SCI 발표논문

1. 1852020

   제1저자 안정남, 주세경 · 교신저자 김원

   An JN, Joo SK, Koo BK, Kim JH, Oh S, Kim W

   Portal inflammation predicts renal dysfunction in patients with nonalcoholic fatty liver disease.

   Hepatol Int. 2020;14(5):798-807.

   Abstract

   BACKGROUND The association between nonalcoholic fatty liver disease (NAFLD) and renal function changes remains inconclusive. We explored whether the histological severity of NAFLD is associated with early deterioration of renal function.

   METHODS Patients with biopsy-proven NAFLD were prospectively followed for renal function monitoring. A renal outcome was defined as a ≥ 50% increase in serum creatinine, a < 30% decrease in the estimated glomerular filtration rate (eGFR) or an eGFR < 45 mL/min/1.73 m².

   RESULTS Among 455 NAFLD patients, 221 (48.6%) had nonalcoholic steatohepatitis (NASH), and no difference in baseline eGFR was found between NASH and NAFL patients. During a median follow-up of 32 months, a renal outcome occurred in 15 patients; the incidence rate was 12.3 per 1,000 person-years. Compared with NAFL, NASH did not increase the risk of renal outcomes. Among the histological components of NAFLD, lobular inflammation (≥ 2), fibrosis (≥ F3), and portal inflammation (≥ 3) significantly increased the risk of renal outcomes in the crude analysis (HR 3.35, 95% CI 1.10-9.11; HR 3.25, 95% CI 1.12-8.84; and HR 7.73, 95% CI 2.86-22.22). After adjustment for risk factors for renal dysfunction, including sex, age, diabetes, hypertension, and chronic kidney disease, only portal inflammation significantly increased the risk of renal outcomes (HR 5.88, 95% CI 1.87-18.42, p = 0.002).

   CONCLUSIONS Portal inflammation predicts early deterioration of renal function in patients with biopsy-proven NAFLD. Individualized monitoring of renal function based on the histological severity of NAFLD may be helpful for early identification of long-term renal outcomes.

   PubMed IF 7.8 소화기내과
2. 1842020

   제1저자 김상아 · 교신저자 김지원

   Kim SA, Kim JW, Suh KJ, Chang W, Kim JW, Oh HK, Cho JY, Kim DW, Cho S, Kim JH, Kim K, Kang SB, Jheon S, Lee KW

   Conversion surgery after cetuximab or bevacizumab plus FOLFIRI chemotherapy in colorectal cancer patients with liver- and/or lung-limited metastases.

   J Cancer Res Clin Oncol. 2020;146(9):2399-2410.

   Abstract

   PURPOSE Some metastatic colorectal cancer (mCRC) patients receive conversion surgery (CS), including metastasectomy after palliative chemotherapy. Although targeted agents significantly improved the outcomes, the clinical outcome of CS in the targeted agent era has not yet been thoroughly investigated.

   METHODS We analyzed the clinical data of 96 mCRC patients who initially had unresectable liver- and/or lung-limited metastases and underwent first-line cetuximab or bevacizumab plus FOLFIRI between January 2013 and June 2017.

   RESULTS Liver-limited metastasis was seen in 44 patients (45.8%), lung-limited metastases in 21 patients (21.9%), and both liver and lung metastases in 31 patients (32.3%). Among them, 37 patients (38.5%) received cetuximab, and 59 patients (61.5%) received bevacizumab plus FOLFIRI. Overall response rate was 63.9% and 40.7%, respectively (p = 0.035). After median 8.7 (range 2.5-27.3) months, CS was performed in 11 patients (29.7%) in cetuximab group and 15 patients (25.4%) in bevacizumab group (p = 0.646). Median overall survival has not been reached in R0-resected patients (n = 23), during the median follow-up period of 22.5 (range 9.8-54.5) months. Median disease-free survival was 7.1 (95% CI 2.5-11.7) months: 11.0 (95% CI 3.1-19.0) months in cetuximab group and 3.2 (95% CI 0.0-7.8) months in bevacizumab group (p = 0.422). There was no progression after 18.5 months and disease-free survival reached a plateau at 19.9%.

   CONCLUSIONS A substantial proportion of patients could receive CS after cetuximab or bevacizumab plus FOLFIRI chemotherapy. R0-resected patients had excellent overall survival, although 80.1% of them eventually experienced recurrence. Some patients could achieve durable disease-free state.

   PubMed IF 3.3 혈액종양내과
3. 1832020

   제1저자 공성혜 · 교신저자 김정희

   Kong SH, Kim JH, Shin CS

   Contralateral adrenal thinning as a distinctive feature of mild autonomous cortisol excess of the adrenal tumors.

   Eur J Endocrinol. 2020;183(3):325-333.

   Abstract

   OBJECTIVE To identify radiologic features that correlate with mild autonomous cortisol excess using planar and volumetric analysis.

   DESIGN Cross-sectional study.

   METHODS In the study, 64 patients with overt Cushing syndrome (CS), 59 patients with mild autonomous cortisol excess (MACE), and 64 patients with nonfunctioning adrenal tumors (NFAT) with evaluable CT scans were included. Patients with NFAT and MACE were BMI-matched with those with overt CS. Planar and volumetric analyses of CT scans were performed in DICOM images using OsiriX software.

   RESULTS The mean age was 56.6 ± 1.01 years, and 123 patients (65.1%) were female. In the order of NFAT, MACE, and overt CS, the diameters and volumes of the adenoma increased, while limb widths and volumes of the contralateral adrenal gland decreased. Patients with MACE or overt CS were more likely to have osteoporosis than those with NFAT (P = 0.006), and patients with overt CS were more likely to experience a fragility fracture than those with NFAT or MACE (P = 0.002). Among radiologic features, the limb width of the contralateral adrenal gland correlated with the cortisol level after overnight dexamethasone suppression test (r = -0.583, P < 0.001).

   CONCLUSIONS The study showed that the contralateral adrenal limb thinning was a distinctive radiologic feature of autonomous cortisol excess in the planar and volumetric analysis.

   PubMed IF 6.7 내분비대사내과
4. 1822020

   제1저자 김학령 · 교신저자 김학령

   Kim HL, Lim WH, Seo JB, Kim SH, Zo ZH, Kim MA

   Prediction of cardiovascular events using brachial-ankle pulse wave velocity in hypertensive patients.

   J Clin Hypertens (Greenwich). 2020;22(9):1659-1665.

   Abstract

   The prognostic value of arterial stiffness in Korean hypertensive patients has not been specified. This study was performed to evaluate the prognostic value of brachial-ankle pulse wave velocity (baPWV) in Korean hypertensive patients and to propose a cutoff value of baPWV predicting future cardiovascular events. A total of 2561 hypertensive patients without documented cardiovascular disease (mean age, 63 years; 47% females) who underwent baPWV measurement were retrospectively analyzed. Composite events of cardiac death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke were assessed during the clinical follow-up period. During a median follow-up period of 4.14 years (interquartile range, 2.18-5.48 years), there were 69 cases of composite events (2.7%). In receiver operating characteristic curve analysis, the best cutoff value of baPWV predicting composite events was 1630 cm/s (sensitivity, 79.7%; specificity, 49.1%; area under curve, 0.674; 95% confidence interval [CI], 0.613-0.735; P < .001). In multivariable Cox regression analysis, higher baPWV (≥1630 cm/s) was independently associated with higher risk of the occurrence of composite events even after controlling for potential confounders (hazard ratio, 2.83; 95% confidence interval, 1.49-5.36; P = .001). In conclusion, increased baPWV in Korean hypertensive patients was associated with an increased risk of future cardiovascular events. In addition, we suggested 1630 cm as a cutoff value of baPWV for predicting cardiovascular events, which will be helpful in guiding the treatment strategy of Korean hypertensive patients.

   PubMed IF 2.9 순환기내과
5. 1812020

   제1저자 김규리, 임수 · 교신저자 이문규

   Kim G, Lim S, Kwon HS, Park IB, Ahn KJ, Park CY, Kwon SK, Kim HS, Park SW, Kim SG, Moon MK, Kim ES, Chung CH, Park KS, Kim M, Chung DJ, Lee CB, Kim TH, Lee MK

   Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active-controlled, randomized, double-blind study with open-label extension (the EVERGREEN study).

   Diabetes Obes Metab. 2020;22(9):1527-1536.

   Abstract

   AIM To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes.

   MATERIALS AND METHODS In this 12-week, multicentre, randomized, double-blind, active-controlled, and 12-week open-label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%-10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92).

   RESULTS After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was -0.85% and -0.75%, respectively. The between-group difference was -0.10% (95% CI: -0.32 to 0.11), showing non-inferiority based on a non-inferiority margin of 0.4%. The change in MAGE was -24.6 mg/dL in the evogliptin group and -16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by -0.94%, with HbA1c values of <7.0% in 80.2% of the patients. The incidence and types of adverse events were comparable between the two groups for 24 weeks.

   CONCLUSION In this study, the glucose-lowering efficacy of evogliptin was non-inferior to linagliptin. It was maintained at week 24 with a 0.94% reduction in HbA1c. Evogliptin therapy improved glycaemic variability without causing any serious adverse events in patients with type 2 diabetes.

   PubMed IF 6.1 내분비대사내과
6. 1802020

   제1저자 조재영 · 교신저자 이창훈

   Cho J, Lee CH, Kim DK, Hwang HG, Kim YI, Choi HS, Park JW, Yoo KH, Jung KS, Lee SD, KOLD and KOCOSS Investigators

   Impact of gender on chronic obstructive pulmonary disease outcomes: a propensity score-matched analysis of a prospective cohort study.

   Korean J Intern Med. 2020;35(5):1154-1163.

   Abstract

   BACKGROUND/AIMS Despite increasing awareness of the burden of chronic obstructive pulmonary disease (COPD) in women, knowledge regarding gender differences in COPD outcomes is limited. Therefore, we aimed to evaluate whether COPD outcomes, including exacerbations, lung function, and symptoms differ by gender.

   METHODS We recruited patients with COPD from two Korean multicenter prospective cohorts. After propensity score matching, the main outcome, the incidence of moderate or severe exacerbations was analyzed using a negative binomial regression model. We also assessed changes in lung function and symptom scores including the St. George's respiratory questionnaire for COPD (SGRQ-C), COPD assessment test (CAT), and the modified Medical Research Council (mMRC) dyspnea score.

   RESULTS After propensity score matching, 74 women and 74 men with COPD were included. The incidence rates of exacerbations in women and men were not significantly different (incidence rate ratio, 1.49; 95% confidence interval [CI], 0.88 to 2.54). There was no significant difference in the incidence rates adjusted for medication possession ratios of long-acting muscarinic antagonists, long-acting β-agonists, and inhaled corticosteroids during the follow-up period (incidence rate ratio, 1.47; 95% CI, 0.86 to 2.52). Rates of decline in post-bronchodilator forced expiratory volume in 1 second and forced vital capacity did not differ between women and men during 48 months of follow-up. The changes in scores on the SGRQ-C, CAT, and mMRC Questionnaire in women were also similar to those in men.

   CONCLUSION We observed no gender differences in the rate of exacerbations of COPD in a prospective longitudinal study. Further studies are needed to confirm these findings in the general COPD population.

   PubMed IF 2.2 호흡기내과
7. 1792020

   제1저자 노기탁 · 교신저자 김나영

   Noh G, Kim N, Choi Y, Lee HS, Hwang YJ, Kim HJ, Yoon H, Shin CM, Park YS, Lee DH

   Long-term follow up of serum pepsinogens in patients with gastric cancer or dysplasia after Helicobacter pylori eradication.

   J Gastroenterol Hepatol. 2020;35(9):1540-1548.

   Abstract

   BACKGROUND AND AIM Few studies have evaluated the change in serum pepsinogen (sPG) levels after the eradication of Helicobacter pylori. The aim of this study was to evaluate the effect of H. pylori eradication on sPG levels in patients with gastric cancer/dysplasia in comparison to a control group.

   METHODS We prospectively enrolled 368 patients with gastric cancer/dysplasia and 610 control subjects. H. pylori status and sPG levels were measured before and after eradication. The follow-up time points were classified as < 12, 12-23, 24-35, and ≥ 36 months.

   RESULTS In 179 H. pylori-eradicated patients with gastric cancer/dysplasia and 168 control group subjects, sPG I significantly decreased, and the sPG I/II ratio significantly increased after eradication compared to baseline, and this improvement in sPG values was maintained during all follow-up time points. Significant differences in sPG I and the sPG I/II ratio were observed between the gastric cancer/dysplasia group and the control group < 24 months after eradication. However, these differences in sPG values disappeared after ≥ 24 months of follow up. Moreover, significant differences in the intestinal metaplasia grade were observed between these two groups before eradication until < 24 months after eradication. However, these differences in the intestinal metaplasia grade disappeared after ≥ 24 months of follow up in the corpus.

   CONCLUSION The sPG values and intestinal metaplasia grade (corpus) in the gastric cancer/dysplasia group became similar to those in the control group at long-term follow up after H. pylori eradication. It might be related with the reduction of metachronous gastric neoplasm.

   PubMed IF 3.5 소화기내과
8. 1782020

   제1저자 공성혜 · 교신저자 신찬수

   Kong SH, Kim JH, Kim SW, Shin CS

   Aromatase inhibitors attenuate the effect of alendronate in women with breast cancer.

   J Bone Miner Metab. 2020;38(5):730-736.

   Abstract

   INTRODUCTION Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment.

   MATERIALS AND METHODS In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months.

   RESULTS The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (-0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (- 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar.

   CONCLUSION The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.

   PubMed IF 2.9 내분비대사내과
9. 1772020

   제1저자 이종찬, 우상명 · 교신저자 황진혁

   Lee JC, Woo SM, Shin DW, Kim J, Yang SY, Kim MJ, Kim JW, Kim JW, Lee WJ, Cha HS, Park P, Kim J, Hwang JH

   Comparison of FOLFIRINOX and Gemcitabine Plus Nab-paclitaxel for Treatment of Metastatic Pancreatic Cancer: Using Korean Pancreatic Cancer (K-PaC) Registry.

   Am J Clin Oncol. 2020;43(9):654-659.

   Abstract

   OBJECTIVE By using the Korean Pancreatic Cancer (K-PaC) registry, we compared the clinical outcomes of FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GNP) in patients with metastatic pancreatic cancer (MPC).

   METHODS We constructed a web-based database of 3748 anonymized patients diagnosed with pancreatic ductal adenocarcinoma. MPC patients who received first-line FFX or GNP were enrolled. Overall survival (OS), progression-free survival, grade III to IV toxicity, and cross-over treatment were analyzed.

   RESULTS A total of 413 patients (232 vs. 181, FFX vs. GNP; all data are presented in this sequence) were eligible. Median age was 63 years (60 vs. 69 y) with 43% (39% vs. 47%) comprising female individuals. The major metastatic sites were the liver (64%), peritoneum (25%), and distant lymph nodes (18%). The median OS was 11.5 versus 12.7 months (hazard ratio [HR]=0.87, 95% confidence interval [CI]: 0.68-1.12, P=0.286), and median progression-free survival was 7.5 versus 8.1 months (HR=0.92, 95% CI: 0.70-1.20, P=0.517), respectively. The frequency of grade III to IV febrile neutropenia was higher in the FFX group (18% vs. 11%, P=0.040), and that of peripheral neuropathy was higher in the GNP group (8% vs. 14%, P=0.046). The chance to receive second-line chemotherapy was higher in the GNP group (45% vs. 56%, P=0.036). In the cross-over treatment, the median OS of the FFX-GNP group (n=43) and the GNP-FFX group (n=47) was 16.8 versus 17.7 months (HR=0.79, 95% CI: 0.44-1.41, P=0.425).

   CONCLUSIONS FFX and GNP showed similar efficacy and comparable toxicity in MPC patients. Although the GNP group had a higher chance to receive second-line chemotherapy, they did not have improved overall survival.

   PubMed IF 1.8 소화기내과
10. 1762020

    제1저자 김진용, 윤혁 · 교신저자 박상형, Edward V Loftus Jr

    Kim JY, Yoon H, Hwang JS, Yang SK, Park SH, Loftus EV

    Comparison of Disease-related Knowledge of Patients With Inflammatory Bowel Disease Between the West and the East Using an Updated Questionnaire (IBD-KNOW).

    J Clin Gastroenterol. 2020;54(8):720-724.

    Abstract

    GOALS The study aimed to compare the level and characteristics of disease-related knowledge of patients with inflammatory bowel disease (IBD) between the West and the East using an international version of a questionnaire regarding knowledge of inflammatory bowel disease (IBD-KNOW).

    BACKGROUND The authors recently developed a new questionnaire regarding IBD-KNOW, which showed excellent test characteristics in Korea.

    STUDY The IBD-KNOW questionnaire was administered to 100 patients with IBD from tertiary referral hospitals in the United States and Korea. Scores were calculated and compared between US and Korean patients, and factors associated with high scores were analyzed.

    RESULTS A total of 196 (100 US and 96 Korean) patients with IBD completed the questionnaires. Analysis of the baseline characteristics revealed that male sex, smoking status, disease duration, history of IBD-related operations, family history of IBD, and use of corticosteroids or biologics were significantly different between US and Korean patients. The mean IBD-KNOW score was higher in US patients than in Korean patients (14.8 vs. 11.3; P<0.001). Multivariate analyses showed that a high IBD-KNOW score (top 25%) was associated with a positive family history of IBD (odds ratio, 2.90; P=0.025) in US patients with IBD and with the use of biologics (odds ratio, 3.65; P=0.008) in Korean patients with IBD.

    CONCLUSIONS The IBD-KNOW questionnaire, an updated assessment tool of IBD-related knowledge, is simple, reliable, and available in various patient populations. IBD-KNOW can be used to identify the factors affecting the level of IBD-related knowledge to improve the quality of care in patients with IBD through a personalized approach.

    PubMed IF 2.7 소화기내과
11. 1752020

    제1저자 김민주 · 교신저자 박영주

    Kim MJ, Kim SC, Chung S, Kim S, Yoon JW, Park YJ

    Exploring the role of copper and selenium in the maintenance of normal thyroid function among healthy Koreans.

    J Trace Elem Med Biol. 2020;61:126558.

    Abstract

    BACKGROUND Selenium and iodine are trace elements well known to have important roles in the synthesis and metabolism of thyroid hormones. However, the effects of other trace elements on thyroid hormones are still inconclusive. We investigated the association between several trace elements and thyroid hormones.

    METHODS The data of 448 subjects who were measured for both, trace elements and TSH/free T4, at the Heath Checkup Center were retrospectively reviewed. The presence of thyroiditis (from thyroid echogenicity) and thyroid nodules were reviewed in the subjects who underwent thyroid ultrasonography.

    RESULTS Blood concentrations of manganese, copper, selenium, and molybdenum were associated with TSH or free T4. After adjusting for age, sex, BMI, smoking, and alcohol consumption, blood copper levels were positively associated with free T4 in both sexes and selenium levels were positively associated with free T4 in women. There was no association between trace elements and thyroiditis. Blood copper concentration had a weak non-linear association with the presence of thyroid nodules.

    CONCLUSIONS This study demonstrated that blood concentrations of copper and selenium were significantly associated with free T4 in healthy Korean subjects with sufficient iodine intake suggesting their role in maintaining normal thyroid function.

    PubMed IF 4.1 내분비대사내과
12. 1742020

    제1저자 김지현, 김영찬 · 교신저자 강혜련, 김혜영

    Kim J, Kim YC, Ham J, Sohn KH, Lee SY, Chung DH, Cho SH, Kang HR, Kim HY

    The effect of air pollutants on airway innate immune cells in patients with asthma.

    Allergy. 2020;75(9):2372-2376.

    PubMed IF 11.3 알레르기내과
13. 1732020

    제1저자 강은애 · 교신저자 김주성

    Kang EA, Soh H, Park S, Lee HJ, Im JP, Kim JS

    Soluble Siglec-9 alleviates intestinal inflammation through inhibition of the NF-κB pathway.

    Int Immunopharmacol. 2020;86:106695.

    Abstract

    BACKGROUND Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a superfamily of immunoreceptors recognizing sialic acid. Siglec-9 has been shown to mediate inhibitory immune responses. The aim of this study was to evaluate the effect of a soluble form of Siglec-9 (sSiglec-9) on inflamed intestinal epithelial cells (IECs), murine macrophages, and experimental murine colitis models.

    METHODS COLO 205 human IECs and RAW 264.7 murine macrophages were pretreated with sSiglec-9 and then stimulated with TNF-α or lipopolysaccharides, respectively. The expression of proinflammatory cytokines such as IL-8 and TNF-α was measured using real-time RT-PCR and ELISA. To demonstrate the inhibitory effects of sSiglec-9 on the NF-κB pathway, IκBα phosphorylation/degradation was determined using western blotting and the DNA binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay. Further, mouse models with dextran sulfate sodium-induced acute colitis and piroxicam-induced IL-10^-/- chronic colitis were generated. Intraperitoneal injections of sSiglec-9 were performed, and body weight, colon length, and histopathologic findings were examined.

    RESULTS sSiglec-9 suppressed IL-8 and TNF-α gene expression in stimulated COLO 205 and RAW 264.7 cells. sSiglec-9 inhibited IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. sSiglec-9 injections significantly ameliorated weight loss, colon shortening, and the severity of intestinal inflammation in acute and chronic colitis mouse models.

    CONCLUSION sSiglec-9 may inhibit NF-κB activation in IECs and macrophages and alleviate experimental colitis in mice, suggesting that sSiglec-9 is a potential therapeutic agent for the treatment of inflammatory bowel disease.

    PubMed IF 5.6 소화기내과
14. 1722020

    제1저자 이윤규, 강은주 · 교신저자 김범석, 윤환중

    Lee YG, Kang EJ, Keam B, Choi JH, Kim JS, Park KU, Lee KE, Kwon JH, Lee KW, Kim MK, Ahn HK, Shin SH, Kim HR, Kim SB, Yun HJ

    Treatment strategy and outcomes in locally advanced head and neck squamous cell carcinoma: a nationwide retrospective cohort study (KCSG HN13-01).

    BMC Cancer. 2020;20(1):813.

    Abstract

    BACKGROUND By investigating treatment patterns and outcomes in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), we aimed at providing valuable insights into the optimal therapeutic strategy for physicians in real-world practice.

    METHODS This is a multi-institutional study enrolled the patients with stage III to IVB LA-HNSCC, except for nasopharyngeal carcinoma, from 2004 to 2015 in thirteen referral hospitals capable of multidisciplinary care.

    RESULTS A total of 445 LA-HNSCC patients were analyzed. The median age was 61 years (range, 24-89). The primary tumor location was the oropharynx in 191 (43%), oral cavity in 106 (24%), hypopharynx in 64 (14%), larynx in 57 (13%) and other sites in 27 (6%). The most common stage was T2 in 172 (39%), and N2 in 245 (55%). Based on treatment intents, 229 (52%) of the patients received definitive concurrent chemoradiotherapy (CCRT) and 187 (42%) underwent surgery. Approximately 158 (36%) of the study population received induction chemotherapy (IC). Taken together, 385 (87%) of the patients underwent combined therapeutic modalities. The regimen for definitive CCRT was weekly cisplatin in 58%, 3-weekly cisplatin in 28% and cetuximab in 3%. The preferred regimen for IC was docetaxel with cisplatin in 49%, and docetaxel, cisplatin plus fluorouracil in 27%. With a median follow-up of 39 months, one-year and two-year survival rates were 89 and 80%, respectively. Overall survival was not significantly different between CCRT and surgery group (p = 0.620).

    CONCLUSIONS In patients with LA-HNSCC, the majority of patients received combined therapeutic modalities. Definitive CCRT, IC then definitive CCRT, and surgery followed by adjuvant CCRT or radiotherapy are the preferred multidisciplinary strategies in real-world practice.

    PubMed IF 4.1 혈액종양내과
15. 1712020

    제1저자 김윤지, 황선덕 · 교신저자 임수

    Kim YJ, Hwang SD, Lim S

    Effects of Sodium-Glucose Cotransporter Inhibitor/Glucagon-Like Peptide-1 Receptor Agonist Add-On to Insulin Therapy on Glucose Homeostasis and Body Weight in Patients With Type 1 Diabetes: A Network Meta-Analysis.

    Front Endocrinol (Lausanne). 2020;11:553.

    Abstract

    Many patients with type 1 diabetes (T1D) do not achieve the glycemic target goal with insulin treatment. In this study, we aimed to evaluate the efficacy and safety of add-on to insulin therapy in patients with T1D. We conducted direct and indirect network meta-analyses using Bayesian models and ranked hypoglycemic agents via mixed treatment comparison, using data from the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases. Randomized controlled trials (RCTs) involving patients with T1D treated with insulin and add-on metformin or sodium-glucose cotransporter inhibitors or glucagon-like peptide-1 receptor agonists from January 1970 to September 2019 were included in this study. Twenty-three RCTs with 5,151 subjects were divided into the following groups: insulin alone, insulin+metformin, insulin+canagliflozin, insulin+dapagliflozin, insulin+empagliflozin, insulin+sotagliflozin, insulin+liraglutide, and insulin+exenatide. HbA1c level in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group (mean difference: -0.43, 95% credible interval: -0.62 to -0.23). Total daily insulin dose in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group. Compared with that in the insulin alone group, body weight in the groups treated with insulin+add-on canagliflozin, sotagliflozin, and exenatide was significantly decreased by 4.5, 2.8, and 5.1 kg, respectively. Hypoglycemic episodes did not differ among the groups. In patients with T1D, insulin+sotagliflozin decreased the HbA1c level, daily insulin dose, and body weight without hypoglycemia compared with insulin monotherapy. Insulin+canagliflozin or insulin+exenatide was effective in reducing body weight compared with insulin alone. In conclusion, sotagliflozin treatment decreased not only the HbA1c levels and insulin dose but also the body weight without causing hypoglycemia in patients with T1D. Treatment with canagliflozin and exenatide effectively reduced body weight in patients with T1D. However, ketoacidosis associated with the use of SGLT inhibitors should be considered in these patients. Thus, our results suggest that sotagliflozin has a high probability of being ranked first as an adjunctive therapy to insulin in patients with T1D.

    PubMed IF 5.7 내분비대사내과
16. 1702020

    제1저자 조재호, 신철민 · 교신저자 이동호

    Cho JH, Shin CM, Yoon H, Park YS, Kim N, Lee DH

    Efficacy of a high-dose proton pump inhibitor in patients with gastroesophageal reflux disease: a single center, randomized, open-label trial.

    BMC Gastroenterol. 2020;20(1):275.

    Abstract

    BACKGROUND The extraesophageal manifestations of gastroesophageal reflux disease (GERD) are more difficult to manage than the typical symptoms. The efficacy of high-dose and standard-dose proton pump inhibitors against these atypical symptoms is not yet established.

    METHODS In this single center, randomized, open-label study, patients with GERD received rabeprazole for 8 weeks, either 20 mg once daily (standard-dose group) or 20 mg twice daily (high-dose group). Patients were assessed before treatment and at weeks 4 and 8 with a 5-graded scale questionnaire consisting of 2 typical symptoms (heartburn and acid regurgitation) and 8 atypical symptoms (chest pain, cough, globus, wheezing, laryngopharyngitis, hoarseness, belching, and dysphagia). Sufficient improvement of reflux symptoms was defined as ≥50% reduction from the initial questionnaire score.

    RESULTS Final analyses included 35 patients in the standard-dose group and 38 patients in the high-dose group. The rate of sufficient improvement for typical symptoms was significantly higher in the high-dose group than in the standard-dose group (100.0% vs. 84.0%, P = 0.040). For atypical symptoms, the rate of sufficient improvement tended to be higher in the high-dose group than in the standard-dose group (82.4% vs. 63.0%, P = 0.087). Scores of typical and some atypical symptoms (cough and globus) improved after treatment, with significant inter-group differences in time-course changes.

    CONCLUSIONS High-dose rabeprazole is more effective for relieving typical GERD symptoms and some atypical symptoms such as cough and globus than a standard-dose regimen.

    TRIAL REGISTRATION This research was enrolled in a registry of clinical trials run by United States National Library of Medicine at the National Institutes of Health ( ClinicalTrials.gov Protocol Registration and Results system ID: NCT04001400 ). This study was registered on June 26, 2019 - Retrospectively registered.

    PubMed IF 3.2 소화기내과
17. 1692020

    제1저자 곽순구, 최유정 · 교신저자 김형관

    Kwak S, Choi YJ, Kwon S, Lee SY, Yang S, Moon I, Lee HJ, Lee H, Park JB, Han K, Kim YJ, Kim HK

    De novo malignancy risk in patients undergoing the first percutaneous coronary intervention: A nationwide population-based cohort study.

    Int J Cardiol. 2020;313:25-31.

    Abstract

    BACKGROUND Although percutaneous coronary intervention (PCI) has been the mainstay of revascularization strategy for significant coronary artery disease, future cancer risk after PCI has never been explored. We aimed to investigate the risk of incident cancer in patients undergoing PCI for the first time.

    METHODS We studied 125,613 patients who underwent the first PCI between 2010 and 2015 without a prior history of cancer. For comparison, we selected 628,065 age- and sex-matched controls without any history of cancer or PCI who completed the assigned national health examination during the same period.

    RESULTS During a median 4.56 years (interquartile range, 3.06-6.13 years), 8528 patients from the PCI group and 40,166 controls were newly diagnosed with cancer (incidence rate, 15.1 vs. 13.9 per 1000 person-years, p < 0.0001). Patients undergoing PCI presented a higher risk for cancer development than the controls in multivariable Cox analysis (adjusted HR [aHR] 1.06, 95% CI 1.04-1.09, p < 0.0001). To minimize potential surveillance bias, we performed 1-year lag analysis by eliminating participants who developed cancer within 1 year from the PCI. In this analysis, the increased risk of overall cancer in the PCI group became insignificant (aHR 1.02, 95% CI 0.99-1.05, p = 0.2017). Regarding site-specific cancers, however, the risk of lung and hematologic malignancies remained higher and the risk of gastrointestinal, liver/biliary/pancreas, thyroid, and breast cancers remained lower in the PCI group.

    CONCLUSIONS Differential future cancer risks were observed in patients undergoing PCI. The results suggest that specialized surveillance strategy might be warranted for this expanding population.

    PubMed IF 3.3 순환기내과
18. 1682020

    제1저자 김학령 · 교신저자 김학령

    Kim HL, Lee JY, Lim WH, Seo JB, Kim SH, Zo JH, Kim MA

    Relationship of Socioeconomic Status to Arterial Stiffness: Comparison Between Medical Aid Beneficiaries and National Health Insurance Beneficiaries.

    Am J Hypertens. 2020;33(8):718-725.

    Abstract

    BACKGROUND There is no general agreement on underlying pathophysiology explaining the high burden of cardiovascular disease on people at low socioeconomic status (SES). This study was conducted to investigate the association between healthcare systems and arterial stiffness.

    METHODS A total of 8,929 subjects (60 years old and 55% were male) who underwent brachial-ankle pulse wave velocity (baPWV) measurement were retrospectively analyzed. There were 8,237 National Health Insurance (NHI) beneficiaries (92.2%) and 692 medical aid (MA) beneficiaries (7.8%). The median value of baPWV was 1,540 cm/s.

    RESULTS Subjects with higher baPWV values (≥1,540 cm/s) were older, and more frequently had cardiovascular risk factors and unfavorable laboratory findings than those with lower values baPWV (<1,540 cm/s). The baPWV values were significantly higher in MA beneficiaries than in NHI beneficiaries (1,966 ± 495 vs. 1,582 ± 346 cm/s, P < 0.001). The proportion of MA beneficiaries was significantly higher in subjects with higher baPWV than those with lower baPWV (13.1% vs. 2.3%, P < 0.001). In multivariable analysis, MA beneficiaries were significantly associated with higher baPWV values even after controlling for potential confounders (odds ratio, 5.41; 95% confidence intervals, 4.02-7.27; P < 0.001).

    CONCLUSIONS The baPWV values were significantly higher in MA beneficiaries than in NHI beneficiaries. The result of this study provides additional evidence on the association between low SES and arterial stiffening.

    PubMed IF 2.9 순환기내과
19. 1672020

    제1저자 손미경, 박진주 · 교신저자 김원호, 최동주

    Son MK^*, Park JJ^*, Lim NK, Kim WH, Choi DJ

    Impact of atrial fibrillation in patients with heart failure and reduced, mid-range or preserved ejection fraction.

    Heart. 2020;106(15):1160-1168.

    Abstract

    OBJECTIVE To determine the prognostic value of atrial fibrillation (AF) in patients with heart failure (HF) and preserved, mid-range or reduced ejection fraction (EF).

    METHODS Patients hospitalised for acute HF were enrolled in the Korean Acute Heart Failure registry, a prospective, observational, multicentre cohort study, between March 2011 and February 2014. HF types were defined as reduced EF (HFrEF, LVEF <40%), mid-range EF (HFmrEF, LVEF 40%-49%) or preserved EF (HFpEF, LVEF ≥50%).

    RESULTS Of 5414 patients enrolled, HFrEF, HFmrEF and HFpEF were seen in 3182 (58.8%), 875 (16.2%) and 1357 (25.1%) patients, respectively. The prevalence of AF significantly increased with increasing EF (HFrEF 28.9%, HFmrEF 39.8%, HFpEF 45.2%; p for trend <0.001). During follow-up (median, 4.03 years; IQR, 1.39-5.58 years), 2806 (51.8%) patients died. The adjusted HR of AF for all-cause death was 1.06 (0.93-1.21) in the HFrEF, 1.10 (0.87-1.39) in the HFmrEF and 1.22 (1.02-1.46) in the HFpEF groups. The HR for the composite of all-cause death or readmission was 0.97 (0.87-1.07), 1.14 (0.93-1.38) and 1.03 (0.88-1.19) in the HFrEF, HFmrEF and HFpEF groups, respectively, and the HR for stroke was 1.53 (1.03-2.29), 1.04 (0.57-1.91) and 1.90 (1.13-3.20), respectively. Similar results were observed after propensity score matching analysis.

    CONCLUSIONS AF was more common with increasing EF. AF was seen to be associated with increased mortality only in patients with HFpEF and was associated with an increased risk of stroke in patients with HFrEF or HFpEF.

    TRIAL REGISTRATION NUMBER NCT01389843.

    PubMed IF 4.4 순환기내과
20. 1662020

    제1저자 이상협 · 교신저자 박도중

    Lee SH, Jang DK, Yoo MW, Hwang SH, Ryu SY, Kwon OK, Hur H, Man Yoon H, Eom BW, Ahn HS, Son T, Song KY, Lee HH, Choi MG, An JY, Lee SI, Lee KH, Ahn S, Park YS, Park DJ, Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study (PEGASUS-D) Group

    Efficacy and Safety of Ursodeoxycholic Acid for the Prevention of Gallstone Formation After Gastrectomy in Patients With Gastric Cancer: The PEGASUS-D Randomized Clinical Trial.

    JAMA Surg. 2020;155(8):703-711.

    Abstract

    IMPORTANCE The incidence of gallstones has been reported to increase after gastrectomy. However, few studies have been conducted on the prevention of gallstone formation in patients who have undergone gastrectomy.

    OBJECTIVE To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing gallstone formation after gastrectomy in patients with gastric cancer.

    DESIGN, SETTING, AND PARTICIPANTS The PEGASUS-D study (Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study) was a randomized, double-blind, placebo-controlled clinical trial conducted at 12 institutions in the Republic of Korea. Adults (aged ≥19 years) with a diagnosis of gastric cancer who underwent total, distal, or proximal gastrectomy were enrolled between May 26, 2015, and January 9, 2017; follow-up ended January 8, 2018. Efficacy was evaluated by both the full analysis set, based on the intention-to-treat principle, and the per-protocol set; full analysis set findings were interpreted as the main results.

    INTERVENTIONS Eligible participants were randomly assigned to receive 300 mg of UDCA, 600 mg of UDCA, or placebo at a ratio of 1:1:1. Ursodeoxycholic acid and placebo were administered daily for 52 weeks.

    MAIN OUTCOMES AND MEASURES Gallstone formation was assessed with abdominal ultrasonography every 3 months for 12 months. Randomization and allocation to trial groups were carried out by an interactive web-response system. The primary end point was the proportion of patients developing gallstones within 12 months after gastrectomy.

    RESULTS A total of 521 patients (175 received 300 mg of UDCA, 178 received 600 mg of UDCA, and 168 received placebo) were randomized. The full analysis set included 465 patients (311 men; median age, 56.0 years [interquartile range, 48.0-64.0 years]), with 151 patients in the 300-mg group, 164 patients in the 600-mg group, and 150 patients in the placebo group. The proportion of patients developing gallstones within 12 months after gastrectomy was 8 of 151 (5.3%) in the 300-mg group, 7 of 164 (4.3%) in the 600-mg group, and 25 of 150 (16.7%) in the placebo group. Compared with the placebo group, odds ratios for gallstone formation were 0.27 (95% CI, 0.12-0.62; P = .002) in the 300-mg group and 0.20 (95% CI, 0.08-0.50; P < .001) in the 600-mg group. No significant adverse drug reactions were detected among the enrolled patients.

    CONCLUSIONS AND RELEVANCE Administration of UDCA for 12 months significantly reduced the incidence of gallstones after gastrectomy for gastric cancer. These findings suggest that UDCA administration prevents gallstone formation after gastrectomy in patients with gastric cancer.

    TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02490111.

    PubMed IF 15.6 소화기내과
21. 1652020

    제1저자 이영아, 임선화 · 교신저자 박영주, 김종일

    Lee YA, Im SW, Jung KC, Chung EJ, Shin CH, Kim JI, Park YJ

    Predominant DICER1 Pathogenic Variants in Pediatric Follicular Thyroid Carcinomas.

    Thyroid. 2020;30(8):1120-1131.

    Abstract

    Background: Pediatric thyroid cancer has characteristics that are distinct from adulthood thyroid cancer. Due to its very low prevalence, little is known about the genetic characteristics of pediatric follicular thyroid cancer (FTC). Methods: We investigated genetic alterations in tumor tissues from 15 patients aged <20 years (median: 14.3 years; range: 2.4 - 19.0 years) using multifaceted approaches. Whole-exome sequencing, targeted next-generation sequencing using a cancer gene panel, and Sanger sequencing of the major exons of the H/K/N-RAS and DICER1 genes and the promoter region of the TERT gene were performed. Normal tissues or blood of patients with DICER1- or PTEN-positive tumors was also evaluated to determine whether the variant is germ line. Results: The median tumor size was 3.1 cm (range: 0.6 - 6.4 cm). Four patients exhibited angioinvasion and one extensive capsular invasion; none showed evidence of disease over a median of 8.1 years. Eight patients (53.3%) had DICER1 variants, including four with DICER1 syndrome (three patients were <10 years of age). One patient had a germ line PTEN frameshift variant with the diagnosis of PTEN hamartoma tumor syndrome. One patient had a PAX8/PPARγ rearrangement, and two patients had no genetic driver alteration other than multiple loss of heterozygosity with or without copy number alterations in their tumors. No RAS or TERT variants were found. Nodular hyperplasia and follicular adenoma (FA) coexisted in DICER1 variant-positive FTCs more frequently than variant-negative FTCs (p = 0.026). All DICER1 variant-positive FTCs had a somatic missense variant at metal binding sites (six at codon p.E1813 and two at codon p.D1709) within the RNase IIIb domain; seven had other missense, nonsense, or frameshift variants in the DICER1 gene. Six coexisting FAs of two patients with DICER1 syndrome (three of each) had additional somatic variants at metal binding sites within the RNase IIIb domain (codon p.E1705, p.D1709, p.D1810, or p.E1813), different from each other and from the indexed FTC tumor. Conclusions: Pediatric FTCs have distinct genomic alterations and pathogenesis compared with adults, particularly those characterized by DICER1 variants. The DICER1 variant should be considered in pediatric FTCs, especially in cases <10 years of age. In all DICER1 variant-positive FTCs and FAs, recurrent hotspot variants were found at metal binding sites within the RNase IIIb domain, suggesting they impact tumorigenesis.

    PubMed IF 6.6 내분비대사내과
22. 1642020

    제1저자 김민관, 김학령 · 교신저자 조주희

    Kim M, Kim HL, Park KT, Kim YN, Lim JS, Lim WH, Seo JB, Kim SH, Kim MA, Zo JH

    Echocardiographic parameters determining cardiovascular outcomes in patients after acute ischemic stroke.

    Int J Cardiovasc Imaging. 2020;36(8):1445-1454.

    Abstract

    Previous studies have focused on only 1 or 2 echocardiographic parameters as prognostic markers in patients with acute ischemic stroke (AIS). A total of 900 patients with AIS who underwent transthoracic echocardiography (72.6 ± 12.0 years and 60% males) were retrospectively reviewed. Composite clinical events, including all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and coronary revascularization, were assessed during clinical follow-ups. During a median follow-up of 3.3 years (interquartile range 0.6-5.1 years), there were 151 (16.8%) composite events. In the multivariable analyses after controlling for potential confounders, left ventricular ejection fraction (LVEF) < 62% (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.14-2.30; p = 0.007) and AV sclerosis (AVs) (HR 1.56; 95% CI 1.10-2.21; p = 0.013) were independent prognostic factors associated with composite events. Multivariable analyses showed that HR for composite events gradually increased according to LVEF and AVs: HR was 2.6-fold higher in the highest-risk group than in the lowest group (p < 0.001). Compared with a clinical model (global chi-square = 69.6), LVEF, AVs, and both of them were significantly improved outcome prediction in sequential Cox model analysis (global chi-square = 75.6, 75.7, and 78.8, respectively; p < 0.05 for each) for each. In patients with AIS, LVEF < 62%, and the presence of AV sclerosis can predict future vascular events. Patients with AIS exhibiting reduced LVEF and AV sclerosis may benefit from aggressive secondary prevention.

    PubMed IF 1.5 순환기내과
23. 1632020

    제1저자 조혜기, 장영 · 교신저자 이정훈

    Cho H, Chang Y, Lee JH, Cho YY, Nam JY, Lee YB, Lee DH, Cho EJ, Yu SJ, Kim YJ, Lee JM, Yoon JH

    Radiologic Nonalcoholic Fatty Liver Disease Increases the Risk of Hepatocellular Carcinoma in Patients With Suppressed Chronic Hepatitis B.

    J Clin Gastroenterol. 2020;54(7):633-641.

    Abstract

    BACKGROUND AND GOALS Although nonalcoholic fatty liver disease (NAFLD) is a risk factor of hepatocellular carcinoma (HCC), it is unclear whether NAFLD additionally increases the risk of HCC among chronic hepatitis B (CHB) patients. This study evaluated the association between NAFLD and the risk of HCC in patients whose hepatitis B virus (HBV) was well controlled.

    STUDY This study included consecutive CHB patients whose serum HBV DNA levels were continuously suppressed <2000 IU/mL with antiviral treatment. Fatty liver was radiologically diagnosed. Patients with concomitant hepatitis C infection, autoimmune hepatitis, or excessive alcohol use were excluded.

    RESULTS Among 826 patients, 86 patients (10.4%) developed HCC during the study period (median, 43.1 mo). The patients with NAFLD (N=260) had a significantly higher risk for HCC compared with patients without NAFLD (N=566) (adjusted hazard ratio, 1.67; 95% confidence interval, 1.05-2.63; P=0.03) after adjustment for age, the presence of cirrhosis, hepatitis B envelop antigen positivity, low-level viremia and hypertension. There was significant association between incomplete biochemical response (IBR) (alanine aminotransferase levels ≥40 IU/L) and the presence of NAFLD (P<0.001 by χ test). IBR at the time of virological response was associated with a significantly higher risk of HCC development (adjusted hazard ratio, 1.63; 95% confidence interval, 1.06-2.54; P=0.03).

    CONCLUSIONS NAFLD increases the risk of HCC in patients with CHB in whom HBV is effectively suppressed by antivirals. Patients with IBR should be suspected of concurrent NAFLD. Further study is warranted to evaluate whether improvement of NAFLD might decrease the risk of HCC development.

    PubMed IF 2.7 소화기내과
24. 1622020

    제1저자 최평균 · 교신저자 오명돈

    Choe PG, Park WB, Choi SJ, Kang CK, Koh Y, Kim NJ, Oh MD

    Prolonged (6-Month) Shedding of Middle East Respiratory Syndrome Coronavirus RNA in the Sputum of a Lymphoma Patient.

    Open Forum Infect Dis. 2020;7(8):ofaa292.

    Abstract

    During the 2015 Korea Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, a lymphoma patient developed MERS pneumonia. His pneumonia improved by 45 days after illness onset, but the polymerase chain reaction tests remained (+) for 6 months. However, replication-competent virus was detected by 60 days after illness onset.

    PubMed IF 3.8 감염내과
25. 1612020

    제1저자 박지은 · 교신저자 김범석

    Park JE, Kim SE, Keam B, Park HR, Kim S, Kim M, Kim TM, Doh J, Kim DW, Heo DS

    Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines.

    J Immunother Cancer. 2020;8(2):jitc-2020-000873.

    Abstract

    BACKGROUND Although programmed cell death-1/programmed death-ligand 1 (PD-L1) inhibitors show remarkable antitumor activity, a large portion of patients with cancer, even those with high PD-L1-expressing tumors, do not respond to their effects. Most PD-L1 inhibitors contain modified fragment crystallizable region (Fc) receptor binding sites to prevent antibody-dependent cellular cytotoxicity (ADCC) against PD-L1-expressing non-tumor cells. However, natural killer (NK) cells have specific antitumor activity in the presence of tumor-targeting antibody through ADCC, which could enhance NK cell-induced cytotoxicity. We evaluated the antitumor efficacy of ADCC via anti-PD-L1 monoclonal antibodies (mAbs) and NK cells against several PD-L1-positive cancer cell lines.

    METHODS Various cancer cell lines were used as target cell lines. Surface PD-L1 expression was analyzed by flow cytometry. IMC-001 and anti-hPD-L1-hIgG1 were tested as anti-PD-L1 mAbs with ADCC and atezolizumab as an anti-PD-L1 mAb without ADCC. NK cell cytotoxicity was measured by ⁵¹Cr-release assay and CD107a degranulation assay. Also, live cell imaging was performed to evaluate cytotoxicity in a single-cell level. NK-92-CD16 (CD16-transduced NK-92 cell line) and peripheral blood mononuclear cells from healthy donors, respectively, were used as an effector cell. FcγRIIIa (CD16a)-V158F genotyping was performed for healthy donors.

    RESULTS We demonstrated that the cytotoxicity of NK-92-CD16 cells toward PD-L1-positive cancer cell lines was significantly enhanced in the presence of anti-PD-L1 mAb with ADCC. We also noted a significant increase in primary human NK cell cytotoxicity against PD-L1-positive human cancer cells when cocultured with anti-PD-L1 mAb with ADCC. Moreover, NK cells expressing a FCGR3A high-affinity genotype displayed higher anti-PD-L1 mAb-mediated ADCC lysis of tumor cells than donors with a low-affinity genotype.

    CONCLUSION These results suggest that NK cells induce an ADCC response in combination with anti-PD-L1 mAbs, which helps promote ADCC antitumor activity against PD-L1-positive tumors. This study provides support for NK cell immunotherapy against high PD-L1-expressing tumors in combination with ADCC through anti-PD-L1 mAbs.

    PubMed IF 11.7 혈액종양내과
26. 1602020

    제1저자 박지숙, 한정규 · 교신저자 김효수

    Park J, Han JK, Chang M, Ki YJ, Kang J, Yang HM, Cho HJ, Park KW, Kang HJ, Koo BK, Kim HS

    Impact of Intensive Glucose Control in Patients with Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: 3-Year Clinical Outcomes.

    J Clin Med. 2020;9(8):jcm9082464.

    Abstract

    We investigated whether intensive glucose control after percutaneous coronary intervention (PCI) improves clinical outcomes in diabetic patients. From the Grand-DES registry, we analyzed 2576 diabetic patients (median age 66 years, male 65.6%) who underwent PCI and had at least 2 records of HbA1c during the follow-up. Patients were categorized according to the mean HbA1c (≥7% or <7%). Primary outcome was major adverse cardiovascular event (MACE), a composite of cardiac death, non-fatal myocardial infarction, and any revascularization. During a median follow-up of 33.6 months, MACE occurred in 335 (13.0%) patients. Intensive glucose control with follow-up mean HbA1c < 7.0% (42.2%; n = 1087) was not associated with lower risk of MACE, compared to control with mean HbA1c ≥ 7.0% (adjusted hazard ratio [aHR] [95% confidence interval] 1.06 [0.82-1.37], p = 0.672). In subgroup analysis, patients with sustained HbA1c of <7.0% throughout the follow-up were not associated with a lower risk of MACE compared to those with sustained HbA1c of ≥7.0% (aHR 1.15 [0.71-1.89], p = 0.566). More intensive glucose control with mean HbA1c ≤ 6.5% was not associated with lower risk of MACE, compared to loose control with a mean HbA1c ≥ 8.0% (aHR 1.15 [0.71-1.86], p = 0.583). Intensive glucose control after PCI was not associated with better clinical outcomes in diabetic patients undergoing PCI than lenient control.

    PubMed IF 3.3 순환기내과
27. 1592020

    제1저자 강창경, 한기찬, 김민지 · 교신저자 김항래, 오명돈

    Kang CK, Han GC, Kim M, Kim G, Shin HM, Song KH, Choe PG, Park WB, Kim ES, Kim HB, Kim NJ, Kim HR, Oh MD

    Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity.

    Int J Infect Dis. 2020;97:313-321.

    Abstract

    OBJECTIVES We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases.

    METHODS We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry.

    RESULTS The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4⁺ and CD8⁺ T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4⁺ or CD8⁺ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in the severe group.

    CONCLUSIONS Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.

    PubMed IF 4.6 감염내과
28. 1582020

    제1저자 김영선 · 교신저자 김나영

    Kim YS, Kim N

    Functional Dyspepsia: A Narrative Review With a Focus on Sex-Gender Differences.

    J Neurogastroenterol Motil. 2020;26(3):322-334.

    Abstract

    Functional dyspepsia (FD) is among the most common gastrointestinal disorders affecting quality of life (QoL). As it frequently occurs in women than in men the comparison of various aspects including prevalence, clinical manifestations, and QoL in FD between women and men is very important for understanding the disease distribution and burden, evaluating treatment options, developing new drugs, and allocating medical resources. However, little is known about sex or gender differences among patients with FD. In spite of limited studies, consistent points are that FD occurs more often in women than in men and there are several symptom differences between men and women with FD. In addition, women with FD tend to have lower QoL than men with FD. Similarly, the pathophysiology of FD likely to vary depending on gender. Furthermore, a sex-gender-oriented approach in healthcare system could enhance understanding heterogeneous patients suffering from FD. Due to the sex-gender differences in physiological and psychological factors, treatment strategies should differ between women and men with FD. In conclusion, an individualized and multicomponent approach that considers sex and gender issues might improve FD treatment and improve patient Qol, especially for women.

    PubMed IF 3.7 소화기내과
29. 1572020

    제1저자 김재형 · 교신저자 황진혁

    Kim JH, Youn Y, Lee JC, Kim J, Hwang JH

    Involvement of the NF-κB signaling pathway in proliferation and invasion inhibited by Zwint-1 deficiency in Pancreatic Cancer Cells.

    J Cancer. 2020;11(19):5601-5611.

    Abstract

    Pancreatic cancer (PC) is an intractable cancer that is difficult to diagnose early and has a 5-year survival rate of less than 8%. ZW10-interacting kinetochore protein (ZWINT) is a crucial gene that contributes to chromosome instability and is essential for spindle assembly and kinetochore-microtubule attachment during meiosis and mitosis. However, the mechanism through which Zwint-1 promotes PC progression is yet to be elucidated. Here, we report that Zwint-1 is highly expressed in clinical PC specimens (based on analysis of the Gene Expression Profiling Interactive Analysis database) and various PC cell lines. Importantly, Zwint-1-deficient PC cells showed reduced nuclear factor-kappa B (NF-κB) (Ser536) phosphorylation along with inhibited proliferation and colony formation due to downregulation of NF-κB-regulated genes such as CCND1, cIAP1/2, and XIAP. In addition, Zwint-1-deficient PC cells showed reduced invasion and migration abilities, and decreased expression levels of the metalloproteinases MMP2 and MMP9. Furthermore, Zwint-1 deficiency arrested the PC cell cycle at the G₂/M phase because the chromosomes failed to segregate properly, and the apoptosis rate in these cells gradually increased, accompanied by increased caspase-3 activation and anti-poly (ADP ribose) polymerase cleavage. Apoptosis caused by Zwint-1 deficiency was demonstrated to occur through caspase-dependent pathways based on experiments involving treatment with a pan-caspase inhibitor (Z-VAD-Fmk). Thus, Zwint-1 contributes to cell growth, invasion, and survival through NF-κB signaling pathways, suggesting that it could serve as a PC biomarker and new therapeutic target.

    PubMed IF 3.4 소화기내과
30. 1562020

    제1저자 박진균 · 교신저자 송영욱

    Park JK, Jang YJ, Oh BR, Shin J, Bae D, Ha N, Choi YI, Youn GS, Park J, Lee EY, Lee EB, Song YW

    Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis.

    Arthritis Res Ther. 2020;22(1):176.

    Abstract

    OBJECTIVES Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA).

    METHODS HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA).

    RESULTS Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect.

    CONCLUSION The novel HDAC6 inhibitor CKD-506 suppresses inflammatory responses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA.

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