SCI 발표논문

2018년 245편

652018

제1저자 김효진 · 교신저자 오국환

, , , , , , , , ,
The association between soluble klotho and cardiovascular parameters in chronic kidney disease: results from the KNOW-CKD study.
BMC Nephrol. 2018;19(1):51.

Abstract
BACKGROUND Klotho, a protein linked to aging, has emerged as a pivotal player in mineral bone metabolism and might explain the relationship between chronic kidney disease (CKD) and cardiovascular disease (CVD). The present study aimed to investigate the association between serum klotho and cardiac parameters from a large-scale Korean CKD cohort.
METHODS We analyzed 2101 participants from KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort who had been measured for serum klotho levels. Left ventricular hypertrophy evaluated by left ventricular mass index (LVMI) and arterial stiffness measured by brachial-to-ankle pulse wave velocity (baPWV) were explored as cardiovascular parameters.
RESULTS Patients were 53.6 ± 12.2 years old and 61.1% were male. The mean estimated glomerular filtration rate (eGFR) was 53.0 ± 30.7 mL/min/1.73m². The median serum klotho level was 536 (interquartile range [IQR]: 420-667) pg/mL. Advanced CKD stages were associated with lower serum klotho levels (P < 0.001, P for linear trend < 0.001). Ascending quartiles of klotho were significantly associated with decreased LMVI (P < 0.001, P for linear trend< 0.001). A multivariable linear regression model showed serum klotho had a significant inverse association with LVMI (β - 0.04; 95% CI [confidence interval] -0.004, - 0.00007; P = 0.041). However, there was no significant association between serum klotho and baPWV after adjustment (β 0.003; 95% CI -0.04, 0.05; P = 0.876).
TRIAL REGISTRATION This trial was registered on ClinicalTrials.gov on 28 June 2012 ( NCT01630486 ).
CONCLUSIONS Serum klotho was an independent biomarker of LVMI, but not arterial stiffness.
PubMed IF 2.9 신장내과
642018

제1저자 박진주 · 교신저자 윤창환

, , , , , , ,
Effect of β-Blockers Beyond 3 Years After Acute Myocardial Infarction.
J Am Heart Assoc. 2018;7(5):JAHA.117.007567.

Abstract
BACKGROUND The optimal duration of β-blocker therapy in patients with acute myocardial infarction (AMI) is unknown. We aimed to evaluate the late effect of β-blockers in patients with AMI.
METHODS AND RESULTS We enrolled all consecutive patients who presented with AMI at Seoul National University Bundang Hospital, between June 3, 2003 and February 24, 2015. The primary end point was 5-year all-cause mortality, depending on the use of β-blockers at discharge, 1 year after AMI, and 3 years after AMI. Of 2592 patients, the prescription rates of β-blockers were 72%, 69%, 63%, and 60% at discharge and 1, 3, and 5 years after AMI, respectively. The patients who were receiving β-blocker therapy had more favorable clinical characteristics, such as younger age (62 versus 65 years; P<0.001). They received reperfusion therapy more often (92% versus 80%; P<0.001) than those without β-blocker prescription. In the univariate analysis, the patients with β-blocker prescription had lower 5-year mortality at all time points. In the Cox model after adjustment for significant covariates, β-blocker prescription at discharge was associated with a 29% reduced mortality risk (hazard ratio, 0.71; 95% confidence interval, 0.55-0.90; P=0.006); however, β-blocker prescriptions at 1 and 3 years after AMI were not associated with reduced mortality.
CONCLUSIONS The beneficial effect of β-blocker therapy after AMI may be limited until 1 year after AMI. Whether late β-blocker therapy beyond 1 year after AMI offers clinical benefits should be confirmed in further clinical trials.
PubMed IF 6 순환기내과
632018

제1저자 강지훈, 김학령 · 교신저자 김상현

, , , , , ,
Relationship between brachial-ankle pulse wave velocity and invasively measured aortic pulse pressure.
J Clin Hypertens (Greenwich). 2018;20(3):462-468.

Abstract
Although brachial-ankle pulse wave velocity (baPWV) has been widely used as an index of arterial stiffness, no consensus exists about whether baPWV can reflect central aortic stiffness. The authors investigated the association between baPWV and invasively measured aortic pulse pressure (APP) in a total of 109 consecutive patients (mean age, 62.3 ± 11.3 years; 67.9% men). Most patients (91%) had obstructive coronary artery disease, and mean baPWV and APP values were 1535 ± 303 cm/s and 66.8 ± 22.5 mm Hg, respectively. In univariate analysis, there was a significant linear correlation between baPWV and APP (r = .635, P < .001). The correlation between baPWV and APP remained significant even after controlling for potential confounders (β = 0.574, P < .001; R² = .469). Arterial stiffness measured by baPWV showed a strong positive correlation with invasively measured APP, independent of clinical confounders. Therefore, baPWV can be a good marker of central aortic stiffness.
PubMed IF 2.9 순환기내과
622018

제1저자 유수종, 권지혜 · 교신저자 김원, 윤정환

, , , , , , , , , ,
Initial Alpha-Fetoprotein Response Predicts Prognosis in Hepatitis B-related Solitary HCC Patients After Radiofrequency Ablation.
J Clin Gastroenterol. 2018;52(3):e18-e26.

Abstract
BACKGROUND Radiofrequency ablation (RFA) is effective for early-stage hepatocellular carcinoma but recurrence is problem.
GOALS To identify prognostic factors including alpha-fetoprotein (AFP) for overall survival and intrahepatic recurrence after RFA.
PATIENTS AND METHODS Not only naïve but also previously treated patients with solitary hepatitis B virus-related hepatocellular carcinoma <5 cm were prospectively enrolled and a ≥50% decrease from baseline to 1 month after RFA was defined as an initial AFP response. Tumor responses were assessed by the modified response evaluation criteria in solid tumors.
RESULTS Among 255 patients, 156 patients (61.2%) developed intrahepatic recurrence. Radiologic progression occurred in 54.8% (86/157) in the AFP responders and 71.4% (70/98) in the AFP nonresponders. In multivariate analysis, a history of previous treatment [hazard ratio (HR), 2.037; P=0.015 for percutaneous ethanol injection vs. none; and HR, 2.642; P<0.001 for transarterial chemoembolization vs. none] and an initial AFP nonresponse (HR, 1.899; P<0.001) were independent predictors of accelerated progression after RFA. Moreover, those who had a history of previous treatment and did not achieve an initial AFP response had significantly unfavorable overall survival (HR, 3.581; P<0.001) and the increased risk of intrahepatic remote recurrence (HR, 5.385; P<0.001) compared with those with an initial AFP response and no history of previous treatment.
CONCLUSIONS Biological response evaluation by the measurement of serial AFP levels is a useful predictor of overall survival and intrahepatic remote recurrence after RFA. Therefore, an initial AFP response may aid in determining the need of closer follow-up as a therapeutic response indicator of RFA.
PubMed IF 2.7 소화기내과
612018

제1저자 양민석 · 교신저자 장윤석

, , , , , , ,
Electronic Consultation Support System for Radiocontrast Media Hypersensitivity Changes Clinicians' Behavior.
Allergy Asthma Immunol Res. 2018;10(2):165-171.

Abstract
PURPOSE Patients with a history of radiocontrast media (RCM) hypersensitivity can be overlooked, resulting in repeated reactions. Therefore, a consultation support system for RCM hypersensitivity has been in operation at Seoul National University Bundang Hospital since December 2011. We analyzed the effect of this system on physicians' practice.
METHODS A retrospective study was conducted on patients with previous RCM reactions (December 1, 2010 to November 30, 2012). The control period was December 2010 to November 2011, and the intervention period was December 2011 to November 2012. The primary outcome was the composite outcome of premedication and consultation. Premedication was defined as preventive medication prescribed by the physician who ordered RCM-enhanced computed tomography (CT) at the same time. The secondary outcome was the recurrence rate after using the consultation support system.
RESULTS A total of 189 clinicians prescribed 913 CT scans during the control period and 225 clinicians performed 1,153 examinations during the intervention period. The odds ratio (OR) of achieving the composite outcome increased significantly after use of the consultation support system (OR, 1.54; 95% confidence interval [CI], 1.15-2.05). Clinicians in both medical (OR, 1.48; 95% CI, 1.06-2.07) and surgical (OR, 2.07; 95% CI, 1.24-3.46) departments showed significant changes in their behavior, whereas those in the emergency department did not (OR, 1.07; 95% CI, 0.41-2.78). Professors (OR, 1.47; 95% CI, 1.06-2.04) and trainees (OR, 1.97, 95% CI, 1.22-3.18) showed significant changes in their behavior toward patients with previous RCM reactions. The behavior of 86 clinicians who ordered CT scans during both the control and intervention periods was unchanged.
CONCLUSIONS The consultation support system for those with previous RCM hypersensitivity reactions changed physicians' practice patterns and decreased recurrent RCM hypersensitivity reactions as well.
PubMed IF 4.3 알레르기내과
602018

제1저자 박찬순 · 교신저자 박준빈, 이승훈

, , , , , , , , ,
Left Ventricular Geometry Determines Prognosis and Reverse J-Shaped Relation Between Blood Pressure and Mortality in Ischemic Stroke Patients.
JACC Cardiovasc Imaging. 2018;11(3):373-382.

Abstract
OBJECTIVES This study sought to investigate the prognostic significance of left ventricular (LV) mass and geometry in ischemic stroke survivors, as well as the LV geometry-specific differences in the blood pressure-mortality relationship.
BACKGROUND LV mass and geometry are well-known prognostic factors in various populations; however, there are no data on their role in ischemic stroke patients.
METHODS We prospectively recruited 2,328 consecutive patients admitted with acute ischemic stroke to our institute between 2002 and 2010. Of these, 2,069 patients were analyzed in whom echocardiographic data were available to assess LV mass and geometry.
RESULTS All-cause mortality was significantly greater in patients with concentric hypertrophy (adjusted hazard ratio [HR]: 1.417; 95% confidence interval [CI]: 1.045 to 1.920) and concentric remodeling (HR: 1.540; 95% CI: 1.115 to 2.127) but nonsignificantly in those with eccentric hypertrophy (HR: 1.388; 95% CI: 0.996 to 1.935) compared with normal geometry in multivariate analyses. Relative wall thickness was a significant predictor of all-cause mortality (HR: 1.149 per 0.1-U increase in relative wall thickness; 95% CI: 1.021 to 1.307), whereas LV mass index was not (HR: 1.003 per 1 g/m² increase in LV mass index; 95% CI: 0.999 to 1.007). Similar results were observed with cardiovascular mortality. In multivariable fractional polynomials, patients with altered LV geometry showed reverse J-curve relationships between acute-phase systolic blood pressure and all-cause or cardiovascular mortality, with the highest risks in the lower extremes, whereas those with normal geometry did not.
CONCLUSIONS Echocardiographic assessment of LV geometry provided independent and additive prognostic information in ischemic stroke patients. A reverse J-shaped relation of mortality with blood pressure was found in patients with abnormal LV geometry.
PubMed IF 19 순환기내과
592018

제1저자 황도연 · 교신저자 박경우

, , , , , , , , , , ,
Efficacy and safety of dual antiplatelet therapy after coronary stenting in patients with chronic kidney disease.
Am Heart J. 2018;197:103-112.

Abstract
BACKGROUND We compared efficacy and safety of short- (3 or 6 months) versus long-term (≥12 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation, according to the presence of chronic kidney disease (CKD).
METHODS Patient-level pooled analysis was performed with 7242 patients (87.2% with 2nd generation DES) from 5 randomized controlled trials.
RESULTS In both CKD (1273 patients) and non-CKD (5969 patients) population, the rates of patient-oriented composite outcomes at 1-year (POCO, all-cause death, any myocardial infarction [MI], stroke and TIMI major bleeding) were not different between the short- and long-term DAPT (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.76-1.86, P=.449 in CKD population; HR 1.14, 95% CI 0.83-1.56, P=.434 in non-CKD population). The rates of coronary thrombotic events (any MI and definite/probable stent thrombosis) also did not differ between short- and long-term DAPT in either CKD or non-CKD population. As for bleeding events, long-term DAPT increased the TIMI major bleeding (HR 2.91, 95% CI 1.31-6.48, P=.009) in non-CKD population. The similar trend was observed with long-term DAPT in CKD population. But it did not reach statistical significance (HR 3.15, 95% CI 0.64-15.63, P=.160).
CONCLUSIONS The rates of POCO and coronary thrombotic events were significantly higher in patients with CKD compared with those without CKD, which were not affected by short- or long-term DAPT. Higher bleeding incidence by long-term DAPT was only observed in non-CKD patients but not in CKD patients. Further large scale studies are warranted to confirm our findings.
PubMed IF 3.4 순환기내과
582018

제1저자 양효준 · 교신저자 김상균

, , , , ,
Helicobacter pylori-induced modulation of the promoter methylation of Wnt antagonist genes in gastric carcinogenesis.
Gastric Cancer. 2018;21(2):237-248.

Abstract
BACKGROUND This study aimed to investigate the changes in the promoter methylation and gene expression of multiple Wnt antagonists between the chronic infection and eradication of Helicobacter pylori (H. pylori) in gastric carcinogenesis.
METHODS The levels of methylation and corresponding mRNA expression of seven Wnt antagonist genes (SFRP1, -2, -5, DKK1, -2, -3, WIF1) were compared among the patients with H. pylori-positive gastric cancers (GCs), and H. pylori-positive and H. pylori-negative controls, by quantitative MethyLight assay and real-time reverse transcription (RT)-polymerase chain reaction (PCR), respectively. The changes of the methylation and expression levels of the genes were also compared between the H. pylori eradication and H. pylori-persistent groups 1 year after endoscopic resection of GCs.
RESULTS The methylation levels of SFRP and DKK family genes were significantly increased in the patients with H. pylori-positive GCs and followed by H. pylori-positive controls compared with H. pylori-negative controls (P < 0.001). SFRP1, -2, and DKK3 gene expression was stepwise downregulated from H. pylori-negative controls, H. pylori-positive controls, and to H. pylori-positive GCs (P < 0.05). Among the Wnt antagonists, only the degrees of methylation and downregulation of DKK3 were significantly reduced after H. pylori eradication (P < 0.05).
CONCLUSION Epigenetic silencing of SFRP and DKK family genes may facilitate the formation of an epigenetic field during H. pylori-associated gastric carcinogenesis. The epigenetic field may not be reversed even after H. pylori eradication except by DKK3 methylation.
PubMed IF 6.1 소화기내과
572018

제1저자 김민주 · 교신저자 정혜승

, , , , , , , ,
Attenuation of PERK enhances glucose-stimulated insulin secretion in islets.
J Endocrinol. 2018;236(3):125-136.

Abstract
PERK is a pancreatic endoplasmic reticulum (ER) kinase. Its complete deletion in pancreatic β cells induces insulin deficiency; however, the effects of partial Perk suppression are unclear. We investigated the effect of partial PERK suppression using the specific PERK inhibitors GSK2606414 and GSK2656157. Low-dose GSK2606414 treatment for 24 h enhanced glucose-stimulated insulin secretion (GSIS), islet insulin content and calcium transit in mouse (at 40 nM) and human (at 50-100 nM) pancreatic islets. GSK2606414 also induced the expression of the ER chaperone BiP and the release of calcium from the ER. When Bip expression was inhibited using a Bip siRNA, the GSK2606414-induced augmentation of the ER calcium level, islet insulin contents, glucose-stimulated cytosolic calcium transit and GSIS were abrogated. In both wild-type and insulin-deficient Atg7-knockout mice, 8 weeks of GSK2656157 treatment enhanced GSIS and improved hyperglycemia without affecting body weight. In conclusion, partial PERK inhibition induced BiP expression in islets, increased glucose-stimulated calcium transit and islet insulin contents and enhanced GSIS, suggesting that low-dose PERK inhibitors could potentially be used to treat insulin deficiency.
PubMed IF 5.7 내분비대사내과
562018

제1저자 배지윤 · 교신저자 김남중

, , , , , , , ,
Concordance of results of blood and tissue cultures from patients with pyogenic spondylitis: a retrospective cohort study.
Clin Microbiol Infect. 2018;24(3):279-282.

Abstract
OBJECTIVES To investigate the concordance of results of blood and tissue cultures in patients with pyogenic spondylitis.
METHODS We searched for patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures by retrospective review of medical records in three tertiary university-affiliated hospitals between January 2005 and December 2015. The species and antimicrobial susceptibility patterns of isolates from blood and tissue cultures were compared.
RESULTS Among 141 patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures, the species of blood and tissue isolates were identical in 135 patients (95.7%, 135/141). Excluding the four anaerobic isolates, we investigated antimicrobial susceptibility patterns of 131 isolates of the same species from blood and tissue cultures. Antibiotic susceptibility patterns were identical in 128 patients (97.7%, 128/131). The most common isolates were Staphylococcus aureus (86 patients; 85 concordant and one discordant), followed by streptococcus (24 patients; 22 concordant and two discordant), and Escherichia coli (eight patients; all concordant).
CONCLUSIONS We suggest that a positive blood culture from patients with pyogenic spondylitis could preclude the need for additional tissue cultures, especially when S. aureus and streptococcus grew in blood cultures.
PubMed IF 8.7 감염내과
552018

제1저자 김민주,원재경 · 교신저자 박영주

, , , , , ,
Clinical Characteristics of Subtypes of Follicular Variant Papillary Thyroid Carcinoma.
Thyroid. 2018;28(3):311-318.

Abstract
BACKGROUND Among follicular variant papillary thyroid carcinomas (FVPTCs), the noninvasive encapsulated subtype has an excellent prognosis. For this reason, reclassification of noninvasive encapsulated FVPTC (EFVPTC) as a new entity called "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) has been proposed, but controversy remains. To characterize noninvasive EFVPTC in an Asian population, the clinicopathologic features of each FVPTC subtype were compared in a Korean population.
METHODS FVPTC patients (n = 142) who underwent thyroidectomy between 2009 and 2014, and whose tumor size was >1 cm, were included in the study. The surgical pathology of each patient was reevaluated by two independent expert pathologists.
RESULTS The percentages of noninvasive and invasive EFVPTC and infiltrative FVPTC (IFVPTC) in the study were 30%, 31%, and 39%, respectively. There was no difference in preoperative cytological diagnosis or the extent of surgery between noninvasive and invasive EFVPTC. However, the proportion of Bethesda category IV was lower in IFVPTC (16%) than in noninvasive and invasive EFVPTC (35% and 36%, respectively). Therefore, thyroid lobectomy was more common in noninvasive or invasive EFVPTC (54% or 48%, respectively) than in IFVPTC (16%). Noninvasive EFVPTC showed lower multiplicity, extrathyroidal extension, and BRAF^V600E mutation frequency (three cases; 8%) than did invasive EFVPTC, but other pathological characteristics were similar. However, IFVPTC showed significant differences in tumor size, extrathyroidal extension, lymph node metastasis, Tumor Node Metastasis stage, and American Thyroid Association high-risk category compared with noninvasive and invasive EFVPTC. In the noninvasive EFVPTC group, there were six (14%) cases with multifocality and three (7%) cases with lymph node metastasis. However, only two cases with multifocality and one case with lymph node metastasis originated from noninvasive FVPTC, while the other cases were from coexisting conventional PTCs.
CONCLUSIONS Noninvasive EFVPTC has favorable pathological features, but lymph node metastasis or BRAF^V600E mutations were observed in some patients. Therefore, in order for the distinction between noninvasive EFVPTC and invasive EFVPTC to have more clinical significance, the criteria for NIFTP need to be more strictly revised.
PubMed IF 6.6 내분비대사내과
542018

제1저자 이선민 · 교신저자 김나영

, , , , , , ,
rdxA, frxA, and efflux pump in metronidazole-resistant Helicobacter pylori: Their relation to clinical outcomes.
J Gastroenterol Hepatol. 2018;33(3):681-688.

Abstract
BACKGROUND AND AIM rdxA and frxA mutations and enhancement of efflux pump have been suggested as the cause of metronidazole resistance in Helicobacter pylori. This study was performed to investigate the resistance mechanisms related to clinical eradication outcome, and to examine direct involvement of hefA in metronidazole-resistant isolates with intact rdxA and frxA.
METHODS A total of 53 H. pylori-positive patients who were treated with metronidazole-containing sequential or quadruple therapy from 2011 to 2015 were enrolled. The metronidazole susceptibility of H. pylori isolates was examined by agar dilution test. Mutations in rdxA and frxA, were analyzed with DNA sequencing, and impact of hefA on metronidazole resistance was examined with quantitative real-time reverse transcription polymerase chain reaction, knockout and genetic complementation test for hefA.
RESULTS Seven mutation types of rdxA and/or frxA were found in H. pylori isolated from non-eradicated subjects. rdxA mutation was associated with eradication failure (P = 0.002), and nonsense mutation in rdxA reduced eradication efficacy (P = 0.009). hefA expression was significantly higher in resistant isolates (P < 0.001), especially in rdxA(-)frxA(-) as compared to rdxA(+)frxA(+) (P = 0.027). Resistant isolates with no mutation in rdxA and frxA became susceptible after hefA knockout. Genetic complementation for hefA recovered metronidazole resistance in all of three hefA knockout mutants.
CONCLUSIONS These results suggest that rdxA mutations play a critical role in metronidazole resistance as well as the outcomes of eradication therapy. In addition, hefA seems to be directly involved in metronidazole resistance, which explains the resistance in clinical isolates with intact rdxA and frxA.
PubMed IF 3.5 소화기내과
532018

제1저자 박세훈 · 교신저자 유경돈, 이하정

, , , , , , , , , , , , ,
Pregnancy in women with immunoglobulin A nephropathy: are obstetrical complications associated with renal prognosis?
Nephrol Dial Transplant. 2018;33(3):459-465.

Abstract
BACKGROUND Recent studies regarding immunoglobulin A nephropathy (IgAN) suggest no relationship between pregnancy and disease progression, although complicated pregnancies and impaired renal function are closely related.
METHODS This study used a propensity-score-matched cohort analysis. Among biopsy-confirmed IgAN women in three hospitals in Korea, those who experienced pregnancy after their diagnosis were included in the study group. Renal outcome was the composite of serum creatinine doubling, estimated glomerular filtration rate (eGFR) halving and events of end-stage renal disease. Pregnancies with preterm birth, low birth weight and pre-eclampsia were defined as complicated.
RESULTS Overall, 59 IgAN women who became pregnant after their diagnosis, and the same number of IgAN women who did not experience pregnancy were included in the control group. Although pregnancy itself did not worsen renal outcomes [adjusted hazard ratio (HR): 1.51; 95% confidence interval (CI) 0.57-4.01; P = 0.41], mothers with complicated pregnancies experienced worse renal prognosis, even after adjustment for baseline and pre-gestational characteristics (adjusted HR: 5.07; 95% CI 1.81-14.22; P = 0.002). Moreover, this relationship was only significant in mothers with decreased renal function (eGFR <60 mL/min/1.73 m2) (adjusted HR: 18.70; 95% CI 1.63-214.40; P = 0.02), baseline hypertension (adjusted HR: 4.17; 95% CI 1.13-15.33; P = 0.03) and overt proteinuria (≥1 g/day) (adjusted HR: 4.21; 95% CI 1.24-14.27; P = 0.02). In contrast, patients who experienced pregnancies without complications showed better renal outcomes than did those without post-biopsy pregnancy (P = 0.01).
CONCLUSION Obstetric complications in patients with high renal risk, rather than pregnancy itself, are associated with renal progression of IgAN women.
PubMed IF 8.3 신장내과
522018

제1저자 조나리야 · 교신저자 임석아

, , , , , , , , , ,
Integrated 18F-FDG PET/MRI in breast cancer: early prediction of response to neoadjuvant chemotherapy.
Eur J Nucl Med Mol Imaging. 2018;45(3):328-339.

Abstract
PURPOSE To explore whether integrated ¹⁸F-FDG PET/MRI can be used to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with breast cancer.
METHODS Between November 2014 and April 2016, 26 patients with breast cancer who had received NAC and subsequent surgery were prospectively enrolled. Each patient underwent ¹⁸F-FDG PET/MRI examination before and after the first cycle of NAC. Qualitative MRI parameters, including morphological descriptors and the presence of peritumoral oedema were assessed. Quantitatively, PET parameters, including maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis (TLG), and MRI parameters, including washout proportion and signal enhancement ratio (SER), were measured. The performance of the imaging parameters singly and in combination in predicting a pathological incomplete response (non-pCR) was assessed.
RESULTS Of the 26 patients, 7 (26.9%) exhibited a pathological complete response (pCR), and 19 (73.1%) exhibited a non-pCR. No significant differences were found between the pCR and non-pCR groups in the qualitative MRI parameters. The mean percentage reductions in TLG_30% on PET and SER on MRI were significantly greater in the pCR group than in the non-pCR group (TLG_30% -64.8 ± 15.5% vs. -25.4 ± 48.7%, P = 0.005; SER -34.6 ± 19.7% vs. -8.7 ± 29.0%, P = 0.040). The area under the receiver operating characteristic curve for the percentage change in TLG_30% (0.789, 95% CI 0.614 to 0.965) was similar to that for the percentage change in SER (0.789, 95% CI 0.552 to 1.000; P = 1.000).The specificity of TLG_30% in predicting pCR) was 100% (7/7) and that of SER was 71.4% (5/7). The sensitivity of TLG_30% in predicting non-pCR was 63.2% (12/19) and that of SER was 84.2% (16/19). When the combined TLG_30% and SER criterion was applied, sensitivity was 100% (19/19), and specificity was 71.4% (5/7).
CONCLUSION ¹⁸F-FDG PET/MRI can be used to predict non-pCR after the first cycle of NAC in patients with breast cancer and has the potential to improve sensitivity by the addition of MRI parameters to the PET parameters.
PubMed IF 7.6 혈액종양내과
512018

제1저자 민세희 · 교신저자 임수

, , , , , , , , ,
Independent Association of Serum Aldosterone Level with Metabolic Syndrome and Insulin Resistance in Korean Adults.
Korean Circ J. 2018;48(3):198-208.

Abstract
BACKGROUND AND OBJECTIVES A relationship between renin-angiotensin system (RAS) components and metabolic syndrome (MetS) has been suggested, but not elucidated clearly. We examined the levels of RAS components in patients with and without MetS and their association with MetS in Korean population.
METHODS This study was approved by the review boards of the participating institutions and endorsed by the Korean Society of Lipid and Atherosclerosis. We screened 892 Koreans aged ≥20 years who underwent evaluation of hypertension, diabetes, or dyslipidemia at 6 tertiary hospitals in 2015-2016. After excluding patients who were taking diuretics, β-blockers, or RAS blockers, or suspected of primary aldosteronism, 829 individuals were enrolled. Anthropometric and biochemical parameters including aldosterone, plasma renin activity (PRA), and aldosterone-to-PRA ratio were evaluated. The homeostasis model assessment for insulin resistance (HOMA-IR) were used for evaluating insulin resistance.
RESULTS The mean age of the participants was 52.8±12.8 years, 56.3% were male, and their mean systolic and diastolic blood pressures were 133.9±20.0 and 81.2±14.6 mmHg, respectively. The levels of serum aldosterone, but not PRA, were significantly higher in subjects with MetS than in those without (20.6±33.6 vs. 15.3±12.2 ng/dL, p<0.05), and positively correlated with waist circumference, blood pressure, triglycerides, and glycated hemoglobin. The levels of aldosterone were independently associated with the number of MetS components and HOMA-IR after adjusting for conventional risk factors.
CONCLUSIONS Serum aldosterone levels were higher in Korean adults with MetS than in those without. This finding suggests that increased aldosterone level might be closely associated with insulin resistance.
PubMed IF 3.4 내분비대사내과
502018

제1저자 곽민선 · 교신저자 정수진

, , , , , ,
Long-term Outcome of Small, Incidentally Detected Rectal Neuroendocrine Tumors Removed by Simple Excisional Biopsy Compared With the Advanced Endoscopic Resection During Screening Colonoscopy.
Dis Colon Rectum. 2018;61(3):338-346.

Abstract
BACKGROUND Incidental, small rectal neuroendocrine tumors during colonoscopy screening are sometimes removed using biopsy forceps. Few studies have examined the clinical course of rectal neuroendocrine tumors removed by simple excisional biopsy.
OBJECTIVE We investigated the long-term outcome of rectal neuroendocrine tumors removed by simple excisional biopsy compared with standard endoscopic resection.
DESIGN This was a cohort study.
SETTINGS This study was performed at a healthcare center in Korea.
PATIENTS We enrolled patients with rectal neuroendocrine tumors detected during a screening colonoscopy between 2003 and 2015.
MAIN OUTCOME MEASURES The clinical characteristics and long-term outcomes (overall survival and disease-free survival) of small neuroendocrine tumors <10 mm were compared between the simple excisional biopsy group and advanced endoscopic resection group.
RESULTS In total, 166 patients were diagnosed with rectal neuroendocrine tumors (≤5 mm, n = 100; 6-9 mm, n = 50; 10-19 mm, n = 15; ≥20 mm, n = 1). Among the 150 patients with neuroendocrine tumors <10 mm, follow-up endoscopy was performed on 99 (59.6%). All of the tumors were confined to the mucosa or submucosa. Thirty-one and 68 patients were included in the simple excisional biopsy and advanced endoscopic resection groups. The overall follow-up duration was 6.5 years (range, 1.0-12.8 y). Neither overall nor disease-related death occurred. Two patients exhibited local recurrence (6.5%, at 8 and 11 y) in the simple excisional biopsy group and 1 patient (1.5%, at 7 y) in the advanced endoscopic resection group, resulting in no significant difference (p = 0.37). All of the recurrences were diagnosed >5 years from initial diagnosis and successfully treated endoscopically.
LIMITATIONS More long-term data should be warranted.
CONCLUSIONS The long-term outcome of small rectal neuroendocrine tumors <10 mm removed by simple excisional biopsy was excellent. Neither overall survival nor disease-free survival significantly differed between the simple excisional biopsy group and the advanced endoscopic resection group. Thus, simple excisional biopsy and long-term follow-up can be cautiously applied for small rectal neuroendocrine tumors in clinical practice. See Video Abstract at http://links.lww.com/DCR/A406.
PubMed IF 3.1 소화기내과
492018

제1저자 김정한,김택수 · 교신저자 박완범

, , , , , , , , , , , , , , , ,
Direct rapid antibiotic susceptibility test (dRAST) for blood culture and its potential usefulness in clinical practice.
J Med Microbiol. 2018;67(3):325-331.

Abstract
PURPOSE The direct rapid antibiotic susceptibility test (dRAST), based on analysing changes in bacterial micro-colonies under antibiotic conditions, detects antibiotic resistance within 6 h of direct smear examination results. This study aimed to assess the accuracy of dRAST and evaluate its potential usefulness for improving selection of appropriate antibiotic in real clinical practice settings.
METHODOLOGY We evaluated the accuracy of dRAST by comparing the antibiotic treatments that should have been administered based on dRAST results and the broth microdilution (BMD) test and its potential usefulness via simulation.
RESULT For 49/52 (94.2 %) patients with Gram-positive bacteraemia and 66/67 (98.5 %) patients with Gram-negative bacteraemia, antibiotics indicated by dRAST results were the same as those indicated by the BMD test. Among 34 patients with ineffective and suboptimal treatment, 19 (55.9 %) of patients could have received optimal treatment 1 to 2 days earlier with dRAST results. Among 33 patients given unnecessary broad-spectrum antibiotics, 1 to 2 days earlier de-escalation could have been possible for 27 (81.8 %) patients based on dRAST results.
CONCLUSION The introduction of dRAST could increase the use of optimal antibiotics and reduce unnecessary broad-spectrum antibiotic use in the early period of bacteraemia.
PubMed IF 2.7 감염내과
482018

제1저자 변자민 · 교신저자 윤성수

, , , , , , ,
Distinct predictive impact of FISH abnormality in proteasome inhibitors and immunomodulatory agents response: redefining high-risk multiple myeloma in Asian patients.
Cancer Med. 2018;7(3):831-841.

Abstract
For risk-adaptive therapeutic approaches in multiple myeloma (MM) treatment, we analyzed treatment outcome according to in situ hybridization (FISH) profiles to investigate the prognostic and predictive values of structural variations in a large series of Asian population. A total of 565 newly diagnosed patients with multiple myeloma between January 2005 and June 2015 were evaluated. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), t(14;16) in 2.5% (8/326), t(4;14) in 27.9% (109/390), IgH rearrangement in 47.7% (248/520), and +1q21 in 40.8% (211/517). The presence of del(17p13), IgH rearrangement, and t(14;16) was associated with worse overall survival. Interestingly, however, the presence of t(4;14) conferred little prognostic impact. Treatment-specific analysis revealed the presence of del(17p13), t(14;16), IgH rearrangement, and trisomy 1q21 was predictive of unsatisfactory response to bortezomib. On the other hand, patients with del(13q14) and del(9p21) were less likely to benefit from lenalidomide. Autologous stem cell transplantation (autoSCT) was less effective in patients with del(17p13), t(14;16), and trisomy 1q21. Predictive values of del(17p13) and t(14;16) to bortezomib and autoSCT are seemingly universal, but predictive marker del(13q14) and del(9p21) for lenalidomide response appears ethnicity-specific. Thus, FISH profiles in MM treatment should be interpreted with regards to patient's ethnicity.
PubMed IF 3.5 혈액종양내과
472018

제1저자 김민석 · 교신저자 김학령

, , , , , , ,
Body mass index and the risk of low femoral artery puncture in coronary angiography under fluoroscopy guidance.
Medicine (Baltimore). 2018;97(9):e0070.

Abstract
The inferior border of the femoral head (IBFH) is widely used as a landmark in femoral artery puncture during invasive coronary angiography (ICA). However, application of this technique can be challenging especially in obese patients. This study was performed to investigate the association between body mass index (BMI) and the risk of low puncture in femoral artery puncture.A total of 464 patients (64.8 ± 11.1 years, 55.8% male) who underwent ICA via trans-femoral access were retrospectively reviewed. IBFH was used as a landmark for a skin nick and the femoral artery cannulation site was confirmed by femoral angiography. Cannulation at the bifurcation of the common femoral artery (CFA) or below were considered low puncture.Twenty-nine patients (5.8%) were identified as having an angiographically high CFA bifurcation and low femoral artery puncture occurred in 27 (93.1%) patients of them. Among patients with normal bifurcation (n = 464), low puncture occurred in 74 (15.9%) patients. Underweight (BMI < 18.5 kg/m) or obese (BMI ≥ 30 kg/m) patients were more common in the low puncture group than in the proper puncture group (36.5% vs. 5.9%, P < .001). Multivariable analysis showed underweight or obesity (odd ratio, 9.10; 95% confidential interval, 4.77-17.35; P < .001) was an independent risk factor of low puncture even after controlling for clinical covariates. The average distance from IBFH to the CFA puncture site was shorter in patients with underweight (1.74 ± 0.71 cm) or obesity (1.75 ± 0.60 cm) than in those with normal BMI or overweight (2.07 ± 0.83 cm) (P = .030). Trigonometric calculation showed that the average distance from IBFH to the CFA puncture site was 0.5 to 2.59 cm (mean = 1.32 cm) shorter in underweight patients compared with those of normal weight or overweight patients.In patients with normal CFA bifurcation, underweight or obesity were associated with increased risk of low puncture. The puncture site should be chosen about 1 finger width more proximal to IBFH for ICA in such patients.
PubMed IF 2 순환기내과
462018

제1저자 강시혁 · 교신저자 서정원

, , , , ,
Cardiac Auscultation Using Smartphones: Pilot Study.
JMIR Mhealth Uhealth. 2018;6(2):e49.

Abstract
BACKGROUND Cardiac auscultation is a cost-effective, noninvasive screening tool that can provide information about cardiovascular hemodynamics and disease. However, with advances in imaging and laboratory tests, the importance of cardiac auscultation is less appreciated in clinical practice. The widespread use of smartphones provides opportunities for nonmedical expert users to perform self-examination before hospital visits.
OBJECTIVE The objective of our study was to assess the feasibility of cardiac auscultation using smartphones with no add-on devices for use at the prehospital stage.
METHODS We performed a pilot study of patients with normal and pathologic heart sounds. Heart sounds were recorded on the skin of the chest wall using 3 smartphones: the Samsung Galaxy S5 and Galaxy S6, and the LG G3. Recorded heart sounds were processed and classified by a diagnostic algorithm using convolutional neural networks. We assessed diagnostic accuracy, as well as sensitivity, specificity, and predictive values.
RESULTS A total of 46 participants underwent heart sound recording. After audio file processing, 30 of 46 (65%) heart sounds were proven interpretable. Atrial fibrillation and diastolic murmur were significantly associated with failure to acquire interpretable heart sounds. The diagnostic algorithm classified the heart sounds into the correct category with high accuracy: Galaxy S5, 90% (95% CI 73%-98%); Galaxy S6, 87% (95% CI 69%-96%); and LG G3, 90% (95% CI 73%-98%). Sensitivity, specificity, positive predictive value, and negative predictive value were also acceptable for the 3 devices.
CONCLUSIONS Cardiac auscultation using smartphones was feasible. Discrimination using convolutional neural networks yielded high diagnostic accuracy. However, using the built-in microphones alone, the acquisition of reproducible and interpretable heart sounds was still a major challenge.
TRIAL REGISTRATION ClinicalTrials.gov NCT03273803; https://clinicaltrials.gov/ct2/show/NCT03273803 (Archived by WebCite at http://www.webcitation.org/6x6g1fHIu).
PubMed IF 6.3 순환기내과
452018

제1저자 김지현 · 교신저자 김주성

, , , , ,
Role of iRhom2 in intestinal ischemia-reperfusion-mediated acute lung injury.
Sci Rep. 2018;8(1):3797.

Abstract
Intestinal ischemia-reperfusion (I/R) may cause acute systemic and lung inflammation. However, the detailed mechanism of this inflammatory cascade has not been fully elucidated. Inactive rhomboid protein 2 (iRhom2) is essential for the maturation of TNF-α converting enzyme (TACE), which is required for TNF-α secretion. We evaluated the role of iRhom2 in a mouse model of intestinal I/R using iRhom2 knockout (KO) and wild-type (WT) mice. Lung injury following intestinal I/R was significantly attenuated in iRhom2 KO mice compared with WT mice. After intestinal I/R, lungs from iRhom2 KO mice showed significantly lower myeloperoxidase (MPO) activity and markedly reduced cell apoptosis associated with a decreased level of active caspase 3 and decreased TUNEL staining compared with lungs from WT mice. TNF-α levels were elevated in the serum and lungs of WT mice with intestinal I/R and significantly reduced in iRhom2 KO mice with intestinal I/R. iRhom2 may play a critical role in the pathogenesis of acute lung injury (ALI) after intestinal I/R and thus may be a novel therapeutic target for ALI after intestinal I/R injury.
PubMed IF 4.9 소화기내과
442018

제1저자 조용숙 · 교신저자 이창훈

, , , ,
The cutoff point of clinical chronic obstructive pulmonary disease questionnaire for more symptomatic patients.
BMC Pulm Med. 2018;18(1):38.

Abstract
BACKGROUND An adequate threshold for the Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (CCQ) defining more symptomatic COPD patients has not been determined. We aimed to determine the efficacy of the CCQ and the appropriate CCQ threshold for more symptomatic COPD patients.
METHODS COPD patients aged > 40 years who smoked/had smoked ≥10 packs/year were prospectively enrolled over 1 year from three South Korean hospitals (n = 126). Correlations between the CCQ and St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), the modified Medical Round Council (mMRC) scale, lung function, and exercise capacity were evaluated. "More symptomatic patients" were those with an SGRQ score ≥ 25. Area under the receiver operating curve and classification and regression tree analyses were performed to determine the CCQ threshold equivalent to an SGRQ score ≥ 25.
RESULTS The CCQ significantly correlated with the SGRQ, CAT, and mMRC scale (r = 0.76, 0.69, and 0.53, respectively). A CCQ cutoff of 1.4 predicted an SGRQ score of 25 better than others. A CCQ score of 1.4 was a significant determinant of an SGRQ score ≥ 25 even after adjusting for potential confounders.
CONCLUSIONS The CCQ was correlated with other symptom indicators, lung function, and exercise capacity. A CCQ cutoff of 1.4 agreed better than CCQ cutoff of 1.0, suggested by guideline, and this cutoff value may identify more symptomatic COPD patients well.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02527486 . Date of registration: December 19, 2014, retrospectively registered.
PubMed IF 3.1 호흡기내과
432018

제1저자 박종한 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , ,
Clinical Relevance of Functionally Insignificant Moderate Coronary Artery Stenosis Assessed by 3-Vessel Fractional Flow Reserve Measurement.
J Am Heart Assoc. 2018;7(4):JAHA.117.008055.

Abstract
BACKGROUND Understanding of the risk conferred by functionally insignificant lesions in multiple coronary vessels is limited. We investigated the prognostic implications of coronary artery disease (CAD) based on 3-vessel fractional flow reserve (FFR).
METHODS AND RESULTS A total of 1,136 patients underwent FFR measurement in the 3 major epicardial arteries. We defined vessels with "Moderate CAD" as vessels with FFR, 0.81 to 0.87. Patients were classified into Group 1: No apparent CAD (FFR>0.87 in all 3-vessels); Group 2: Single-vessel moderate CAD; Group 3: Multivessel moderate CAD; and Group 4: Functionally significant CAD (FFR≤0.80) in any vessel. The primary end point was 2-year major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Forty-three percent of patients had moderate CAD (Group 2: 403/1136, 35.5%; Group 3: 84/1136, 7.4%). The 2-year risk of major adverse cardiac events was not significantly different between patients with single-vessel moderate CAD and no apparent CAD (2.6 versus 2.6%; HR, 1.1; 95% confidence interval, 0.4%-2.8%; P=0.89). However, patients with multivessel moderate CAD were at significantly higher risk than Group 1 (7.4 versus 2.6%; hazard ratio, 3.3; 95% confidence interval, 1.1%-9.8%; P=0.03). The risk of major adverse cardiac events in patients with multivessel moderate CAD was comparable to that of patients with functionally significant CAD (hazard ratio, 1.2; 95% confidence interval, 0.5%-3.0%; P=0.67). In a multivariable regression model, multivessel moderate CAD was an independent predictor of greater risk of 2-year major adverse cardiac events.
CONCLUSIONS Global physiologic assessment with FFR measurement of 3 vessels can identify multivessel moderate CAD. The prognostic implication of multivessel moderate CAD appears comparable to that of functionally significant CAD.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.
PubMed IF 6 순환기내과
422018

제1저자 손경희 · 교신저자 강혜련

, , , , , ,
Incidence and Risk of Oxaliplatin-Induced Hypersensitivity in Patients with Asymptomatic Prior Exposure: A Prospective Observational Study.
J Allergy Clin Immunol Pract. 2018;6(5):1642-1648.e2.

Abstract
BACKGROUND Oxaliplatin-related hypersensitivity reactions (HSRs), which can be life threatening, have introduced a dilemma regarding the use of chemotherapeutic agents. Because repeated exposure to oxaliplatin may increase the risk of sensitization, patients with a history of prior asymptomatic exposure require risk-stratified care.
OBJECTIVE This study aimed to elucidate the incidence and risk of oxaliplatin HSRs in patients with a history of asymptomatic prior exposure.
METHODS We performed a prospective observational study of patients who completed oxaliplatin-based chemotherapy between March 2013 and January 2015. Prior exposure to oxaliplatin, the oxaliplatin-free interval, reaction severity, eosinophil counts, and premedication were reviewed to assess the risk factors.
RESULTS A total of 793 patients were enrolled, among whom 148 (18.7%) experienced an HSR. The HSR incidence was 15.2% among oxaliplatin-naive patients but increased to 31.9% among those with a history of asymptomatic exposure and 75.0% among those with a history of oxaliplatin HSRs during the previous exposure, despite prophylaxis. The mean HSR onset cycle was earliest in the previous HSR group, followed by the previous asymptomatic exposure and nonexposure groups. The HSR severity also differed according to the previous exposure history and HSRs. In the multivariate analysis, prior exposure to oxaliplatin (odds ratio [OR], 3.78; 95% confidence interval [CI], 2.46-5.79) and a longer oxaliplatin-free interval (≥36 months; OR, 4.85; 95% CI, 1.60-14.37) were independent risk factors for HSRs.
CONCLUSIONS Previous exposure to oxaliplatin is a risk factor for earlier HSR onset and more severe and frequent HSR episodes, even if prior therapy was well tolerated.
PubMed IF 6.6 알레르기내과
412018

제1저자 박찬순,최동주 · 교신저자 박진주

, , , , , , , , , , , , , ,
Assessment of clinical effect and treatment quality of immediate-release carvedilol-IR versus SLOW release carvedilol-SR in Heart Failure patients (SLOW-HF): study protocol for a randomized controlled trial.
Trials. 2018;19(1):103.

Abstract
BACKGROUND Carvedilol is a non-selective, third-generation beta-blocker and is one of the cornerstones for treatment for patients with heart failure and reduced ejection fraction (HFrEF). However, due to its short half-life, immediate-release carvedilol (IR) needs to be prescribed twice a day. Recently, slow-release carvedilol (SR) has been developed. The aim of this study is to evaluate whether carvedilol-SR is non-inferior to standard carvedilol-IR in terms of its clinical efficacy in patients with HFrEF.
METHODS/DESIGN Patients with stable HFrEF will be randomly assigned in a 1:1 ratio to the carvedilol-SR group (160 patients) and the carvedilol-IR group (160 patients). Patients aged ≥ 20 years, with a left ventricular ejection fraction ≤ 40%, N-terminal pro B-natriuretic peptide (NT-proBNP) ≥ 125 pg/ml or BNP ≥ 35 pg/ml, who are clinically stable and have no evidence of congestion or volume retention, will be eligible. After randomization, patients will be followed up for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the proportion of patients with NT-proBNP increment > 10% from baseline, composite of all-cause mortality and readmission, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance.
DISCUSSIONS The SLOW-HF trial is a prospective, randomized, open-label, phase-IV, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in HFrEF patients. If carvedilol-SR proves to be non-inferior to carvedilol-IR, a once-daily prescription of carvedilol may be recommended for patients with HFrEF.
TRIAL REGISTRATION ClinicalTrials.gov, ID: NCT03209180 . Registered on 6 July 2017.
PubMed IF 2.1 순환기내과
402018

제1저자 최기홍 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , , , , ,
Prognostic Implication of Functional Incomplete Revascularization and Residual Functional SYNTAX Score in Patients With Coronary Artery Disease.
JACC Cardiovasc Interv. 2018;11(3):237-245.

Abstract
OBJECTIVES The aim of this study was to investigate the prognostic implication of functional incomplete revascularization (IR) and residual functional SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (rFSS) in comparison with 3-vessel fractional flow reserve (FFR) and residual SYNTAX score.
BACKGROUND IR is associated with poor clinical outcomes in patients who underwent percutaneous coronary intervention.
METHODS A total of 385 patients who underwent 3-vessel FFR measurement after stent implantation were included in this study. The rFSS was defined as residual SYNTAX score measured only in vessels with FFR ≤0.8. The study population was divided into the functional IR group (rFSS ≥1) and the functional complete revascularization (CR) group (rFSS = 0). The primary outcome was major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) at 2 years.
RESULTS Functional CR was achieved in 283 patients (73.5%). At 2-year follow-up, the functional IR group showed a significantly higher risk for MACEs (functional IR vs. CR, 14.6% vs. 4.2%; hazard ratio: 4.09; 95% confidence interval: 1.82 to 9.21; p < 0.001) than the functional CR group. In a multivariate-adjusted model, functional IR was an independent predictor of MACEs (adjusted hazard ratio: 4.17; 95% confidence interval: 1.85 to 9.44; p < 0.001). The rFSS showed a significant association with estimated 2-year MACE rate (hazard ratio: 1.09 per 1-U increase; 95% confidence interval: 1.02 to 1.17; p = 0.018). When added to clinical risk factors, rFSS showed the highest integrated discrimination improvement value for MACEs (3.5%; p = 0.002) among 3-vessel FFR, residual SYNTAX score, and rFSS.
CONCLUSIONS Patients with functional IR showed significantly higher rate of 2-year MACEs than those with functional CR. A combined anatomic and physiological scoring system (rFSS) after stent implantation better discriminated the risk for adverse events than anatomic or physiological assessment alone. (Clinical Implication of 3-Vessel Fractional Flow Reserve [FFR]; NCT01621438).
PubMed IF 12.7 순환기내과
392018

제1저자 황성욱 · 교신저자 김주성

, , , ,
Intestinal alkaline phosphatase ameliorates experimental colitis via toll-like receptor 4-dependent pathway.
Eur J Pharmacol. 2018;820:156-166.

Abstract
Intestinal alkaline phosphatase (IAP) is an intestinal brush border enzyme which plays an important role in gut homeostasis and mucosal inflammation. However, the mechanism of the protective effect of IAP is not fully elucidated. The aim of the present study was to evaluate whether the protective effect of IAP on colitis is mediated via the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway. For in vitro analysis, peritoneal macrophages from the wild-type (WT) and TLR4-deficient (TLR4^-/-) C57BL/6 mice were used. IAP strongly inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by suppressing the LPS-induced phosphorylation of IκBα and the DNA-binding activity of NF-κB in WT macrophages; however, the inhibitory effects mediated by IAP were reduced in the TLR4^-/- macrophages. For in vivo analysis, the protective mechanisms of IAP on dextran sulfate sodium (DSS)-induced colitis were evaluated using WT and TLR4^-/- mice. Although oral administration of IAP significantly attenuated the severity of colitis in both preventive and therapeutic models of WT mice, these protective effects were not significant in TLR4^-/- mice. When immunohistochemical analysis of IκBα was performed in the colitic tissues, the inhibitory effects of IAP on IκBα phosphorylation were also observed in the colon of WT mice, but these effects decreased in the colon of TLR4^-/- mice. In conclusion, the protective effects of IAP on colitis were mediated via the TLR4/NF-κB pathway. These results of this study shall be helpful in tailoring treatment against colitis using IAP.
PubMed IF 5.7 소화기내과
382018

제1저자 이근욱, 이대호 · 교신저자 방영주

, , , , , , , ,
Phase I Pharmacokinetic Study of Nivolumab in Korean Patients with Advanced Solid Tumors.
Oncologist. 2018;23(2):155-e17.

Abstract
LESSONS LEARNED This pharmacokinetic study of nivolumab showed that there is little ethnic difference in the handling of nivolumab.Nivolumab was well tolerated in Korean patients.
BACKGROUND This phase I study of nivolumab, an anti-programmed cell death-1 (anti-PD-1) monoclonal antibody, investigated the pharmacokinetics and safety of nivolumab in Korean patients with advanced solid tumors. Findings were compared with results from Japan and the U.S.
MATERIALS AND METHODS In this two-part study, patients received a single dose of nivolumab (1, 3, and 10 mg/kg; ONO-4538-13) and were followed up for 3 weeks. Those who met the required criteria proceeded to the second part (ONO-4538-14), and received the same dose as in part one every 2 weeks.
RESULTS Six patients per dose level were enrolled (n = 18). The mean elimination half-life of nivolumab among the groups ranged from 15.0 to 19.1 days. The maximum serum concentration and area under serum concentration-time curve increased almost dose-proportionally at doses from 1 to 10 mg/kg. Adverse drug reactions (ADRs; mostly grade ≤2) were reported in seven patients (38.9%). ADRs grade ≥3 occurred in one patient (5.6%; pneumonitis). Three patients (16.7%) developed ADRs related to thyroid dysfunction.
CONCLUSION The pharmacokinetic parameters of nivolumab were similar among patients from Korea, Japan, and the U.S. The safety profile was consistent with findings from previous studies.
PubMed IF 4.7 혈액종양내과
372018

제1저자 황호영, 구본권 · 교신저자 김기봉

, , , ,
Endothelial Shear Stress of the Saphenous Vein Composite Graft Based on the Internal Thoracic Artery.
Ann Thorac Surg. 2018;105(2):564-571.

Abstract
BACKGROUND Endothelial shear stress (ESS) has been suggested as a factor affecting atherosclerosis and remodeling of native vessels and bypass conduits. We compared ESS levels of internal thoracic artery (ITA) and saphenous vein (SV) composite grafts intraoperatively and 1 year after coronary artery bypass grafting (CABG).
METHODS Intraoperative ESS was calculated by measuring flow volumes and diameters of proximal and distal ITAs and SV conduits in 23 patients who received SV Y-composite grafts based on the in situ left ITA. Early (1.2 ± 0.5 days) and 1-year (12.9 ± 1.1 months) postoperative angiograms were performed in 23 and 15 patients, respectively. An intragraft Doppler-guidewire study for ESS measurement was performed in 6 patients during 1-year angiography.
RESULTS Intraoperative diameters of proximal and distal ITAs and SV conduits were 2.0 ± 0.2 mm, 1.8 ± 0.3 mm, and 3.2 ± 0.4 mm, respectively. ESS levels were significantly different between them (41.0 ± 21.0, 28.4 ± 25.2, and 4.3 ± 3.0 dyne/cm², respectively). Proximal and distal ITA diameters increased significantly on early angiograms and remained unchanged, but SV diameter increased to 3.7 mm (95% confidence interval, 3.5 to 4.0 mm; p < 0.001) on the early angiogram and decreased to 2.9 mm (95% confidence interval, 2.7 to 3.2 mm; p < 0.001) at 1 year. Significant correlations were found between the initial ESS and proportional changes in conduit diameters during postoperative year 1. SV ESS increased in all 6 patients at 1 year, with no significant differences in ESS levels between the 3 conduits (29.9 ± 7.9, 28.8 ± 7.9, and 21.6 ± 16.3 dyne/cm², respectively).
CONCLUSIONS Initial ESS appears to be associated with proportional changes in conduit diameters in the first year after CABG. ESS values of SV composite grafts were similar to left ITA conduits 1 year after CABG.
PubMed IF 5.3 순환기내과
362018

제1저자 이현정 · 교신저자 김학령

, , , , , , ,
Interaction of Metabolic Health and Obesity on Subclinical Target Organ Damage.
Metab Syndr Relat Disord. 2018;16(1):46-53.

Abstract
BACKGROUND Metabolically healthy obese (MHO) individuals generally show better cardiovascular prognosis compared with metabolically unhealthy counterparts, which may be related to different patterns of target organ damage (TOD). We aimed to investigate the patterns of TOD related to obesity and metabolic unhealthiness.
METHODS A total of 659 Korean adults (mean age, 60.0 ± 11.8 years; male, 51.1%) undergoing health examinations were stratified into four groups according to obesity (body mass index ≥25.0 kg/m²) and metabolic healthiness (meeting ≤1 criteria of metabolic syndrome excluding abdominal circumference): metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), MHO, and metabolically unhealthy obese (MUO). Four measures of TOD were evaluated: arterial stiffness, renal dysfunction, left ventricular (LV) diastolic dysfunction, and LV hypertrophy (LVH).
RESULTS In multivariable analyses, compared with the MHNO group, the MHO group showed 2.31 times higher odds for LVH, whereas, the MUNO group showed 3.14 and 6.28 times higher odds for increased arterial stiffness and renal dysfunction, respectively. Metabolic unhealthiness was associated with increased arterial stiffness [odds ratio (OR) 2.73; confidence interval (95% CI) 1.72-4.34], renal dysfunction (OR 4.02; 95% CI 1.54-10.49), and LV diastolic dysfunction (OR 2.28; 95% CI 1.14-4.55). Meanwhile, obesity showed weaker association with LVH and LV diastolic dysfunction, and was not associated with increased arterial stiffness and renal dysfunction in multivariable analyses.
CONCLUSIONS Metabolic unhealthiness shows more association with TOD than obesity, which may contribute to the higher risk of cardiometabolic abnormalities in MUNO compared with MHO.
PubMed IF 1.6 순환기내과

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