SCI 발표논문

1. 22782017

   제1저자 오윤규 · 교신저자 오국환

   Oh YK, Chin HJ, Ahn SY, An JN, Lee JP, Lim CS, Oh KH

   Discrepancies in Clinic and Ambulatory Blood Pressure in Korean Chronic Kidney Disease Patients.

   J Korean Med Sci. 2017;32(5):772-781.

   Abstract

   Blood pressure (BP) control is considered the most important treatment for preventing chronic kidney disease (CKD) progression and associated cardiovascular complications. However, clinic BP is insufficient to diagnose hypertension (HT) and to monitor overall BP control because it does not correlate well with ambulatory blood pressure monitoring (ABPM). We enrolled 387 hypertensive CKD patients (stages G1-G4, 58.4% male with median age 61 years) from 3 hospitals in Korea. HT of clinic BP and ABPM was classified as ≥ 140/90 and ≥ 130/80 mmHg, respectively. Clinic BP control rate was 60.2%. The median 24-hour systolic blood pressures (SBPs) of CKD G3b and CKD G4 were significantly higher than those of CKD G1-2 and CKD G3a. However, the median 24-hour SBPs were not different between CKD G1-2 and CKD G3a or between CKD G3b and CKD G4. Of all patients, 5.7%, 38.0%. 42.3%, and 14.0% were extreme-dippers, dippers, non-dippers, and reverse-dippers, respectively. Non-/reverse-dippers independently correlated with higher Ca × P product, higher intact parathyroid hormone (iPTH), and lower albumin. Normal BP was 33.3%, and sustained, masked, and white-coat HT were 29.7%, 26.9%, and 10.1%, respectively. White-coat HT independently correlated with age ≥ 61 years and masked HT independently correlated with CKD G3b/G4. In conclusion, ABPM revealed a high prevalence of non-/reverse-dippers and sustained/masked HT in Korean CKD patients. Clinicians should try to obtain a CKD patient's ABPM, especially among those who are older or who have advanced CKD as well as those with abnormal Ca × P product, iPTH, and albumin.

   PubMed IF 3.2 신장내과
2. 22772017

   제1저자 김학령 · 교신저자 조주희

   Kim HL, Kim YN, Kim HJ, Lim WH, Seo JB, Kim SH, Kim MA, Zo JH

   The value of diastolic flow reversal in the descending thoracic aorta as a determinant of invasively measured aortic pulse pressure.

   Echocardiography. 2017;34(5):649-655.

   Abstract

   AIM Although the diastolic flow reversal of the descending aorta has been recognized in patients with aortic regurgitation, its generation without this condition is still unknown. This study was performed to investigate whether flow patterns of the descending thoracic aorta, as measured by echocardiography, can represent invasively measured aortic pulse pressure (APP).

   METHODS A total of 100 patients (age, 62.3±11.0 years; men, 62.0%) undergoing invasive coronary angiography (ICA) was analyzed. APP was measured at ascending thoracic aorta using pigtail catheter before ICA. Flow in the descending thoracic aorta was assessed using pulse wave Doppler echocardiography, and R/F ratio was defined as reverse peak velocity (R)/forward peak velocity (F).

   RESULTS Eighty patients (80.0%) had obstructive coronary artery disease (CAD) (≥50% stenosis of one or more epicardial coronary arteries) in ICA. APP and R/F ratio were significantly higher in patients with obstructive CAD than those without (P<.05 for each). Both R/F ratio (β=0.379, P<.001) and APP (β=0.255, P<.001) were positively correlated with age. In simple linear regression analysis, there was a significant positive correlation between R/F ratio and APP (β=0.266, P<.001). This correlation remained significant even after controlling for potential confounders including age, gender, E/e', and left atrial volume index in multiple linear regression analysis (β=0.193, P=.036).

   CONCLUSIONS R/F ratio may be independently associated with APP in patients undergoing ICA.

   PubMed IF 1.8 순환기내과
3. 22762017

   제1저자 임유주, 방지인 · 교신저자 한세원, 팽진철

   Lim Y, Bang JI, Han SW, Paeng JC, Lee KH, Kim JH, Kang GH, Jeong SY, Park KJ, Kim TY

   Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib.

   Eur J Nucl Med Mol Imaging. 2017;44(5):757-764.

   Abstract

   PURPOSE This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC).

   METHODS Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome.

   RESULTS A total of 40 patients were evaluable for PET image analysis. Among various PET parameters, total lesion glycolysis (TLG) measured in the same target lesions for RECIST 1.1 analysis were the most significant in predicting prognosis, with the lowest p-value observed in TLG calculated using the margin threshold of 40 % (TLG_{40 %}). Further analysis using TLG_{40 %} showed significantly longer overall survival (OS) in patients with lower baseline TLG_{40 %} (<151.8) (p = 0.003, median 14.2 vs. 9.1 months in <151.8 and ≥151.8, respectively). Patients showing higher decrease in TLG_{40 %} after treatment showed significantly longer progression-free survival (PFS) (p = 0.001, median 8.0 vs. 2.4 months in %ΔTLG_{40 %} < -9.6 % and ≥ -9.6 %, respectively) and OS (p = 0.002, median 16.4 vs. 9.1 months in %ΔTLG_{40 %} < -9.6 % and ≥ -9.6 %, respectively). The same cutoff could discriminate patients with longer survival among the patients who were under the stable disease category according to RECIST 1.1 (median PFS 8.4 vs. 6.8 months, p = 0.020; median OS 18.3 vs. 11.5 months, p = 0.049).

   CONCLUSION Measurement of TLG can predict treatment outcome of regorafenib in mCRC.

   PubMed IF 7.6 혈액종양내과
4. 22752017

   제1저자 김민재 · 교신저자 김남중

   Kim MJ, Nam EY, Park KU, Choe PG, Park WB, Song KH, Kim ES, Kim HB, Oh MD, Kim NJ

   Limited usefulness of the interferon-gamma release assay in patients with HIV infections and negative tuberculin skin test results in a country with an intermediate tuberculosis burden.

   Infect Dis (Lond). 2017;49(5):420-422.

   PubMed IF 2.5 1.932
5. 22742017

   제1저자 이현정 · 교신저자 이해영

   Lee H, Dominiczak AF, Jennings GL, Cho EJ, Lee HY

   Case of Chronic Indolent Pheochromocytoma That Caused Medically Controlled Hypertension but Treatment-Resistant Diabetes Mellitus.

   Hypertension. 2017;69(5):740-746.

   PubMed IF 9.8 손환기내과
6. 22732017

   제1저자 이종찬 · 교신저자 황진혁

   Lee JC, Kim JW, Ahn S, Kim HW, Lee J, Kim YH, Paik KH, Kim J, Hwang JH

   Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity.

   Eur J Cancer. 2017;76:125-133.

   Abstract

   BACKGROUND FOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC).

   METHODS We reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012-2015. We established a modified Hryniuk model (http://www.rdicalc.com) and defined cumulative RDI (cRDI, %). The optimal cRDI thresholds for response rate (RR) and disease control rate (DCR) were assessed using receiver operating characteristic (ROC) analysis. Relationships between cRDI and haematologic toxicities (neutropenia and febrile neutropenia [FN]) were also analysed according to use of granulocyte colony-stimulating factor (G-CSF).

   RESULTS Among 156 eligible patients, 133 (48 locally advanced PC and 85 metastatic PC) completed initial treatment plan prior to the first radiological evaluation (median 58 days; 71.8% cRDI). For optimal cRDI thresholds, ROC curves showed a 71.2% cRDI for RR (83.3% sensitivity, 64.7% specificity, and 0.746 area under the curve [AUC]) and a 55.3% cRDI for DCR (93.6% sensitivity, 62.5% specificity and 0.805 AUC). Among 96 patients who did not receive prophylactic G-CSF, cRDI ≥80.1% was a significant predictor for frequent FN (73.7% sensitivity, 72.7% specificity and 0.793 AUC). There was no correlation between cRDI and haematologic toxicities in patients receiving prophylactic G-CSF.

   CONCLUSION To preserve optimal RR and DCR in advanced PC, cRDI values for FOLFIRINOX >70% and >55%, respectively, are recommended. If cRDI is >80%, primary G-CSF prophylaxis is needed.

   PubMed IF 7.9 소화기내과
7. 22722017

   제1저자 배은진 · 교신저자 이정표

   Bae E, Cha RH, Kim YC, An JN, Kim DK, Yoo KD, Lee SM, Kim MH, Park JT, Kang SW, Park JY, Lim CS, Kim YS, Yang SH, Lee JP

   Circulating TNF receptors predict cardiovascular disease in patients with chronic kidney disease.

   Medicine (Baltimore). 2017;96(19):e6666.

   Abstract

   Cardiovascular disease (CVD) is the main public health problem in patients with chronic kidney disease (CKD); however, there is no established biomarker for predicting CVD morbidity and mortality in CKD. The aim of this study was to evaluate the role of circulating tumor necrosis factor receptors (cTNFRs) in predicting CVD risk in CKD patients.We prospectively recruited 984 patients with CKD from 11 centers between 2006 and 2012. The levels of cTNFR1 and cTNFR2 were determined by performing an enzyme-linked immunosorbent assay. During the mean follow-up period of 4 years, 36 patients experienced a CVD event. The median serum concentrations of cTNFR1 and cTNFR2 were 2703.4 (225.6-13,057.7) and 5661.0 (634.9-30,599.6) pg/mL, respectively, and the cTNFR1 level was closely correlated with the cTNFR2 level (r = 0.86, P < .0001). The urinary protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) were significantly correlated with the cTNFR2 level (r = 0.21 for UPCR, r = -0.67 for eGFR; P < .001 for all). Similar correlations were observed for serum cTNFR1 (r = 0.21 for UPCR, r = -0.75 for eGFR; P < .001 for all). In the Cox proportional hazard analyses, cTNFR1 (hazard ratio [HR] 2.506, 95% confidence interval [CI] 1.186-5.295, P = .016) and cTNFR2 (HR 4.156, 95% CI 1.913-9.030, P < .001) predicted CVD risk even after adjustment for clinical covariates, such as UPCR, eGFR, and high-sensitivity C-reactive protein. cTNFR1 and 2 are associated with CVD and other risk factors in CKD, independently of eGFR and UPCR. Furthermore, cTNFRs could be relevant predictors of CVD in CKD patients.

   PubMed IF 2 신장내과
8. 22712017

   제1저자 이해영 · 교신저자 오병희

   Lee HY, Oh BH

   Heart Transplantation in Asia.

   Circ J. 2017;81(5):617-621.

   Abstract

   Heart transplantation (HTx) is the effective way to improve quality of life as well as survival in terminal heart failure (HF) patients. Since the first heart transplant in 1968 in Japan and in earnest in 1987 at Taiwan, HTx has been continuously increasing in Asia. Although the current percentage of heart transplants from Asia comprises only 5.7% of cases in the International Society of Heart and Lung Transplantation (ISHLT) registry, the values were under-reported and soon will be greatly increased. HTx in Asia shows comparable with or even better results compared with ISHLT registry data. Several endemic infections, including type B hepatitis, tuberculosis, and cytomegalovirus, are unique aspects of HTx in Asia, and need special attention in transplant care. Although cardiac allograft vasculopathy (CAV) is considered as a leading cause of death after HTx globally, multiple observations suggest less prevalence and benign nature of CAV among Asian populations. Although there are many obstacles such as religion, social taboo or legal process, Asian countries will keep overcoming obstacles and broaden the field of HTx.

   PubMed IF 5.8 순환기내과
9. 22702017

   제1저자 황도연 · 교신저자 구본권

   Hwang D, Jeon KH, Lee JM, Park J, Kim CH, Tong Y, Zhang J, Bang JI, Suh M, Paeng JC, Na SH, Cheon GJ, Cook CM, Davies JE, Koo BK

   Diagnostic Performance of Resting and Hyperemic Invasive Physiological Indices to Define Myocardial Ischemia: Validation With 13N-Ammonia Positron Emission Tomography.

   JACC Cardiovasc Interv. 2017;10(8):751-760.

   Abstract

   OBJECTIVES The authors sought to compare the diagnostic performance of fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and resting distal coronary artery pressure/aortic pressure (Pd/Pa) using ¹³N-ammonia positron emission tomography (PET).

   BACKGROUND The diagnostic performance of invasive physiological indices was reported to be different according to the reference to define the presence of myocardial ischemia.

   METHODS A total of 115 consecutive patients with left anterior descending artery stenosis who underwent both ¹³N-ammonia PET and invasive physiological measurement were included. Optimal cutoff values and diagnostic performance of FFR, iFR, and resting Pd/Pa were assessed using PET-derived coronary flow reserve (CFR) and relative flow reserve (RFR) as references. To compare discrimination and reclassification ability, each index was compared with integrated discrimination improvement (IDI) and category-free net reclassification index (NRI).

   RESULTS All invasive physiological indices correlated with CFR and RFR (all p values <0.001). The overall diagnostic accuracies of FFR, iFR, and resting Pd/Pa were not different for CFR <2.0 (FFR 69.6%, iFR 73.9%, and resting Pd/Pa 70.4%) and RFR <0.75 (FFR 73.9%, iFR 71.3%, and resting Pd/Pa 74.8%). Discrimination and reclassification abilities of invasive physiological indices were comparable for CFR. For RFR, FFR showed better discrimination and reclassification ability than resting indices (IDI = 0.170 and category-free NRI = 0.971 for iFR; IDI = 0.183 and category-free NRI = 1.058 for resting Pd/Pa; all p values <0.001).

   CONCLUSIONS The diagnostic performance of invasive physiological indices showed no differences in the prediction of myocardial ischemia defined by CFR. Using RFR as a reference, FFR showed a better discrimination and reclassification ability than resting indices.

   PubMed IF 12.7 순환기내과
10. 22692017

    제1저자 박재윤 · 교신저자 이정표

    Park JY, Yoo KD, Kim YC, Kim DK, Joo KW, Kang SW, Yang CW, Kim NH, Kim YL, Lim CS, Kim YS, Lee JP

    Early dialysis initiation does not improve clinical outcomes in elderly end-stage renal disease patients: A multicenter prospective cohort study.

    PLoS One. 2017;12(4):e0175830.

    Abstract

    BACKGROUND The optimal timing for initiating dialysis in end-stage renal disease (ESRD) is controversial, especially in the elderly.

    METHODS 665 patients ≥65 years old who began dialysis from August 2008 to February 2015 were prospectively enrolled in the Clinical Research Center for End-Stage Renal Disease cohort study. Participants were divided into 2 groups based on the median estimated glomerular filtration rate at the initiation of dialysis. Propensity score matching (PSM) was used to compare the overall survival rate, cardiovascular events, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) results, Karnofsky performance scale values, Beck's depression inventory values, and subjective global assessments.

    RESULTS The mean patient age was 72.0 years, and 61.7% of the patients were male. Overall, the cumulative survival rates were lower in the early initiation group, although the difference was not significant after PSM. Additionally, the survival rates of the 2 groups did not differ after adjusting for age, sex, Charlson comorbidity index and hemoglobin, serum albumin, serum calcium and phosphorus levels. Although the early initiation group showed a lower physical component summary score on the KDQOL-36 3 months after dialysis, the difference in scores was not significant 12 months after dialysis. Furthermore, the difference was not significant after PSM. The Karnofsky performance scale, Beck's depression inventory, and subjective global assessments were not significantly different 3 and 12 months after dialysis initiation.

    CONCLUSIONS The timing of dialysis initiation is not associated with clinical outcomes in elderly patients with ESRD.

    PubMed IF 2.8 신장내과
11. 22682017

    제1저자 문선준 · 교신저자 조영민

    Moon SJ, Ahn CH, Cho YM

    Effect of prescribing metformin according to eGFR instead of serum creatinine level: A study based on Korean National Health and Nutrition Examination Survey (KNHANES) 2009-2014.

    PLoS One. 2017;12(4):e0175334.

    Abstract

    BACKGROUND The metformin label has recently been changed from serum creatinine (sCr)-based to estimated glomerular filtration rate (eGFR)-based indication, which is expected to expand its use for patients with mild renal insufficiency. However, because the sCr level is lower in Asians than in Caucasians at the same level of renal function, this change might not expand metformin use in the Asian population. We investigated the effect of this change among Korean patients with diabetes.

    METHODS Data from the Korean National Health and Nutrition Examination Survey 2009 to 2014 were used and included 4,127 adult patients with diabetes. The metformin eligibility was assessed by the sCr level (1.4 mg/dL for women and 1.5 mg/dL for men) or by eGFR categories (contraindicated, <30; indeterminate, ≥30, <45; likely safe, ≥45 mL/min/1.73 m2) calculated by various eGFR equations including MDRD equation. We designated the 'expanding' and 'contracting' population as those who are likely safe according to eGFR among sCr-ineligible patients and those contraindicated according to eGFR among sCr-eligible patients, respectively. Results were weighted to the whole Korean adult population.

    RESULTS All eGFR equations showed expansion in the population for whom metformin is likely safe, ranging from 14.3% to 19.9% of the sCr-ineligible population. With the MDRD equation, the expanding population was 15,264 (15.8%) and the contracting population was 0 (0.0%). Male sex and younger age were significantly associated with the expanding population.

    CONCLUSIONS Contrary to our concern, prescribing metformin according to eGFR substantially expanded the indication of its use among the Korean diabetic patients.

    PubMed IF 2.8 내분비대사내과
12. 22672017

    제1저자 김학령, 김자연 · 교신저자 이진용

    Kim HL, Kim J, Kim HJ, Lim WH, Lee JY

    Incidence and factors associated with mortality in 2,476 patients with variant angina in Korea.

    Sci Rep. 2017;7:46031.

    Abstract

    This study investigated the incidence and risk factors of mortality in 2,476 patients with variant angina (VA) using the National Health Insurance Service-National Sample Cohort between 2004 and 2011. The risk factors of all-cause and cardiac mortality were investigated using Cox proportional hazards model. Most patients (69.5%) were less than 65 years and 42.9% were women. During the median follow-up duration of 4.9 years, there were 178 (7.2%) and 95 (3.8%) cases of all-cause and cardiac mortality, respectively. Older age, hypertension, diabetes mellitus, poor medication adherence, low household income and tertiary teaching hospitals were independent predictors for all-cause mortality, while older age, hypertension, low household income and tertiary teaching hospitals were independent predictors for cardiac mortality. In conclusion, our findings suggest that traditional risk factor control and continued medication are important to improve VA outcomes, and that household income-level factors should be considered in the assessment of risk of VA patients.

    PubMed IF 4.9 순환기내과
13. 22662017

    제1저자 전희중 · 교신저자 이정표

    Jeon HJ, Kim YC, Park S, Kim CT, Ha J, Han DJ, Oh J, Lim CS, Jung IM, Ahn C, Kim YS, Lee JP, Kim YH

    Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant Recipients.

    Clin J Am Soc Nephrol. 2017;12(4):653-662.

    Abstract

    BACKGROUND AND OBJECTIVES Hyperphosphatemia in kidney transplant recipients has been shown to predict poorer graft and patient survival. However, studies examining hypophosphatemia are scarce.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS To evaluate the association of serum phosphorus level with patient and graft survival, we performed a retrospective multicenter cohort study. Between January of 1997 and August of 2012, 2786 kidney transplant recipients (41.7±11.4 years; 59.3% men; 73.5% living donors; 26.1% with diabetes; 3.8% with prior history of cardiovascular disease) were classified into seven groups according to serum phosphorus levels 1 year after transplantation, with intervals of 0.5 mg/dl (lowest group, <2.5 mg/dl; highest group, ≥5.0 mg/dl; reference group, 3.5-3.99 mg/dl). Survival analysis was performed by defining baseline time point as 1 year after transplantation.

    RESULTS During median follow-up of 78.5 months, 60 patient deaths and 194 cases of graft loss occurred. In multivariate analysis, both lowest and highest serum phosphorus groups were associated with higher mortality, compared with the reference group (hazard ratio [HR], 4.82; 95% confidence interval [95% CI], 1.36 to 17.02; P=0.01; and HR, 4.24; 95% CI, 1.07 to 16.84; P=0.04, respectively). Higher death-censored graft loss was observed in the lowest and highest groups (HR, 3.32; 95% CI, 1.42 to 7.79; P=0.01; and HR, 2.93; 95% CI, 1.32 to 6.49; P=0.01, respectively), despite eGFR exhibiting no difference between the lowest group and reference group (65.4±19.3 versus 61.9±16.7 ml/min per 1.73 m²; P=0.33). Moreover, serum phosphorus showed a U-shape association with patient mortality and graft failure in restricted cubic spline curve analysis.

    CONCLUSIONS Serum phosphorus level 1 year after transplantation exhibits a U-shape association with death-censored graft failure and patient mortality in kidney transplant patients characterized by relatively high rate of living donor transplant and low incidence of diabetes and prior cardiovascular disease compared with Western countries.

    PubMed IF 7 신장내과
14. 22652017

    제1저자 김미소 · 교신저자 김범석

    Kim M, Keam B, Kim TM, Kim HG, Kim JS, Lee SS, Shin SH, Kim MK, Park KU, Kim DW, Yun HJ, Lee JS, Heo DS

    Phase II Study of Irinotecan and Cisplatin Combination Chemotherapy in Metastatic, Unresectable Esophageal Cancer.

    Cancer Res Treat. 2017;49(2):416-422.

    Abstract

    PURPOSE The objective of this multicenter phase II study was to evaluate the efficacy and safety of irinotecan and cisplatin combination chemotherapy in metastatic, unresectable esophageal cancer.

    MATERIALS AND METHODS Patients were treated with irinotecan 65 mg/m² and cisplatin 30 mg/m² on days 1 and 8 of each 21-day treatment cycle. The primary endpoint was response rate, and secondary endpoints were survival, duration of response, initial metabolic response rate, and toxicity.

    RESULTS A total of 27 patients with squamous cell histology were enrolled in the study. The median age of the patients was 61 years. The objective response rate of the 20 patients in the perprotocol group was 30.0% (90% confidence interval [CI], 13.2 to 46.9). The median follow-up duration was 10.0 months, and the median progression-free survival and overall survival were 4.5 months (95% CI, 1.6 to 6.2) and 8.8 months (95% CI, 4.7 to 10.5), respectively. Four of 13 patients (30.8%) evaluated showed initial metabolic response. The median duration of response for partial responders was 5.0 months (range, 3.4 to 8.0 months). The following grade 3/4 treatment-related hematologic toxicities were reported: neutropenia (40.7%), anaemia (22.2%), and thrombocytopenia (7.4%). Two patients experienced febrile neutropenia. The most common grade 3/4 non-hematologic toxicities were asthenia (14.8%) and diarrhoea (11.1%).

    CONCLUSION Irinotecan and cisplatin combination chemotherapy showed modest anti-tumour activity and manageable toxicity for patients with metastatic, unresectable esophageal cancer.

    PubMed IF 4.2 혈액종양내과
15. 22642017

    제1저자 김동완 · 교신저자 김동완

    Kim DW, Garon EB, Jatoi A, Keefe DM, Lacouture ME, Sonis S, Gernhardt D, Wang T, Giri N, Doherty JP, Nadanaciva S, O'Connell J, Sbar E, Cho BC

    Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042).

    Lung Cancer. 2017;106:76-82.

    Abstract

    OBJECTIVES Dacomitinib is a pan-HER inhibitor for advanced non-small-cell lung cancer (NSCLC). We explored the impact of a planned 4-day dacomitinib dose interruption on plasma exposure of dacomitinib and adverse events (AEs) of interest in Cohort III of the ARCHER 1042 study.

    MATERIALS AND METHODS Patients, treatment-naïve for advanced NSCLC with EGFR activating mutations, received oral dacomitinib 45mg QD (once daily). A planned dose interruption occurred in Cycle 1 from Days 11 through 14. The primary endpoint was the pharmacokinetic (PK) characteristics of dacomitinib in Cycle 1Day 10 and during dose interruption. Secondary endpoints included safety and concomitant medications used to treat AEs of interest.

    RESULTS Cohort III enrolled 25 patients. Median plasma C_max of dacomitinib in Cycle 1 Day 10 was 83.40ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63ng/mL. In the first 8 weeks of treatment 1) 80% of patients used concomitant medications for dermatologic AEs, 76% for diarrhea, and 44% for stomatitis, and 2) all patients experienced treatment-emergent AEs and 28% had all-causality Grade 3 AEs.

    CONCLUSION At 45mg QD dosing, PK parameters of plasma dacomitinib in Cycle 1 Day 10 were comparable to that obtained in Cycle 1 Day 14 from other dacomitinib studies. Average median plasma dacomitinib concentration during the 4-day dose interruption was approximately half of the median plasma C_max of dacomitinib observed prior to dose interruption. The toxicity profile was consistent with that from other studies of dacomitinib.

    PubMed IF 5.3 혈액종양내과
16. 22632017

    제1저자 박찬순 · 교신저자 최의근

    Park CS, Choi EK, Kim HM, Lee SR, Cha MJ, Oh S

    Increased risk of major bleeding in underweight patients with atrial fibrillation who were prescribed non-vitamin K antagonist oral anticoagulants.

    Heart Rhythm. 2017;14(4):501-507.

    Abstract

    BACKGROUND There is a paucity of evidence regarding the effects of non-vitamin K antagonist oral anticoagulants (NOACs) in underweight patients with atrial fibrillation (AF).

    OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of NOACs in underweight AF patients.

    METHODS We analyzed 1353 AF patients who were prescribed NOACs according to their body mass index (BMI): underweight (UW: n = 62, BMI <18.5 kg/m²), normal weight (NW: n = 753, BMI 18.5-24.9 kg/m²), and overweight to obese (OW: n = 538, BMI ≥25.0 kg/m²). We analyzed the association between clinical outcomes and BMI.

    RESULTS During the median 7 months (interquartile range 3-10 months) of follow-up, there were 29 major bleeding events, 11 thromboembolic events, and 15 deaths. The risks of major bleeding and all-cause death were significantly higher in the UW group compared to the NW group (adjusted hazard ratio [HR] 4.135, 95% confidence interval [CI] 1.442-11.854, P = .008; adjusted HR 10.524, 95% CI 2.949-37.561, P < .001) and the OW group (adjusted HR 5.352, 95% CI 1.597-17.935, P = .007; adjusted HR 11.385, 95% CI 2.523-51.386, P = .002). However, there was no significant difference in the risk of thromboembolism among these groups.

    CONCLUSION In AF patients taking NOACs, being underweight was associated with an increased risk of major bleeding and all-cause death compared with being normal weight or overweight to obese, whereas the risk of thromboembolism was not different. Dose reduction should be considered in underweight patients who are at high risk for bleeding.

    PubMed IF 7 순환기내과
17. 22622017

    제1저자 김예안, 조선욱 · 교신저자 박영주, 이가희

    Kim YA, Cho SW, Choi HS, Moon S, Moon JH, Kim KW, Park DJ, Yi KH, Park YJ, Cho BY

    The Second Antithyroid Drug Treatment Is Effective in Relapsed Graves' Disease Patients: A Median 11-Year Follow-Up Study.

    Thyroid. 2017;27(4):491-496.

    Abstract

    BACKGROUND Antithyroid drug (ATD) is a widely used treatment for Graves' disease (GD). However, its long-term efficiency remains unclear. This study investigated the long-term disease prognosis and predictive factors for relapse in ATD-treated GD patients.

    METHODS Newly diagnosed, ATD-treated GD patients with at least four years of follow-up were recruited (n = 187). Remission was defined as maintaining a euthyroid status for more than one year after ATD withdrawal.

    RESULTS During 11.1 years (range 4.0-23.7 years) of median follow-up, overall, 51.9% of the newly diagnosed ATD-treated GD patients achieved remission, 32.1% continued ATD treatment, and 13.4% underwent other ablation treatments. The 10-year remission rates were higher in the first (34.2%) and second (25.5%) ATD courses than in any of the other subsequent ATD courses, and decreased as ATD treatments were repeated. The 10-year relapse rate was the highest after the third ATD treatment (71.4%) compared with that after the first (60.5%) and second (58.3%) courses. Longer duration of ATD treatment (odds ratio [OR] = 1.4 [confidence interval (CI) 1.2-1.7], p < 0.001), higher number of relapses (OR = 4.7 [CI 2.3-9.8], p < 0.001), and moderate to severe Graves' ophthalmopathy (OR = 4.1 [CI 1.1-15.2], p = 0.032) were associated with persistent disease status.

    CONCLUSIONS A second course of ATD can be considered for GD patients after the first relapse because the chance of remission and the relapse rate are similar to the one after the first ATD treatment course. For GD patients with more than two relapses, or with an ATD treatment duration of more than four to five years, low-dose maintenance of ATD or ablative treatment needs to be considered.

    PubMed IF 6.6 내분비대사내과
18. 22612017

    제1저자 방영주 · 교신저자 방영주

    Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, Li H, Chichili GR, Moore PA, Hong S, Stewart SJ, Baughman JE, Lechleider RJ, Burris HA

    First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors.

    Ann Oncol. 2017;28(4):855-861.

    Abstract

    BACKGROUND Margetuximab is an anti-HER2 antibody that binds with elevated affinity to both the lower and higher affinity forms of CD16A, an Fc-receptor important for antibody dependent cell-mediated cytotoxicity (ADCC) against tumor cells. A Phase 1 study was initiated to evaluate the toxicity profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of margetuximab in patients with HER2-overexpressing carcinomas.

    PATIENTS AND METHODS Patients with HER2-positive breast or gastric cancer, or other carcinomas that overexpress HER2, for whom no standard therapy was available, were treated with margetuximab by intravenous infusion at doses of 0.1-6.0 mg/kg for 3 of every 4 weeks (Regimen A) or once every 3 weeks (10-18 mg/kg) (Regimen B).

    RESULTS Sixty-six patients received margetuximab (34 patients for Regimen A and 32 patients for Regimen B). The MTD was not reached for either regimen. Treatment was well-tolerated, with mostly Grade 1 and 2 toxicities consisting of constitutional symptoms such as pyrexia, nausea, anemia, diarrhea, and fatigue. Among 60 response-evaluable patients, confirmed partial responses and stable disease were observed in 7 (12%) and 30 (50%) patients, respectively; 26 (70%) of these patients had received prior HER2-targeted therapy. Tumor reductions were observed in over half (18/23, 78%) of response-evaluable patients with breast cancer including durable (>30 weeks) responders. Ex vivo analyses of patient peripheral blood mononuclear cell samples confirmed the ability of margetuximab to support enhanced ADCC compared with trastuzumab.

    CONCLUSIONS Margetuximab was well-tolerated and has promising single-agent activity. Further development efforts of margetuximab as single agent and in combination with other therapeutic agents are ongoing.

    TRIAL REGISTRATION ID NCT01148849.

    PubMed IF 80.4 혈액종양내과
19. 22602017

    제1저자 이준구 · 교신저자 김태민, 주영석

    Lee JK, Louzada S, An Y, Kim SY, Kim S, Youk J, Park S, Koo SH, Keam B, Jeon YK, Ku JL, Yang F, Kim TM, Ju YS

    Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma.

    Ann Oncol. 2017;28(4):890-897.

    Abstract

    BACKGROUND Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored.

    PATIENTS AND METHODS We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes.

    RESULTS Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%-75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells.

    CONCLUSION Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.

    PubMed IF 80.4 혈액종양내과
20. 22592017

    제1저자 홍아람 · 교신저자 김정희

    Hong AR, Kim JH, Lee KH, Kim TY, Im SA, Kim TY, Moon HG, Han WS, Noh DY, Kim SW, Shin CS

    Long-term effect of aromatase inhibitors on bone microarchitecture and macroarchitecture in non-osteoporotic postmenopausal women with breast cancer.

    Osteoporos Int. 2017;28(4):1413-1422.

    Abstract

    UNLABELLED In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index.

    INTRODUCTION AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer.

    METHODS We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >-2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry.

    RESULTS BMD significantly decreased from baseline to 5 years at the lumbar spine (-6.15%), femur neck (-7.12%), and total hip (-6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (-2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD.

    CONCLUSIONS Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs.

    PubMed IF 5.4 내분비대사내과
21. 22582017

    제1저자 이연주 · 교신저자 박상헌

    Lee YJ, Lee DS, Min H, Choi YY, Lee EY, Song I, Yoon YE, Kim JW, Park JS, Cho YJ, Lee JH, Suh JW, Jo YH, Kim K, Park S

    Differences in the Clinical Characteristics of Rapid Response System Activation in Patients Admitted to Medical or Surgical Services.

    J Korean Med Sci. 2017;32(4):688-694.

    Abstract

    Variability in rapid response system (RRS) characteristics based on the admitted wards is unknown. We aimed to compare differences in the clinical characteristics of RRS activation between patients admitted to medical versus surgical services. We reviewed patients admitted to the hospital who were detected by the RRS from October 2012 to February 2014 at a tertiary care academic hospital. We compared the triggers for RRS activation, interventions performed, and outcomes of the 2 patient groups. The RRS was activated for 460 patients, and the activation rate was almost 2.3 times higher for surgical services than that for medical services (70% vs. 30%). The triggers for RRS activation significantly differed between patient groups (P = 0.001). They included abnormal values for the respiratory rate (23.2%) and blood gas analysis (20.3%), and low blood pressure (18.8%) in the medical group; and low blood pressure (32.0%), low oxygen saturation (20.8%), and an abnormal heart rate (17.7%) in the surgical group. Patients were more likely classified as do not resuscitate or required intensive care unit admission in the medical group compared to those in the surgical group (65.3% vs. 54.7%, P = 0.045). In multivariate analysis, whether the patient belongs to medical services was found to be an independent predictor of mortality after adjusting for the modified early warning score, Charlson comorbidity index, and intervention performed by the RRS team. Our data suggest that RRS triggers, interventions, and outcomes greatly differ between patient groups. Further research is needed to evaluate the efficacy of an RRS approach tailored to specific patient groups.

    PubMed IF 3.2 호흡기내과
22. 22572017

    제1저자 김원, 김병관 · 교신저자 김윤준

    Kim W, Kim BG, Lee JS, Lee CK, Yeon JE, Chang MS, Kim JH, Kim H, Yi S, Lee J, Cho JY, Kim SG, Lee JH, Kim YJ

    Randomised clinical trial: the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease.

    Aliment Pharmacol Ther. 2017;45(8):1073-1083.

    Abstract

    BACKGROUND Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model.

    AIM To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD).

    METHODS We performed a multicentre, double-blind, placebo-controlled, phase II study. Subjects with a liver fat >20% and hypertransaminasemia were randomised to the three groups: placebo (n = 22), 30 mg of oltipraz (n = 22) or 60 mg of oltipraz (n = 24) twice daily for 24 weeks. Changes in the liver fat from baseline to 24 weeks quantified using magnetic resonance spectroscopy were the primary outcome.

    RESULTS Compared with the placebo group (-3.2 ± 11.1%), absolute changes in the liver fat content increased in a dose-dependent manner: -7.7 ± 7.0% and -13.9 ± 10.7% for the low-dose and high-dose groups (P = 0.13 and P < 0.01). Per cent reduction in the liver fat content was also significantly greater in the high-dose group than in the placebo group (-34.6 ± 29.4% vs. -0.6 ± 62.9%, P = 0.046). Body mass indices (-1.0 ± 0.9% vs. -0.5 ± 1.4%, P = 0.04) significantly decreased in the high-dose group compared to the placebo group. However, absolute changes in insulin resistance, liver enzymes, lipids and cytokines were not significantly different among groups. The incidence of adverse events was comparable among groups.

    CONCLUSIONS Twenty-four-week oltipraz treatment significantly reduced the liver fat content in patients with NAFLD. Clinicaltrials.gov (NCT01373554).

    PubMed IF 6.8 소화기내과
23. 22562017

    제1저자 오태정,임수 · 교신저자 장학철, 조남한

    Oh TJ, Lim S, Kim KM, Moon JH, Choi SH, Cho YM, Park KS, Jang H, Cho NH

    One-hour postload plasma glucose concentration in people with normal glucose homeostasis predicts future diabetes mellitus: a 12-year community-based cohort study.

    Clin Endocrinol (Oxf). 2017;86(4):513-519.

    Abstract

    OBJECTIVE In Caucasians, plasma glucose concentration at 1 h during an oral glucose tolerance test (OGTT) may be a better predictor of future diabetes mellitus than the fasting or 2-h postload glucose concentration. We investigated whether the 1-h glucose concentration could be used to predict future diabetes mellitus in Asian ethnicity.

    MEASUREMENTS A total of 5703 Koreans with normal glucose tolerance were enrolled from the Korean Genome and Epidemiology Study. Indices of insulin sensitivity and β-cell function estimated from standard 75-g OGTTs performed every 2 years for 12 years were used to identify whether the 1-h glucose concentration could predict future diabetes mellitus.

    RESULTS The mean age and body mass index at baseline were 51·3 ± 8·7 years and 24·2 ± 3·0 kg/m² , respectively. During the 12-year follow-up, 593 subjects (10·3%) developed diabetes mellitus. The area under the receiver-operating characteristic curve for incident diabetes mellitus was higher for the 1-h postload glucose concentration than for the fasting or postload 2-h glucose concentration (0·74 vs 0·61 or 0·63). The cut-off value of ≥8·0 mmol/l identified incident diabetes mellitus with 70% sensitivity and 68% specificity. After adjusting for typical risk factors, subjects with a 1-h postload glucose concentration ≥8·0 mmol/l had lower β-cell function and a 2·84-fold increased risk of incident diabetes mellitus compared with their counterparts.

    CONCLUSIONS In this community-based 12-year prospective cohort study, 1-h postload plasma glucose concentration was an independent predictor of future diabetes mellitus and 8·0 mmol/l was suggested as a cut-off value.

    PubMed IF 2.8 내분비대사내과
24. 22552017

    제1저자 정숙향,박병주 · 교신저자 조인수

    Jeong SH, Park BJ, Kim YH, Choi YS, Ahn HS, Han SH, Choi IS

    Isolation of hepatitis E virus genotype 4 from patients with acute cryptogenic hepatitis in Korea.

    J Clin Virol. 2017;89:10-13.

    Abstract

    BACKGROUND Autochthonous hepatitis E occurs sporadically in developed countries. The consumption of undercooked pork containing hepatitis E virus genotype 3 (HEV-3) or 4 (HEV-4) is the major risk factor for infection. The serological diagnostic kits currently used in hospitals sometimes produce false-negative or -positive results. Therefore, detection of both HEV RNA and antibodies to the virus is required for confirmative diagnosis of hepatitis E.

    OBJECTIVES We aimed to detect HEV in serum samples from patients with cryptogenic hepatitis and to determine the origin of HEV.

    STUDY DESIGN A nested polymerase chain reaction (PCR) method was developed for detection of HEV-3 and HEV-4 in patients with hepatitis. A total of 23 serum samples, deposited in 2006-2012, from patients with acute cryptogenic hepatitis who were serologically negative for hepatitis A, B, C, and E were examined using this method. The amplified PCR products were genetically analyzed.

    RESULTS Four HEV-4 isolates were detected from the 23 serum samples. Phylogenetic analysis indicated that three of the four isolates were closely related to HEV-4 isolates found in pigs in Korea and in patients with hepatitis E in Japan.

    CONCLUSIONS The newly developed nested PCR method was useful for detection of HEV in patients with cryptogenic hepatitis. The close relationship between the human HEV-4 isolates identified in this study and swine isolates implied that zoonotic transmission of HEV might be a source of infection in patients with hepatitis.

    PubMed IF 3.7 소화기내과
25. 22542017

    제1저자 류신혜 · 교신저자 김인호

    Yoo SH, Koh Y, Kim DY, Lee JH, Lee JH, Lee KH, Yoon SS, Park S, Park SK, Hong DS, Yi HG, Kim CS, Jang JE, Cheong JW, Moon J, Min YH, Sohn SK, Kim I, Korean Society of Blood and Marrow Transplantation

    Salvage therapy for acute chemorefractory leukemia by allogeneic stem cell transplantation: the Korean experience.

    Ann Hematol. 2017;96(4):605-615.

    Abstract

    Little is known about the characteristics that make patients with acute leukemia suitable for undergoing salvage therapy by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we analyzed the clinical outcomes of 223 patients with acute leukemia who underwent allo-HSCT while not in complete remission (CR). The primary end points were overall survival (OS) and CR rate. CR was achieved in 79.8% of patients after allo-HSCT. Acute graft-versus-host disease (GVHD) was significantly associated with CR (P = 0.045). During a median follow-up of 30.1 months, the median OS was 6.1 months. OS was significantly longer in patients with good or standard risk cytogenetic characteristics than in those with poor risk cytogenetic characteristics (P = 0.029, P = 0.030, respectively). Patients who received allo-HSCT from a matched sibling donor had better survival than those with unrelated donors (P = 0.015). Primary chemorefractoriness was not associated with poor survival (P = 0.071). The number of chemotherapies before allo-HSCT was significantly correlated with outcome (P = 0.006). Chronic GVHD was a strong predictor of a longer OS (P = 0.025). In conclusion, survival of patients with primary chemorefractory acute leukemia is not lower when treated upfront with allo-HSCT. Hence, allo-HSCT should be actively considered in such patients. Acute and chronic GVHD is associated with better outcomes patients with acute leukemia who have undergone allo-HSCT and not achieved CR.

    PubMed IF 2.3 혈액종양내과
26. 22532017

    제1저자 이민종 · 교신저자 김윤준

    Lee M, Jo A, Lee S, Kim JB, Chang Y, Nam JY, Cho H, Cho YY, Cho EJ, Lee JH, Yu SJ, Yoon JH, Kim YJ

    3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells.

    PLoS One. 2017;12(3):e0174271.

    Abstract

    BACKGROUND & AIMS Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells.

    METHODS We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells. Expression of hexokinase II, gamma-glutamylcysteine synthetase (rGCS), and epithelial-mesenchymal transition (EMT) markers in AR cells was assessed. Anti-tumor effects of a combination treatment of 3-BP and BSO were evaluated in AR cells and an HCC xenograft mouse model.

    RESULTS AR HCC cells showed significantly higher chemoresistance, glycolysis and lower ROS production than attached cells. Expression of hexokinase II, rGCS, and EMT markers was higher in AR HCC cells than attached cells. A combination treatment of 3-BP/BSO effectively suppressed proliferation of AR HCC cells through apoptosis by blocking glycolysis and enhancing ROS levels. In xenograft mouse models, tumor growth derived from AR HCC cells was significantly suppressed in the group treated with 3-BP/BSO compared to the group treated with 3-BP or sorafenib.

    CONCLUSIONS These results demonstrated that a combination treatment of 3-BP/BSO had a synergistic anti-tumor effect in an AR HCC model. This strategy may be an effective adjuvant therapy for patients with sorafenib-resistant HCC.

    PubMed IF 2.8 소화기내과
27. 22522017

    제1저자 허혁 · 교신저자 임춘수

    Huh H, Lee H, Lee JP, Kim DK, Oh S, Oh YK, Kim YS, Lim CS

    Factors affecting the long-term outcomes of idiopathic membranous nephropathy.

    BMC Nephrol. 2017;18(1):104.

    Abstract

    BACKGROUND We attempted to describe the clinical features and determine the factors associated with renal survival in idiopathic membranous nephropathy (iMN) patients with nephrotic syndrome (NS) and to determine the factors associated with spontaneous complete remission (sCR) and progression to NS in iMN patients with subnephrotic proteinuria.

    METHODS This retrospective study involved 166 iMN patients with NS and 65 patients with subnephrotic proteinuria. The primary end point was a doubling of serum creatinine or initiation of dialysis. In patients with subnephrotic proteinuria, we determined the factors associated with sCR and factors associated with progression to NS.

    RESULTS Remission of NS was achieved in 125 out of 166 patients (75.3%). Of those who reached remission, 26 patients (20.8%) experienced relapse that was followed by second remission. The relapse or persistence of proteinuria was associated with the primary end points (hazard ratio [HR] = 12.40, P = 0.037, HR = 173, P < 0.001, respectively). In patients with subnephrotic proteinuria, sCR occurred in 35.4% of the patients. The patients with sCR had lower proteinuria and serum creatinine levels and higher serum albumin concentrations at baseline. The serum albumin level at diagnosis was a prognostic factor for progression to NS (Odds ratio [OR] = 0.015, P < 0.001).

    CONCLUSIONS The occurrence of relapse or persistence of proteinuria had negative effects on renal survival in iMN patients with NS, and low serum albumin levels at baseline were associated with non-achievement of sCR and progression to NS.

    PubMed IF 2.9 신장내과
28. 22512017

    제1저자 차명진 · 교신저자 조구영

    Cha MJ, Kim HS, Kim SH, Park JH, Cho GY

    Prognostic power of global 2D strain according to left ventricular ejection fraction in patients with ST elevation myocardial infarction.

    PLoS One. 2017;12(3):e0174160.

    Abstract

    BACKGROUNDS We aimed to evaluate the predictive power of longitudinal and circumferential fibers according to left ventricular ejection fraction (LVEF) in successfully reperfused acute ST elevation myocardial infarction (STEMI) patients.

    METHODS Total 691 patients (age 59±13, 20% female) underwent clinical evaluation and conventional and strain echocardiography (Global longitudinal strain (GLS), global circumferential strain (GCS)). The clinical outcome was defined as the composite of death, hospitalization for heart failure, non-fatal myocardial infarction, and ventricular arrhythmia.

    RESULTS During a follow-up of 39±19 months, there were 47 (6.8%) clinical events. In multivariate Cox models adjusted clinical risk factors, age (HR 1.08, p = 0.001) and GLS (HR 1.37, p = 0.001) were independent predictors. The addition of GLS resulted in significant incremental improvement in the predictive value on LVEF (χ2 = 31.8→45.8, p<0.001), although GCS offers no additional benefit. In the subgroup analysis according to LVEF, adjusted with clinical factors, GLS was significant predictive for outcome for the patients with mildly depressed (LVEF 40-50%, HR 2.25, p<0.001) and significantly depressed (LVEF<40%, HR 1.28, p = 0.016) systolic function, although GCS and LVEF lost their power with LVEF<40%. For the patients with preserved LVEF (>50%), GLS, GCS and LVEF did not show significant predictive power.

    CONCLUSIONS GLS is a most powerful predictor of outcome in successfully reperfused STEMI patients, especially with depressed LV dysfunction, although GCS and LVEF lost their predictive power for the patients with significantly depressed LV function. However, GLS did not predict outcome for the patients with preserved LVEF (>50%).

    PubMed IF 2.8 순환기내과
29. 22502017

    제1저자 김형우 · 교신저자 황진혁

    Kim HW, Lee JC, Lee J, Kim JW, Kim J, Hwang JH

    Early versus delayed initiation of adjuvant treatment for pancreatic cancer.

    PLoS One. 2017;12(3):e0173960.

    Abstract

    BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC.

    METHODS We retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20-83 days]).

    RESULTS Patient baseline characteristics were comparable in both groups, except for grade III or IV postoperative complications (5.4% in the early group vs. 22.8% in the delayed group). With a median 20.3-month follow-up, the overall survival (OS) and disease-free survival (DFS) times were 29.5 and 14.7 months, respectively. The early group had significantly prolonged OS (39.1 vs. 21.1 months, p = 0.018) and DFS (18.8 vs. 10.0 months, p = 0.034), compared to the delayed group. Among 71 patients who completed planned adjuvant treatment, patients in the early group tended to have longer, though not statistically significant, OS and DFS times than those in the delayed group. In 67 patients without postoperative complications, patients in the early group had longer OS (42.8 vs. 20.5 months, p = 0.002) and DFS (19.6 vs. 9.1 months, p = 0.005) than those in the delayed group. By multivariate analysis, incompletion of treatment (hazard ratio [HR]: 4.039, 95% confidence interval [CI]: 2.334-6.992), delayed treatment initiation (HR: 1.822, 95% CI: 1.081-3.070), and positive angiolymphatic invasion (HR: 2.116, 95% CI: 1.160-3.862) were significantly associated with shorter OS.

    CONCLUSIONS Adjuvant treatment should be delivered earlier and completed for better outcomes in resected PDAC patients, especially without postoperative complications.

    PubMed IF 2.8 소화기내과
30. 22492017

    제1저자 임주현 · 교신저자 김상균

    Lim JH, Kim SG, Song JH, Hwang JJ, Lee DH, Han JP, Hong SJ, Kim JH, Jeon SW, Kim GH, Shim KN, Shin WG, Kim TH, Kim SM, Chung IK, Kim HS, Kim HU, Lee J, Kim JG

    Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of Helicobacter pylori in Peptic Ulcer Disease.

    Gut Liver. 2017;11(2):226-231.

    Abstract

    BACKGROUND/AIMS The resistance rate of Helicobacter pylori is gradually increasing. We aimed to evaluate the efficacy of levofloxacin-based third-line H. pylori eradication in peptic ulcer disease.

    METHODS Between 2002 and 2014, 110 patients in 14 medical centers received levofloxacin-based third-line H. pylori eradication therapy for peptic ulcer disease. Of these, 88 were included in the study; 21 were excluded because of lack of follow-up and one was excluded for poor compliance. Their eradication rates, treatment regimens and durations, and types of peptic ulcers were analyzed.

    RESULTS The overall eradiation rate was 71.6%. The adherence rate was 80.0%. All except one received a proton-pump inhibitor, amoxicillin, and levofloxacin. One received a proton-pump inhibitor, amoxicillin, levofloxacin, and clarithromycin, and the eradication was successful. Thirty-one were administered the therapy for 7 days, 25 for 10 days, and 32 for 14 days. No significant differences were observed in the eradication rates between the three groups (7-days, 80.6% vs 10-days, 64.0% vs 14-days, 68.8%, p=0.353). Additionally, no differences were found in the eradiation rates according to the type of peptic ulcer (gastric ulcer, 73.2% vs duodenal/gastroduodenal ulcer, 68.8%, p=0.655).

    CONCLUSIONS Levofloxacin-based third-line H. pylori eradication showed efficacy similar to that of previously reported first/second-line therapies.

    PubMed IF 4.1 소화기내과

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.