitric oxide synthase (iNOS) (male, P = 0.002; female, P <0.001) and cyclooxygenase-2 (COX-2) (male, P <0.001; female, P <0.001). Collectively, our findings indicate that estrogen ameliorates the immune microenvironment represented by PD-L1 expression and enhances its effect in the absence of Nrf2.

   PubMed IF 3.4 소화기내과
5. 35042021

   제1저자 박재형 · 교신저자 조구영

   Park JH, Hwang IC, Park JJ, Park JB, Cho GY

   Left Atrial Strain to Predict Stroke in Patients With Acute Heart Failure and Sinus Rhythm.

   J Am Heart Assoc. 2021;10(13):e020414.

   Abstract

   Background Stroke is a major comorbidity in patients with heart failure (HF), especially in those with decreased left atrial (LA) function, and thus, identifying patients highly at risk of stroke can prevent its occurrence. We evaluated the predictive value of global longitudinal strain of LA (LAGLS) in patients with acute HF and sinus rhythm. Methods and Results In this retrospective study, 2461 patients (53.3% men, 69.7±14.4 years old) with sinus rhythm and LAGLS among 4312 consecutive patients with acute HF from 3 tertiary hospitals were included. HF phenotypes were defined as HF with reduced ejection fraction (EF) (left ventricular EF ≤40%), HF with midrange EF (40% <left ventricular EF <50%), and HF with preserved ejection fraction (left ventricular EF ≥50%). Primary outcome was new-onset stroke. The mean left ventricular EF was 39.4%±15.6%. Moreover, 1388 (57.5%), 342 (14.2%), and 682 (28.3%) were classified with HF with reduced EF, HF with midrange EF, and HF with preserved EF, retrospectively. LAGLS was 17.2%±10.4%. During the follow-up duration (mean: 30.3±25.4 months), 100 patients experienced stroke. Patients with stroke had higher LA diameter (P=0.031) and lower LAGLS (P=0.010) than those without stroke. In the univariate analysis, age, diabetes mellitus, LA diameter, LA volume index, and LAGLS were significant risk factors for stroke. In the multivariate analysis, each 1% decrease in LAGLS was associated with a 3.8% increased risk for stroke (hazard ratio [HR], 1.038; 95% CI, 1.013-1.065; P=0.003). When applying a LAGLS cutoff point of 14.5%, patients with LAGLS <14.5% had approximately twice the risk for stroke after adjusting other significant variables (HR, 1.940; 95% CI, 1.269-2.965; P=0.002). Conclusions In patients with acute HF and sinus rhythm, decreased LAGLS (<14.5%) was associated with an increased risk for stroke, with an annual incidence of 2.38%.

   PubMed IF 6 순환기내과
6. 35032021

   제1저자 박진균 · 교신저자 송영욱

   Park JK, Shon S, Yoo HJ, Suh DH, Bae D, Shin J, Jun JH, Ha N, Song H, Choi YI, Pap T, Song YW

   Inhibition of histone deacetylase 6 suppresses inflammatory responses and invasiveness of fibroblast-like-synoviocytes in inflammatory arthritis.

   Arthritis Res Ther. 2021;23(1):177.

   Abstract

   BACKGROUND To investigate the effects of inhibiting histone deacetylase (HDAC) 6 on inflammatory responses and tissue-destructive functions of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA).

   METHODS FLS from RA patients were activated with interleukin (IL)-1β in the presence of increasing concentrations of M808, a novel specific HDAC6 inhibitor. Production of ILs, chemokines, and metalloproteinases (MMPs) was measured in ELISAs. Acetylation of tubulin and expression of ICAM-1 and VCAM-1 were assessed by Western blotting. Wound healing and adhesion assays were performed. Cytoskeletal organization was visualized by immunofluorescence. Finally, the impact of HDAC6 inhibition on the severity of arthritis and joint histology was examined in a murine model of adjuvant-induced arthritis (AIA).

   RESULTS HDAC6 was selectively inhibited by M808. The HDAC6 inhibitor suppressed the production of MMP-1, MMP-3, IL-6, CCL2, CXCL8, and CXCL10 by RA-FLS in response to IL-1β. Increased acetylation of tubulin was associated with decreased migration of RA-FLS. Inhibiting HDAC6 induced cytoskeletal reorganization in RA-FLS by suppressing the formation of invadopodia following activation with IL-1β. In addition, M808 tended to decrease the expression of ICAM-1 and VCAM-1. In the AIA arthritis model, M808 improved the clinical arthritis score in a dose-dependent manner. Also, HDAC6 inhibition was associated with less severe synovial inflammation and joint destruction.

   CONCLUSION Inhibiting HDAC6 dampens the inflammatory and destructive activity of RA-FLS and reduces the severity of arthritis. Thus, targeting HDAC6 has therapeutic potential.

   PubMed IF 5.4 류마티스내과
7. 35022021

   제1저자 한미연 · 교신저자 오국환

   Han M, Kim H, Kim HJ, Kang E, Kim YS, Choi KH, Kim SW, Ahn C, Oh KH

   Serum uric acid is associated with coronary artery calcification in early chronic kidney disease: a cross-sectional study.

   BMC Nephrol. 2021;22(1):247.

   Abstract

   BACKGROUND Although uric acid (UA) is regarded as a risk factor for cardiovascular disease, whether UA is an independent risk factor contributing to coronary artery calcification in chronic kidney disease (CKD) is not well known. We evaluated whether UA level is associated with coronary artery calcium (CAC) score in a predialysis CKD cohort.

   METHODS A total of 1,350 subjects who underwent coronary computed tomography as part of the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease were analysed. We conducted a logistic regression analysis to evaluate the association between UA and the presence of CAC.

   RESULTS CAC was detected in 705 (52.2 %) patients, and the level of UA was significantly higher in CAC > 0 patients. UA showed a positive relationship with CAC > 0 in age- and sex-adjusted logistic regression analysis (Odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.04-1.19, P = 0.003). However, UA showed no association with CAC > 0 in multivariate analysis. Further analysis showed that UA showed a positive association with CAC > 0 only in estimated glomerual filtration rate (eGFR) > 60 ml/min/1.73 m² (OR 1.23, 95 % CI 1.02-1.49, P = 0.036) but not in eGFR 30-59 ml/min/1.73 m² (OR 0.92, 95 % CI 0.78-1.08, P = 0.309) or < 30 ml/min/1.73 m² (OR 0.92, 95 % CI 0.79-1.08, P = 0.426).

   CONCLUSIONS UA level was significantly associated with CAC in early CKD, but not in advanced CKD.

   PubMed IF 2.9 신장내과
8. 35012021

   제1저자 이태민 · 교신저자 김학령

   Rhee TM, Kim HL, Lim WH, Seo JB, Kim SH, Zo JH, Kim MA

   Age-specific association between invasively measured central blood pressure and left ventricular mass index.

   Clin Exp Hypertens. 2021;43(5):419-427.

   Abstract

   Background: The impact of age on the association between central aortic hemodynamics and left ventricular (LV) remodeling has not been well elucidated. We compared the relationship between measurements of central blood pressure (CBP) and LV mass index (LVMI) according to their ages (<50 years versus ≥50 years). Methods: A total of 305 consecutive subjects (64.4 ± 10.9 years, 60.7% males) who underwent invasive coronary angiography (ICA) for the evaluation of coronary artery disease were prospectively enrolled. Just before ICA, CBP was measured at the aortic root using a pig-tail catheter, and CBP indices, including aortic systolic blood pressure (aSBP), aortic pulse pressure (aPP), aortic fractional pulse pressure (=aPP/mean aortic pressure), and aortic pulsatility index (=aPP/diastolic aortic pressure), were recorded. All subjects underwent transthoracic echocardiography, and LVMI was measured on the same day of ICA. Results: In simple linear correlation analyses, LVMI was associated with all CBP indices in subjects aged <50 years (n = 29) (P < .05 for each), but not in those aged ≥50 years (n = 276) (P > .05 for each). In the younger age group (≤50 years), multivariable analysis showed that aSBP (β= 0.457, P= .021) and aPP (β= 0.610, P= .006) had a significant association with LVMI after adjusting for possible confounding factors. The results remained consistent even when analyzed in a 1:1 propensity score-matched cohort. In conclusion, invasively measured aPP showed the closest association with LVMI in subjects aged <50 years, but not those aged ≥50 years. Conclusion: Aortic pulsatile hemodynamic status appears to have a greater effect on LV remodeling in younger people than in older people.

   PubMed IF 6.8 순환기내과
9. 35002021

   제1저자 강창경, 김민지 · 교신저자 김항래, 오명돈

   Kang CK, Kim M, Lee S, Kim G, Choe PG, Park WB, Kim NJ, Lee CH, Kim IS, Jung K, Lee DS, Shin HM, Kim HR, Oh MD

   Longitudinal Analysis of Human Memory T-Cell Response According to the Severity of Illness up to 8 Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

   J Infect Dis. 2021;224(1):39-48.

   Abstract

   BACKGROUND Understanding the memory T-cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for assessing the longevity of protective immunity after SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination. However, the longitudinal memory T-cell response up to 8 months post-symptom onset (PSO) according to the severity of illness is unknown.

   METHODS We analyzed peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with COVID-19 who experienced asymptomatic, mild, or severe illness at 2, 5, and 8 months PSO. SARS-CoV-2 spike, nucleocapsid, and membrane protein-stimulated PBMCs were subjected to flow cytometry analysis.

   RESULTS A total of 24 patients (7 asymptomatic, 9 with mild disease, and 8 with severe disease) and 6 healthy volunteers were analyzed. SARS-CoV-2-specific OX40+CD137+CD4+ T cells and CD69+CD137+CD8+ T cells persisted at 8 months PSO. Also, antigen-specific cytokine-producing or polyfunctional CD4+ T cells were maintained for up to 8 months PSO. Memory CD4+ T-cell responses tended to be greater in patients who had severe illness than in those with mild or asymptomatic disease.

   CONCLUSIONS Memory response to SARS-CoV-2, based on the frequency and functionality, persists for 8 months PSO. Further investigations involving its longevity and protective effect from reinfection are warranted.

   PubMed IF 4.1 감염내과
10. 34992021

    제1저자 김아이린, 박효민 · 교신저자 이은주, 김효수

    Kim I^*, Park H^*, Hwang I, Moon D, Yun H, Lee EJ, Kim HS

    Discovery of chemerin as the new chemoattractant of human mesenchymal stem cells.

    Cell Biosci. 2021;11(1):120.

    Abstract

    BACKGROUND The homing capacity of human mesenchymal stem cells (hMSCs) to the injured sites enables systemic administration of hMSCs in clinical practice. In reality, only a small proportion of MSCs are detected in the target tissue, which is a major bottleneck for MSC-based therapies. We still don't know the mechanism how MSCs are chemo-attracted to certain target organ and engrafted through trans-endothelial migration. In this study, we aimed to determine the mechanism how the circulating hMSCs home to the injured liver.

    METHODS AND RESULTS When we compare the cytokine array between normal and injured mouse liver at 1-day thioacetamide (TAA)-treatment, we found that chemerin, CXCL2, and CXCL10 were higher in the injured liver than normal one. Among three, only chemerin was the chemoattractant of hMSCs in 2D- and 3D-migration assay. Analysis of the signal transduction pathways in hMSCs showed that chemerin activated the phosphorylation of JNK1/2, ERK1/2 and p38, and finally upregulated CD44, ITGA4, and MMP-2 that are involved in the transendothelial migration and extravasation of MSCs. Upstream transcription regulators of CD44, ITGA4, and MMP-2 after chemerin treatment were MZF1, GATA3, STAT3, and STAT5A. To develop chemerin as a chemoattractant tool, we cloned gene encoding the active chemerin under the CMV promoter (CMV-aChemerin). We analyzed the migration of hMSCs in the 3D model for space of the Disse, which mimics transmigration of hMSCs in the liver. CMV-aChemerin-transfected hepatocytes were more effective to attract hMSC than control hepatocytes, leading to the enhanced transendothelial migration and homing of hMSCs to liver. The homing efficiency of the intravascularly-delivered hMSCs to liver was evaluated after systemic introduction of the CMV-aChemerin plasmid packed in liposome-vitamin A conjugates which target liver. CMV-aChemerin plasmid targeting liver significantly enhanced homing efficiency of hMSCs to liver compared with control plasmid vector.

    CONCLUSIONS Chemerin is the newly found chemoattractant of hMSCs and may be a useful tool to manipulate the homing of the intravascularly-administered hMSC to the specific target organ.

    PubMed IF 6.5 순환기내과
11. 34982021

    제1저자 서경진, 윤성혜 · 교신저자 김진원

    Suh KJ, Yoon S, Kim JW, Yoon SH, Kim JW, Kim SH, Kim YJ, Lee KW, Lee JS, Kim JH

    A single-arm feasibility study of gradual dose de-escalation of antiemetic dexamethasone for older patients receiving chemotherapy.

    J Geriatr Oncol. 2021;12(6):922-929.

    Abstract

    OBJECTIVES To investigate whether discontinuation of prophylactic dexamethasone by gradual dose de-escalation is practicable in older patients with cancer undergoing moderately emetogenic chemotherapy.

    MATERIALS AND METHODS This single-arm, feasibility study prospectively enrolled 40 patients (≥70 years old) with colorectal cancer, who were scheduled to undergo adjuvant FOLFOX chemotherapy, and ten patients ≤60 years old to serve as a control group for pharmacokinetic study. All patients received an antiemetic regimen consisting of intravenous dexamethasone 8 mg and palonosetron at day 1 of the first cycle and underwent phone interviews using symptom questionnaires at day 7 of each cycle. Dexamethasone was tapered off through gradual de-escalation by 2 mg per cycle, when complete response (CR; no emesis and no rescue therapy) was achieved. Primary endpoint was the proportion of patients who discontinued dexamethasone completely.

    RESULTS The median age of the patient was 74 years, and 50% were male. Of the 40 patients, 36 completed twelve cycles of chemotherapy, and 73% (N = 29) were able to discontinue dexamethasone completely. The mean (±SD) dose of dexamethasone per cycle was 3.0 mg (±2.4 mg), which was reduced to 37.5% of the initial dose level. The severity of patient-reported nausea did not significantly change over chemotherapy cycle. Geriatric assessment revealed no decline in any domain and fasting blood glucose and hemoglobin A1c levels were not elevated after twelve cycles of chemotherapy, compared to the baseline.

    CONCLUSION Gradual dose de-escalation and discontinuation of prophylactic dexamethasone is feasible without compromising its antiemetic effect in older patients undergoing chemotherapy.

    PubMed IF 2.9 혈액종양내과
12. 34972021

    제1저자 김정현 · 교신저자 김세훈

    Kim JH, Choi SI, Lee YJ, Kim BK, Park HW, Cho SH, Chang YS, Kim SH

    Pharmacological prevention of delayed hypersensitivity reactions caused by iodinated contrast media.

    World Allergy Organ J. 2021;14(7):100561.

    Abstract

    BACKGROUND Delayed hypersensitivity reactions (DHRs) to radiocontrast media (RCM) occur in approximately 0.5-23.0% of patients and are thought to be caused by T cell-mediated mechanisms. However, an optimal pharmacological preventive strategy is not yet established in patients with histories of delayed reactions to RCM.

    OBJECTIVE We aimed to evaluate the efficacy of pharmacological prevention in patients with histories of delayed reactions to non-ionic low-osmolar RCM when re-exposed to RCM.

    METHODS A retrospective review of electronic medical records of 117 patients with previous histories of DHRs to RCM who visited an allergy clinic for the prevention of reactions after the re-exposure to RCM was conducted. The effects of pharmacological prevention were compared according to the symptom scores of previous reactions based on their intensities and durations with electronic medical records (EMRs).

    RESULTS Of the 117 patients who experienced DHRs after RCM injection, we confirmed the outcomes of RCM re-exposure in 101 patients. For pharmacological prevention, 92 patients (91.1%) received steroids before RCM injection and among them, 50 patients (49.5%) received additional steroids after RCM injection. With this pharmacological prevention, patients of symptoms improved or no recurrence, recurrence of similar previous symptoms, and recurrence of worse symptoms were 98 (97.0%), 2 (2.0%), and 1 (1.0%), respectively. The proportions of no recurrence after pharmacological prevention were lower in patients with severe reactions and higher symptom scores.

    CONCLUSION Pharmacological prevention showed a beneficial effect in most patients with delayed hypersensitivity to RCM. Further investigations are needed to establish an effective protocol for the prevention of delayed reactions to RCM.

    PubMed IF 4 알레르기내과
13. 34962021

    제1저자 황도연, 김한얼 · 교신저자 이승표, 임선희

    Hwang D, Kim HJ, Lee SP, Lim S, Koo BK, Kim YJ, Kook W, Andreini D, Al-Mallah MH, Budoff MJ, Cademartiri F, Chinnaiyan K, Choi JH, Conte E, Marques H, de Araújo Gonçalves P, Gottlieb I, Hadamitzky M, Leipsic JA, Maffei E, Pontone G, Raff GL, Shin S, Lee BK, Chun EJ, Sung JM, Lee SE, Berman DS, Lin FY, Virmani R, Samady H, Stone PH, Narula J, Bax JJ, Shaw LJ, Min JK, Chang HJ

    Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis.

    JACC Cardiovasc Imaging. 2021;14(7):1410-1421.

    Abstract

    OBJECTIVES This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).

    BACKGROUND Coronary CTA can noninvasively assess coronary plaques quantitatively.

    METHODS Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.

    RESULTS Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm³ [interquartile range (IQR): 0.0 to 39.6 mm³]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm³ [IQR: 0.0 to 127.4 mm³]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm³ [IQR: 96.7 to 306.4 mm³]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.

    CONCLUSIONS The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).

    PubMed IF 19 순환기내과
14. 34952021

    제1저자 김기욱 · 교신저자 김나영

    Kim KW, Kim N, Choi Y, Kim WS, Yoon H, Shin CM, Park YS, Lee DH, Park YS, Ahn SH, Park DJ, Kim HH, Lee HS, Kim JW, Kim JW, Lee KW, Chang W, Park JH, Lee YJ, Lee KH, Kim YH

    Different effects of p53 protein overexpression on the survival of gastric cancer patients according to Lauren histologic classification: a retrospective study.

    Gastric Cancer. 2021;24(4):844-857.

    Abstract

    BACKGROUND Inactivation of TP53, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the correlation between the overexpression of p53 and survival in different Lauren-type GCs.

    METHODS From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression.

    RESULTS Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (P = 0.026) and Early gastric cancer (P = 0.044) in intestinal-type GC, and with advanced TNM stage (P < 0.001) and Advanced gastric cancer (P < 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio [aHR] = 1.423, P = 0.022; OS in diffuse-type: aHR = 1.401 P = 0.035; cancer recurrence in diffuse-type: aHR = 1.502, P = 0.039).

    CONCLUSION p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.

    PubMed IF 6.1 소화기내과
15. 34942021

    제1저자 임수 · 교신저자 임수, Giovanni Targher

    Lim S, Kim JW, Targher G

    Links between metabolic syndrome and metabolic dysfunction-associated fatty liver disease.

    Trends Endocrinol Metab. 2021;32(7):500-514.

    Abstract

    Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition characterized by hepatic fat accumulation combined with underlying metabolic dysregulation. Having evolved from the previous term of nonalcoholic fatty liver disease (NAFLD), the term MAFLD more closely implicates the presence of overweight/obesity, type 2 diabetes, or metabolic dysregulation as essential pathogenic factors, leading to better identification of individuals with this metabolic liver disease. Low-grade inflammation, increased oxidative stress, mitochondrial dysfunction, and intestinal dysbiosis are also involved in its pathogenesis. MAFLD is not only associated with liver-related complications, but also with adverse cardiometabolic outcomes. Further studies are needed to assess whether the newly proposed definition of MAFLD is more accurate than the NAFLD in predicting the adverse liver-related and extrahepatic outcomes.

    PubMed IF 20.1 내분비대사내과
16. 34932021

    제1저자 하유정, 김효진 · 교신저자 윤혁, 강유선

    Ha YJ, Kim HJ, Lee E, Park JH, Park YS, Lee YJ, Kang Y, Yoon H

    Subclinical sacroiliitis detected by abdominopelvic computed tomography in Korean patients with Crohn's disease.

    Korean J Intern Med. 2021;36(4):868-877.

    Abstract

    BACKGROUND/AIMS Sacroiliitis is a frequent extraintestinal manifestation of inflammatory bowel diseases (IBDs). This study aimed to assess the prevalence of sacroiliitis using a validated screening tool based on abdominopelvic computed tomography (APCT) in Korean patients with Crohn's disease (CD) and examine potential associations between clinical characteristics and sacroiliitis.

    METHODS One hundred five patients with CD undergoing APCT for any indication at an IBD clinic were matched 1:1 for age and sex with 105 controls without underlying chronic illnesses. Using a validated APCT screening tool that defines sacroiliitis as either ankylosis or a total erosion score (TES) ≥ 3, all computed tomography scans were assessed by two independent, blinded radiologists. We compared the prevalence of sacroiliitis between CD patients and controls and clinical characteristics between CD patients with and without sacroiliitis.

    RESULTS The prevalence of sacroiliitis was significantly higher in CD patients than in controls (13.3% vs. 4.8%, p = 0.030). All subjects with sacroiliitis had a TES ≥ 3, but no ankylosis. The assessment of sacroiliitis in APCT showed excellent interreader reliability (Cohen's kappa = 0.933 for presence of sacroiliitis). Sacroiliitis in CD patients was bilateral and asymptomatic. There were no significant associations between sacroiliitis and any demographic data or clinical characteristics in these patients.

    CONCLUSION The prevalence of APCT-detected sacroiliitis in CD patients was higher than that in controls, but the condition was asymptomatic. The clinical significance of asymptomatic sacroiliitis in Korean CD patients remains unclear.

    PubMed IF 2.2 소화기내과
17. 34922021

    제1저자 김세훈, 박진주 · 교신저자 최동주

    Kim S, Park JJ, Shin MS, Kwak CH, Lee BR, Park SJ, Lee HY, Kim SH, Kang SM, Yoo BS, Chung JW, Choi SW, Jo SH, Shin J, Choi DJ

    Apparent treatment-resistant hypertension among ambulatory hypertensive patients: a cross-sectional study from 13 general hospitals.

    Korean J Intern Med. 2021;36(4):888-897.

    Abstract

    BACKGROUND/AIMS To examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients.

    METHODS We enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics.

    RESULTS Among 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses.

    CONCLUSION Apparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.

    PubMed IF 2.2 순환기내과
18. 34912021

    제1저자 오윤규 · 교신저자 오윤규

    Oh YK, Park HC, Ryu H, Kim YC, Oh KH

    Clinical and genetic characteristics of Korean autosomal dominant polycystic kidney disease patients.

    Korean J Intern Med. 2021;36(4):767-779.

    Abstract

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is characterized by cyst growth in the kidneys, resulting in kidney enlargement and end-stage kidney disease. The polycystic kidney disease 1 (PKD1) and PKD2 have been identified as genes related to ADPKD and their significance in the molecular pathology of the disease has been studied. A disease-modifying drug has been approved; therefore, it has become important to identify patients at a high risk of kidney disease progression. Genetic tests, image analysis methods, and clinical factors for kidney disease progression prediction have been established. This review describes genetic and clinical characteristics, and discusses ongoing studies in Korean ADPKD patients.

    PubMed IF 2.2 신장내과
19. 34902021

    제1저자 문정민 · 교신저자 임종필, 김동희

    Moon JM, Im JP, Kim D, Han YM, Soh H, Song JH, Yang SY, Kim YS, Yim JY, Lim SH, Kim JS

    Increasing changes in visceral adiposity is associated with higher risk for colorectal adenoma: Multilevel analysis in a prospective cohort.

    J Gastroenterol Hepatol. 2021;36(7):1836-1842.

    Abstract

    BACKGROUND AND AIM While many studies demonstrated an association between visceral adiposity and colorectal adenoma (CRA), the effect of longitudinal changes in body fat composition on CRA is unclear. We investigated the longitudinal association between changes in visceral adiposity and CRA occurrence.

    METHODS Between 2006 and 2018, 732 (62.8%) of the 1165 subjects in a prospective cohort voluntarily underwent follow-up abdominal fat computed tomography and colonoscopy. We defined incident and recurrent CRA as adenoma detected at follow-up colonoscopy from negative and positive adenoma at baseline colonoscopy, respectively. Multilevel survival analysis examined the longitudinal association between changes in visceral fat and CRA.

    RESULTS During a median follow-up of 7.4 years, 400 (54.6%) subjects developed CRA. In multivariable analysis, increasing changes in visceral adipose tissue (VAT) area were associated with higher risk of incident adenoma (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.00-1.46 for change per 10 cm² increase; HR 1.79, 95% CI 1.08-2.97 for highest vs lowest quartile, P values for trend = 0.045). Likewise, increasing changes in VAT area were independently associated with a higher risk of recurrent adenoma (HR 1.35, 95% CI 1.13-1.62 for change per 10 cm² increase; HR 1.62, 95% CI 1.04-2.52 for highest vs lowest quartile, P values for trend = 0.001). Changes in subcutaneous adipose tissue area were not independently associated with CRA.

    CONCLUSION Increasing changes in VAT area were longitudinally associated with a higher risk of incident and recurrent CRA, independent of risk factors, suggesting that visceral adiposity may be an important target in CRA prevention.

    PubMed IF 3.5 소화기내과
20. 34892021

    제1저자 이해영, 오규철 · 교신저자 조명찬

    Lee HY^*, Oh GC^*, Sohn IS, Park S, Shin J, Pyun WB, Cho MC

    Suboptimal Management Status of Younger Hypertensive Population in Korea.

    Korean Circ J. 2021;51(7):598-606.

    Abstract

    BACKGROUND AND OBJECTIVES Hypertension (HTN) is the most contributable risk factor for cardiovascular disease. May Measurement Month (MMM) is a global initiative to raise awareness of HTN and act as a temporary solution to the lack of screening programs worldwide.

    METHODS An opportunistic cross-sectional survey of participants aged ≥18 was carried out in May 2019. Over 10,000 participants were recruited in the MMM 2019 Korea, with a slogan of "A simple measure to save lives - #checkyourpressure."

    RESULTS A total of 9,950 participants with valid clinical blood pressure (BP) data were used for analysis. All participants were Korean in ethnicity. The mean age was 57.2±21.2 years, 57.8% were females, and the mean body mass index was 23.4±3.3 kg/m². Among the enrolled population, 20.1% were less than 30 years old, and 5.0% were 30-39 years old. 37.0% of the participants reported a previous diagnosis of HTN, and 91.3% of those diagnosed were on antihypertensive medications. Notably, more than 20% of the participants had not measured their BP during the last 12 months, and the awareness rate in the young hypertensive participants (aged <40) was less than 10%. Among hypertensive participants, the treatment rate was 69.3%, and the control rate among those taking medications was 61.2%.

    CONCLUSION MMM 2019 Korea campaign reported high BP control rates in individuals with HTN, reaching 60%. However, the awareness rate in young hypertensive participants was less than 10% along with suboptimal management status. The MMM 2019 Korea again raised the importance of regular BP measurement in the younger population.

    PubMed IF 3.4 순환기내과
21. 34882021

    제1저자 이해영 · 교신저자 김태현

    Lee HY, Lee SW, Kim HC, Ihm SH, Park SH, Kim TH

    Cost-Effectiveness Analysis of Hypertension Screening in the Korea National Health Screening Program.

    Korean Circ J. 2021;51(7):610-622.

    Abstract

    BACKGROUND AND OBJECTIVES To evaluate the cost-effectiveness of routine hypertension (HTN) screening as a part of the national health-screening program.

    METHODS Two aspects of cost-effectiveness were examined using the national general health-screening program. First, the cost of case-finding was computed for 5-year interval age groups. Second, the cost per quality adjusted life years (QALYs) gained were estimated for 12 different scenarios varying examination starting age, pattern and interval compared with no screening.

    RESULTS The cost of finding one new HTN case was low as 26,284 Korean won (KRW) (approximately [approx.] United States Dollar 21) for 70-79 years old to as high as 70,552 KRW for 40-44 years old. Compared with no screening, the costs per QALYs of the following screening strategies were below the incremental cost-effectiveness ratio threshold (approx. KRW 30.5 million): first screening examination with the second confirmatory examination in adults aged ≥40 years every 3 years (KRW 10.2 million), every 2 years (KRW 13.2 million), or annually (KRW 19.9 million). One-way sensitivity analyses suggest that the results were mostly influenced by the sensitivity of the first screening examination, followed by the examination rate of the second confirmatory examination.

    CONCLUSIONS HTN screening as a part of routine national health screening program was cost-effective for adults aged 40 years or older. The most cost-effective HTN screening strategy was the first screening examination with the second confirmatory examination in aged 40 years or older every 3 years.

    PubMed IF 3.4 순환기내과
22. 34872021

    제1저자 정고은, 조은주 · 교신저자 한경도, 유수종

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

    Nonalcoholic fatty liver disease is associated with the development of obstructive sleep apnea.

    Sci Rep. 2021;11(1):13473.

    Abstract

    Increasing evidence suggests that obstructive sleep apnea (OSA) is a metabolic syndrome-related disease; however, the association between nonalcoholic fatty liver disease (NAFLD) and OSA is not firmly established. In this study, we investigated the relationship between NAFLD and OSA in a general population drawn from a nationwide population-based cohort. Data from the Korean National Health Insurance System between January 2009 and December 2009 were analyzed using Cox proportional hazards model. NAFLD was defined as a fatty liver index (FLI) ≥ 60 in patients without excessive alcohol consumption (who were excluded from the study). Newly diagnosed OSA during follow-up was identified using claims data. Among the 8,116,524 participants, 22.6% had an FLI score of 30-60 and 11.5% had an FLI ≥ 60. During median follow-up of 6.3 years, 45,143 cases of incident OSA occurred. In multivariable analysis, the risk of OSA was significantly higher in the higher FLI groups (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.12-1.18 for FLI 30-60 and aHR 1.21, 95% CI 1.17-1.26 for FLI ≥ 60). These findings were consistent regardless of body mass index and presence of abdominal obesity. In conclusion, a high FLI score may help identify individuals with a high risk of OSA. Understanding the association between NAFLD and OSA may have clinical implications for risk-stratification of individuals with NAFLD.

    PubMed IF 4.9 소화기내과
23. 34862021

    제1저자 구본권, 강지훈, 박경우 · 교신저자 김효수

    Koo BK, Kang J, Park KW, Rhee TM, Yang HM, Won KB, Rha SW, Bae JW, Lee NH, Hur SH, Yoon J, Park TH, Kim BS, Lim SW, Cho YH, Jeon DW, Kim SH, Han JK, Shin ES, Kim HS, HOST-EXAM investigators

    Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial.

    Lancet. 2021;397(10293):2487-2496.

    Abstract

    BACKGROUND Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population.

    METHODS We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250.

    FINDINGS Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035).

    INTERPRETATION Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events.

    FUNDING ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.

    PubMed IF 109 순환기내과
24. 34852021

    제1저자 송진희 · 교신저자 김나영

    Song CH, Kim N, Nam RH, Choi SI, Yu JE, Nho H, Surh YJ

    Changes in Microbial Community Composition Related to Sex and Colon Cancer by Nrf2 Knockout.

    Front Cell Infect Microbiol. 2021;11:636808.

    Abstract

    The frequency of azoxymethane/dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in male mice is higher than that in female mice. Previous studies have reported that 17β-estradiol inhibits tumorigenesis in males by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2). This study aimed to investigate the changes in mouse gut microbiome composition based on sex, AOM/DSS-induced colorectal cancer (CRC), and Nrf2 genotype. The gut microbiome composition was determined by 16S rRNA gene sequencing fecal samples obtained at week 16 post-AOM administration. In terms of sex differences, our results showed that the wild-type (WT) male control mice had higher alpha diversity (i.e. Chao1, Shannon, and Simpson) than the WT female control mice. The linear discriminant analysis effect size (LEfSe) results revealed that the abundances of Akkermansia muciniphila and Lactobacillus murinus were higher in WT male control mice than in WT female controls. In terms of colon tumorigenesis, the alpha diversity of the male CRC group was lower than that of the male controls in both WT and Nrf2 KO, but did not show such changes in females. Furthermore, the abundance of A. muciniphila was higher in male CRC groups than in male controls in both WT and Nrf2 KO. The abundance of Bacteroides vulgatus was higher in WT CRC groups than in WT controls in both males and females. However, the abundance of L. murinus was lower in WT female CRC and Nrf2 KO male CRC groups than in its controls. The abundance of A. muciniphila was not altered by Nrf2 KO. In contrast, the abundances of L. murinus and B. vulgatus were changed differently by Nrf2 KO depending on sex and CRC. Interestingly, L. murinus showed negative correlation with tumor numbers in the whole colon. In addition, B. vulgatus showed positive correlation with inflammatory markers (i.e. myeloperoxidase and IL-1β levels), tumor numbers, and high-grade adenoma, especially, developed mucosal and submucosal invasive adenocarcinoma at the distal part of the colon. In conclusion, Nrf2 differentially alters the gut microbiota composition depending on sex and CRC induction.

    PubMed IF 5.5 소화기내과
25. 34842021

    제1저자 신철민 · 교신저자 이동호

    Shin CM, Choi YJ, Lee DH, Moon JS, Kim TY, Kim YK, Lee WH, Yoon H, Park YS, Kim N

    Validity and safety of ID-JPL934 in lower gastrointestinal symptom improvement.

    Sci Rep. 2021;11(1):13046.

    Abstract

    The study evaluated the efficacy of ID-JPL934, a probiotic preparation containing Lactobacillus johnsonii IDCC 9203, Lactobacillus plantarum IDCC 3501 and Bifidobacterium lactis IDCC 4301, in relieving lower gastrointestinal symptoms. A total of 112 subjects with lower gastrointestinal symptoms were consecutively enrolled. They were randomized into either ID-JPL934 administration group or placebo group. Bristol stool form, stool frequency, and abnormal bowel movement symptoms were recorded at baseline and week 2, 6, and 8. Primary endpoint was improvement in overall symptoms at week 8. Fecal samples were collected to measure the probiotic levels in feces using quantitative polymerase chain reaction (qPCR), and to perform metagenomic analysis of microbiome originating from bacteria-derived extracellular vesicles and bacterial cells via 16S rDNA sequencing. Of the 112 subjects, 104 (54 in ID-JPL934 group and 50 in placebo group) completed the entire study protocol. A higher relief of overall symptoms was found in ID-JPL934 group than in placebo group (p = 0.016). Among lower gastrointestinal symptoms, abdominal pain and bloating scores were more decreased in ID-JPL934 group than in placebo group (p < 0.05). The fecal microbiome profiles of the two groups did not differ. However, the qPCR analysis showed significant increase in the levels of Lactobacillus johnsonii and Bifidobacterium lactis in feces post-treatment in ID-JPL934 group than in placebo group (p < 0.05 by repeated measure ANOVA). In conclusion, ID-JPL934 is effective in relieving lower gastrointestinal symptoms. Exposure to ID-JPL934 may increase the abundance of Lactobacillus johnsonii and Bifidobacterium lactis in the gut.Trial registration: ClinicalTrials.gov number, NCT03395626.

    PubMed IF 4.9 소화기내과
26. 34832021

    제1저자 이은영, 황우창 · 교신저자 김남중, 박진균

    Lee EE^*, Hwang W^*, Song KH, Jung J, Kang CK, Kim JH, Oh HS, Kang YM, Lee EB, Chin BS, Song W, Kim NJ, Park JK

    Predication of oxygen requirement in COVID-19 patients using dynamic change of inflammatory markers: CRP, hypertension, age, neutrophil and lymphocyte (CHANeL).

    Sci Rep. 2021;11(1):13026.

    Abstract

    The objective of the study was to develop and validate a prediction model that identifies COVID-19 patients at risk of requiring oxygen support based on five parameters: C-reactive protein (CRP), hypertension, age, and neutrophil and lymphocyte counts (CHANeL). This retrospective cohort study included 221 consecutive COVID-19 patients and the patients were randomly assigned randomly to a training set and a test set in a ratio of 1:1. Logistic regression, logistic LASSO regression, Random Forest, Support Vector Machine, and XGBoost analyses were performed based on age, hypertension status, serial CRP, and neutrophil and lymphocyte counts during the first 3 days of hospitalization. The ability of the model to predict oxygen requirement during hospitalization was tested. During hospitalization, 45 (41.8%) patients in the training set (n = 110) and 41 (36.9%) in the test set (n = 111) required supplementary oxygen support. The logistic LASSO regression model exhibited the highest AUC for the test set, with a sensitivity of 0.927 and a specificity of 0.814. An online risk calculator for oxygen requirement using CHANeL predictors was developed. "CHANeL" prediction models based on serial CRP, neutrophil, and lymphocyte counts during the first 3 days of hospitalization, along with age and hypertension status, provide a reliable estimate of the risk of supplement oxygen requirement among patients hospitalized with COVID-19.

    PubMed IF 4.9 감염내과
27. 34822021

    제1저자 조영윤 · 교신저자 김윤준

    Cho YY, Yu SJ, Lee HW, Kim DY, Kang W, Paik YH, Sung PS, Bae SH, Park SC, Doh YS, Kim KM, Jang ES, Kim IH, Kim W, Kim YJ

    Clinical Characteristics of Long-Term Survivors After Sorafenib Treatment for Unresectable Hepatocellular Carcinoma: A Korean National Multicenter Retrospective Cohort Study.

    J Hepatocell Carcinoma. 2021;8:613-623.

    Abstract

    BACKGROUND/AIM Sorafenib is the first systemic therapy for the treatment of advanced-stage hepatocellular carcinoma (HCC) and progressive HCC after locoregional therapy. The aim of this study was to evaluate the prognostic factors of long-term survivors after sorafenib treatment.

    METHODS This multicenter, retrospective, cohort study included 1,566 unresectable HCC patients who received sorafenib treatment between 2007 and 2014 in nine tertiary centers in Korea. The patients were classified into a long-term survivor group (survival more than two years, n = 257) or a control group (n = 1309). The primary outcomes were the prognostic factors affecting long-term survival. Secondary endpoints included time-to-progression and other safety profiles.

    RESULTS The patients were predominantly men (83.8%) with chronic hepatitis B (77.3%) and Barcelona clinic of liver cancer-stage C (BCLC-C) (78.3%). The median overall survival was 9.0 months. After treatment, eight patients (0.4%) achieved complete response and 139 patients (8.8%) achieved partial response according to the mRECIST criteria. The prognostic factors predicting long-term survival were metformin use (adjusted hazard ratio [aHR] = 3.464; P < 0.001), hand-foot skin reaction (aHR = 1.688; P = 0.003), and concomitant treatment with chemoembolization or radiotherapy (aHR = 2.766; P < 0.001). Poor prognostic factors of long-term survival were a Child-Pugh score of B (HR = 0.422; P < 0.001), the presence of extrahepatic metastasis (HR = 0.639; P = 0.005), main portal vein invasion (HR = 0.502; P = 0.001), and elevated alpha-fetoprotein (>1,000 ng/mL; HR = 0.361; P < 0.001).

    CONCLUSION This large, multicenter, retrospective study showed an objective response rate of 9.1% and a proportion of long-term survivors of 16.4% in Korean patients. The prognostic factors derived in our study can be used in clinical practice during sorafenib treatment.

    PubMed IF 3.9 소화기내과
28. 34812021

    제1저자 이현정 · 교신저자 김형관

    Lee HJ, Kim HK, Kim BS, Han KD, Park JB, Lee H, Lee SP, Kim YJ

    Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy.

    PLoS One. 2021;16(6):e0253310.

    Abstract

    BACKGROUND Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs.

    METHODS Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013-2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke.

    RESULTS During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65-0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation.

    CONCLUSION In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

    PubMed IF 2.8 순환기내과
29. 34802021

    제1저자 박준빈 · 교신저자 김형관, 한경도

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

    Effect of Moderately but Persistently Elevated Lipid Levels on Risks of Stroke and Myocardial Infarction in Young Korean Adults.

    J Am Heart Assoc. 2021;10(12):e020050.

    Abstract

    Background Identifying predictive markers for future atherosclerotic cardiovascular diseases may be helpful to motivate young adults to promote healthy lifestyle. We sought to determine the association between persistently elevated low-density lipoprotein-cholesterol (LDL-C) and/or triglyceride levels and the atherosclerotic cardiovascular diseases risks in young adults. Methods and Results We conducted a nationwide population-based cohort study of 1 887 853 statin-naive adults aged 20 to 39 years, with LDL-C <190 mg/dL, using the Korean National Health Insurance Service database. Persistently elevated LDL-C and triglyceride levels were defined by ≥3 measurements of ≥160 and ≥175 mg/dL, respectively. The primary outcome was a composite of stroke and myocardial infarction. Among the study population, 11 121 (0.59%) and 167 373 (8.87%) had persistently elevated LDL-C and triglycerides, respectively. During a median follow-up of 5.2 years, 2170 and 1537 incidences of stroke (0.16%) and myocardial infarction (0.23%) occurred. Persistently elevated LDL-C levels were significantly associated with increased risks of the primary outcome, with an adjusted hazard ratio (HR) of 1.396 (95% CI, 1.005-1.940). This association was independent of high-density lipoprotein cholesterol. Persistently elevated triglycerides were significantly associated with increased risks of the primary outcome (HR, 1.120; 95% CI, 1.015-1.236), but attenuated after adjustment for high-density lipoprotein cholesterol. Conclusions Persistently elevated LDL-C and triglyceride levels were associated with atherosclerotic cardiovascular diseases risk in young Korean adults without severe hypercholesterolemia. These lipid abnormalities should be considered risk factors in young adults since their effects on lifetime atherosclerotic cardiovascular diseases risk may become more pronounced over the life course.

    PubMed IF 6 순환기내과
30. 34792021

    제1저자 송진희 · 교신저자 김나영

    Song CH, Kim N, Nam RH, Choi SI, Yu JE, Nho H, Shin E, Lee HN, Surh YJ

    Testosterone strongly enhances azoxymethane/dextran sulfate sodium-induced colorectal cancer development in C57BL/6 mice.

    Am J Cancer Res. 2021;11(6):3145-3162.

    Abstract

    Colorectal cancer (CRC) is known to occur more frequently in males than in females, with sex hormones reportedly influencing the development. The purpose of the study was to investigate whether orchiectomy in C57BL/6 male mice reduces colorectal tumorigenesis and whether testosterone administration increases tumorigenesis after orchiectomy in an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. Clinical symptoms, including colitis and tumor incidence, were evaluated in the absence or presence of testosterone in AOM/DSS-treated male, as well as orchiectomized (ORX) male and female mice. The levels of serum testosterone and colonic myeloperoxidase, interleukin (IL)-1β, and IL-6 were measured by ELISA. Target mRNA expression was assessed by quantitative real-time PCR. Orchiectomy significantly diminished the AOM/DSS-induced colitis indices, including disease activity index, colon shortening, and histological severity at week 2, and decreased tumor numbers and incidence rates in the distal part of the colon increased following AOM/DSS administration at week 13; this reduction was reversed by testosterone supplementation. Furthermore, it was confirmed that the ELISA level (MPO and IL-1β) and the mRNA expression of the inflammatory mediators (COX-2 and iNOS) were maintained at high levels in the tumors of the testosterone-treated group compared with AOM/DSS groups. Interestingly, both endogenous and exogenous testosterone administrations were associated with tumor development (> 2 mm in size) and submucosal invasive cancer. Based on multivariate logistic regression analysis, testosterone was identified as a reasonable hazard factor for the progression of submucosal invasive cancer of the distal colon. In conclusion, endogenous and exogenous testosterone presented a stimulating effect on AOM/DSS-induced colitis and carcinogenicity.

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