SCI 발표논문

1. 26382018

   제1저자 김낙현 · 교신저자 박완범,김홍빈

   Kim NH, Park WB^*, Cho JE, Choi YJ, Choi SJ, Jun SY, Kang CK, Song KH, Choe PG, Bang JH, Kim ES, Park SW, Kim NJ, Oh MD, Kim HB^*

   Effects of Phage Endolysin SAL200 Combined with Antibiotics on Staphylococcus aureus Infection.

   Antimicrob Agents Chemother. 2018;62(10):AAC.00731-18.

   Abstract

   Phages and their derivatives are increasingly being reconsidered for use in the treatment of bacterial infections due to the rising rates of antibiotic resistance. We assessed the antistaphylococcal effect of the endolysin SAL200 in combination with standard-of-care (SOC) antibiotics. The activity of SAL200 when it was combined with SOC antibiotics was assessed in vitro by checkerboard and time-kill assays and in vivo with murine bacteremia and Galleria mellonella infection models. SAL200 reduced the SOC antibiotic MICs and showed a ≥3-log₁₀-CFU/ml reduction of Staphylococcus aureus counts within 30 min in time-kill assays. Combinations of SAL200 and SOC antibiotics achieved a sustained decrease of >2 log₁₀ CFU/ml. SAL200 significantly lowered the blood bacterial density within 1 h by >1 log₁₀ CFU/ml in bacteremic mice (P < 0.05 versus untreated mice), and SAL200 and SOC antibiotic combinations achieved the lowest levels of bacteremia. The bacterial density in splenic tissue at 72 h postinfection was the lowest in mice treated with SAL200 and SOC antibiotic combinations. SAL200 combined with SOC antibiotics also improved Galleria mellonella larva survival at 96 h postinfection. The combination of the phage endolysin SAL200 with SOC antistaphylococcal antibiotics showed synergistic effects in vitro and in vivo The combination of SAL200 with SOC antibiotics could help in the treatment of difficult-to-treat S. aureus infections.

   PubMed IF 4.2 감염내과
2. 26372018

   제1저자 이주연 · 교신저자 송영욱

   Lee JY, Kang MJ, Choi JY, Park JS, Park JK, Lee EY, Lee EB, Pap T, Yi EC, Song YW

   Apolipoprotein B binds to enolase-1 and aggravates inflammation in rheumatoid arthritis.

   Ann Rheum Dis. 2018;77(10):1480-1489.

   Abstract

   OBJECTIVE Immune cells from patients with rheumatoid arthritis (RA) express more enolase-1 (ENO1) on their surface than those from healthy subjects, and they elicit an enhanced inflammatory response. This study is aimed to identify the ligands of ENO1 that could promote inflammatory loops in vitro and enhance the arthritis severity in vivo.

   METHODS ENO1-binding proteins in RA synovial fluid were identified by mass spectromety, and affinity to ENO1 was evaluated by means of a ligand blotting and binding assay, surface plasmon resonance and confocal microscopy. Proinflammatory response by the interaction between ENO1 and apolipoprotein B (apoB) was tested in vitro and in vivo using peripheral blood mononuclear cells and a K/BxN serum transfer arthritis model and low-density lipoproteins receptor (LDLR) knockout mice.

   RESULTS ApoB in the synovid fluid of patients with RA was identified as a specific ligand to ENO1 with a higher affinity than plasminogen, a known ENO1 ligand. ApoB binding to ENO1 on monocytes elicited the production of tumour necrosis factor-α, interleukins (IL)-1β and IL-6 through both p38 mitogen-activated protein kinase and NF-κB pathways. In the K/BxN serum transfer arthritis model, administration of apoB increased the production of proinflammatory cytokines and exaggerated arthritis severity. The severity of K/BxN serum transfer arthritis in LDLR knockout mice was comparable with wild-type mice.

   CONCLUSIONS A key component of atherogenic lipids, apoB, aggravated arthritis by potentiating the inflammatory response via its interaction with ENO1 expressed on the surface of immune cells. This suggests a novel mechanism by which lipid metabolism regulates chronic inflammation in RA.

   PubMed IF 24 류마티스내과
3. 26362018

   제1저자 채세현 · 교신저자 박경수

   Chae S^*, Kim SJ^*, Do Koo Y^*, Lee JH, Kim H, Ahn BY, Ha YC, Kim YH, Jang MG, Koo KH, Choi SH, Lim S, Park YJ, Jang HC, Hwang D, Lee SW, Park KS

   A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles.

   Exp Mol Med. 2018;50(9):1-14.

   Abstract

   The pathogenesis of type 2 diabetes mellitus (T2DM) is closely associated with mitochondrial functions in insulin-responsive tissues. The mitochondrial proteome, compared with the mitochondrial genome, which only contains 37 genes in humans, can provide more comprehensive information for thousands of mitochondrial proteins regarding T2DM-associated mitochondrial functions. However, T2DM-associated protein signatures in insulin-responsive tissues are still unclear. Here, we performed extensive proteome profiling of mitochondria from skeletal muscles in nine T2DM patients and nine nondiabetic controls. A comparison of the mitochondrial proteomes identified 335 differentially expressed proteins (DEPs) between T2DM and nondiabetic samples. Functional and network analyses of the DEPs showed that mitochondrial metabolic processes were downregulated and mitochondria-associated ER membrane (MAM) processes were upregulated. Of the DEPs, we selected two (NDUFS3 and COX2) for downregulated oxidative phosphorylation and three (CALR, SORT, and RAB1A) for upregulated calcium and protein transport as representative mitochondrial and MAM processes, respectively, and then confirmed their differential expression in independent mouse and human samples. Therefore, we propose that these five proteins be used as a potential protein profile that is indicative of the dysregulation of mitochondrial functions in T2DM, representing downregulated oxidative phosphorylation and upregulated MAM functions.

   PubMed IF 17.5 내분비대사내과
4. 26352019

   제1저자 강성호 · 교신저자 김범석,안용운

   Kang SH, Keam B, Ahn YO, Park HR, Kim M, Kim TM, Kim DW, Heo DS

   Inhibition of MEK with trametinib enhances the efficacy of anti-PD-L1 inhibitor by regulating anti-tumor immunity in head and neck squamous cell carcinoma.

   Oncoimmunology. 2019;8(1):e1515057.

   Abstract

   Major histocompatibility complex (MHC) class I downregulation is the primary immune evasion mechanism associated with failure in anti-PD-1/PD-L1 blockade therapies for cancer. Here, we examined the role of MEK signaling pathway inhibition in head and neck squamous cell carcinoma (HNSCC) both in vitro and in vivo. We found that trametinib, a small molecule inhibitor of MEK, significantly enhanced MHC class I and PD-L1 expression in human HNSCC cell lines, and this occurred via STAT3 activation. Trametinib also further upregulated the increase in CXCL9 and CXCL10 expression caused by IFN-γ in HNSCC cells, which is associated with T cell infiltration in tumor tissues. Finally, we evaluated the therapeutic efficacy of trametinib combined with an anti-PD-L1 monoclonal antibody in vivo, using SCCVII mouse syngeneic tumor model for HNSCC. While neither PD-L1 blockade nor trametinib treatment alone affected tumor growth, the combined therapy significantly delayed tumor growth. Our results indicate that in the combined therapy trametinib increases CD8⁺ T cell infiltration in the tumor site and upregulates antigen presentation, and this may be associated with enhanced PD-L1 blockade efficacy. Furthermore, our results suggest that this combination would therapeutically benefit patients with HNSCC.

   PubMed IF 5.503 혈액종양내과
5. 26342018

   제1저자 이선민 · 교신저자 김나영

   Lee SM, Kim N, Yoon H, Nam RH, Lee DH

   Microbial Changes and Host Response in F344 Rat Colon Depending on Sex and Age Following a High-Fat Diet.

   Front Microbiol. 2018;9:2236.

   Abstract

   Gut microbiota, an important component that affects host health, change rapidly and directly in response to altered diet composition. Recently, the role of diet-microbiome interaction on the development of colon cancer has been the focus of interest. Colon cancer occurs more frequently in an aged population, and in males. However, the effect of dietary changes on the gut microbiome has been studied mainly in young males, even though it may vary with age and sex. The aim of this study was to investigate microbial changes and host response in the colons of male and female 6-week-old (young) and 2-year-old (old) Fisher-344 rats exposed to a high-fat diet (HFD). Our results showed that exposure to HFD for 8 weeks decreased the species richness of microbiota (Chao1) and increased Firmicutes/Bacteroidetes ratio only in aged rats, and not in young rats. Sex differences underlying the alteration by HFD in the gut microbiome were observed in the microbiome of aged rats. For instance, the abundance ratio of Akkermansia muciniphila and Desulfovibrio spp. increased in response to HFD in young rats and female aged rats, but not in male aged rats. Histological inflammation and cell proliferation of colon mucosa (indexed by Ki67) were significantly increased by HFD even in young rats; aged rats showed significantly higher cell proliferation in the HFD group than in the control. The HFD-induced decrease of species richness and the increase in specific species (Desulfovibrio spp. and Clostridium lavalense), which produce carcinogenic compounds such as H₂S and N-nitroso compounds, were significantly correlated with Ki67 index. In colon mucosa, the concentration of myeloperoxidase was increased by HFD only in males, and not in females. In conclusion, the results suggest a link between HFD-induced gut dysbiosis (particularly the low species richness and high abundance ratios of Desulfovibrio spp. and C. lavalense) and cell proliferation of colon mucosa (indicated by Ki67 IHC). In addition, sex differences influence the response of gut microbiome to HFD particularly in old age. Such sex differences in the gut microbiota might be related to sex differences in inflammation in the colon mucosa.

   PubMed IF 5.8 소화기내과
6. 26332018

   제1저자 최윤진 · 교신저자 이동호

   Choi YJ, Lee DH, Han KD, Yoon H, Shin CM, Park YS, Kim N

   Is nonalcoholic fatty liver disease associated with the development of prostate cancer? A nationwide study with 10,516,985 Korean men.

   PLoS One. 2018;13(9):e0201308.

   Abstract

   BACKGROUND Growing evidence supports that prostate cancer (PCa) is a metabolic syndrome-related cancer, but the evidence is lacking regarding the association between nonalcoholic fatty liver disease (NAFLD) and PCa. We aimed to investigate whether PCa is related with NAFLD in Korean adults.

   METHODS Data from the National Health Insurance Corporation between 2009 and 2012 were analyzed using multivariate logistic regression method. NALFD was defined based on the fatty liver index (FLI) and hepatic steatosis index (HSI). Newly diagnosed PCa was identified using the claims data.

   RESULTS NAFLD based on FLI and HSI was identified in 2,002,375 (19%) and 2,629,858 (25%) of 10,516,985 subjects, respectively. Each FLI ≥ 60 and HSI ≥ 36 was independently associated with the development of PCa after adjusting for other confounders (hazard ratio (HR) 1.09, 95% CI: 1.06-1.12 and HR 1.19, 95% CI: 1.16-1.23). The association was more prominent among those who were older (FLI, ≥ 65 years old and HSI, ≥ 40 years old), were not currently smoking, were presently consuming alcohol (< 30g/day) and had null components of metabolic syndrome than each counterpart. Non-obese persons with NAFLD defined by HSI had a higher risk of developing PCa than those with body mass index > 25 Kg/m2.

   CONCLUSIONS NAFLD defined by FLI or HSI may help identify high-risk individuals for developing PCa particular in the elderly, even in the absence of obesity or metabolic syndrome. Future studies on this topic should necessarily be repeated based on ultrasonographic findings.

   PubMed IF 2.8 소화기내과
7. 26322018

   제1저자 윤혁 · 교신저자 이동호

   Yoon H, Lee DH, Lee YH, Jeong JC, Lee ST, Choi MG, Jeon SW, Shim KN, Baik GH, Kim JG, Moon JS, Sung IK, Lee SK, Rhee PL, Jung HY, Lee BE, Kim HS, Kim SG, Lee KM, Seong JK, Jang JS, Park JJ

   Efficacy and Safety of UI05MSP015CT in Functional Dyspepsia: A Randomized, Controlled Trial.

   Gut Liver. 2018;12(5):516-522.

   Abstract

   BACKGROUND/AIMS To evaluate the efficacy and safety of a controlled release, once-daily formulation of mosapride (UI05MSP015CT) in patients with functional dyspepsia (FD).

   METHODS Patients with FD were randomly assigned (1:1) to receive either UI05MSP015CT (15 mg once a day, study group) or mosapride (5 mg three times a day, control group) and corresponding placebo for 4 weeks. The primary endpoint was a change in the gastrointestinal symptom score (GIS) evaluated at enrollment and after 4 weeks. Secondary endpoints were changes in the Nepean Dyspepsia Index-Korean version (NDI-K), rate of satisfactory symptom relief, and rate of adverse events.

   RESULTS A total of 138 patients were enrolled (female, 73.9%; mean age, 44.0±15.4 years). After excluding patients who violated the study protocol, 59 and 58 patients from the study and control groups, respectively, were included in the per-protocol analysis. No difference was observed in drug compliance between the control and study groups (97.07%±4.52% vs 96.85%±6.05%, p=0.870). Changes in GIS scores were -9.69±6.44 and -10.01±5.92 in the study and control groups. The mean difference in GIS change between groups was 0.33 (95% confidence interval, -1.75 to 2.41), demonstrating non-inferiority of UI-05MSP015CT (p=0.755). The rate of satisfactory symptom relief was not different between the study and control groups (39.0% vs 56.9%, p=0.053). No differences in change in NDI-K score (14.3 vs 16.9, p=0.263) or rates of adverse events (12.9% vs. 4.4%, p=0.062) were observed between the study and control groups.

   CONCLUSIONS Once-daily mosapride is not inferior to conventional mosapride in efficacy and is safe in patients with FD.

   PubMed IF 4.1 소화기내과
8. 26312018

   제1저자 천재영,임종필 · 교신저자 김지원

   Chun J, Im JP, Kim JW, Lee KL, Choi CH, Kim H, Cheon JH, Ye BD, Kim YH, Kim YS, Jeen YT, Han DS, Kim WH, Kim JS

   Association of Perianal Fistulas with Clinical Features and Prognosis of Crohn's Disease in Korea: Results from the CONNECT Study.

   Gut Liver. 2018;12(5):544-554.

   Abstract

   BACKGROUND/AIMS The disease course and factors associated with poor prognosis in Korean patients with Crohn's disease (CD) have not been fully determined. The aim of this study was to explore potential associations between the clinical characteristics and long-term outcomes of CD and perianal fistulas in a Korean population.

   METHODS The retrospective Crohn's Disease Clinical Network and Cohort (CONNECT) study enrolled patients diagnosed with CD between July 1982 and December 2008 from 32 hospitals. Those followed for ＜12 months were excluded. Clinical outcomes were CD-related surgery and complications, including nonperianal fistulas, strictures, and intra-abdominal abscesses.

   RESULTS The mean follow-up period was 8.77 years (range, 1.0 to 25.8 years). A total of 1,193 CD patients were enrolled, of whom 465 (39.0%) experienced perianal fistulas. Perianal fistulizing CD was significantly associated with younger age, male gender, CD diagnosed at primary care clinics, and ileocolonic involvement. Both nonperianal fistulas (p=0.034) and intra-abdominal abscesses (p=0.020) were significantly more common in CD patients with perianal fistulas than in those without perianal fistulas. The rates of complicated strictures and CD-related surgery were similar between the groups. Independently associated factors of nonperianal fistulas were perianal fistulas (p=0.015), female gender (p=0.048), CD diagnosed at referral hospital (p=0.003), and upper gastrointestinal (UGI) involvement (p=0.001). Furthermore, perianal fistulas (p=0.048) and UGI involvement (p=0.012) were independently associated with the risk of intra-abdominal abscesses.

   CONCLUSIONS Perianal fistulas predicted the development of nonperianal fistulas and intra-abdominal abscesses in Korean CD patients. Therefore, patients with perianal fistulizing CD should be carefully monitored for complicated fistulas or abscesses.

   PubMed IF 4.1 소화기내과
9. 26302018

   제1저자 이민종 · 교신저자 김윤준

   Lee M, Chang Y, Oh S, Cho YY, Jung DE, Kim HH, Nam JY, Cho H, Cho EJ, Lee JH, Yu SJ, Yi NJ, Lee KW, Lee DH, Lee JM, Yoon JH, Suh KS, Kim YJ

   Assessment of the Surveillance Interval at 1 Year after Curative Treatment in Hepatocellular Carcinoma: Risk Stratification.

   Gut Liver. 2018;12(5):571-582.

   Abstract

   BACKGROUND/AIMS Guidelines recommend surveillance for hepatocellular carcinoma (HCC) recurrence at 3-month intervals during the first year after curative treatment and 6-month intervals thereafter in all patients. This strategy does not reflect individual risk of recurrence. We aimed to stratify risk of recurrence to optimize surveillance intervals 1 year after treatment.

   METHODS We retrospectively analyzed 1,316 HCC patients treated with resection/radiofrequency ablation at Barcelona Clinic Liver Cancer stage 0/A. In patients without 1-year recurrence under 3-monthly surveillance, a new model for recurrence was developed using backward elimination methods: training (n=582)/validation cohorts (n=291). Overall survival (OS) according to risk stratified by the new model was compared according to surveillance intervals: 3-monthly versus 6-monthly (n=401) after lead time bias correction and propensity-score matching analyses.

   RESULTS Among patients without 1-year recurrence, age and international normalized ratio values were significant factors for recurrence (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00 to 1.03; p=0.009 and HR, 5.63; 95% CI, 2.24 to 14.18; p<0.001; respectively). High-risk patients stratified by the new model showed significantly higher recurrence rates than low-risk patients in the validation cohort (HR, 1.73; 95% CI, 1.18 to 2.53; p=0.005). After propensity-score matching between the 3-monthly and 6-monthly surveillance groups, OS in high-risk patients under 3-monthly surveillance was significantly higher than that under 6-monthly surveillance (p=0.04); however, OS in low-risk patients under 3-monthly surveillance was not significantly different from that under 6-monthly surveillance (p=0.17).

   CONCLUSIONS In high-risk patients, 3-monthly surveillance can prolong survival compared to 6-monthly surveillance. However, in low-risk patients, 3-monthly surveillance might not be beneficial for survival compared to 6-monthly surveillance.

   PubMed IF 4.1 소화기내과
10. 26292018

    제1저자 이윤빈,남준열 · 교신저자 이정훈

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

    Differential Effect of HCV Eradication and Fibrosis Grade on Hepatocellular Carcinoma and All-cause Mortality.

    Sci Rep. 2018;8(1):13651.

    Abstract

    Whether a sustained virological response (SVR) improves long-term outcomes in chronic hepatitis C patients with earlier-stage fibrosis has not been established. We investigated the differential effect of SVR on the risk of outcomes according to hepatic fibrosis grade. Fibrosis grade was categorised using FIB-4: <1.45, low-probability of significant fibrosis; 1.45-3.25, intermediate-probability; and ≥3.25, high-probability. Primary and secondary endpoints were hepatocellular carcinoma (HCC) occurrence and death, respectively. Among 1,373 included chronic hepatitis C patients, 744 patients were treated with interferon-based or -free regimens and 622 (83.6%) achieved SVR. SVR was independently associated with lower risk of HCC (vs. untreated: adjusted hazard ratio [aHR], 0.165; 95% confidence interval [CI], 0.077-0.350; P < 0.001) and overall death (vs. untreated; aHR, 0.146; 95% CI, 0.050-0.424; P < 0.001) during the median observation of 3.5 (interquartile range, 1.9-6.6) years. The SVR group had significantly lower risk of HCC than the untreated group among patients with intermediate-probability (n = 492: aHR, 0.171; 95% CI, 0.051-0.578; P = 0.004) and high-probability (n = 446: aHR, 0.243; 95% CI, 0.107-0.551; P < 0.001) of significant fibrosis. HRs were maintained after balancing with inverse probability weighting. SVR was associated with reduced risk of HCC development and all-cause mortality in patients with chronic hepatitis C.

    PubMed IF 4.9 소화기내과
11. 26282018

    제1저자 이지현 · 교신저자 강시혁

    Lee JH, Kim SH, Kang SH, Cho JH, Cho Y, Oh IY, Yoon CH, Lee HY, Youn TJ, Chae IH, Kim CH

    Blood Pressure Control and Cardiovascular Outcomes: Real-world Implications of the 2017 ACC/AHA Hypertension Guideline.

    Sci Rep. 2018;8(1):13155.

    Abstract

    The 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline lowered the threshold defining hypertension and treatment target from 140/90 mmHg to 130/80 mmHg. We compared the 2017 ACC/AHA guideline and the Eighth Joint National Committee (JNC8) report with regard to the current status of hypertension using the Korean National Health and Nutrition Examination Survey. The association between blood pressure (BP) control and long-term major cardiovascular outcomes (MACEs) was analyzed using the Korea National Health Insurance Service cohort. In the cross-sectional study with 15,784 adults, the prevalence of hypertension was expected to be 49.2 ± 0.6% based on the definition suggested by the 2017 ACC/AHA guideline versus 30.4 ± 0.6% based on the JNC8 report. In a longitudinal analysis with 373,800 hypertensive adults for the median follow-up periods of 11.0 years, the adults meeting the target goal BP goal of 2017 ACC/AHA guideline were associated with 21% reduced risk of MACEs compared with adults, not meeting 2017 ACC/AHA BP goal but meeting JNC8 target goal. In conclusion, substantial increase of prevalence of hypertension is expected by the 2017 ACC/AHA guideline. This study also suggests endorsing the aggressive approach would lead to an improvement in cardiovascular care.

    PubMed IF 4.9 순환기내과
12. 26272018

    제1저자 박흥우 · 교신저자 박흥우

    Park HW, Kim SH, Chang YS, Kim SH, Jee YK, Lee AY, Jang IJ, Park HS, Min KU

    The Fas Signaling Pathway Is a Common Genetic Risk Factor for Severe Cutaneous Drug Adverse Reactions Across Diverse Drugs.

    Allergy Asthma Immunol Res. 2018;10(5):555-561.

    Abstract

    PURPOSE Human leukocyte antigen (HLA) has been recognized as the most important genetic risk factor for severe cutaneous adverse drug reactions (SCARs) caused by certain drugs. However, cumulated observations suggest the presence of genetic risk factors for SCARs other than drug-specific HLA. We aimed to identify a common genetic risk factor of SCARs across multiple drugs.

    METHODS We performed 2 independent genome-wide association studies (GWASs). A total of 68 and 38 subjects with a diagnosis of SCAR were enrolled in each GWAS. Their allele frequencies were compared to those of healthy subjects in Korea.

    RESULTS No single nucleotide polymorphism (SNP) with genome-wide significance was found in either GWAS. We next selected and annotated the 200 top-ranked SNPs from each GWAS. These 2 sets of annotated genes were then entered into the web interface of ConsensusPathDB for a pathway-level analysis. The Fas signaling pathway was significantly over-represented in each gene set from the 2 GWASs.

    CONCLUSIONS Our observations suggest that the Fas signaling pathway may be a common genetic risk factor for SCARs across multiple drugs.

    PubMed IF 4.3 알레르기내과
13. 26262018

    제1저자 이승표 · 교신저자 Marco Perez

    Lee SP, Ashley EA, Homburger J, Caleshu C, Green EM, Jacoby D, Colan SD, Arteaga-Fernández E, Day SM, Girolami F, Olivotto I, Michels M, Ho CY, Perez MV, SHaRe Investigators

    Incident Atrial Fibrillation Is Associated With MYH7 Sarcomeric Gene Variation in Hypertrophic Cardiomyopathy.

    Circ Heart Fail. 2018;11(9):e005191.

    Abstract

    Background Although atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM) patients, the relationship between genetic variation and AF has been poorly defined. Characterizing genetic subtypes of HCM and their associations with AF may help to improve personalized medical care. We aimed to investigate the link between sarcomeric gene variation and incident AF in HCM patients. Methods and Results Patients from the multinational Sarcomeric Human Cardiomyopathy Registry were followed for incident AF. Those with likely pathogenic or pathogenic variants in sarcomeric genes were included. The AF incidence was ascertained by review of medical records and electrocardiograms at each investigative site. One thousand forty adult HCM patients, without baseline AF and with likely pathogenic or pathogenic variation in either MYH7 (n=296), MYBPC3 (n=659), or thin filament genes (n=85), were included. Compared with patients with variation in other sarcomeric genes, those with MYH7 variants were younger on first clinical encounter at the Sarcomeric Human Cardiomyopathy Registry site and more likely to be probands than the MYBPC3 variants. During an average follow-up of 7.2 years, 198 incident AF events occurred. Patients with likely pathogenic or pathogenic mutations in MYH7 had the highest incidence of AF after adjusting for age, sex, proband status, left atrial size, maximal wall thickness, and peak pressure gradient (hazard ratio, 1.7; 95% CI, 1.1-2.6; P=0.009). Conclusions During a mean follow-up of 7.2 years, new-onset AF developed in 19% of HCM patients with sarcomeric mutations. Compared with other sarcomeric genes, patients with likely pathogenic or pathogenic variation in MYH7 had a higher rate of incident AF independent of clinical and echocardiographic factors.

    PubMed IF 8.3 순환기내과
14. 26252018

    제1저자 안창호 · 교신저자 정혜승

    Ahn CH, Jang JY, Lee SO, Yoon JW, Kim SW, Park KS, Jung HS

    Liver transaminase levels after intraportal autologous islet transplantation after partial pancreatectomy were associated with long-term metabolic outcomes.

    Diabetes Res Clin Pract. 2018;143:232-238.

    Abstract

    AIMS To investigate the changes of post-procedural liver transaminase levels after autologous islet transplantation (ITx), and their associations with glycemic outcomes.

    METHODS Non-diabetic patients who underwent distal pancreatectomy for benign tumors were enrolled. Islets isolated from the healthy part of the resected pancreas were transplanted via the portal vein. Metabolic parameters were evaluated in the subjects for 5 years.

    RESULTS Eight patients completed the study and four developed postoperative diabetes mellitus (PODM). Disposition index (DI) at postoperative 1 year showed prominent difference between the patients who develop PODM or not: DI was preserved in the PODM-free patients (49.7 ± 4.5 to 70.8 ± 14.4, P = 0.182), while it significantly decreased in the PODM patients (69.3 ± 9.9 to 28.5 ± 3.9, P = 0.019). The preoperative liver transaminase levels were not different between the two groups. However, transient increase in liver transaminase levels during the first week after ITx was observed only in the PODM patients, and their peak values demonstrated significant negative correlation with the changes in DI (r = -0.774 for alanine transaminase, r = -0.759 for aspartate transaminase; P < 0.05).

    CONCLUSIONS Elevation of serum transaminases after ITx could be one of the factors determining insulin secretion and PODM.

    PubMed IF 4.6 내분비대사내과
15. 26242018

    제1저자 고동진 · 교신저자 송영욱

    Go DJ, Lee JY, Kang MJ, Lee EY, Lee EB, Yi EC, Song YW

    Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis, predicts the development of proteinuric flare.

    Lupus. 2018;27(10):1600-1615.

    Abstract

    Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Conventional biomarkers for assessing renal disease activity are imperfect in predicting clinical outcomes associated with LN. The aim of this study is to identify urinary protein biomarkers that reliably reflect the disease activity or predict clinical outcomes. A quantitative proteomic analysis was performed to identify protein biomarker candidates that can differentiate between SLE patients with and without LN. Selected biomarker candidates were further verified by enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE patients ( n = 121) to investigate their predictive values for LN activity measure. Furthermore, the association between urinary levels of a selected panel of potential biomarkers and prognosis of LN was assessed with a four-year follow-up study of renal outcomes. Urinary vitamin D-binding protein (VDBP), transthyretin (TTR), retinol binding protein 4 (RBP4), and prostaglandin D synthase (PTGDS) were significantly elevated in SLE patients with LN, especially in patients with active LN ( n = 21). Among them, VDBP well correlated with severity of proteinuria (rho = 0.661, p < 0.001) and renal SLE Disease Activity Index (renal SLEDAI) (rho = 0.520, p < 0.001). In the four-year follow-up, VDBP was a significant risk factor (hazard ratio 9.627, 95% confidence interval 1.698 to 54.571, p = 0.011) for the development of proteinuric flare in SLE patients without proteinuria ( n = 100) after adjustments for multiple confounders. Urinary VDBP correlated with proteinuria and renal SLEDAI, and predicted the development of proteinuria.

    PubMed IF 1.8 류마티스내과
16. 26232018

    제1저자 문신제 · 교신저자 박영주

    Moon S, Kim MJ, Yu JM, Yoo HJ, Park YJ

    Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies.

    Thyroid. 2018;28(9):1101-1110.

    Abstract

    OBJECTIVES To determine the impact of subclinical hypothyroidism (SCH) on the risk of cardiovascular disease (CVD) and all-cause mortality, a comprehensive meta-analysis was performed according to the age or coexisting CVD risk status of the participants.

    METHODS Studies regarding the association of SCH with all-cause mortality from PubMed and Embase databases were included. The pooled relative risk (RR) of CVD and all-cause mortality was calculated using the Mantel-Haenszel method. A subgroup analysis of participants with high CVD risk was conducted, including history of coronary, cerebral, or peripheral artery disease; dilated cardiomyopathy; heart failure; atrial fibrillation; venous thromboembolism; diabetes mellitus; or chronic kidney disease.

    RESULTS In total, 35 eligible articles incorporating 555,530 participants were included. SCH was modestly associated with CVD and all-cause mortality (RR for CVD = 1.33 [confidence interval (CI) 1.14-1.54]; RR for all-cause mortality = 1.20 [CI 1.07-1.34]). However, the association was not observed in participants aged ≥65 years. Subgroup analysis showed that participants with SCH and high CVD risk showed a significantly higher risk of all-cause mortality (RR for CVD = 2.20 [CI 1.28-3.77]; RR for all-cause mortality = 1.66 [CI 1.41-1.94]), whereas those with SCH and low CVD risk did not. Additional subgroup analysis of six studies with a mean participant age of ≥65 years and high CVD risk showed a significant high risk of all-cause mortality in the SCH group (RR = 1.41 [CI 1.08-1.85]; I² = 0%).

    CONCLUSIONS SCH is associated with an increased CVD risk and all-cause mortality, particularly in participants with high CVD risk.

    PubMed IF 6.6 내분비대사내과
17. 26222018

    제1저자 김정 · 교신저자 김상균

    Kim J, Kim SG, Chung H, Lim JH, Choi JM, Park JY, Yang HJ, Han SJ, Oh S, Kim MS, Kim HJ, Hong H, Lee HJ, Kim JL, Lee E, Jung HC

    Clinical efficacy of endoscopic ultrasonography for decision of treatment strategy of gastric cancer.

    Surg Endosc. 2018;32(9):3789-3797.

    Abstract

    BACKGROUND Accurate preoperative tumor staging of gastric cancer is indispensable with expansion of indications for laparoscopic surgery and endoscopic resection. It is important to distinguish mucosal cancer (T1a) in smaller lesion and differentiate early gastric cancer (EGC) in larger lesion considering endoscopic resection indication and laparoscopic surgery indication. We evaluated the clinical outcomes of endoscopic ultrasonography (EUS) for the decision of treatment strategy of gastric cancer compared with pathological staging.

    METHODS The patients who underwent EUS and surgical or endoscopic resection for gastric cancer were retrospectively reviewed between September 2005 and February 2016. The depth of tumor invasion (T staging) by EUS was compared with the pathological staging after endoscopic or surgical resection.

    RESULTS A total of 6084 patients were finally analyzed. The accuracy rates for T1a and EGC were 75.0 and 89.4%, respectively. The overall accuracy of T staging by EUS was 66.3% when divided by T1a, T1b, and over T2. The accuracy of EUS prior to endoscopic resection was 75.1% in absolute indication and 73.1% in expanded criteria, respectively. The accuracy rates for T1a with lesion ≤ 2 cm in miniprobe EUS and EGC with lesion > 2 cm in conventional EUS were 84.6 and 83.2%, respectively. In multivariate analysis, presence of ulcer, large tumor size, and radial EUS were associated with overestimation, and small tumor size and miniprobe were associated with underestimation in T staging.

    CONCLUSIONS EUS showed the high accuracy of 84.6% for T1a in lesion ≤ 2 cm in miniprobe EUS and 83.2% for EGC in lesion > 2 cm in conventional EUS, respectively. EUS can be a complementary diagnostic method to determine endoscopic or surgical treatment modality.

    PubMed IF 3.3 소화기내과
18. 26212018

    제1저자 백우현 · 교신저자 이상협

    Paik WH, Lee SH, Ahn DW, Jeong JB, Kang JW, Son JH, Ryu JK, Kim YT

    Optimal time of resuming anticoagulant after endoscopic sphincterotomy in patients at risk for thromboembolism: a retrospective cohort study.

    Surg Endosc. 2018;32(9):3902-3908.

    Abstract

    BACKGROUND One major adverse event of endoscopic sphincterotomy (EST) is bleeding, which could be more common and severe in patients receiving anticoagulant therapy. However, the cessation of anticoagulants for long periods could lead to thromboembolic events. We aimed to evaluate the optimal timing of resumption of anticoagulants after EST in patients at risk for thromboembolism.

    MATERIALS AND METHODS From January 2010 through October 2017, a retrospective cohort at risk for thromboembolism who had taken warfarin and bridging therapy with heparin around EST from three tertiary hospitals in South Korea was investigated. The primary outcome was to compare the incidence of post-EST delayed bleeding according to the resumption time of anticoagulant. The secondary outcome was to investigate any thromboembolic adverse events related to interruption of the anticoagulant.

    RESULTS A total of 96 patients (46 males and 50 females; median age 75 years [range, 24-91 years]) were enrolled. Overall, the patient numbers of very early (< 24 h), early (24-48 h), and late resumption (> 48 h) of anticoagulant after EST were 56, 23, and 17, respectively. The baseline characteristics were similar between groups except resumption time of anticoagulant. There was no significant difference in the rate of post-EST delayed bleeding (5% in very early group vs. 9% in early group vs. 0 in late group, p = 0.47). The rate of thromboembolic adverse events was significantly higher in the late resumption of anticoagulant group (0 vs. 0 vs. 24%, p < 0.001).

    CONCLUSION There was no significant difference in the incidence of post-EST delayed bleeding according to the resuming time of anticoagulant. Since long cessation of anticoagulant could increase the risk of thrombotic adverse events, the early resumption of anticoagulant seems to be preferred.

    PubMed IF 3.3 소화기내과
19. 26202018

    제1저자 백선하 · 교신저자 진호준

    Baek SH, Kim S, Na KY, Kim S, Chin HJ

    Predialysis hyponatremia and mortality in elderly patients beginning to undergo hemodialysis.

    Korean J Intern Med. 2018;33(5):970-979.

    Abstract

    BACKGROUND/AIMS Predialysis hyponatremia has been recently reported to be associated with mortality in incident hemodialysis patients. However, whether hyponatremia is associated with unfavorable outcomes in elderly patients remains unknown. We hypothesized that nephrology referral inf luences hyponatremia, and aimed to define how nephrology referral affects the association between hyponatremia and mortality in the elderly.

    METHODS We retrospectively assessed mortality in 599 incident hemodialysis patients aged ≥ 70 at a tertiary university hospital, between 2000 and 2010. We analyzed 90-day and 1-year all-cause mortality (ACM) in relation to predialysis serum sodium (sNa). We divided the patients into two groups according to predialysis glucose-corrected sNa: hyponatremia (< 135 mmol/L) and normonatremia (135 to 145 mmol/L).

    RESULTS Low estimated glomerular filtration rate, high phosphorus, low albumin, nonpreparation of arteriovenous fistula or graft, and late referral were associated with a low sNa in the elderly. Among 599 patients, 106 and 174 patients died at the 90-day and 1-year follow-ups, respectively. Each 10-mmol/L increase in predialysis sNa tended to be associated with lower 90-day and 1-year ACM. When patients were stratified by nephrology referral, hyponatremia was associated with increased mortality in early referral group (90-day ACM: hazard ratio [HR] = 2.335, p = 0.041; 1-year ACM: HR = 1.790, p = 0.024). However, hyponatremia was not associated with mortality in late referral group.

    CONCLUSION Predialysis hyponatremia at hemodialysis initiation is associated with late referra.

    PubMed IF 2.2 신장내과
20. 26192018

    제1저자 남궁석 · 교신저자 김윤준

    Namgoong S, Shin JG, Cheong HS, Kim LH, Kim JO, Seo JY, Shin HD, Kim YJ

    Genetic association of complement component 2 variants with chronic hepatitis B in a Korean population.

    Liver Int. 2018;38(9):1576-1582.

    Abstract

    BACKGROUND & AIMS Numerous single nucleotide polymorphisms associated with an increased risk of liver diseases, chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma have been identified. In this study, we scrutinized the genetic effects of C2 variants, which were conflicting in previous results, on the risk of chronic hepatitis B in a Korean population.

    METHODS We genotyped 22 common C2 genetic variants of 977 chronic hepatitis B cases including 302 chronic hepatitis B-related hepatocellular carcinoma cases and 785 population controls. Statistical analysis was performed to examine the effects of genotype on the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma.

    RESULTS Logistic regression analyses showed that six C2 single nucleotide polymorphisms had significant associations with the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma among the Korean subjects. Stepwise analysis revealed that causal markers (rs9267665 and rs10947223) were identified among the C2 variants (stepwise P = 3.32 × 10^-9 and 2.04 × 10^-5 respectively). In further conditional analysis with previous chronic hepatitis B-associated loci, these two single nucleotide polymorphisms were independently associated with the risk of chronic hepatitis B. In addition, we investigated the ability of genetic risk scores combining 12 multi-chronic hepatitis B loci to predict the risk of chronic hepatitis B. Individuals with higher genetic risk scores showed increased risk for chronic hepatitis B.

    CONCLUSIONS Our results suggested that the C2 gene might be a susceptibility locus for chronic hepatitis B in Korean populations. The cumulative genetic effects may contribute to future etiological explanations for chronic hepatitis B.

    PubMed IF 6.2 소화기내과
21. 26182018

    제1저자 김경희 · 교신저자 김형관

    Kim KH, Kim HK, Chan SY, Kim YJ, Sohn DW

    Hemodynamic and Histopathologic Benefits of Early Treatment with Macitentan in a Rat Model of Pulmonary Arterial Hypertension.

    Korean Circ J. 2018;48(9):839-853.

    Abstract

    BACKGROUND AND OBJECTIVES Macitentan (MAC) reduces morbidity and mortality among advanced-stage pulmonary arterial hypertension (PAH) patients. However, data regarding the histopathologic and hemodynamic benefits of MAC treatment at an early stage of PAH is lacking.

    METHODS One week after monocrotaline (MCT) injection, rats were randomly assigned to MAC (n=16), MAC combined with sildenafil (SIL) (MAC+SIL, n=16), or normal saline (MCT, n=16). Twelve sham rats (Sham) were included for comparison. Right ventricular (RV) systolic function was assessed via echocardiography as the RV fractional area change (RV-FAC). An invasive pressure-volume analysis using a Millar conductance catheter was performed 7 weeks after MCT injection. Rats were subsequently euthanized for histopathologic analysis.

    RESULTS RV-right atrial pressure gradient on echocardiography was significantly increased 3 weeks after MCT injection, but was maintained in the Sham. RV-FAC was less deteriorated in the MAC, compared to that in the MCT (44±3% vs. 25±7%, p<0.05), and the co-administration of SIL showed no additional benefit (45±8%, p>0.05 vs. the MAC). On invasive hemodynamic analyses, RV end-systolic (196±78 μL) and end-diastolic volumes (310±86 μL), pulmonary artery systolic pressure (89±7.2 mmHg), and end-systolic pressure-volume relationship (-254±25.1) were significantly worse in the MCT vs. in the MAC (101±45 μL, 235±55 μL, 40±10.5 mmHg, and -145±42.1, respectively) and MAC+SIL (109±47 μL, 242±46 μL, 38±9.2 mmHg, and -151±39.2, respectively) (all p<0.05). However, the MAC and MAC+SIL did not differ (all p>0.05). On histopathology, both RV and lung fibrosis were significantly reduced in the MAC and MAC+SIL vs. in the MCT (all p<0.05); the 2 treatment groups did not differ.

    CONCLUSIONS MAC treatment at an earlier stage significantly attenuated experimental PAH progression hemodynamically and histopathologically.

    PubMed IF 3.4 순환기내과
22. 26172018

    제1저자 허자윤,이희승 · 교신저자 이상협,방승민

    Heo JY^*, Lee HS^*, Son JH, Lee SH, Bang S

    Clinical Outcomes of Bilateral Stent-in-Stent Placement Using Self-Expandable Metallic Stent for High-Grade Malignant Hilar Biliary Obstruction.

    Yonsei Med J. 2018;59(7):827-833.

    Abstract

    PURPOSE Endoscopic bile duct decompression using bilateral self-expandable metallic stents (SEMSs) deployed via a stent-in-stent (SIS) method is considered a preferred procedure for malignant hilar biliary obstruction (MHBO). However, occlusion thereof occurs frequently. Here, we investigated stent patency duration and risk factors related to stent obstruction with bilateral SIS placement for MHBO at two large centers.

    MATERIALS AND METHODS The present study reviewed data on patients with MHBO who underwent endoscopic biliary drainage using the SIS method. Clinical outcomes, including stent patency duration and patient overall survival, were analyzed. Factors associated with stent patency were evaluated using Cox proportional hazards models.

    RESULTS Seventy patients with MHBO underwent endoscopic biliary drainage using the SIS method. Median age was 68 years old, and median follow-up duration was 140 days (interquartile range, 57-329). The proportion of high-grade MHBOs (Bismuth type IV) was 57.1%. Median stent patency duration with the SIS method was 108 days according to Kaplan-Meier curves. Median patient survival analyzed by the Kaplan-Meier method was 181 days. Multivariate analysis indicated that higher baseline bilirubin (> 6.1 mg/dL) as an independent risk factor related to stent patency (p<0.05).

    CONCLUSION In endoscopic biliary decompression using SEMS placed with the SIS method, obstructive jaundice was a risk factor for stent patency. The SIS method for high-grade MHBO showed short stent patency.

    PubMed IF 3.1 소화기내과
23. 26162018

    제1저자 곽수헌 · 교신저자 박경수

    Kwak SH, Chae J, Lee S, Choi S, Koo BK, Yoon JW, Park JH, Cho B, Moon MK, Lim S, Cho YM, Moon S, Kim YJ, Han S, Hwang MY, Cho YS, Lee MS, Jang HC, Kang HM, Park T, Cho NH, Kim K, Kim JI, Park KS

    Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in an East Asian Population.

    Diabetes. 2018;67(9):1892-1902.

    Abstract

    We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In silico replication was conducted for seven nonsynonymous variants in an additional 13,122 participants. Single-variant and gene-based association tests for T2D were analyzed. A total of 728,838 variants were identified by whole-exome sequencing. Among nonsynonymous variants, PAX4 Arg192His increased risk of T2D and GLP1R Arg131Gln decreased risk of T2D in genome-wide significance (odds ratio [OR] 1.48, P = 4.47 × 10^-16 and OR 0.84, P = 3.55 × 10^-8, respectively). Another variant at PAX4 192 codon Arg192Ser was nominally associated with T2D (OR 1.62, P = 5.18 × 10^-4). In T2D patients, PAX4 Arg192His was associated with earlier age at diagnosis, and GLP1R Arg131Gln was associated with decreased risk of cardiovascular disease. In control subjects without diabetes, the PAX4 Arg192His was associated with higher fasting glucose and GLP1R Arg131Gln was associated with lower fasting glucose and HbA_1c level. Gene-based analysis revealed that SLC30A8 was most significantly associated with decreased risk of T2D (P = 1.0 × 10^-4). In summary, we have identified nonsynonymous variants associated with risk of T2D and related phenotypes in Koreans.

    PubMed IF 9.3 내분비대사내과
24. 26152018

    제1저자 이예지 · 교신저자 이은봉

    Lee YJ, Park JA, Kwon H, Choi YS, Jung KC, Park SH, Lee EB

    Role of Stem Cell-Like Memory T Cells in Systemic Lupus Erythematosus.

    Arthritis Rheumatol. 2018;70(9):1459-1469.

    Abstract

    OBJECTIVE Stem cell-like memory T (Tscm) cells are long-lived memory T cells that have multipotent capacity to differentiate into different subsets. However, the role of Tscm cells in autoimmune diseases remains unclear. Here, we performed phenotypic studies to identify Tscm cells in patients experiencing systemic lupus erythematosus (SLE).

    METHODS CD4+ and CD8+ Tscm cells were identified in SLE patients and healthy controls (HCs). In in vitro culture systems, CD4+ Tscm cells were induced to differentiate into subsets of T cells, including follicular helper T (Tfh) cells, and cytokine production patterns were assessed after stimulation. After confirming induction of transcription factors for Tfh cells, the capacity of CD4+ Tscm-derived Tfh cells to help B cells was analyzed by measuring antibody secretion.

    RESULTS The percentages of CD4+ and CD8+ Tscm cells among the naive CD4+/CD8+ or total CD4+ T cell populations were significantly higher in SLE patients than in HCs. Stimulated Tscm cells from SLE patients could replenish themselves and differentiate into other T lymphocyte subsets, including Tfh cells upon stimulation with T cell receptor. Production of T cell factor 1, which is an inducer of Tfh, was also increased. The differentiated Tfh cells increased antibody production by autologous B cells.

    CONCLUSION Taken together, these findings suggest that Tscm cells play a role in the pathogenesis of SLE by maintaining Tfh cells.

    PubMed IF 9.9 류마티스내과
25. 26142018

    제1저자 양민석 · 교신저자 강혜련

    Yang MS, Kang DY, Seo B, Park HJ, Park SY, Kim MY, Park KH, Koo SM, Nam YH, Kim S, Jung JW, Kim TB, Jang GC, Yang HJ, Ahn YM, Park JW, Kang HR, Drug Allergy Work Group of KAAACI

    Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

    Allergy. 2018;73(9):1833-1841.

    Abstract

    BACKGROUND Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests.

    METHODS In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins.

    RESULTS We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06).

    CONCLUSIONS The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

    PubMed IF 11.3 알레르기내과
26. 26132018

    제1저자 최지민 · 교신저자 김상균

    Choi JM, Kim SG, Choi J, Park JY, Oh S, Yang HJ, Lim JH, Im JP, Kim JS, Jung HC

    Effects of Helicobacter pylori eradication for metachronous gastric cancer prevention: a randomized controlled trial.

    Gastrointest Endosc. 2018;88(3):475-485.e2.

    Abstract

    BACKGROUND AND AIMS Whether eradication of Helicobacter pylori reduces the incidence of metachronous gastric cancer (MGC) is still debatable. We aimed to evaluate the long-term effect of H pylori eradication on the development of MGC after endoscopic gastric tumor resection.

    METHODS We undertook an open-label, prospective, randomized controlled trial at a tertiary hospital in Seoul, Korea. Participants were recruited during April 2005 to February 2011 and followed until December 2016. We assigned 898 patients with H pylori infection treated with endoscopic resection (ER) for gastric dysplasia or early gastric cancer to receive (n =442) or not receive (n =456) eradication therapy using a random-number chart. Eradication group patients received oral omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for a week, whereas control group patients received no H pylori treatment. The primary outcome was the incidence of MGC (intention-to-treat analysis).

    RESULTS The 877 patients who attended ≥1 follow-up examination (eradication group, 437; control group, 440) were analyzed. Median follow-up was 71.6 months (interquartile range, 42.1-90.0). MGC developed in 18 (4.1%) eradication and 36 (8.2%) control group patients (log-rank test, P = .01). In our yearly analysis, the effect of eradication showed a significant difference in 5 years after allocation (log-rank test, P = .02). The adjusted hazard ratio for the control group was 2.02 (95% CI, 1.14-3.56; P = .02), compared with the eradication group.

    CONCLUSIONS H pylori eradication significantly reduces the incidence of MGC after ER of gastric tumors and should be considered for H pylori-positive gastric tumor patients treated with ER. (Clinical trial registration number: NCT01510730.).

    PubMed IF 8 소화기내과
27. 26122018

    제1저자 배재현 · 교신저자 조영민

    Bae JH, Kim LK, Min SH, Ahn CH, Cho YM

    Postprandial glucose-lowering effect of premeal consumption of protein-enriched, dietary fiber-fortified bar in individuals with type 2 diabetes mellitus or normal glucose tolerance.

    J Diabetes Investig. 2018;9(5):1110-1118.

    Abstract

    AIMS/INTRODUCTION Protein preload improves postprandial glycemia by stimulating secretion of insulin and incretin hormones. However, it requires a large dose of protein to produce a significant effect. The present study was carried out to investigate the postprandial glucose-lowering effect of a premeal protein-enriched, dietary fiber-fortified bar (PFB), which contains moderate amounts of protein, in individuals with type 2 diabetes mellitus or normal glucose tolerance (NGT).

    MATERIALS AND METHODS The participants (15 type 2 diabetes mellitus and 15 NGT) were randomly assigned to either a premeal or postmeal PFB group and underwent two mixed meal tolerance tests, 1 week apart in reverse order. Plasma levels of glucose, insulin, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide were measured.

    RESULTS During the mixed meal tolerance tests, the incremental area under the curve from 0 to 180 min of plasma glucose levels was lower with premeal PFB than with postmeal PFB in the type 2 diabetes mellitus (14,723 ± 1,310 mg min/dL vs 19,642 ± 1,367 mg min/dL; P = 0.0002) and NGT participants (3,943 ± 416 mg min/dL vs 4,827 ± 520 mg min/dL, P = 0.0296). In the type 2 diabetes mellitus participants, insulinogenic index and the incremental area under the curve from 0 to 180 min of plasma total glucagon-like peptide-1 levels were higher with premeal PFB than with postmeal PFB, but not in the NGT participants. There was no difference in postprandial glucose-dependent insulinotropic polypeptide levels between premeal and postmeal PFB in both groups.

    CONCLUSIONS Acute administration of premeal PFB decreased postprandial glucose excursion in both type 2 diabetes mellitus and NGT participants. In the type 2 diabetes mellitus participants, premeal PFB augmented the early-phase insulin secretion, possibly through enhancing glucagon-like peptide-1 secretion.

    PubMed IF 3.6 내분비대사내과
28. 26112018

    제1저자 송진화 · 교신저자 이창훈

    Song JH, Lee CH, Kim DK, Yoon H, Byun MK, Rhee CK, Lee J, Kim WJ, Hwang YI, Yoo KH, Jung KS

    Differences in prevalence of asthma-COPD overlap according to different criteria.

    Medicine (Baltimore). 2018;97(36):e12049.

    Abstract

    Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases. Overlap in the clinical features of these 2 diseases is observed in many cases, and thus, the concept of asthma-COPD overlap (ACO) has recently been proposed. However, the definition of ACO and the clinical significance remains to be determined.We evaluated the prevalence and risk of acute exacerbation in ACO among Korean COPD patients as defined by modified Spanish criteria and American Thoracic Society (ATS) Roundtable criteria.The prevalence of ACO was 47.7% (660/1383) by modified Spanish criteria and 1.9% (26/1383) by ATS Roundtable criteria. ACO, regardless of criteria, did not significant affect the exacerbation risk during at least 1-year follow-up period.Substantial discrepancies were found in the prevalence and outcome of ACO according to different diagnostic criteria, which would compromise implementation of ACO before the definition is established.

    PubMed IF 2 호흡기내과
29. 26102018

    제1저자 이경희 · 교신저자 유철규

    Lee KH, Jeong J, Woo J, Lee CH, Yoo CG

    Globular Adiponectin Exerts a Pro-Inflammatory Effect via IκB/NF-κB Pathway Activation and Anti-Inflammatory Effect by IRAK-1 Downregulation.

    Mol Cells. 2018;41(8):762-770.

    Abstract

    Adiponectin, a hormone produced by adipose tissue, is very abundant in plasma, and its anti- and pro-inflammatory effects are reported. However, the mechanisms of these pro- and anti-inflammatory effects are not fully defined. Herein, we evaluated the dual inflammatory response mechanism of adiponectin in macrophages. Short-term globular adiponectin (gAd) treatment induced IκBα degradation, NF-κB nuclear translocation, and TNF-α production in RAW 264.7 cells. Polymyxin B pretreatment did not block gAd-induced IκBα degradation, and heated gAd was unable to degrade IκBα, suggesting that the effects of gAd were not due to endotoxin contamination. gAd activated IKK and Akt, and inhibition of either IKK or Akt by dominant-negative IKKβ (DN-IKKβ) or DN-Akt overexpression blocked gAd-induced IκBα degradation, suggesting that short-term incubation with gAd mediates inflammatory responses by activating the IκB/NF-κB and PI3K/Akt pathways. Contrastingly, long-term stimulation with gAd induced, upon subsequent stimulation, tolerance to gAd, lipopolysaccharide, and CpG-oligodeoxynucleotide, which is associated with gAd-induced downregulation of IL-receptor-associated kinase-1 (IRAK-1) due to IRAK-1 transcriptional repression. Conclusively, our findings demonstrate that the pro- and anti-inflammatory responses to gAd in innate immune cells are time-dependent, and mediated by the activation of the IκB/NF-κB pathway, and IRAK-1 downregulation, respectively.

    PubMed IF 8.2 호흡기내과
30. 26092018

    제1저자 Bodokhsuren · 교신저자 오국환

    Tsogbadrakh B, Ju KD, Lee J, Han M, Koh J, Yu Y, Lee H, Yu KS, Oh YK, Kim HJ, Ahn C, Oh KH

    HL156A, a novel pharmacological agent with potent adenosine-monophosphate-activated protein kinase (AMPK) activator activity ameliorates renal fibrosis in a rat unilateral ureteral obstruction model.

    PLoS One. 2018;13(8):e0201692.

    Abstract

    BACKGROUND Renal fibrosis is characterized by excessive production and deposition of extracellular matrix (ECM), which leads to progressive renal failure. Adenosine-monophosphate-activated protein kinase (AMPK) is a highly conserved kinase that plays a key role in Smad-3 signaling. Here, we examined the effect of a novel AMPK activator, HL156A, on the inhibition of renal fibrosis in in vivo and in vitro models.

    METHODS Unilateral ureteral obstruction (UUO) was induced in male Wistar rats. Rats with UUO were administered HL156A (20mg/kg/day), and then the kidneys were harvested 10 days after ligation for further analysis.

    RESULTS In the rat UUO model, HL156A attenuated ECM protein deposition. After HL156A treatment, expressions of TGF-β1, p-Smad3, α-SMA, fibronectin, and type IV collagen were suppressed, and E-cadherin expression was up-regulated. In the in vitro experiment, NRK52E cells were treated with HL156A before TGF-β1 stimulation. The inhibitory effects of HL156A upon the signaling pathways and markers of the epithelial-to-mesenchymal transition (EMT) were analyzed. In TGF-β1-treated NRK-52E cells, HL156A co-treatment inhibited the TGF-β1-induced Smad3 signaling pathway and EMT markers.

    CONCLUSION Taken together, the above findings suggest that HL156A, a novel AMPK activator, ameliorates renal fibrosis in vivo and in vitro.

    PubMed IF 2.8 신장내과

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