SCI 발표논문

2023년 248편

382023

제1저자 주달래, 조선욱 · 교신저자 박수경, 송윤주

, , , , , , , , , ,
High intakes of iodine among women during pregnancy and the postpartum period has no adverse effect on thyroid function.
Eur J Nutr. 2023;62(1):239-249.

Abstract
PURPOSE Given the high consumption of seaweed soup by pregnant and lactating Korean women, concerns have been raised about excessive iodine intake. We evaluated the effects of maternal iodine intake on maternal thyroid function and birth outcomes. We also evaluated iodine intake via seaweed soup during late pregnancy and the early postpartum period.
METHODS A total of 349 pregnant women of the Ideal Breast Milk cohort were recruited in late pregnancy, of whom 302 revisited after delivery. Three-day dietary records were assessed at each visit. Blood was collected for thyroid function test. Obstetrical and birth outcomes were obtained.
RESULTS The median dietary iodine intake was 459 μg/day (interquartile range [IQR] 326.5-647.4 μg/day) during pregnancy. Dietary iodine intake by quartile was not significantly associated with maternal thyroid status, or obstetrical or neonatal outcomes. However, the dietary iodine intake in the early postpartum period was 1759 μg/day (IQR 1026.7-2491.1 μg/day) because of a marked increase in seaweed soup consumption. Of all women, 25.8% consumed seaweed soup more than once over the 3 days of dietary records when pregnant, but the figure rose to 93.4% postpartum. Of postpartum women who consumed seaweed soup daily, the median dietary iodine intakes were 1355, 2394, and 3063 μg/day (soup at one, two, and three-or-four meals).
CONCLUSIONS In these iodine-replete pregnant women, dietary iodine intake during pregnancy showed no effect on maternal thyroid function or birth outcomes. However, iodine intake in the early postpartum period was markedly increased by the frequency of seaweed soup consumption.
PubMed IF 4.5 내분비대사내과
372023

제1저자 강창경, 김민강, 박성욱, 김용우 · 교신저자 이창한, 신현무, 김항래, 오명돈

, , , , , , , , , , , , , ,
Comparable humoral and cellular immunity against Omicron variant BA.4/5 of once-boosted BA.1/2 convalescents and twice-boosted COVID-19-naïve individuals.
J Med Virol. 2023;95(2):e28558.

Abstract
The fourth vaccination dose confers additional protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with no prior coronavirus disease-19 (COVID-19). However, its immunological benefit against currently circulating BA.4/5 is unclear in individuals who have received a booster shot and been infected with Omicron variant BA.1/2. We analyzed immune responses in whom had been boosted once and did not have COVID-19 (n = 16), boosted once and had COVID-19 when BA.1/2 was dominant in Korea (Hybrid-6M group, n = 27), and boosted twice and did not have COVID-19 (Vx4 group, n = 15). Antibody binding activities against RBD_{o BA.1} and RBD_{o BA.4/5} , antigen-specific memory CD4⁺ and CD8⁺ T-cell responses against BA.4/5, and B-cell responses against SARS-CoV-2 wild-type did not differ statistically between the Hybrid-6M and Vx4 groups. The humoral and cellular immune responses of the Hybrid-6M group against BA.4/5 were comparable to those of the Vx4 group. Individuals who had been boosted and had an Omicron infection in early 2022 may not have high priority for an additional vaccination.
PubMed IF 3.7 감염내과
362023

제1저자 정재욱, 이소령 · 교신저자 최의근

, , , , , , , , , , , , ,
Cumulative Alcohol Consumption Burden and the Risk of Stroke in Young Adults: A Nationwide Population-Based Study.
Neurology. 2023;100(5):e505-e515.

Abstract
BACKGROUND AND OBJECTIVE Alcohol consumption is one of the important modifiable risk factors for stroke in young adults. The association between the cumulative burden of alcohol consumption and its impact on incident stroke in young adults is unknown. We aimed to investigate the association between cumulative alcohol burden and the risk for stroke among young adults.
METHODS Using data from the Korean National Health Insurance Service database, patients age between 20 and 39 years, who underwent 4 consecutive annual health examinations between 2009 and 2012, were included. The cumulative alcohol burden score of moderate-to-heavy drinking was evaluated by assigning a score of 1 for alcohol consumption ≥105 g/wk at the health examination each year and calculating the sum of 4 years (0-4). The main outcome was incident stroke and its subtypes, ischemic stroke, and hemorrhagic stroke during the follow-up period.
RESULTS Of 1 536 668 patients (mean age of 29.5 years, 71.5% male, and median follow-up of 6-year), 3 153 experienced an incident stroke (incidence rate, 0.37 per 1,000 person-years). After multivariable adjustment, patients with alcohol burden scores of 2, 3, and 4, who consumed more than 105 g/wk of alcohol for 2, 3, and 4 years, demonstrated significantly higher risks for stroke (hazard ratio [HR] 1.19, 95% CI 1.05-1.34 for 2; HR 1.22, 95% CI 1.09-1.38 for 3; HR 1.23, 95% CI 1.10-1.38 for 4) compared with those with a burden score of 0. This positive dose-response relationship was primarily driven by hemorrhagic rather than ischemic stroke. High alcohol burden scores (i.e., 2, 3, and 4) were significantly associated with higher risks for hemorrhagic stroke (HR 1.30, 95% CI 1.10-1.54 for 2; HR 1.42, 95% CI 1.21-1.67 for 3; HR 1.36, 95% CI 1.16-1.59 for 4) compared with a burden score of 0.
DISCUSSION Young adults who engaged in moderate-to-heavy drinking demonstrated a higher risk for incident stroke, especially hemorrhagic stroke. Reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any stroke prevention strategy.
PubMed IF 8.9 순환기내과
352023

제1저자 이소령, 안효정 · 교신저자 최의근

, , , , , ,
Improved prognosis with integrated care management including early rhythm control and healthy lifestyle modification in patients with concurrent atrial fibrillation and diabetes mellitus: a nationwide cohort study.
Cardiovasc Diabetol. 2023;22(1):18.

Abstract
BACKGROUND Patients with concurrent atrial fibrillation (AF) and diabetes mellitus (DM) [AF-DM] have a high risk of cardiovascular and diabetes-related complications, but are less engaged in a comprehensive treatment approach. We evaluated the association of early rhythm control (ERC), lifestyle modification (LSM), and a combination of ERC and LSM with cardiovascular or diabetes-related complication risk in patients with AF-DM (type 2).
METHODS From the National Health Information Database, 47,940 patients diagnosed with AF-DM in 2009-2016 were included. We defined ERC as rhythm control therapy within two years of AF diagnosis and LSM as adherence to ≥ 2 of the healthy behaviors among non-current smoking, non-drinking, and regular exercise. We compared the primary (ischemic stroke) and secondary (macro- and microvascular complications, glycemic emergency, and all-cause death) outcomes in four groups: non-ERC and non-LSM (group 1), LSM only (group 2), ERC only (group 3), and both ERC and LSM (group 4).
RESULTS Of total, 10,617 (22%), 26,730 (55.8%), 2,903 (6.1%), and 7,690 (16.0%) were classified into groups 1 to 4, in sequence. The mean duration from AF diagnosis to ERC was 25.6 ± 75.5 days. During 4.0 (interquartile range: 2.5-6.2) years' follow-up, groups 2 and 3 were associated with 23% and 33% lower risks of stroke than group 1, respectively. Group 4 was associated with the lowest risk of stroke: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51-0.67, p < 0.001. Regarding secondary outcomes, the lowest risks were also observed in group 4; macro- and microvascular complications, glycemic emergency, and all-cause death had HRs (95% CIs) of 0.63 (0.56-0.70), 0.88 (0.82-0.94), 0.72 (0.62-0.84), and 0.80 (0.73-0.87), respectively, all p < 0.001.
CONCLUSIONS For AF-DM patients, ERC and LSM exert a synergistic effect in preventing cardiovascular and diabetes-related complications with the greatest lowered risk of stroke. A comprehensive treatment approach should be pursued in AF-DM patients.
PubMed IF 15.6 순환기내과
342023

제1저자 곽순구, 이승아 · 교신저자 김대희,이승표

, , , , , , , , , , , , , , , ,
Long-term outcomes in distinct phenogroups of patients with primary mitral regurgitation undergoing valve surgery.
Heart. 2023;109(4):305-313.

Abstract
OBJECTIVES Patients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after mitral valve (MV) surgery.
METHODS The retrospective cohort of patients with severe primary MR undergoing MV surgery (derivation, n=1629; validation, n=692) was analysed. Latent class analysis was used to classify patients into subgroups using 15 variables. The primary outcome was all-cause mortality after MV surgery.
RESULTS During follow-up (median 6.0 years), 149 patients (9.1%) died in the derivation cohort. In the univariable Cox analysis, age, female, atrial fibrillation, left ventricular (LV) end-systolic dimension/volumes, LV ejection fraction, left atrial dimension and tricuspid regurgitation peak velocity were significant predictors of mortality following MV surgery. Five distinct phenogroups were identified, three younger groups (group 1-3) and two older groups (group 4-5): group 1, least comorbidities; group 2, men with LV enlargement; group 3, predominantly women with rheumatic MR; group 4, low-risk older patients; and group 5, high-risk older patients. Cumulative survival was the lowest in group 5, followed by groups 3 and 4 (5-year survival for groups 1-5: 98.5%, 96.0%, 91.7%, 95.6% and 83.4%; p<0.001). Phenogroups had similar predictive performance compared with the Mitral Regurgitation International Database score in patients with degenerative MR (3-year C-index, 0.763 vs 0.750, p=0.602). These findings were reproduced in the validation cohort.
CONCLUSION Five phenogroups of patients with severe primary MR with different risk profiles and outcomes were identified. This phenogrouping strategy may improve risk stratification when optimising the timing and type of interventions for severe MR.
PubMed IF 4.4 순환기내과
332023

제1저자 원기범, 신은석 · 교신저자 김효수

, , , , , , , , , , , , , , ,
Body Mass Index and Major Adverse Events During Chronic Antiplatelet Monotherapy After Percutaneous Coronary Intervention With Drug-Eluting Stents - Results From the HOST-EXAM Trial.
Circ J. 2023;87(2):268-276.

Abstract
BACKGROUND This study evaluated the association of body mass index (BMI) with adverse clinical outcomes during chronic maintenance antiplatelet monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
METHODS AND RESULTS Overall, 5,112 patients were stratified (in kg/m²) into underweight (BMI ≤18.4), normal weight (18.5-22.9), overweight (23.0-24.9), obesity (25.0-29.9) and severe obesity (≥30.0) categories with randomized antiplatelet monotherapy of aspirin 100 mg or clopidogrel 75 mg once daily for 24 months. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome and major bleeding of Bleeding Academic Research Consortium type ≥3. Compared with normal weight, the risk of primary composite outcomes was higher in the underweight (hazard ratio [HR] 2.183 [1.199-3.974]), but lower in the obesity (HR 0.730 [0.558-0.954]) and severe obesity (HR 0.518 [0.278-0.966]) categories, which is partly driven by the difference in all-cause death. The risk of major bleeding was significantly higher in the underweight (HR 4.140 [1.704-10.059]) than in the normal weight category. A decrease in categorical BMI was independently associated with the increased risk of primary composite outcomes.
CONCLUSIONS Lower BMI is associated with a higher risk of primary composite outcomes, which is primarily related to the events of all-cause death or major bleeding during chronic maintenance antiplatelet monotherapy after PCI with DES.
PubMed IF 5.8 순환기내과
322023

제1저자 김대욱, 변자민 · 교신저자 고영일, 김재영

, , , ,
Chemotherapy delivery time affects treatment outcomes of female patients with diffuse large B cell lymphoma.
JCI Insight. 2023;8(2):164767.

Abstract
BACKGROUNDChronotherapy is a drug intervention at specific times of the day to optimize efficacy and minimize adverse effects. Its value in hematologic malignancy remains to be explored, in particular in adult patients.METHODSWe performed chronotherapeutic analysis using 2 cohorts of patients with diffuse large B cell lymphoma (DLBCL) undergoing chemotherapy with a dichotomized schedule (morning or afternoon). The effect of a morning or afternoon schedule of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on survival and drug tolerability was evaluated in a survival cohort (n = 210) and an adverse event cohort (n = 129), respectively. Analysis of about 14,000 healthy individuals followed to identify the circadian variation in hematologic parameters.RESULTSBoth progression-free survival (PFS) and overall survival (OS) of female, but not male, patients were significantly shorter when patients received chemotherapy mostly in the morning (PFS HR 0.357, P = 0.033; and OS HR 0.141, P = 0.032). The dose intensity was reduced in female patients treated in the morning (cyclophosphamide 10%, P = 0.002; doxorubicin 8%, P = 0.002; and rituximab 7%, P = 0.003). This was mainly attributable to infection and neutropenic fever: female patients treated in the morning had a higher incidence of infections (16.7% vs. 2.4%) and febrile neutropenia (20.8% vs. 9.8%) as compared with those treated in the afternoon. The sex-specific chronotherapeutic effects can be explained by the larger daily fluctuation of circulating leukocytes and neutrophils in female than in male patients.CONCLUSIONIn female DLBCL patients, R-CHOP treatment in the afternoon can reduce toxicity while it improves efficacy and survival outcome.FUNDINGNational Research Foundation of Korea (NRF) grant funded by the Korean government (grant number NRF-2021R1A4A2001553), Institute for Basic Science IBS-R029-C3, and Human Frontiers Science Program Organization Grant RGY0063/2017.
PubMed IF 6.8 혈액종양내과
312023

제1저자 최정민, 이소령 · 교신저자 최의근

, , , , , , , , , ,
Accumulated hypertension burden on atrial fibrillation risk in diabetes mellitus: a nationwide population study.
Cardiovasc Diabetol. 2023;22(1):12.

Abstract
BACKGROUND Patients with diabetes mellitus have an increased risk of incident atrial fibrillation (AF). The effect of accumulated hypertension burden is a less well-known modifiable risk factor. We explored the relationship between accumulated hypertension burden and incident AF in these patients.
METHODS We evaluated data for 526,384 patients with diabetes who underwent three consecutive health examinations, between 2009 and 2012, from the Korean National Health Insurance Service. Hypertension burden was calculated by assigning points to each stage of hypertension in each health examination: 1 for stage 1 hypertension (systolic blood pressure [SBP] 130-139 mmHg; diastolic blood pressure [DBP] 80-89 mmHg); 2 for stage 2 (SBP 140-159 mmHg and DBP 90-99 mmHg); and 3 for stage 3 (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg). Patients were categorized into 10 hypertensive burden groups (0-9). Groups 1-9 were then clustered into 1-3, 4-6, and 7-9.
RESULTS During a mean follow-up duration of 6.7 ± 1.7 years, AF was newly diagnosed in 18,561 (3.5%) patients. Compared to patients with hypertension burden 0, those with burden 1 to 9 showed a progressively increasing risk of incident AF: 6%, 11%, 16%, 24%, 28%, 41%, 46%, 57%, and 67% respectively. Clusters 1-3, 4-6, and 7-9 showed increased risks by 10%, 26%, and 45%, respectively, when compared to a hypertension burden of 0.
CONCLUSIONS Accumulated hypertension burden was associated with an increased risk of incident AF in patients with diabetes. Strict BP control should be emphasized for these patients.
PubMed IF 15.6 순환기내과
302023

제1저자 허민, 박영수 · 교신저자 윤혁

, , , , , , ,
Potential of Gut Microbe-Derived Extracellular Vesicles to Differentiate Inflammatory Bowel Disease Patients from Healthy Controls.
Gut Liver. 2023;17(1):108-118.

Abstract
BACKGROUND/AIMS This study aimed to evaluate the potential of the stool microbiome and gut microbe-derived extracellular vesicles (EVs) to differentiate between patients with inflammatory bowel disease (IBD) and healthy controls, and to predict relapse in patients with IBD.
METHODS Metagenomic profiling of the microbiome and bacterial EVs in stool samples of controls (n=110) and patients with IBD (n=110) was performed using 16S rRNA sequencing and then compared. Patients with IBD were divided into two enterotypes based on their microbiome, and the cumulative risk of relapse was evaluated.
RESULTS There was a significant difference in the composition of the stool microbiome and gut microbe-derived EVs between patients with IBD and controls. The alpha diversity of the microbiome in patients with IBD was significantly lower than that in controls, while the beta diversity also differed significantly between the two groups. These findings were more prominent in gut microbe-derived EVs than in the stool microbiome. The survival curve tended to be different for enterotypes based on the gut microbe-derived EVs; however, this difference was not statistically significant (log-rank test, p=0.166). In the multivariable analysis, elevated fecal calprotectin (>250 mg/kg) was the only significant risk factor associated with relapse (adjusted hazard ratio, 3.147; 95% confidence interval, 1.545 to 6.408; p=0.002).
CONCLUSIONS Analysis of gut microbe-derived EVs is better at differentiating patients with IBD from healthy controls than stool microbiome analysis.
PubMed IF 4.1 소화기내과
292023

제1저자 이상협 · 교신저자 이홍식

, , , , , , , , , , , , ,
Revised Clinical Practice Guidelines of the Korean Pancreatobiliary Association for Acute Pancreatitis.
Gut Liver. 2023;17(1):34-48.

Abstract
Acute pancreatitis can range from a mild, self-limiting disease requiring no more than supportive care, to severe disease with life-threatening complications. With the goal of providing a recommendation framework for clinicians to manage acute pancreatitis, and to contribute to improvements in national health care, the Korean Pancreatobiliary Association (KPBA) established the Korean guidelines for acute pancreatitis management in 2013. However, many challenging issues exist which often lead to differences in clinical practices. In addition, with newly obtained evidence regarding acute pancreatitis, there have been great changes in recent knowledge and information regarding this disorder. Therefore, the KPBA committee underwent an extensive revision of the guidelines. The revised guidelines were developed using the Delphi method, and the main topics of the guidelines include the following: diagnosis, severity assessment, initial treatment, nutritional support, convalescent treatment, and the treatment of local complications and necrotizing pancreatitis. Specific recommendations are presented, along with the evidence levels and recommendation grades.
PubMed IF 4.1 소화기내과
282023

제1저자 이현우, 정고은 · 교신저자 김덕겸, 김원

, , , , , , , , , ,
Impact of Evolutionary Changes in Nonalcoholic Fatty Liver Disease on Lung Function Decline.
Gut Liver. 2023;17(1):139-149.

Abstract
BACKGROUND/AIMS A relationship between fatty liver and lung function impairment has been identified, and both are independently associated with metabolic dysfunction. However, the temporal relationship between changes in fatty liver status and lung function and their genome-wide association remain unclear.
METHODS This longitudinal cohort consisted of subjects who received serial health check-ups, including liver ultrasonography and spirometry, for ≥3 years between 2003 and 2015. Lung function decline rates were classified as "slow" and "accelerated" and compared among four different sonographic changes in steatosis status: "normal," "improved," "worsened," and "persistent." A genome-wide association study was conducted between the two groups: normal/improved steatosis with a slow decline in lung function versus worsened/persistent steatosis with an accelerated decline in lung function.
RESULTS Among 6,149 individuals, the annual rates of decline in forced vital capacity (FVC) and forced expiratory volume measured in the first second of exhalation (FEV₁) were higher in the worsened/persistent steatosis group than in the normal/improved steatosis group. In multivariable analysis, persistent or worsened status of fatty liver was significantly associated with accelerated declines in FVC (persistent status, odds ratio [OR]=1.22, 95% confidence interval [CI]=1.04-1.44; worsened status, OR=1.30, 95% CI=1.12-1.50), while improved status of fatty liver was significantly associated with slow declines in FEV₁ (OR=0.77, 95% CI=0.64-0.92). The PNPLA3 risk gene was most strongly associated with steatosis status change and accelerated declines in FVC (rs12483959, p=2.61×10^-7) and FEV₁ (rs2294433, p=3.69×10^-8).
CONCLUSIONS Regression of fatty liver is related to lung function decline. Continuing efforts to improve fatty liver may preserve lung function, especially for subjects with a high genetic risk.
PubMed IF 4.1 소화기내과
272023

제1저자 김민혜 · 교신저자 박성주, 김세훈

, , , , , , , , , , , , , , , ,
Clinical aspects of severe cutaneous adverse reactions caused by beta-lactam antibiotics: A study from the Korea SCAR registry.
World Allergy Organ J. 2023;16(1):100738.

Abstract
BACKGROUND Although beta-lactams are 1 of the major causative agents of severe cutaneous adverse reactions (SCAR), their epidemiology and clinical aspects have been poorly studied. This study aimed to investigate the characteristics of SCAR caused by beta-lactams in the Korean SCAR registry.
METHODS We retrospectively analyzed beta-lactam-induced SCAR cases collected from 28 tertiary university hospitals in Korea between 2010 and 2015. The SCAR phenotypes included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap, and drug reaction with eosinophilia and systemic symptoms (DRESS). Beta-lactams were classified according to their chemical structures: penicillins, cephalosporins, and carbapenems. The causative beta-lactams, clinical and laboratory features, treatments, and outcomes were evaluated.
RESULTS Among the 275 antibiotic-induced SCAR cases, 170 patients developed SCAR induced by beta-lactams. Beta-lactam antibiotic-induced SCAR showed more frequent SJS/TEN compared to SCAR induced by non-beta-lactam antibiotics (SJS/TEN/SJS-TEN overlap/DRESS: 36.5/11.2/5.9/46.5% vs. 23.8/10.5/2.9/62.9%, P = 0.049). Cephalosporin was the most common culprit drug. Particularly, 91 and 79 patients presented with SJS/TEN and DRESS, respectively. The odds ratio (OR) for poor prognosis, such as sequelae and death, was significantly increased in subjects with SJS-TEN overlap and TEN and carbapenem as culprit drug in the multivariate analysis (OR, 35.61; P = 0.016, OR, 28.07; P = 0.006, OR 30.46; P = 0.027).
CONCLUSION Among antibiotic-induced SCAR, clinical features were different depending on whether the culprit drug was a beta-lactam antibiotic or SCAR type. The poor prognosis was related to SJS-TEN overlap, TEN type, and carbapenem as the culprit drug.
PubMed IF 4 순환기내과
262023

제1저자 박준빈, 윤제연 · 교신저자 김형관

, , , , , , , , , , , , , ,
Risk of incident mental disorders in hypertrophic cardiomyopathy: a nationwide propensity-matched study.
Eur J Prev Cardiol. 2023;30(1):85-94.

Abstract
AIMS We sought to determine the risk of mental disorders in patients with hypertrophic cardiomyopathy (HCM) compared with those without HCM.
METHODS AND RESULTS This is a retrospective propensity score-matched cohort study using nationwide population-based data from the Korean National Health Insurance Service. Overall, 4046 patients with HCM and 12138 matched individuals were followed up until the first diagnosis of mental disorders or the end of the follow up. The primary outcome was a composite of incident mood, anxiety, stress-related, or somatoform disorders. Secondary outcomes included two components of the primary outcome (i.e. mood disorders and anxiety/stress-related/somatoform disorders). During a median follow-up period of 4.1 years, the incidence rate of the primary outcome was 54.4 and 31.5/1000 person-years among the HCM and control groups, respectively, resulting in a hazard ratio (HR) of 1.719 (95% confidence interval: 1.589-1.860). Within the first month after HCM diagnosis, the HR for the primary outcome was 3.074 (2.096-4.508). Beyond 1 month, the HRs decreased, ranging from 2.281 (1.952-2.665) during 1-12 months, to 2.087 (1.831-2.380) during 12-36 months and 1.258 (1.090-1.452) after 36 months of follow up. Similar results were observed for the secondary outcomes. In sensitivity analysis, the risk of the specific categories of mental disorders, including single or recurrent depressive episodes and anxiety disorders, was also higher in patients with HCM than matched controls.
CONCLUSION HCM was significantly associated with the risk of incident mental disorders, particularly within 1 year after HCM diagnosis, underscoring the importance of screening mental health problems, including mood and anxiety disorders, in patients with HCM.
PubMed IF 10 순환기내과
252023

제1저자 강지훈, 박경우 · 교신저자 김효수, 구본권

, , , , , , , , , , , ,
Aspirin Versus Clopidogrel for Long-Term Maintenance Monotherapy After Percutaneous Coronary Intervention: The HOST-EXAM Extended Study.
Circulation. 2023;147(2):108-117.

Abstract
BACKGROUND Long-term outcomes of antiplatelet monotherapy in patients who receive percutaneous coronary intervention are unknown. The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) Extended study reports the posttrial follow-up results of the original HOST-EXAM trial.
METHODS From March 2014 through May 2018, 5438 patients who maintained dual antiplatelet therapy without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents were randomly assigned in a 1:1 ratio to receive clopidogrel (75 mg once daily) or aspirin (100 mg once daily). The primary end point (a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission attributable to acute coronary syndrome, and Bleeding Academic Research Consortium type 3 or greater bleeding), secondary thrombotic end point (cardiac death, nonfatal myocardial infarction, ischemic stroke, readmission attributable to acute coronary syndrome, and definite or probable stent thrombosis), and bleeding end point (Bleeding Academic Research Consortium type 2 or greater bleeding) were analyzed during the extended follow-up period. Analysis was performed on the per-protocol population (2431 patients in the clopidogrel group and 2286 patients in the aspirin group).
RESULTS During a median follow-up of 5.8 years (interquartile range, 4.8-6.2 years), the primary end point occurred in 12.8% and 16.9% in the clopidogrel and aspirin groups, respectively (hazard ratio, 0.74 [95% CI, 0.63-0.86]; P<0.001). The clopidogrel group had a lower risk for the secondary thrombotic end point (7.9% versus 11.9%; hazard ratio, 0.66 [95% CI, 0.55-0.79]; P<0.001) and secondary bleeding end point (4.5% versus 6.1%; hazard ratio, 0.74 [95% CI, 0.57-0.94]; P=0.016). There was no significant difference in the incidence of all-cause death between the 2 groups (6.2% versus 6.0%; hazard ratio, 1.04 [95% CI, 0.82-1.31]; P=0.742). Landmark analysis at 2 years showed that the beneficial effect of clopidogrel was consistent throughout the follow-up period.
CONCLUSIONS During an extended follow-up of >5 years after randomization, clopidogrel monotherapy compared with aspirin monotherapy was associated with lower rates of the composite net clinical outcome in patients without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents.
REGISTRATION URL: https://www.
CLINICALTRIALS gov; Unique identifier: NCT02044250.
PubMed IF 41.3 순환기내과
242023

제1저자 강지훈 · 교신저자 김효수

, , , , , , , , , , , ,
Real-world evidence of switching P2Y12 receptor-inhibiting therapies to prasugrel after PCI in patients with ACS: results from EFF-K registry.
BMC Cardiovasc Disord. 2023;23(1):6.

Abstract
BACKGROUND Potent P2Y₁₂ inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS.
METHODS The EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting).
RESULTS A total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56-2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups.
CONCLUSIONS Dual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI.
TRIAL REGISTRATION KCT0002356, registered June 13, 2017.
PubMed IF 3.1 순환기내과
232023

제1저자 유기연 · 교신저자 유기연, 박흥우

, , , , ,
Increased Risk of Anemia in Patients with Asthma.
Clin Epidemiol. 2023;15:31-38.

Abstract
PURPOSE Asthma can cause a systemic inflammatory response, and anemia of chronic disease (ACD) is known to be caused by other disorders with a chronic inflammatory state. However, it is unclear whether the incidence of anemia is increased in patients with asthma. The objective of this study was to compare the incidence of anemia in patients with asthma and healthy adults.
PATIENTS AND METHODS This retrospective cohort study included patients newly diagnosed with asthma at Seoul National University Hospital from 2010 to 2017. Patients with comorbidities before the first visit (index date) that may increase anemia risk were excluded. Cox regression models adjusting for patient age, sex, and obesity were used to compare anemia hazard ratios (HRs) between asthma patients (n=1354) and healthy adults (n=1731).
RESULTS This study included 3085 patients. During 5-y follow-up, anemia occurred in 203 (15.0%) patients with asthma and 79 (4.6%) healthy adults. Compared with healthy adults, the HR for anemia after adjusting for age, sex, and obesity was 4.06 (95% CI: 2.70-6.09) in patients with asthma. In patients aged 18-64.9 y, the adjusted HR of anemia was 3.27 (95% CI: 2.12-5.04) in patients with asthma, compared to healthy patients. In patients >65 y, this adjusted HR was 5.56 (95% CI: 1.31-23.67).
CONCLUSION The risk of anemia was increased in patients with asthma after adjusting for sex, age, and obesity and excluding comorbidities that can cause anemia. These results suggest the need for regular monitoring for anemia in patients with asthma.
PubMed IF 4.3 알레르기내과
222023

제1저자 김학령 · 교신저자 김학령

, , ,
Prognostic value of reactive hyperemia index using peripheral artery tonometry in patients with heart failure.
Sci Rep. 2023;13(1):125.

Abstract
Given the high prevalence and poor prognosis of heart failure (HF), finding prognostic factors for patients with HF is crucial. This study investigated the prognostic value of reactive hyperemia index (RHI), a measure of endothelial function, in HF. A total of 90 HF patients (mean age, 63.7 ± 13.2 years; female, 25.6%) with a history of hospitalization for HF treatment were prospectively enrolled. RHI was measured using digital arterial tonometry in a stable condition. Clinical events, including all-cause death and HF admission, were assessed. During the median follow-up of 3.66 years (interquartile range, 0.91-4.94 years), 26 clinical events (28.9%) occurred. Although there were no significant differences in risk factors and laboratory findings according to the occurrence of clinical events, the RHI value was significantly lower in patients with clinical events than in those without (1.21 ± 0.34 vs. 1.68 ± 0.48; P < 0.001). Kaplan-Meier survival analysis showed that a lower RHI value (< 1.48) was associated with a significantly higher incidence rate of clinical events (log-rank P < 0.001). In multivariable cox regression analysis, a low RHI value (< 1.48) was associated with an increased risk of clinical events (hazard ratio, 14.09; 95% confidence interval, 3.61-54.99; P < 0.001) even after controlling for potential confounders. Our study showed that reduced RHI was associated with an increased risk of adverse clinical outcomes in HF. This suggests that endothelial dysfunction may be an important prognostic marker in patients with HF.
PubMed IF 4.9 순환기내과
212023

제1저자 정고은, 유수종 · 교신저자 한경도, 조은주

, , , , , , , , , ,
Lean or diabetic subtypes predict increased all-cause and disease-specific mortality in metabolic-associated fatty liver disease.
BMC Med. 2023;21(1):4.

Abstract
BACKGROUND Metabolic-associated fatty liver disease (MAFLD) encompasses diverse disease groups with potentially heterogeneous clinical outcomes. We investigated the risk of all-cause and disease-specific mortality in MAFLD subgroups.
METHODS Using the Korean National Health Insurance Service database, participants were divided into four subgroups: no MAFLD, MAFLD-diabetes, MAFLD-overweight/obese, and MAFLD-lean. Hazard ratios (HRs) and 95% confidence interval (CI) values for all-cause and disease-specific mortality according to MAFLD subgroups were analyzed using Cox proportional hazards models.
RESULTS Among 9,935,314 participants, those with MAFLD-diabetes showed the highest risk of all-cause and disease-specific mortality. The HRs (95% CI) for all-cause mortality were 1.61 (1.59-1.63), 1.36 (1.34-1.38), and 1.19 (1.18-1.20) in the MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obese groups, respectively. The magnitude of cardiovascular disease and cancer-related risk showed the same pattern. The risk of liver-related mortality in the MAFLD-lean group (HR: 2.84, 95% CI: 2.72-2.97) was comparable with that in the MAFLD-diabetes group (HR: 2.85, 95% CI: 2.75-2.95). When stratified by body mass index, liver-related mortality was the highest in MAFLD-lean individuals in the underweight group (HR, 5.03, 95% CI: 4.23-5.97).
CONCLUSIONS The MAFLD-lean and MAFLD-diabetes groups had a higher risk of all-cause and disease-specific mortality than did the MAFLD-overweight/obese group. Classifying MAFLD subgroups based on metabolic phenotypes might help risk stratification of patients with MAFLD.
PubMed IF 8.7 소화기내과
202023

제1저자 손민지, 임수 · 교신저자 임수

, , , ,
Effects of Initial Combinations of Gemigliptin Plus Metformin Compared with Glimepiride Plus Metformin on Gut Microbiota and Glucose Regulation in Obese Patients with Type 2 Diabetes: The INTESTINE Study.
Nutrients. 2023;15(1):nu15010248.

Abstract
The efficacy and safety of medications can be affected by alterations in gut microbiota in human beings. Among antidiabetic medications, incretin-based therapy such as dipeptidyl peptidase 4 inhibitors might affect gut microbiomes, which are related to glucose metabolism. This was a randomized, controlled, active-competitor study that aimed to compare the effects of combinations of gemigliptin−metformin vs. glimepiride−metformin as initial therapies on gut microbiota and glucose homeostasis in drug-naïve patients with type 2 diabetes. Seventy drug-naïve patients with type 2 diabetes (mean age, 52.2 years) with a glycated hemoglobin (HbA1c) level ≥7.5% were assigned to either gemigliptin−metformin or glimepiride−metformin combination therapies for 24 weeks. Changes in gut microbiota, biomarkers linked to glucose regulation, body composition, and amino acid blood levels were investigated. Although both treatments decreased the HbA1c levels significantly, the gemigliptin−metformin group achieved HbA1c ≤ 7.0% without hypoglycemia or weight gain more effectively than did the glimepiride−metformin group (59% vs. 24%; p < 0.05). At the phylum level, the Firmicutes/Bacteroidetes ratio tended to decrease after gemigliptin−metformin therapy (p = 0.065), with a notable depletion of taxa belonging to Firmicutes, including Lactobacillus, Ruminococcus torques, and Streptococcus (all p < 0.05). However, regardless of the treatment modality, a distinct difference in the overall gut microbiome composition was noted between patients who reached the HbA1c target goal and those who did not (p < 0.001). Treatment with gemigliptin−metformin resulted in a higher achievement of the glycemic target without hypoglycemia or weight gain, better than with glimepiride−metformin; these improvements might be related to beneficial changes in gut microbiota.
PubMed IF 5.8 내분비대사내과
192023

제1저자 최광용 · 교신저자 이현우

, , , , , ,
Rapid FEV1/FVC Decline Is Related With Incidence of Obstructive Lung Disease and Mortality in General Population.
J Korean Med Sci. 2023;38(1):e4.

Abstract
BACKGROUND Forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) naturally decreases with age; however, an excessive decline may be related with increased morbidity and mortality. This study aimed to evaluate the FEV₁/FVC decline rate in the Korean general population and to identify whether rapid FEV₁/FVC decline is a risk factor for obstructive lung disease (OLD) and all-cause and respiratory mortality.
METHODS We evaluated individuals aged 40-69 years who underwent baseline and biannual follow-up spirometric assessments for up to 18 years, excluding those with airflow limitations at baseline. Based on the quartiles of the annual FEV₁/FVC decline rate, the most negative FEV₁/FVC change (1^st quartile of annual FEV₁/FVC decline rate) was classified as rapid FEV₁/FVC decline. We investigated the risk of progression to OLD and all-cause and respiratory mortality in individuals with rapid FEV₁/FVC decline.
RESULTS The annual FEV₁/FVC decline rate in the eligible 7,768 patients was 0.32 percentage point/year. The incidence rate of OLD was significantly higher in patients with rapid FEV₁/FVC decline than in those with non-rapid FEV₁/FVC decline (adjusted incidence rate, 2.119; 95% confidence interval [CI], 1.932-2.324). Rapid FEV₁/FVC decline was an independent risk factor for all-cause mortality (adjusted hazard [HR], 1.374; 95% CI, 1.105-1.709) and respiratory mortality (adjusted HR, 1.353; 95% CI, 1.089-1.680).
CONCLUSION The annual FEV₁/FVC decline rate was 0.32%p in the general population in Korea. The incidence rate of OLD and the hazards of all-cause and respiratory mortality were increased in rapid FEV₁/FVC decliners.
PubMed IF 3.2 호흡기내과
182023

제1저자 강창경, 최백규 · 교신저자 이지연, 문준호, 송경호, 정인경

, , , , , , , , , , , , , , , , , , , , , , ,
Clinical impact of clonal hematopoiesis on severe COVID- 19 patients without canonical risk factors.
Haematologica. 2023;108(1):257-260.

PubMed IF 8.2 감염내과
172023

제1저자 안효정, 이소령 · 교신저자 최의근

, , , , , , ,
Evaluation of the Paradoxical Association Between Lipid Levels and Incident Atrial Fibrillation According to Statin Usage: A Nationwide Cohort Study.
J Lipid Atheroscler. 2023;12(1):73-86.

Abstract
OBJECTIVE Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are associated with a lower risk of atrial fibrillation (AF). Statin use might exert confounding effects on the paradoxical associations; however, the relationships that distinguish statin users from non-users have not been thoroughly evaluated.
METHODS From the Korean National Health Insurance Database, we included 9,778,014 adults who underwent a health examination in 2009. The levels of TC and LDL-C at the health examination were categorized into quartile values of the total study population. We grouped the study population into statin users and non-users and investigated the associations between TC, LDL-C, and the risk of incident AF.
RESULTS Of the total population, 867,336 (8.9%) were taking statins. During a mean follow-up of 8.2 years, inverse associations of TC - AF and LDL-C - AF were observed; higher levels of TC and LDL-C were associated with the lower risk of AF in the total population. Overall, statin users showed higher AF incidence rate than non-users, but the inverse associations of TC - AF and LDL-C - AF were consistently observed irrespective of statin usage; adjusted hazard ratio with 95% confidence interval was 0.81 (0.79-0.84) for statin users and 0.81 (0.80-0.83) for non-users in the highest TC quartile, and 0.84 (0.82-0.87) for statin users and 0.85 (0.84-0.86) for non-users in the highest LDL-C quartile (all p<0.001).
CONCLUSION The paradoxical relationship between lipid levels (TC and LDL-C) and the risk of AF remains consistent in both statin users and non-users.
PubMed IF 2.34 순환기내과
162023

제1저자 양한모, 김준오 · 교신저자 김효수

, , , , , , ,
Resistin impairs mitochondrial homeostasis via cyclase-associated protein 1-mediated fission, leading to obesity-induced metabolic diseases.
Metabolism. 2023;138:155343.

Abstract
OBJECTIVE One of the suggested mechanisms of obesity-induced insulin resistance is mitochondrial dysfunction in target tissues such as skeletal muscle. In our study, we examined whether resistin, an adipokine associated with obesity-mediated insulin resistance, induced metabolic disorders by impairing mitochondrial homeostasis.
METHODS The morphology and function of mitochondria of skeletal muscle were examined in resistin-knockout and humanized resistin mice that were subjected to high-fat diet for 3 months. Morphology was examined by transmission electron microscopy. Mitochondria bioenergetics of skeletal muscle were evaluated using a Seahorse XF96 analyzer. Human skeletal myoblasts were used for in vitro studies on signaling mechanisms in responses to resistin.
RESULTS A high-fat diet in humanized resistin mice increased fragmented and shorter mitochondria in the skeletal muscle, whereas resistin-knockout mice had healthy normal mitochondria. In vitro studies showed that human resistin treatment impaired mitochondrial homeostasis by inducing mitochondrial fission, leading to a decrease in ATP production and mitochondrial dysfunction. Induction of mitochondrial fission by resistin was accompanied by increased formation of mitochondria-associated ER membranes (MAM). At the same time, resistin induced up-regulation of the protein kinase A (PKA) pathway. This activation of PKA induced phosphorylation of Drp1 at serine 616, leading to Drp1 activation and subsequent induction of mitochondrial fission. The key molecule that mediated human resistin-induced mitochondrial fission was adenylyl cyclase-associated protein 1 (CAP1), which was reported as a bona fide receptor for human resistin. Moreover, our newly developed biomimetic selective blocking peptide could repress human resistin-mediated mitochondrial dysfunction. High-fat diet-fed mice showed lower exercise capacity and higher insulin resistance, which was prevented by a novel peptide to block the binding of resistin to CAP1 or in the CAP1-knockdown mice.
CONCLUSIONS Our study demonstrated that human resistin induces mitochondrial dysfunction by inducing abnormal mitochondrial fission. This result suggests that the resistin-CAP1 complex could be a potential therapeutic target for the treatment of obesity-related metabolic diseases such as diabetes and cardiometabolic diseases.
PubMed IF 16.7 순환기내과
152023

제1저자 권주성, 윤창환 · 교신저자 채인호

, , , , , , , , , , , , , , , ,
BioMatrix Versus Orsiro Stents for Coronary Artery Disease: A Multicenter, Randomized, Open-Label Study.
Circ Cardiovasc Interv. 2023;16(1):e012307.

Abstract
BACKGROUND Comparative studies of ultrathin-strut biodegradable polymer sirolimus-eluting stent (BP-SES) have reported promising results and validated its excellent outcomes in terms of safety and efficacy. However, there are limited studies comparing BP drug-eluting stents with struts of different thicknesses. We compared the long-term clinical outcomes of patients treated with an ultrathin-strut BP-SES or a thick-strut biodegradable polymer biolimus-eluting stent (BP-BES).
METHODS The BIODEGRADE trial (Biomatrix and Orsiro Drug-Eluting Stents in Angiographic Result in Patients With Coronary Artery Disease) is a multicenter prospective randomized study comparing coronary revascularization in patients with ultrathin-strut BP-SES and thick-strut BP-BES with the primary end point of target lesion failure at 18 months posttreatment. We performed the prespecified analysis of 3-year clinical outcomes.
RESULTS In total, 2341 patients were randomized to receive treatment with ultrathin-strut BP-SES (N=1175) or thick-strut BP-BES (N=1166). The 3-year incidence rate of target lesion failure was 3.2% for BP-SES and 5.1% for BP-BES (P=0.023). The difference was primarily due to differences in ischemia-driven target lesion revascularization (BP-SES, 1.5%; BP-BES, 2.8%; P=0.035) between groups. A landmark analysis of the late follow-up period showed significant differences in target lesion failure, with outcomes being better in BP-SES. Cardiac death and target lesion revascularization were significantly lower in the BP-SES group.
CONCLUSIONS In a large, randomized trial, the long-term clinical outcome of target lesion failure at 3 years was significantly better among patients treated with the ultrathin-strut BP-SES. The results indicate the superiority of the ultrathin-strut BP-SES compared with the thick-strut BP-BES.
REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT02299011.
PubMed IF 7.2 순환기내과
142023

제1저자 조수민 · 교신저자 조재영

,
Impact of the COVID-19 pandemic on adherence to positive airway pressure treatment in patients with obstructive sleep apnea: systematic review and meta-analysis.
Ther Adv Respir Dis. 2023;17:17534666231214040.

Abstract
BACKGROUND The adverse effects of the COVID-19 pandemic on sleep have been well studied. However, whether the COVID-19 pandemic impacted positive airway pressure (PAP) adherence in patients with obstructive sleep apnea (OSA) remains unclear.
OBJECTIVES To evaluate the impact of the COVID-19 pandemic on adherence to PAP therapy in patients with OSA.
DESIGN A retrospective cohort study, systematic review, and meta-analysis.
DATA SOURCES AND METHODS The retrospective study included adults with OSA who received PAP prescriptions within the year before and the year after the start date of COVID-19 social distancing (22 March 2020) in South Korea. The threshold of clinical significance for PAP adherence was defined as 0.5 h/day. We also searched for relevant studies published up to 15 January 2023 using the MEDLINE and Embase databases. We performed a random-effects meta-analysis of our findings with the identified studies regarding the standardized mean change (SMC) with a 95% CI of PAP adherence.
RESULTS Our study included a total of 306 patients (mean age, 59.7 years; men, 73.5%). The average daily PAP usage was 5.10 ± 1.63 h before the COVID-19 pandemic and 4.79 ± 1.96 h during the pandemic (mean difference, -0.31 h/day; 95% CI, -0.46 to -0.15 h/day; p < 0.001 using paired t-test). After identifying 10 observational before-and-after studies through a systematic review, we conducted a meta-analysis that included our original data and showed that adherence to PAP treatment was not different before and during the COVID-19 pandemic (SMC, 0.01; 95% CI, -0.18 to 0.19; p = 0.952).
CONCLUSION Although the COVID-19 pandemic had a statistically negative impact on adherence to PAP treatment in South Korea, the effect was not clinically relevant in patients with OSA. According to our meta-analysis, adherence to PAP treatment was not different before and during the COVID-19 pandemic in patients with OSA.
TRIAL REGISTRATION PROSPERO database; No.: CRD42023414268; URL: https://www.crd.york.ac.uk/PROSPERO.
PubMed IF 3.2 호흡기내과
132023

제1저자 배세연, 김기병 · 교신저자 이은영, 박성호, 박민경현

, , , , , , , , , , , ,
RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts.
Cell Mol Immunol. 2023;20(1):94-109.

Abstract
Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to the development of osteoclast-specific therapeutic interventions.
PubMed IF 23.9 류마티스내과
122023

제1저자 윤지선 · 교신저자 오도연

, ,
Recent Progress in Immunotherapy for Gastric Cancer.
J Gastric Cancer. 2023;23(1):207-223.

Abstract
Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.
PubMed IF 5.1 혈액종양내과
112023

제1저자 임수 · 교신저자 임수

,
How to cope with emerging viral diseases: lessons from South Korea's strategy for COVID-19, and collateral damage to cardiometabolic health.
Lancet Reg Health West Pac. 2023;30:100581.

Abstract
South Korea is a unique country in many aspects in terms of its strategy against the COVID-19 pandemic. From February 2020, the South Korean government adopted active epidemiological investigations, strict isolation of affected patients, and extensive public lockdowns, which were helpful in controlling spread until the end of 2021. This stable situation in South Korea has changed dramatically since the Omicron variant-reportedly less severe but more infective than the original strain-became dominant from January 2022. From mid-February to mid-April 2022, daily cases of COVID-19 in South Korea increased steeply, reaching > 600,000 cases/day: the highest incidence rate in the world at that time. Despite this rapid increase, the South Korean government has eased its preventive strategies progressively, based on the belief in the efficacy of >80% of vaccine coverage in the population. Now, in June 2022, the COVID-19 situation in South Korea is improving. The mortality rate is 0·13%: the lowest among the 30 countries with the highest case counts. High vaccine coverage rate (87·7%), the efficient healthcare system, and active co-operation between private sectors and the central government seem to have contributed to this. However, it should also be noted that the COVID-19 pandemic and its preventive measures have had a negative influence on cardiometabolic profiles in the country. Considering the likelihood of another novel variant of SARS-CoV-2 or new infectious disease emerging in the future, understanding the situation in South Korea and the strategies flexibly adopted by its government could be beneficial for many countries.
PubMed IF 8.559 내분비대사내과
102023

제1저자 손준혁 · 교신저자 이상협

, , , , ,
Flavokawain B Inhibits Growth of Cholangiocarcinoma Cells by Suppressing the Akt Pathway.
In Vivo. 2023;37(3):1077-1084.

Abstract
BACKGROUND/AIM Cholangiocarcinoma is a devastating malignancy with limited treatment options and poor prognosis. Natural products have gained considerable attention for showing antitumor effects with less toxicities. Flavokawain B (FKB), a natural product, has been studied for its antitumor effects on various cancer cells. However, the anti-tumor effect of FKB on cholangiocarcinoma cells remains unknown. This study aimed at investigating the antitumor effect of FKB on cholangiocarcinoma cells in vitro and in vivo.
MATERIALS AND METHODS SNU-478, a human cholangiocarcinoma cell line, was used in this study. Effects of FKB on cell growth inhibition and apoptosis were investigated. The synergistic anti-tumor effect of FKB and cisplatin in combination was also evaluated. Western blotting was performed to examine the underlying molecular mechanisms of the effect of FKB. A xenograft mouse model study was performed to investigate the effect of FKB in vivo.
RESULTS FKB inhibited cell proliferation of cholangiocarcinoma cells in a concentration- and time-dependent manner. FKB also induced cellular apoptosis additively in combination with cisplatin. Akt pathway was suppressed by FKB either alone or in combination with cisplatin. In the xenograft model, FKB treatment in combination with cisplatin/gemcitabine significantly inhibited tumor growth of SNU-478 cells.
CONCLUSION FKB showed an antitumor effect through the induction of apoptosis, which was mediated by suppressing the Akt pathway in cholangiocarcinoma cells. However, the synergistic effect of FKB and cisplatin was not definite.
PubMed IF 1.8 소화기내과
92023

제1저자 이진용 · 교신저자 이해영

, , , , , , , , , , , , , , , , ,
Long-term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort.
Korean J Intern Med. 2023;38(1):56-67.

Abstract
BACKGROUND/AIMS This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension.
METHODS The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension.
RESULTS The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events.
CONCLUSION This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.
PubMed IF 2.2 순환기내과

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