SCI 발표논문

1. 1552020

   제1저자 김귀진, 김지원 · 교신저자 이근욱

   Kim KJ^*, Kim JW^*, Sung JH, Suh KJ, Lee JY, Kim SH, Lee JO, Kim JW, Kim YJ, Kim JH, Bang SM, Lee JS, Kim HK, Lee KW

   PI3K-targeting strategy using alpelisib to enhance the antitumor effect of paclitaxel in human gastric cancer.

   Sci Rep. 2020;10(1):12308.

   Abstract

   PIK3CA mutations are frequently observed in various human cancers including gastric cancer (GC). This study was conducted to investigate the anti-tumor effects of alpelisib, a PI3K p110α-specific inhibitor, using preclinical models of GC. In addition, the combined effects of alpelisib and paclitaxel on GC were evaluated. Among the SNU1, SNU16, SNU484, SNU601, SNU638, SNU668, AGS, and MKN1 GC cells, three PIK3CA-mutant cells were predominantly sensitive to alpelisib. Alpelisib monotherapy decreased AKT and S6K1 phosphorylation and induced G₀/G₁ phase arrest regardless of PIK3CA mutational status. The alpelisib and paclitaxel combination demonstrated synergistic anti-proliferative effects, preferentially on PIK3CA-mutant cells, resulting in increased DNA damage response and apoptosis. In addition, alpelisib and paclitaxel combination potentiated anti-migratory activity in PIK3CA-mutant cells. Alpelisib partially reversed epithelial-mesenchymal transition markers in PIK3CA-mutant cells. In a xenograft model of MKN1 cells, the alpelisib and paclitaxel combination significantly enhanced anti-tumor activity by decreasing Ki-67 expression and increasing apoptosis. Moreover, this combination tended to prolong the survival of tumor-bearing mice. Our data suggest promising anti-tumor efficacy of alpelisib alone or in combination with paclitaxel in PIK3CA-mutant GC cells.

   PubMed IF 4.9 혈액종양내과
2. 1542020

   제1저자 송진희 · 교신저자 김나영

   Song CH, Kim N, Nam RH, Choi SI, Lee HN, Surh YJ

   17β-Estradiol supplementation changes gut microbiota diversity in intact and colorectal cancer-induced ICR male mice.

   Sci Rep. 2020;10(1):12283.

   Abstract

   The composition of the gut microbiota is influenced by sex hormones and colorectal cancer (CRC). Previously, we reported that 17β-estradiol (E2) inhibits azoxymethane/dextran sulfate sodium (AOM/DSS)-induced tumorigenesis in male mice. Here, we investigated whether the composition of the gut microbiota is different between male and female, and is regulated by estrogen as a secondary outcome of previous studies. We established four groups of mice based on the sex and estrogen status [ovariectomized (OVX) female and E2-treated male]. Additionally, three groups of males were established by treating them with AOM/DSS, and E2, after subjecting them to AOM/DSS treatment. The mice were sacrificed at 21 weeks old. The composition of the gut microbiota was analyzed using 16S rRNA metagenomics sequencing. We observed a significant increase in the microbial diversity (Chao1 index) in females, males supplemented with E2, and males treated with AOM/DSS/E2 compared with normal males. In normal physiological condition, sex difference and E2 treatment did not affect the ratio of Firmicutes/Bacteroidetes (F/B). However, in AOM/DSS-treated male mice, E2 supplementation showed significantly lower level of the F/B ratio. The ratio of commensal bacteria to opportunistic pathogens was higher in females and E2-treated males compared to normal males and females subjected to OVX. Unexpectedly, this ratio was higher in the AOM/DSS group than that determined in other males and the AOM/DSS/E2 group. Our findings suggest that estrogen alters the gut microbiota in ICR (CrljOri:CD1) mice, particularly AOM/DSS-treated males, by decreasing the F/B ratio and changing Shannon and Simpson index by supply of estrogen. This highlights another possibility that estrogen could cause changes in the gut microbiota, thereby reducing the risk of developing CRC.

   PubMed IF 4.9 소화기내과
3. 1532020

   제1저자 안수민, 이종찬 · 교신저자 황진혁

   Ahn S^*, Lee JC^*, Shin DW, Kim J, Hwang JH

   High PD-L1 expression is associated with therapeutic response to pembrolizumab in patients with advanced biliary tract cancer.

   Sci Rep. 2020;10(1):12348.

   Abstract

   Pembrolizumab appears promising for patients with programmed cell death ligand-1 (PD-L1)-positive solid tumors. However, data on immunotherapy for biliary tract cancers (BTC) are limited. We aimed to investigate the predictive value of PD-L1 expression as an immunotherapeutic biomarker in BTC. Patients with advanced BTC (n = 175) were screened for PD-L1 expression using PharmDx assay and microsatellite instability (MSI) status. Of the total of 175 patients, 125 (71%) showed tumoral PD-L1 positivity (≥ 1%) while only two (2/142, 1.4%) showed MSI-High. Among 175 patients, 26 patients were treated with pembrolizumab as a second-line therapy, and tumor response was evaluated. Separating these patients into two groups by PD-L1 expression (high [≥ 50%] vs. low [< 50%]), overall response rate was 23% (56% [5/9] in high PD-L1 group vs. 6% [1/17] in low PD-L1 group, P = 0.004). Disease control rate was also higher in high PD-L1 group (78% vs. 35%, P = 0.019). The six responders showed median progression-free survival of 5.8 months after starting pembrolizumab, and none of them was MSI-High. High PD-L1 expression was associated with a better response to pembrolizumab. PD-L1 expression can potentially serve as an alternative predictive biomarker for pembrolizumab therapy in advanced BTC.

   PubMed IF 4.9 소화기내과
4. 1522020

   제1저자 박현경 · 교신저자 변자민, 윤성수

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

   Allogeneic Stem Cell Transplantation in Relapsed/Refractory Multiple Myeloma Treatment: Is It Still Relevant? (Running Title: The Role of Salvage alloSCT in MM).

   J Clin Med. 2020;9(8):jcm9082354.

   Abstract

   BACKGROUND Despite offering an attractive option, the role of allogeneic stem cell transplantation (alloSCT) for treatment of multiple myeloma (MM) remains unclear.

   METHODS Recognizing the paucity of data in the Asian population, we retrospectively evaluated the outcomes of 24 patients (median age 52) undergoing alloSCT between April 2003 and November 2017.

   RESULTS The median time from diagnosis to alloSCT was 39.4 months. The majority of the patients (70.8%) underwent alloSCT followed by reduced intensity conditioning regimens after a median of five lines of therapy. Among 24 patients, 15 patients (62.5%) had a high-risk MM feature. The two-year relapse-free survival (RFS) and overall survival (OS) of the total patients were 29.2 ± 9.3% and 44.3 ± 10.3%, respectively. Patients who were treated with less chemotherapy lines (<5) before alloSCT had a prolonged RFS and OS. All patients (seven patients) who received a myeloablative conditioning regimen had high-risk features, but two out of seven patients showed long-term survival without lasting sequelae. Nine patients (37.5%) experienced non-relapse mortality (NRM) within one year after alloSCT (the one-year cumulative incidence of NRM was 38.3 ± 10.1%).

   CONCLUSION AlloSCT can still be implemented as effective salvage option in the treatment of relapsed/refractory high-risk MM. The optimal timing of alloSCT remains to be determined.

   PubMed IF 3.3 혈액종양내과
5. 1512020

   제1저자 변자민 · 교신저자 윤성수, 이정림

   Byun JM, Hong J, Oh D, Yhim HY, Do YR, Park JS, Jung CW, Yang DH, Won JH, Lee HG, Moon JH, Mun YC, Jo DY, Han JJ, Lee JH, Lee JH, Lee J, Yoon SS

   Optimizing Preparative Regimen for Umbilical Cord Blood Transplantation in Adult Acute Leukemia Patients: Acute Lymphoblastic Leukemia Requires Myeloablative Conditioning but Not Acute Myeloid Leukemia.

   J Clin Med. 2020;9(7):jcm9072310.

   Abstract

   Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) (p = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG (p = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC (p = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT.

   PubMed IF 3.3 혈액종양내과
6. 1502020

   제1저자 강은정, 한승석 · 교신저자 오국환

   Kang E, Han SS, Kim J, Park SK, Chung W, Oh YK, Chae DW, Kim YS, Ahn C, Oh KH

   Discrepant glomerular filtration rate trends from creatinine and cystatin C in patients with chronic kidney disease: results from the KNOW-CKD cohort.

   BMC Nephrol. 2020;21(1):280.

   Abstract

   BACKGROUND Serum creatinine (Cr) and cystatin C (CysC) can both be used to estimate glomerular filtration rate (eGFR_Cr and eGFR_CysC). However, certain conditions may cause discrepancies between eGFR trends from Cr and CysC, and these remain undetermined in patients with chronic kidney disease (CKD).

   METHODS A total of 1069 patients from the Korean CKD cohort (KNOW-CKD), which enrolls pre-dialytic CKD patients, whose Cr and CysC had been followed for more than 4 years were included in the sample. We performed trajectory analysis using latent class mixed modeling and identified members of the discrepancy group when patient trends between eGFR_Cr and eGFR_CysC differed. Multivariate logistic analyses with Firth's penalized likelihood regression models were performed to identify conditions related to the discrepancy.

   RESULTS Trajectory patterns of eGFR_Cr were classified into three groups: two groups with stable eGFR_Cr (stable with high eGFR_Cr and stable with low eGFR_Cr) and one group with decreasing eGFR_Cr. Trajectory analysis of eGFR_CysC also showed similar patterns, comprising two groups with stable eGFR_CysC and one group with decreasing eGFR_CysC. Patients in the discrepancy group (decreasing eGFR_Cr but stable & low eGFR_CysC; n = 55) were younger and had greater proteinuria values than the agreement group (stable & low eGFR_Cr and eGFR_CysC; n = 706), differences that remained consistent irrespective of the measurement period (4 or 5 years).

   CONCLUSIONS In the present study, we identify conditions related to discrepant trends of eGFR_Cr and eGFR_CysC. Clinicians should remain aware of such potential discrepancies when tracing both Cr and CysC.

   PubMed IF 2.9 신장내과
7. 1492020

   제1저자 조인국, 김혜령 · 교신저자 황진혁

   Cho IK, Kim H, Lee JC, Lee J, Kim J, Ahn S, Park H, Hwang JH

   Higher Tumor Cellularity in Resected Pancreatic Ductal Adenocarcinoma Is a Negative Prognostic Indicator.

   Gut Liver. 2020;14(4):521-528.

   Abstract

   BACKGROUND/AIMS Desmoplasia is a prominent feature of pancreatic ductal adenocarcinoma (PDA). Stromal desmoplasia reflects the low cellularity that is characteristic of PDA, and it may play a role in PDA chemoresistance. In this retrospective study, we evaluated the relationship between tumor cellularity in resected PDA specimens and long-term patient outcomes.

   METHODS We retrospectively reviewed the data from 175 patients who underwent PDA resection between January 2010 and December 2015 at Seoul National University Bundang Hospital, and analyzed their clinicopathological features and the relationship between tumor cellularity (high vs low based on a cutoff of 30% cellularity) and patient outcomes.

   RESULTS The high-cellularity group had significantly shorter overall survival (OS) (18.7 months vs 26.6 months, p=0.006) and disease-free survival (11.0 months vs 16.9 months, p=0.031) than the low-cellularity group. Multivariate analysis revealed that high tumor cellularity was an independent risk factor for poor OS (hazard ratio, 2.008; 95% confidence interval, 1.361 to 2.962; p<0.001). Adjuvant therapy improved OS in the low-cellularity group (16.3 months vs 41.3 months, p=0.001) but not in the high-cellularity group (15.9 months vs 24.4 months, p=0.107).

   CONCLUSIONS Tumor cellularity in PDA specimens may be a prognostic and predictive biomarker that could aid in identifying patients who would benefit from adjuvant therapy for PDA.

   PubMed IF 4.1 소화기내과
8. 1482020

   제1저자 백성민 · 교신저자 김나영

   Baek SM, Kim N, Kwon YJ, Lee HS, Kim HY, Lee J, Yoon H, Shin CM, Park YS, Lee DH

   Role of Serum Pepsinogen II and Helicobacter pylori Status in the Detection of Diffuse-Type Early Gastric Cancer in Young Individuals in South Korea.

   Gut Liver. 2020;14(4):439-449.

   Abstract

   BACKGROUND/AIMS The utility of serum pepsinogen (sPG) I and the sPGI/II ratio as biomarkers for screening individuals with gastric cancer (GC) has not been established in Korea. The aim of this study was to define the role of sPG, especially sPGII, in GC screening.

   METHODS This study enrolled 2,940 subjects, including patients with GC (n=1,124) or gastric dysplasia (n=353) and controls (n=1,463). Tests to determine sPG levels and Helicobacter pylori (HP) infection status were performed. Area under the curve and receiver operating characteristic curve were calculated to identify the optimal cutoff values for sPG. The usefulness of sPG levels for the detection of GC and gastric dysplasia was validated by multivariate logistic regression.

   RESULTS The sPGI/II ratio was associated with the risk of gastric dysplasia and advanced-stage intestinal-type GC (IGC). In contrast, sPGII was associated with the risk of early-stage diffuse-type GC (DGC). Significantly higher risk was indicated by an sPGI/II ratio <3 for gastric dysplasia and advanced-stage IGC and by sPGII levels ≥20 µg/L for early-stage DGC. Positive HP status showed a stronger association with DGC than with IGC. When sPGII level and HP status were combined, the prevalence of DGC was higher in the ≥20 µg/L sPGII and HP-positive group. Age younger than 40 years was strongly related to early-stage DGC, especially in females (odds ratio, 21.00; p=0.006).

   CONCLUSIONS sPGII ≥20 ng/mL and positive HP status suggest a risk of early-stage DGC, particularly in young adult females in South Korea.

   PubMed IF 4.1 소화기내과
9. 1472020

   제1저자 기유정, 정지현 · 교신저자 한정규

   Ki YJ, Jung JH, Han JK, Hong S, Cho JH, Gwon HC, Lee SY, Rhew JY, Chae JK, Chae IH, Yang HM, Park KW, Kang HJ, Koo BK, Kim HS

   Clinical Implications of Bifurcation Angles in Left Main Bifurcation Intervention Using a Two-Stent Technique.

   J Interv Cardiol. 2020;2020:2475930.

   Abstract

   OBJECTIVES The aim of this study was to assess the clinical impact of 3 bifurcation angles in left main (LM) bifurcation treated with the 2-stent technique.

   BACKGROUND Data are limited regarding the impact of bifurcation angles after LM percutaneous coronary intervention (PCI).

   METHODS Using patient-level 4 multicenter registries in Korea, 462 patients undergoing LM bifurcation PCI with the 2-stent technique were identified (181 crush, 167 T-stenting; 63% 1^st generation drug-eluting stent (DES), 37% 2^nd generation DES). Three bifurcation angles, between the LM and left anterior descending (LAD), the LM and left circumflex (LCX), and the LAD and LCX, were measured. The primary outcome was target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR).

   RESULTS In patients treated with the crush technique, the best cutoff value (BCV) to predict TLF was 152° of the LM-LAD angle. In the crush group, a significantly higher TLF rate, mostly driven by TLR, was observed in the LM-LAD angle ≥152° group compared with the <152° group (35.7% vs. 14.6%; adjusted hazard ratio 3.476; 95% confidence interval 1.612-7.492). An LM-LAD angle ≥152° was an independent predictor of TLF. In the T-stenting, no bifurcation angle affected the clinical outcomes.

   CONCLUSIONS In LM bifurcation PCI using the 2-stent technique, wide LM-LAD angle (≥152°) was associated with a greater risk of TLF in the crush, whereas none of the bifurcation angles affected T-stenting outcomes.

   PubMed IF 1.4 순환기내과
10. 1462020

    제1저자 김범석, 강창경 · 교신저자 박완범, 김유정

    Keam B, Kang CK, Jun KI, Moon SM, Suh KJ, Lee DW, Ock CY, Kim M, Choi Y, Lim Y, Lee KH, Kim SH, Kim TM, Kim TY, Oh DY, Kim DW, Im SA, Lee JS, Kim ES, Kim HB, Kim NJ, Kim YJ, Park WB, Oh MD

    Immunogenicity of Influenza Vaccination in Patients with Cancer Receiving Immune Checkpoint Inhibitors.

    Clin Infect Dis. 2020;71(2):422-425.

    Abstract

    Among prospectively enrolled adult patients with cancer receiving immune checkpoint inhibitors (ICIs; n = 46) or cytotoxic agents (n = 90), seroprotection and seroconversion rates after seasonal quadrivalent influenza vaccinations were higher with ICI than with cytotoxic chemotherapy. These results support annual influenza vaccinations for cancer patients receiving ICIs. Clinical Trials Registration clinicaltrials.gov (NCT03590808).

    PubMed IF 8.3 감염내과
11. 1452020

    제1저자 박혜주 · 교신저자 윤성수, 고영일

    Park H, Kim D, Kim D, Park J, Koh Y, Yoon SS

    Truncation of MYH8 tail in AML: a novel prognostic marker with increase cell migration and epithelial-mesenchymal transition utilizing RAF/MAPK pathway.

    Carcinogenesis. 2020;41(6):817-827.

    Abstract

    MYH8 is an actin-based motor protin involved in integrin-mediated cell adhesion and migration. Heretofore, the association of MYH8 mutation and cancer is unclear. In this study, we investigated the biologic significance of novel MYH8 tail truncation mutation, R1292X, in acute myeloid leukemia (AML) which was discovered by whole-exome sequencing and targeted re-sequencing of 209 AML patients. The patients harboring the mutation all relapsed within 3.8-20.9 months. To explore the functional consequence of the mutation in AML progress, we established knock-in cell lines using CRISPR-Cas9 genome editing. Using the established mutant model, we assessed traits of cancer progress. The mutant cells had improved motility, which was confirmed by immunofluorescence staining, wound healing, transwell migration and adhesion assay. The cell morphology and cell cycle were altered to be accessible to migration and epithelial-to-mesenchymal transition (EMT) transcription factors were also increased. The Raf and p44/42 MAPK pathway was a major regulator of these characteristics proved by a screening of signal transduction and inhibitor assay. Further, a public cancer genome database (cBioPortal) shows that MYH8 tail truncation mutations occurring near the R1292 position of the genome may have a significant function in cancer. In conclusion, truncation of MYH8 could be a novel prognostic marker related to poor prognosis by inducing cell migration and EMT features, and inhibition of the Raf/MAPK pathway would be a therapeutic strategy for AML patients with MYH8 tail truncation.

    PubMed IF 3.8 혈액종양내과
12. 1442020

    제1저자 허건, 최진호 · 교신저자 이상협

    Huh G^*, Choi JH^*, Lee SH, Paik WH, Ryu JK, Kim YT, Jeong S, Lee DH, Kim GH, Kang SG

    Innovation of EUS-guided transmural gallbladder drainage using a novel self-expanding metal stent.

    Sci Rep. 2020;10(1):11159.

    Abstract

    Endoscopic ultrasonography (EUS)-guided transmural drainage has been accepted as a modality of choice in peripancreatic fluid collection and acute cholecystitis. Each type of stent, including double-pigtail plastic stents, tubular self-expandable metal stents (SEMS), and lumen-apposing metal stents, for these procedure has its own advantages and disadvantages. To overcome their disadvantages, this animal study evaluated the feasibility of a newly designed twisted fully covered SEMS with spiral coiled ends. We performed the EUS-guided cholecystogastrostomy with a newly developed metal stent in eight mini pigs with surgically induced gallbladder distension. This novel stent is a twisted fully covered SEMS with spiral coiled ends, a diameter of 8 mm, and a length of 6 cm. The stent has been maintained for four to seven weeks after EUS-guided cholecystogastrostomy. The primary outcome was the technical success rate, and the secondary outcomes were adverse events, stent dysfunction, stent removability, and fistula formation. The stent was placed successfully between the gallbladder and the stomach in all cases without any adverse event. We observed neither stent migration nor dysfunction during the study period, and all the stents were removed easily as scheduled. We confirmed successful cholecysto-gastric fistula formation at endoscopic and histologic level in all cases. EUS-guided transmural drainage and fistula formation using a new twisted fully covered metal stent with spiral coiled ends was technically feasible without any adverse event in this animal study. Further clinical studies are needed to evaluate its efficacy and safety in real practice.

    PubMed IF 4.9 소화기내과
13. 1432020

    제1저자 윤준식, 이동호 · 교신저자 조은주, 배은정

    Yoon JS, Lee DH, Cho EJ, Song MK, Choi YH, Kim GB, Lee YB, Lee JH, Yu SJ, Kim H, Kim YJ, Yoon JH, Bae EJ

    Risk of Liver Cirrhosis and Hepatocellular Carcinoma after Fontan Operation: A Need for Surveillance.

    Cancers (Basel). 2020;12(7):cancers12071805.

    Abstract

    Liver cirrhosis and hepatocellular carcinoma (HCC) are serious late complications that can occur after the Fontan procedure. This study aimed to investigate the cumulative incidence of cirrhosis and HCC and to identify specific features distinguishing HCC from benign arterial-phase hyperenhancing (APHE) nodules that developed after the Fontan operation. We retrospectively enrolled 313 post-Fontan patients who had been followed for more than 5 years and had undergone ultrasound or computed tomography (CT) of the liver between January 2000 and August 2018. Cirrhosis was diagnosed radiologically. The estimated cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. Multiphasic CT revealed that 18 patients had APHE nodules that were ≥1 cm in size and showed washout in the portal venous phase (PVP)/delayed phase, which met current noninvasive HCC diagnosis criteria. Among them, only seven patients (38.9%, 7/18) were diagnosed with HCC. After cirrhosis developed, the annual incidence of HCC was 1.04%. The appearance of washout in the PVP (p = 0.006), long time elapsed since the initial Fontan operation (p = 0.04), large nodule size (p = 0.03), and elevated serum α-fetoprotein (AFP) level (p < 0.001) were significantly associated with HCC. In conclusion, cirrhosis is a frequent late complication after Fontan operation, especially after 10 years, and HCC is not a rare complication after cirrhosis development. Diagnosis of HCC should not be based solely on the current imaging criteria, and washout on PVP and clinical features might be helpful to differentiate HCC nodules from benign APHE nodules.

    PubMed IF 4.8 소화기내과
14. 1422020

    제1저자 손경희, 함종호 · 교신저자 강혜련, 김혜영

    Sohn KH, Ham J, Chung SJ, Kang HR, Kim HY

    Analysis of Innate and Adaptive Immunological Characteristics in Patients with IgG4-Related Disease.

    Int Arch Allergy Immunol. 2020;181(10):807-812.

    Abstract

    BACKGROUND Immunoglobulin G4-related disease (IgG4-RD) is a systemic immunological disorder characterized by fibro-inflammatory conditions; however, the pathobiology of IgG4-RD has not been fully identified.

    OBJECTIVE This study aimed to analyze systemic differences of innate and adaptive immune cells from healthy controls and patients with IgG4-RD.

    METHODS Healthy controls (n = 9) and IgG4-RD patients (n = 7) were recruited with informed consent. Peripheral blood was collected from healthy controls and IgG4-RD patients, and three blood samples from IgG4-RD patients were re-collected two months after the last rituximab (RTX) treatment. The various immune cells and cytokine productions were measured by flow cytometry.

    RESULTS Blood CD14+ monocytes and steady-state follicular helper T cells were increased in patients with IgG4-RD. However, there were no changes in other immune cell populations, including B cells, CD4 T cells, CD8 T cells, and innate lymphoid cells. Also, the TGF-β-producing CD14+ monocytes were significantly augmented in patients with IgG4-RD. Two months after RTX treatment, total B cells (CD19+) were depleted; however, the expressions of TGF-β from CD14+ monocytes remained unchanged.

    CONCLUSION These findings showed that IgG4-RD is related to the increment of CD14+ monocytes. Besides, controlling increased TGF-β-producing CD14+ monocytes with RTX treatment might be a conducive way to regulate IgG4-RD.

    PubMed IF 2.3 알레르기내과
15. 1412020

    제1저자 박소영, 김정희 · 교신저자 조남한

    Park SY, Kim JH, Choi HJ, Ku EJ, Hong AR, Lee JH, Shin CS, Cho NH

    Longitudinal changes in bone mineral density and trabecular bone score in Korean adults: a community-based prospective study.

    Arch Osteoporos. 2020;15(1):100.

    Abstract

    UNLABELLED The bone mineral densities (BMDs) of the femoral neck and total hip, and the lumbar spine trabecular bone score (TBS), tended to decrease with age in both men and women, whereas the lumbar spine BMD tended to increase. Lumbar spine BMD is thus inappropriate for evaluating longitudinal changes in bone loss; the lumbar spine TBS is an alternative measure.

    PURPOSE Aging is associated with a decrease in bone mass and quality. This community-based prospective cohort study investigated longitudinal changes in bone phenotype in Korean adults.

    METHODS We analyzed data from a prospective community-based cohort study, the Korean Genome and Epidemiology Study. Postmenopausal women and men who underwent dual-energy X-ray absorptiometry at least twice from 2007 to 2014 were included. Longitudinal changes in bone mineral density (BMD) and trabecular bone score (TBS) over 6 years were analyzed by sex, age, and body mass index.

    RESULTS A total of 1895 subjects were enrolled (men 965; postmenopausal women 929). The femoral neck (FN) BMD, total hip (TH) BMD, and lumbar spine (LS) TBS decreased significantly over time, but the LS BMD increased significantly. In men, the average annual changes were 0.3% in LS BMD (p < 0.001), - 0.33% in FN BMD (p < 0.001), - 0.26% in TH BMD (p = 0.001), and - 0.27% in LS TBS (p < 0.001). In women, the average annual changes were 0.27% in LS BMD (p < 0.001), - 0.67% in FN BMD (p < 0.001), - 0.66% in TH BMD (p < 0.001), and - 0.27% in LS TBS (p < 0.001). The longitudinal decrease in TH BMD over time was significantly greater in women (versus men) and those who were older (versus younger).

    CONCLUSION The FN and TH BMDs decreased with aging. But, the LS BMD was inappropriate to evaluate longitudinal changes of bone loss. The LS TBS could be alterative.

    PubMed IF 2.7 내분비대사내과
16. 1402020

    제1저자 강민규 · 교신저자 박흥우

    Kang MG, Lee HS, Tantisira KG, Park HW

    Genetic Signatures of Acute Asthma Exacerbation Related With Ineffective Response to Corticosteroid.

    Allergy Asthma Immunol Res. 2020;12(4):626-640.

    Abstract

    PURPOSE Acute exacerbation (AE) is an important domain of asthma management and may be related with ineffective response to corticosteroid. This study aimed to find mechanisms of AE using genome-wide gene expression profiles of blood cells from asthmatics and its perturbation by in vitro dexamethasone (Dex)-treatment.

    METHODS We utilized lymphoblastoid B cells from 107 childhood asthmatics and peripheral blood mononuclear cells from 29 adult asthmatics who were treated with inhaled corticosteroids. We searched for a preserved co-expression gene module significantly associated with the AE rate in both cohorts and measured expression changes of genes belong to this module after Dex-treatment.

    RESULTS We identified a preserved module composed of 77 genes. Among them, expressions of 2 genes (EIF2AK2 and NOL11) decreased significantly after Dex-treatment in both cohorts. EIF2AK2, a key gene acting antiviral defense mechanism, showed significantly higher expressions in asthmatics with AE. The protein repair pathway was enriched significantly in 64 genes which belong to the preserved module but showed no expression differences after Dex-treatment in both cohorts. Among them, MSRA and MSRB2 may play key roles by controlling oxidative stress.

    CONCLUSIONS Many genes belong to the AE rate-associated and preserved module identified in blood cells from childhood and adults asthmatics showed no expression changes after in vitro Dex-treatment. These findings suggest that we may need alternative treatment options to corticosteroids to prevent AE. EIF2AK2, MSRA and MSRB2 expressions on blood cells may help us select AE-susceptible asthmatics and adjust treatments to prevent AE.

    PubMed IF 4.3 알레르기내과
17. 1392020

    제1저자 이철형, 이윤빈 · 교신저자 김윤준

    Lee CH, Lee YB, Kim MA, Jang H, Oh H, Kim SW, Cho EJ, Lee KH, Lee JH, Yu SJ, Yoon JH, Kim TY, Kim YJ

    Effectiveness of nivolumab versus regorafenib in hepatocellular carcinoma patients who failed sorafenib treatment.

    Clin Mol Hepatol. 2020;26(3):328-339.

    Abstract

    BACKGROUND/AIMS Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients.

    METHODS Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias.

    RESULTS Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0-10.8) months for regorafenib and 5.9 (95% CI, 3.7-8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30-0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51-1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04).

    CONCLUSION After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.

    PubMed IF 21.7 소화기내과
18. 1382020

    제1저자 김연욱 · 교신저자 박종선

    Kim YW, Kwon BS, Lim SY, Lee YJ, Cho YJ, Yoon HI, Lee JH, Lee CT, Park JS

    Diagnostic value of bronchoalveolar lavage and bronchial washing in sputum-scarce or smear-negative cases with suspected pulmonary tuberculosis: a randomized study.

    Clin Microbiol Infect. 2020;26(7):911-916.

    Abstract

    OBJECTIVES Bronchoalveolar lavage (BAL) and bronchial washing (BW) are two major methods used to obtain high-quality respiratory specimens from patients with suspected pulmonary tuberculosis (TB) but a sputum-scarce or smear-negative status. We aimed to compare the value of BAL and BW in the diagnosis of TB in such patients.

    METHODS We enrolled patients with suspected pulmonary TB but with a sputum-scarce or smear-negative status who were referred for bronchoscopy between October 2013 and January 2016. Participants were randomized into the BAL and BW groups for evaluation. The primary outcome was the diagnostic yield for TB detection. Secondary outcomes included culture positivity, positivity of nucleic acid amplification tests (NAATs) for Mycobacterium tuberculosis and procedure-related complications.

    RESULTS A total of 94 patients were assessed and 91 (43 in the BAL group, 48 in the BW group) were analysed. Twenty-one patients (48.8%) in the BAL group and 30 (62.5%) in the BW group had a final diagnosis of pulmonary TB. The detection rate of M. tuberculosis by culture or NAAT was significantly higher in BAL specimens than in BW specimens (85.7% vs 50.0%, p 0.009). The procedure-related complications were hypoxic events, 2/43 (4.7%) in the BAL group and 5/48 (10.4%) in the BW group; and post-bronchoscopic fever, 3/43 (7.0%) in the BAL group and 4/48 (8.3%) in the BW group.

    DISCUSSION As long as it is tolerable, BAL rather than BW, should be used to obtain specimens for the diagnosis of pulmonary TB in sputum-scarce or smear-negative cases.

    PubMed IF 8.7 호흡기내과
19. 1372020

    제1저자 김수환 · 교신저자 임윤정

    Kim SH, Lim YJ, Park J, Shim KN, Yang DH, Chun J, Kim JS, Lee HS, Chun HJ, Research Group for Capsule Endoscopy/Small Bowel Endoscopy

    Changes in performance of small bowel capsule endoscopy based on nationwide data from a Korean Capsule Endoscopy Registry.

    Korean J Intern Med. 2020;35(4):889-896.

    Abstract

    BACKGROUND/AIMS Capsule endoscopy (CE) is widely used for the diagnosis of small bowel diseases. The clinical performance and complications of small bowel CE, including completion rate, capsule retention rate, and indications, have been previously described in Korea. This study aimed at estimating the recent changes in clinical performance and complications of small bowel CE based on 17-year data from a Korean Capsule Endoscopy Registry.

    METHODS CE registry data from 35 hospitals were retrospectively analyzed. Clinical information, including completion rate, capsule retention rate, and indications, was collected and analyzed. In addition, the most recent 5-year data for CE examinations were compared with the previous 12-year data.

    RESULTS A total of 4,650 CE examinations were analyzed. The most common indication for CE was obscure gastrointestinal bleeding (OGIB). The overall incomplete examination rate was 16% and the capsule retention rate was 3%. Crohn's disease was a risk factor for capsule retention. Inadequate bowel preparation was significantly associated with capsule retention and incomplete examination. An indication other than OGIB was a risk factor for incomplete examination. A recent increasing trend of CE diagnosis of Crohn's disease was observed. The most recent 5-year incomplete examination rate for CE examinations decreased compared with that of the previous 12 years.

    CONCLUSION The 17-year data suggested that CE is a useful and safe tool for diagnosing small bowel diseases. The incomplete examination rate of CE decreased with time, and OGIB was consistently the main indication for CE. Inadequate bowel preparation was significantly associated with capsule retention and incomplete examination.

    PubMed IF 2.2 소화기내과
20. 1362020

    제1저자 최평균, 강은교, 이선영 · 교신저자 김남중

    Choe PG, Kang EK, Lee SY, Oh B, Im D, Lee HY, Jung H, Kang CK, Kim MS, Park WB, Choi EH, Cho B, Oh MD, Kim NJ

    Selecting coronavirus disease 2019 patients with negligible risk of progression: early experience from non-hospital isolation facility in Korea.

    Korean J Intern Med. 2020;35(4):765-770.

    Abstract

    BACKGROUND/AIMS As the novel coronavirus (coronavirus disease 2019 [COVID-19]) outbreak progresses rapidly, staying home is recommended for suspected patients; however, the safety of this recommendation is uncertain. In Korea, non-hospital facilities called "living and treatment centers (LTCs)" have been established since 5 March 2020. The LTCs provided a unique opportunity to evaluate the safety of selection criteria for low-risk groups.

    METHODS Between 5 March and 9 April 2020, patients with COVID-19 who met the following criteria were admitted to the LTC; alert, age below 65 years old, no underlying disease or well-controlled underlying disease, body temperature below 38.0°C, whether taking antipyretics or not, and no dyspnea. Patients were closely observed by doctors or nurses' interviews twice a day and transferred to hospitals when symptoms worsened.

    RESULTS A total of 113 patients were admitted to the LTC; 52.2% were female, with a median age of 25 years (interquartile range, 21.5 to 39.5). Of 113 patients, 54 (47.8%) were asymptomatic at diagnosis, and 15 (13.3%) had no symptoms until they were released from isolation. During the follow-up period, two (1.8%) patients were transferred to a hospital but did not progress to severe status during hospitalization.

    CONCLUSION The risk of progression was negligible in COVID-19 patients who met the admission criteria for LTC at the time of diagnosis. LTCs could be a safe alternative considering shortage of hospital beds.

    PubMed IF 2.2 감염내과
21. 1352020

    제1저자 주선미 · 교신저자 이진우

    Ju S, Choi SM, Park YS, Lee CH, Lee SM, Yoo CG, Kim YW, Han SK, Lee J

    Rapid Muscle Loss Negatively Impacts Survival in Critically Ill Patients With Cirrhosis.

    J Intensive Care Med. 2020;35(7):663-671.

    Abstract

    PURPOSE To assess the impact of rapid muscle loss before admission to intensive care unit (ICU) in critically ill patients with cirrhosis.

    MATERIALS AND METHODS Patients with cirrhosis who had undergone 2 or more recent computed tomography scans before admission to the medical ICU were included. Muscle cross-sectional area at the level of the third lumbar vertebra was quantified using OsiriX software. The rate of muscle mass change and skeletal muscle index (SMI) were also calculated. Multivariable Cox proportional hazards regression was used to evaluate the association between muscle loss and mortality.

    RESULTS Among 125 patients, 113 (90.4%) patients were classified as having sarcopenia. The mean body mass index was 22.6 (3.9) kg/m². Thirty-nine (31.2%) patients were within the normal range for muscle mass change, while 86 (68.8%) patients demonstrated rapid decline in muscle mass before admission to the ICU. Patients with rapid muscle loss showed high ICU mortality (59.3%) and in-hospital mortality (77.9%). Multivariate Cox analysis showed that ICU mortality and in-hospital mortality were independently associated with malignancy, Acute Physiology and Chronic Health Evaluation (APACHE) II score, SMI, and rapid muscle loss.

    CONCLUSION Rapid muscle decline is correlated with increased ICU mortality and in-hospital mortality in critically ill patients with cirrhosis.

    PubMed IF 2.3 호흡기내과
22. 1342020

    제1저자 김학령 · 교신저자 김응주

    Kim HL, Jung MH, Choi JH, Lee S, Kong MG, Na JO, Cho YH, Cho KI, Choi DJ, Kim EJ

    Factors Associated with Low Awareness of Heart Failure in the General Population of Korea.

    Korean Circ J. 2020;50(7):586-595.

    Abstract

    BACKGROUND AND OBJECTIVES Factors associated with low heart failure (HF) awareness have not been well-evaluated. This study was conducted to find out which demographic features would be associated with low HF awareness in the general population of Korea.

    METHODS A telephone interview was conducted with 1,032 adults (58 years and 50.6% were male) across the country. Based on answer to 15 questions about HF, we scored from 0 to 15 points (mean, 7.53±2.75; median, 8; interquartile range, 6-9). A score of <8 was defined as low HF awareness, and a score of ≥8 was defined as high HF awareness.

    RESULTS A total of 478 subjects (46.3%) had low HF awareness. HF awareness scores were 5.18±1.85 and 9.55±1.50 in subjects of low and high HF awareness groups, respectively. Subjects with low HF awareness were older, more female-dominant, more diabetic, lower educational and house hold income levels, and more frequently living in rural areas, compared to those with high HF awareness (p<0.05 for each). In multivariable logistic regression analyses, older age (≥67 years: odds ratio [OR], 1.61; 95% confidence interval [CI], 1.16-2.19; p=0.004), female sex (OR, 1.33; 95% CI, 1.02-1.73; p=0.034) and low educational level (high school graduate or less vs. college graduate: OR, 2.38; 95% CI, 1.75-3.22; p<0.001) were significantly associated with low HF awareness even after controlling for potential confounders.

    CONCLUSIONS Older age, female sex, and lower level of education were independently associated with low HF awareness in the general Korean population. More attention and education are needed for these vulnerable groups to improve HF awareness.

    PubMed IF 3.4 순환기내과
23. 1332020

    제1저자 남아롱, 김미화 · 교신저자 오도연

    Nam AR, Jin MH, Bang JH, Oh KS, Seo HR, Oh DY, Bang YJ

    Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer.

    Cancer Res Treat. 2020;52(3):945-956.

    Abstract

    PURPOSE Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC.

    MATERIALS AND METHODS In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models.

    RESULTS AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy.

    CONCLUSION Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

    PubMed IF 4.2 혈액종양내과
24. 1322020

    제1저자 이현우 · 교신저자 최선미

    Lee HW, Cho J, Kwak N, Hwang I, Park YS, Lee CH, Lee SM, Yoo CG, Kim YW, Choi SM

    Clinical course of asymptomatic small enhancing brain nodules in patients with nonsmall cell lung cancer: do we have to follow them up?

    ERJ Open Res. 2020;6(3):00109-2020.

    Abstract

    AIMS Brain magnetic resonance imaging (MRI) is recommended during the initial work-up for nonsmall cell lung cancer (NSCLC). Although small enhancing brain nodules not radiologically confirmed as metastatic lesions have often been detected, their clinical course has not been well studied.

    METHODS This nested case-control study included NSCLC patients who had small enhancing brain nodules detected by serial brain MRIs from January 2014 through December 2018 at a tertiary university hospital. Small enhancing brain nodules were defined as round enhancing nodules of ≤10 mm diameter without oedema in thin-section (1 mm) contrast MRIs. The incidence, natural course and risk factors of growing nodules were evaluated.

    RESULTS A total of 171 small enhancing brain nodules in 123 patients were observed over an average of 22.1 months. The incidence of nodule growth was 49.1% with mean growth rate of 11 mm·year^-1. We found that 25.0% of the growing nodules contributed to clinical upstaging compared to the initial stage. Cerebral events were more common in growing nodules; therefore, local therapy was performed more often. However, there was no difference in the cerebral event-related mortality. Nodule growth was more frequent in younger individuals, multiple nodules, advanced disease, poorly differentiated carcinoma, rim enhancement and larger initial size. In multivariable analysis, predictors of growth were N stage ≥1, existence of epidermal growth factor receptor mutation and larger initial size.

    CONCLUSION Considering the clinical course of small enhancing brain nodules, more intensive evaluation is required for early detection and pre-emptive intervention when accompanied by risk factors.

    PubMed IF 4.4 호흡기내과
25. 1312020

    제1저자 송명진 · 교신저자 박종선, 이상훈

    Song MJ, Kim DJ, Paik HC, Cho S, Kim K, Jheon S, Lee SH, Park JS

    Impact of idiopathic pulmonary fibrosis on recurrence after surgical treatment for stage I-III non-small cell lung cancer.

    PLoS One. 2020;15(6):e0235126.

    Abstract

    BACKGROUND Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, its effect on recurrence after curative surgery remains unclear.

    OBJECTIVES This study aimed to determine the impact of IPF on recurrence-free survival following curative surgical resection of stage I-III non-small cell lung cancer (NSCLC) and investigate the effects of patient and surgical factors on the risk of recurrence.

    METHODS We reviewed retrospectively collected data of patients with surgically resected stage I-III NSCLC from two tertiary care hospitals in South Korea. By propensity score matching, patients with IPF (LC with IPF) were matched to those without IPF (LC without IPF).

    RESULTS In total, 3416 patients underwent surgical resection, and 96 were diagnosed with underlying IPF. In the LC with IPF group, 89.6% patients were men, and the average age was 69.7 years. Sublobar resection was performed more frequently in the LC with IPF group than in the LC without IPF group, while the rate of mediastinal lymph node dissection and dissected node number were lower in the former group. The 5-year recurrence-free survival rate was significantly lower in the LC with IPF group (49.2%) than in the LC without IPF group (69.1%; P<0.001). Multivariable Cox regression analysis revealed that IPF and postoperative stage III were independent risk factors for recurrence.

    CONCLUSIONS IPF may increase the risk of recurrence after curative surgical treatment for NSCLC. Close surveillance for recurrence is mandatory for patients with underlying IPF.

    PubMed IF 2.8 호흡기내과
26. 1302020

    제1저자 임수 · 교신저자 임수

    Lim S, Moon JH, Shin CM, Jeong D, Kim B

    Effect of Lactobacillus sakei, a Probiotic Derived from Kimchi, on Body Fat in Koreans with Obesity: A Randomized Controlled Study.

    Endocrinol Metab (Seoul). 2020;35(2):425-434.

    Abstract

    BACKGROUND The increased prevalence of obesity has led to increases in the prevalence of chronic diseases worldwide. There is interest whether probiotics have an effect on obesity, but the effectiveness and safety of only a few probiotics for the treatment of obesity have been reported. The purpose of this study was to investigate whether ingestion of Lactobacillus sakei (CJLS03) derived from kimchi causes weight loss in people with obesity.

    METHODS This randomized, double-blind, placebo-controlled, clinical trial involved 114 adults with a body mass index (BMI) ≥25 kg/m2 who were assigned randomly to a CJLS03 or placebo group. The groups received two allocations of either 5×109 colony-forming units of CJLS03/allocation or the equivalent vehicle for 12 weeks. Demographic and biochemical parameters, and body composition including fat and muscle mass were measured at baseline and after 12 weeks. Changes in body fat, weight, and waist circumference were compared between the two treatment groups. Adverse events were monitored during study period.

    RESULTS Body fat mass decreased by 0.2 kg in the CJLS03 group and increased by 0.6 kg in the placebo group (0.8 kg difference, P=0.018). After the 12 weeks, waist circumference was 0.8 cm smaller in the CJLS03 group than in the placebo group (P=0.013). BMI and body weight did not change after the 12 weeks. Adverse events were mild and did not differ between the two groups.

    CONCLUSION These data suggest that L. sakei (CJLS03) might help people with obesity reduce body fat mass without serious side effects (ClinicalTrials.gov: NCT03248414).

    PubMed IF 5.1 내분비대사내과
27. 1292020

    제1저자 신유진 · 교신저자 임수

    Shin Y, Moon JH, Chin HJ, Ferrannini E, Lim S

    Glycemic Efficacy and Metabolic Consequences of an Empagliflozin Add-on versus Conventional Dose-Increasing Strategy in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea.

    Endocrinol Metab (Seoul). 2020;35(2):329-338.

    Abstract

    BACKGROUND We assessed the glucose-lowering efficacy of adding empagliflozin versus dose escalating existing medications in patients with uncontrolled type 2 diabetes (T2D).

    METHODS This was a 6-month retrospective case-control study in subjects with uncontrolled T2D (glycated hemoglobin [HbA1c] &gt;7%) on conventional treatment. The study group started add-on therapy with empagliflozin (10 mg once a day) while the control group was up-titrated with existing medication, using either monotherapy or a combination of metformin, sulfonylurea, and a dipeptidyl peptidase-4 inhibitor. The primary endpoints included changes in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (PP2) levels. Secondary outcomes included changes in body composition, body mass index (BMI), and serum ketone bodies, and urinary excretion of sodium, potassium, chlorine, calcium, phosphorus, and glucose.

    RESULTS After treatment, the reduction in HbA1c was significantly greater in the empagliflozin group than in controls (from 8.6%±1.6% to 7.6%±1.5% vs. 8.5%±1.1% to 8.1%±1.1%; P&lt;0.01). Similar patterns were found in FPG and PP2 levels. Empagliflozin decreased systolic and diastolic blood pressure, triglycerides, and alanine and aspartate aminotransferase levels. Body weight, BMI, waist circumference, fat mass, and abdominal visceral fat area decreased significantly while lean body mass was maintained. Total ketones, β-hydroxybutyrate, and acetoacetate levels increased significantly after empagliflozin.

    CONCLUSION In addition to glucose lowering, an empagliflozin add-on regimen decreased blood pressure and body fat, and improved metabolic profiles significantly. Empagliflozin add-on is superior to dose escalation in patients with T2D who have inadequate glycemic control on standard medications.

    PubMed IF 5.1 내분비대사내과
28. 1282020

    제1저자 김하나 · 교신저자 박영주, 임청

    Kim H, Kong SH, Moon JH, Kim SY, Park KH, Kim JS, Choh JH, Park YJ, Lim C

    Subclinical Hypothyroidism Affects the Long-Term Outcomes of Patients Who Undergo Coronary Artery Bypass Grafting Surgery but Not Heart Valve Surgery.

    Endocrinol Metab (Seoul). 2020;35(2):308-318.

    Abstract

    BACKGROUND The aim of this study was to determine the associations between subclinical hypothyroidism (SCH) and long-term cardiovascular outcomes after coronary artery bypass grafting (CABG) or heart valve surgery (HVS).

    METHODS We retrospectively reviewed and compared all-cause mortality, cardiovascular mortality, and cardiovascular events in 461 patients who underwent CABG and 104 patients who underwent HVS.

    RESULTS During a mean±standard deviation follow-up duration of 7.6±3.8 years, there were 187 all-cause deaths, 97 cardiovascular deaths, 127 major adverse cardiovascular events (MACE), 11 myocardial infarctions, one unstable angina, 70 strokes, 30 hospitalizations due to heart failure, 101 atrial fibrillation, and 33 coronary revascularizations. The incidence of all-cause mortality after CABG was significantly higher in patients with SCH (n=36, 55.4%) than in euthyroid patients (n=120, 30.3%), with a hazard ratio of 1.70 (95% confidence interval, 1.10 to 2.63; P=0.018) after adjustment for age, sex, current smoking status, body mass index, underlying diseases, left ventricular dysfunction, and emergency operation. Interestingly, low total triiodothyronine (T3) levels in euthyroid patients who underwent CABG were significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and MACE, but those associations were not observed in HVS patients. Both free thyroxine and thyroid-stimulating hormone levels in euthyroid patients were not related with any cardiovascular outcomes in either the CABG or HVS group.

    CONCLUSION SCH or low total T3 might be associated with a poor prognosis after CABG, but not after HVS, implying that preoperative thyroid hormonal status may be important in ischemic heart disease patients.

    PubMed IF 5.1 내분비대사내과
29. 1272020

    제1저자 김지은 · 교신저자 김봉수, 이하정

    Kim JE, Kim HE, Park JI, Cho H, Kwak MJ, Kim BY, Yang SH, Lee JP, Kim DK, Joo KW, Kim YS, Kim BS, Lee H

    The Association between Gut Microbiota and Uremia of Chronic Kidney Disease.

    Microorganisms. 2020;8(6):microorganisms8060907.

    Abstract

    Chronic kidney disease (CKD)-associated uremia aggravates-and is aggravated by-gut dysbiosis. However, the correlation between CKD severity and gut microbiota and/or their uremic metabolites is unclear. We enrolled 103 CKD patients with stage 1 to 5 and 46 healthy controls. We analyzed patients' gut microbiota by MiSeq system and measured the serum concentrations of four uremic metabolites (p-cresyl sulfate, indoxyl sulfate, p-cresyl glucuronide, and trimethylamine N-oxide) by liquid chromatography-tandem mass spectrometry. Serum concentrations of the uremic metabolites increased with kidney function deterioration. Gut microbial diversity did not differ among the examined patient and control groups. In moderate or higher stage CKD groups, Oscillibacter showed positive interactions with other microbiota, and the proportions of Oscillibacter were positively correlated with those of the uremic metabolites. The gut microbiota, particularly Oscillibacter, was predicted to contribute to pyruvate metabolism which increased with CKD progression. Relative abundance of Oscillibacter was significantly associated with both serum uremic metabolite levels and kidney function. Predicted functional analysis suggested that kidney-function-associated changes in the contribution of Oscillibacter to pyruvate metabolism in CKD may greatly affect the gut environment according to kidney function, resulting in dysbiosis concomitant with uremic toxin production. The gut microbiota could be associated with uremia progression in CKD. These results may provide basis for further metagenomics analysis of kidney diseases.

    PubMed IF 4.7 신장내과
30. 1262020

    제1저자 박진주 · 교신저자 조구영

    Park JJ, Mebazaa A, Hwang IC, Park JB, Park JH, Cho GY

    Phenotyping Heart Failure According to the Longitudinal Ejection Fraction Change: Myocardial Strain, Predictors, and Outcomes.

    J Am Heart Assoc. 2020;9(12):e015009.

    Abstract

    Background Many patients with heart failure (HF) experience changes in left ventricular ejection fraction (LVEF) during follow-up. We sought to evaluate the predictors and outcomes of different HF phenotypes according to longitudinal changes in EF. Methods and Results A total of 2104 patients with acute HF underwent echocardiography at baseline and follow-up. Global longitudinal strain was measured at index admission. HF phenotypes were defined as persistent HF with reduced EF (persistent HFrEF, LVEF ≤40% at baseline and follow-up), heart failure with improved ejection fraction (LVEF≤40% at baseline and improved to >40% at follow-up), heart failure with declined ejection fraction (LVEF>40% at baseline and declined to ≤40% at follow up), and persistent HF with preserved EF (persistent HFpEF, LVEF>40% at baseline and follow-up). Overall, 1130 patients had HFrEF at baseline; during follow-up, 54.2% and 46.8% had persistent HFrEF and heart failure with improved ejection fraction, respectively. Among 975 patients with HFpEF at baseline, 89.5% and 10.5% had persistent HFpEF and heart failure with declined ejection fraction at follow-up, respectively. The 5-year all-cause mortality rates were 43.1%, 33.1%, 24%, and 17% for heart failure with declined ejection fraction, persistent HFrEF, persistent HFpEF, and heart failure with improved ejection fraction, respectively (global log-rank P<0.001). In multivariable analyses, each 1% increase in global longitudinal strain (greater contractility) was associated with 10% increased odds for heart failure with improved ejection fraction among patients with HFrEF at baseline and 7% reduced odds for heart failure with declined ejection fraction among patients with HFpEF at baseline. Conclusions LVEF changed during follow-up. Each HF phenotype according to longitudinal LVEF changes has a distinct prognosis. Global longitudinal strain can be used to predict the HF phenotype. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03513653.

    PubMed IF 6 순환기내과

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