SCI 발표논문

2021년 358편

1182021

제1저자 이동호, 조은주 · 교신저자 이재영

, , , , , , , ,
Accuracy of Two-Dimensional Shear Wave Elastography and Attenuation Imaging for Evaluation of Patients With Nonalcoholic Steatohepatitis.
Clin Gastroenterol Hepatol. 2021;19(4):797-805.e7.

Abstract
BACKGROUND & AIMS We evaluated the accuracy of a multiparametric approach using attenuation imaging and 2-dimensional shear wave elastography (2D-SWE) for the detection of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).
METHODS We studied 102 patients with increased levels of liver enzymes or suspicion of NAFLD, examined by attenuation imaging and 2D-SWE, immediately before biopsy collection and analysis (reference standard), from January 2018 to July 2019. We collected data on the attenuation coefficient (dB/cm/MHz) from attenuation imaging, liver stiffness measurements, and shear wave dispersion slope (SWDS, [m/s]/kHz) from 2D-SWE. Multivariate linear regression analysis was performed to identify factors associated with each parameter. Diagnostic performance was determined from area under the receiver operating curve (AUROC) values.
RESULTS The attenuation coefficient was associated with steatosis grade (P < .01) and identified patients with steatosis grades S1 or higher, S2 or higher, and S3 or higher, with AUROC values of 0.93, 0.88, and 0.83, respectively. Liver stiffness associated with fibrosis stage (P < .01) and lobular inflammatory activity was the only factor associated with SWDS (P < .01). SWDS detected inflammation grades I1 or higher, I2 or higher, and I3 or higher with AUROC values of 0.89, 0.85, and 0.78, respectively. We developed a risk scoring system to detect steatohepatitis based on the attenuation coefficient (score of 1 for 0.64 < attenuation coefficient ≤ 0.70; score of 2 for 0.70 < attenuation coefficient ≤ 0.73; and score of 3 for attenuation coefficient >0.73) and SWDS (score of 2 for 10.5 [m/s]/kHz < SWDS ≤ 11.7 [m/s]/kHz; and score of 3 for SWDS >11.7 [m/s]/kHz), using an unweighted sum of each score. Based on histopathology analysis, 55 patients had steatohepatitis. Risk scores correlated with NAFLD activity score (rho = 0.73; P < .01). Our scoring system identified patients with steatohepatitis with an AUROC of 0.93-this value was significantly higher than that of other parameters (P < .05), except SWDS (AUROC, 0.89; P = .18).
CONCLUSIONS In the evaluation of patients with suspected NAFLD, the attenuation coefficient can identify patients with steatosis and liver stiffness can detect fibrosis accurately. SWDS was associated significantly with lobular inflammation. We developed a risk scoring system based on the attenuation coefficient and SWDS that might be used to detect steatohepatitis.
PubMed IF 16.2 소화기내과
1172021

제1저자 이진호 · 교신저자 오국환

, , , , , , , , , ,
Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously.
Am J Physiol Renal Physiol. 2021;320(4):F559-F568.

Abstract
Hypercalciuria is one of the early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal Ca²⁺ reabsorption. Soluble klotho has been previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose, where sialic acid is located, on TRPV5, rather than cleave it. Here, we report that soluble klotho tethers TRPV5 on the membrane by binding both TRPV5 and galectin-1, thereby protecting membrane TRPV5 from diabetes-induced endocytosis. In the present study, we injected recombinant soluble α-klotho protein (rKL) into db/db and db/m mice for 8 wk and collected urine and kidneys. We administered rKL, AZD4547 [fibroblast growth factor (FGF) receptor type 1 inhibitor], and OTX008 (galectin-1 inhibitor) to cultured mouse distal tubular cells with or without 30 mM high-glucose (HG) exposure. db/db mice showed increased renal Ca²⁺ excretion and decreased renal TRPV5 expression. rKL treatment reversed this change. In vitro, TRPV5 expression in distal tubular cells decreased under HG conditions, and rKL successfully upregulated TRPV5 with or without FGF23. Also, immunofluorescence showed colocalization of klotho, TRPV5, and galectin-1 in distal tubule cells, suggesting that klotho binds to both TRPV5 and galectin-1. Moreover, when both FGF receptor type 1 and galectin-1 were inhibited, rKL failed to increase TRPV5 under HG conditions. Our results indicate that soluble klotho prevents TRPV5 from degradation and subsequent diabetes-induced endocytosis by anchoring TRPV5 through binding with both TRPV5 and galectin-1.NEW & NOTEWORTHY Soluble α-klotho anchors transient receptor potential vanilloid type 5 (TRPV5) on the apical membrane of the distal tubule by binding both TRPV5 and a membrane-abundant protein, galectin-1. This newly discovered mechanism works even when fibroblast growth factor (FGF)23 signaling is inhibited by treatment with FGF receptor type 1 inhibitor. Therefore, we identified how soluble α-klotho increases TRPV5 without FGF23. We confirmed this mechanism by observing that soluble α-klotho fails to enhance TRPV5 when both FGF receptor type 1 and galectin-1 are inhibited.
PubMed IF 3.6 신장내과
1162021

제1저자 김민주 · 교신저자 박영주, 오병철

, , , , , , ,
DEHP Down-Regulates Tshr Gene Expression in Rat Thyroid Tissues and FRTL-5 Rat Thyrocytes: A Potential Mechanism of Thyroid Disruption.
Endocrinol Metab (Seoul). 2021;36(2):447-454.

Abstract
BACKGROUND Di-2-ethylhexyl phthalate (DEHP) is known to disrupt thyroid hormonal status. However, the underlying molecular mechanism of this disruption is unclear. Therefore, we investigated the direct effects of DEHP on the thyroid gland.
METHODS DEHP (vehicle, 50 mg/kg, and 500 mg/kg) was administered to Sprague-Dawley rats for 2 weeks. The expression of the thyroid hormone synthesis pathway in rat thyroid tissues was analyzed through RNA sequencing analysis, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemical (IHC) staining. DEHP was treated to FRTL-5 rat thyroid cells, and an RT-PCR analysis was performed. A reporter gene assay containing the promoter of thyroid stimulating hormone receptor (TSHR) in Nthy-ori 3-1 human thyroid cells was constructed, and luciferase activity was determined.
RESULTS After DEHP treatment, the free thyroxine (T4) and total T4 levels in rats significantly decreased. RNA sequencing analysis of rat thyroid tissues showed little difference between vehicle and DEHP groups. In the RT-PCR analysis, Tshr expression was significantly lower in both DEHP groups (50 and 500 mg/kg) compared to that in the vehicle group, and IHC staining showed that TSHR expression in the 50 mg/kg DEHP group significantly decreased. DEHP treatment to FRTL-5 cells significantly down-regulated Tshr expression. DEHP treatment also reduced luciferase activity in a reporter gene assay for TSHR.
CONCLUSION Although overall genetic changes in the thyroid hormone synthesis pathway are not clear, DEHP exposure could significantly down-regulate Tshr expression in thyroid glands. Down-regulation of Tshr gene appears to be one of potential mechanisms of thyroid disruption by DEHP exposure.
PubMed IF 5.1 내분비대사내과
1152021

제1저자 이승훈 · 교신저자 김정희

, , , , , ,
Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age.
Endocrinol Metab (Seoul). 2021;36(2):401-412.

Abstract
BACKGROUND Guidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients <35 years old with marked primary aldosteronism (PA) (hypokalemia and elevated plasma aldosterone concentration [PAC]) and a unilateral lesion on computed tomography (CT) are based on limited number of studies. We aimed to determine the accuracy of CT in PA patients according to age.
METHODS In this retrospective study, we investigated the concordance between CT and AVS in 466 PA patients from two tertiary centers who successfully underwent AVS.
RESULTS CT had an overall accuracy of 64.4% (300/466). In the group with unilateral lesion, patients with hypokalemia had higher concordance than those without hypokalemia (85.0% vs. 43.6%, P<0.001). In the group with marked PA (hypokalemia and PAC >15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged <35 years; 100.0% (20/20), aged 35 to 39 years; 89.4% (59/66), aged 40 to 49 years; and 79.8% (79/99), aged ≥50 years. Cut-off age and PAC for concordance was <50 years and >29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the <50-year age group and ≥50-year age group (90.9% vs. 79.8%, P=0.044) disappeared in 139 of 198 patients with PAC > 30.0 ng/dL (91.9% vs. 87.7%, P=0.590).
CONCLUSION Patients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.
PubMed IF 5.1 내분비대사내과
1142021

제1저자 박정하, 김주영 · 교신저자 임수

, , , , , , , , , , ,
Effectiveness of liraglutide 3 mg for the treatment of obesity in a real-world setting without intensive lifestyle intervention.
Int J Obes (Lond). 2021;45(4):776-786.

Abstract
OBJECTIVE We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea.
METHODS People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values.
RESULTS The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m², and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment: -2.94 kg and -1.08 kg/m² at 2 months; -4.23 kg and -1.55 kg/m² at 4 months, and -5.14 kg and -1.89 kg/m² at 6 months (all P < 0.001). In the 6-month cohort, 52.5% and 18.3% of subjects lost ≥5% and ≥10% of body weight, respectively. After 6 months, systolic and diastolic blood pressure decreased significantly by 3.90 and 1.93 mmHg, respectively. In those with diabetes mellitus, HbA1c and fasting glucose levels decreased significantly by 1.14% and 27.8 mg/dl, respectively. Among all participants, 27.6% experienced adverse effects, including nausea (20.8%), vomiting (5.2%), diarrhoea (2.5%), and skin rash (3.6%). Documented reasons for discontinuation of treatment were lack of effect (4.4%), adverse events (4.3%), and high cost (3.1%).
CONCLUSIONS In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.
PubMed IF 5.4 내분비대사내과
1132021

제1저자 조의현, 이진용 · 교신저자 고성준, 박현선

, , , , , ,
Various skin manifestations related to inflammatory bowel disease: A nationwide cross-sectional study on the Korean population.
J Dermatol. 2021;48(4):431-438.

Abstract
Inflammatory bowel disease (IBD) presents with various extraintestinal manifestations. As part of them, various skin diseases are suggested to be related to IBD. We aimed to identify the epidemiology and risk of developing skin manifestations in patients with IBD. We used Korean insurance claims data and selected patients with IBD and age/sex-matched non-IBD subjects between 2013 and 2017 using the diagnosis code and prescription records of IBD-specific medications. The prevalence and risk of concurrent skin diseases were estimated. We identified 64 837 patients with IBD. Reactive skin eruptions including pyoderma gangrenosum and erythema nodosum were associated with IBD with highest odds ratios among three categories of reactive, inflammatory, and autoimmune skin diseases. Inflammatory skin diseases including rosacea, psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne conglobata were significantly associated with IBD, but the association was less marked compared to reactive skin eruptions. The patients with IBD also had a higher risk of autoimmune skin diseases including vitiligo and alopecia areata than non-IBD subjects. We determined that IBD was related to various skin diseases including reactive, inflammatory, and autoimmune skin diseases. Considering these relationships can allow better management of patients with IBD and comorbid skin diseases.
PubMed IF 2.3 소화기내과
1122021

제1저자 윤지선 · 교신저자 오도연

, , , ,
Targeting Hypoxia Using Evofosfamide and Companion Hypoxia Imaging of FMISO-PET in Advanced Biliary Tract Cancer.
Cancer Res Treat. 2021;53(2):471-479.

Abstract
PURPOSE Hypoxia is widely known as one of the mechanisms of chemoresistance and as an environmental condition which triggers invasion and metastasis of cancer. Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard conjugated with 2-nitroimidazole. Biliary tract cancer (BTC) is known to contain large hypoxic area. This study evaluated the efficacy and safety of evofosfamide as a second-line treatment of advanced BTC.
MATERIALS AND METHODS Patients received evofosfamide at a dose of 340 mg/m2 on days 1, 8, and 15 of every 28-day cycle. Primary end-point was progression-free survival (PFS) rate at 4-months (4m-PFSR). Secondary end-points included overall survival (OS), PFS, disease control rate (DCR), metabolic response by 18F-fluorodeoxyglucose positron emission tomography (PET), hypoxic parameters evaluated by 18F-fluoromisonidazole (FMISO) PET and toxicity.
RESULTS Twenty patients were treated with evofosfamide, with 16 response-evaluable patients. There was no objective response; stable disease was observed in nine patients, with a DCR of 56.25%. 4m-PFSR was 40.6%. Median PFS was 3.60 months (95% confidence interval [CI], 1.68 to 5.52). Median OS was 6.37 months (95% CI, 3.94 to 8.79). Reduction of tumor metabolic activity was observed in eight of 15 patients (53.3%). High baseline hypoxic parameters were associated with poor PFS. Change of hypoxic parameters between pretreatment and post-treatment reflected hypoxic-activated drug response. There was no treatment-related death.
CONCLUSION Evofosfamide as second-line treatment of advanced BTC showed acceptable safety and comparable efficacy to other agents. Changes in volumetric parameters measured with FMISO PET, showing the degree of tumor hypoxia, reflected the response to evofosfamide based on the mode of action.
PubMed IF 4.2 혈액종양내과
1112021

제1저자 조유리, 조은주 · 교신저자 신동욱, 유수종

, , , , , , , , ,
Association between Lipid Profiles and the Incidence of Hepatocellular Carcinoma: A Nationwide Population-Based Study.
Cancers (Basel). 2021;13(7):cancers13071599.

Abstract
BACKGROUND AND AIMS Altered lipid metabolism has been implicated in the development of hepatocellular carcinoma (HCC). This study investigated the relationships between lipid profiles and HCC development.
METHODS Data were obtained from the Korean National Health Insurance Service from 2009 to 2017. Cox regression analysis was used to examine the hazard ratios of HCC in 8,528,790 individuals who had undergone health check-ups in 2009.
RESULTS During a median of 7.3 years follow-up, 26,891 incidents of HCCs were identified. The incidence of HCC (per 100,000 person-years) gradually decreased according to the increase in total-cholesterol and LDL-cholesterol; the incidence of HCC was 69.2, 44.0, 33.9, and 25.8 in quartile-1 (Q1), Q2, Q3, and Q4 population of total-cholesterol, and 63.6, 44.5, 37.2, and 28.3 in Q1, Q2, Q3, and Q4 population of LDL-cholesterol, respectively. Compared to Q1 of total-cholesterol, subjects in higher total-cholesterol levels were associated with a lower incidence of HCC (multiple covariates-adjusted hazard ratio (aHR): Q2 0.61; Q3 0.46; Q4 0.36). These associations were consistently observed in stratified subgroup analysis by the presence of liver cirrhosis or viral hepatitis.
CONCLUSIONS Low serum lipid levels were significantly associated with the increased risk of developing HCC. A low lipid profile might be an independent risk factor and preclinical marker for HCC.
PubMed IF 4.8 소화기내과
1102021

제1저자 손민지 · 교신저자 임수

, , , ,
Correlation of dynamic membrane fluctuations in red blood cells with diabetes mellitus and cardiovascular risks.
Sci Rep. 2021;11(1):7007.

Abstract
The rheological and physiological properties of red blood cells (RBCs) are affected by many factors in the vascular environment. Among them, membrane fluctuations (MFs), particularly dynamic fluctuations in RBC cell membrane thickness (RBC-MFs), are likely to be altered by the level of glycation of haemoglobin in patients with diabetes mellitus (DM). We investigated the associations of RBC-MFs with physiological variables associated with DM and cardiovascular diseases (CVDs). Forty-one healthy control subjects and 59 patients with DM were enrolled. Five-microliter samples of blood were collected and diluted 400 times. To measure the RBC-MFs, holotomography was used, which non-invasively and precisely analyses the optical characteristics of RBCs. Associations between the RBC-MFs and biochemical parameters related to glucose homeostasis and lipid profiles were investigated. Independent associations of the RBC-MFs with the presence of CVDs were also analysed. RBC-MFs were lower in patients with DM than in healthy participants (61.64 ± 7.49 nm vs 70.65 ± 6.65 nm, P = 1.4 × 10^-8). RBC-MFs correlated modestly with glycated haemoglobin level (ρ = - 0.47) and weakly with age (ρ = - 0.36), duration of diabetes (ρ = - 0.36), fasting plasma glucose level (ρ = - 0.37), and the 10-year Framingham risk score (ρ = - 0.38) (all P < 0.05). Low RBC-MFs were independently associated with the presence of CVDs after adjusting for CVD risk factors. The weak but significant associations of RBC-MFs with cardiometabolic risk factors and CVDs suggest that such deformity of circulating RBCs may be a useful marker of vascular complications of DM.
PubMed IF 4.9 내분비대사내과
1092021

제1저자 김광일 · 교신저자 김철호

, , , , ,
Ten-year trends of hypertension treatment and control rate in Korea.
Sci Rep. 2021;11(1):6966.

Abstract
We analyzed the Korean National Health and Nutrition Examination Survey (KNHANES) database to determine the trends of hypertension treatment and control rate in Korea over the past 10 years. In addition, we tried to investigate the effect of chronic medical conditions on hypertension management. We investigated the hypertension prevalence, awareness, treatment, and control rate from 2008 to 2017. KNHANES, which uses a stratified multistage sampling design, is a cross-sectional, nationally representative survey conducted by the Korean government. A total of 59,282 adults (≥ 20 years) were included, which was representative of the total population of around 40 million Koreans per year. The mean age was 50.7 ± 16.4 years and 42.6% were male. The prevalence of hypertension, hypercholesterolemia, diabetes mellitus, and obesity significantly increased over the 10 years. During this period, the hypertension treatment and control rate significantly improved. Hypertension treatment rate was significantly lower in the younger age group compared to the older age group, but the control rate among the treated patients was not significantly different between age groups. The treatment and control rates of hypertension were higher in patients with multimorbidity, which implies that it has a favorable effect on the treatment and control of hypertension. Hypertension treatment and control rate have improved over the past 10 years. The higher treatment and control rate in patients with multimorbidity suggest that the more aggressive surveillance might be associated with the improvement of hypertension treatment and control rate in Korea.
PubMed IF 4.9 노인병내과
1082021

제1저자 윤연이 · 교신저자 윤연이

, , ,
Breast Arterial Calcification: A Potential Biomarker for Atherosclerotic Cardiovascular Disease Risk?
Curr Atheroscler Rep. 2021;23(5):21.

Abstract
PURPOSE OF REVIEW We aimed to summarize the current evidence regarding the association between breast arterial calcification (BAC) and atherosclerotic cardiovascular disease (ASCVD) in women and discuss the potential role of BAC in the risk stratification and preventive approaches for ASCVD.
RECENT FINDINGS BAC has emerged as a potential women-specific risk marker for ASCVD. Although BAC presents as a medial calcification of the arteries, notably different from the intimal atherosclerotic process, current evidence supports a correlation between BAC and ASCVD risk factors or subclinical and clinical ASCVD, such as coronary artery disease or stroke. As millions of women undergo mammograms each year, the potential clinical application of BAC in enhanced ASCVD risk estimation, with no additional cost or radiation, has tremendous appeal. Although further research regarding optimal risk assessment and management in women with BAC is required, the presence of BAC should prompt healthy cardiovascular lifestyle modifications.
PubMed IF 6.6 순환기내과
1072021

제1저자 박진주 · 교신저자 박진주

Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes.
Diabetes Metab J. 2021;45(2):146-157.

Abstract
The cardiovascular disease continuum begins with risk factors such as diabetes mellitus (DM), progresses to vasculopathy and myocardial dysfunction, and finally ends with cardiovascular death. Diabetes is associated with a 2- to 4-fold increased risk for heart failure (HF). Moreover, HF patients with DM have a worse prognosis than those without DM. Diabetes can cause myocardial ischemia via micro- and macrovasculopathy and can directly exert deleterious effects on the myocardium. Hyperglycemia, hyperinsulinemia, and insulin resistance can cause alterations in vascular homeostasis. Then, reduced nitric oxide and increased reactive oxygen species levels favor inflammation leading to atherothrombotic progression and myocardial dysfunction. The classification, diagnosis, and treatment of HF for a patient with and without DM remain the same. Until now, drugs targeting neurohumoral and metabolic pathways improved mortality and morbidity in HF with reduced ejection fraction (HFrEF). Therefore, all HFrEF patients should receive guideline-directed medical therapy. By contrast, drugs modulating neurohumoral activity did not improve survival in HF with preserved ejection fraction (HFpEF) patients. Trials investigating whether sodium-glucose cotransporter-2 inhibitors are effective in HFpEF are on-going. This review will summarize the epidemiology, pathophysiology, and treatment of HF in diabetes.
PubMed IF 8.2 순환기내과
1062021

제1저자 김민주, 김선미 · 교신저자 박정임, 천기정

, , , , , , , , , , ,
Association of exposure to polycyclic aromatic hydrocarbons and heavy metals with thyroid hormones in general adult population and potential mechanisms.
Sci Total Environ. 2021;762:144227.

Abstract
Air pollution and fuel emissions are the common sources of human exposure to polycyclic aromatic hydrocarbons (PAHs) and heavy metals. Several studies have suggested potential associations between PAHs/heavy metals and thyroid hormones, however, reports have been inconsistent. In this study, we employed a subpopulation of the adults (n = 1254) who participated in the Korean National Environmental Health Survey 2015-2017, and investigated the association of PAHs and major heavy metals with thyroid hormones, and explored the underlying mechanisms of thyroid disruption. Four PAH metabolites and three heavy metals of lead (Pb), mercury (Hg), and cadmium (Cd) were measured either in urine or in total blood. In addition, thyroid hormones (T3 and T4), TSH, thyroxine-binding globulin (TBG), and thyroid autoantibodies were measured, and peripheral deiodinase activity (G_D) and thyroid's secretory capacity (G_T) were calculated. Urinary Hg was negatively associated with total T3 in both males and females, while it was positively associated with total T4 among females only. Urinary Hg was related to decreased G_D and increased G_T in both sexes. In contrast, urinary Cd was positively associated with total T3 and G_D in both male and female populations. Urinary Cd also showed a positive association with thyroid autoantibodies, but only in males. A multi-factor model considering co-exposure to multiple chemicals also resulted in similar associations. Among the measured PAH metabolites, only urinary 1-hydroxypyrene showed a negative association with total T3 in males. However, this association was marginal, and disappeared in a multi-chemical model. The present observations are suggestive that exposures to Hg and Cd might disrupt thyroid hormones, possibly through an alteration of deiodinase activity. Association of PAH exposure with thyroid hormone appears to be insignificant.
PubMed IF 8 내분비대사내과
1052021

제1저자 황인창 · 교신저자 이승표

, , , , , , , , ,
Time trajectory of cardiac function and its relation with survival in patients with light-chain cardiac amyloidosis.
Eur Heart J Cardiovasc Imaging. 2021;22(4):459-469.

Abstract
AIMS We aimed to analyse the time-serial change of cardiac function in light-chain (AL) cardiac amyloidosis patients undergoing active chemotherapy and its relationship with patient outcome.
METHODS AND RESULTS Seventy-two patients with AL cardiac amyloidosis undergoing active chemotherapy who had two or more echocardiographic examinations were identified from a prospective observational cohort (n = 34) and a retrospective cohort (n = 38). Echocardiographic parameters were obtained immediately prior to 1-3, 3-6, 6-12, and 12-24 months after the first chemotherapy. Study endpoint was a composite of death or heart transplantation (HT). During a median of 32 months (interquartile range 8-51) follow-up, 33 patients (45.8%) died and 4 patients (5.6%) underwent HT. Echocardiograms immediately prior to the first chemotherapy did not show differences between the patients with adverse events vs. those without. Significant increase in mitral E/e' ratio and decline in left ventricular global longitudinal strain (LV-GLS) was observed, starting at 3-6 months after the first chemotherapy only in those who experienced adverse events on follow-up, which was also evident in those who responded to chemotherapy. Multivariate analysis demonstrated that B-natriuretic peptide >500 pg/mL and troponin I >0.15 ng/dL at initial diagnosis, hospitalization for heart failure, E/e' >15, and LV-GLS <10% during follow-up were independent predictors of outcome.
CONCLUSIONS In AL cardiac amyloidosis patients undergoing active chemotherapy, the deterioration of LV function may occur, starting even at 3-6 months after the first chemotherapy. Serial echocardiography may help identify those who experience a clinical event in the near future despite active chemotherapy.
PubMed IF 6.1 순환기내과
1042021

제1저자 공민규 · 교신저자 한정규

, , , , , , , , , ,
Clinical outcomes of long stenting in the drug-eluting stent era: patient-level pooled analysis from the GRAND-DES registry.
EuroIntervention. 2021;16(16):1318-1325.

Abstract
AIMS We aimed to understand the association between stent length and clinical outcomes after percutaneous coronary intervention (PCI) using newer-generation drug-eluting stents (DES).
METHODS AND RESULTS We analysed 9,217 patients who underwent stenting for a single lesion from the GRAND-DES registry, a patient-level pooled registry including five Korean multicentre DES registries. The median follow-up duration was 730 days (interquartile range 708 to 752 days). A total of 8,035 patients were classified into the short stenting group (≤40 mm), and 1,182 into the long stenting group (>40 mm). The primary endpoint was target lesion failure (TLF). Long stenting (>40 mm) was significantly associated with higher TLF (IPTW adjusted HR 1.88, 95% CI: 1.67-2.13; p<0.001), and definite or probable stent thrombosis (IPTW adjusted HR 2.20, 95% CI: 1.51-3.20; p<0.001). In the landmark analysis, the incidence of TLF was significantly higher with long stenting during the first 30 days after PCI (log-rank p=0.001) and also after 30 days (log-rank p<0.001). Long stenting was associated with a higher risk of early stent thrombosis (log-rank p=0.001), but not with that of late stent thrombosis (log-rank p=0.887).
CONCLUSIONS In the contemporary second-generation DES era, stenting longer than 40 mm continues to be associated with less favourable clinical outcomes such as TLF and stent thrombosis.
PubMed IF 9.2 순환기내과
1032021

제1저자 김수환 · 교신저자 정지봉

, , , , , , , , , ,
Association between sarcopenia level and metabolic syndrome.
PLoS One. 2021;16(3):e0248856.

Abstract
AIMS Metabolic syndrome (MetS) increases the risk of diabetes mellitus (DM), cardiovascular disease (CVD), cancer, and mortality. Sarcopenia has been reported as a risk factor for MetS, non-alcoholic fatty liver disease, and CVD. To date, the association between sarcopenia and MetS has been investigated. However, there have been few studies on the dose-response relationship between sarcopenia and MetS. We investigated the association between sarcopenia and the prevalence of MetS. We also aimed to analyze the dose-response relationship between skeletal muscle mass and the prevalence of MetS.
METHODS We enrolled 13,620 participants from October 2014 to December 2019. Skeletal muscle mass was measured using bioelectrical impedance analysis (BIA). Appendicular skeletal muscle mass (ASM) was divided by body weight (kg) and was expressed as a percentage (ASM x 100/Weight, ASM%). The quartiles of ASM% were calculated for each gender, with Q1 and Q4 being the lowest and highest quartiles of ASM%, respectively. The quartiles of ASM% were calculated for each gender, with Q1 and Q4 being the lowest and highest quartiles of ASM%, respectively. Linear regression and logistic regression analyses were used to compare the clinical parameters according to ASM%, adjusted for age, sex, obesity, hypertension (HT), DM, dyslipidemia (DL), smoking, alcohol intake, and C-reactive protein (CRP). Multiple logistic regression analysis was performed to determine the risk of MetS in each group.
RESULTS A dose-response relationship was identified between ASM% and MetS. Sarcopenia was associated with an increased prevalence of MetS. After adjustment for age, sex, obesity, HT, DM, DL, smoking, alcohol intake, and CRP, sarcopenia remained significantly associated with MetS. For each 1 quartile increment in ASM%, the risk of MetS decreased by 56% (P< 0.001). After adjusting for age, sex, obesity, HT, DM, DL, smoking, alcohol intake, and CRP, the risk of MetS decreased by 25% per 1Q increment in ASM% (P < 0.001).
CONCLUSIONS Sarcopenia by BIA is independently associated with the risk of MetS and has a dose-response relationship.
PubMed IF 2.8 소화기내과
1022021

제1저자 김병근 · 교신저자 박흥우

, , ,
Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma.
Front Med (Lausanne). 2021;8:652824.

Abstract
Gene regulatory networks address how transcription factors (TFs) and their regulatory roles in gene expression determine the responsiveness to anti-asthma therapy. The purpose of this study was to assess gene regulatory networks of adult patients with asthma who showed good or poor lung function improvements in response to inhaled corticosteroids (ICSs). A total of 47 patients with asthma were recruited and classified as good responders (GRs) and poor responders (PRs) based on their responses to ICSs. Genome-wide gene expression was measured using peripheral blood mononuclear cells obtained in a stable state. We used Passing Attributes between Networks for Data Assimilations to construct the gene regulatory networks associated with GRs and PRs to ICSs. We identified the top-10 TFs that showed large differences in high-confidence edges between the GR and PR aggregate networks. These top-10 TFs and their differentially-connected genes in the PR and GR aggregate networks were significantly enriched in distinct biological pathways, such as TGF-β signaling, cell cycle, and IL-4 and IL-13 signaling pathways. We identified multiple TFs and related biological pathways influencing ICS responses in asthma. Our results provide potential targets to overcome insensitivity to corticosteroids in patients with asthma.
PubMed IF 3.6 알레르기내과
1012021

제1저자 차명진 · 교신저자 오세일, 장지현

, , , , , , ,
Early Changes in Rat Heart After High-Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation.
J Am Heart Assoc. 2021;10(6):e019072.

Abstract
Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early-period antiarrhythmic effects induced by high-dose irradiation are unknown. This study investigated dose-responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild-type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks' postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high-dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose-responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell-related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high-dose irradiation. ECG indicated intracardiac conduction delay with prominent ST-segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.
PubMed IF 6 순환기내과
1002021

제1저자 김효수, 강지훈 · 교신저자 박경우

, , , , , , , , , , , , , ,
Durable Polymer Versus Biodegradable Polymer Drug-Eluting Stents After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome: The HOST-REDUCE-POLYTECH-ACS Trial.
Circulation. 2021;143(11):1081-1091.

Abstract
BACKGROUND Large-scale randomized comparison of drug-eluting stents (DES) based on durable polymer versus biodegradable polymer technology is currently insufficient in patients with acute coronary syndrome (ACS). The present study aimed to prove the noninferiority of the durable polymer DES (DP-DES) compared with the biodegradable polymer DES (BP-DES) in such patients.
METHODS The HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) trial is an investigator-initiated, randomized, open-label, adjudicator-blinded, multicenter, noninferiority trial comparing the efficacy and safety of DP-DES and BP-DES in patients with ACS. The primary end point was a patient-oriented composite outcome (a composite of all-cause death, nonfatal myocardial infarction, and any repeat revascularization) at 12 months. The key secondary end point was device-oriented composite outcome (a composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) at 12 months.
RESULTS A total of 3413 patients were randomized to receive the DP-DES (1713 patients) and BP-DES (1700 patients). At 12 months, patient-oriented composite outcome occurred in 5.2% in the DP-DES group and 6.4% in the BP-DES group (absolute risk difference, -1.2%; P_non_inferiority<0.001). The key secondary end point, device-oriented composite outcome, occurred less frequently in the DP-DES group (DP-DES vs BP-DES, 2.6% vs 3.9%; hazard ratio, 0.67 [95% CI, 0.46-0.98]; P=0.038), mostly because of a reduction in target lesion revascularization. The rate of spontaneous nonfatal myocardial infarction and stent thrombosis were extremely low, with no significant difference between the 2 groups (0.6% versus 0.8%; P=0.513 and 0.1% versus 0.4%; P=0.174, respectively).
CONCLUSIONS In ACS patients receiving percutaneous coronary intervention, DP-DES was noninferior to BP-DES with regard to patient-oriented composite outcomes at 12 months after index percutaneous coronary intervention. Registration: URL: https://wwwclinicaltrials.gov; Unique identifier: NCT02193971.
PubMed IF 41.3 순환기내과
992021

제1저자 정정화, 최화영 · 교신저자 정숙향

, , , ,
Comorbidities and Prescribed Medications in Korean Patients with Chronic Hepatitis C: A Nationwide, Population-Based Study.
Gut Liver. 2021;15(2):295-306.

Abstract
BACKGROUND/AIMS Extrahepatic comorbidities and comedication are important to consider in the treatment of chronic hepatitis C (CHC) patients with direct-acting antivirals (DAAs) due to the risk of drug-drug interaction (DDI) and the effect of comorbidities on clinical outcomes. This study aimed to investigate the detailed profiles of comorbidities and comedication among Korean CHC patients.
METHODS All adult patients (≥18 years old) with a primary diagnostic code of CHC in 2013 were selected from the National Health Insurance claims database. For each patient, all ICD-10 codes listed as primary or secondary diagnoses and all prescribed medications were collected.
RESULTS Among 47,104 CHC patients (median age, 57 years; male, 49.3%), 84.8% had at least one comorbidity for a mean number of 2.4, which increased with age. The most prevalent comorbidities were hypertension, esophagitis, dyslipidemia, diabetes mellitus, and peptic ulcer. Overall, 96.8% of the patients took at least one prescribed medication, with a mean of 8.1 medications/ year, and the three most common drug types were analgesics, gastrointestinal agents, and antibacterials. Use of at least one drug with a DDI risk category of "contraindicated medication" or "required dose-reduction/additional monitoring" was observed in 97% of the overall patients. The proportion of prescribed medications that were contraindicated with DAAs varied from 2.0% to 38.9% depending on the hepatitis C virus regimen.
CONCLUSIONS The majority of CHC patients had comorbidities; almost all patients took multiple prescribed medications, the number of which increased with age, and significant DDI risk was present in 97% of this Korean patient cohort. Comorbidities and comedication profiles should be considered during DAA therapy.
PubMed IF 4.1 소화기내과
982021

제1저자 윤혁 · 교신저자 이동호, 김병용

, , , , , , , , , ,
Characteristics of the Gut Microbiome of Healthy Young Male Soldiers in South Korea: The Effects of Smoking.
Gut Liver. 2021;15(2):243-252.

Abstract
BACKGROUND/AIMS South Korean soldiers are exposed to similar environmental factors. In this study, we sought to evaluate the gut microbiome of healthy young male soldiers (HYMS) and to identify the primary factors influencing the microbiome composition.
METHODS We prospectively collected stool from 100 HYMS and performed next-generation sequencing of the 16S rRNA genes of fecal bacteria. Clinical data, including data relating to the diet, smoking, drinking, and exercise, were collected.
RESULTS The relative abundances of the bacterial phyla Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria were 72.3%, 14.5%, 8.9%, and 4.0%, respectively. Fifteen species, most of which belonged to Firmicutes (87%), were detected in all examined subjects. Using cluster analysis, we found that the subjects could be divided into the two enterotypes based on the gut microbiome bacterial composition. Compared with enterotype 2 subjects, subjects classified as enterotype 1 tended to be characterized by higher frequencies of potentially harmful lifestyle habits (current smoker: 55.6% vs 36.6%, p=0.222; heavy drinker: 16.7% vs 3.7%, p=0.120; insufficient physical activity: 27.8% vs 14.6%, p=0.318). We identified a significant difference in the microbiome compositions of current and noncurrent smokers (p=0.008); the former differed from the latter mainly in a relatively lower abundance of Bifidobacterium species and a higher abundance of Negativicutes.
CONCLUSIONS A high abundance of Actinobacteria and low abundance of Bacteroidetes were the main features distinguishing the gut microbiomes of HYMS, and current smokers could be differentiated from noncurrent smokers by their lower abundance of Bifidobacterium and higher abundance of Negativicutes.
PubMed IF 4.1 소화기내과
972021

제1저자 최영훈 · 교신저자 이상협

, , , , , , , , ,
Prognostic Factors for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer Receiving Neoadjuvant FOLFIRINOX.
Gut Liver. 2021;15(2):315-323.

Abstract
BACKGROUND/AIMS There has been growing evidence on the utility of neoadjuvant FOLFIRINOX in borderline resectable (BR) or locally advanced (LA) pancreatic cancer. However, factors predicting survival in these patients remain to be identified, and we aimed to identify these prognostic factors.
METHODS Between January 2013 and April 2017, patients with BR or LA pancreatic cancer who received FOLFIRINOX as their initial treatment were identified. Demographic data and clinical outcomes, including the chemotherapy response, conversion to resection, and survival, were reviewed.
RESULTS A total of 117 patients with BR (n=39) or LA (n=78) pancreatic cancer were included. Of these patients, 29 (24.8%) underwent curative surgery, and R0 resection was achieved in 21 patients (72.4%). The median progression-free survival and overall survival time of all patients were 11.6 and 19.0 months, respectively. In resected patients, the median relapse-free survival and overall survival times were 14.8 and 28.6 months, respectively. In the multivariate Cox model, the lowest level of serum carbohydrate antigen 19-9 (CA 19-9) and resection after FOLFIRINOX were independent factors for improved overall survival. In the subgroup analysis of patients with initial ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images, the maximum standardized uptake value (SUVmax) of the pancreatic mass was also shown as an independent factor for improved overall survival.
CONCLUSIONS In patients with BR or LA pancreatic cancer, FOLFIRINOX is a valuable neoadjuvant treatment that enables curative surgery in approximately one-quarter of patients and significantly improves overall survival. In these patients, the prognosis can be estimated using the lowest level of serum CA 19-9, operative status, and initial FDG-PET SUVmax.
PubMed IF 4.1 소화기내과
962021

제1저자 이선민 · 교신저자 김나영

, , , , , ,
Compositional and Functional Changes in the Gut Microbiota in Irritable Bowel Syndrome Patients.
Gut Liver. 2021;15(2):253-261.

Abstract
BACKGROUND/AIMS This study aimed to characterize the changes in the gut microbiota of irritable bowel syndrome (IBS) patients and to investigate the consequent alterations in bacterial functions.
METHODS We performed 16S rRNA metagenomic sequencing and a phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analyses using fecal samples from control (n=12) and diarrhea-dominant IBS patients (n=7).
RESULTS The samples were clustered by the principal coordinates analysis depending on the presence of IBS (p=0.003). In the IBS patients, the abundances of Acidaminococcaceae, Sutterellaceae, and Desulfovibrionaceae were significantly increased, while those of Enterococcaceae, Leuconostocaceae, Clostridiaceae, Peptostreptococcaceae, and Lachnospiraceae were significantly decreased. The PICRUSt results indicated that two orthologues involved in secondary bile acid biosynthesis were significantly decreased in IBS patients. Modules involved in multidrug resistance, lipopolysaccharide biosynthesis, the reductive citrate cycle, and the citrate cycle were significantly increased in the IBS patients. In contrast, modules involved in cationic antimicrobial peptide resistance, and some transport systems were more abundant in controls than in IBS patients.
CONCLUSIONS Changes in the gut microbiota composition in IBS patients lead to alterations in bacterial functions, such as bile acid transformation and the induction of inflammation, which is a known pathophysiological mechanism of IBS.
PubMed IF 4.1 소화기내과
952021

제1저자 이창훈, 한경도 · 교신저자 곽민선

, , ,
The Repeatedly Elevated Fatty Liver Index Is Associated With Increased Mortality: A Population-Based Cohort Study.
Front Endocrinol (Lausanne). 2021;12:638615.

Abstract
AIMS Non-alcoholic fatty liver disease (NAFLD) has a dynamic disease course, therefore repeated measurements of NAFLD status could have benefits rather than single one. The aim of this study was to investigate the effects of persistent NAFLD on the incidence of myocardial infarction (MI) and stroke and all-cause mortality by using repeated measurement of fatty liver index (FLI).
METHODS About 3 million subjects who had undergone the health screening four times from 2009 until 2013 were included. NAFLD was defined as an FLI ≥60. FLI points were defined as the number of times participants meeting the criteria of NAFLD (0-4). Outcomes included all-cause mortality, MI, and stroke.
RESULTS The higher the FLI points, the higher the risk of all-cause mortality, MI, and stroke (P for trend <0.001, all). Subjects with four FLI points had a higher risk of all-cause mortality (aHR, 1.86; 95% CI, 1.75-1.98; P < 0.001), incidence of MI (aHR, 1.3; 95% CI, 1.21-1.40; P < 0.001), and stroke (aHR, 1.27; 95% CI, 1.19-1.37; P < 0.001) after adjustment for age, sex, smoking, alcohol consumption, income, hypertension, dyslipidemia, diabetes, body mass index, and physical activity. When the 1^st and the last FLI were compared, the "incident NAFLD" group had a higher risk for death compared to the "no NAFLD" group (aHR, 1.46; 95% CI, 1.37-1.55), and the "regression of NAFLD" group had a decreased risk for death compared to the "persistent NAFLD" group (aHR, 0.83; 95% CI, 0.77-0.89).
CONCLUSION Repeated evaluations of NAFLD status based on FLI measurements could help physicians identify higher-risk groups in terms of mortality, MI, and stroke. The association between FLI worsening or improvement and outcomes also suggests clinical benefits of the prevention and treatment of NAFLD.
PubMed IF 5.7 호흡기내과
942021

제1저자 박세훈 · 교신저자 김동기

, , , , , , , , , , , ,
Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study.
Nutrients. 2021;13(3):nu13030906.

Abstract
Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for blood homocysteine, folate, and cobalamin levels were introduced from a previous genome-wide association (GWAS) meta-analysis of European individuals. Summary-level MR analysis was performed for the estimated glomerular filtration rate (eGFR) from the CKDGen consortium GWAS that included 567,460 European ancestry individuals. For replication, allele-score-based MR was performed with an independent U.K. Biobank cohort of 337,138 individuals of white British ancestry. In summary-level MR for the CKDGen data, high genetically predicted homocysteine levels were significantly associated with low eGFR (per 1 standard deviation, beta for eGFR change -0.95 (-1.21, -0.69) %), supported by pleiotropy-robust MR sensitivity analysis. Genetically predicted high folate levels were significantly associated with high eGFR change (0.86 (0.30, 1.42) %); however, causal estimates from cobalamin were nonsignificant (-0.11 (-0.33, 0.11) %). In the U.K. Biobank data, the results were consistently identified. Therefore, a high blood homocysteine level causally decreases eGFR. Future trials with appropriate homocysteine-lowering interventions may be helpful for the primary prevention of kidney function impairment.
PubMed IF 5.8 신장내과
932021

제1저자 Feng Gao · 교신저자 김원, Ming-Hua Zheng

, , , , , , , , , ,
Individualized Polygenic Risk Score Identifies NASH in the Eastern Asia Region: A Derivation and Validation Study.
Clin Transl Gastroenterol. 2021;12(3):e00321.

Abstract
INTRODUCTION Strong evidence indicates that multiple genetic and environmental risk factors play a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). We aimed to develop and validate a novel nomogram, incorporating both genetic and clinical factors, for predicting NASH.
METHODS A total of 1,070 Asian individuals with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) from 2 countries (China and South Korea) were recruited. The histological spectrum of NAFLD was classified according to the NASH clinical research network scoring system. The nomogram was developed in the Chinese training set (n = 402), and then, it was validated in both the Chinese internal validation set (n = 136) and the external Korean validation cohort (n = 532), respectively.
RESULTS Sex, metabolic syndrome, insulin resistance, serum aspartate aminotransferase levels, and PNPLA3 (rs738409) and HSD17B13 (rs72613567) genetic variants were strongly associated with NASH. Based on their regression coefficients, we developed a nomogram with good discriminatory ability (area under the receiver operating characteristic curve: 0.81, 95% confidence interval [CI] 0.77-0.85) and good calibration (Hosmer-Lemeshow test, P = 0.794) for identifying NASH. In the 2 validation cohorts, the nomogram showed high area under the receiver operating characteristic curves (internal validation set: 0.80, 95% CI 0.72-0.88; external validation cohort: 0.76, 95% CI 0.72-0.80) and good calibration.
DISCUSSION Our newly developed and externally validated nomogram, incorporating both genetic and clinical risk factors, may be conveniently used to predict NASH. Further validation studies in other ethnic groups are warranted to confirm its diagnostic utility to identify NASH, among patients with biopsy-proven NAFLD.
PubMed IF 3.6 소화기내과
922021

제1저자 최영훈, 임영균 · 교신저자 류지곤

, , , , , ,
Excision Repair Cross-Complementation Group 6 Gene Polymorphism Is Associated with the Response to FOLFIRINOX Chemotherapy in Asian Patients with Pancreatic Cancer.
Cancers (Basel). 2021;13(6):cancers13061196.

Abstract
FOLFIRINOX is currently one of the standard chemotherapy regimens for pancreatic cancer patients, but little is known about the factors that can predict a response to it. We performed a study to discover novel DNA damage repair (DDR) gene variants associated with the response to FOLFIRINOX chemotherapy in patients with pancreatic cancer. We queried a cohort of pancreatic cancer patients who received FOLFIRINOX chemotherapy as the first treatment and who had tissue obtained through an endoscopic ultrasound-guided biopsy that was suitable for DNA sequencing. We explored variants of 148 DDR genes based on whole exome sequencing and performed multivariate Cox regression to find genetic variants associated with progression-free survival (PFS). Overall, 103 patients were included. Among 2384 variants of 141 DDR genes, 612 non-synonymous variants of 123 genes were selected for Cox regression analysis. The multivariate Cox model showed that rs2228528 in ERCC6 was significantly associated with improved PFS (hazard ratio 0.54, p = 0.001). The median PFS was significantly longer in patients with rs2228528 genotype AA vs. genotype GA and GG (23.5 vs. 16.2 and 8.6 months; log-rank p < 0.001). This study suggests that rs2228528 in ERCC6 could be a potential predictor of response to FOLFIRINOX chemotherapy in patients with pancreatic cancer.
PubMed IF 4.8 소화기내과
912021

제1저자 문재훈, 류창환 · 교신저자 박영주, 이은경

, , , , , , , , , , , , , , , , , , , , , ,
Effect of Initial Treatment Choice on 2-year Quality of Life in Patients with Low-risk Papillary Thyroid Microcarcinoma.
J Clin Endocrinol Metab. 2021;106(3):724-735.

Abstract
CONTEXT The long-term quality of life (QoL) in patients with low-risk papillary thyroid microcarcinoma (PTMC) underwent active surveillance (AS) and immediate surgery is unclear.
OBJECTIVE The aim of this study was to investigate the effect of initial treatment choice on 2-year QoL in patients with low-risk PTMC.
DESIGN, SETTING, AND PARTICIPANTS We analyzed 2652 QoL surveys from 1055 subjects enrolled in ongoing multicenter prospective cohort study on active surveillance of PTMC, in which the median follow-up duration was 24.4 months.
MAJOR OUTCOME MEASURE We evaluated QoL of patients with low-risk PTMC according to their treatment modality using generalized estimating equation.
RESULTS Six hundred and seventy-four subjects (male = 161; mean age = 48.8 ± 11.9 years) with low-risk PTMC chose AS while 381 subjects (male = 75; mean age = 45.7 ± 10.4 years) chose immediate surgery, including lobectomy/isthmusectomy (L/I) and total thyroidectomy (TT). Among the 817 subjects who completed baseline QoL surveys, 2-year QoL was good in order of AS (n = 500), L/I (n = 238), and TT (n = 79) groups after adjustment for age, sex, baseline tumor size, and baseline QoL scores. Among the 101 subjects who changed their treatment from AS to surgery during the follow-up period, 35 subjects who changed treatment due to disease progression had better QoL than 66 subjects who had no disease progression.
CONCLUSIONS This study identified QoL as a major issue in choosing an initial treatment of low-risk PTMC and highlighted the possibility of using AS as the primary treatment.
PubMed IF 5.4 내분비대사내과
902021

제1저자 안창호 · 교신저자 김정희

, , ,
Epidemiology and Comorbidity of Adrenal Cushing Syndrome: A Nationwide Cohort Study.
J Clin Endocrinol Metab. 2021;106(3):e1362-e1372.

Abstract
CONTEXT Adrenal Cushing syndrome (CS) is a major subtype of CS and has a high surgical cure rate. However, only a few studies have investigated the epidemiology and long-term outcomes of adrenal CS.
OBJECTIVE We aimed to investigate the nationwide epidemiology, long-term prognosis, and postoperative glucocorticoid replacement therapies of adrenal CS in Korea.
DESIGN Retrospective cohort study.
SETTING A nationwide claim database.
PATIENTS Adrenal CS patients who were defined as having undergone adrenalectomy, a diagnosis code of CS, and not having pituitary gland surgery.
MAIN OUTCOME MEASURES Crude incidence and age-standardized incidence rates, long-term mortality, comorbidities diagnosed preoperatively or developed postoperatively, and the pattern of postoperative glucocorticoid replacement therapy.
RESULTS From 2002 to 2017, there were a total of 1199 new adrenal CS patients, including 72 patients with adrenocortical carcinoma (malignant adrenal CS), in Korea. The crude and age-standardized incidence rates were 1.51 and 1.27 per million person-years, respectively. The overall standardized mortality ratio was 3.0 (95% confidence interval [CI], 2.4-3.7) for benign adrenal CS and 13.1 (95% CI, 7.6-18.6) for malignant adrenal CS. Adrenal CS patients had a high risk of having coronary artery disease, stroke, metabolic diseases, and depression. A similar proportion of patients were diagnosed with these comorbidities both preoperatively and postoperatively, suggesting a significant residual risk even after adrenalectomy. The median time of postoperative glucocorticoid replacement therapy was 10.1 months, and the major types of glucocorticoids used were prednisolone (66.6%) and hydrocortisone (22.4%).
CONCLUSIONS Adrenal CS is associated with multiple comorbidities even after treatment, which necessitates meticulous postoperative care.
PubMed IF 5.4 내분비대사내과
892021

제1저자 이진우 · 교신저자 조현재, 김효수

, , , , , ,
Lysophosphatidic Acid Receptor 4 Is Transiently Expressed during Cardiac Differentiation and Critical for Repair of the Damaged Heart.
Mol Ther. 2021;29(3):1151-1163.

Abstract
Efficient differentiation of pluripotent stem cells (PSCs) into cardiac cells is essential for the development of new therapeutic modalities to repair damaged heart tissue. We identified a novel cell surface marker, the G protein-coupled receptor lysophosphatidic acid receptor 4 (LPAR4), specific to cardiac progenitor cells (CPCs) and determined its functional significance and therapeutic potential. During in vitro differentiation of mouse and human PSCs toward cardiac lineage, LPAR4 expression peaked after 3-7 days of differentiation in cardiac progenitors and then declined. In vivo, LPAR4 was specifically expressed in the early stage of embryonal heart development, and as development progressed, LPAR4 expression decreased and was non-specifically distributed. We identified the effective agonist octadecenyl phosphate and a p38 MAPK blocker as the downstream signal blocker. Sequential stimulation and inhibition of LPAR4 using these agents enhanced the in vitro efficiency of cardiac differentiation from mouse and human PSCs. Importantly, in vivo, this sequential stimulation and inhibition of LPAR4 reduced the infarct size and rescued heart dysfunction in mice. In conclusion, LPAR4 is a novel CPC marker transiently expressed only in heart during embryo development. Modulation of LPAR4-positive cells may be a promising strategy for repairing myocardium after myocardial infarction.
PubMed IF 11.4 순환기내과

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