SCI 발표논문

2017년 269편

2392017

제1저자 이태민 · 교신저자 박경우

, , , , , , , , , , , , , , , , , , ,
Predictors and Long-Term Clinical Outcome of Longitudinal Stent Deformation: Insights From Pooled Analysis of Korean Multicenter Drug-Eluting Stent Cohort.
Circ Cardiovasc Interv. 2017;10(11):CIRCINTERVENTIONS.117.005518.

Abstract
BACKGROUND There are limited data on the frequency of and factors associated with quantitative coronary angiography (QCA)-defined longitudinal stent deformation (LSD) in various contemporary drug-eluting stents platforms. This study sought to evaluate the predictors of LSD and its long-term clinical implication.
METHODS AND RESULTS A patient-level pooled analysis was performed with 7350 lesions in 5871 patients treated with platinum-chromium-based everolimus-eluting stent (Promus Element), cobalt-chromium-based everolimus-eluting stent (Promus/Xience V), or cobalt-chromium-based zotarolimus-eluting stent (Endeavor Resolute). QCA was performed to analyze differences of stent length between immediate post-deployment and final post-procedure. Independent factors associated with LSD were identified. Clinical outcomes at 3 years were compared between those with and without QCA-based LSD. The frequency of QCA-based LSD was 1.12% (82 cases). Nine of these cases were angiographically overt. Left main or ostial lesion, bifurcation treatment with provisional side branch stenting or ballooning, additional downstream intervention of a distal lesion, intravascular ultrasound use, and adjunctive post-dilatation were independently associated with QCA-based LSD. The type of stent was not associated with QCA-based LSD. Rates of target lesion failure were nominally higher in lesions with QCA-based LSD than in those without (8.97% versus 5.88%; hazard ratio, 1.415; 95% confidence interval, 0.631-3.175; P=0.399).
CONCLUSIONS LSD is uncommon with contemporary drug-eluting stents, regardless of the type of stent platform. LSD is mainly associated with procedural factors, especially with additional downstream procedures which require the passage of devices through the stent. Careful manipulation of poststent imaging or procedural devices is required to prevent LSD. More data are needed to clarify the impact of LSD on clinical events.
PubMed IF 7.2 순환기내과
2382017

제1저자 Tatiana T, 이동화 · 교신저자 임수

, , , , , , ,
Effectiveness of a Smartphone Application for the Management of Metabolic Syndrome Components Focusing on Weight Loss: A Preliminary Study.
Metab Syndr Relat Disord. 2017;15(9):465-473.

Abstract
BACKGROUND There are inconsistent results for the effectiveness of using smartphone applications (apps) or websites on weight loss. We investigated the efficacy of a smartphone intervention using a designated app that utilizes a lifestyle intervention-focused approach, including a human coaching element, toward weight loss in overweight or obese Korean adults.
METHODS One hundred four adults aged 20-60 years with a body mass index ≥23 kg/m², who signed up for a smartphone program for weight loss (using the Noom app), were recruited. Participants received an in-person orientation about the study and app use, and a baseline blood sample was obtained. The in-app intervention with daily behavior and nutrition education content and coaching lasted 15 weeks. The primary endpoint of the study was a change in weight. The secondary endpoints were changes in metabolic risk factors such as blood pressure, waist circumference, and glucose and lipid profiles. Body composition changes were also assessed, and body weight at 52 weeks was measured to ascertain long-term effects.
RESULTS Participants showed a clinically significant weight loss effect of -7.5% at the end of the 15-week program (P < 0.001), and at a 52-week follow-up, a weight loss effect of -5.2% was maintained. At 15 weeks, percent body fat and visceral fat decreased by -6.0 ± 5.4% and -3.4 ± 2.7 kg, respectively (both P < 0.001). Fasting glucose level also decreased significantly by -5.7 ± 14.6 mg/dL at 15 weeks. Lipid parameters showed significant improvements, except for high-density lipoprotein cholesterol. The frequency of logging meals and exercise was associated with body fat loss.
CONCLUSIONS This advanced smartphone app was a useful tool to maintain weight loss in overweight or obese people.
PubMed IF 1.6 내분비대사내과
2372017

제1저자 최윤진 · 교신저자 이동호

, , , , , , , , , , , , , , , , , , , , ,
Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.
J Korean Med Sci. 2017;32(11):1807-1813.

Abstract
This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670).
PubMed IF 3.2 소화기내과
2362017

제1저자 이성우 · 교신저자 진호준

, , , , , , , ,
Is Frailty a Modifiable Risk Factor of Future Adverse Outcomes in Elderly Patients with Incident End-Stage Renal Disease?
J Korean Med Sci. 2017;32(11):1800-1806.

Abstract
Little is known about the clinical significance of frailty and changes of frailty after dialysis initiation in elderly patients with end-stage renal disease (ESRD). We prospectively enrolled 46 elderly patients with incident ESRD at a dialysis center of a tertiary hospital between May 2013 and March 2015. Frailty was assessed by using a comprehensive geriatric assessment protocol and defined as a multidimensional frailty score of ≥ 10. The main outcome was the composite of all-cause death or cardiovascular hospitalization, as determined in June 2016. The median age of the 46 participants was 71.5 years, and 63.0% of them were men. During the median 17.7 months follow-up, the rate of composite outcome was 17.4%. In multivariate logistic regression analysis, after adjusting for age, sex, diabetes, body mass index (BMI), and time of predialytic nephrologic care, female sex, and increased BMI were associated with increased and decreased odds of frailty, respectively. In multivariate Cox proportional hazards analysis, after adjusting for age, sex, diabetes, BMI, and time of predialytic nephrologic care, frailty was significantly associated with the composite adverse outcome. In repeated frailty assessments, the multidimensional frailty score significantly improved 12 months after the initiation of dialysis, which largely relied on improved nutrition. Therefore, frailty needs to be assessed for risk stratification in elderly patients with incident ESRD.
PubMed IF 3.2 신장내과
2352017

제1저자 이해영 · 교신저자 오병희

, , , , , ,
24-Hour blood pressure response to lower dose (30 mg) fimasartan in Korean patients with mild to moderate essential hypertension.
Korean J Intern Med. 2017;32(6):1025-1036.

Abstract
BACKGROUND/AIMS Fimasartan is an angiotensin type 1 receptor blocker (ARB) which has comparable efficacy and tolerability with other ARBs. The aim of this study was to evaluate 24-hour blood pressure (BP) lowering efficacy and the tolerability of the low dose fimasartan compared with valsartan in patients with mild to moderate hypertension.
METHODS This study was a phase II, prospective, multicenter, randomized, double-blind, parallel-grouped trial. A total of 75 hypertensive patients, whose mean ambulatory BP monitoring values were ≥ 135/85 mmHg, were randomized to either fimasartan 30 mg or valsartan 80 mg daily. The primary efficacy endpoint was the change in the mean 24-hour systolic BP (SBP) values from the baseline and at the week 8. Secondary endpoints included the change in the mean 24-hour diastolic BP values, the daytime and the nighttime mean BP values at week 8, the trough-to-peak (T/P) ratio and the smoothness index.
RESULTS At week 8, the mean 24-hour SBP values significantly decreased in both groups; -10.5 ± 11.9 mmHg (p < 0.0001) in the fimasartan group and -5.5 ± 11.6 mmHg (p = 0.0307) in the valsartan group. The difference between two groups was 4.3 ± 2.9 mmHg but there was no statistical significance (p = 0.1392). The global T/P ratio in the fimasartan 30 mg groups were 0.48 and 0.40 in the valsartan 80 mg group, respectively (p = 0.3411). The most frequent adverse events (AEs) were acute pharyngitis and there were no cases of severe AEs.
CONCLUSIONS In mild-to-moderate hypertensive patients, low dose (30 mg) fimasartan showed comparable 24-hour BP lowering efficacy compared with valsartan (80 mg). There was no difference in tolerability between two groups.
PubMed IF 2.2 순환기내과
2342017

제1저자 이현정 · 교신저자 최의근

, , , , , , , ,
Cirrhosis is a risk factor for atrial fibrillation: A nationwide, population-based study.
Liver Int. 2017;37(11):1660-1667.

Abstract
BACKGROUND & AIMS Information is lacking regarding whether cirrhosis is associated with atrial fibrillation development. We aimed to investigate the incidence and clinical significance of atrial fibrillation in cirrhotic patients.
METHODS Cirrhotic patients (n=3596; mean age, 54.7±12.3 years; male, 72.5%) without previous atrial fibrillation were selected from the Korean National Health Insurance Service National Sample Cohort database between 2004 and 2008. Age- and sex-matched controls (n=17 980) were randomly sampled in a 5:1 ratio from non-cirrhotic individuals. Both cohorts were followed up for incident atrial fibrillation and death until 2013.
RESULTS During 9 years of follow-up, atrial fibrillation was newly detected in 113 (3.1%) cirrhosis patients and 385 (2.1%) controls (incidence: 3.48 and 2.16 per 1000 person-years respectively). Cirrhotic patients were at higher risk for atrial fibrillation development compared to controls (hazard ratio, 1.46; 95% confidence interval, 1.18-1.80) after multivariate adjustment. On subgroup analysis, cirrhosis increased the risk for atrial fibrillation, especially in younger (age younger than 65 years) men without comorbidities (CHA₂ DS₂ -VASc score, 0). Cirrhotic patients showed increased overall mortality compared to controls (hazard ratio, 4.80; 95% confidence interval, 4.47-5.15) as well as increased cardiovascular mortality (hazard ratio, 1.37; 95% confidence interval, 1.07-1.75). However, there was no significant association between development of atrial fibrillation and increased mortality in cirrhosis patients (P=.188 and .260).
CONCLUSIONS Cirrhosis was an independent risk factor for atrial fibrillation development, especially in younger, otherwise healthy men, stressing the importance of cardiac assessment in cirrhotic patients. Meanwhile, atrial fibrillation development in cirrhosis patients was not associated with increased mortality.
PubMed IF 6.2 순환기내과
2332017

제1저자 강성희, 이윤빈 · 교신저자 이정훈

, , , , , , , , , , , , ,
Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.
Aliment Pharmacol Ther. 2017;46(9):845-855.

Abstract
BACKGROUND Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth.
AIM To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications.
METHODS We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding.
RESULTS In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338).
CONCLUSIONS In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy.
PubMed IF 6.8 소화기내과
2322017

제1저자 이해영 · 교신저자 김재중

, , ,
Initial Report of the Korean Organ Transplant Registry (KOTRY): Heart Transplantation.
Korean Circ J. 2017;47(6):868-876.

Abstract
BACKGROUND AND OBJECTIVES The Korean Organ Transplant Registry (KOTRY), which was the first national transplant registry in Korea, was founded by the Korean Society for Transplantation and the Korean Center for Disease Control in 2014. Here, we present the initial report of the Korean Heart Transplant Registry.
METHODS A total of 183 heart transplantation (HTPL) patients performed at 4 nationally representative hospitals were collected from April 2014 to December 2015. We analyzed donor and recipient characteristics, treatment patterns, and immediate post-transplantation outcomes.
RESULTS One hundred and eighty-three patients were enrolled. The mean age of the patients was 50.5±13.5 years. The mean age of the male recipients was 4 years greater than that of the female recipients (51.7±13.3 years vs. 47.9±13.7 years, p<0.050). The mean age of donors was more than 12 years younger than that of heart recipients (37.6±10.1 years). Dilated cardiomyopathy was the predominant cause (69%) of heart failure in recipients, followed by ischemic heart diseases (14%) and valvular heart disease (4%). Rejection episodes were most frequent in the 1-6-month period after transplantation (48%), and rarely required intensive treatment. Infection episodes were most frequent <1 month after transplantation (66%) and bacterial and viral infections were equally reported. The 1-year survival rate was 91.6% and most mortality cases occurred during the perioperative period within 1 month after transplantation.
CONCLUSION With the establishment of the KOTRY in 2014, it is now possible to present nationwide epidemiological data for HTPL in Korea for the first time. The KOTRY is the first national HTPL registry in Korea, and will continue until 2023.
PubMed IF 3.4 순환기내과
2312017

제1저자 Gyojeong Gu · 교신저자 이해영

, , , ,
Zebrafish Larvae Model of Dilated Cardiomyopathy Induced by Terfenadine.
Korean Circ J. 2017;47(6):960-969.

Abstract
BACKGROUND AND OBJECTIVES Dilated cardiomyopathy can be the end-stage of severe cardiac disorders and directly affects the cardiac muscle, inducing cardiomegaly and heart failure (HF). Although a wide variety of animal models are available to study dilated cardiomyopathy, there is no model to assess dilated cardiomyopathy with non-invasive, simple, and large screening methods.
METHODS We developed a dilated cardiomyopathy model in zebrafish larvae using short duration terfenadine, a known cardiotoxic drug that induces ventricular size dilation. Fractional shortening of zebrafish hearts was calculated.
RESULTS We treated zebrafish with 5 to 10 μM terfenadine for 24 hours. In terfenadine-treated zebrafish, blood frequently pooled and clotted in the chamber, and circulation was remarkably reduced. Atria and ventricles were swollen, and fluid was deposited around the heart, mimicking edema. Cardiac contractility was significantly reduced, and ventricular area was significantly enlarged. Heart rate was markedly reduced even after terfenadine withdrawal. Acridine orange staining also showed that terfenadine increased cardiomyocyte apoptosis. A significant increase of natriuretic peptide B (NPPB) mRNA was found in terfenadine-treated zebrafish. A low dose of terfenadine (5-10 μM) did not show mortality in short-term treatment (24 hours). However, moderate dose (35-45 μM) terfenadine treatment reduced zebrafish survival within 1 hour.
CONCLUSION With advantages of rapid sample preparation procedure and transparent observation of the live heart, this model can potentially be applied to large-scale drug screening and toxicity assays for non-ischemic HF.
PubMed IF 3.4 순환기내과
2302017

제1저자 차명진 · 교신저자 최의근

, , , , , ,
Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation.
Stroke. 2017;48(11):3040-3048.

Abstract
BACKGROUND AND PURPOSE There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients.
METHODS Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA₂DS₂-VASc score ≥2) between 2014 and 2015.
RESULTS NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant-naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH.
CONCLUSIONS In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban.
PubMed IF 11.1 순환기내과
2292017

제1저자 최원묵 · 교신저자 유수종

, , , , , , , , , , , ,
A model to estimate survival in ambulatory patients with hepatocellular carcinoma: Can it predict the natural course of hepatocellular carcinoma?
Dig Liver Dis. 2017;49(11):1273-1279.

Abstract
BACKGROUND Several hepatocellular carcinoma (HCC) staging systems are available including the newly developed staging system, the Model to Estimate Survival in Ambulatory HCC patients (MESIAH); however, whether these staging systems could predict the natural course of HCC is largely unknown.
METHODS 1013 patients with history of HCC treatment and 111 patients without any history of treatment till death or last follow-up at a single tertiary hospital were included.
RESULTS The MESIAH score showed a better discrimination ability, with a C-statistic of 0.835 [95% confidence interval (CI), 0.810-0.861] in the group of treated patients compared to the Barcelona Clinic Liver Cancer (BCLC) staging system [0.739 (95% CI, 0.709-0.769)] before propensity score matching. However, the MESIAH score failed to stratify patients according to their risk of death in the group of untreated patients unlike the BCLC staging system. Propensity score matching analysis confirmed that the MESIAH score was most strongly influenced by whether treatment was given or not.
CONCLUSIONS Although the MESIAH score provided better prognostic stratification than other staging systems in treated HCC patients, it was not helpful in predicting the natural course of HCC. Since the treatment affects patient outcome and prognosis, it is necessary to develop a new staging system that can also reflect the natural course of HCC.
PubMed IF 4.9 소화기내과
2282017

제1저자 이상언 · 교신저자 이해영

, , , , , , , , , , , , , , , , ,
Reverse J-Curve Relationship Between On-Treatment Blood Pressure and Mortality in Patients With Heart Failure.
JACC Heart Fail. 2017;5(11):810-819.

Abstract
OBJECTIVES This study aimed to assess the relationship between on-treatment blood pressure (BP) and clinical outcomes of patients with heart failure (HF).
BACKGROUND Lower BP has been reported to be related to increased mortality in various cardiovascular diseases. The optimal BP level for patients already experiencing HF is contentious.
METHODS The Korean Acute Heart Failure registry prospectively enrolled a total of 5,625 consecutive patients hospitalized for acute HF in 10 tertiary university hospitals in Korea between March 2011 and February 2014. Clinical profiles including BP were collected at admission, discharge, and during outpatient follow-up. Mean on-treatment BP was calculated from BP at discharge and at each follow-up visit. We evaluated the effects of mean on-treatment BP on the clinical outcomes of patients.
RESULTS Patients were followed up for a median 2.2 years. One-year mortality after discharge was 18.2%. The relationship between on-treatment BP and all-cause mortality followed a reversed J-curve relationship. A nonlinear, multivariable Cox proportional hazard model identified a nadir of systolic and diastolic BPs of 132.4/74.2 mm Hg in patients, for whom the mortality rate was lowest (p < 0.0001). The relationship with increased mortality above and below the reference BP was more definitive for diastolic BP and for HF with a preserved ejection fraction.
CONCLUSIONS Systolic and diastolic BPs <130/70 mm Hg at discharge and during follow-up was associated with worse survival in HF patients. These data suggest that the lowest BP possible might not be an optimal target for HF patients. Further studies should establish a proper BP goal in HF patients. (Registry [Prospective Cohort] for Heart Failure in Korea [KorAHF]; NCT01389843).
PubMed IF 11.9 순환기내과
2272017

제1저자 신철민 · 교신저자 이동호

, , , , , ,
Association Among Obesity, Metabolic Health, and the Risk for Colorectal Cancer in the General Population in Korea Using the National Health Insurance Service-National Sample Cohort.
Dis Colon Rectum. 2017;60(11):1192-1200.

Abstract
BACKGROUND In Korea, the incidence of colorectal cancer has increased and obesity is on a rising trend because of a Westernized lifestyle in men.
OBJECTIVE The purpose of this study was to evaluate the relationship between metabolic health status, as well as BMI, and the incidence of colorectal cancer.
DESIGN This was a prospective cohort study.
SETTINGS The study was conducted with the National Health Insurance Service-National Sample Cohort.
PATIENTS A total of 408,931 Korean adults without cancer at baseline were followed up until 2013 (mean follow-up, 9 y).
MAIN OUTCOME MEASURES Demographic, anthropometric, and laboratory data at baseline were collected and categorized. The presence of diabetes mellitus, hypertension, and dyslipidemia was defined using the criteria of previous studies. The incidence of colorectal cancer was also defined according to the International Classification of Disease, 10 Revision, codes and the claim data on endoscopy with biopsy.
RESULTS During the follow-up, 5108 new cases of colorectal cancer occurred. Being underweight (<18.5 kg/m) reduced the risk for colorectal cancer among women (adjusted HR = 0.646 (95% CI, 0.484-0.863)), whereas high BMI significantly increased the risk in men and in the elderly. Obesity (≥25 kg/m), diabetes mellitus, and hypertension were identified as risk factors for colorectal cancer in men but not for women. Although metabolically unhealthy nonobese men had a higher risk for colorectal cancer than metabolically healthy nonobese men (adjusted HR = 1.114 (95% CI, 1.004-1.236)), the risk was lower than that in the obese men.
LIMITATIONS The study population consisted of people who underwent health examinations, thus there could be selection bias.
CONCLUSIONS In Korean adults, obesity contributes to the incidence of colorectal cancer with a sex difference. Nonobese but metabolically unhealthy men are considered to be a high-risk group for colorectal cancer, but obesity itself is more important in colorectal carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A475.
PubMed IF 3.1 소화기내과
2262017

제1저자 박상원 · 교신저자 Nuermberger E.

, , ,
Immunodeficiency and Intermittent Dosing Promote Acquired Rifamycin Monoresistance in Murine Tuberculosis.
Antimicrob Agents Chemother. 2017;61(11):AAC.01502-17.

Abstract
More-permissive preclinical models may be useful in evaluating antituberculosis regimens for their propensity to select drug-resistant mutants. To evaluate whether acquired rifamycin monoresistance could be recapitulated in mice and, if so, to evaluate the effects of immunodeficiency, intermittent dosing, and drug exposures, athymic nude and BALB/c mice were infected. Controls received daily rifapentine alone or 2 months of rifampin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampin/isoniazid, either daily or twice weekly with one of two isoniazid doses. Test groups received the same intensive regimen followed by once-weekly rifapentine or isoniazid/rifapentine with rifapentine doses of 10, 15, or 20 mg/kg of body weight plus one of two isoniazid doses. All combination regimens rendered BALB/c mouse cultures negative but selected mutants resistant to isoniazid (8.5%, 12/140) or rifampin (3.5%, 5/140) in nude mice (P < 0.001). Intermittently dosed intensive-phase therapy selected isoniazid and rifampin resistance in 10% (8/80, P < 0.001) and 20% (16/80, P = 0.009) of nude mice, respectively, compared to 0% treated with a daily regimen. Once-weekly rifapentine-containing continuation-phase regimens selected rifampin-resistant mutants at a rate of 18.0% (18/100, P = 0.035 compared to rifampin/isoniazid regimens). Higher isoniazid doses in the intermittent-treatment control regimen and higher rifapentine doses in once-weekly regimens were associated with less selection of isoniazid resistance. Acquired resistance, including rifamycin monoresistance, was more likely to occur in nude mice despite administration of combination therapy. These results recapitulate clinical outcomes and indicate that nude mice may be useful for evaluating the ability of novel regimens to prevent the selection of resistance.
PubMed IF 4.2 감염내과
2252017

제1저자 이민종, 정고은 · 교신저자 이정훈

, , , , , , , , , , , , , , , , ,
Antiplatelet therapy and the risk of hepatocellular carcinoma in chronic hepatitis B patients on antiviral treatment.
Hepatology. 2017;66(5):1556-1569.

Abstract
UNLABELLED Antiplatelet therapy has shown protective effects against hepatocellular carcinoma (HCC) in preclinical studies. However, it is unclear whether antiplatelet therapy lowers the risk of HCC in patients with chronic hepatitis B. A retrospective analysis was conducted of data from 1,674 chronic hepatitis B patients, enrolled between January 2002 and May 2015, whose serum hepatitis B virus DNA levels were suppressed by antivirals to <2,000 IU/mL. The primary and secondary outcomes were development of HCC and bleeding events, respectively. Risk was compared between patients with antiplatelet treatment (aspirin, clopidogrel, or both; antiplatelet group) and patients who were not treated (non-antiplatelet group) using a time-varying Cox proportional hazards model for total population and propensity score-matching analysis. The antiplatelet group included 558 patients, and the non-antiplatelet group had 1,116 patients. During the study period, 63 patients (3.8%) developed HCC. In time-varying Cox proportional analyses, the antiplatelet group showed a significantly lower risk of HCC (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.85; P = 0.01), regardless of antiplatelet agent. In propensity score-matched pairs, antiplatelet therapy significantly reduced the risk of HCC (HR, 0.34; 95% CI, 0.15-0.77; P = 0.01). However, the overall risk of bleeding was higher in the antiplatelet group (HR, 3.28; 95% CI, 1.98-5.42; P < 0.001), particularly for clopidogrel with or without aspirin. Treatment with aspirin alone was not associated with a higher bleeding risk (HR, 1.11; 95% CI, 0.48-2.54; P = 0.81).
CONCLUSION Antiplatelet therapy reduces the risk of HCC in chronic hepatitis B patients whose hepatitis B virus is effectively suppressed. However, antiplatelet therapy containing clopidogrel may increase the risk of bleeding. (Hepatology 2017;66:1556-1569).
PubMed IF 18 소화기내과
2242017

제1저자 박준빈 · 교신저자 김형관

, , , , , , , ,
Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM): study protocol for a randomized controlled trial.
Trials. 2017;18(1):501.

Abstract
BACKGROUND The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS).
METHODS/DESIGN The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease.
DISCUSSION In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy.
TRIAL REGISTRATION ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.
PubMed IF 2.1 순환기내과
2232017

제1저자 정재훈, 한정규 · 교신저자 김효수

, , , , , , , , , , , , , , , ,
Benefit of Vasodilating β-Blockers in Patients With Acute Myocardial Infarction After Percutaneous Coronary Intervention: Nationwide Multicenter Cohort Study.
J Am Heart Assoc. 2017;6(10):JAHA.117.007063.

Abstract
BACKGROUND Although current guidelines recommend β-blocker after acute myocardial infarction (MI), the role of β-blocker has not been well investigated in the modern reperfusion era. In particular, the benefit of vasodilating β-blocker over conventional β-blocker is still unexplored.
METHODS AND RESULTS Using nation-wide multicenter Korean Acute Myocardial Infarction Registry data, we analyzed clinical outcomes of 7127 patients with acute MI who underwent successful percutaneous coronary intervention with stents and took β-blockers: vasodilating β-blocker (n=3482), and conventional β-blocker (n=3645). In the whole population, incidence of cardiac death at 1 year was significantly lower in the vasodilating β-blocker group (vasodilating β-blockers versus conventional β-blockers, 1.0% versus 1.9%; P=0.003). In 2882 pairs of propensity score-matched population, the incidence of cardiac death was significantly lower in the vasodilating β-blocker group (1.1% versus 1.8%; P=0.028). Although incidences of MI (1.1% versus 1.5%; P=0.277), any revascularization (2.8% versus 3.0%; P=0.791), and hospitalization for heart failure (1.4% versus 1.9%; P=0.210) were not different between the 2 groups, incidences of cardiac death or MI (2.0% versus 3.1%; P=0.010), cardiac death, MI, or hospitalization for heart failure (3.0% versus 4.5%; P=0.003), cardiac death, MI, or any revascularization (3.9% versus 5.3%; P=0.026), and cardiac death, MI, any revascularization, or hospitalization for heart failure (4.8% versus 6.5%; P=0.011) were significantly lower in the vasodilating β-blocker group.
CONCLUSIONS Vasodilating β-blocker therapy resulted in better clinical outcomes than conventional β-blocker therapy did in patients with acute MI in the modern reperfusion era. Vasodilating β-blockers could be recommended preferentially to conventional ones for acute MI patients.
PubMed IF 6 순환기내과
2222017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , ,
Similarity and Difference of Resting Distal to Aortic Coronary Pressure and Instantaneous Wave-Free Ratio.
J Am Coll Cardiol. 2017;70(17):2114-2123.

Abstract
BACKGROUND Instantaneous wave-free ratio (iFR) has been used in clinical practice to identify functionally significant stenosis and to guide treatment strategy. However, there are limited clinical data regarding another resting pressure-derived index, resting distal to aortic coronary pressure (Pd/Pa), and similarities and differences between resting Pd/Pa and iFR.
OBJECTIVES The authors investigated the changes in resting Pd/Pa and iFR according to anatomic and hemodynamic stenosis severity and their prognostic implications.
METHODS From the 3V FFR-FRIENDS (Clinical Implication of 3-vessel Fractional Flow Reserve) and the IRIS-FFR (Study of the Natural History of FFR Guided Percutaneous Coronary Intervention) studies, 1,024 vessels (n = 435) with available pre-intervention resting Pd/Pa and iFR were used to explore the changes in resting physiological indices according to percent diameter stenosis. Among 115 patients who underwent ¹³N-ammonia positron emission tomography, the changes in those indices according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between physiological indices and the risk of 2-year major adverse cardiac events (MACE) (a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) were analyzed among 375 deferred patients.
RESULTS There was a significant linear correlation between resting Pd/Pa and iFR (R = 0.970; p < 0.001, iFR = 1.370 × resting Pd/Pa - 0.370). Both resting Pd/Pa and iFR changed significantly according to percent diameter stenosis, basal and hyperemic stenosis resistance, and hyperemic absolute myocardial blood flow (all p values <0.001). Percent difference of iFR according to the increase in anatomic and hemodynamic severity was higher than that of resting Pd/Pa. Both resting Pd/Pa and iFR showed a significant association with the risk of 2-year MACE (resting Pd/Pa hazard ratio [per 0.10 increase]: 0.480; 95% confidence interval: 0.250 to 0.923; p = 0.027; iFR hazard ratio [per 0.1 increase]: 0.586; 95% confidence interval: 0.373 to 0.919; p = 0.020) in deferred patients. However, the difference between the upper- and lower-bound estimated MACE rates according to the approximate measurement variability of each index was significantly higher with resting Pd/Pa compared with iFR (resting Pd/Pa 3.85 ± 4.00% and iFR 3.27 ± 3.39%; p < 0.001).
CONCLUSIONS Both resting Pd/Pa and iFR showed similar associations with anatomic and hemodynamic stenosis severity and the risk of MACE. However, iFR was more sensitive to the difference in stenosis severity and showed a lower maximum difference in estimated MACE risk influenced by the measurement variability compared with resting Pd/Pa. (Clinical Implication of 3-Vessel Fractional Flow Reserve [3V FFR-FRIENDS]; NCT01621438; and Study of the Natural History of FFR Guided Percutaneous Coronary Intervention [IRIS-FFR]; NCT01366404).
PubMed IF 22.3 순환기내과
2212017

제1저자 이소령 · 교신저자 최의근

, , , ,
Association between γ-glutamyltransferase level and incidence of atrial fibrillation: A nationwide population-based study.
Int J Cardiol. 2017;245:149-155.

Abstract
BACKGROUND Information on the association between γ-glutamyltransferase (GGT) and the incidence of atrial fibrillation (AF) is scarce. We evaluated the association between GGT and AF incidence, and the interaction between GGT and obesity on developing AF in a large population-based cohort.
METHODS We evaluated 266,550 individuals (mean age, 53±11; men, 48.4%) who underwent the national insurance health checkup between 2004 and 2008. Subjects were categorized in accordance with quartiles of GGT levels (range: Q1, 0-15U/L; Q2, 16-22U/L; Q3, 23-38U/L; Q4, ≥39U/L). The association between GGT levels and AF incidence was analyzed by using multivariable Cox proportional-hazards regression models.
RESULTS During a median of 8years' follow-up, 5034 individuals (1.9%) were newly diagnosed with AF. The crude AF incidence gradually increased with increases in GGT level (1.9, 2.5, 2.8, and 3.1 per 1000 person-years in the Q1, Q2, Q3, and Q4 GGT groups, respectively; p for trend <0.001). In the multivariable Cox proportional hazard models, GGT level showed a dose-response relationship with AF incidence. The subjects with the highest quartile of GGT levels had a significantly higher risk of AF (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.18-1.45; p<0.001). When the analysis was stratified by body mass index (BMI), GGT level showed good discrimination for AF incidence only in the non-obese population (BMI<25kg/m²), and not in the obese population (BMI≥25kg/m²; p interaction<0.001).
CONCLUSIONS In this large population-based study, elevated GGT level showed a significant association with increased risk of AF, especially in a non-obese population.
PubMed IF 3.3 순환기내과
2202017

제1저자 이주명 · 교신저자 구본권

, , , , , , , ,
Discrepancy between fractional flow reserve and instantaneous wave-free ratio: Clinical and angiographic characteristics.
Int J Cardiol. 2017;245:63-68.

Abstract
BACKGROUND The invasive physiologic index such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) is used in clinical practice to identify ischemia-causing stenosis and to guide treatment strategy. We investigated clinical and angiographic characteristics of lesions with discrepancy between FFR and iFR.
METHODS From the 3V FFR-FRIENDS study, 975 vessels (393 patients) with available pre-intervention FFR and iFR were included in this study. The vessels were classified according to FFR and iFR into: concordant normal (Group 1 [n=724]: FFR>0.80 and iFR≥0.90); high FFR and low iFR (Group 2 [n=33]: FFR>0.80 and iFR<0.90); low FFR and high iFR (Group 3 [n=82]: FFR≤0.80 and iFR≥0.90); and concordant abnormal (Group 4 [n=136]: FFR≤0.80 and iFR<0.90).
RESULTS Angiographic stenosis severity assessed by percent diameter stenosis, minimum lumen diameter and lesion length was increased from Group 1 to Group 4 (all p<0.001). SYNTAX score increased and FFR decreased proportionally from Group 1 to Group 4 (all p<0.001). In multivariable GEE model, female, diabetes mellitus, smaller reference vessel diameter, and higher %DS were significantly associated with low iFR among high FFR groups (Group 2 discordance). Conversely, males, absence of diabetes mellitus and lower %DS were significantly associated with high iFR among low FFR groups (Group 3 discordance).
CONCLUSIONS Four groups classified according to FFR and iFR were different in clinical and angiographic characteristics, SYNTAX score, and predictors of discordance. The lesions with discordant FFR and iFR may need to be interpreted as a different clinical entity.
PubMed IF 3.3 순환기내과
2192017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , ,
Prognosis of deferred non-culprit lesions according to fractional flow reserve in patients with acute coronary syndrome.
EuroIntervention. 2017;13(9):e1112-e1119.

Abstract
AIMS There are limited data on the prognosis of deferred non-culprit lesions in patients with acute coronary syndrome (ACS) based on fractional flow reserve (FFR). We aimed to investigate the prognosis of deferred non-culprit lesions in ACS patients, compared with deferred lesions in patients with stable coronary artery disease (SCAD), on the basis of FFR.
METHODS AND RESULTS The clinical outcomes of 449 non-culprit lesions (301 patients with ACS) were compared with 2,484 lesions (1,295 patients with SCAD) in which revascularisation was deferred on the basis of a high FFR (>0.80). The primary outcome was major adverse cardiac events (MACE), a composite of cardiac death, target vessel-related myocardial infarction (MI) and ischaemia-driven revascularisation. Among the ACS population, 65.8% presented with unstable angina and 34.2% with non-ST-segment elevation MI. Mean angiographic percent diameter stenosis and FFR of the deferred lesions were 39.3±15.0% and 0.92±0.06, respectively. During the median follow-up duration of 722.0 days, the deferred non-culprit lesions of ACS patients showed a significantly higher rate of MACE (3.8% vs. 1.6%, HRadj 2.97, 95% CI: 1.23-7.17, p=0.016), mainly driven by the higher rate of ischaemia-driven revascularisation (2.8% vs. 1.1%, HRadj 3.39, 95% CI: 1.29-8.92, p=0.013) than the deferred lesions in SCAD patients. Regardless of the range of FFR in the deferred lesions (0.81-0.85, 0.86-0.90, 0.91-0.95, and 0.95-1.00), non-culprit lesions of ACS showed a more than twofold higher rate of MACE than that of SCAD. In a multivariable marginal Cox model, ACS was the most powerful independent predictor of MACE (HRadj 2.74, 95% CI: 1.13-6.64, p=0.026).
CONCLUSIONS Compared to the deferred lesions of SCAD patients, deferred non-culprit lesions of ACS on the basis of FFR showed a higher rate of clinical events, regardless of FFR range.
PubMed IF 9.2 순환기내과
2182017

제1저자 김치훈, 한정규 · 교신저자 김효수

, , , , , , , , , , , , , , , , , ,
Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis - coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial.
BMJ Open. 2017;7(10):e016617.

Abstract
INTRODUCTION We have recently seen the introduction of newer generation drug-eluting stents with ultrathin struts that use advanced polymer technologies. However, the efficacy and safety of these newest stents have not yet been fully explored. In addition, there are still controversies over the optimal duration of dual antiplatelet therapy (DAPT) after stent implantation, particularly for ultrathin stents with the newest polymer technologies.
METHODS AND ANALYSIS The HOST-IDEA trial is a randomised, open-label, multicentre, non-inferiority trial and the first study to directly compare two of these ultrathin sirolimus-eluting stents: Orsiro stent with biodegradable polymer, and polymer-free Coroflex ISAR (CX-ISAR) stent. This study has a scheme of 2×2 factorial design according to the stent type and DAPT duration (3 vs 12 months). A total of 2152 patients will be randomised and stratified to demonstrate the non-inferiority of CX-ISAR to Orsiro, or of the abbreviated DAPT duration to the conventional 12 months (both in 1:1 ratio). For the comparison of stent type, the primary endpoint is target lesion failure (TLF), which is a composite of cardiac death, target vessel-related myocardial infarction and clinically driven target lesion revascularisation. For the comparison of DAPT duration, the net adverse clinical event is the coprimary endpoint, which is defined as a composite of TLF, definite/probable stent thrombosis and major bleeding.
ETHIC APPROVAL AND DISSEMINATION All the institutions involved in this study are required to have ethical approval prior to patient enrolment. This multicentre study will recruit patients through competitive registration, but institutions that have not yet obtained ethical approvals have made it impossible to enrol patients in a centralised web database. The final results will be presented at relevant international conferences and will be materialised in the form of papers.
TRIAL REGISTRATION NUMBER NCT02601157; Pre-results.
PubMed IF 2.5 순환기내과
2172017

제1저자 우현구 · 교신저자 김윤준

, , , , , , , , , , ,
Integrative analysis of genomic and epigenomic regulation of the transcriptome in liver cancer.
Nat Commun. 2017;8(1):839.

Abstract
Hepatocellular carcinoma harbors numerous genomic and epigenomic aberrations of DNA copy numbers and DNA methylation. Transcriptomic deregulation by these aberrations plays key driver roles in heterogeneous progression of cancers. Here, we profile DNA copy numbers, DNA methylation, and messenger RNA expression levels from 64 cases of hepatocellular carcinoma specimens. We find that the frequencies of the aberrancies of the DNA copy-number-correlated (CNVcor) expression genes and the methylation-correlated expression (METcor) genes are co-regulated significantly. Multi-omics integration of the CNVcor and METcor genes reveal three prognostic subtypes of hepatocellular carcinoma, which can be validated by an independent data. The most aggressive subtype expressing stemness genes has frequent BAP1 mutations, implying its pivotal role in the aggressive tumor progression. In conclusion, our integrative analysis of genomic and epigenomic regulation provides new insights on the multi-layered pathobiology of hepatocellular carcinoma, which might be helpful in developing precision management for hepatocellular carcinoma patients.Hepatocellular carcinoma is known to harbour numerous genomic and epigenomic aberrations, driving transcriptomic deregulation. Here, the authors integrate genomic, epigenomic, and expression data to reveal three prognostic subtypes, providing insight to the pathobiology of hepatocellular carcinoma.
PubMed IF 18.1 소화기내과
2162017

제1저자 온정헌, 황지연 · 교신저자 문민경

, , , , , , , , , ,
Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice.
PLoS One. 2017;12(10):e0186021.

Abstract
The small heterodimer partner (SHP) regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR) γ expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing not only heart structure and function but also lipid metabolism and related gene expression in a SHP deletion animal model. Transcriptional profiling with a microarray revealed that genes participating in cell growth, cytokine signalling, phospholipid metabolism, and extracellular matrix are up-regulated in the myocardia of SHP knockout (KO) mice compared to those of wild-type (WT) mice (nominal p value < 0.05). Consistent with these gene expression changes, the left ventricular masses of SHP KO mice were significantly higher than WT mice (76.8 ± 20.5 mg vs. 52.8 ± 6.8 mg, P = 0.0093). After 12 weeks of high fat diet (HFD), SHP KO mice gained less weight and exhibited less elevation in serum-free fatty acid and less ectopic lipid accumulation in the myocardium than WT mice. According to microarray analysis, genes regulated by PPARγ1 and PPARα were down-regulated in myocardia of SHP KO mice compared to their expression in WT mice after HFD, suggesting that the reduction in lipid accumulation in the myocardium resulted from a decrease in lipogenesis regulated by PPARγ. We confirmed the reduced expression of PPARγ1 and PPARα target genes such as CD36, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase by SHP KO after HFD.
PubMed IF 2.8 내분비대사내과
2152017

제1저자 박세훈 · 교신저자 임춘수

, , , , , , ,
Association between postoperative hyponatremia and renal prognosis in major urologic surgery.
Oncotarget. 2017;8(45):79935-79947.

Abstract
Recent evidence for the clinical significance of postoperative hyponatremia after urologic surgeries remains scarce. We examined the incidence, risk factors, and outcomes of electrolyte imbalance in urologic surgery. Patients with newly developed hyponatremia, defined as a sodium level lower than 135 mEq/L within 7 days after surgery, were included in our study group. The primary outcome was progression to end-stage renal disease (ESRD). Secondary outcome was composition of progression to ESRD and creatinine doubling/eGFR halving from baseline. A survival analysis with a multivariable Cox proportional hazard model was performed. We included 9,206 cases of bladder, prostate, ureter, and kidney surgery. Incidence of new-onset postoperative hyponatremia was 15.4% (1,414/9,206). Postoperative hyponatremia mostly developed in patients with high-risk perioperative characteristics. The development of postoperative hyponatremia was independently associated with progression to ESRD (adjusted HR 1.343, 95% CI 1.082-1.680, P = 0.007). The secondary outcome was also related to the electrolyte imbalance in prostate (adjusted HR 1.729, 95% CI 1.145-2.612, P = 0.009) and kidney (adjusted HR 1.339, 95% CI 1.099-1.632, P = 0.004) surgery. Postoperative hyponatremia in urologic surgery was a common electrolyte imbalance in patients with high-risk perioperative status, and associated with worse renal prognosis.
PubMed IF 5.168 신장내과
2142017

제1저자 조경민 · 교신저자 오도연

, , , , , , , ,
Skeletal muscle depletion predicts survival of patients with advanced biliary tract cancer undergoing palliative chemotherapy.
Oncotarget. 2017;8(45):79441-79452.

Abstract
BACKGROUND No prior study has investigated the dynamics of body weight with body muscle mass as a prognostic factor in advanced biliary tract cancer (BTC) patients undergoing palliative chemotherapy. We investigated whether low skeletal muscle mass affects survival in patients with BTC, with a co-analysis of body weight loss and body mass index (BMI).
RESULTS By multivariate analysis, low skeletal muscle mass at diagnosis and decreased SMI during chemotherapy (p = 0.008 and p < 0.001, respectively) were poor prognostic factors for overall survival (OS). Subgroup analysis revealed that low skeletal muscle mass patients who were overweight or obese (BMI ≥ 25 kg/m²) showed worse OS (p < 0.001). Additionally, patients with both decreased BMI and SMI during chemotherapy had worse OS (p < 0.001). Furthermore, patients with decreased SMI had shorter survival regardless of change in BMI. However, for patients with SMI maintained during chemotherapy, decreased BMI had no effect on survival (p = 0.576).
MATERIALS AND METHODS We consecutively enrolled 524 patients with advanced BTC who received palliative chemotherapy between 2003 and 2013. Total muscle cross-sectional area (cm²) at the L3 level assessed by computed tomography was analyzed. We defined low skeletal muscle mass as a skeletal muscle index (SMI) < 48.5 cm²/m² (men) and < 39.5 cm²/m² (women) using ROC curves.
CONCLUSIONS Low skeletal muscle mass, obesity and muscle depletion during palliative chemotherapy are meaningful prognostic factors in advanced BTC. Considering muscle depletion with weight change could help to more accurately predict prognoses of patients with BTC.
PubMed IF 5.168 혈액종양내과
2132017

제1저자 Kohei Shitara · 교신저자 방영주

, , , , , , , , , , , , ,
Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.
Oncotarget. 2017;8(45):79546-79555.

Abstract
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m²) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort (N = 19; unselected population, including three patients with MET-amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m². Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m² in the dose-expansion cohort, comprising patients with MET-amplified tumors (N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m² has acceptable tolerability and modest antitumor activity in patients with MET-amplified gastric cancer.
PubMed IF 5.168 혈액종양내과
2122017

제1저자 이희선 · 교신저자 박준빈

, , , , , , , , , , , , , , , ,
Impact of a Telehealth Program With Voice Recognition Technology in Patients With Chronic Heart Failure: Feasibility Study.
JMIR Mhealth Uhealth. 2017;5(10):e127.

Abstract
BACKGROUND Despite the advances in the diagnosis and treatment of heart failure (HF), the current hospital-oriented framework for HF management does not appear to be sufficient to maintain the stability of HF patients in the long term. The importance of self-care management is increasingly being emphasized as a promising long-term treatment strategy for patients with chronic HF.
OBJECTIVE The objective of this study was to evaluate whether a new information communication technology (ICT)-based telehealth program with voice recognition technology could improve clinical or laboratory outcomes in HF patients.
METHODS In this prospective single-arm pilot study, we recruited 31 consecutive patients with chronic HF who were referred to our institute. An ICT-based telehealth program with voice recognition technology was developed and used by patients with HF for 12 weeks. Patients were educated on the use of this program via mobile phone, landline, or the Internet for the purpose of improving communication and data collection. Using these systems, we collected comprehensive data elements related to the risk of HF self-care management such as weight, diet, exercise, medication adherence, overall symptom change, and home blood pressure. The study endpoints were the changes observed in urine sodium concentration (uNa), Minnesota Living with Heart Failure (MLHFQ) scores, 6-min walk test, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) as surrogate markers for appropriate HF management.
RESULTS Among the 31 enrolled patients, 27 (87%) patients completed the study, and 10 (10/27, 37%) showed good adherence to ICT-based telehealth program with voice recognition technology, which was defined as the use of the program for 100 times or more during the study period. Nearly three-fourths of the patients had been hospitalized at least once because of HF before the enrollment (20/27, 74%); 14 patients had 1, 2 patients had 2, and 4 patients had 3 or more previous HF hospitalizations. In the total study population, there was no significant interval change in laboratory and functional outcome variables after 12 weeks of ICT-based telehealth program. In patients with good adherence to ICT-based telehealth program, there was a significant improvement in the mean uNa (103.1 to 78.1; P=.01) but not in those without (85.4 to 96.9; P=.49). Similarly, a marginal improvement in MLHFQ scores was only observed in patients with good adherence (27.5 to 21.4; P=.08) but not in their counterparts (19.0 to 19.7; P=.73). The mean 6-min walk distance and NT-proBNP were not significantly increased in patients regardless of their adherence.
CONCLUSIONS Short-term application of ICT-based telehealth program with voice recognition technology showed the potential to improve uNa values and MLHFQ scores in HF patients, suggesting that better control of sodium intake and greater quality of life can be achieved by this program.
PubMed IF 6.3 순환기내과
2112017

제1저자 박상원 · 교신저자 박상원

, , , ,
Implementation of central line-associated bloodstream infection prevention bundles in a surgical intensive care unit using peer tutoring.
Antimicrob Resist Infect Control. 2017;6:103.

Abstract
BACKGROUND Central line-associated bloodstream infections (CLABSIs) can be prevented through well-coordinated, multifaceted programs. However, implementation of CLABSI prevention programs requires individualized strategies for different institutional situations, and the best strategy in resource-limited settings is uncertain. Peer tutoring may be an efficient and effective method that is applicable in such settings.
METHODS A prospective intervention was performed to reduce CLABSIs in a surgical intensive care unit (SICU) at a tertiary hospital. The core interventions consisted of implementation of insertion and maintenance bundles for CLABSI prevention. The overall interventions were guided and coordinated by active educational programs using peer tutoring. The CLABSI rates were compared for 9 months pre-intervention, 6 months during the intervention and 9 months post-intervention. The CLABSI rate was further observed for three years after the intervention.
RESULTS The rate of CLABSIs per 1000 catheter-days decreased from 6.9 infections in the pre-intervention period to 2.4 and 1.8 in the intervention (6 m; P = 0.102) and post-intervention (9 m; P = 0.036) periods, respectively. A regression model showed a significantly decreasing trend in the infection rate from the pre-intervention period (P < 0.001), with incidence-rate ratios of 0.348 (95% confidence interval [CI], 0.98-1.23) in the intervention period and 0.257 (95% CI, 0.07-0.91) in the post-intervention period. However, after the 9-month post-intervention period, the yearly CLABSI rates reverted to 3.0-5.4 infections per 1000 catheter-days over 3 years.
CONCLUSIONS Implementation of CLABSI prevention bundles using peer tutoring in a resource-limited setting was useful and effectively reduced CLABSIs. However, maintaining the reduced CLABSI rate will require further strategies.
PubMed IF 5.2 감염내과
2102017

제1저자 김윤지 · 교신저자 임수

, , , , , , , ,
Association Between Obesity and Chronic Kidney Disease, Defined by Both Glomerular Filtration Rate and Albuminuria, in Korean Adults.
Metab Syndr Relat Disord. 2017;15(8):416-422.

Abstract
BACKGROUND Chronic kidney disease (CKD) has often been defined based on glomerular filtration rate (GFR) alone. The Kidney Disease: Improving Global Outcomes guideline highlights albuminuria in the CKD definition. Thus, we investigated the association between obesity and CKD, as defined by both GFR and albuminuria, in Korean adults.
METHODS We used Korea National Health and Nutrition Examination Survey 2011-2014 data (N = 19,331, ≥19 years old) representing the national Korean population. CKD was classified by (1) estimated GFR (eGFR) < 60 mL/min/1.73 m² (CKD_GFR); (2) albumin-to-creatinine ratio (ACR) ≥30 mg/gram (CKD_ACR); and (3) eGFR < 60 mL/min/1.73 m² or ACR ≥30 mg/gram (CKD_Risk). Associations between obesity and each CKD category were evaluated using multivariate logistic regression analysis.
RESULTS The prevalence rates of CKD_GFR, CKD_ACR, and CKD_Risk were 2.2%, 6.7%, and 8.1%, respectively. Compared with the normal body mass index (BMI; 18.5-22.9 kg/m²) group, men with BMI ≥ 25 kg/m² had 1.88 times greater risk of CKD_GFR in the adjusted model [95% confidence interval (CI), 1.26-2.80; P = 0.002]; BMI was not significantly associated with CKD_GFR in women. In contrast, both men and women with BMI ≥ 25 kg/m² had 1.58 and 1.40 times higher risk of CKD_ACR (95% CI, 1.21-2.07 and 1.08-1.81, respectively, both P < 0.01). Obese men and women had 1.65 and 1.38 times higher risk of CKD_Risk (95% CI, 1.29-2.12 and 1.09-1.75, respectively, both P < 0.01).
CONCLUSIONS Obesity was significantly associated with an increased ACR-based CKD risk. Longitudinal studies are needed to investigate the role of overweight and obesity in the development and progression of CKD.
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