SCI 발표논문

전체 4,588편

34782021

제1저자 윤준필 · 교신저자 최의근

, , , , , , , , ,
Risk of Atrial Fibrillation According to Cancer Type: A Nationwide Population-Based Study.
JACC CardioOncol. 2021;3(2):221-232.

Abstract
BACKGROUND Patients with cancer have an increased risk of atrial fibrillation (AF). However, there is a paucity of information regarding the association between cancer type and risk of AF.
OBJECTIVES This study sought to evaluate the risk of AF according to the type of cancer.
METHODS We enrolled 816,811 patients who were diagnosed with cancer from the Korean National Health Insurance Service database between 2009 and 2016. Age- and sex-matched noncancer control subjects (1:2; n = 1,633,663) were also selected. Newly diagnosed AF was identified based on the type of cancer.
RESULTS During a median follow-up of 4.5 years, AF was newly diagnosed in 25,356 patients with cancer (6.6 per 1,000 person-years). In multivariable Fine and Gray's regression analysis, cancer was an independent risk factor for incident AF (adjusted subdistribution hazard ratio [aHR]: 1.63; 95% confidence interval [CI]: 1.61 to 1.66). Multiple myeloma showed a higher association with incident AF (aHR: 3.34; 95% CI: 2.98 to 3.75). Esophageal cancer showed the highest risk among solid cancers (aHR: 2.69; 95% CI: 2.45 to 2.95), and stomach cancer showed the lowest association with AF risk (aHR: 1.27; 95% CI 1.23 to 1.32).
CONCLUSIONS Although patients with cancer were found to have a higher risk of AF, the impact on AF development varied by cancer type.
PubMed IF 15.5 순환기내과
34772021

제1저자 정성원, 박민경, 조영윤 · 교신저자 이정훈

, , , , , , , , , , , , , , , , ,
Effectiveness of Transarterial Chemoembolization-First Treatment for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.
J Hepatocell Carcinoma. 2021;8:587-598.

Abstract
BACKGROUND Still in real-world practice, advanced hepatocellular carcinoma (HCC) patients are treated with transarterial chemoembolization (TACE). This study compared the therapeutic effectiveness of initial TACE treatment and initial sorafenib treatment in advanced HCC patients.
PATIENT AND METHODS Advanced HCC patients initially treated with sorafenib or TACE were included in this study. Treatment crossover due to an unfavorable response to initial treatment was allowed. Propensity score (PS) matching was applied for balancing baseline characteristics. The primary outcome was overall survival (OS) and the secondary outcomes included tumor response.
RESULTS A total of 554 patients were included in this study: 85 were initially treated with sorafenib (the sorafenib-first group) and 469 with TACE (the TACE-first group). In the entire cohort, the TACE-first group was associated with lower risk of death [adjusted hazard ratio (HR)=0.75, P=0.04]. In the PS-matched cohort (85 patients per group), the TACE-first group showed longer OS than the sorafenib-first group in both univariable (HR=0.68, P=0.02) and multivariable analyses (adjusted HR=0.58, P=0.002). Specifically, within both the entire and the PS-matched cohorts, the TACE-first group showed longer OS in subgroups with major portal vein tumor thrombosis (HR=0.72, P=0.048; HR=0.52, P=0.003) or infiltrative HCC (HR=0.42, P<0.001; HR=0.30, P=0.004, respectively). The objective response rate was higher in the TACE-first group (29.3% vs 14.7%, P=0.03) within the PS-matched cohort.
CONCLUSION For advanced HCC, initial TACE leads to longer OS with a more favorable tumor response than initial sorafenib treatment. Intrahepatic tumor control with initial locoregional therapy may be a potent strategy for advanced HCC.
PubMed IF 3.9 소화기내과
34762021

제1저자 권유욱, 이신혜 · 교신저자 김효수

, , , , , , , , ,
Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells.
Stem Cell Res Ther. 2021;12(1):346.

Abstract
BACKGROUND The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs.
METHODS Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO₂ laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry.
RESULTS The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis.
CONCLUSIONS These results indicate that shikimic acid is an effective agent for tissue regeneration.
PubMed IF 7.8 순환기내과
34752021

제1저자 어원, 임수 · 교신저자 김진욱

, ,
Sodium-Glucose Cotransporter-2 Inhibitors Ameliorate Liver Enzyme Abnormalities in Korean Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.
Front Endocrinol (Lausanne). 2021;12:613389.

Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are reported to reduce body fat in patients with type 2 diabetes mellitus (T2DM), and SGLT2i-induced weight reduction may help improve comorbid nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the potential benefit of SGLT2is over other oral antidiabetic drugs (OADs) in patients with T2DM-associated NAFLD. We enrolled real-world Korean patients with T2DM-associated NAFLD in whom initial metformin therapy had been modified by stepwise addition of OAD(s) due to insufficient glucose control. Propensity score (PS) matching was used for the comparison of changes in clinical and biochemical parameters to balance potential covariates. Among the 765 enrolled patients, 663 patients received additional OADs other than SGLT2i and 102 patients received SGLT2i therapy. PS matching selected 150 and 100 patients from the control and the SGLT2i group, respectively. The SGLT2i group lost more weight than the control group at 6 months (mean -1.3 kg vs. 0.0 kg; P < 0.001). Alanine aminotransferase (ALT) levels also decreased more in the SGLT2i group at 3 (-11 U/L vs. -1 U/L), 6 (-12 U/L vs. -1 U/L), and 12 months (-14 U/L vs. -2 U/L) (all P < 0.05). Addition of SGLT2is was an independent predictor of ALT improvement in a multivariate logistic regression model (odds ratio 1.91; P = 0.016). Compared with other OADs, addition of SGLT2is was more effective in weight reduction and ALT improvement in patients with T2DM and comorbid NAFLD.
PubMed IF 5.7 소화기내과
34742021

제1저자 안현정, 이소령 · 교신저자 최의근

, , , , , , , , ,
Association between exercise habits and stroke, heart failure, and mortality in Korean patients with incident atrial fibrillation: A nationwide population-based cohort study.
PLoS Med. 2021;18(6):e1003659.

Abstract
BACKGROUND There is a paucity of information about cardiovascular outcomes related to exercise habit change after a new diagnosis of atrial fibrillation (AF). We investigated the association between exercise habits after a new AF diagnosis and ischemic stroke, heart failure (HF), and all-cause death.
METHODS AND FINDINGS This is a nationwide population-based cohort study using data from the Korea National Health Insurance Service. A retrospective analysis was performed for 66,692 patients with newly diagnosed AF between 2010 and 2016 who underwent 2 serial health examinations within 2 years before and after their AF diagnosis. Individuals were divided into 4 categories according to performance of regular exercise, which was investigated by a self-reported questionnaire in each health examination, before and after their AF diagnosis: persistent non-exercisers (30.5%), new exercisers (17.8%), exercise dropouts (17.4%), and exercise maintainers (34.2%). The primary outcomes were incidence of ischemic stroke, HF, and all-cause death. Differences in baseline characteristics among groups were balanced considering demographics, comorbidities, medications, lifestyle behaviors, and income status. The risks of the outcomes were computed by weighted Cox proportional hazards models with inverse probability of treatment weighting (IPTW) during a mean follow-up of 3.4 ± 2.0 years. The new exerciser and exercise maintainer groups were associated with a lower risk of HF compared to the persistent non-exerciser group: the hazard ratios (HRs) (95% CIs) were 0.95 (0.90-0.99) and 0.92 (0.88-0.96), respectively (p < 0.001). Also, performing exercise any time before or after AF diagnosis was associated with a lower risk of mortality compared to persistent non-exercising: the HR (95% CI) was 0.82 (0.73-0.91) for new exercisers, 0.83 (0.74-0.93) for exercise dropouts, and 0.61 (0.55-0.67) for exercise maintainers (p < 0.001). For ischemic stroke, the estimates of HRs were 10%-14% lower in patients of the exercise groups, yet differences were statistically insignificant (p = 0.057). Energy expenditure of 1,000-1,499 MET-min/wk (regular moderate exercise 170-240 min/wk) was consistently associated with a lower risk of each outcome based on a subgroup analysis of the new exerciser group. Study limitations include recall bias introduced due to the nature of the self-reported questionnaire and restricted external generalizability to other ethnic groups.
CONCLUSIONS Initiating or continuing regular exercise after AF diagnosis was associated with lower risks of HF and mortality. The promotion of exercise might reduce the future risk of adverse outcomes in patients with AF.
PubMed IF 9.9 순환기내과
34732021

제1저자 서경진 · 교신저자 김진원

, , , , , , , , , , ,
Correlation between tumor infiltrating immune cells and peripheral regulatory T cell determined using methylation analyses and its prognostic significance in resected gastric cancer.
PLoS One. 2021;16(6):e0252480.

Abstract
Peripheral regulatory T cells (pTregs) are a highly immunosuppressive fraction of CD4+ T cells. We aimed to evaluate the clinical significance of pTregs in patients with gastric cancer and to determine the correlation between pTregs and immune cell infiltration in tumor microenvironment. pTregs status was determined by assessing the pTreg/total T-cell ratio (ratio of Foxp3 Treg-specific demethylated region (TSDR) to CD3G/CD3D demethylation, so-called Cellular Ratio of Immune Tolerance "ImmunoCRIT") using methylation analyses in 433 patients with gastric cancer who received curative surgery. Among 422 evaluable patients, 230 (54.5%) had high ImmunoCRIT (> 21.0). Patients with high ImmunoCRIT had significantly shorter disease-free survival (DFS) and overall survival (OS) than those with high ImmunoCRIT (p = 0.030, p = 0.008, respectively). In multivariate analysis, high ImmunoCRIT kept a prognostic role for shorter OS (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.4-2.9; p = 0.005). CD3+ cell density and CD4+ cell density was significantly higher within the tumor in high ImmunoCRIT group than those in low ImmunoCRIT group (CD3+ cell, 202.12/mm2 vs. 172.2/mm2, p = 0.029; CD4+ cell, 56.5/mm2 vs. 43.5/mm2, p = 0.007). In conclusion, the peripheral ImmunoCRIT determined by epigenetic methylation analysis provides prognostic information in resected gastric tumors.
PubMed IF 2.8 혈액종양내과
34722021

제1저자 곽순구 · 교신저자 박준빈, 조구영

, , , , ,
Sex-specific impact of diabetes mellitus on left ventricular systolic function and prognosis in heart failure.
Sci Rep. 2021;11(1):11664.

Abstract
We aimed to investigate the sex differences in associations of diabetes mellitus (DM) with echocardiographic phenotypes and clinical outcomes of heart failure (HF). We studied 4,180 patients admitted for acute HF between 2009 and 2016 (median follow-up, 31.7 months) whose left ventricular global longitudinal strain (LV-GLS) data were available. Patients were compared by sex and DM. Structural equation model (SEM) analysis was performed to evaluate the moderating effects of two causal paths, via ischemic heart disease (IHD) and LV-GLS, linking DM with mortality. Compared to non-diabetic women, diabetic women had significantly lower LV-GLS (11.3% versus 10.1%, p < 0.001), but the difference was attenuated within men (9.7% versus 9.2%, p = 0.014) (p-for-interaction by sex = 0.018). In Cox analyses, DM was an independent predictor for higher mortality in both sexes (women: adjusted hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.15-1.59 versus men: HR 1.24, 95% CI 1.07-1.44, p-for-interaction by sex = 0.699). Restricted cubic spline curves showed that LV-GLS consistently declined, and mortality increased in women with worsening hyperglycemia, but these trends were not evident in men. In SEM analysis, the main driver from DM to mortality differed by sex; men had a stronger effect via IHD than LV-GLS, whereas LV-GLS was the only predominant path in women.
PubMed IF 4.9 순환기내과
34712021

제1저자 박세훈 · 교신저자 이하정

, , , , , , , , , , , ,
Increasing prescription of renin-angiotensin-aldosterone system blockers associated with improved kidney prognosis in Korean IgA nephropathy patients.
Clin Kidney J. 2021;14(6):1673-1680.

Abstract
BACKGROUND We aimed to describe the characteristics of immunoglobulin A nephropathy (IgAN) in Korea with assessment for time trends.
METHODS We performed a multicenter retrospective observational cohort study including biopsy-confirmed native IgAN cases from four tertiary hospitals in Korea. Time eras of diagnosis were stratified into 1979-2003, 2004-9 and 2010-17. The prognostic variable was progression to end-stage kidney disease (ESKD) analyzed by multivariable Cox regression analysis.
RESULTS We included 1366 (from 1979 to 2003), 1636 (from 2004 to 2009) and 1442 (from 2010 to 2017) IgAN patients in this study. In the recent periods, IgAN had relatively better clinical characteristics, as patients had higher estimated glomerular filtration rates and lower baseline blood pressures than before. The use of renin-angiotensin-aldosterone system (RAAS) blockers increased from 57.7% in 1979-2003 to 80.0% in 2010-17. During a median follow-up duration of 11.3 years, 722 patients progressed to ESKD with an incidence rate of 12.5 per 1000 person-years. The 10-year risk of progression to ESKD was lower in 2010-17 compared with that of 1979-2003 [adjusted hazard ratio 0.692 (95% confidence interval 0.523-0.915)], even after adjustment for multiple clinicopathologic characteristics. The use of RAAS blockers was a significant mediator (P < 0.001) for the association between time trends and lower 10-year ESKD risk.
CONCLUSIONS Clinicopathologic characteristics of IgAN in Korea have changed over time. Although the limitation of a retrospective observational study remains, the result showed that the prognosis of IgAN has improved over the study period, possibly related to increased prescription of RAAS blockers.
PubMed IF 5.3 신장내과
34702021

제1저자 이연주, 조경재 · 교신저자 조유한

, , , , , , , , , , , ,
A multicentre validation study of the deep learning-based early warning score for predicting in-hospital cardiac arrest in patients admitted to general wards.
Resuscitation. 2021;163:78-85.

Abstract
BACKGROUND The recently developed deep learning (DL)-based early warning score (DEWS) has shown potential in predicting deteriorating patients. We aimed to validate DEWS in multiple centres and compare the prediction, alarming and timeliness performance with the modified early warning score (MEWS) to identify patients at risk for in-hospital cardiac arrest (IHCA).
METHOD/RESEARCH DESIGN This retrospective cohort study included adult patients admitted to the general wards of five hospitals during a 12-month period. The occurrence of IHCA within 24 h of vital sign observation was the outcome of interest. We assessed the discrimination using the area under the receiver operating characteristic curve (AUROC).
RESULTS The study population consists of 173,368 patients (224 IHCAs). The predictive performance of DEWS was superior to that of MEWS in both the internal (AUROC: 0.860 vs. 0.754, respectively) and external (AUROC: 0.905 vs. 0.785, respectively) validation cohorts. At the same specificity, DEWS had a higher sensitivity than MEWS, and at the same sensitivity, DEWS reduced the mean alarm count by nearly half of MEWS. Additionally, DEWS was able to predict more IHCA patients in the 24-0.5 h before the outcome, and DEWS was reasonably calibrated.
CONCLUSION Our study showed that DEWS was superior to MEWS in three key aspects (IHCA predictive, alarming, and timeliness performance). This study demonstrates the potential of DEWS as an effective, efficient screening tool in rapid response systems (RRSs) to identify high-risk patients.
PubMed IF 6 호흡기내과
34692021

제1저자 안경민, 김선신 · 교신저자 박흥우

, , , ,
Vitamin D deficiency and lung function decline in healthy individuals: A large longitudinal observation study.
Respir Med. 2021;182:106395.

Abstract
AIM A reliable evidence from a comprehensive large-scale study supporting associations between serum vitamin D (25-hydroxyvitamin D) level (SVDL) and lung function decline (LFD) in healthy individuals has been unavailable. Using a well-established health screening database, we assessed the associations between SVDL and LFDs, measured as the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio.
METHODS Serial SVDL and lung function data were analyzed using linear mixed models, which were performed in smokers and non-smokers, separately. Vitamin D-deficient individuals (VDDs) were defined when their SVDLs were consistently lower than 20 ng/mL at all measurements.
RESULTS A total of 1371 individuals were analyzed. The mean FEV1 decline rates of VDDs and vitamin D-normal individuals (VDNs) in smokers were -33.35 mL/year (95% CI: 39.44 to -27.26 mL/year) and -15.61 mL/year (95% CI: 27.29 to -4.21 mL/year) respectively, over a mean of 6.29 years of observation with statistical significance (P < 0.001). However, there was no significant differences observed between decline rates of FEV1 in non-smokers. Similarly, FVC decline rates of VDDs were significantly greater than those of VDNs only in smokers (P < 0.001). However, FEV1/FVC ratio decline rates showed no significant difference between VDDs and VDNs regardless of their smoking status.
CONCLUSIONS Consistently low SVDLs predicted more rapid FEV1 and FVC declines in smokers. However, FEV1/FVC decline rate was not associated with SVDL. SVDL may be used to identify healthy smoking individuals at high risk for accelerated LFD.
PubMed IF 3.3 알레르기내과
34682021

제1저자 신동우 · 교신저자 황진혁

, , , , , ,
Tailored adjuvant gemcitabine versus 5-fluorouracil/folinic acid based on hENT1 immunohistochemical staining in resected pancreatic ductal adenocarcinoma: A biomarker stratified prospective trial.
Pancreatology. 2021;21(4):796-804.

Abstract
BACKGROUND The study aimed to evaluate the clinical outcomes of tailored adjuvant chemotherapy according to human equilibrative nucleoside transporter 1 (hENT1) expression in resected pancreatic ductal adenocarcinoma (PDA).
METHODS Patients who underwent pancreatectomy for PDA were enrolled prospectively. According to intra-tumoral hENT1 expression, the high hENT1 (≥50%) group received gemcitabine and the low hENT1 (<50%) group received 5-fluorouracil plus folinic acid (5-FU/FA). The propensity score-matched control consisted of patients who received hENT1-independent adjuvant chemotherapy. The primary outcome was recurrence free survival (RFS) and the secondary outcomes were overall survival (OS) and toxicities.
RESULTS Between May 2015 and June 2017, we enrolled 44 patients with resected PDA. During a median follow-up period of 28.5 months, the intention-to-treat population showed much longer median RFS [22.9 (95% CI, 11.3-34.5) vs. 10.9 (95% CI, 6.9-14.9) months, P = 0.043] and median OS [36.2 (95% CI, 26.5-45.9) vs. 22.1 (95% CI, 17.7-26.6) months, P = 0.001] compared to the controls. Among 5 patients in the low hENT1 group who discontinued treatment, 2 patients receiving 5-FU/FA discontinued treatment due to drug toxicities (febrile neutropenia and toxic epidermal necrolysis).
CONCLUSION Tailored adjuvant chemotherapy based on hENT1 staining provides excellent clinical outcomes among patients with resected PDA.
CLINICAL TRIAL REGISTRATION clinicaltrials.gov identifier: NCT02486497.
PubMed IF 3.9 소화기내과
34672021

제1저자 안창호, 이채린 · 교신저자 김정희, 최만호

, , , , , , , , ,
Metabolic changes in serum steroids for diagnosing and subtyping Cushing's syndrome.
J Steroid Biochem Mol Biol. 2021;210:105856.

Abstract
To evaluate the diagnostic value of serum levels of adrenal steroids for diagnosing and subtyping Cushing's syndrome. Patients diagnosed with endogenous Cushing's syndrome (34 and 19 patients with adrenal and pituitary Cushing's syndrome, respectively) and healthy controls (n = 34) were consecutively enrolled at Seoul National University from 2016 to 2020. Morning serum samples were collected before and 3 months after treatment. Serum steroids were profiled using liquid chromatography-mass spectrometry. The diagnostic value of each and the combination of steroids were assessed using the area under the curve of receiver operating characteristic (AUROC) and decision tree analysis. Tetrahydrocortisone and 6β-hydroxycortisol showed the highest AUROC (0.893 and 0.890, respectively) for the diagnosis of endogenous Cushing's syndrome. The decision tree composed of tetrahydrocortisone and 6β-hydroxycortisol correctly classified 79/87 (90.8 %) subjects. For subtyping into adrenal or pituitary Cushing's syndrome, dehydroepiandrosterone sulfate (DHEA-S) showed the highest AUROC (0.988), which was similar to that of plasma ACTH (0.994, P = 0.458). The decision tree composed of only DHEA-S correctly classified 51/53 (96.2 %) of the Cushing's syndrome subtype. DHEA-S showed a significant linear correlation with the plasma ACTH level, but not with the 24 -h urine free cortisol or dexamethasone suppression test results. All steroids, except allo-tetrahydrocortisol and tetrahydrocortisone, decreased significantly at 3 months post-treatment with similar patterns in both adrenal and pituitary Cushing's syndrome. Serum steroid profiling using a single morning serum sample provides valuable information for diagnosing and subtyping Cushing's syndrome.
PubMed IF 3.1 내분비대사내과
34662021

제1저자 박세훈, 이주은, 양승희 · 교신저자 황금숙, 김동기

, , , , , , , , , , , , , , , , , , ,
Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker.
J Cell Mol Med. 2021;25(11):5177-5190.

Abstract
Identification of a urinary metabolite biomarker with diagnostic or prognostic significance for early immunoglobulin A nephropathy (IgAN) is needed. We performed nuclear magnetic resonance-based metabolomic profiling and identified 26 metabolites in urine samples. We collected urine samples from 201, 77, 47, 36 and 136 patients with IgAN, patients with membranous nephropathy, patients with minimal change disease, patients with lupus nephritis and healthy controls, respectively. We determined whether a metabolite level is associated with the prognosis of IgAN through Cox regression and continuous net reclassification improvement (cNRI). Finally, in vitro experiments with human kidney tubular epithelial cells (hTECs) were performed for experimental validation. As the results, the urinary glycine level was higher in the IgAN group than the control groups. A higher urinary glycine level was associated with lower risk of eGFR 30% decline in IgAN patients. The addition of glycine to a predictive model including clinicopathologic information significantly improved the predictive power for the prognosis of IgAN [cNRI 0.72 (0.28-0.82)]. In hTECs, the addition of glycine ameliorated inflammatory signals induced by tumour necrosis factor-α. Our study demonstrates that urinary glycine may have diagnostic and prognostic value for IgAN and indicates that urinary glycine is a protective biomarker for IgAN.
PubMed IF 4.7 신장내과
34652021

제1저자 이영아, 윤효리 · 교신저자 박영주, 김신곤

, , , , , ,
Trends in Pediatric Thyroid Cancer Incidence, Treatment, and Clinical Course in Korea During 2004-2016: A Nationwide Population-Based Study.
Thyroid. 2021;31(6):902-911.

Abstract
Background: The incidence of thyroid cancer has increased worldwide. We investigated nationwide trends in the incidence and treatment course of pediatric thyroid cancer in South Korea. Methods: Using the National Health Information Database, we analyzed 1580 patients (324 males) <20 years of age diagnosed with thyroid cancer during 2004-2016 in South Korea. The annual percentage change (APC) in the age-standardized incidence rate (ASR) was calculated by joinpoint regression analysis. The initial treatment modality was categorized as either surgery only or surgery with radioactive-iodine treatment (surgery+RAIT), and we defined new treatment events as reoperations or additional RAITs among 1464 patients followed up for ≥12 months. Results: During 2004-2016, the mean ASR per 100,000 person-years increased from 0.6 [confidence interval; CI 0.5-0.8] to 0.9 [CI 0.8-1.1], with a mean APC of 4.0% [CI 1.8-6.2]. The ASRs (APCs) among 0-9-, 10-14-, 15-17-, and 18-19-year olds were 0.07 (9.9% [CI 0.08-20.7]), 0.6 (4.6% [CI 0.2-9.2]), 2.2 (3.9 [CI 1.7-6.0]), and 4.2 (3.5% [CI 0.9-6.2]), respectively. The lobectomy and lymph-node-dissection rates increased (from 18.5% to 33.6%, p = 0.0014; and from 29.6% to 84.5%, p < 0.001; respectively), but the RAIT rate decreased (67.9-39.7%, p < 0.001) during the study period. During a median 6.3-year follow-up, two patients died. New treatment events occurred in 56 (10.7%) of patients in the initial surgery-only group (n = 523). In the initial surgery+RAIT group (n = 941), 316 patients received two or more RAITs within 2 years, and 80 (12.8%) of the remaining 625 patients underwent new treatment events. In the surgery+RAIT subgroup, the event-free survival rate was lower in 0-14-year olds than in 18-19-year olds (hazard ratio 2.5 [CI 1.4-4.4]). Conclusions: The pediatric thyroid cancer incidence increased from 2004 to 2012 in South Korea. The lobectomy and lymph-node-dissection rates increased, but the RAIT rate decreased. The higher risk for new treatment events in patients younger than 15 years requiring initial RAIT may be linked to advanced stage at diagnosis, and it needs to be further evaluated.
PubMed IF 6.6 내분비대사내과
34642021

제1저자 박세훈 · 교신저자 김동기

, , , , , , , , , , , , ,
Causal Effects of Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism on Kidney Function: A Mendelian Randomization Study.
J Am Soc Nephrol. 2021;32(6):1484-1496.

Abstract
BACKGROUND Further investigation of the causal effects of psychologic wellbeing on kidney function is warranted.
METHODS In this Mendelian randomization (MR) study, genetic instruments for positive affect, life satisfaction, depressive symptoms, and neuroticism were introduced from a previous genome-wide association study meta-analysis of European individuals. Summary-level MR was performed using the CKDGen data of European ancestry (n=567,460), and additional allele score-based MR was performed in the individual-level data of White British UK Biobank participants (n=321,024).
RESULTS In summary-level MR with the CKDGen data, depressive symptoms were a significant causative factor for kidney function impairment (CKD OR, 1.45; 95% confidence interval, 1.07 to 1.96; eGFR change [%] beta -2.18; 95% confidence interval, -3.61 to -0.72) and pleiotropy-robust sensitivity analysis results supported the causal estimates. A genetic predisposition for positive affect was significantly associated with better kidney function (CKD OR, 0.69; 95% confidence interval, 0.52 to 0.91), eGFR change [%] beta 1.50; 95% confidence interval, 0.09 to 2.93) and sensitivity MR analysis results supported the finding for CKD outcome, but was nonsignificant for eGFR. Life satisfaction and neuroticism exposures showed nonsignificant causal estimates. In the UK Biobank with covariate-adjusted allele score MR analysis, allele scores for positive affect and life satisfaction were causally associated with reduced risk of CKD and higher eGFR. In contrast, neuroticism allele score was associated with increased risk of CKD and lower eGFR, and depressive symptoms allele score was associated with lower eGFR, but showed nonsignificant association with CKD.
CONCLUSIONS Health care providers in the nephrology field should be aware of the causal linkage between psychologic wellbeing and kidney function.
PubMed IF 9.7 신장내과
34632021

제1저자 이은경, 강예은 · 교신저자 박영주, 구본석

, , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol.
Endocrinol Metab (Seoul). 2021;36(3):574-581.

Abstract
BACKGROUND Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy.
METHODS This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years.
CONCLUSION The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.
PubMed IF 5.1 내분비대사내과
34622021

제1저자 박세훈 · 교신저자 김동기

, , , , , , , , , , , , ,
Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study.
Kidney Res Clin Pract. 2021;40(2):282-293.

Abstract
BACKGROUND An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation.
METHODS The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities.
RESULTS Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02-1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity.
CONCLUSION The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.
PubMed IF 3.5 신장내과
34612021

제1저자 최유정, 한경도 · 교신저자 최의근

, , , , , ,
Alcohol Abstinence and the Risk of Atrial Fibrillation in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide Population-Based Study.
Diabetes Care. 2021;44(6):1393-1401.

Abstract
OBJECTIVE To investigate the effects of alcohol abstinence on prevention of new-onset atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM).
RESEARCH DESIGN AND METHODS A total of 1,112,682 patients newly diagnosed with T2DM between 2011 and 2014 were identified from the Korean National Health Insurance Service database. After excluding those with a history of AF, 175,100 patients were included. The primary outcome was new-onset AF.
RESULTS During a mean follow-up of 4.0 years, AF occurred in 4,174 patients. Those with heavy alcohol consumption (alcohol intake ≥40 g/day) before T2DM diagnosis had a higher risk of AF (adjusted hazard ratio [aHR] 1.22; 95% CI 1.06-1.41) compared with patients with no alcohol consumption. After T2DM diagnosis, those with moderate to heavy alcohol consumption (alcohol intake ≥20 g/day) who abstained from alcohol had a lower risk of AF (aHR 0.81; 95% CI 0.68-0.97) compared with constant drinkers. Alcohol abstinence showed consistent trends toward lower incident AF in all subgroups and was statistically significant in men (aHR 0.80; 95% CI 0.67-0.96), those aged >65 years (aHR 0.69; 95% CI 0.52-0.91), those with CHA₂DS₂-VASc score <3 points (aHR 0.71; 95% CI 0.59-0.86), noninsulin users (aHR 0.77; 95% CI 0.63-0.94), and those with BMI <25 kg/m² (aHR 0.68; 95% CI 0.53-0.88).
CONCLUSIONS In patients with newly diagnosed T2DM, alcohol abstinence was associated with a low risk of AF development. Lifestyle modifications, such as alcohol abstinence, in patients newly diagnosed with T2DM should be recommended to reduce the risk of AF.
PubMed IF 22.6 순환기내과
34602021

제1저자 김예안, 김영아 · 교신저자 박영주

, , , , , , , ,
Increased expression of thyroid hormone receptor alpha and estrogen receptor alpha in breast cancer associated with thyroid cancer.
Eur J Surg Oncol. 2021;47(6):1316-1323.

Abstract
INTRODUCTION Breast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings.
MATERIAL AND METHODS Tissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERβ, TRα, and TRβ expression levels were analyzed by immunohistochemistry.
RESULTS TRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p < 0.001).
CONCLUSION Enhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.
PubMed IF 3.5 내분비대사내과
34592021

제1저자 백우현, 우상명 · 교신저자 이상협

, , , , , , , , , ,
Efficacy of an internal anchoring plastic stent to prevent migration of a fully covered metal stent in malignant distal biliary strictures: a randomized controlled study.
Endoscopy. 2021;53(6):578-585.

Abstract
BACKGROUND Two types of self-expandable metal stents (SEMS) are available for malignant distal biliary obstruction: fully covered SEMS (FCSEMS) and uncovered SEMS. FCSEMS can prevent stent ingrowth, but a major concern is spontaneous migration. This study aimed to determine whether the additional insertion of a double-pigtail plastic stent to anchor the FCSEMS can prevent migration.
METHODS 68 patients with unresectable, malignant, distal, biliary obstruction were included in this multicenter, randomized, superiority trial. The patients were randomly assigned to receive either the FCSEMS plus an anchoring plastic stent (n = 33) or an FCSEMS alone (n = 35). After placement of the FCSEMS, the anchoring stent was inserted inside the FCSEMS. The primary outcome was the rate of stent migration during the 6-month follow-up. The secondary outcomes were stent-related adverse events, stent patency, and survival rates.
RESULTS The baseline characteristics were similar between the two groups. The rate of stent migration at 6 months was significantly lower in patients with the FCSEMS plus anchoring stent (15 % vs. 40 %; P = 0.02). The mean stent patency was significantly longer in the FCSEMS plus anchoring group (237 days [95 % confidence interval [CI] 199 to 275] vs. 173 days [95 %CI 130 to 217]; P = 0.048). There were no significant differences in stent-related adverse events and overall survival rates at 6 months between the two groups.
CONCLUSIONS Our data suggest that the additional double-pigtail plastic stent anchored the FCSEMS to prevent migration and prolonged patency without any serious adverse events.
PubMed IF 11.8 소화기내과
34582021

제1저자 유신혜, 윤지희 · 교신저자 김범석

, , , , , , , , , , , , ,
Discovery of acquired molecular signature on immune checkpoint inhibitors in paired tumor tissues.
Cancer Immunol Immunother. 2021;70(6):1755-1769.

Abstract
BACKGROUND Immune checkpoint inhibitor (ICI) has an emerging role in several types of cancer. However, the mechanisms of acquired resistance (AR) to ICI have not been elucidated yet. To identify these mechanisms, we analyzed the pre- and post-ICI paired tumor samples in patients with AR.
METHODS Six patients with renal cell carcinoma, urothelial cell carcinoma, or head and neck cancer, who showed an initial response to ICI followed by progression and had available paired tissue samples, were retrospectively analyzed. Whole exome sequencing, RNA sequencing, and multiplex immunohistochemistry were performed on pre-treatment and resistant tumor samples.
RESULTS The median time to AR was 370 days (range, 210 to 739). Increased expression of alternative immune checkpoints including TIM3, LAG3, and PD-1 as well as increased CD8⁺ tumor-infiltrating lymphocytes were observed in post-treatment tumor than in pre-treatment tumor of a renal cell carcinoma patient. In contrast, CD8⁺ T cells and immunosuppressive markers were all decreased at AR in another patient with human papillomavirus-positive head and neck squamous cell carcinoma. This patient had an evident APOBEC-associated signature, and the tumor mutation burden increased at AR. Resistant tumor tissue of this patient harbored a missense mutation (E542K) in PIK3CA. No significant aberrations of antigen-presenting machinery or IFN-γ pathway were detected in any patient.
CONCLUSIONS Our study findings suggest that the observed increase in immunosuppressive markers after ICI might contribute to AR. Moreover, APOBEC-mediated PIK3CA mutagenesis might be an AR mechanism. To validate these mechanisms of AR, further studies with enough sample size are required.
PubMed IF 5.8 혈액종양내과
34572021

제1저자 이윤빈, 문혜미, 이정훈 · 교신저자 이윤빈, 이준영

, , , , , , , ,
Association of Metabolic Risk Factors With Risks of Cancer and All-Cause Mortality in Patients With Chronic Hepatitis B.
Hepatology. 2021;73(6):2266-2277.

Abstract
BACKGROUND AND AIMS Long-term antiviral therapy can effectively suppress viral replication and improve clinical outcomes in patients with chronic hepatitis B (CHB), but it cannot eliminate risk of HCC. We investigated the association of metabolic risk factors with the risks of cancer and all-cause mortality in patients with CHB.
APPROACH AND RESULTS This nationwide population-based study from the Korean National Health Insurance Service database consisted of adults with CHB who underwent health examinations from 2007 through 2012. We collected baseline data on metabolic risk factors, including obesity, high blood pressure, hypercholesterolemia, and diabetes. The risks of developing HCC, non-HCC cancer, and overall death were analyzed according to the metabolic risk profile. The study population composed of 317,856 patients (median age, 46 years [interquartile range, 37-54 years]; 219,418 men [69.0%]) had 2,609,523.8 person-years of follow-up. A total of 18,850 HCCs, 22,164 non-HCC cancers, and 15,768 deaths were observed during a median follow-up period of 8.5 years. The metabolic risk factor burden was positively associated with the risks of HCC, non-HCC cancer, and all-cause mortality (all P < 0.0001 for trend). Patients with ≥3 metabolic risk factors, compared with those without metabolic risk factors, showed adjusted hazard ratios of 1.23 (95% CI, 1.16-1.31) for HCC, 1.34 (95% CI, 1.27-1.41) for non-HCC cancer, and 1.31 (95% CI, 1.23-1.39) for all-cause mortality. Among patients receiving antiviral therapy for over 5 years, the risk-increasing association of the sum of metabolic risk factors with the risks of HCC and overall death was consistent.
CONCLUSION The metabolic risk factor burden was associated with increased risks of HCC, non-HCC cancer, and all-cause mortality in patients with CHB.
PubMed IF 18 소화기내과
34562021

제1저자 이은지, 신철민 · 교신저자 이동호, 한경도

, , , , , , , ,
The Association Between Cholecystectomy and the Risk for Fracture: A Nationwide Population-Based Cohort Study in Korea.
Front Endocrinol (Lausanne). 2021;12:657488.

Abstract
OBJECTIVES To evaluate the risk of fracture in individuals with a history of cholecystectomy in Korean population.
METHODS Individuals (n = 143,667) aged ≥ 40 y who underwent cholecystectomy between 2010 and 2015 and the controls (n = 255,522), matched by age and sex, were identified from the database of the Korean National Health Insurance Services. The adjusted hazard ratio (aHR) and 95% confidence interval (CI) of fracture were estimated following cholecystectomy, and a Cox regression analysis was performed.
RESULTS The incidence rates of all fractures, vertebral, and hip fractures were 14.689, 6.483 and 1.228 cases per 1000 person-years respectively in the cholecystectomy group, whereas they were 13.862, 5.976, and 1.019 cases per 1000 person-years respectively in the control group. After adjustment for age, sex, income, place of residence, diabetes mellitus, hypertension, dyslipidemia, smoking, alcohol drinking, exercise, and body mass index, patients who underwent cholecystectomy showed an increased risk of all fractures, vertebral fractures, and hip fractures (aHR [95% CI]: 1.095 [1.059-1.132], 1.134 [1.078-1.193], and 1.283 [1.139-1.444] for all fractures, vertebral fractures, and hip fractures, respectively). The risk of vertebral fractures following cholecystectomy was more prominent in the young age group (40 to 49 y) than in the old age group (≥ 65 y) (1.366 [1.082-1.724] vs. 1.132 [1.063-1.206], respectively). However, the incidence of hip fractures following cholecystectomy was not affected by age.
CONCLUSION Individuals who underwent cholecystectomy have an increased risk of fracture. In the younger population, the risk of vertebral fractures may be further increased following cholecystectomy.
PubMed IF 5.7 소화기내과
34552021

제1저자 정재원 · 교신저자 박영주, 배정모

, , , , , , ,
Decreased Expression of Ileal Thyroid Hormone Transporters in a Hypothyroid Patient: A Case Report.
Front Endocrinol (Lausanne). 2021;12:664839.

Abstract
BACKGROUND Malabsorption of levothyroxine (LT4) is a common problem faced in clinical practice. It is usually solved, if there are no complexities including gastrointestinal absorption disorder, by taking medicines on an empty stomach and avoiding foods interfering with LT4. Herein we present a rare case of a patient exhibiting malabsorption of LT4 with decreased membranous expression of ileal transporters.
CASE The 22-Year-old female presented with sustained hypothyroid status despite medication of 7.8 μg/kg LT4. Medical history and LT4 absorption test (the absorption rate 8.4%) excluded pseudomalabsorption. No organic gastrointestinal disorder was found in the patient by blood chemistry, endoscopies, and abdominal computed tomography scan. The immunohistochemical analysis showed decreased membranous expression of LAT1 and LAT2 in distal ileum and ascending colon in the patient compared to 20 controls who have no thyroid disease. The expression of MCT8 in colon appeared at both nucleus and brush border in the patient, while it was limited to brush border in controls. The expression of other transporters was similar between the patient and controls.
CONCLUSION The changes of the expression of LAT1 and LAT2 in this patient showing LT4 malabsorption might help to understand the role of intestinal transporters in the absorption of LT4 in humans. The functional relevance of the decrement of LAT1 and LAT2 in this patient remains to be elucidated.
PubMed IF 5.7 내분비대사내과
34542021

제1저자 김지은 · 교신저자 한승석, 윤순호

, , , , , , ,
Deep Learning-Based Quantification of Visceral Fat Volumes Predicts Posttransplant Diabetes Mellitus in Kidney Transplant Recipients.
Front Med (Lausanne). 2021;8:632097.

Abstract
Background: Because obesity is associated with the risk of posttransplant diabetes mellitus (PTDM), the precise estimation of visceral fat mass before transplantation may be helpful. Herein, we addressed whether a deep-learning based volumetric fat quantification on pretransplant computed tomographic images predicted the risk of PTDM more precisely than body mass index (BMI). Methods: We retrospectively included a total of 718 nondiabetic kidney recipients who underwent pretransplant abdominal computed tomography. The 2D (waist) and 3D (waist or abdominal) volumes of visceral, subcutaneous, and total fat masses were automatically quantified using the deep neural network. The predictability of the PTDM risk was estimated using a multivariate Cox model and compared among the fat parameters using the areas under the receiver operating characteristic curves (AUROCs). Results: PTDM occurred in 179 patients (24.9%) during the median follow-up period of 5 years (interquartile range, 2.5-8.6 years). All the fat parameters predicted the risk of PTDM, but the visceral and total fat volumes from 2D and 3D evaluations had higher AUROC values than BMI did, and the best predictor of PTDM was the 3D abdominal visceral fat volumes [AUROC, 0.688 (0.636-0.741)]. The addition of the 3D abdominal VF volume to the model with clinical risk factors increased the predictability of PTDM, but BMI did not. Conclusions: A deep-learning based quantification of visceral fat volumes on computed tomographic images better predicts the risk of PTDM after kidney transplantation than BMI.
PubMed IF 3.6 신장내과
34532021

제1저자 이연희 · 교신저자 한승석

, , , , , , , , , , ,
Cardiovascular Risk Comparison between Expanded Hemodialysis Using Theranova and Online Hemodiafiltration (CARTOON): A Multicenter Randomized Controlled Trial.
Sci Rep. 2021;11(1):10807.

Abstract
Expanded hemodialysis (HDx) with medium cutoff (MCO) membranes, which remove middle-to-large molecules well, may be a good option to replace online hemodiafiltration (online-HDF). To provide more evidence, this randomized controlled trial compared several cardiovascular parameters between patients undergoing HDx and online-HDF. Eighty patients undergoing thrice-weekly hemodialysis were randomly assigned to receive either HDx with a Theranova membrane (n = 43) or online-HDF (n = 37). The primary endpoints were changes in brachial-ankle pulse wave velocity (baPWV), echocardiographic parameters, and coronary artery calcium (CAC) scores over 1 year, and the secondary endpoints included blood cardiovascular biomarkers, mortality, and patient-reported outcomes. A linear mixed model and log-rank test were used to estimate the group differences. 65 patients had completed the trial. The changes in baPWV and echocardiographic parameters did not differ between the two groups. The CAC scores remained stable in the online-HDF group, whereas an increasing trend was shown in the HDx group (P = 0.012). Other endpoints, including cardiovascular and all-cause mortalities, were similar between the two groups. The changes in cardiovascular parameters did not differ between HDx with an MCO membrane and online-HDF. However, attention may be needed in patients with high CAC scores or scores with an increasing tendency when online-HDF is replaced with HDx with an MCO membrane.
PubMed IF 4.9 신장내과
34522021

제1저자 김소정 · 교신저자 조재영

, , , , , , , ,
Sleep Duration and Its Associations with Mortality and Quality of Life in Chronic Obstructive Pulmonary Disease: Results from the 2007-2015 KNAHNES.
Respiration. 2021;100(11):1043-1049.

Abstract
BACKGROUND While extreme sleep duration negatively affects mortality and health-related quality of life (HRQOL) in general populations, the relationship remains uncertain in patients with chronic obstructive pulmonary disease (COPD).
OBJECTIVES To evaluate the association between sleep duration and mortality and HRQOL in patients with COPD.
METHODS We analyzed 3,349 participants with COPD enrolled in the 2007-2015 Korea National Health and Nutrition Examination Survey (KNHANES). Participants aged 40 years or older with a smoking history and prebronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7 were eligible. The participants were categorized as short sleepers (<6 h), 6-8 h, and long sleepers (>8) according to self-reported sleep duration. The outcome variables were all-cause mortality and HRQOL. HRQOL was measured using the European Quality of Life-5 Dimensions (EQ-5D) index.
RESULTS During a median of 6.5 years, 386 (11.5%) participants died. In unadjusted Cox regression analysis, short sleepers with COPD had an increased risk of death (hazard ratio, 1.35; 95% confidence interval [CI]: 1.07-1.71). However, this association was not significant after adjusting for sociodemographic factors, BMI, FEV1, and comorbidities. In unadjusted and adjusted multiple linear regression, short sleepers had significantly worse HRQOL. The adjusted means of the EQ-5D index were 0.88 (95% CI: 0.87-0.89) for short sleepers, 0.90 (95% CI: 0.90-0.91) for 6- to 8-h sleepers, and 0.89 (95% CI: 0.87-0.91) for long sleepers (p = 0.01).
CONCLUSIONS In patients with COPD, sleep duration was not associated with all-cause mortality. However, short sleep duration was significantly associated with worse HRQOL.
PubMed IF 2.6 호흡기내과
34512021

제1저자 이소령 · 교신저자 최의근

, , , , ,
Smoking Cessation after Diagnosis of New-Onset Atrial Fibrillation and the Risk of Stroke and Death.
J Clin Med. 2021;10(11):jcm10112238.

Abstract
Limited data are available regarding the impact of smoking cessation after atrial fibrillation (AF) diagnosis on clinical outcomes. Using the Korean National Health Insurance Service database, we included patients newly diagnosed with AF and categorized them into four groups as follows: (i) never smokers, (ii) ex-smokers, (iii) smoking cessation after AF diagnosis ("quitters"), and (iv) current smokers. The primary outcomes were incident ischemic stroke and all-cause death during follow-up. Fatal ischemic stroke and death from cerebrovascular events were evaluated as secondary outcomes. Among 97,637 patients (mean age, 61 years; mean CHA₂DS₂-VASc score, 2.3), 6.9% stopped smoking after AF diagnosis. The mean follow-up duration was 3.2 ± 2.0 years. After multivariable adjustment, quitters had lower risks of ischemic stroke (hazard ratio (HR), 0.702; 95% confidence interval (CI), 0.595-0.827) and all-cause death (HR, 0.842; 95% CI, 0.748-0.948) than current smokers. Quitters after AF diagnosis were associated with lower risks of fatal ischemic stroke (HR, 0.454; 95% CI, 0.287-0.718) and death from cerebrovascular events (HR, 0.664; 95% CI, 0.465-0.949) compared with current smokers. Quitting smoking may reduce the risk of ischemic stroke, the severity of ischemic stroke, and the incidence of cerebrovascular events in patients with new-onset AF.
PubMed IF 3.3 순환기내과
34502021

제1저자 곽낙원, 이경희 · 교신저자 유철규

, , , , ,
Synergistic cycles of protease activity and inflammation via PPARγ degradation in chronic obstructive pulmonary disease.
Exp Mol Med. 2021;53(5):947-955.

Abstract
Inflammation, oxidative stress, and protease-antiprotease imbalance have been suggested to be a pathogenic triad in chronic obstructive pulmonary disease (COPD). However, it is not clear how proteases interact with components of inflammatory pathways. Therefore, this study aimed to evaluate the effect of neutrophil elastase (NE) on lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) production and determine the molecular mechanism in human bronchial epithelial cells (HBECs). Immortalized bronchial epithelial cells and primary HBECs were used to investigate the impact of NE on LPS-induced IL-8 production. The molecular mechanism by which NE modulated LPS-induced IL-8 production was confirmed in elastase-treated C57BL/6 mice and primary HBECs obtained from COPD patients and healthy controls. The results showed that NE treatment synergistically augmented LPS-induced IL-8 production in both immortalized bronchial epithelial cells and primary HBECs. NE partially degraded peroxisome proliferator-activated receptor gamma (PPARγ), which is known to regulate IL-8 production in the nucleus. Treatment with a PPARγ agonist and overexpression of PPARγ reversed the NE-induced synergistic increase in LPS-induced IL-8 production. Moreover, PPARγ levels were lower in lung homogenates and lung epithelial cells from elastase-treated mice than in those from saline-treated mice. In accordance with the findings in mice, PPARγ levels were lower in primary HBECs from COPD patients than in those from healthy never-smokers or healthy smokers. In conclusion, a vicious cycle of mutual augmentation of protease activity and inflammation resulting from PPARγ degradation plays a role in the pathogenesis of COPD.
PubMed IF 17.5 호흡기내과
34492021

제1저자 권유욱, 안효석 · 교신저자 김효수

, , , , , , , , , ,
HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells.
Stem Cells Int. 2021;2021:8873383.

Abstract
Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing. Transcription activator-like effector nucleases (TALENs) were designed for selective elimination of HLA DR expression. The engineered nucleases completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDF) that did not express HLA DR even after stimulation with IFN-γ. Teratomas formed by HLA DR knockout iPSCs did not express HLA DR, and dendritic cells differentiated from HLA DR knockout iPSCs reduced CD4⁺ T cell activation. These engineered iPSCs might provide a novel translational approach to treat multiple recipients from a limited number of cell donors.
PubMed IF 3.6 순환기내과

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