SCI 발표논문

1. 1782021

   제1저자 박세훈, 이주은, 양승희 · 교신저자 황금숙, 김동기

   Park S, Lee J, Yang SH, Lee H, Kim JY, Park M, Kim KH, Moon JJ, Cho S, Lee S, Kim Y, Lee H, Lee JP, Jeong CW, Kwak C, Joo KW, Lim CS, Kim YS, Hwang GS, Kim DK

   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
2. 1772021

   제1저자 이영아, 윤효리 · 교신저자 박영주, 김신곤

   Lee YA, Yun HR, Lee J, Moon H, Shin CH, Kim SG, Park YJ

   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
3. 1762021

   제1저자 박세훈 · 교신저자 김동기

   Park S, Lee S, Kim Y, Lee Y, Kang MW, Kim K, Kim YC, Han SS, Lee H, Lee JP, Joo KW, Lim CS, Kim YS, Kim DK

   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
4. 1752021

   제1저자 이은경, 강예은 · 교신저자 박영주, 구본석

   Lee EK, Kang YE, Park YJ, Koo BS, Chung KW, Ku EJ, Won HR, Yoo WS, Jeon E, Paek SH, Lee YS, Lim DM, Suh YJ, Park HK, Kim HJ, Kim BH, Kim M, Kim SW, Yi KH, Park SK, Jung EJ, Choi JY, Bae JS, Hong JH, Nam KH, Lee YK, Yu HW, Go S, Kang YM, MASTER study group

   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
5. 1742021

   제1저자 박세훈 · 교신저자 김동기

   Park S, Lee S, Kim Y, Lee Y, Kang MW, Kim K, Kim YC, Han SS, Lee H, Lee JP, Joo KW, Lim CS, Kim YS, Kim DK

   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
6. 1732021

   제1저자 최유정, 한경도 · 교신저자 최의근

   Choi YJ, Han KD, Choi EK, Jung JH, Lee SR, Oh S, Lip GYH

   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
7. 1722021

   제1저자 김예안, 김영아 · 교신저자 박영주

   Kim YA, Kim YA, Cho SW, Song YS, Min HS, Park IA, Park DJ, Hwang KT, Park YJ

   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
8. 1712021

   제1저자 백우현, 우상명 · 교신저자 이상협

   Paik WH^*, Woo SM^*, Chun JW, Song BJ, Lee WJ, Ahn DW, Lee YS, Choi YH, Ryu JK, Kim YT, Lee SH

   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
9. 1702021

   제1저자 유신혜, 윤지희 · 교신저자 김범석

   Yoo SH^*, Yun J^*, Keam B, Hong SP, Ock CY, Koh J, Kim S, Jeon YK, Jung KC, Kim M, Kim TM, Kim DW, Kim JI, Heo DS

   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
10. 1692021

    제1저자 이윤빈, 문혜미, 이정훈 · 교신저자 이윤빈, 이준영

    Lee YB^*, Moon H^*, Lee JH^*, Cho EJ, Yu SJ, Kim YJ, Zoulim F, Lee J, Yoon JH

    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
11. 1682021

    제1저자 이은지, 신철민 · 교신저자 이동호, 한경도

    Lee EJ, Shin CM, Lee DH, Han K, Park SH, Kim YJ, Yoon H, Park YS, Kim N

    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
12. 1672021

    제1저자 정재원 · 교신저자 박영주, 배정모

    Chung CW, Mo EY, Jung GS, Kim YH, Cho SW, Park DJ, Bae JM, Park YJ

    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
13. 1662021

    제1저자 김지은 · 교신저자 한승석, 윤순호

    Kim JE, Park SJ, Kim YC, Min SI, Ha J, Kim YS, Yoon SH, Han SS

    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
14. 1652021

    제1저자 이연희 · 교신저자 한승석

    Lee Y, Jang MJ, Jeon J, Lee JE, Huh W, Choi BS, Park CW, Chin HJ, Kang CL, Kim DK, Han SS, Joo KW

    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
15. 1642021

    제1저자 김소정 · 교신저자 조재영

    Kim SJ, Kwak N, Choi SM, Lee J, Park YS, Lee CH, Lee SM, Yoo CG, Cho J

    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
16. 1632021

    제1저자 이소령 · 교신저자 최의근

    Lee SR, Choi EK, Jung JH, Han KD, Oh S, Lip GYH

    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
17. 1622021

    제1저자 곽낙원, 이경희 · 교신저자 유철규

    Kwak N^*, Lee KH^*, Woo J, Kim J, Lee CH, Yoo CG

    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
18. 1612021

    제1저자 권유욱, 안효석 · 교신저자 김효수

    Kwon YW^*, Ahn HS^*, Lee JW, Yang HM, Cho HJ, Kim SJ, Lee SH, Yang HM, Jang HD, Kim SJ, Kim HS

    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
19. 1602021

    제1저자 백선하 · 교신저자 이하정

    Baek SH, Park S, Yu MY, Kim JE, Park SH, Han K, Kim YC, Kim DK, Joo KW, Kim YS, Lee H

    Incident Parkinson's disease in kidney transplantation recipients: a nationwide population-based cohort study in Korea.

    Sci Rep. 2021;11(1):10541.

    Abstract

    This nation-wide population based retrospective cohort study evaluated risk of incident Parkinson' disease in kidney transplant (KT) recipients in Korea. From Korean National Health Insurance Service database, we identified incident KT recipients aged ≥ 40 years without any history of Parkinson's disease between 2007 and 2015. We established two control cohorts without a history of Parkinson' disease: (1) General population (GP) cohort of insured subjects without a history of kidney disease, (2) end-stage renal disease (ESRD) cohort of incident ESRD subjects, with frequency matched for age, sex, and inclusion year. Parkinson's disease data were obtained from baseline until December 2017. We followed 8372 KT recipients, ESRD patients, and GP for 45,723, 38,357, and 47,476 patient-years, respectively. Their mean age was 51.2 years and 60.1% were men. During follow-up period, 19 KT recipients, 53 ESRD patients, and 15 GP developed Parkinson' disease. Risk of incident Parkinson's disease in KT recipients was similar to that in GP (adjusted hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.35 to 2.13, P = 0.75) and significantly lower than that in ESRD patients (adjusted HR 0.31, 95% CI 0.18 to 0.52, P < 0.001). Older age was the strongest predictor for incident Parkinson's disease in KT recipients.

    PubMed IF 4.9 신장내과
20. 1592021

    제1저자 기유정 · 교신저자 한정규

    Ki YJ, Kang J, Yang HM, Woo Park K, Kang HJ, Koo BK, Cho MC, Kim CJ, Ahn Y, Jeong MH, Han JK, Kim HS, investigators for Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH)

    Immediate Compared With Delayed Percutaneous Coronary Intervention for Patients With ST-Segment-Elevation Myocardial Infarction Presenting ≥12 Hours After Symptom Onset Is Not Associated With Improved Clinical Outcome.

    Circ Cardiovasc Interv. 2021;14(5):e009863.

    Abstract

    [Figure: see text].

    PubMed IF 7.2 순환기내과
21. 1582021

    제1저자 안경민 · 교신저자 김선신, 박흥우

    Ahn KM, Lee SY, Lee SH, Kim SS, Park HW

    Lung function decline is associated with serum uric acid in Korean health screening individuals.

    Sci Rep. 2021;11(1):10183.

    Abstract

    We performed a retrospective cohort study of 19,237 individuals who underwent at least three health screenings with follow-up periods of over 5 years to find a routinely checked serum marker that predicts lung function decline. Using linear regression models to analyze associations between the rate of decline in the forced expiratory volume in 1 s (FEV1) and the level of 10 serum markers (calcium, phosphorus, uric acid, total cholesterol, total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, creatinine, and C-reactive protein) measured at two different times (at the first and third health screenings), we found that an increased uric acid level was significantly associated with an accelerated FEV1 decline (P = 0.0014 and P = 0.037, respectively) and reduced FEV1 predicted % (P = 0.0074 and P = 8.64 × 10^-7, respectively) at both visits only in non-smoking individuals. In addition, we confirmed that accelerated forced vital capacity (FVC) and FEV1/FVC ratio declines were observed in non-smoking individuals with increased serum uric acid levels using linear mixed models. The serum uric acid level thus potentially predicts an acceleration in lung function decline in a non-smoking general population.

    PubMed IF 4.9 알레르기내과
22. 1572021

    제1저자 박세훈 · 교신저자 김동기

    Park S, Lee S, Kim Y, Lee Y, Kang MW, Kim K, Kim YC, Han SS, Lee H, Lee JP, Joo KW, Lim CS, Kim YS, Kim DK

    Observational or Genetically Predicted Higher Vegetable Intake and Kidney Function Impairment: An Integrated Population-Scale Cross-Sectional Analysis and Mendelian Randomization Study.

    J Nutr. 2021;151(5):1167-1174.

    Abstract

    BACKGROUND Further exploration of the possible effects of vegetable intake on kidney function is warranted.

    OBJECTIVE We aimed to study the causality of the association between vegetable intake and kidney function by implementing Mendelian randomization (MR) analysis.

    METHODS This study comprised a cross-sectional dietary investigation using UK Biobank data and MR analysis. For the cross-sectional investigation, 432,732 participants aged 40-69 y from the UK Biobank cohort were included. Self-reported vegetable intake was the exposure, and the outcomes were the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). Next, we included 337,138 participants of white British ancestry in the UK Biobank, and a genome-wide association study (GWAS) was performed to generate a genetic instrument. For MR, we first performed polygenic score (PGS)-based 1-sample MR. In addition, 2-sample MR was performed with CKDGen GWAS for kidney function traits, and the inverse variance weighted method was the main MR method.

    RESULTS Higher vegetable intake was cross-sectionally associated with a higher eGFR (per heaped tablespoon increase; β: 0.154; 95% CI: 0.144, 0.165) and lower odds of CKD (OR: 0.975; 95% CI: 0.968, 0.982). A PGS for vegetable intake was significantly associated with a higher eGFR [per ordinal category increase (0, 1-3, 4-6, ≥7 tablespoons per day); β: 4.435; 95% CI: 2.337, 6.533], but the association with CKD remained nonsignificant (OR: 0.468; 95% CI: 0.143, 1.535). In the 2-sample MR, the causal estimates indicated that a higher genetically predicted vegetable intake was associated with a higher eGFR (percent change; β: 3.071; 95% CI: 0.602, 0.560) but nonsignificantly associated with the risk of CKD (OR: 0.560; 95% CI: 0.289, 1.083) in the European ancestry data from the CKDGen.

    CONCLUSIONS This study suggests that higher vegetable intake may have a causal effect on higher eGFRs in the European population.

    PubMed IF 4.2 신장내과
23. 1562021

    제1저자 전중원 · 교신저자 이상협

    Chun JW, Lee SH, Kim JS, Park N, Huh G, Cho IR, Paik WH, Ryu JK, Kim YT

    Comparison between FOLFIRINOX and gemcitabine plus nab-paclitaxel including sequential treatment for metastatic pancreatic cancer: a propensity score matching approach.

    BMC Cancer. 2021;21(1):537.

    Abstract

    BACKGROUND FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GnP) have been recommended as the first-line chemotherapy for metastatic pancreatic cancer (mPC). However, the evidence is lacking comparing not only two regimens, but also sequential treatment (FFX-GnP vs. GnP-FFX).

    METHODS Data of 528 patients (FFX, n = 371; GnP, n = 157) with mPC were collected retrospectively. Propensity score matching was conducted to alleviate imbalance of the two groups. Overall survival (OS), progression free survival (PFS), and toxicity of patients were analyzed.

    RESULTS In the whole population, OS (12.5 months vs. 10.3 months, P = 0.05) and PFS (7.1 months vs. 5.8 months, P = 0.02) were longer in the FFX group before matching and after matching (OS: 11.8 months vs. 10.3 months, P = 0.02; PFS: 7.2 months vs. 5.8 months, P < 0.01). For sequential treatment, OS and PFS showed no significant difference. Interruptions of chemotherapy due to toxicities were more frequent (6.8 vs. 29.3%, P < 0.001) in the GnP group, and cessation of chemotherapy showed a significant association with mortality (z = - 1.94, P = 0.03).

    CONCLUSIONS FFX achieved a longer overall survival than GnP in mPC, but not in the comparison for sequential treatment. More frequent adverse events followed by treatment interruptions during GnP might lead to a poor survival outcome. Therefore, FFX would be a better first-line treatment option than GnP for mPC.

    PubMed IF 4.1 소화기내과
24. 1552021

    제1저자 박진균, 이예지 · 교신저자 송영욱

    Park JK, Lee YJ, Park JS, Lee EB, Song YW

    CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus.

    Cells. 2021;10(5):cells10051151.

    Abstract

    BACKGROUND To investigate the role of CD47 in inflammatory responses in systemic lupus erythematosus (SLE).

    METHODS Expression of CD47 and signal regulatory protein alpha (SIRPα) by peripheral blood mononuclear cells (PBMCs) and changes in CD47 expression after exposure to SLE serum, healthy control (HC) serum, recombinant interferon (IFN)-α, or tumor necrosis factor (TNF)-α were examined. Human monocytes and THP1 cells were incubated with lipopolysaccharide (LPS), an anti-CD47 antibody, or both. TNF-α production was examined. Sera from SLE patients and HCs were screened to detect autoantibodies specific for CD47.

    RESULTS Twenty-five SLE patients and sixteen HCs were enrolled. CD47 expression by monocytes from SLE patients was higher than those from HCs (mean fluorescence intensity ± SD: 815.9 ± 269.4 vs. 511.5 ± 199.4, respectively; p < 0.001). CD47 expression by monocytes correlated with SLE disease activity (Spearman's rho = 0.467, p = 0.019). IFN-α but not TNF-α, increased CD47 expression. Exposing monocytes to an anti-CD47 antibody plus LPS increased TNF-α production by 21.0 ± 10.9-fold (compared with 7.3 ± 5.5-fold for LPS alone). Finally, levels of autoantibodies against CD47 were higher in SLE patients than in HCs (21.4 ± 7.1 ng/mL vs. 16.1 ± 3.1 ng/mL, respectively; p = 0.02). Anti-CD47 antibody levels did not correlate with disease activity (Spearman's rho = -0.11, p = 0.759) or CD47 expression on CD14 monocytes (Spearman's rho = 0.079, p = 0.838) in patients.

    CONCLUSIONS CD47 expression by monocytes is upregulated in SLE and correlates with disease activity. CD47 contributes to augmented inflammatory responses in SLE. Targeting CD47 might be a novel treatment for SLE.

    PubMed IF 6 류마티스내과
25. 1542021

    제1저자 곽순구 · 교신저자 김학령

    Kwak S, Kim HL, In M, Lim WH, Seo JB, Kim SH, Zo JH, Kim MA

    Associations of Brachial-Ankle Pulse Wave Velocity With Left Ventricular Geometry and Diastolic Function in Untreated Hypertensive Patients.

    Front Cardiovasc Med. 2021;8:647491.

    Abstract

    Background: Although brachial-ankle pulse wave velocity (baPWV) is simple and convenient, its usefulness as an initial screening test for hypertensive patients is not well-known. This study aimed to investigate the association of baPWV with left ventricular (LV) geometry and diastolic function in treatment-naive hypertensive patients. Methods: A total of 202 untreated hypertensive patients (mean age, 62 years; males, 51.5%) without documented cardiovascular diseases were prospectively enrolled. Both baPWV and transthoracic echocardiography were performed on the same day before antihypertensive treatment. Results: In multiple linear regression analysis after adjustment for potential confounders, baPWV had significant correlations with structural measurements of LV including relative wall thickness (β = 0.219, P = 0.021) and LV mass index (β = 0.286, P = 0.002), and four diastolic parameters including septal e' velocity (β = -0.199, P = 0.018), E/e' (β = 0.373, P < 0.001), left atrial volume index (β = 0.334, P < 0.001), and maximal velocity of tricuspid regurgitation (β = 0.401, P < 0.001). The baPWV was significantly increased in patients with LV hypertrophy, abnormal LV remodeling, or diastolic dysfunction, compared to those without (P = 0.008, P = 0.035, and P < 0.001, respectively). In the receiver operating characteristic curve analysis, the discriminant ability of baPWV in predicting LV hypertrophy and diastolic dysfunction had an area under the curve of 0.646 (95% confidence interval 0.544-0.703, P = 0.004) and 0.734 (95% confidence interval 0.648-0.800, P < 0.001), respectively. Conclusion: baPWV was associated with parameters of LV remodeling and diastolic function in untreated hypertensive patients. The baPWV could be a useful screening tool for the early detection of adverse cardiac features among untreated hypertensive patients.

    PubMed IF 3 순환기내과
26. 1532021

    제1저자 김형준, 황현택 · 교신저자 이진우

    Kim HJ^*, Hwang H^*, Hong H, Yim JJ, Lee J

    A systematic review and meta-analysis of regional risk factors for critical outcomes of COVID-19 during early phase of the pandemic.

    Sci Rep. 2021;11(1):9784.

    Abstract

    The mortality rates of COVID-19 vary across the globe. While some risk factors for poor prognosis of the disease are known, regional differences are suspected. We reviewed the risk factors for critical outcomes of COVID-19 according to the location of the infected patients, from various literature databases from January 1 through June 8, 2020. Candidate variables to predict the outcome included patient demographics, underlying medical conditions, symptoms, and laboratory findings. The risk factors in the overall population included sex, age, and all inspected underlying medical conditions. Symptoms of dyspnea, anorexia, dizziness, fatigue, and certain laboratory findings were also indicators of the critical outcome. Underlying respiratory disease was associated higher risk of the critical outcome in studies from Asia and Europe, but not North America. Underlying hepatic disease was associated with a higher risk of the critical outcome from Europe, but not from Asia and North America. Symptoms of vomiting, anorexia, dizziness, and fatigue were significantly associated with the critical outcome in studies from Asia, but not from Europe and North America. Hemoglobin and platelet count affected patients differently in Asia compared to those in Europe and North America. Such regional discrepancies should be considered when treating patients with COVID-19.

    PubMed IF 4.9 호흡기내과
27. 1522021

    제1저자 박송이 · 교신저자 변자민, 윤성수

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

    Busulfan plus melphalan versus melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma.

    Ther Adv Hematol. 2021;12:20406207211012985.

    Abstract

    BACKGROUND High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented.

    METHODS This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019.

    RESULT In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates.

    CONCLUSION BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient's response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.

    PubMed IF 2.8 혈액종양내과
28. 1512021

    제1저자 김중희 · 교신저자 이연주

    Kim J, Park SJ, Choi S, Seo WW, Lee YJ

    Hospitalization for acute coronary syndrome increases the long-term risk of pneumonia: a population-based cohort study.

    Sci Rep. 2021;11(1):9696.

    Abstract

    It is well established that the risk of acute coronary syndrome (ACS) increases after respiratory infection. However, the reverse association has not been evaluated. We tested the hypothesis that the long-term risk of pneumonia is increased after a new ACS event. A matched-cohort study was conducted using a nationally representative dataset. We identified patients with admission for ACS between 2004 and 2014, without a previous history of ACS or pneumonia. Incidence density sampling was used to match patients, on the basis of age and sex, to 3 controls who were also free from both ACS and pneumonia. We examined the incidence of pneumonia after ACS until the end of the cohort observation (Dec 31, 2014). The analysis cohort consisted of 5469 ACS cases and 16,392 controls (median age, 64 years; 68.3% men). The incidence rate ratios of the first and the total pneumonia episodes in the ACS group relative to the control group was 1.25 (95% confidence interval [CI], 1.11-1.41) and 1.23(95% CI 1.11-1.36), respectively. A significant ACS-related increase in the incidence of pneumonia was observed in the Cox-regression, shared frailty, and joint frailty model analyses, with hazard ratios of 1.25 (95% CI 1.09-1.42), 1.35 (95% CI 1.15-1.58), and 1.24 (95% CI 1.10-1.39), respectively. In this population-based cohort of patients who were initially free from both ACS and pneumonia, we found that hospitalization for ACS substantially increased the long term risk of pneumonia. This should be considered when formulating post-discharge care plans and preventive vaccination strategies in patients with ACS.

    PubMed IF 4.9 호흡기내과
29. 1502021

    제1저자 이효진 · 교신저자 조재영

    Lee HJ, Kwak N, Kim YC, Choi SM, Lee J, Park YS, Lee CH, Lee SM, Yoo CG, Cho J

    Impact of Sleep Duration on Mortality and Quality of Life in Chronic Kidney Disease: Results from the 2007-2015 KNHANES.

    Am J Nephrol. 2021;52(5):396-403.

    Abstract

    INTRODUCTION In the general population, short and long sleep durations have been associated with adverse health outcomes. However, this association remains unclear in patients with chronic kidney disease (CKD). We examined the relationship of sleep duration to mortality and health-related quality of life (HRQOL) in individuals with CKD.

    METHODS A total of 1,783 adults with CKD who participated in the 2007-2015 Korea National Health and Nutrition Examination Survey were analyzed. CKD was defined as an estimated glomerular filtration rate of <60 mL/min per 1.73 m2. Participants were categorized into 3 groups according to self-reported sleep duration: <6 h (short sleepers), 6-8 h, and >8 h (long sleepers). The outcome variables were all-cause mortality and HRQOL. HRQOL was assessed using the European Quality of Life-5 Dimensions (EQ-5D) index.

    RESULTS During a median of 6.4 years, 481 (27%) deaths occurred. In unadjusted Cox regression analysis, long sleepers with CKD had an increased risk of death (hazard ratio [HR], 1.62; 95% confidence interval [CI]: 1.26-2.09). This significant association remained after adjusting for age, sex, and BMI (HR, 1.36; 95% CI: 1.05-1.75); however, it was lost after adjusting for CKD stage, social and lifestyle factors, and presence of comorbidities (HR, 1.15; 95% CI: 0.89-1.49). Compared with 6- to 8-h sleepers with CKD, long sleepers with CKD had significantly worse HRQOL in multivariable linear regression models. The adjusted means of the EQ-5D index were 0.80 (95% CI: 0.77-0.82) for short sleepers, 0.81 (95% CI: 0.80-0.82) for 6- to 8-h sleepers, and 0.76 (95% CI: 0.73-0.79) for long sleepers (p = 0.01).

    DISCUSSION/CONCLUSION Long sleep duration is associated with poor HRQOL in Korean adults with CKD. The weak association between long sleep duration and mortality was attenuated after multivariable adjustment in this study.

    PubMed IF 3.8 호흡기내과
30. 1492021

    제1저자 김민관, 이현정 · 교신저자 김형관, 장성아

    Kim M, Lee HJ, Park JB, Kim J, Lee SP, Kim YJ, Chang SA, Kim HK

    Preoperative Right Ventricular Free-Wall Longitudinal Strain as a Prognosticator in Isolated Surgery for Severe Functional Tricuspid Regurgitation.

    J Am Heart Assoc. 2021;10(9):e019856.

    Abstract

    Background Severe tricuspid regurgitation (TR) should be intervened before the development of irreversible right ventricular (RV) dysfunction. However, current guidelines do not provide criterion related to RV systolic function to guide optimal surgical timing. We investigated the prognostic value of RV longitudinal strain in patients undergoing isolated surgery for severe functional TR. Methods and Results We enrolled 115 consecutive patients (aged 62±10 years; 23.5% men; 62.6% [n=72] with previous left-sided valve surgery) who underwent isolated surgery for severe functional TR at 2 tertiary centers. Preoperative clinical and echocardiographic parameters, including RV free-wall longitudinal strain (RVFWSL), were collected. The primary end point was a composite of cardiac death and unplanned readmission attributable to cardiovascular causes 5 years after surgery. Forty patients (34.8%) reached the primary end point during 333 person-years of follow-up. There were 11 cardiac deaths and 34 unplanned readmissions attributable to cardiovascular causes, with 5 patients experiencing both. An absolute preoperative RVFWSL <24% was associated with the primary end point (hazard ratio, 2.30; 95% CI, 1.22-4.36; P=0.011), independent of clinical risk factors, including European System for Cardiac Operative Risk Evaluation II and hemoglobin levels. Meanwhile, other conventional echocardiographic measures of RV systolic function were not significant. The addition of an absolute RVFWSL <24% provided incremental prognostic value to the clinical model for predicting the primary end point. Conclusions Preoperative RVFWSL as an indicator of RV dysfunction was an independent prognosticator in patients undergoing isolated surgery for severe functional TR. Thus, preoperative RVFWSL could help determine the optimal surgical timing for severe functional TR.

    PubMed IF 6 순환기내과

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