SCI 발표논문

2023년 248편

1282023

제1저자 김학령 · 교신저자 김상현

, , , , ,
Efficacy, safety and clinical outcome associated with statin use for primary prevention in Korean patients with low-density lipoprotein cholesterol level ≥ 190 mg/dL: A retrospective cohort study.
PLoS One. 2023;18(6):e0280586.

Abstract
BACKGROUND Although the current guideline recommends the use of high-intensity statin to reduce the low-density lipoprotein cholesterol (LDL-C) level by 50% in patients with baseline value of ≥ 190 mg/dL, direct application of this recommendation to Asian populations is still questionable. This study was performed to investigate the statin response of LDL-C in Korean patients with LDL-C ≥ 190 mg/dL.
METHODS A total of 1,075 Korean patients (age 60.7 ± 12.2 years, women 68%) with baseline LDL-C ≥ 190 mg/dL without cardiovascular disease was retrospectively reviewed. Lipid profiles at 6 months, side effects and clinical outcomes during the follow-up period after statin treatment were assessed according to statin intensity.
RESULTS Most of the patients (76.3%) were treated with moderate-intensity statins, 11.4% with high-intensity statins, and 12.3% with a statin + ezetimibe. The reductions in LDL-C percentage at 6 months were 48.0%, 56.0% and 53.3% in patients treated with moderate-intensity statins, high-intensity statins and statin + ezetimibe, respectively (P < 0.001). Side effects requiring dose reduction, medication switch or drug interruption were observed in 1.3%, 4.9% and 2.3% of patients treated with moderate-intensity statin, high-intensity statin and statin + ezetimibe, respectively (P = 0.024). During the median follow-duration of 815 days (interquartile range, 408-1,361 days), the incidences of cardiovascular events were not different among the 3 groups (log-rank P = 0.823).
CONCLUSIONS Compared to high-intensity statin, moderate-intensity statin was effective enough in reaching target goal of LDL-C without increase in cardiovascular risk and with fewer side effects in Korean patients with LDL-C ≥ 190 mg/dL.
PubMed IF 2.8 순환기내과
1272023

제1저자 조은주 정고은 · 교신저자 한경도 유수종

, , , , , , , ,
The association between alcohol consumption and the risk of hepatocellular carcinoma according to glycemic status in Korea: A nationwide population-based study.
PLoS Med. 2023;20(6):e1004244.

Abstract
BACKGROUND Alcohol and diabetes are known risk factors for hepatocellular carcinoma (HCC); however, it is unclear whether the association between alcohol consumption and HCC risk differs by fasting serum glucose level and diabetes. We investigated the dose-response relationship between alcohol consumption and the risk of HCC according to glycemic status.
METHODS AND FINDINGS This population-based observational cohort study included patients who underwent general health checkups in 2009 using the Korean National Health Insurance Service Database. The primary outcome was HCC incidence, and Cox proportional hazard regression analysis was performed to estimate the relationship between alcohol consumption and HCC risk according to glycemic status. A total of 34,321 patients newly diagnosed with HCC were observed in the median follow-up period of 8.3 years. In the multivariable model, we adjusted for age, sex, smoking, regular exercise, income, hypertension, dyslipidemia, and body mass index. Mild-to-moderate alcohol consumption increased the risk of HCC in all glycemic statuses (normoglycemia: hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.02 to 1.10; prediabetes: HR, 1.19; 95% CI, 1.14 to 1.24; and diabetes: HR, 2.02; 95% CI, 1.93 to 2.11) compared to normoglycemic nondrinking. Heavy alcohol consumption also increased the risk of HCC in all glycemic statuses (normoglycemia: HR, 1.39; 95% CI, 1.32 to 1.46; prediabetes: HR, 1.67; 95% CI, 1.58 to 1.77; and diabetes: HR, 3.29; 95% CI, 3.11 to 3.49) compared to normoglycemic nondrinking. Since alcohol consumption information in this study was based on a self-administered questionnaire, there may be a possibility of underestimation. Although we excluded patients with a history of viral hepatitis using diagnosis codes, we could not obtain information on hepatitis B or hepatitis C serum markers.
CONCLUSIONS Both mild-to-moderate and heavy alcohol consumption was associated with an increased risk of HCC in all glycemic statuses. The increased risk of HCC according to alcohol consumption was the highest in the diabetes group, suggesting that more intensive alcohol abstinence is required for patients with diabetes.
PubMed IF 9.9 소화기내과
1262023

제1저자 Purevsuren Losol · 교신저자 김세훈

, , , , , , , ,
Bronchial epithelial cells release inflammatory markers linked to airway inflammation and remodeling in response to TLR5 ligand flagellin.
World Allergy Organ J. 2023;16(6):100786.

Abstract
BACKGROUND/AIMS Flagellin, which is abundant in gram-negative bacteria, including Pseudomonas, is reported to influence on inflammatory responses in various lung diseases. However, its effect on airway epithelial cells in contribution to asthma pathogenesis is not elucidated yet. We aimed to investigate the effect of TLR5 ligand flagellin on the transcriptomic profile of primary human epithelial cells and to determine the markers of airway inflammation.
METHODS Normal human bronchial epithelial (NHBE) cells were grown and differentiated in air-liquid interface (ALI) culture for 14-16 days. The cells were treated with flagellin in vitro at 10 and 100 ng/ml for 3 and 24 h. The conditioned media and cells were harvested to validate inflammatory markers involved in airway inflammation using ELISA, Western blot, and quantitative PCR methods. RNA-sequencing was performed to investigate the transcriptional response to flagellin in ALI-NHBE cells.
RESULTS Altered transcriptional responses to flagellin in differentiated bronchial epithelial cells were determined, including genes encoding chemokines, matrix metalloproteinases, and antimicrobial biomolecules. Pathway analysis of the transcriptionally responsive genes revealed enrichment of signaling pathways. Flagellin induced the mRNA expressions of proinflammatory cytokines and chemokines, and secretion of GM-CSF, CXCL5, CCL5 and CXCL10. Flagellin enhanced the protein expression of MMP-13 in TGF-β1 and TGF-β2 pretreated cell lysates and Wnt/β-catenin signaling.
CONCLUSIONS These findings suggest that flagellin could be a potent inducer of inflammatory markers that may contribute to airway inflammation and remodeling.
PubMed IF 4 순환기내과
1252023

제1저자 하혜림, 고예희 · 교신저자 김광수, 홍준식

, , , , , , ,
Application of the Khorana score for cancer-associated thrombosis prediction in patients of East Asian ethnicity undergoing ambulatory chemotherapy.
Thromb J. 2023;21(1):63.

Abstract
BACKGROUND The Khorana score (KS) has not been well studied in East Asian cancer patients, who have different genetic backgrounds for inherited thrombophilia, body metabolism, and cancer epidemiology.
METHODS By using the Common Data Model, we retrospectively collected deidentified data from 11,714 consecutive newly diagnosed cancer patients who underwent first-line chemotherapy from December 2015 to December 2021 at a single institution in Korea, and we applied the KS for cancer-associated thrombosis (CAT) prediction. Age at diagnosis, sex, and use of highly thrombogenic chemotherapeutics were additionally investigated as potential risk factors for CAT development.
RESULTS By 6 months after chemotherapy initiation, 207 patients (1.77%) experienced CAT. Only 0.4% had a body mass index (BMI) ≥ 35 kg/m² and changing the cutoff to 25 kg/m² improved the prediction of CAT. Age ≥ 65 years and the use of highly thrombogenic chemotherapeutics were independently associated with CAT development. KS values of 1 ~ 2 and ≥ 3 accounted for 52.3% and 7.6% of all patients, respectively, and the incidence of CAT in these groups was 2.16% and 4.16%, respectively, suggesting a lower incidence of CAT in the study population than in Westerners. The KS component regarding the site of cancer showed a good association with CAT development but needed some improvement.
CONCLUSION The KS was partially validated to predict CAT in Korean cancer patients undergoing modern chemotherapy. Modifying the BMI cutoff, adding other risk variables, and refining the use of cancer-site data for CAT risk prediction may improve the performance of the KS for CAT prediction in East Asian patients.
PubMed IF 2.7 혈액종양내과
1242023

제1저자 심지수, 김선신 · 교신저자 박흥우

, , , , ,
Fat mass index and airway hyperresponsiveness in Korean adults.
Postgrad Med. 2023;135(5):480-485.

Abstract
OBJECTIVE Airway hyperresponsiveness (AHR) is associated with asthma and obesity, which is defined as a high body mass index. Body mass mainly comprises fat mass (FM) and muscle mass (MM), which are independent of each other. We investigated the effect of changes in FM over time on the development of asymptomatic AHR in adults.
METHODS This long-term longitudinal study included adults who were underwent health checkups at the Seoul National University Hospital Gangnam Center. The participants underwent two methacholine bronchial provocation tests with a follow-up period (between the first and second tests) of more than 3 years and bioelectrical impedance analysis (BIA) at all visits. FM index (FMI; FM normalized for height) and MM index (MMI; MM normalized for height) were calculated using BIA.
RESULTS The study included 328 adult participants (61 women and 267 men). The mean number of BIA measurements was 6.96 and the follow-up duration was 6.69 years. In total, 13 participants showed a positive conversion of AHR. Multivariate analysis indicated that a high rate of change in FMI ([g/m²]/year), not MMI, was significantly associated with the risk of AHR development (P = 0.037) after adjustment for age, sex, smoking status, and FEV1 predicted.
CONCLUSION A rapid gain of FM over time may be a risk factor for developing AHR in adults. Prospective studies are needed to confirm our results and evaluate the role of FM reduction in preventing AHR development in obese adults.
PubMed IF 2.7 알레르기내과
1232023

제1저자 박승신, 김용휘, 김정희, 최만호 · 교신저자 김정희, 최만호

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Serum and hair steroid profiles in patients with nonfunctioning pituitary adenoma undergoing surgery: A prospective observational study.
J Steroid Biochem Mol Biol. 2023;230:106276.

Abstract
Patients who undergo transsphenoidal surgery (TSS) experience perioperative hormonal changes, but there are few studies on the perioperative changes of serum and hair steroid profiles. This study investigated the perioperative changes in steroid metabolic signatures in patients with nonfunctioning pituitary adenoma (NFPA) who underwent transsphenoidal surgery (TSS). A total of 55 participants who underwent TSS for NFPA at a single center between July 2017 and October 2018 were enrolled. Fifteen serum steroids and their metabolic ratios were profiled using gas chromatography-mass spectrometry (GC-MS) before and 1 day, 1 week, and 3 months after TSS. Five steroids from hair samples collected 1 day and 3 months after TSS were also quantitatively compared. Serum cortisol and its A-ring reductive metabolites, as well as 6β-hydroxycortisol, increased dramatically 1 day after TSS and then gradually decreased. Seven serum steroids, including adrenal androgens and mineralocorticoids, and hair cortisone levels were significantly lower in patients with preoperative adrenocorticotropic hormone (ACTH) deficiency (N = 7) than in those without ACTH deficiency (N = 48). Serum levels of dehydroepiandrosterone (DHEA) levels 1 week after TSS predicted ACTH deficiency 3 months after TSS, with 100 % sensitivity and 86 % specificity. A significant positive correlation between the preoperative serum and hair DHEA levels (r = 0.356, P = 0.008) was observed. These findings suggest that the levels of DHEA in both the serum and hair could be an early marker of ACTH deficiency after TSS. In addition, hair cortisone may be a useful preoperative indicator of chronic ACTH deficiency.
PubMed IF 3.1 내분비대사내과
1222023

제1저자 장용준 · 교신저자 이해영

, , , ,
Feasibility, credence, and usefulness of out-of-office cuffless blood pressure monitoring using smartwatch: a population survey.
Clin Hypertens. 2023;29(1):15.

Abstract
BACKGROUND Cuffless blood pressure (BP) measurement, enabled by recent advances in wearable devices, allows for BP monitoring in daily life. This study aims to evaluate the feasibility, cresdence, and usefulness of cuffless BP monitoring through a population survey.
METHODS During the "Daily BP Measurement with Your Galaxy Watch" campaign held by the Korean Society of Hypertension, participants were asked to share their experiences with cuffless BP measurement using a smartwatch application through an online survey. The questionnaire included questions about age, underlying medical conditions, smartwatch utilization, experience with BP calibration, the reliability of BP values measured by a smartwatch, and willingness to use the BP monitoring function in the future.
RESULTS A total of 1071 participants responded to the survey. The largest age group (decile) was 50-59 years old (33.3%), followed by 40-49 years old (29.9%). Although nearly half of the participants (47.5%) had no chronic diseases, 40.1% reported having hypertension. BP monitoring was the most frequently utilized smartwatch function (95.8%), followed by heart rate measurement (87.1%). 31.8% of participants reported that BP values measured by the smartphone application were "very accurate and helpful," while 63.5% rated them as "slightly lower (44.4%)" or "higher (19.1%)" compared to the standard home BP monitoring device. 93% of the participants reported utilizing the BP monitoring function at least once a week. Regarding the BP calibration process, most participants (93.9%) calibrated the BP measurement application themselves, and 50.8% rated the difficulty level as "very easy."
CONCLUSION Cuffless BP measurement using a smartwatch application was feasible in the general population, including the self-calibration process. However, the satisfaction level in terms of accuracy is still modest, indicating a need for further development.
PubMed IF 6.2 순환기내과
1212023

제1저자 박민경, 이동호 · 교신저자 이정훈

, , , , , , , ,
Effectiveness of US Surveillance of Hepatocellular Carcinoma in Chronic Hepatitis B: US LI-RADS Visualization Score.
Radiology. 2023;307(5):e222106.

Abstract
Background US is a standard surveillance tool of hepatocellular carcinoma (HCC), but its effectiveness varies depending on the degree of fibrosis or steatosis and the etiologies of liver disease. Purpose To evaluate the detection power of US and the occurrence of HCC according to the US Liver Imaging Reporting and Data System (LI-RADS) visualization score in chronic hepatitis B (CHB). Materials and Methods Consecutive patients with CHB undergoing regular US surveillance of HCC at a tertiary referral hospital were retrospectively included in this study. During the follow-up, all patients underwent regular HCC surveillance mainly with US and, in some cases, alternative CT or MRI. Outcomes of interest included cumulative incidence of HCC and false-negative rate of US in the optimal (LI-RADS visualization A) versus suboptimal groups (visualization B or C). Cox regression analysis was conducted to calculate the hazard ratio (HR) of HCC occurrence. Results A total of 2002 patients (median age, 54 years [IQR, 46-60 years]; 1192 men) were included: 972 and 1030 in the optimal and suboptimal groups, respectively. Causes of suboptimal visualization included parenchymal heterogeneity from advanced cirrhosis (n = 489), limited penetration from fatty liver (n = 200), and limited window from overlying organ shadow (n = 341). During a median follow-up of 75 months (IQR, 69-77 months), 163 patients developed HCC. Compared with the optimal group, the suboptimal group had a higher risk of HCC (2.38% per year vs 0.48% per year: hazard ratio, 4.93; 95% CI: 3.28, 7.41; P < .001) and higher odds of a false-negative rate of US (43.9% vs 16.7%: odds ratio, 3.90; 95% CI: 1.02, 15.00; P = .04). Conclusion Among patients with CHB, those with suboptimal US LI-RADS visualization of B or C had a higher risk of HCC and higher odds of false-negative rates of US for detecting HCC than those with optimal visualization of A. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Barr and Scoutt in this issue.
PubMed IF 17.6 소화기내과
1202023

제1저자 김인호 · 교신저자 석승혁, 이해영

, , , ,
Comparison of the effects of empagliflozin and sotagliflozin on a zebrafish model of diabetic heart failure with reduced ejection fraction.
Exp Mol Med. 2023;55(6):1174-1181.

Abstract
The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMPA) and dual SGLT1/2 inhibitor sotagliflozin (SOTA) are emerging as heart failure (HF) medications in addition to having glucose-lowering effects in diabetes mellitus (DM). However, the precise mechanism underlying this cardioprotective effect has not yet been elucidated. Here, we evaluated the effects of EMPA and SOTA in a zebrafish model of DM combined with HF with reduced ejection fraction (DM-HFrEF). To compare the effects of the two drugs, survival, locomotion, and myocardial contractile function were evaluated. The structural binding and modulating effects of the two medications on sodium-hydrogen exchanger 1 (NHE1) were evaluated in silico and in vitro. DM-HFrEF zebrafish showed impaired cardiac contractility and decreased locomotion and survival, all of which were improved by 0.2-5 μM EMPA or SOTA treatment. However, the 25 μM SOTA treatment group had worse survival rates and less locomotion preservation than the EMPA treatment group at the same concentration, and pericardial edema and an uninflated swim bladder were observed. SOTA, EMPA and cariporide (CARI) showed similar structural binding affinities to NHE1 in a molecular docking analysis and drug response affinity target stability assay. In addition, EMPA, SOTA, and CARI effectively reduced intracellular Na⁺ and Ca²⁺ changes through the inhibition of NHE1 activity. These findings suggest that both EMPA and SOTA exert cardioprotective effects in the DM-HFrEF zebrafish model by inhibiting NHE1 activity. In addition, despite the similar cardioprotective effects of the two drugs, SOTA may be less effective than EMPA at high concentrations.
PubMed IF 17.5 순환기내과
1192023

제1저자 최용훈, 최수인 · 교신저자 김나영

, , , , , , , , , ,
Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids.
Dig Dis Sci. 2023;68(6):2427-2440.

Abstract
BACKGROUND/AIMS A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex.
METHODS Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured.
RESULTS HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation.
CONCLUSIONS The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.
PubMed IF 2.8 소화기내과
1182023

제1저자 이태민 · 교신저자 박경우

, , , , , , , , , , , , , , , , , , , , ,
Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the HOST-EXAM Trial.
JAMA Cardiol. 2023;8(6):535-544.

Abstract
IMPORTANCE Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking.
OBJECTIVE To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes.
DESIGN, SETTING, AND PARTICIPANTS This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021.
INTERVENTIONS AND EXPOSURES Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes.
MAIN OUTCOMES AND MEASURES The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up.
RESULTS Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71).
CONCLUSION AND RELEVANCE In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02044250.
PubMed IF 15.2 순환기내과
1172023

제1저자 김지혜, 허문행 · 교신저자 김윤준

, , , , , , , , , , , , , , , , , , , , , , , , , ,
Inverse Propensity Score-Weighted Analysis of Entecavir and Tenofovir Disoproxil Fumarate in Patients with Chronic Hepatitis B: A Large-Scale Multicenter Study.
Cancers (Basel). 2023;15(11):cancers15112936.

Abstract
Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) in preventing hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients; however, it remains controversial. This study aimed to conduct comprehensive comparisons between the two antivirals. CHB patients initially treated with ETV or TDF between 2012 and 2015 at 20 referral centers in Korea were included. The primary outcome was the cumulative incidence of HCC. The secondary outcomes included death or liver transplantation, liver-related outcome, extrahepatic malignancy, development of cirrhosis, decompensation events, complete virologic response (CVR), seroconversion rate, and safety. Baseline characteristics were balanced using the inverse probability of treatment weighting (IPTW). Overall, 4210 patients were enrolled: 1019 received ETV and 3191 received TDF. During the median follow-ups of 5.6 and 5.5 years, 86 and 232 cases of HCC were confirmed in the ETV and TDF groups, respectively. There was no difference in HCC incidence between the groups both before (p = 0.36) and after IPTW was applied (p = 0.81). Although the incidence of extrahepatic malignancy was significantly higher in the ETV group than in the TDF group before weighting (p = 0.02), no difference was confirmed after IPTW (p = 0.29). The cumulative incidence rates of death or liver transplantation, liver-related outcome, new cirrhosis development, and decompensation events were also comparable in the crude population (p = 0.24-0.91) and in the IPTW-adjusted population (p = 0.39-0.80). Both groups exhibited similar rates of CVR (ETV vs. TDF: 95.1% vs. 95.8%, p = 0.38), and negative conversion of hepatitis B e antigen (41.6% vs. 37.2%, p = 0.09) or surface antigen (2.8% vs. 1.9%, p = 0.10). Compared to the ETV group, more patients in the TDF group changed initial antivirals due to side effects, including decreased kidney function (n = 17), hypophosphatemia (n = 20), and osteoporosis (n = 18). In this large-scale multicenter study, ETV and TDF demonstrated comparable effectiveness across a broad range of outcomes in patients with treatment-naïve CHB during similar follow-up periods.
PubMed IF 4.8 소화기내과
1162023

제1저자 박성수, 이종철, 변자민 · 교신저자 민창기, 구자민

, , , , , , , , , , ,
ML-based sequential analysis to assist selection between VMP and RD for newly diagnosed multiple myeloma.
NPJ Precis Oncol. 2023;7(1):46.

Abstract
Optimal first-line treatment that enables deeper and longer remission is crucially important for newly diagnosed multiple myeloma (NDMM). In this study, we developed the machine learning (ML) models predicting overall survival (OS) or response of the transplant-ineligible NDMM patients when treated by one of the two regimens-bortezomib plus melphalan plus prednisone (VMP) or lenalidomide plus dexamethasone (RD). Demographic and clinical characteristics obtained during diagnosis were used to train the ML models, which enabled treatment-specific risk stratification. Survival was superior when the patients were treated with the regimen to which they were low risk. The largest difference in OS was observed in the VMP-low risk & RD-high risk group, who recorded a hazard ratio of 0.15 (95% CI: 0.04-0.55) when treated with VMP vs. RD regimen. Retrospective analysis showed that the use of the ML models might have helped to improve the survival and/or response of up to 202 (39%) patients among the entire cohort (N = 514). In this manner, we believe that the ML models trained on clinical data available at diagnosis can assist the individualized selection of optimal first-line treatment for transplant-ineligible NDMM patients.
PubMed IF 9.9 혈액종양내과
1152023

제1저자 조인래, 한경도 · 교신저자 이상협, 최영훈

, , , , , , , , , ,
Association between glycemic status and the risk of acute pancreatitis: a nationwide population-based study.
Diabetol Metab Syndr. 2023;15(1):104.

Abstract
BACKGROUND Although diabetes is reportedly associated with the occurrence of acute pancreatitis (AP), the risk of AP according to the duration and severity of diabetes is not yet clear. We aimed to investigate the risk of AP based on glycemic status and the presence of comorbidities using a nationwide population-based study.
METHODS We enrolled 3,912,496 adults who underwent health examinations under the National Health Insurance Service in 2009. All participants were categorized by glycemic status as normoglycemic, impaired fasting glucose (IFG), or diabetes. Baseline characteristics and the presence of comorbidities at the time of health check-up were investigated, and the occurrence of AP was followed up until 31 December 2018. We estimated the adjusted hazard ratios (aHRs) for AP occurrence according to the glycemic status, duration of diabetes (new-onset, duration < 5 years, or ≥ 5 years), type and number of anti-diabetic medications, and presence of comorbidities.
RESULTS During the observation period of 32,116,716.93 person-years, 8,933 cases of AP occurred. Compared with normoglycemia, the aHRs (95% confidence interval) were 1.153 (1.097-1.212) in IFG, 1.389 (1.260-1.531) in new-onset diabetes, 1.634 (1.496-1.785) in known diabetes < 5 years, and 1.656 (1.513-1.813) in patients with known diabetes aged ≥ 5 years. The presence of comorbidities associated with diabetes severity had a synergistic effect on the relationship between diabetes and AP occurrence.
CONCLUSION As glycemic status worsens, the risk of AP increases, and there is a synergistic effect when comorbidities coexist. To reduce the risk of AP, active control of factors that can cause AP should be considered in patients with long-standing diabetes and comorbidities.
PubMed IF 4.9 소화기내과
1142023

제1저자 정고은, 조은주 · 교신저자 신동욱, 유수종

, , , , , , , , , ,
Association between the fatty liver index and the risk of fracture among individuals over the age of 50 years: a nationwide population-based study.
Front Endocrinol (Lausanne). 2023;14:1156996.

Abstract
BACKGROUND AND PURPOSE The association between fatty liver and fracture risk has not been firmly established. In this study, we investigated the relationship between the fatty liver index (FLI) and the incidence of fractures among individuals ≥50 years of age, using a nationwide population-based cohort.
METHODS Data from the Korean National Health Insurance System between January 2009 and December 2019 were analyzed using the Cox proportional hazards model. Fatty liver status was defined using FLI. Newly diagnosed fractures were identified based on insurance claim data.
RESULTS Among the 3,384,457 individuals who met our inclusion criteria over the study period, 444,203 cases of incident fractures were identified over a median follow-up of 10.3 years. On multivariate analysis, the risk of fracture was significantly higher among individuals with a higher FLI score compared to those with an FLI<30, with adjusted hazard ratio [aHR] and 95% confidence interval [CI] as follows: FLI 30-59 group, aHR 1.04 and 95% CI 1.03-1.05; and FLI ≥60 group, aHR 1.12 and 95% CI 1.10-1.13. A higher FLI was associated with a greater risk of hip (aHR 1.23 and 1.52 for the FLI 30-59 and FLI ≥60 group, respectively) and vertebral fracture (aHR 1.08 and 1.16 for the FLI 30-59 and FLI≥60 group, respectively). The association between the risk for fracture and FLI ≥60 was prominent for non-obese than obese individuals (aHR 1.25 and 95% CI, 1.22-1.27 versus 1.06 and 1.05-1.08, respectively).
CONCLUSIONS A high FLI is associated with an increased risk of hip and vertebral fractures among individuals ≥50 years of age, suggestive of an association between a higher FLI and osteoporotic fractures.
PubMed IF 5.7 소화기내과
1132023

제1저자 허문행, 송우진, 천덕현 · 교신저자 남궁철, 최형진, 이정훈

, , , , , , , , , , ,
Chemogenetic stimulation of the parasympathetic nervous system lowers hepatic lipid accumulation and inflammation in a nonalcoholic steatohepatitis mouse model.
Life Sci. 2023;321:121533.

Abstract
AIMS The role of the parasympathetic nervous system (PNS) in the pathogenesis of nonalcoholic steatohepatitis (NASH) is largely unknown. In this study, the effect of PNS modulation on NASH was investigated using chemogenetics.
MAIN METHODS A streptozotocin (STZ) and high-fat diet (HFD)-induced NASH mouse model was used. To activate or inhibit the PNS, chemogenetic human M3-muscarinic receptor coupled with either Gq or Gi protein-containing viruses was injected into the dorsal motor nucleus of the vagus at week 4 and clozapine N-oxide was administered intraperitoneally for a week from week 11. Three groups (PNS-stimulation, PNS-inhibition, and control) were compared in terms of heart rate variability (HRV), histological lipid droplet area, nonalcoholic fatty liver disease activity score (NAS), the area of F4/80-positive macrophages, and biochemical responses.
KEY FINDINGS The STZ/HFD-treated mouse model showed typical histological characteristics of NASH. HRV analysis confirmed that PNS-stimulation and PNS-inhibition groups had significantly higher and lower PNS activity, respectively (both P < 0.05). The PNS-stimulation group showed a significantly smaller hepatic lipid droplet area (14.3 % vs. 20.6 %, P = 0.02) and lower NAS (5.2 vs. 6.3, P = 0.047) than the control group. The area of F4/80-positive macrophages was significantly smaller in the PNS-stimulation group than in the control group (4.1 % vs. 5.6 %, P = 0.04). The PNS-stimulation group showed a lower serum aspartate aminotransferase level than the control group (119.0 vs. 356.0 U/L, P = 0.04).
SIGNIFICANCE In STZ/HFD-treated mice, chemogenetic stimulation of the PNS significantly reduced hepatic fat accumulation and inflammation. The hepatic PNS may play a pivotal role in the pathogenesis of NASH.
PubMed IF 6.4 소화기내과
1122023

제1저자 남창현, 육정환 · 교신저자 권현우, 김민정, 주영석

, , , , , , , , , , , , , , , , ,
Widespread somatic L1 retrotransposition in normal colorectal epithelium.
Nature. 2023;617(7961):540-547.

Abstract
Throughout an individual's lifetime, genomic alterations accumulate in somatic cells^1-11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome^12-14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.
PubMed IF 56.1 혈액종양내과
1112023

제1저자 김형준 · 교신저자 이재호

, , , , , , , , ,
Usefulness of the BACES score in nontuberculous mycobacterial pulmonary disease for various clinical outcomes.
Sci Rep. 2023;13(1):7495.

Abstract
A uniform prognostic marker is needed for nontuberculous mycobacterial pulmonary disease (NTM-PD) due to the diverse clinical course. We aimed to seek the utility of the BACES score, originally derived to predict all-cause mortality, for various outcomes. To calculate the BACES score, one point was given for each of the following factors: body mass index < 18.5 kg/m², age ≥ 65 years, presence of cavities, elevated erythrocyte sedimentation rate, or male sex. The study included 681 patients, of whom 97 (14.2%), 189 (27.7%), 192 (28.2%), 143 (21.0%), 47 (6.9%), and 13 (1.9%) had BACES scores of 0 to 5. Those with greater BACES scores were more likely to experience dyspnea, body weight loss, and anorexia. With severe disease, the risk of disease progression increased while the rate of treatment culture conversion decreased. After adjustment of comorbidities, higher BACES score was independently associated with the risk of mortality from respiratory causes or infection. As a simple and efficient bedside tool for assessing the severity of NTM-PD, the BACES score has the potential to be utilized as a surrogate marker for uniform severity assessment.
PubMed IF 4.9 호흡기내과
1102023

제1저자 리우준 · 교신저자 홍준식

, , , , , , , , , ,
Epigenetic priming improves salvage chemotherapy in diffuse large B-cell lymphoma via endogenous retrovirus-induced cGAS-STING activation.
Clin Epigenetics. 2023;15(1):75.

Abstract
BACKGROUND Although most patients with diffuse large B-cell lymphoma (DLBCL) achieve complete remission after first-line rituximab-containing immunochemotherapy, up to 40% of patients relapse and require salvage therapy. Among those patients, a substantial proportion remain refractory to salvage therapy due to insufficient efficacy or intolerance of toxicities. A hypomethylating agent, 5-azacytidine, showed a chemosensitizing effect when primed before chemotherapy in lymphoma cell lines and newly diagnosed DLBCL patients. However, its potential to improve outcomes of salvage chemotherapy in DLBCL has not been investigated.
RESULTS In this study, we demonstrated the mechanism of 5-azacytidine priming as a chemosensitizer in a platinum-based salvage regimen. This chemosensitizing effect was associated with endogenous retrovirus (ERV)-induced viral mimicry responses via the cGAS-STING axis. We found deficiency of cGAS impaired the chemosensitizing effect of 5-azacytidine. Furthermore, combining vitamin C and 5-azacytidine to synergistically activate STING could be a potential remedy for insufficient priming induced by 5-azacytidine alone.
CONCLUSIONS Taken together, the chemosensitizing effect of 5-azacytidine could be exploited to overcome the limitations of the current platinum-containing salvage chemotherapy in DLBCL and the status of cGAS-STING has the potential to predict the efficacy of 5-azacytidine priming.
PubMed IF 5.7 혈액종양내과
1092023

제1저자 한정규, 황도연 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , , ,
Comparison of 3- to 6-Month Versus 12-Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-Eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial.
Circulation. 2023;147(18):1358-1368.

Abstract
BACKGROUND Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention using third-generation drug-eluting stents with ultrathin struts and advanced polymer technology. We investigated whether 3- to 6-month DAPT was noninferior to 12-month DAPT after implantation of drug-eluting stents with ultrathin struts and advanced polymer technology.
METHODS We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing percutaneous coronary intervention using the Orsiro biodegradable-polymer sirolimus-eluting stents or the Coroflex ISAR polymer-free sirolimus-eluting stents. Patients with ST-segment-elevation myocardial infarction were excluded. Patients were randomly assigned to receive either 3- to 6-month or 12-month DAPT after percutaneous coronary intervention. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and major bleeding.
RESULTS A total of 2013 patients (mean age, 65.7±10.5 years; 1487 males [73.9%]; 1110 [55.1%] presented with acute coronary syndrome) were randomly assigned to 3- to 6-month DAPT (n=1002) or 12-month DAPT (n=1011). The primary outcome occurred in 37 (3.7%) patients in the 3- to 6-month DAPT group and 41 (4.1%) in the 12-month DAPT group. The noninferiority of the 3- to 6-month DAPT group to the 12-month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% CI, -∞% to 1.1%]; P<0.001 for noninferiority). There were no significant differences in target lesion failure (hazard ratio, 0.98 [95% CI, 0.56-1.71], P=0.94) or major bleeding (hazard ratio, 0.82 [95% CI, 0.41-1.61], P=0.56) between the 2 groups. Across various subgroups, the treatment effect of 3- to 6-month DAPT was consistent for net adverse clinical event.
CONCLUSIONS Among patients undergoing percutaneous coronary intervention using third-generation drug-eluting stents, 3- to 6-month DAPT was noninferior to 12-month DAPT for net adverse clinical event. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3- to 6-month DAPT.
REGISTRATION URL: https://www.
CLINICALTRIALS gov; Unique identifier: NCT02601157.
PubMed IF 41.3 순환기내과
1082023

제1저자 손희준, 구보경 · 교신저자 김원

, , , , , , , ,
PNPLA3 genotypes modify the adverse effect of the total energy intake on high-risk nonalcoholic steatohepatitis development.
Am J Clin Nutr. 2023;117(5):910-917.

Abstract
BACKGROUND The relationship between diet and risk genotypes in nonalcoholic steatohepatitis (NASH) development and fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD) remains unclear.
OBJECTIVE We aimed to investigate the effects of diet on NASH development and fibrosis progression in patients with NAFLD stratified by the PNPLA3 genotype.
METHODS We performed a prospective study in a cohort of patients with biopsy-confirmed NAFLD. Histologic deterioration was obtained using serial transient elastography at every 1 or 2 y. The primary outcome was fibrosis progression, and the secondary outcome was development of high-risk NASH, defined as FibroScan-aspartate aminotransferase score ≥0.67 during the follow-up of patients with nonalcoholic fatty liver at the baseline. Dietary intake was evaluated using a semiquantitative food frequency questionnaire.
RESULTS The primary outcome was observed in 42 (29.0%) of the 145 patients during a median follow-up of 49 mo; neither the total energy intake nor each macronutrient intake significantly affected the primary outcome occurrence. Conversely, the total energy intake (HR per 1-SD: 3.03; 95% CI: 1.31, 7.01) and the PNPLA3 rs738409 genotype [HR per 1 risk allele (G): 2.06; 95% CI: 1.11, 3.83)] were independent risk factors for high-risk NASH. The significant interaction between the total energy intake and PNPLA3 genotype was noted in developing high-risk NASH (P = 0.044). As the number of PNPLA3 risk alleles decreased, the effect of the total energy intake on high-risk NASH increased; the HR per 1-SD increment in total energy intake was 1.52 (95% CI: 0.42, 5.42), 3.54 (95% CI: 1.23, 10.18), and 8.27 (95% CI: 1.20, 57.23) for the GG, CG, and CC genotypes, respectively.
CONCLUSIONS The total energy intake adversely affected the development of high-risk NASH in patients with biopsy-confirmed NAFLD. The effect was more prominent in patients without the PNPLA3 risk allele, highlighting the importance of personalized dietary interventions in NAFLD treatment.
PubMed IF 6.9 소화기내과
1072023

제1저자 이현덕 · 교신저자 조수정

, , , , , , ,
A Randomized Controlled Trial of Fibrin Glue to Prevent Bleeding After Gastric Endoscopic Submucosal Dissection.
Am J Gastroenterol. 2023;118(5):892-899.

Abstract
INTRODUCTION This study evaluated the efficacy of fibrin glue for preventing postendoscopic submucosal dissection (ESD) bleeding in high-risk patients for bleeding (expected iatrogenic ulcer size ≥40 mm or receiving antithrombotic therapy).
METHODS A multicenter, open-label, randomized controlled trial was performed at 4 tertiary medical centers in South Korea between July 1, 2020, and June 22, 2022. Patients with gastric neoplasm and a high risk of post-ESD bleeding were enrolled and allocated at 1:1 to a control group (standard ESD) or a fibrin glue group (fibrin glue applied to iatrogenic ulcers after standard ESD). The primary outcome was overall bleeding events within 4 weeks. The secondary outcomes were acute bleeding (within 48 hours post-ESD) and delayed bleeding (48 hours to 4 weeks post-ESD).
RESULTS In total, 254 patients were randomized, and 247 patients were included in the modified intention-to-treat population (125 patients in the fibrin glue group and 122 patients in the control group). Overall bleeding events occurred in 12.0% (15/125) of the fibrin glue group and 13.1% (16/122) of the control group ( P = 0.791). Acute bleeding events were significantly less common in the fibrin glue group than in the control group (1/125 vs 7/122, P = 0.034). Delayed bleeding events occurred in 11.2% (14/125) in the fibrin glue group and 7.3% (9/122) in the control group ( P = 0.301).
DISCUSSION This trial failed to show a preventive effect of fibrin glue on overall post-ESD bleeding in high-risk patients. However, the secondary outcomes suggest a potential sealing effect of fibrin glue during the acute period.
PubMed IF 7.6 소화기내과
1062023

제1저자 곽순구 · 교신저자 박준빈

, , , , , , , , , , , , , , ,
Atrial Functional Tricuspid Regurgitation: Importance of Atrial Fibrillation and Right Atrial Remodeling and Prognostic Significance.
JACC Cardiovasc Imaging. 2023;16(5):575-587.

Abstract
BACKGROUND Little is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR).
OBJECTIVES The authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications.
METHODS The authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR.
RESULTS Of 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm²; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001).
CONCLUSIONS In patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR.
PubMed IF 19 순환기내과
1052023

제1저자 김동완 · 교신저자 김동완

, , , , , , , , , , , , , , ,
CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFR-Mutated NSCLC: A Brief Report.
J Thorac Oncol. 2023;18(5):650-656.

Abstract
INTRODUCTION CD73 is overexpressed in EGFR-mutated NSCLC and may promote immune evasion, suggesting potential for combining CD73 blockers with EGFR tyrosine kinase inhibitors (TKIs). This phase 1b-2 study (NCT03381274) evaluated the anti-CD73 antibody oleclumab plus the third-generation EGFR TKI osimertinib in advanced EGFR-mutated NSCLC.
METHODS Patients had tissue T790M-negative NSCLC with TKI-sensitive EGFR mutations after progression on a first- or second-generation EGFR TKI and were osimertinib naive. They received osimertinib 80 mg orally once daily plus oleclumab 1500 mg (dose level 1 [DL1]) or 3000 mg (DL2) intravenously every 2 weeks. Primary end points included safety and objective response rate by Response Evaluation Criteria in Solid Tumors version 1.1.
RESULTS By July 9, 2021, five patients received DL1 and 21 received DL2. Of these patients, 60.0% and 85.7% had any-grade treatment-related adverse events (TRAEs) and 20.0% and 14.3% had grade 3 TRAEs, respectively. No dose-limiting toxicities, serious TRAEs, or deaths occurred. Four patients were T790M positive on retrospective circulating tumor DNA (ctDNA) testing; three had objective partial responses. In patients who were T790M negative in tumor and ctDNA, objective response rate was 25.0% at DL1 and 11.8% at DL2 (all partial responses); response durations at DL2 were 14.8 and 16.6 months. In patients receiving DL2, excluding those who were T790M positive by ctDNA, median progression-free survival was 7.4 months, and median overall survival was 24.8 months. DL2 was the recommended phase 2 dose.
CONCLUSIONS Oleclumab plus osimertinib was found to have moderate activity with acceptable tolerability in previously treated patients with advanced EGFR-mutated NSCLC.
PubMed IF 23.3 혈액종양내과
1042023

제1저자 이현우, 진광남, 김은영 · 교신저자 조영준

, , , , , , , , , , , ,
Artificial Intelligence Solution for Chest Radiographs in Respiratory Outpatient Clinics: Multicenter Prospective Randomized Clinical Trial.
Ann Am Thorac Soc. 2023;20(5):660-667.

Abstract
Rationale: Artificial intelligence (AI)-assisted diagnosis imparts high accuracy to chest radiography (CXR) interpretation; however, its benefit for nonradiologist physicians in detecting lung lesions on CXR remains unclear. Objectives: To investigate whether AI assistance improves the diagnostic performance of physicians for CXR interpretation and affects their clinical decisions in clinical practice. Methods: We randomly allocated eligible patients who visited an outpatient clinic to the intervention (with AI-assisted interpretation) and control (without AI-assisted interpretation) groups. Lung lesions on CXR were recorded by seven nonradiologists with or without AI assistance. The reference standard for lung lesions was established by three radiologists. The primary and secondary endpoints were the physicians' diagnostic accuracy and clinical decision, respectively. Results: Between October 2020 and May 2021, 162 and 161 patients were assigned to the intervention and control groups, respectively. The area under the receiver operating characteristic curve was significantly larger in the intervention group than in the control group for the CXR level (0.840 [95% confidence interval (CI), 0.778-0.903] vs. 0.718 [95% CI, 0.640-0.796]; P = 0.017) and lung lesion level (0.800 [95% CI, 0.740-0.861] vs. 0.677 [95% CI, 0.605-0.750]; P = 0.011). The intervention group had higher sensitivity in terms of both CXR and lung lesion level and a lower false referral rate for the lung lesion level. AI-assisted CXR interpretation did not affect the physicians' clinical decisions. Conclusions: AI-assisted CXR interpretation improves the diagnostic performance of nonradiologist physicians in detecting abnormal lung findings. Clinical trial registered with Clinical Research Information Service of the Republic of Korea (KCT 0005466).
PubMed IF 6 호흡기내과
1032023

제1저자 이우진, 정근화 · 교신저자 최수연, 박경일

, , , , , , ,
Clonal hematopoiesis with DNMT3A mutation is associated with lower white matter hyperintensity volume.
CNS Neurosci Ther. 2023;29(5):1243-1253.

Abstract
BACKGROUND Clonal hematopoiesis of indeterminate potential (CHIP) increases the risk of cerebrovascular events, while its association with cerebral white matter hyperintensity (WMH) is undemonstrated. We evaluated the effect of CHIP and its major driving mutations on cerebral WMH severity.
METHODS From an institutional cohort of a routine health check-up program with a DNA repository database, subjects who were ≥50 years of age, with one or more cardiovascular risk factors but no central nervous system disorder, and performed brain MRI were included. Along with the presence of CHIP and its major driving mutations, clinical and laboratory data were obtained. WMH volume was measured in total, periventricular, and subcortical regions.
RESULTS Among the total 964 subjects, 160 subjects were classified as CHIP positive group. CHIP was most frequently associated with DNMT3A mutation (48.8%), followed by TET2 (11.9%) and ASXL1 (8.1%) mutations. Linear regression analysis adjusting for age, sex, and conventional cerebrovascular risk factors suggested that CHIP with DNMT3A mutation was associated with the lower log-transformed total WMH volume, unlike other CHIP mutations. When classified according to variant allele fraction (VAF) value of DNMT3A mutation, higher VAF classes were associated with the lower log-transformed total WMH and the lower log-transformed periventricular WMH volume, but not with the log-transformed subcortical WMH volumes.
CONCLUSIONS Clonal hematopoiesis with DNMT3A mutation is quantitatively associated with a lower volume of cerebral WMH, especially in the periventricular region. CHIP with DNMT3A mutation might have a protective role in the endothelial pathomechanism of WMH.
PubMed IF 6.6 순환기내과
1022023

제1저자 심지수, 이현승 · 교신저자 박흥우

, , , , ,
Inhibition of glutaminase 1 activity reverses airway hyperresponsiveness and decreases IL-1β+ M1s and IL-17 producing ILC3s in high-fat diet-fed obese mice.
Am J Physiol Lung Cell Mol Physiol. 2023;324(5):L625-L638.

Abstract
In obesity, disturbed glutamine metabolism contributes to enhanced inflammation by inducing alterations in immune cells. As macrophages and innate lymphoid cells (ILCs) are known to be involved in the pathogenesis of obesity-related asthma, we tested our hypothesis that altered glutamine metabolism may link obesity to airway hyperresponsivenss (AHR), a cardinal feature of asthma, focusing on these innate immune cells. Four-week-old male C57BL/6 mice were fed a high-fat diet (HFD) for 13 wk in the presence or absence of BPTES [Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, a selective inhibitor of glutaminase 1 which converts glutamine to glutamate] and their blood, lung, and adipose tissues were analyzed. We then conducted in vitro experiments using bone marrow-derived macrophages (BMDMs) and mouse alveolar macrophage cell line. Furthermore, we investigated plasma glutamine and glutamate levels in obese and nonobese asthmatics. BPTES treatment prevented HFD-induced AHR and significantly decreased IL-1β⁺ classically activated macrophages (M1s) and type 3 ILCs (ILC3s) which increased in the lungs of HFD-fed obese mice. In in vitro experiments, BPTES treatment or glutamine supplement significantly reduced the proportion of IL-1β⁺NLRP3⁺ M1s in lipopolysaccharide-stimulated BMDMs and mouse alveolar macrophage cell line. BPTES treatment also significantly reduced the IL-17 producing ILC3s differentiated from ILCs in naïve mouse lung. In addition, plasma glutamate/glutamine ratios were significantly higher in obese asthmatics compared to nonobese asthmatics. Inhibition of glutaminolysis reverses AHR in HFD-induced obese mice and decreases IL-1β⁺NLRP3⁺ M1s and IL-17 producing ILC3s, which suggests altered glutamine metabolism may have a role in the pathogenesis of obesity-related AHR.
PubMed IF 3.8 알레르기내과
1012023

제1저자 한미연, 문성지 · 교신저자 오국환, 박수경

, , , , , , , , , , , , , , , , , ,
Novel Genetic Variants Associated with Chronic Kidney Disease Progression.
J Am Soc Nephrol. 2023;34(5):857-875.

Abstract
SIGNIFICANCE STATEMENT eGFR slope has been used as a surrogate outcome for progression of CKD. However, genetic markers associated with eGFR slope among patients with CKD were unknown. We aimed to identify genetic susceptibility loci associated with eGFR slope. A two-phase genome-wide association study identified single nucleotide polymorphisms (SNPs) in TPPP and FAT1-LINC02374 , and 22 of them were used to derive polygenic risk scores that mark the decline of eGFR by disrupting binding of nearby transcription factors. This work is the first to identify the impact of TPPP and FAT1-LINC02374 on CKD progression, providing predictive markers for the decline of eGFR in patients with CKD.
BACKGROUND The incidence of CKD is associated with genetic factors. However, genetic markers associated with the progression of CKD have not been fully elucidated.
METHODS We conducted a genome-wide association study among 1738 patients with CKD, mainly from the KoreaN cohort study for Outcomes in patients With CKD. The outcome was eGFR slope. We performed a replication study for discovered single nucleotide polymorphisms (SNPs) with P <10 -6 in 2498 patients with CKD from the Chronic Renal Insufficiency Cohort study. Several expression quantitative trait loci (eQTL) studies, pathway enrichment analyses, exploration of epigenetic architecture, and predicting disruption of transcription factor (TF) binding sites explored potential biological implications of the loci. We developed and evaluated the effect of polygenic risk scores (PRS) on incident CKD outcomes.
RESULTS SNPs in two novel loci, TPPP and FAT1-LINC02374 , were replicated (rs59402340 in TPPP , Pdiscovery =7.11×10 -7 , PCRIC =8.13×10 -4 , Pmeta =7.23×10 -8 ; rs28629773 in FAT1-LINC02374 , Pdiscovery =6.08×10 -7 , PCRIC =4.33×10 -2 , Pmeta =1.87×10 -7 ). The eQTL studies revealed that the replicated SNPs regulated the expression level of nearby genes associated with kidney function. Furthermore, these SNPs were near gene enhancer regions and predicted to disrupt the binding of TFs. PRS based on the independently significant top 22 SNPs were significantly associated with CKD outcomes.
CONCLUSIONS This study demonstrates that SNP markers in the TPPP and FAT1-LINC02374 loci could be predictive markers for the decline of eGFR in patients with CKD.
PubMed IF 9.7 신장내과
1002023

제1저자 최유정 · 교신저자 김형관

, , , , , , , , , ,
Prognosis of patients with hypertrophic cardiomyopathy and low-normal left ventricular ejection fraction.
Heart. 2023;109(10):771-778.

Abstract
OBJECTIVE To investigate whether low-normal left ventricular ejection fraction (LVEF) is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM) and evaluate the incremental value of predictive power of LVEF in the conventional HCM sudden cardiac death (SCD)-risk model.
METHODS This retrospective study included 1858 patients with HCM from two tertiary hospitals between 2008 and 2019. We classified LVEF into three categories: preserved (≥60%), low normal (50%-60%) and reduced (<50%); there were 1399, 415, and 44 patients with preserved, low-normal, and reduced LVEF, respectively. The primary outcome was a composite of SCD, ventricular tachycardia/fibrillation and appropriate implantable cardioverter-defibrillator shocks. Secondary outcomes were hospitalisation for heart failure (HHF), cardiovascular death and all-cause death.
RESULTS During the median follow-up of 4.09 years, the primary outcomes occurred in 1.9%. HHF, cardiovascular death, and all-cause death occurred in 3.3%, 1.9%, and 5.3%, respectively. Reduced LVEF was an independent predictor of SCD/equivalent events (adjusted HR (aHR) 5.214, 95% CI 1.574 to 17.274, p=0.007), adding predictive value to the HCM risk-SCD model (net reclassification improvement 0.625). Compared with patients with HCM with preserved LVEF, those with low-normal and reduced LVEF had a higher risk of HHF (LVEF 50%-60%, aHR 2.457, 95% CI 1.423 to 4.241, p=0.001; LVEF <50%, aHR 7.937, 95% CI 3.315 to 19.002, p<0.001) and cardiovascular death (LVEF 50%-60%, aHR 2.641, 95% CI 1.314 to 5.309, p=0.006; LVEF <50%, aHR 5.405, 95% CI 1.530 to 19.092, p=0.009), whereas there was no significant association with all-cause death.
CONCLUSIONS Low-normal LVEF was an independent predictor of HHF and cardiovascular death in patients with HCM.
PubMed IF 4.4 순환기내과
992023

제1저자 선우성혁, 한상인, 정동준 · 교신저자 이승표, 현택환, 김대형

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Stretchable Low-Impedance Conductor with Ag-Au-Pt Core-Shell-Shell Nanowires and in Situ Formed Pt Nanoparticles for Wearable and Implantable Device.
ACS Nano. 2023;17(8):7550-7561.

Abstract
Mechanically soft metallic nanocomposites have gained much attention as a key material for intrinsically stretchable biointegrated devices. However, it has been challenging to develop a stretchable conductive nanocomposite with all the desired material characteristics including high conductivity, high stretchability, low cytotoxicity, and low impedance. Here, we present a material strategy for the stretchable conductive nanocomposite, particularly emphasizing low impedance, by combining silver-gold-platinum core-shell-shell nanowires and homogeneously dispersed in situ synthesized platinum nanoparticles (Pt NPs). The highly embossed structure of the outermost Pt shell, together with the intrinsic electrical property of Pt, contributes to minimizing the impedance. The gold-platinum double-layer sheath prevents leaching of cytotoxic Ag ions, thus improving biocompatibility. Homogeneously dispersed Pt NPs, synthesized in situ during fabrication of the nanocomposite, simultaneously enhance conductivity, reduce impedance, and improve stretchability by supporting the percolation network formation. This intrinsically stretchable nanocomposite conductor can be applied to wearable and implantable bioelectronics for recording biosignals and delivering electrical stimulations in vivo.
PubMed IF 17.3 순환기내과

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