SCI 발표논문

1. 352018

   제1저자 안창호 · 교신저자 조영민

   Ahn CH, Oh TJ, Kwak SH, Cho YM

   Sodium-glucose cotransporter-2 inhibition improves incretin sensitivity of pancreatic β-cells in people with type 2 diabetes.

   Diabetes Obes Metab. 2018;20(2):370-377.

   Abstract

   AIM To test the hypothesis that dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, improves β-cell responses to incretin hormones (or β-cell incretin sensitivity) by alleviating glucose toxicity in people with type 2 diabetes mellitus (T2DM).

   METHODS A total of 19 people with T2DM underwent a 3-hour hyperglycaemic clamp study with incretin infusion before and after 8-week treatment with dapagliflozin added to the background treatment. In addition, 10 people with normal glucose tolerance (NGT) underwent a single hyperglycaemic clamp study. The hyperglycaemic clamp was targeted at 15.5 mmol/L for 3 hours, with synthetic glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) infusion over a 60- to 180-minute and a 120- to 180-minute period, respectively.

   RESULTS Compared with baseline, the C-peptide response to GLP-1 (incremental area under the curve [iAUC] of C-peptide_{60-120 minutes} ) significantly increased (83.6 ± 42.1 to 106.6 ± 45.7 nmol/L × min; P = .011), and the C-peptide response to GIP/GLP-1 (iAUC of C-peptide_{120-180 minutes} ) tended to increase after dapagliflozin treatment (82.5 ± 58.4 to 101.9 ± 50.3 nmol/L × min; P = .087), whereas both the insulin responses to GLP-1 and GIP/GLP-1 increased significantly. First-phase C-peptide response, which reflects β-cell function, significantly increased after dapagliflozin treatment; however, all these improved values in the participants with T2DM were far lower than those in the participants with NGT. In addition, the improvement in insulin responses to hyperglycaemia was correlated with the improvement in insulin responses to incretin infusion.

   CONCLUSIONS Dapagliflozin improved β-cell responses to incretin hormones as well as glucose during the hyperglycaemic clamp in patients with inadequately controlled T2DM.

   PubMed IF 6.1 내분비대사내과
2. 342018

   제1저자 이신원, 송경호 · 교신저자 김홍빈

   Lee S, Song KH, Jung SI, Park WB, Lee SH, Kim YS, Kwak YG, Kim YK, Kiem SM, Kim HI, Kim ES, Park KH, Kim NJ, Jang HC, Kim HB, Korea INfectious Diseases (KIND) study group

   Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea.

   Clin Microbiol Infect. 2018;24(2):152-158.

   Abstract

   OBJECTIVES No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia.

   METHODS A prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics.

   RESULTS Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group.

   CONCLUSIONS Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.

   PubMed IF 8.7 감염내과
3. 332018

   제1저자 양효준 · 교신저자 김상균

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

   Surveillance strategy according to age after endoscopic resection of early gastric cancer.

   Surg Endosc. 2018;32(2):846-854.

   Abstract

   BACKGROUND Whether surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) differs in young patients is unclear. This study aimed to evaluate the risk of metachronous and extragastric recurrence in young patients with EGC after curative ESD.

   METHODS We retrospectively enrolled 1237 consecutive patients who underwent curative ESD for EGC from 2005 to 2014 at a single tertiary hospital. The patients were divided into group 1 (<50 years of age, n = 86), group 2 (age 50-74, n = 985), or group 3 (≥75 years of age, n = 166). The clinical characteristics and outcomes were compared among the three age groups.

   RESULTS Group 1 had more frequent Helicobacter pylori infection (P < 0.001), less frequent intestinal metaplasia (P = 0.021), and more frequent undifferentiated tumors (P = 0.039). Although the 5-year risk of developing metachronous recurrence appeared to be lower in group 1 (2.7%) than in groups 2 (8.6%) or 3 (8.7%), the risk became quite similar at the 7-year follow-up (6.4, 12.7, and 8.7% for groups 1, 2, and 3, respectively; P = 0.409 by log-rank test). Extragastric recurrences developed in only 2 cases in group 2 (0.2%).

   CONCLUSIONS Surveillance for metachronous and extragastric recurrence after curative ESD in patients <50 years of age should not be different from that in patients ≥50 years of age. Endoscopic surveillance for metachronous recurrence should be continued for longer than 5 years, even in young patients.

   PubMed IF 3.3 소화기내과
4. 322018

   제1저자 고동진 · 교신저자 송영욱

   Go DJ, Shin K, Baek HJ, Kang SW, Kang YM, Jun JB, Lee YJ, Park SH, Song YW

   Pivotal factors for successful withdrawal of nonsteroidal anti-inflammatory drugs in rheumatoid arthritis patients in remission or with low-disease activity.

   Clin Rheumatol. 2018;37(2):307-314.

   Abstract

   The purpose of this study is to examine the patient-reported outcomes (PRO) after discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical factors associated with a favorable outcome in patients with rheumatoid arthritis (RA) in remission or with low-disease activity (LDA). A 16-week prospective open-label trial was conducted at eight rheumatology clinics in Korea. RA patients with 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) < 3.2 who were on NSAIDs for more than a month were enrolled, and NSAIDs were discontinued. Acetaminophen (AAP) was used as the rescue medication, and NSAIDs were restarted when joint pain was intolerable with AAP. The endpoint was to analyze the group of patients who continued to withdraw NSAIDs. Among 109 enrolled patients, 105 completed the 16-week follow-up. Eighty-nine (84.8%) patients remained without restarting NSAIDs. In these patients, there was a slight increase in their pain levels compared with baseline (median 14.0 versus 19.0 using the pain-visual analog scale, p = 0.010). However, changes in DAS28-ESR (p = 0.638) and routine assessment of patient index data 3 (RAPID-3) (p = 0.128) were insignificant. Moreover, 66 (62.9%) patients showed sustained effectiveness on PRO without restarting NSAIDs. In the multivariate regression models, joint swelling was the detrimental factor in NSAID withdrawal (odds ratio [OR] 0.149, 95% confidence interval [CI] 0.033-0.680, p = 0.014) and sustained effectiveness (OR 0.284, 95% CI 0.091-0.883, p = 0.030). Joint pain in RA patients in remission or with LDA can be well managed without NSAIDs, especially in those without swollen joints at the time of cessation.

   PubMed IF 2.7 류마티스내과
5. 312018

   제1저자 주세경 · 교신저자 김원

   Joo SK, Kim W, Kim D, Kim JH, Oh S, Lee KL, Chang MS, Jung YJ, So YH, Lee MS, Bae JM, Kim BG

   Steatosis severity affects the diagnostic performances of noninvasive fibrosis tests in nonalcoholic fatty liver disease.

   Liver Int. 2018;38(2):331-341.

   Abstract

   BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of heterogeneous metabolic subtypes. This study compared the diagnostic performances of noninvasive fibrosis tests in predicting advanced fibrosis among patients with NAFLD and examined the effects of the subgroups on their diagnostic performances.

   METHODS Three hundred fifteen patients with biopsy-proven NAFLD were prospectively enrolled. Acoustic radiation force impulse imaging (ARFI) was performed to obtain liver stiffness measurements (LSMs). The aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis 4 index (FIB-4), NAFLD fibrosis score (NFS) and BARD score were calculated. The diagnostic performances of noninvasive fibrosis tests were evaluated using the area under the receiver operating characteristic curve (AUROC).

   RESULTS Fibrosis 4 index (FIB-4) showed the highest AUROC for advanced fibrosis (0.866; 95% CI, 0.811-0.922). AUROC subgroup analyses were performed to assess the effects of the subgroups on diagnostic performance. For patients with advanced fibrosis, the APRI, BARD, FIB-4 and NFS AUROCs were significantly different among the radiological steatosis grades. Additionally, the AUROC of ARFI tended to decrease with increasing radiological steatosis severity. FIB-4 and NFS showed significantly lower AUROCs for advanced fibrosis in obese NAFLD than in nonobese NAFLD (P = .002 and P < .001 respectively). However, only radiological steatosis severity was independently associated with advanced fibrosis in multivariable analysis.

   CONCLUSIONS Steatosis severity may affect the diagnostic performances of noninvasive fibrosis tests in patients with NAFLD. The application of different tools should be tailored for various NAFLD subgroups to optimize noninvasive fibrosis assessments.

   PubMed IF 6.2 소화기내과
6. 302018

   제1저자 박찬순 · 교신저자 최의근

   Park CS, Choi EK, Han KD, Lee HJ, Rhee TM, Lee SR, Cha MJ, Lim WH, Kang SH, Oh S

   Association between adult height, myocardial infarction, heart failure, stroke and death: a Korean nationwide population-based study.

   Int J Epidemiol. 2018;47(1):289-298.

   Abstract

   BACKGROUND The association between adult height and cardiovascular (CV) events and mortality has been suggested, albeit inconsistently. We sought to discover the comprehensive relationship between height, CV-related morbidity and all-cause death according to age.

   METHODS We investigated the association between adult height and myocardial infarction (MI), heart failure (HF), stroke incidence and mortality in 16 528 128 Korean patients who underwent regular health check-ups (2005-08). Height was stratified by decile according to age (20-39 years, 40-59 years and ≥60 years) and gender.

   RESULTS During a 9-year follow-up period, 590 346 participants died and 232 093 were admitted to hospital for MI, 201 411 for HF and 267 566 for stroke. An inverse relationship between height and MI, HF, stroke and all-cause death was observed in the overall cohort analysis. The association was unchanged after adjusting for CV risk and behavioural and adulthood socioeconomic factors. Both male and female sex showed an inverse relationship with height in adulthood, CV events and mortality. Adult height showed an inverse association in all CV events and mortality, especially in the older groups (≥40 years). In a subgroup analysis of body mass index, there was an inverse relationship between height, CV events and mortality in each group.

   CONCLUSIONS Shorter height in adulthood was strongly related to an increased risk of MI, HF, stroke and all-cause death. A suitable environment and appropriate nutrition early in life could influence adult height and eventually reduce the risk of CV events and mortality.

   PubMed IF 5.7 순환기내과
7. 292018

   제1저자 황영재 · 교신저자 김나영

   Hwang YJ, Kim N, Lee HS, Lee JB, Choi YJ, Yoon H, Shin CM, Park YS, Lee DH

   Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years.

   Aliment Pharmacol Ther. 2018;47(3):380-390.

   Abstract

   BACKGROUND Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial.

   AIM To evaluate the reversibility of atrophic gastritis and intestinal metaplasia by H. pylori eradication with long-term follow-up.

   METHODS 598 subjects were prospectively enrolled and followed for up to 10 years. They were categorised as H. pylori-negative (n = 65), H. pylori non-eradicated (n = 91), and H. pylori-eradicated (n = 442). Histological assessment was performed for antrum and corpus by Sydney classification.

   RESULTS Histological follow-up was performed regularly at 1, 2, 3-4 and ≥5 years, with mean follow-up of 1.07 ± 0.21, 2.29 ± 0.83, 3.93 ± 1.02, and 6.45 ± 1.28 years, respectively. Atrophic gastritis in antrum and corpus gradually and significantly (both P < .05 for all timepoints) improved only in the H. pylori-eradicated group compared to that at baseline. Significant difference in atrophic gastritis between H. pylori-eradicated and H. pylori-negative groups disappeared from 1-year follow-up. Similarly, intestinal metaplasia in antrum and corpus improved significantly (both P < .05 for all timepoints) only in the H. pylori-eradicated group in comparison with that at baseline. Significant difference in intestinal metaplasia between H. pylori-eradicated and H. pylori-negative groups disappeared from ≥5 years of follow-up in the antrum and from 3 years of follow-up in the corpus.

   CONCLUSION H. pylori eradication may be a preventative strategy for intestinal-type gastric cancer by regression of atrophic gastritis and intestinal metaplasia.

   PubMed IF 6.8 소화기내과
8. 282018

   제1저자 윤창환 · 교신저자 김효수

   Yoon CH, Kim TW, Koh SJ, Choi YE, Hur J, Kwon YW, Cho HJ, Kim HS

   Gata6 in pluripotent stem cells enhance the potential to differentiate into cardiomyocytes.

   BMB Rep. 2018;51(2):85-91.

   Abstract

   Pluripotent stem cell (PSC) variations can cause significant differences in the efficiency of cardiac differentiation. This process is unpredictable, as there is not an adequate indicator at the undifferentiated stage of the PSCs. We compared global gene expression profiles of two PSCs showing significant differences in cardiac differentiation potential. We identified 12 up-regulated genes related to heart development, and we found that 4 genes interacted with multiple genes. Among these genes, Gata6 is the only gene that was significantly induced at the early stage of differentiation of PSCs to cardiomyocytes. Gata6 knock-down in PSCs decreased the efficiency of cardiomyocyte production. In addition, we analyzed 6 mESC lines and 3 iPSC lines and confirmed that a positive correlation exists between Gata6 levels and efficiency of differentiation into cardiomyocytes. In conclusion, Gata6 could be utilized as a biomarker to select the best PSC lines to produce PSC-derived cardiomyocytes for therapeutic purposes. [BMB Reports 2018; 51(2): 85-91].

   PubMed IF 4.1 순환기내과
9. 272018

   제1저자 신동엽 · 교신저자 윤성수

   Shin DY, Lee JH, Park S, Lee JO, Moon JH, Ahn JS, Choi Y, Song IC, Shin HJ, Lee WS, Lee HS, Yoon SS

   Role of thymoglobulin in matched sibling allogeneic hematopoietic stem cell transplantation with busulfan and fludarabine conditioning in myeloid malignanicies.

   Bone Marrow Transplant. 2018;53(2):207-212.

   Abstract

   In vivo T-cell depletion using anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis of GvHD. We investigated the influence of thymoglobulin dose (an ATG) on GvHD following matched sibling donor (MSD) HSCT with a busulfan and fludarabine preparative regimen. Medical records of 180 patients who received MSD HSCT with a conditioning regimen of busulfan, fludarabine, and ATG (BuFluATG) were reviewed retrospectively. The median age was 53 years (range 18-68). Initial diagnoses were acute myeloid leukemia (73.3%) and myelodysplastic syndrome (26.7%). Forty-four and 68 patients (24.4 and 37.7%) experienced acute and chronic GvHD of any grade, respectively. High-dose (⩾4.5 mg/kg) ATG was independently associated with decreased risk of acute GvHD (hazard ratio=0.36, 95% confidence interval (CI): 0.15-0.84, P=0.019) compared to low-dose ATG (<4.5 mg/kg). Although ATG dose was associated with the risk of acute GvHD, it was not associated with the risk of chronic GvHD in our study. A higher dose (⩾4.5 mg/kg) of ATG decreases the risk of acute GvHD but had no significant impact on disease-free survival in MSD HSCT patients conditioned with BuFluATG. The optimal dose of ATG should be further investigated in a large prospective study context.

   PubMed IF 5.1 혈액종양내과
10. 262018

    제1저자 양효준 · 교신저자 김상균

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

    Novel risk stratification for metachronous recurrence after curative endoscopic submucosal dissection for early gastric cancer.

    Gastrointest Endosc. 2018;87(2):419-428.e3.

    Abstract

    BACKGROUND AND AIMS This study stratified the risk of developing metachronous gastric cancer (MGC) after curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) to enable customization of endoscopic surveillance for MGC.

    METHODS A total of 1115 patients who underwent curative ESD based on the expanded criteria for differentiated EGC from 2005 to 2014 at a single tertiary hospital were enrolled in this retrospective cohort study. They were followed up with annual endoscopy for a median of 50.1 months. Helicobacter pylori and histologic intestinal metaplasia (IM) were evaluated. The Kaplan-Meier method and Cox regression analysis were used for risk stratification.

    RESULTS Three risk groups were identified: group 1 comprised patients with a synchronous neoplasm; group 2 comprised male patients with corpus IM; and group 3 comprised male patients without corpus IM or female patients. The 5- and 7-year cumulative risks (95% confidence interval [CI]) for metachronous recurrence were 15.1% (95% CI, 7.7-22.5) and 26.1% (95% CI, 14.9-37.3), respectively, in group 1; 5.6% (95% CI, 3.1-8.1) and 9.3% (95% CI, 5.4-13.2), respectively, in group 2; and 3.8% (95% CI, 1.6-6.0) and 4.9% (95% CI, 2.4-7.4), respectively, in group 3 (P < .001 by log-rank test). The incidence of MGCs increased constantly even after 5 years in groups 1 and 2 but not in group 3. There was not enough evidence to show an association between H pylori eradication and metachronous recurrence in the data.

    CONCLUSIONS Meticulous annual endoscopic surveillance for MGC for more than 5 years is recommended for patients with synchronous neoplasm. Endoscopic surveillance may also be extended beyond 5 years in male patients with corpus IM.

    PubMed IF 8 소화기내과
11. 252018

    제1저자 오국환 · 교신저자 나기영

    Oh KH, Baek SH, Joo KW, Kim DK, Kim YS, Kim S, Oh YK, Han BG, Chang JH, Chung W, Na KY, Control of fluid balance guided by body composition monitoring in patients on peritoneal dialysis (COMPASS) study

    Does Routine Bioimpedance-Guided Fluid Management Provide Additional Benefit to Non-Anuric Peritoneal Dialysis Patients? Results from COMPASS Clinical Trial.

    Perit Dial Int. 2018;38(2):131-138.

    Abstract

    INTRODUCTION In peritoneal dialysis (PD) patients, volume overload is related to cardiac dysfunction and mortality, while intravascular volume depletion is associated with a rapid decline in the residual renal function (RRF). This study sought to determine the clinical usefulness of bioimpedance spectroscopy (BIS)-guided fluid management for preserving RRF and cardiac function in PD patients.

    SUBJECTS AND METHODS This is a multicenter, prospective, open-label study that was conducted over a 1-year period (NCT01887262). Non-anuric (urine volume > 500 mL/day) subjects on PD were enrolled. Subjects in the control group received fluid management based on the clinical information alone. Those in the BIS group received BIS-guided fluid management along with clinical information.

    RESULTS The subjects (N = 137, mean age 51.3 ± 12.8 years, 54% male) were randomly assigned to the BIS group (n = 67) or to the control group (n = 70). There were no significant differences between the 2 groups with regard to age, sex ratio, cause of kidney failure, duration of PD, baseline comorbidity, RRF, PD method, or peritoneal transport type. At baseline, the 2 groups were not different in terms of RRF (glomerular filtration rate [GFR], 5.1 ± 2.9 vs 5.5 ± 3.7 mL/min/1.73 m²). After follow-up, changes in the GFR between the 2 groups were not different (-1.5 ± 2.4 vs -1.3 ± 2.6 mL/min/1.73 m², p = 0.593). Over the 1-year study period, both groups maintained stability of various fluid status parameters. Between the 2 groups, there were no differences in the net change of various fluid status parameters such as overhydration (OH) and extracellular water/total body water (ECW/TBW). A net change in ECW over 1 year was slightly but significantly higher in the control group (net increase, 0.57 ± 1.27 vs 0.05 ± 1.63 L, p = 0.047). However, this difference was not translated into an improvement in RRF in the BIS group. There were no differences in echocardiographic parameters or arterial stiffness at the end of follow-up.

    CONCLUSION Routine BIS-guided fluid management in non-anuric PD patients did not provide additional benefit in volume control, RRF preservation, or cardiovascular (CV) parameters. However, our study cannot be generalized to the whole PD population. Further research is warranted in order to investigate the subpopulation of PD patients who may benefit from routine BIS-guided fluid management.

    PubMed IF 1.8 신장내과
12. 242018

    제1저자 이성우 · 교신저자 오국환

    Lee SW, Han SH, Yoo TH, Chung W, Park SK, Chae DW, Ahn C, Oh KH

    Relationship between brachial-ankle and heart-femoral pulse wave velocities and the rapid decline of kidney function.

    Sci Rep. 2018;8(1):821.

    Abstract

    The impact of brachial-ankle pulse wave velocity (baPWV) and heart-femoral pulse wave velocity (hfPWV) on rapid decline of estimated glomerular filtration rate (eGFR) has been inconclusive. The database of a multicenter prospective study of 2238 patients in Korea enrolled from 2011 to 2016 was reviewed. After excluding patients with missing baPWV (n = 257) and eGFR change (n = 180), the study included 1801 non-dialysis chronic kidney disease (CKD) patients. The eGFR change <-5ml/min/1.73 m²/year was defined as rapid decline. During a mean of 2.2 years, the mean eGFR change was -3.6 ml/min/1.73 m²/year, and 31.6% of patients were classified as having rapid decline. Older age, causes of CKD, increased heart rate, systolic blood pressures, and proteinuria were associated with the highest baPWV quintile. In multivariate logistic regression analyses, the odds of a rapid decline in eGFR was 1.9 times higher in the fifth quintile than in the first quintile (P = 0.013). In a subset with baPWV and hfPWV (n = 1182), high baPWV was associated with rapid eGFR decline only when accompanied by a high hfPWV. These findings suggest that central and peripheral PWVs may simultaneously affect rapid eGFR decline.

    PubMed IF 4.9 신장내과
13. 232018

    제1저자 이재우 · 교신저자 이상협

    Lee JW, Kim YT, Lee SH, Son JH, Kang JW, Ryu JK, Jang DK, Paik WH, Lee BS

    Tumor Marker Kinetics as Prognosticators in Patients with Unresectable Gallbladder Adenocarcinoma Undergoing Palliative Chemotherapy.

    Gut Liver. 2018;12(1):102-110.

    Abstract

    BACKGROUND/AIMS To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy.

    METHODS One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates.

    RESULTS Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases ＞10-fold were considered to have progressive disease, whereas individuals with increases ＞3-fold were likely to benefit from early imaging follow-up.

    CONCLUSIONS CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy.

    PubMed IF 4.1 소화기내과
14. 222018

    제1저자 강지훈 · 교신저자 조영석

    Kang J, Kim YC, Park JJ, Kim S, Kang SH, Cho YJ, Yoon YE, Oh IY, Yoon CH, Suh JW, Cho YS, Youn TJ, Chae IH, Choi DJ

    Increased epicardial adipose tissue thickness is a predictor of new-onset diabetes mellitus in patients with coronary artery disease treated with high-intensity statins.

    Cardiovasc Diabetol. 2018;17(1):10.

    Abstract

    BACKGROUND Statins are widely used for lipid lowering in patients with coronary artery disease (CAD), but increasing evidence indicates an association between statin use and new-onset of diabetes mellitus (NODM). Epicardial adipose tissue (EAT) refers to the visceral fat surrounding the heart, which is associated with metabolic diseases. We sought to determine the association between EAT thickness and NODM in CAD patients treated with high-intensity statins.

    METHODS We conducted a retrospective medical record review of CAD patients treated with high-intensity statins for at least 6 months after percutaneous coronary intervention performed between January 2009 and June 2013 at Seoul National University Bundang Hospital. EAT thickness was measured by echocardiography using standardized methods.

    RESULTS A total of 321 patients were enrolled, who received high-intensity statins for a mean of 952 days; atorvastatin 40 mg in 204 patients (63.6%), atorvastatin 80 mg in 57 patients (17.8%), and rosuvastatin 20 mg in 60 patients (18.7%). During the follow-up period of 3.9 ± 1.7 years, NODM occurred in 40 patients (12.5%). On Cox proportional-hazard regression analysis, EAT thickness at systole [for each 1 mm: hazard ratio (HR) 1.580; 95% confidence interval (CI) 1.346-1.854; P < 0.001] and prediabetes at baseline (HR 4.321; 95% CI 1.998-9.349; P < 0.001) were the only independent predictors of NODM. Using binary cutoff values derived from the receiver operating characteristic curve analysis, EAT thickness at systole larger than 5.0 mm had an HR of 3.402 (95% CI 1.751-6.611, P < 0.001), sensitivity of 52.5%, and specificity of 80.8% for predicting NODM. Also, patients with EAT thickness ≥ 5 mm and prediabetes at baseline had a 12.0-times higher risk of developing NODM compared to the risk noted in patients with EAT thickness < 5 mm and normal glucose tolerance at baseline.

    CONCLUSION Epicardial adipose tissue thickness at systole is a consistent independent predictor of NODM in patients with CAD treated with high-intensity statins. Such predictors may help physicians plan adequate surveillance for early detection of NODM.

    PubMed IF 15.6 순환기내과
15. 212018

    제1저자 조재영 · 교신저자 이창훈

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

    Clinical Outcome of Eosinophilic Airway Inflammation in Chronic Airway Diseases Including Nonasthmatic Eosinophilic Bronchitis.

    Sci Rep. 2018;8(1):146.

    Abstract

    We enrolled patients with confirmed sputum eosinophilia who had visited our tertiary referral hospital between 2012 and 2015. We evaluated the incidence and predictors of exacerbations in patients with nonasthmatic eosinophilic bronchitis (NAEB), and investigated predictors of improvement in eosinophilic inflammation in chronic airway diseases with or without persistent airflow limitation. In total, 398 patients with sputum eosinophilia were enrolled. Of these, 152 (38.2%) had NAEB. The incidence rate of exacerbations requiring treatment with antibiotics, systemic corticosteroids, or hospital admission was 0.13 per patient-year (95% CI, 0.06-0.19) in NAEB. Inhaled corticosteroid (ICS) did not affect the risk of exacerbations, even in an analysis of propensity score. One hundred seventy-six patients had chronic airway diseases; in 37 of these (21.0%), sputum eosinophilia had improved at the 1-year follow-up. Patients who had persistent airflow limitation were less likely to show an improvement in eosinophilic inflammation (aOR, 0.26; 95% CI, 0.09-0.77) when they were treated with ICSs for less than 75% of the follow-up days. Exacerbations requiring systemic corticosteroids, antibiotics, or hospitalization did occur, although infrequently, in NAEB patients. Among patients with chronic airway diseases, those with persistent airflow limitation were less likely to show an improvement in eosinophilic airway inflammation.

    PubMed IF 4.9 호흡기내과
16. 202018

    제1저자 박종한 · 교신저자 김효수

    Park J, Hwang I, Kim SJ, Youn SW, Hur J, Kim HS

    Atorvastatin prevents endothelial dysfunction in high glucose condition through Skp2-mediated degradation of FOXO1 and ICAM-1.

    Biochem Biophys Res Commun. 2018;495(2):2050-2057.

    Abstract

    OBJECTIVE The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin has been reported to exert vasculo-protective action in diabetes. We investigated the vasculo-protective mechanism of atorvastatin by evaluating its effect on two major pathogenic molecules, FOXO1 and ICAM1, mediated by S-phase kinase-associated protein 2 (Skp2) in diabetic endothelial dysfunction. APPROACH AND RESULTS: [1] FOXO1: Hyperglycemic condition increased FOXO1 protein level in endothelial cells, which was reversed by atorvastatin. This atorvastatin effect was obliterated by treatment of protease inhibitor, suggesting that atorvastatin induces degradation of FOXO1. Immunoprecipitation showed that atorvastatin facilitated the binding of Skp2 to FOXO1, leading to ubiquitination and degradation of FOXO1. [2] ICAM-1: Increased ICAM1 in high glucose condition was reduced by atorvastatin. But this effect of atorvastatin was obliterated when Skp2 was inhibited, suggesting that atorvastatin enhances binding of Skp2 to ICAM1 leading to degradation. Actually, ubiquitination and degradation of ICAM-1 were reduced when Skp2 was inhibited. In vitro monocyte adhesion assay revealed that atorvastatin reduced monocyte adhesion on endothelial cells in high glucose condition, which was reversed by Skp2 knock-down.

    CONCLUSION Atorvastatin strengthens Skp2 binding to FOXO1 or ICAM1, leading to ubiquitination and degradation. Skp2-dependent ubiquitination of major pathogenic molecules is the key mechanism for statin's protective effect on endothelial function in diabetes.

    PubMed IF 2.5 순환기내과
17. 192018

    제1저자 이충섭 · 교신저자 김진욱

    Lee CS, Jung YJ, Kim SS, Cheong JY, Lee GR, Kim HG, Kim BH, Chung JW, Jang ES, Jeong SH, Lee KH, Kim JW

    Liver volume-based prediction model stratifies risks for hepatocellular carcinoma in chronic hepatitis B patients on surveillance.

    PLoS One. 2018;13(1):e0190261.

    Abstract

    BACKGROUND AND AIM The aim of this study was to determine whether dynamic computed tomography (CT)-measured liver volume predicts the risk of hepatocellular carcinoma (HCC) when the CT scans do not reveal evidence of HCC in chronic hepatitis B (CHB) patients on surveillance.

    METHODS This retrospective multicentre cohort study included 1,246 patients who received entecavir and regular HCC surveillance in three tertiary referral centres in South Korea. Liver volumes were measured on portal venous phase CT images. A nomogram was developed based on Cox independent predictors and externally validated. Time-dependent receiver operating characteristic (ROC) analysis was performed for comparison with previous prediction models.

    RESULTS Patients who received dynamic CT studies during surveillance had significantly higher risk for HCC compared to patients without CT studies (hazard ratio [HR] = 3.1; p < 0.001). Expected/measured liver volume ratio was an independent predictor of HCC (HR = 4.2; p = 0.002) in addition to age, sex and cirrhosis. The nomogram based on the four predictors discriminated risks for HCC (HR = 4.1 and 6.0 in derivation and validation cohort, respectively, for volume score > 150; p < 0.001). Time-dependent ROC analysis confirmed better performance of the volume score compared to HCC prediction models with conventional predictors (integrated area under curve = 0.758 vs. 0.661-0.712; p < 0.05).

    CONCLUSIONS CT-measured liver volume is an independent predictor of future HCC, and nomogram-based liver volume score may stratify the risks of HCC in CHB patients who showed negative CT findings for HCC during surveillance.

    PubMed IF 2.8 소화기내과
18. 182018

    제1저자 김학령, 오소원 · 교신저자 조주희

    Kim HL, Oh SW, Lee H, Kim HJ, Kim YN, Lim WH, Seo JB, Kim SH, Kim MA, Zo JH

    Findings of Single-Photon Emission Computed Tomography and Its Relation with Quantitative Coronary Angiography in Patients with Significant Stenosis of the Left Main Coronary Artery.

    Korean J Radiol. 2018;19(1):101-110.

    Abstract

    OBJECTIVE Unrecognized left main coronary artery disease (LMCD) is often fatal; however, accuracy of non-invasive tests for diagnosing LMCD is still unsatisfactory. This study was performed to elucidate single-photon emission computed tomography (SPECT) detection of LMCD using quantitative coronary angiography (QCA) data.

    MATERIALS AND METHODS Fifty-five patients (39 men; mean age, 68.1 ± 10.9 years) diagnosed with significant left main (LM) stenosis (≥ 50%) by invasive coronary angiography (ICA) were retrospectively reviewed. All study patients underwent SPECT with pharmacologic stress within 30 days of ICA. All coronary lesions were quantified via QCA, and SPECT findings were compared with QCA results.

    RESULTS Only four patients (7.3%) had isolated LMCD; all others had combined significant stenosis (≥ 70%) of one or more other epicardial coronary arteries. Patients with more severe coronary artery disease tended to have higher values for summed difference scores in a greater number of regions, but the specific pattern was not clearly defined. Summed stress score of SPECT did not differ according to LM stenosis severity. Only three patients (5.4%) had a typical LM pattern of reversible perfusion defect on SPECT. A significant negative linear correlation between stenosis severity and stress perfusion percent was found in the left anterior descending artery region (r = -0.455, p < 0.001) but not in the left circumflex artery.

    CONCLUSION Single-photon emission computed tomography findings were heterogeneous, not specific and poorly correlated to QCA data in patients with significant LMCD. This may be due to highly prevalent significant stenosis of other epicardial coronary arteries.

    PubMed IF 6.1 순환기내과
19. 172018

    제1저자 김남주 · 교신저자 이근욱

    Kim N, Kim JW, Baek JH, Kim JS, Choung HK, Kim TY, Lee KH, Bang YJ, Khwarg SI, Ahn SH, Park DJ, Kim HH, Chung JY, Ahn S, Lee KW

    S-1-Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study.

    Cancer Res Treat. 2018;50(1):30-39.

    Abstract

    PURPOSE This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma.

    MATERIALS AND METHODS A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma.

    RESULTS Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (≥ 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma ≥ 22.3 ng/mL (median), CDHP concentration in plasma ≥ 42.0 ng/mL (median), and tegafur concentration in tears ≥ 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1-related non-hematologic toxicity more frequently than those without LDO (p=0.016).

    CONCLUSION LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.

    PubMed IF 4.2 혈액종양내과
20. 162018

    제1저자 이은봉 · 교신저자 이은봉

    Lee EB

    A review of sarilumab for the treatment of rheumatoid arthritis.

    Immunotherapy. 2018;10(1):57-65.

    Abstract

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting the peripheral diarthrodial joints. Sarilumab is a human monoclonal antibody against the IL-6 receptor-α. In Phase II and III clinical trials, sarilumab in the background of methotrexate showed superior clinical efficacy over placebo in RA patients with inadequate response to methotrexate or inadequate response or intolerance to TNF inhibitors. Sarilumab monotherapy also showed superior efficacy compared with adalimumab monotherapy in RA patients with inadequate response or intolerance to methotrexate. For safety, injection site reaction, neutropenia and elevation of liver enzymes and serum cholesterol were more commonly observed with sarilumab than with placebo. Overall, sarilumab is expected to serve as another useful antirheumatic drug against active RA.

    PubMed IF 2.3 류마티스내과
21. 152018

    제1저자 김원, 김동희 · 교신저자 김원, 김동희

    Kim D, Kim W, Joo SK, Bae JM, Kim JH, Ahmed A

    Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis.

    Clin Gastroenterol Hepatol. 2018;16(1):123-131.e1.

    Abstract

    BACKGROUND & AIMS Variations in level of thyroid-stimulating hormone (TSH) within the reference range of thyroid hormone could have negative health effects. We evaluated the effect of plasma TSH levels within the euthyroid range on the severity of histological damage associated with nonalcoholic fatty liver disease (NAFLD).

    METHODS We performed a cross-sectional study of 425 subjects with biopsy-proven NAFLD (mean age, 53 years; 52% male) who participated in the Boramae NAFLD study from January 2013 to January 2017. Each subject underwent an anthropometric assessment and laboratory and clinical evaluations. Of the subjects, 282 were assigned to a strict-normal thyroid function group (plasma level of TSH, 0.4 to 2.5 mIU/L). Patients with low thyroid function were assigned to groups of subclinical hypothyroidism (plasma level of TSH above 4.5 mIU/L with a normal thyroid hormone level; n = 59) or low-normal thyroid function (higher plasma TSH level [2.5 to 4.5 mIU/L] with a normal thyroid hormone level; n = 84). Multivariate logistic regression analysis was used to identify factors independently associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis.

    RESULTS NASH and advanced fibrosis were found in higher percentages of subjects with low thyroid function vs strict-normal thyroid function (52.4% vs 37.2% for NASH and 21.0% vs 10.6% for advanced fibrosis; P < .01). Among subjects with low thyroid function, a higher proportion of patients with subclinical hypothyroidism had NASH and associated advanced fibrosis vs patients with low-normal thyroid function (57.6% vs 48.8% for NASH and 25.4% vs 17.9% for advanced fibrosis; P < .01). Subjects with low thyroid function had more extensive hepatic steatosis with greater severity of balloon degeneration and fibrosis. In multivariate analyses, low thyroid function was significantly associated with NASH (odds ratio, 1.61; 95% CI, 1.04-2.50; P = .035) and advanced fibrosis (odds ratio, 2.23; 95% CI, 1.18-4.23; P = .014). Risks of NASH and advanced fibrosis increased significantly with plasma concentration of TSH (Ptrend <.05 for each).

    CONCLUSIONS Subclinical hypothyroidism and low-normal thyroid function are independent predictors of NASH and advanced fibrosis, confirming the relationship between these diseases. ClinicalTrials.gov, Number: NCT02206841.

    PubMed IF 16.2 소화기내과
22. 142018

    제1저자 이성우 · 교신저자 허남주

    Lee SW, Son JY, Kim JM, Hwang SS, Han JS, Heo NJ

    Body fat distribution is more predictive of all-cause mortality than overall adiposity.

    Diabetes Obes Metab. 2018;20(1):141-147.

    Abstract

    AIMS The relationship between directly measured body fat and all-cause mortality has been rarely studied. The aim of this study was to evaluate the predictive significance of computed tomography (CT)-measured body fat, including both visceral fat area (VFA) and subcutaneous fat area (SFA), for mortality.

    METHODS The study included 36 656 participants who underwent abdominal CT as part of a health check-up at a single university-affiliated healthcare center in 2007 to 2015. Of those, 32 593 participants with data regarding vital status as of May 2016 were included in the final analysis. The main factors evaluated were VFA, SFA and visceral-to-subcutaneous fat area ratio (VSR), and the primary outcome was all-cause mortality.

    RESULTS There were 253 deaths during a mean follow-up of 5.7 years. Increased SFA was associated with decreased all-cause mortality, whereas an increased VFA and VSR were related to increased all-cause mortality. Compared with the predictive power of body mass index (BMI), SFA and VSR showed a larger area under the curve than did BMI. In Kaplan-Meier survival curve analysis, increased SFA and VSR were associated with decreased and increased hazard of all-cause death, respectively. However, in multivariate Cox proportional hazard regression analysis, only VSR was independently associated with all-cause mortality. Moreover, this relationship was paralleled by the harmful impact of increased VSR on metabolic profiles.

    CONCLUSION Increased VSR was an independent predictor of all-cause mortality. This suggests that the location of fat deposits may be more important than the actual amount of body fat.

    PubMed IF 6.1 신장내과
23. 132018

    제1저자 곽민선 · 교신저자 이창훈

    Kwak MS, Kim E, Jang EJ, Lee CH

    The association of non-alcoholic fatty liver disease with lung function: A survey design analysis using propensity score.

    Respirology. 2018;23(1):82-88.

    Abstract

    BACKGROUND AND OBJECTIVE Although both non-alcoholic fatty liver disease (NAFLD) and lung function are known to be associated with metabolic syndromes, few studies have evaluated the relationship between NAFLD and lung function. Our population-based study was conducted to investigate whether NAFLD, diagnosed by elevation of liver enzymes without other chronic liver disease or heavy alcohol drinking, is associated with lung function.

    METHODS A survey design analysis was performed using national representative data of health and nutritional status of civilians in Korea (Korean National Health and Nutrition Examination Survey, KNHANES) between 2010 and 2012. The criteria for NAFLD diagnosis was elevated serum alanine aminotransferase (ALT) without other chronic liver disease or heavy alcohol drinking. Covariate-adjusted linear regression analyses and post-stratification adjustments to the survey weights based on the propensity scores (PS) were conducted to evaluate the association of NAFLD and lung function, including the forced expiratory volume in 1 s (FEV₁ ) and forced vital capacity (FVC).

    RESULTS A total of 7417 subjects were included in this analysis. NAFLD was significantly associated with a lower FVC among males as determined by both the covariate-adjusted linear regression analysis (P < 0.01 in all multivariable models) and PS analysis (P = 0.007). In the PS analysis, NAFLD was significantly associated with lower FEV₁ (P = 0.044) among males. Among females, NAFLD was associated with a lower FVC according to the linear regression analysis; this finding was not verified with the PS analysis.

    CONCLUSION NAFLD was significantly associated with lower lung function and this relationship was more prominent among males.

    PubMed IF 7.2 소화기내과
24. 122018

    제1저자 황인창, 진광남 · 교신저자 김학령

    Hwang IC, Jin KN, Kim HL, Kim YN, Im MS, Lim WH, Seo JB, Kim SH, Zo JH, Kim MA

    Additional prognostic value of brachial-ankle pulse wave velocity to coronary computed tomography angiography in patients with suspected coronary artery disease.

    Atherosclerosis. 2018;268:127-137.

    Abstract

    BACKGROUND AND AIMS Increased arterial stiffness is associated with a higher risk of future cardiovascular events. We aimed to investigate whether information about arterial stiffness provides additional prognostic value to coronary computed tomography angiography (CCTA) findings.

    METHODS A total of 523 consecutive patients (mean age, 58.0 ± 10.3 years; male, 60.6%) with suspected coronary artery disease (CAD), who underwent CCTA and brachial-ankle pulse wave velocity (baPWV) measurement within a month, were retrospectively analyzed. A composite of cardiovascular death, nonfatal myocardial infarction (MI), coronary revascularization, nonfatal stroke, and hospitalization for cardiovascular causes was assessed.

    RESULTS During a median 43.9 months of follow-up (interquartile range, 11.6-66.9 months), the composite endpoint occurred in 66 patients (3 cardiovascular deaths, 1 nonfatal MI, 35 coronary revascularizations, 16 nonfatal strokes, and 45 hospitalizations for cardiovascular causes). After adjustment for clinical risk factors and CCTA findings, higher baPWV was an independent prognostic factor for the composite endpoint (adjusted hazard ratio, 4.717; 95% confidence interval, 2.675-8.319; p < 0.001). The addition of baPWV to clinical risk factors and CCTA findings significantly improved the prediction of cardiovascular events (global χ² score, from 132 to 154; p = 0.005).

    CONCLUSIONS Arterial stiffness provides additional prognostic information to CCTA findings in patients with suspected CAD. The baPWV can serve as a useful clinical tool for risk stratification in this population.

    PubMed IF 7.1 순환기내과
25. 112018

    제1저자 진선필,고성준 · 교신저자 박현선

    Jin SP, Koh SJ, Yu DA, Kim MW, Yun HT, Lee DH, Yoon HS, Cho S, Park HS

    Imiquimod-applied Interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state.

    Exp Dermatol. 2018;27(1):43-49.

    Abstract

    Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison with previous models. IL-10 deficient and wild-type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2 days, and the mice were sacrificed on day 3. Imiquimod-applied IL-10 deficient mice showed more persistent psoriasis-like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+ and IL-17+ cell counts on day 15. Quantitative reverse transcription-polymerase chain reaction with skin tissue revealed significantly higher imiquimod-induced IL-23p19 expression in imiquimod-applied IL-10 deficient mice on day 15. IL-10 deficient mice also showed significantly higher serum levels of imiquimod-induced IL-17A and tumor necrosis factor-α by enzyme-linked immunosorbent assay on day 15. Furthermore, IL-10 deficient mice showed more prominent increase of spleen weight and decrease of body weight in response to imiquimod application on day 3 and 15. In conclusion, IL-10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state.

    PubMed IF 3.4 소화기내과
26. 102018

    제1저자 황인창 · 교신저자 조구영

    Hwang IC, Cho GY, Yoon YE, Park JJ

    Association Between Global Longitudinal Strain and Cardiovascular Events in Patients With Left Bundle Branch Block Assessed Using Two-Dimensional Speckle-Tracking Echocardiography.

    J Am Soc Echocardiogr. 2018;31(1):52-63.e6.

    Abstract

    BACKGROUND The prognostic value of left ventricular (LV) global strain and twist in patients with left bundle branch block (LBBB) is not fully investigated. The aim of this study was to investigate the association between myocardial strain and twist and cardiovascular events in patients with LBBB, as assessed using two-dimensional speckle-tracking echocardiography.

    METHODS A total of 269 patients with LBBB (mean age, 69.5 ± 10.9 years; 46.8% men) were retrospectively identified. Using speckle-tracking, LV global longitudinal strain (GLS), global circumferential strain, and twist were measured. Association between LV global function and a composite of cardiovascular mortality and hospitalization for heart failure was compared with clinical risk factors, LV ejection fraction (LVEF), and other echocardiographic parameters.

    RESULTS During a median of 27.5 months (interquartile range, 12.8-43.9 months), the composite end point occurred in 55 patients (20.4%). In univariate analyses, diabetes mellitus, chronic kidney disease, ischemic etiology of LBBB, dilated left atrium, reduced LVEF, dilated left ventricle, and impaired LV global strain (GLS > -12.2%, global circumferential strain > -11.8%, and twist < 6.5°) showed associations with the composite end point. In multivariate analyses, GLS was significantly associated with the composite end point (adjusted hazard ratio, 4.697; 95% CI, 1.344-16.413; P = .015), whereas global circumferential strain, twist, and LVEF were not. GLS showed an additive association with poor prognosis over clinical risk factors and other echocardiographic parameters, including LVEF. Patients with preserved LVEFs (≥40%) but impaired GLS (>-12.2%) had a larger number of clinical events than those with impaired LVEFs but preserved GLS.

    CONCLUSIONS Among patients with LBBB, GLS can provide better risk stratification than LVEF or other echocardiographic parameters.

    PubMed IF 8.3 순환기내과
27. 92018

    제1저자 곽민선 · 교신저자 김동희

    Kwak MS, Kim D

    Non-alcoholic fatty liver disease and lifestyle modifications, focusing on physical activity.

    Korean J Intern Med. 2018;33(1):64-74.

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and the prevalence of non-alcoholic steatohepatitis (NASH) with fibrosis is increasing as the population with NAFLD ages. To date, lifestyle modifications including weight loss, increased physical activity, and dietary changes remain the treatment of choice for NAFLD because there are no approved effective pharmacologic agents. Increased physical activity has therapeutic effects on NAFLD by reducing hepatic fat independent of weight reduction. Indeed, even minimal physical activity below the recommended threshold may have a beneficial impact on NAFLD. Aerobic activity and resistance training have similar effects on NAFLD. Universal recommendations for the optimal intensity and dose of physical activity have not been established. Therefore, physical activity should be tailored based on a patient's clinical characteristics, comorbidities, and fitness capacity. Physical activity also prevents the development of NAFLD and may represent a valuable strategy for reducing the public health burden. However, there are insufficient data supporting the effects of physical activity on the progression of non-alcoholic fatty liver to NASH with advanced fibrosis, and on extrahepatic disease-related morbidity and mortality. In this paper, we review the role of physical activity in the management of NAFLD.

    PubMed IF 2.2 소화기내과
28. 82018

    제1저자 김세훈,박진주 · 교신저자 최동주

    Kim S, Park JJ, Lee SA, Cho Y, Yoon YE, Oh IY, Yoon CH, Suh JW, Cho YS, Youn TJ, Cho GY, Chae IH, Lee HY, Shin J, Park S, Choi DJ

    Diagnostic accuracy of manual office blood pressure measurement in ambulatory hypertensive patients in Korea.

    Korean J Intern Med. 2018;33(1):113-120.

    Abstract

    BACKGROUND/AIMS Currently, office blood pressure (OBP) is the most widely used method of measuring blood pressure (BP) in daily clinical practice. However, data on the diagnostic accuracy of OBP in reference to ambulatory blood pressure (ABP) are scarce in Korea.

    METHODS In retrospective and prospective cohorts, manual OBP and ABP measurements were compared among ambulatory hypertensive patients. Hypertension was defined as systolic OBP ≥ 140 mmHg and/or diastolic OBP ≥ 90 mmHg, and systolic ABP ≥ 130 mmHg and/or diastolic ABP ≥ 80 mmHg.

    RESULTS In the retrospective cohort (n = 903), the mean OBP1 (before ABP measurement) was higher than ABP in both systolic (138 ± 17 mmHg vs. 123 ± 13 mmHg, p < 0.001) and diastolic (84 ± 12 mmHg vs. 78 ± 11 mmHg, p < 0.001) measurements. Interestingly, there was only a weak correlation between OBP and ABP (r² = 0.038, p < 0.001). The overall discordance rate of OBP compared to ABP, which is the reference method for measuring BP, was 43.9%. The prospective cohort (n = 57) showed similar results. In a subgroup analysis, male patients had higher false negative results (masked or under-treated hypertension) than did female patients (26.1% vs. 17.8%, p = 0.003), whereas female patients had a higher false positive rate (white-coat or over-treated hypertension) than did male patients (28.7% vs. 15.2%, p < 0.001).

    CONCLUSIONS The diagnostic accuracy of manual OBP is low in reference to ABP. Men and women have different patterns of discordance. These findings indicate that management of hypertensive patients with manual OBP measurements may be suboptimal and encourages the use of ABP in ambulatory hypertensive patients.

    PubMed IF 2.2 순환기내과
29. 72018

    제1저자 임종필 · 교신저자 김주성

    Im JP, Ye BD, Kim YS, Kim JS

    Changing treatment paradigms for the management of inflammatory bowel disease.

    Korean J Intern Med. 2018;33(1):28-35.

    Abstract

    Inflammatory bowel disease (IBD) is a chronic and progressive inf lammatory condition of the gastrointestinal tract causing bowel damage, hospitalizations, surgeries, and disability. Although there has been much progress in the management of IBD with established and evolving therapies, most current approaches have failed to change the natural course. Therefore, the treatment approach and follow-up of patients with IBD have undergone a significant change. Usage of immunosuppressants and/or biologics early during the course of the disease, known as top-down or accelerated step-up approach, was shown to be superior to conventional management in patients who had been recently diagnosed with IBD. This approach can be applied to selected groups based on prognostic factors to control disease activity and prevent progressive disease. Therapeutic targets have been shifted from clinical remission mainly based on symptoms to objective parameters such as endoscopic healing due to the discrepancies observed between symptoms, objectively evaluated inf lammatory activity, and intestinal damage. The concept of treat-to-target in IBD has been supported by population-based cohort studies, post hoc analysis of clinical trials, and meta-analysis, but more evidence is needed to support this concept to be applied to the clinical practice. In addition, individualized approach with tight monitoring of non-invasive biomarker such as C-reactive protein and fecal calprotectin and drug concentration has shown to improve clinical and endoscopic outcomes. An appropriate de-escalation strategy is considered based on patient demographics, disease features, current disease status, and patients' preferences.

    PubMed IF 2.2 소화기내과
30. 62018

    제1저자 Subbiah V · 교신저자 김범석

    Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME, Urbanowitz G, Mookerjee B, Wang D, Rangwala F, Keam B

    Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.

    J Clin Oncol. 2018;36(1):7-13.

    Abstract

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.

    PubMed IF 44.7 혈액종양내과

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