SCI 발표논문

1. 252022

   제1저자 남준열, 정형진, 최규성, 이혁 · 교신저자 정현수, 이정훈

   Nam JY, Chung HJ, Choi KS, Lee H, Kim TJ, Soh H, Kang EA, Cho SJ, Ye JC, Im JP, Kim SG, Kim JS, Chung H, Lee JH

   Deep learning model for diagnosing gastric mucosal lesions using endoscopic images: development, validation, and method comparison.

   Gastrointest Endosc. 2022;95(2):258-268.e10.

   Abstract

   BACKGROUND AND AIMS Endoscopic differential diagnoses of gastric mucosal lesions (benign gastric ulcer, early gastric cancer [EGC], and advanced gastric cancer) remain challenging. We aimed to develop and validate convolutional neural network-based artificial intelligence (AI) models: lesion detection, differential diagnosis (AI-DDx), and invasion depth (AI-ID; pT1a vs pT1b among EGC) models.

   METHODS This study included 1366 consecutive patients with gastric mucosal lesions from 2 referral centers in Korea. One representative endoscopic image from each patient was used. Histologic diagnoses were set as the criterion standard. Performance of the AI-DDx (training/internal/external validation set, 1009/112/245) and AI-ID (training/internal/external validation set, 620/68/155) was compared with visual diagnoses by independent endoscopists (stratified by novice [<1 year of experience], intermediate [2-3 years of experience], and expert [>5 years of experience]) and EUS results, respectively.

   RESULTS The AI-DDx showed good diagnostic performance for both internal (area under the receiver operating characteristic curve [AUROC] = .86) and external validation (AUROC = .86). The performance of the AI-DDx was better than that of novice (AUROC = .82, P = .01) and intermediate endoscopists (AUROC = .84, P = .02) but was comparable with experts (AUROC = .89, P = .12) in the external validation set. The AI-ID showed a fair performance in both internal (AUROC = .78) and external validation sets (AUROC = .73), which were significantly better than EUS results performed by experts (internal validation, AUROC = .62; external validation, AUROC = .56; both P < .001).

   CONCLUSIONS The AI-DDx was comparable with experts and outperformed novice and intermediate endoscopists for the differential diagnosis of gastric mucosal lesions. The AI-ID performed better than EUS for evaluation of invasion depth.

   PubMed IF 8 소화기내과
2. 242022

   제1저자 이주엽 · 교신저자 김나영

   Lee JY, Kim N, Park JH, Yu JE, Song YJ, Yoon JW, Lee DH

   Sex and Gender Differences in Overlap Syndrome of Functional Gastrointestinal Disorder and Effect of Genetic Polymorphisms in South Korea: A Long-term Follow-up Study.

   J Neurogastroenterol Motil. 2022;28(1):145-158.

   Abstract

   BACKGROUND/AIMS Overlap functional gastrointestinal disorder (FGID) is associated with more severe gastrointestinal symptoms and lower quality of life. The aim of this study is to evaluate clinical features of non-erosive reflux disease (NERD), functional dyspepsia, irritable bowel syndrome, their overlap in terms of sex and gender, and to assess the risk factors, including genetic polymorphisms.

   METHODS A total of 494 FGIDs and 239 controls were prospectively enrolled between 2004 and 2020. FGIDs were diagnosed based on the Rome III criteria and symptoms were evaluated using a questionnaire. Follow-up questionnaires were conducted to determine the change of symptoms during the 75.8-month mean observation period. Risk factors including genetic polymorphisms in neurotransmitter receptor (SLC6A4 5-HTTLPR, GNB3, ADRA2A, CCKAR, and TRPV1) and cytokine (TNFA and IL10) genes.

   RESULTS NERD was more prevalent in men, and functional dyspepsia in women. Overlap FGIDs (n = 239) were more prevalent than nonoverlap FGIDs (n = 255) in women (P = 0.019). Anxiety and depression scores were higher in the overlaps (P = 0.012 and P < 0.001, respectively). Symptoms were more frequent and severe in the overlap FGIDs than in the non-overlaps (P < 0.001). During followup, symptoms progressed more frequently in the overlap FGIDs, especially in patients with the L/S genotype of SLC6A4 5-HTTLPR and anxiety/depression.

   CONCLUSIONS Overlap FGID patients need attention given their association with anxiety/depression and more severe symptoms, especially in women. Genetic polymorphisms also may be associated with certain symptoms of overlap FGIDs.

   PubMed IF 3.7 소화기내과
3. 232022

   제1저자 박현경, 변자민 · 교신저자 고영일, 윤성수

   Park H, Byun JM, Yoon SS, Koh Y, Yoon SW, Shin DY, Hong J, Kim I

   Cyclophosphamide addition to pomalidomide/dexamethasone is not necessarily associated with universal benefits in RRMM.

   PLoS One. 2022;17(1):e0260113.

   Abstract

   In the backdrop of rapidly changing relapsed/refractory (RR) multiple myeloma (MM) treatment schema that mainly evolves around immunotherapies, it is easy to disregard more traditional drugs. Finding the best partner for pomalidomide, a potent third-generation immunomodulatory drug, is an important agenda we face as a community and cyclophosphamide addition has been used for outcomes augmentation. We carried out this real-world study to identify patients who will show durable response to pomalidomide and those who will benefit from cyclophosphamide addition. A total of 103 patients (57 in pomalidomide-dexamethasone [Pd] group versus 46 in pomalidomide-cyclophosphamide-dexamethasone [PCd]) were studied. They were previously treated with bortezomib (98.1%) or lenalidomide (100%) and previous lines of therapy were median 3 lines. Significantly better overall response rate (ORR) was seen in the PCd (75.6%) than Pd (41.7%) group (p = 0.001), but no differences in survival outcomes. Subgroup analysis revealed that high-risk myeloma features, poor response to lenalidomide or bortezomib had superior ORRs when cyclophosphamide was added. Also, long-term responders for pomalidomide were associated with excellent response to previous IMiD treatments. Pomalidomide-based therapy was discontinued in five patients due to intolerance or adverse events, but there was no mortality during treatment. In conclusion, we showed that pomalidomide-based treatment is still relevant and can ensure durable response in RRMM setting, especially for patients who responded well to previous lenalidomide. Addition of cyclophosphamide to Pd is associated with better ORR, and can be positively considered in fit patients with high-risk MM, extramedullary disease, and less-than-satisfactory response to previous lenalidomide treatment.

   PubMed IF 2.8 혈액종양내과
4. 222022

   제1저자 박지혜 · 교신저자 윤혁

   Park J, Yoon H, Shin CM, Park YS, Kim N, Lee DH

   Clinical factors to predict flare-up in patients with inflammatory bowel disease during international air travel: A prospective study.

   PLoS One. 2022;17(1):e0262571.

   Abstract

   BACKGROUNDS AND AIMS Inflammatory bowel disease (IBD) patients often experience disease flare-ups during international air travel. We aimed to identify risk factors associated with IBD flare-up during international air travel.

   METHODS Patients with scheduled international air travel were enrolled in the study from the Seoul National University Bundang Hospital IBD clinic. Flight information and clinical data were collected via questionnaires and personal interviews, and risk factors associated with IBD flares were determined.

   RESULTS Between May 2018 and February 2020, 94 patients were prospectively enrolled in the study (mean age, 33.0 years; males, 53.2%; mean disease duration, 56.7 months), including 56 (59.6%) with ulcerative colitis and 38 (40.4%) with Crohn's disease. Of the 94 patients enrolled, 15 (16.0%) experienced an IBD flare-up and 79 (84.0%) remained in remission throughout travel. Logistic regression analysis revealed that high fecal calprotectin levels before travel (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000-1.001, p = 0.016), the presence of a comorbidity (OR: 6.334, 95% CI: 1.129-35.526, p = 0.036), and history of emergency room visit (OR: 5.283, 95% CI: 1.085-25.724, p = 0.039) were positively associated with disease flare-up. The previous and current use of immunomodulators and biologics, time of flight, altitude, number countries visited, travel duration, objective of visit, and previous medical consultations were not associated with disease flare-up.

   CONCLUSIONS Elevated fecal calprotectin levels, history of emergency room visits, and the presence of a comorbidity predicted IBD flare-up during international air travel.

   PubMed IF 2.8 소화기내과
5. 212022

   제1저자 남진안 · 교신저자 정성수, 박경수

   Nan J, Lee JS, Moon JH, Lee SA, Park YJ, Lee DS, Chung SS, Park KS

   SENP2 regulates mitochondrial function and insulin secretion in pancreatic β cells.

   Exp Mol Med. 2022;54(1):72-80.

   Abstract

   Increasing evidence has shown that small ubiquitin-like modifier (SUMO) modification plays an important role in metabolic regulation. We previously demonstrated that SUMO-specific protease 2 (SENP2) is involved in lipid metabolism in skeletal muscle and adipogenesis. In this study, we investigated the function of SENP2 in pancreatic β cells by generating a β cell-specific knockout (Senp2-βKO) mouse model. Glucose tolerance and insulin secretion were significantly impaired in the Senp2-βKO mice. In addition, glucose-stimulated insulin secretion (GSIS) was decreased in the islets of the Senp2-βKO mice without a significant change in insulin synthesis. Furthermore, islets of the Senp2-βKO mice exhibited enlarged mitochondria and lower oxygen consumption rates, accompanied by lower levels of S616 phosphorylated DRP1 (an active form of DRP1), a mitochondrial fission protein. Using a cell culture system of NIT-1, an islet β cell line, we found that increased SUMO2/3 conjugation to DRP1 due to SENP2 deficiency suppresses the phosphorylation of DRP1, which possibly induces mitochondrial dysfunction. In addition, SENP2 overexpression restored GSIS impairment induced by DRP1 knockdown and increased DRP1 phosphorylation. Furthermore, palmitate treatment decreased phosphorylated DRP1 and GSIS in β cells, which was rescued by SENP2 overexpression. These results suggest that SENP2 regulates mitochondrial function and insulin secretion at least in part by modulating the phosphorylation of DRP1 in pancreatic β cells.

   PubMed IF 17.5 내분비대사내과
6. 202022

   제1저자 안수민 · 교신저자 황진혁

   Ahn S, Lee JC, Kim J, Kim YH, Yoon YS, Han HS, Kim H, Hwang JH

   Four-Tier Pathologic Tumor Regression Grading System Predicts the Clinical Outcome in Patients Who Undergo Surgical Resection for Locally Advanced Pancreatic Cancer after Neoadjuvant Chemotherapy.

   Gut Liver. 2022;16(1):129-137.

   Abstract

   BACKGROUND/AIMS Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response.

   METHODS We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems.

   RESULTS One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333).

   CONCLUSIONS The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.

   PubMed IF 4.1 소화기내과
7. 192022

   제1저자 이계화 · 교신저자 강혜련

   Lee KH, Kang DY, Kim HH, Kim YJ, Kim HJ, Kim JH, Song EY, Yun J, Kang HR

   Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored human leukocyte antigen genotypes.

   Clin Transl Allergy. 2022;12(1):e12098.

   Abstract

   BACKGROUND Several type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre-stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre-stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs.

   METHODS We analyzed the incidence and the risk of ADRs for selected HLA alleles (HLA-B*57:01, HLA-B*58:01, HLA-A*31:01, HLA-B*15:02, HLA-B*15:11, HLA-B*13:01, HLA-B*59:01, and HLA-A*32:01) and seven drugs (abacavir, allopurinol, carbamazepine, oxcarbazepine, dapsone, methazolamide, and vancomycin) using pre-stored HLA information of transplant patients based on the Pharmacogenomics Knowledge Base guidelines and experts' consensus.

   RESULTS Among 11,988 HLA-tested transplant patients, 4092 (34.1%) had high-risk HLA alleles, 4583 (38.2%) were prescribed risk drugs, and 580 (4.8%) experienced type B ADRs. Patients with HLA-B*58:01 had a significantly higher incidence of type B ADR and SCARs associated with allopurinol use than that of patients without HLA-B*58:01 (17.2% vs. 11.9%, odds ratio [OR] 1.53 [95% confidence interval {CI} 1.09-2.13], p = 0.001, 2.3% versus 0.3%, OR 7.13 [95% CI 2.19-22.69], p < 0.001). Higher risks of type B ADR and SCARs were observed in patients taking carbamazepine or oxcarbazepine if they had one of HLA-A*31:01, HLA-B*15:02, or HLA-B*15:11 alleles. Vancomycin and dapsone use in HLA-A*32:01 and HLA-B*13:01 carriers, respectively, showed trends toward increased risk of type B ADRs.

   CONCLUSION Utilization of pre-stored HLA data can prevent type B ADRs including SCARs by screening high-risk patients.

   PubMed IF 4.2 알레르기내과
8. 182022

   제1저자 이권풍 · 교신저자 김학령

   Lee GP, Kim HL

   Incremental value of the measures of arterial stiffness in cardiovascular risk assessment.

   Rev Cardiovasc Med. 2022;23(1):6.

   Abstract

   Predicting the occurrence of organ damage and future cardiovascular events is critical to improving patient prognosis through early personalized treatment. Although many tools have been developed and used for individuals' cardiovascular risk, they have limitations and unmet needs for improved risk stratification. For this purpose, arterial stiffness information can be practical. Arterial walls stiffen with age or prolonged exposure to various noxious stimuli such as high blood pressure, hyperglycemia, inflammation and oxidative stress. Differently from several methods of measuring arterial stiffness, pulse wave velocity (PWV) is most widely used for its non-invasive and easy measurement. It is well authorized that information on arterial stiffness is associated with the development of future cardiovascular events, independent from traditional cardiovascular risk factors, in various patient groups with specific diseases along with the general population. Moreover, when this information of arterial stiffness is associated with other risk stratification tools, it is possible to predict individuals' cardiovascular risk easier. Herein, we will review the incremental value of the measurement of arterial stiffness in cardiovascular risk assessment when combined with other risk factors such as traditional risk factors, biomarkers, other vascular testing and non-invasive cardiac imaging.

   PubMed IF 2.2 순환기내과
9. 172022

   제1저자 김민강, 윤동환 · 교신저자 한승석, 이동섭

   Kim MG, Yun D, Kang CL, Hong M, Hwang J, Moon KC, Jeong CW, Kwak C, Kim DK, Oh KH, Joo KW, Kim YS, Lee DS, Han SS

   Kidney VISTA prevents IFN-γ/IL-9 axis-mediated tubulointerstitial fibrosis after acute glomerular injury.

   J Clin Invest. 2022;132(1):151189.

   Abstract

   Severe glomerular injury ultimately leads to tubulointerstitial fibrosis that determines patient outcome, but the immunological molecules connecting these processes remain undetermined. The present study addressed whether V-domain Ig suppressor of T cell activation (VISTA), constitutively expressed in kidney macrophages, plays a protective role in tubulointerstitial fibrotic transformation after acute antibody-mediated glomerulonephritis. After acute glomerular injury using nephrotoxic serum, tubules in the VISTA-deficient (Vsir-/-) kidney suffered more damage than those in WT kidneys. When interstitial immune cells were examined, the contact frequency of macrophages with infiltrated T cells increased and the immunometabolic features of T cells changed to showing high oxidative phosphorylation and fatty acid metabolism and overproduction of IFN-γ. The Vsir-/- parenchymal tissue cells responded to this altered milieu of interstitial immune cells as more IL-9 was produced, which augmented tubulointerstitial fibrosis. Blocking antibodies against IFN-γ and IL-9 protected the above pathological process in VISTA-depleted conditions. In human samples with acute glomerular injury (e.g., antineutrophil cytoplasmic autoantibody vasculitis), high VISTA expression in tubulointerstitial immune cells was associated with low tubulointerstitial fibrosis and good prognosis. Therefore, VISTA is a sentinel protein expressed in kidney macrophages that prevents tubulointerstitial fibrosis via the IFN-γ/IL-9 axis after acute antibody-mediated glomerular injury.

   PubMed IF 14.3 신장내과
10. 162022

    제1저자 김학령 · 교신저자 김명아

    Kim HL, Kim HJ, Kim M, Park SM, Yoon HJ, Byun YS, Park SM, Shin MS, Hong KS, Kim MA

    Sex differences in coronary angiographic findings in patients with stable chest pain: analysis of data from the KoRean wOmen'S chest pain rEgistry (KoROSE).

    Biol Sex Differ. 2022;13(1):2.

    Abstract

    BACKGROUND Focused evaluations on potential sex differences in the angiographic findings of the coronary arteries are scarce. This study was performed to compare the angiographic extent and localization of coronary stenosis between men and women.

    METHODS A total of 2348 patients (mean age 62.5 years and 60% women) with stable chest pain undergoing invasive coronary angiography (CAG) were recruited from the database of the nation-wide chest pain registry. Obstructive coronary artery disease (CAD) was defined as ≥ 50% stenosis of the left main coronary artery and/or ≥ 70% stenosis of any other epicardial coronary arteries.

    RESULTS Although women were older than men (64.4 ± 10.3 vs. 59.5 ± 11.4 years, P < 0.001), men had worse risk profiles including high blood pressure, more frequent smoking and elevated triglyceride and C-reactive protein. The prevalence of obstructive CAD was significantly higher in men than in women (37.0% vs. 28.4%, P < 0.001). Men had a higher prevalence of LM disease (10.3% vs. 3.5%, P < 0.001) and three-vessel disease (16.1% vs. 9.5%, P = 0.007) compared to women. In multiple binary logistic regression analysis, the risk of men having LM disease or three-vessel disease was 7.4 (95% confidence interval 3.48-15.97; P < 0.001) and 2.7 (95% confidence interval 1.57-4.64; P < 0.001) times that of women, respectively, even after controlling for potential confounders.

    CONCLUSIONS In patients with chest pain undergoing invasive CAG, men had higher obstructive CAD prevalence and more high-risk angiographic findings such as LM disease or three-vessel disease.

    PubMed IF 5.3 순환기내과
11. 152022

    제1저자 이학승 · 교신저자 박경우

    Lee HS, Park KW, Kang J, Han JK, Kim HS

    De-escalation of Prasugrel Results in Higher Percentage of Patients within Optimal Range of Platelet Reactivity: Analysis from the HOST-REDUCE-POLYTECH-ACS Trial.

    Thromb Haemost. 2022;122(1):160-162.

    PubMed IF 5.2 순환기내과
12. 142022

    제1저자 장한나 · 교신저자 정혜승

    Jang HN, Yang YS, Oh TJ, Koo BK, Lee SO, Park KS, Jang HC, Jung HS

    Low fasting glucose-to-estimated average glucose ratio was associated with superior response to insulin degludec/aspart compared with basal insulin in patients with type 2 diabetes.

    J Diabetes Investig. 2022;13(1):85-93.

    Abstract

    AIMS/INTRODUCTION The benefits of once-daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established.

    MATERIALS AND METHODS This was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once-daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated.

    RESULTS The IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C-peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P < 0.001). Considering that the lower FPG despite the comparable HbA1c could be related with the efficacy of IDegAsp, subgroup analysis was carried out according to a ratio of FPG-to-estimated average glucose, which is calculated from HbA1c. When compared with each control group, the superiority of IDegAsp in the reduction of HbA1c was significant only in the patients with a lower FPG-to-estimated average glucose ratio (0.49 ± 0.09), but not in those with a higher FPG-to-estimated average glucose ratio (0.79 ± 0.20).

    CONCLUSIONS We observed that IDegAsp was more effective than basal insulin in patients with an FPG lower than predicted by HbA1c, which might be related with insulin deficiency and postprandial hyperglycemia in patients on basal insulin therapy.

    PubMed IF 3.6 내분비대사내과
13. 132022

    제1저자 강혜나, 유현주 · 교신저자 김원, 고광표

    Kang H, You HJ, Lee G, Lee SH, Yoo T, Choi M, Joo SK, Park JH, Chang MS, Lee DH, Kim W, Ko G, Innovative Target Exploration of NAFLD (ITEN) consortium

    Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis.

    Gut Microbes. 2022;14(1):2078612.

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is associated with high carbohydrate (HC) intake. We investigated whether the relationship between carbohydrate intake and NAFLD is mediated by interactions between gut microbial modulation, impaired insulin response, and hepatic de novo lipogenesis (DNL). Stool samples were collected from 204 Korean subjects with biopsy-proven NAFLD (n = 129) and without NAFLD (n = 75). The gut microbiome profiles were analyzed using 16S rRNA amplicon sequencing. Study subjects were grouped by the NAFLD activity score (NAS) and percentage energy intake from dietary carbohydrate. Hepatic DNL-related transcripts were also analyzed (n = 90). Data from the Korean healthy twin cohort (n = 682), a large sample of individuals without NAFLD, were used for comparison and validation. A HC diet rather than a low carbohydrate diet was associated with the altered gut microbiome diversity according to the NAS. Unlike individuals from the twin cohort without NAFLD, the abundances of Enterobacteriaceae and Ruminococcaceae were significantly different among the NAS subgroups in NAFLD subjects who consumed an HC diet. The addition of these two microbial families, along with Veillonellaceae, significantly improved the diagnostic performance of the predictive model, which was based on the body mass index, age, and sex to predict nonalcoholic steatohepatitis in the HC group. In the HC group, two crucial regulators of DNL (SIRT1 and SREBF2) were differentially expressed among the NAS subgroups. In particular, kernel causality analysis revealed a causal effect of the abundance of Enterobacteriaceae on SREBF2 upregulation and of the surrogate markers of insulin resistance on NAFLD activity in the HC group. Consuming an HC diet is associated with alteration in the gut microbiome, impaired glucose homeostasis, and upregulation of hepatic DNL genes, altogether contributing to NAFLD pathogenesis.

    PubMed IF 15.3 소화기내과
14. 122022

    제1저자 강동윤, 이서영 · 교신저자 강혜련

    Kang DY, Lee SY, Ahn YH, Yoon SH, Choi YH, Lee W, Kang HR

    Incidence and risk factors of late adverse reactions to low-osmolar contrast media: A prospective observational study of 10,540 exposures.

    Eur J Radiol. 2022;146:110101.

    Abstract

    PURPOSE To evaluate the incidence and risk factors of late adverse reactions (ARs) to non-ionic low-osmolar contrast media (LOCM).

    METHODS The occurrence of late AR was monitored on day 1 and from day 7 to day 28 in all patients who received enhanced computed tomography using LOCM during a 5-week study period in a single tertiary hospital. Patients who experienced late AR were followed up for three years.

    RESULTS Among the total 10,540 LOCM exposures, 315 ARs (3.0%) were reported; acute ARs occurred in 108 LOCM exposures (1.0%) and late ARs occurred in 207 LOCM exposures (2.0%) (90.9% within one week, 9.1% developed afterwards by day 20). Previous history of drug allergy (odds ratio [OR] = 4.59; 95% confidence interval [CI] 2.17-9.71) and allergic diseases (OR = 2.54; 95% CI 1.32-4.91) were risk factors of late ARs to LOCM. Although the recurrence rate was lowered with premedication from 8.5% to 1.7% (8/94 vs. 3/178; p = 0.016), LOCM change did not make difference compared to reuse of the culprit LOCM (2/38 vs. 9/234; p = 0.655). In patients with a history of late AR to LOCM, the risk of recurrent reactions decreased with longer time intervals between exposures (OR = 0.86; 95% CI: 0.77-0.97; p = 0.025) and with the use of antihistamine premedication (OR = 0.27; 95% CI: 0.06-0.99; p = 0.049).

    CONCLUSIONS Late ARs to LOCM occurred mostly within one week. The use of premedication may be helpful in reducing the recurrence of late ARs.

    PubMed IF 3.9 알레르기내과
15. 112022

    제1저자 임주현 · 교신저자 신철민, 한경도

    Lim JH, Shin CM, Han K, Yoo J, Jin EH, Choi YJ, Lee DH

    Nationwide cohort study: cholesterol level is inversely related with the risk of gastric cancer among postmenopausal women.

    Gastric Cancer. 2022;25(1):11-21.

    Abstract

    BACKGROUND Recent studies showed inverse relationship between hypercholesterolemia and the risk of gastric cancer, especially among male. However evidence among female is inconsistent. We aimed to investigate the relationship between cholesterol level and the risk of gastric cancer among female according to menopausal status.

    METHODS We analyzed the data from a population-based prospective cohort of female ≥ 30 years old who underwent cancer screening and general health screening provided by the Korean National Health Insurance Corporation in 2009. Under quartile stratification of the level of cholesterol components, we calculated the hazard ratio (HR) for gastric cancer incidence until 2018 for each level group according to the menopausal status at 2009.

    RESULTS Among total 2,722,614 individuals, 17,649 gastric cancer cases developed after mean 8.26 years of follow-up (premenopausal 3746/1180666; postmenopausal 13,903/1541948). Total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) showed inverse relationship with the risk of gastric cancer among postmenopausal women (adjusted HR (95% confidence interval) for the highest quartile vs. lowest quartile and p-for-trend: 0.88 (0.84-0.92) and < 0.001 for total cholesterol; 0.89 (0.85-0.92) and < 0.001 for HDL-C; 0.92 (0.89-0.97) and 0.001 for LDL-C), whereas none showed statistically significant risk relationship among premenopausal women. Triglyceride was not independently related with gastric cancer risk among both pre- and postmenopausal women.

    CONCLUSIONS Cholesterol levels, including total cholesterol, HDL-C, and LDL-C, are inversely related with the risk of gastric cancer among postmenopausal women, but not among premenopausal women.

    PubMed IF 6.1 소화기내과
16. 102022

    제1저자 김혜린, 김경아 · 교신저자 정숙향

    Kim HL, Kim KA, Choi GH, Jang ES, Ki M, Choi HY, Jeong SH

    A cost-effectiveness study of universal screening for hepatitis C virus infection in South Korea: A societal perspective.

    Clin Mol Hepatol. 2022;28(1):91-104.

    Abstract

    BACKGROUND/AIMS This study aimed to evaluate the cost-effectiveness of hepatitis C virus (HCV) screening compared to no screening in the Korean population from societal and healthcare system perspectives.

    METHODS A published decision-tree plus Markov model was used to compare the expected costs and quality-adjusted life years (QALY) between one-time universal HCV screening and no screening in the population aged 40-65 years using the National Health Examination (NHE) program. Input parameters were obtained from analyses of the National Health Insurance claims data, Korean HCV cohort data, or from the literature review. The population aged 40-65 years was simulated in a model spanning a lifetime from both the healthcare system and societal perspectives, which included the cost of productivity loss due to HCV-related deaths. The incremental cost-effectiveness ratio (ICER) between universal screening and no screening was estimated.

    RESULTS The HCV screening strategy had an ICER of $2,666/QALY and $431/QALY from the healthcare system and societal perspectives, respectively. Both ICERs were far less than the willingness-to-pay threshold of $25,000/QALY, showing that universal screening was highly cost-effective compared to no screening. In various sensitivity analyses, the most influential parameters on cost-effectiveness were the antibodies to HCV (anti-HCV) prevalence, screening costs, and treatment acceptance; however, all ICERs were consistently less than the threshold. If the anti-HCV prevalence was over 0.18%, screening could be cost-effective.

    CONCLUSION One-time universal HCV screening in the Korean population aged 40-65 years using NHE program would be highly cost-effective from both healthcare system and societal perspectives.

    PubMed IF 21.7 소화기내과
17. 92022

    제1저자 김재형 · 교신저자 류지곤, 황진혁

    Kim JH, Youn Y, Lee JC, Kim J, Ryu JK, Hwang JH

    Downregulation of ASF1B inhibits tumor progression and enhances efficacy of cisplatin in pancreatic cancer.

    Cancer Biomark. 2022;34(4):647-659.

    Abstract

    Pancreatic cancer is an aggressive and lethal cancer with the highest mortality rate. Hence, the development of new targeting and innovative treatment strategies is needed. Recent studies reported that the histone chaperone anti-silencing function 1B (ASF1B) can be used as a diagnosis and prognosis cancer biomarker. However, functional studies of ASF1B in pancreatic cancer have not been performed. This study compared expression levels of ASF1B in pancreatic cancer specimens with those of normal tissues using publicly available online databases. We found that ASF1B was commonly overexpressed in pancreatic cancer specimens, which is associated with poor prognosis. ASF1B downregulation in pancreatic cancer cells reduced their colony formation, proliferation, migration, and invasion abilities, and inhibited MMP9 activity. Furthermore, ASF1B expression downregulation increased cell cycle S-phase arrest and DNA damage though activation of the checkpoint kinases Chk1 and Chk2 pathways. Additionally, increased caspase (caspases-3 and -9) activation and PARP cleavage led to enhanced caspase-dependent apoptosis and improved cisplatin sensitivity. Collectively, our results indicate that ASF1B may serve as a potential biomarker of pancreatic cancer and a novel therapeutic target.

    PubMed IF 1.8 소화기내과
18. 82022

    제1저자 인지원 · 교신저자 이하정, 송은영

    In JW, Jung K, Shin S, Park KU, Lee H, Song EY

    Association of HLA-DRB1 and -DQB1 Alleles with Susceptibility to IgA Nephropathy in Korean Patients.

    Ann Lab Med. 2022;42(1):54-62.

    Abstract

    BACKGROUND Associations between IgA nephropathy (IgAN) and HLA-DRB1 and -DQB1 alleles have been reported in several ethnic groups. We investigated the association of HLA-DRB1 and -DQB1 alleles with the predisposition for IgAN and disease progression to end-stage kidney disease (ESKD) in Korean patients.

    METHODS We analyzed HLA-DRB1 and -DQB1 genotypes in 399 IgAN patients between January 2000 and January 2019 using a LIFECODES sequence-specific oligonucleotide (SSO) typing kit (Immucor, Stamford, CT, USA) or a LABType SSO Typing Test (One Lambda, Canoga Park, CA, USA). Alleles with a significant difference in two-digit resolution were further analyzed using in-house sequence-based typing and sequence-specific primer PCR. As controls, 613 healthy hematopoietic stem cell donors were included. Kidney survival was analyzed in 281 IgAN patients with available clinical and laboratory data using Cox regression analysis. Where needed, P-values were adjusted using Bonferroni correction.

    RESULTS The allele frequencies of HLA-DRB1*04:05 (corrected P [Pc]<0.001), -DQB1 *04:01 (Pc=0.048), and -DQB1*03:02 (Pc=0.021) were significantly higher in IgAN patients than in controls, whereas those of HLA-DRB1*07:01, -DRB1*15:01, -DQB1*02:02, and -DQB1*06:02 (Pc<0.001 for all) were significantly lower in IgAN patients than in controls. The allele frequency of HLA-DQB1*05:03 (Pc=0.016) was significantly lower in the ESKD group than in the non-ESKD group; however, there was no significant difference for ESKD progression between these groups.

    CONCLUSIONS We report novel associations of HLA-DRB1*15:01, DQB1*02:02, -DQB1*03:02, and -DQB1*04:01 with IgAN. Further studies of HLA alleles associated with IgAN progression in a larger cohort and in various ethnic groups are needed.

    PubMed IF 4.4 신장내과
19. 72022

    제1저자 배재현 · 교신저자 조영민

    Bae JH, Ahn CH, Yang YS, Moon SJ, Kwak SH, Jung HS, Park KS, Cho YM

    Efficacy and Safety of Self-Titration Algorithms of Insulin Glargine 300 units/mL in Individuals with Uncontrolled Type 2 Diabetes Mellitus (The Korean TITRATION Study): A Randomized Controlled Trial.

    Diabetes Metab J. 2022;46(1):71-80.

    Abstract

    BACKGROUND To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM).

    METHODS In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without noct urnal hypoglycemia at week 12.

    RESULTS Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014).

    CONCLUSION The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).

    PubMed IF 8.2 내분비대사내과
20. 62022

    제1저자 이윤규, 강은주 · 교신저자 김범석

    Lee YG, Kang EJ, Keam B, Choi JH, Kim JS, Park KU, Lee KE, Kim HJ, Lee KW, Kim MK, Ahn HK, Shin SH, Kim HR, Kim SB, Yun HJ

    Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01).

    Cancer Res Treat. 2022;54(1):109-117.

    Abstract

    PURPOSE Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.

    MATERIALS AND METHODS Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.

    RESULTS Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).

    CONCLUSION Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients' preference, morbidity, and prognosis.

    PubMed IF 4.2 혈액종양내과
21. 52022

    제1저자 김정희, 김만진 · 교신저자 이규언, 성문우

    Kim JH^*, Kim MJ^*, Kong SH, Kim SJ, Kang H, Shin CS, Park SS, Lee KE^*, Seong MW^*

    Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.

    J Med Genet. 2022;59(1):56-64.

    Abstract

    BACKGROUND Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing neuroendocrine tumours. PPGLs are a rare but important cause of secondary hypertension owing to their high morbidity and mortality. Patients with PPGL exhibit an increased prevalence of mutations in one of the PPGL susceptibility genes according to previous studies. We aimed to investigate the characteristics of germline mutations in the largest number of Korean patients with PPGL.

    METHODS In this study, 161 patients with PPGL were evaluated. Phenotype data, including biochemical, pathological and anatomical imaging results, were collected. Germline mutations in 10 PPGL-related genes were tested by targeted next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification.

    RESULTS Approximately 21% of apparently sporadic PPGLs harboured germline mutations of the PPGL-related genes. The mutation carriers were younger at the first diagnosis and had more bilateral (28.6% vs 4.0%, p<0.001) and multifocal (11.4% vs 1.6%, p=0.027) PPGLs, but showed no metastatic risk (17.1% vs 11.1%, p=0.504), than non-mutation carriers. Missense mutation of SDHD p.V111I was found in this cohort of Asian patients, which was associated with unilateral pheochromocytoma with dominantly epinephrine production.

    CONCLUSION This study covered the largest number of Korean patients with PPGL. To our knowledge, it is the first to compare results of targeted NGS panel with those of conventional sequencing methods in Asia. We demonstrated that the variant type, as well as the mutated gene, may determine the phenotype and prognosis of PPGLs.

    PubMed IF 3.4 내분비대사내과
22. 42022

    제1저자 윤혁 · 교신저자 박영수

    Yoon H, Park YS, Shin CM, Kim N, Lee DH

    Gut Microbiome in Probable Intestinal Tuberculosis and Changes following Anti-Tuberculosis Treatment.

    Yonsei Med J. 2022;63(1):34-41.

    Abstract

    PURPOSE Information on the gut microbiome in patients with intestinal tuberculosis (ITB) and changes therein following anti-tuberculosis treatment (ATT) is lacking. We aimed to elucidate differences in stool microbiome between ITB patients and controls and to evaluate stool microbiome changes after ATT.

    MATERIALS AND METHODS Eleven patients with probable ITB underwent ATT for 6 months, with stool samples collected at 0, 2, and 6 months. We performed next-generation sequencing of 16S rRNA genes in stool bacteria and compared the gut microbiome.

    RESULTS Initially, the relative abundance of Verrucomicrobia was higher (5.0% vs. <1%) and that of Proteobacteria was lower (<1% vs. 6.6%) in ITB patients than in controls. Higher numbers of butyrate-producing bacteria (Blautia and Roseburia) were noted in ITB patients. The alpha-diversity of stool microbiome of ITB patients was lower than that in controls (p=0.045). There was a significant difference in beta-diversity between the groups (p=0.001). At 6 months, the proportion of Verrucomicrobia decreased to <1%, while the proportion of Proteobacteria remained at <1%.

    CONCLUSION There were no significant differences in alpha- and beta-diversity in the stool microbiome at 0, 2, and 6 months after ATT. The stool microbiome composition of probable ITB patients was different from that of controls, and 6 months of ATT did not significantly affect it.

    PubMed IF 3.1 소화기내과
23. 32022

    제1저자 남준열 · 교신저자 김윤준

    Nam JY, Lee YB, Lee JH, Yu SJ, Kim HC, Chung JW, Yoon JH, Kim YJ

    A Prognostic Prediction Model of Transarterial Radioembolization in Hepatocellular Carcinoma: SNAP-HCC.

    Dig Dis Sci. 2022;67(1):329-336.

    Abstract

    BACKGROUND Prognosis prediction in patient with hepatocellular carcinoma (HCC) after transarterial radioembolization (TARE) remains difficult. The aim of this study was to develop a prognostic model to aid in the decision to use TARE.

    METHODS A total of 174 patients in Korea who underwent TARE for HCC as the initial treatment were included. We developed a prediction model for overall survival (OS) based on independent risk factors for OS and validated the model by bootstrap method.

    RESULTS The median maximal size of the tumors was 8.2 cm, the median number of tumors was 2, and the median albumin level was 4.0 g/dL. Portal vein tumor thrombosis was found in 46.0% (Vp1-3 [39.7%] and Vp4 [6.3%]). Four independent risk factors associated with OS (maximal tumor size, tumor number, albumin, and portal vein tumor thrombosis) were used to develop the SNAP-HCC score. Bootstrap validation of the scoring index determined that the Harrell's c-index for OS was 0.756 (95% confidence interval: 0.729-0.783). Patients grouped based on their SNAP-HCC (scores 0-5) were well discriminated, with significant differences between the groups (all P < 0.05). Patients with SNAP-HCC < 3 showed significantly longer OS than patients with SNAP-HCC ≥ 3 (P < 0.001). The respective survival probabilities at years 1 and 3 were 0.81 and 0.73 in the low-risk (SNAP-HCC < 3) and 0.32 and 0.14 in the high-risk (SNAP-HCC ≥ 3) patients.

    CONCLUSIONS The SNAP-HCC scoring system predicted the outcome of HCC patients undergoing TARE as an initial treatment. This model could be helpful for initial planning the treatment of HCC patients.

    PubMed IF 2.8 소화기내과
24. 22022

    제1저자 김영찬, 최성미 · 교신저자 이하나, 강혜련

    Kim YC, Choi S, Sohn KH, Bang JY, Kim Y, Jung JW, Kim HY, Park J, Kim K, Kang MG, Yang MS, Kim S, Kim SH, Choi JH, Park HJ, Lee SM, Kim SH, Park JW, Lee JM, Cho SH, Won S, Yi H, Kang HR

    Selenomonas: A marker of asthma severity with the potential therapeutic effect.

    Allergy. 2022;77(1):317-320.

    PubMed IF 11.3 알레르기내과
25. 12022

    제1저자 안창호 · 교신저자 정경천, 김정희

    Ahn CH, Na HY, Park SY, Yu HW, Kim SJ, Choi JY, Lee KE, Kim SW, Jung KC, Kim JH

    Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism.

    Clin Endocrinol (Oxf). 2022;96(1):30-39.

    Abstract

    OBJECTIVE Primary aldosteronism (PA) shows histological heterogeneity and clinical variability, including the coexistence of hypercortisolemia. Immunohistochemical analyses of steroidogenic enzymes in adrenal tissues have provided new insights into the pathogenesis of PA. However, a comprehensive analysis of the association between enzyme expression and clinical characteristics of PA has rarely been conducted. We aimed to investigate the correlation between clinical characteristics and steroidogenic enzyme expression in PA.

    DESIGN A retrospective case-control study.

    PATIENTS Consecutive patients who underwent unilateral adrenalectomy for PA (n = 180). Patients with adrenal Cushing's syndrome (CS) (n = 29) and nonfunctioning adenoma (n = 6) as comparator groups.

    MEASUREMENTS A tissue microarray of adrenal adenomas was constructed and immunostained for CYP11B1, CYP11B2 and CYP17A1. The expression of the three enzymes was compared between PA and other adrenal diseases and between PA with and without mild autonomous cortisol excess (MACE).

    RESULTS Adrenal adenomas in PA showed lower CYP11B1, higher CYP11B2 and lower CYP17A1 expression than those in adrenal CS (p < .001). Nonfunctioning adenomas showed low expression of the three enzymes. PA with MACE showed higher CYP11B1 expression than PA without MACE. CYP11B1 expression was positively correlated with the severity of hypercortisolemia, and CYP11B2 was positively correlated with that of hyperaldosteronism. The expression of CYP11B1 and CYP11B2 had a negative correlation. Patients with absent clinical improvement after adrenalectomy had lower CYP11B2 expression than those with complete success.

    CONCLUSIONS Variable expression of steroidogenic enzymes in adrenal adenoma underlies the clinical heterogeneity of PA and is associated with treatment outcomes.

    PubMed IF 2.8 내분비대사내과

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.