SCI 발표논문

1. 1192017

   제1저자 이상언 · 교신저자 이해영

   Lee SE, Lee HY, Cho HJ, Choe WS, Kim H, Choi JO, Jeon ES, Kim MS, Kim JJ, Hwang KK, Chae SC, Baek SH, Kang SM, Choi DJ, Yoo BS, Kim KH, Park HY, Cho MC, Oh BH

   Clinical Characteristics and Outcome of Acute Heart Failure in Korea: Results from the Korean Acute Heart Failure Registry (KorAHF).

   Korean Circ J. 2017;47(3):341-353.

   Abstract

   BACKGROUND AND OBJECTIVES The burden of heart failure has increased in Korea. This registry aims to evaluate demographics, clinical characteristics, management, and long-term outcomes in patients hospitalized for acute heart failure (AHF).

   SUBJECTS AND METHODS We prospectively enrolled a total of 5625 consecutive subjects hospitalized for AHF in one of 10 tertiary university hospitals from March 2011 to February 2014. Descriptive statistics were used to determine the baseline characteristics of the study population and to compare them with those from other registries.

   RESULTS The mean age was 68.5±14.5 years, 53.2% were male, and 52.2% had de novo heart failure. The mean systolic and diastolic blood pressures were 131.2±30.3 mmHg and 78.6±18.8 mmHg at admission, respectively. The left ventricular ejection fraction was ≤40% in 60.5% of patients. Ischemia was the most frequent etiology (37.6%) and aggravating factor (26.3%). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and aldosterone antagonists were prescribed in 68.8%, 52.2%, and 46.6% of the patients at discharge, respectively. Compared with the previous registry performed in Korea a decade ago, extracorporeal membrane oxygenation (ECMO) and heart transplantation have been performed more frequently (ECMO 0.8% vs. 2.8%, heart transplantation 0.3% vs. 1.2%), and in-hospital mortality decreased from 7.6% to 4.8%. However, the total cost of hospital care increased by 40%, and one-year follow-up mortality remained high.

   CONCLUSION While the quality of acute clinical care and AHF-related outcomes have improved over the last decade, the long-term prognosis of heart failure is still poor in Korea. Therefore, additional research is needed to improve long-term outcomes and implement cost-effective care.

   PubMed IF 3.4 순환기내과
2. 1182017

   제1저자 구본권 · 교신저자 구본권

   Koo BK

   What Is the Clinical Relevance of the Discordance Between Fractional Flow Reserve and Coronary Flow Reserve?

   JACC Cardiovasc Interv. 2017;10(10):1008-1010.

   PubMed IF 12.7 순환기내과
3. 1172017

   제1저자 이정훈, 탁원영 · 교신저자 김윤준, 배영수

   Lee JH, Tak WY, Lee Y, Heo MK, Song JS, Kim HY, Park SY, Bae SH, Lee JH, Heo J, Kim KH, Bae YS, Kim YJ

   Adjuvant immunotherapy with autologous dendritic cells for hepatocellular carcinoma, randomized phase II study.

   Oncoimmunology. 2017;6(7):e1328335.

   Abstract

   Our previous phase I/IIA study showed that autologous dendritic cells (DCs) pulsed with tumor-associated antigens are well tolerated in patients with hepatocellular carcinoma (HCC). In this randomized, multicenter, open-label, phase II trial, we investigated the efficacy and safety of this DC-based adjuvant immunotherapy with 156 patients, who treated for HCC with no evidence of residual tumor after standard treatment modalities. Patients were randomly assigned to immunotherapy (n = 77; injection of 3 × 10⁷ DC cells, six times over 14 weeks) or control (n = 79; no treatment). The primary end point was recurrence-free survival (RFS), and the secondary endpoints were immune response and safety. The RFS between the immunotherapy and control groups was not significantly different (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.60-1.56; p = 0.90). However, post-hoc subgroup analyses revealed that DC immunotherapy significantly reduced the risk of tumor recurrence of non-radiofrequency ablation (non-RFA) group patients (n = 83, HR, 0.49; 95% CI, 0.26-0.94; p = 0.03), whereas unexpectedly increased the risk of recurrence in RFA group (n = 61, p = 0.01). Tumor-specific immune responses were significantly enhanced (both p < 0.01) in the immunotherapy group. Baseline serum interleukin (IL)-15 was statistically correlated with RFS prolongation (HR, 0.16; 95% CI, 0.03-1.58; p = 0.001) within the immunotherapy groups. Overall adverse events were more frequent in the immunotherapy group (p < 0.001) but were mainly mild to moderate in severity. In conclusion, adjuvant immunotherapy with DC vaccine reduces the risk of tumor recurrence in HCC patients who underwent standard treatment modalities other than RFA. Baseline IL-15 might be a candidate biomarker for DC-based HCC immunotherapy.

   PubMed IF 7.719 소화기내과
4. 1162017

   제1저자 백주영 · 교신저자 정숙향

   Baeg JY, Kim IH, Seo SY, Kim YS, Jung EU, Cho J, Chung JW, Jang ES, Kim JW, Jeong SH

   Prevalence and Incidence of Depression during Interferon-Based Antiviral Therapy in Chronic Hepatitis C Patients in the Republic of Korea.

   Gut Liver. 2017;11(3):426-433.

   Abstract

   BACKGROUND/AIMS The association between depression and chronic hepatitis C virus (HCV) infection or pegylated interferon α and ribavirin therapy (PR therapy) has not been extensively studied in Korea. We aimed to clarify the prevalence of depression and its incidence during PR therapy in chronic hepatitis C (CHC) patients.

   METHODS In this prospective, multicenter study, 114 CHC patients were screened for depression using two self-reported scales, the Beck Depression Inventory-I (BDI-I) and the Hospital Anxiety and Depression scale (HADS). The incidence of depression during PR therapy was evaluated in 62 patients who underwent PR therapy during the study period.

   RESULTS The prevalence of baseline depression was 17.5% according to the BDI-I score ≥10 criterion and 4.4% according to the HADS-D score ≥8 criterion in the 114 CHC patients, and it was significantly associated with an unmarried state. During PR therapy, depression developed in 34.6% according to the BDI-I scale and 29.5% according to the HADS-D, which negatively affected sustained virologic response (SVR).

   CONCLUSIONS The prevalence of depression in Korean CHC patients appears to be low compared to that in Western patients; however, its incidence during PR therapy (approximately 30%) was similar to that of other populations, which led to a lower SVR rate. Active screening and multidisciplinary management of depression during PR therapy is warranted.

   PubMed IF 4.1 소화기내과
5. 1152017

   제1저자 임수경, 고성준 · 교신저자 고성준

   Lim SK, Yoo SJ, Koo DL, Park CA, Ryu HJ, Jung YJ, Jeong JB, Kim BG, Lee KL, Koh SJ

   Stress and sleep quality in doctors working on-call shifts are associated with functional gastrointestinal disorders.

   World J Gastroenterol. 2017;23(18):3330-3337.

   Abstract

   AIM To investigate the role of sleep quality and psychosocial problems as predictors of functional gastrointestinal disorders (FGIDs) in doctors that work 24 hour-on-call shifts.

   METHODS In this cross-sectional observation study, using the Rome III Questionnaire and Pittsburgh Sleep Quality Index (PSQI), we analyzed 170 doctors with 24 hour-on-call shifts.

   RESULTS Among the participants that had experienced a 24 hour-on-call shift within the last 6 mo, 48 (28.2%) had FGIDs. Overall prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) were 16.5% and 17.1%, respectively, with 5.3% exhibiting both. Sleep scores (PSQI) (8.79 ± 2.71 vs 7.30 ± 3.43, P = 0.008), the presence of serious psychosocial alarm (83.3% vs 56.6%, P = 0.004), and the proportion of doctors who experienced over two months of recent on-call work (81.2% vs 68.9%, P = 0.044) were significantly different between individuals with or without FGIDs. Multivariate analysis revealed that presenting serious psychosocial alarm was an independent risk factor for prevalence of FD (OR = 5.47, 95%CI: 1.06-28.15, P = 0.042) and poor sleep quality (PSQI ≥ 6) was a predictor of IBS (OR = 4.17, 95%CI: 1.92-19.02, P = 0.016).

   CONCLUSION Physicians should recognize the role of sleep impairment and psychological stress in the development of FGIDs and a comprehensive approach should be considered to manage patients with FGIDs.

   PubMed IF 7.7 소화기내과
6. 1142017

   제1저자 한미연 · 교신저자 오윤규, 김영훈

   Han M, Lee JP, Park S, Kim Y, Kim YC, Ahn C, Han DJ, Ha J, Jung IM, Lim CS, Kim YS, Kim YH, Oh YK

   Early onset hyperuricemia is a prognostic marker for kidney graft failure: Propensity score matching analysis in a Korean multicenter cohort.

   PLoS One. 2017;12(5):e0176786.

   Abstract

   It remains inconclusive whether hyperuricemia is a true risk factor for kidney graft failure. In the current study, we investigated the association of hyperuricemia and graft outcome. We performed a multi-center cohort study that included 2620 kidney transplant recipients. The patients were classified as either normouricemic or hyperuricemic at 3 months after transplantation. Hyperuricemia was defined as a serum uric acid level ≥ 7.0 mg/dL in males or ≥ 6.0 mg/dL in females or based on the use of urate-lowering medications. The two groups were compared before and after propensity score matching. A total of 657 (25.1%) patients were classified as hyperuricemic. The proportion of hyperuricemic patients increased over time, reaching 44.2% of the total cohort at 5 years after transplantation. Estimated glomerular filtration rate and donor type were independently associated with hyperuricemia. Hyperuricemia was associated with graft loss according to multiple Cox regression analysis before propensity score matching (hazard ratio [HR] = 1.56, 95% confidence interval [CI] = 1.14-2.13, P = 0.005) as well as after matching (HR = 1.65, 95% CI = 1.13-2.42, p = 0.010). Cox regression models using time-varying hyperuricemia or marginal structural models adjusted with time-varying eGFR also demonstrated significant hazards of hyperuricemia for graft loss. Cardiovascular events and recipient survival were not associated with hyperuricemia. Overall, hyperuricemia, especially early onset after transplantation, showed an increased risk for graft failure. Further studies are warranted to determine whether lowering serum uric acid levels would be beneficial to graft survival.

   PubMed IF 2.8 신장내과
7. 1132017

   제1저자 변자민 · 교신저자 고영일

   Byun JM, Koh Y, Shin DY, Kim I, Yoon SS, Lee JO, Bang SM, Kim KH, Jung SH, Lee WS, Park Y, Jang JH, Han JJ, Yhim HY, Kim DS, Lee YJ, Lee H, Choi YS, Lee S, Korean Adult ALL Working Party, Korean Society of Hematology

   BCR-ABL translocation as a favorable prognostic factor in elderly patients with acute lymphoblastic leukemia in the era of potent tyrosine kinase inhibitors.

   Haematologica. 2017;102(5):e187-e190.

   PubMed IF 8.2 혈액종양내과
8. 1122017

   제1저자 심성훈, 김소연 · 교신저자 김태민, 전윤경

   Sim SH, Kim S, Kim TM, Jeon YK, Nam SJ, Ahn YO, Keam B, Park HH, Kim DW, Kim CW, Heo DS

   Novel JAK3-Activating Mutations in Extranodal NK/T-Cell Lymphoma, Nasal Type.

   Am J Pathol. 2017;187(5):980-986.

   Abstract

   Inhibition of the Janus kinase (JAK)-STAT pathway has been implicated as a treatment option for extranodal natural killer/T-cell lymphoma, nasal type (NTCL). However, JAK-STAT pathway alterations in NTCL are variable, and the efficacy of JAK-STAT pathway inhibition has been poorly evaluated. JAK3 mutation and STAT3 genetic alterations were investigated by direct sequencing and immunohistochemistry in 84 patients with newly diagnosed NTCL. Five of 71 patients with NTCL (7.0%) had JAK3 mutations in the pseudokinase domain: two JAK3^A573V, two JAK3^H583Y, and one JAK3^G589D mutation. Proliferation of Ba/F3 cells transduced with novel JAK3 mutations (JAK3^H583Y and JAK3^G589D) was independent of IL-3 and was inhibited by the JAK3 inhibitor tofacitinib (means ± SD drug concentration causing a 50% inhibition of the desired activity, 85 ± 10 nmol/L and 54 ± 9 nmol/L). Ribbon diagrams revealed that these JAK3 pseudokinase domain mutations were located at the pseudokinase-kinase domain interface. Although phosphorylated STAT3 was overexpressed in 35 of 68 patients with NTCL (51.4%), a STAT3 mutation (p.Tyr640Phe; STAT3^Y640F) at the SRC homology 2 domain was detected in 1 of the 63 patients (1.5%). A STAT3 inhibitor was active against STAT3-mutant SNK-6 and YT cells. Novel JAK3 mutations are oncogenic and druggable in NTCL. The JAK3 or STAT3 signal was altered in NTCL, and pathway inhibition might be a therapeutic option for patients with JAK3- or STAT3-mutant NTCL.

   PubMed IF 4.9 혈액종양내과
9. 1112017

   제1저자 안창호 · 교신저자 박경수

   Ahn CH, Han KA, Yu JM, Nam JY, Ahn KJ, Oh TK, Lee HW, Lee DH, Kim J, Chung CH, Park TS, Kim BJ, Park SW, Park HK, Lee KJ, Kim SW, Park JH, Ko KP, Kim CH, Lee H, Jang HC, Park KS

   Efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24-week, multicentre, randomized, double-blind, placebo-controlled study (TROICA study).

   Diabetes Obes Metab. 2017;19(5):635-643.

   Abstract

   AIMS To assess the efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, added to metformin and sulphonylurea in patients with type 2 diabetes (T2DM).

   MATERIALS AND METHODS We conducted a randomized, double-blind, placebo-controlled trial in 219 Korean patients inadequately controlled with metformin and glimepiride. Participants were randomized to gemigliptin 50 mg once daily or placebo added to metformin and glimepiride. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24.

   RESULTS The baseline HbA1c was 8.2% in both groups. The addition of gemigliptin to metformin and glimepiride significantly reduced HbA1c levels at week 24 compared with placebo (between-group difference in adjusted mean change -0.87%, 95% confidence interval [CI] -1.09% to -0.64%). Fasting plasma glucose level was also significantly reduced with gemigliptin (-0.93 mmol/L, 95% CI -1.50 to -0.35 mmol/L), and a higher proportion of participants achieved an HbA1c level of <7% (39.3% vs 5.5%; P <.001) in the gemigliptin group than in the placebo group. Total cholesterol and LDL cholesterol were modestly but significantly reduced in the gemigliptin group compared with the placebo group (-0.21 mmol/L, 95% CI -0.38 to -0.03 mmol/L for total cholesterol, -0.18 mmol/L, 95% CI -0.34 to -0.01 mmol/L for LDL cholesterol). The incidence of hypoglycaemia was 9.4% in the gemigliptin group and 2.7% in the placebo group.

   CONCLUSIONS Gemigliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin and sulphonylurea. The incidence of hypoglycaemia was higher with gemigliptin than with placebo, which highlights the importance of optimal dose adjustment for sulphonylurea.

   PubMed IF 6.1 내분비대사내과
10. 1102017

    제1저자 문신제, 송영신 · 교신저자 박영주

    Moon S, Song YS, Kim YA, Lim JA, Cho SW, Moon JH, Hahn S, Park DJ, Park YJ

    Effects of Coexistent BRAFV600E and TERT Promoter Mutations on Poor Clinical Outcomes in Papillary Thyroid Cancer: A Meta-Analysis.

    Thyroid. 2017;27(5):651-660.

    Abstract

    BACKGROUND The presence of a telomerase reverse transcriptase (TERT) promoter mutation has been suggested as a potential prognostic marker for thyroid cancer, and a synergistic association with the BRAF^V600E mutation has been demonstrated. The aim of this study was to verify the role of this genetic duet in papillary thyroid cancer (PTC).

    METHODS Studies of the association of BRAF^V600E and TERT promoter mutations with clinicopathologic features, recurrence, or PTC-related mortality were included from PubMed and Embase databases (inception to September 2016).

    RESULTS Thirteen eligible studies incorporating 4347 patients with PTC were included, and 283 (median 8.3%) of these patients had coexistent BRAF^V600E and TERT promoter mutations. The coexistence of the two mutations was far more strongly associated with high-risk clinicopathologic features than either mutation alone was, including advanced TNM stage (vs. BRAF^V600E: odds ratio [OR] = 4.19 [confidence interval (CI) 3.07-5.71]; vs. TERT: OR = 4.66 [CI 2.67-8.13]), extrathyroidal extension (vs. BRAF^V600E: OR = 3.1 [CI 2.2-4.37]; vs. TERT: OR = 5.66 [CI 3.02-10.6]), lymph node metastasis (vs. BRAF^V600E: OR = 1.59 [CI 1.16-2.17]; vs. TERT: OR = 2.03 [CI 1.22-3.38]), and distant metastasis (vs. BRAF^V600E: OR = 11.76 [CI 5.63-24.58]). The coexistence of the mutations showed the highest risk of recurrence (coexistence vs. no mutations: hazard ratio [HR] = 6.60 [CI 3.82-11.40]; BRAF^V600E vs. no mutations: HR = 1.31 [CI 0.49-3.46]; TERT vs. no mutations: HR = 3.38 [CI 0.85-13.35]). Moreover, PTC-related mortality was significantly higher with coexistent mutations than in the presence of BRAF^V600E alone (HR = 20.07 [CI 8.37-48.09]).

    CONCLUSIONS Coexistent BRAF^V600E and TERT promoter mutations have a synergistic effect on clinical outcomes in PTC, whereas each mutation alone has a modest effect. Therefore, molecular testing of BRAF^V600E and TERT promoter mutations together is useful in assessing risk stratification of PTC.

    PubMed IF 6.6 내분비대사내과
11. 1092017

    제1저자 이지현, 김정희 · 교신저자 신찬수

    Lee JH, Kim JH, Hong AR, Kim SW, Shin CS

    Skeletal effects of vitamin D deficiency among patients with primary hyperparathyroidism.

    Osteoporos Int. 2017;28(5):1667-1674.

    Abstract

    UNLABELLED Little is known about the association between vitamin D deficiency and the skeletal phenotypes in primary hyperparathyroidism (PHPT) patients. A low 25-hydroxyvitamin D level was associated with a low bone mineral density and deteriorated hip geometry in women with PHPT in an Asian population where vitamin D deficiency is prevalent.

    INTRODUCTION Few studies have examined the effect of vitamin D deficiency on the bone health of primary hyperparathyroidism (PHPT) patients.

    METHODS We investigated the skeletal effects of vitamin D deficiency in 79 PHPT patients by assessing bone mineral density (BMD), the trabecular bone score (TBS), and hip geometry, which were measured using dual-energy X-ray absorptiometry (27 men with median age 60 years [53;69]; 52 postmenopausal women with median age of 57 years [53;67]). Cross-sectional data were collected from subjects enrolled in an ongoing PHPT cohort study at Seoul National University Hospital from March 2008 to December 2015.

    RESULTS We classified PHPT patients according to 25-hydroxyvitamin D (25(OH)D) levels (<20 vs. ≥20 ng/ml). After adjusting for age and body mass index, women with vitamin D deficiency had lower BMDs at the lumbar spine (LS) and femur neck (FN) than women who had sufficient levels of vitamin D (LS, 0.903 ± 0.138 vs. 0.998 ± 0.184 g/cm²; FN, 0.715 ± 0.084 vs. 0.791 ± 0.113 g/cm²; P < 0.05). However, the total hip BMD and the TBS were not significantly different between the two groups. In the hip geometry analysis, the cross-sectional area, cross-sectional moment of inertia, and section modulus were also significantly lower in women with vitamin D deficiency than in those without. No significant difference was found in the BMD, TBS, or hip geometry according to 25(OH)D levels in men.

    CONCLUSION Vitamin D deficiency may be associated with a low BMD and deteriorated hip geometry in postmenopausal women with PHPT.

    PubMed IF 5.4 내분비대사내과
12. 1082017

    제1저자 공성혜 · 교신저자 김정희

    Kong SH, Kim JH, Hong AR, Lee JH, Kim SW, Shin CS

    Dietary potassium intake is beneficial to bone health in a low calcium intake population: the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2011).

    Osteoporos Int. 2017;28(5):1577-1585.

    Abstract

    UNLABELLED Dietary potassium may neutralize acid load and reduce calcium loss from the bone, leading to beneficial effect on bone mineral density. In this nationwide Korean population study, dietary potassium intake was associated with improved bone mineral density in older men and postmenopausal women.

    INTRODUCTION Nutrition is a major modifiable factor that affects bone health. The accompanying anion in dietary potassium may act as an alkaline source by neutralizing the acid load and reducing calcium loss from the bone. We aimed to evaluate the association between dietary potassium intake and bone mineral density (BMD) in the Korean population.

    METHODS We analyzed a total of 3135 men aged >50 years and 4052 postmenopausal women from the Korean National Health and Nutrition Examination Survey (KNHANES). Lumbar spine, total hip, and femur neck BMD were measured using dual energy X-ray absorptiometry. The daily food intake was assessed using a food frequency questionnaire.

    RESULTS When we divided the participants into tertiles based on the intake of potassium intake, the highest potassium intake tertile group showed a significantly higher total hip and femur neck BMD as compared to lower tertile groups (0.914 ± 0.004, 0.928 ± 0.003, 0.925 ± 0.004 mg/day across the tertiles, P = .014 for total hip; 0.736 ± 0.003, 0.748 ± 0.003, 0.750 ± 0.004 mg/day, P = .012 for femur neck). Postmenopausal women in the highest potassium intake tertile group showed significantly higher lumbar, total hip, and femur neck BMD as compared to those in lower potassium intake tertile groups (0.793 ± 0.004, 0.793 ± 0.003, 0.805 ± 0.004 mg/day across the tertiles, P = .029 for lumbar spine; 0.766 ± 0.003, 0.770 ± 0.002, 0.780 ± 0.003 mg/day, P = .002 for total hip; 0.615 ± 0.003, 0.619 ± 0.002, 0.628 ± 0.003 mg/day, P = .002 for femur neck).

    CONCLUSIONS Dietary potassium intake was positively associated with BMD in men aged >50 years and postmenopausal women, indicating the beneficial effects of dietary potassium intake on bone health.

    PubMed IF 5.4 내분비대사내과
13. 1072017

    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
14. 1062017

    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
15. 1052017

    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
16. 1042017

    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
17. 1032017

    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
18. 1022017

    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
19. 1012017

    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
20. 1002017

    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
21. 992017

    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
22. 982017

    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
23. 972017

    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
24. 962017

    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
25. 952017

    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
26. 942017

    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
27. 932017

    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
28. 922017

    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
29. 912017

    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
30. 902017

    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

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.