SCI 발표논문

전체 4,588편

28782019

제1저자 김정희,도윤식 · 교신저자 김용휘

, , , , , ,
Developing an optimal follow-up strategy based on the natural history of nonfunctioning pituitary adenomas.
J Neurosurg. 2019;131(2):500-506.

Abstract
OBJECTIVE The natural history and proper algorithm for follow-up testing of nonfunctioning pituitary adenomas (PAs) are not well known, despite their relatively high prevalence. The aim of this study was to suggest the optimal follow-up algorithm for nonfunctioning PAs based on their natural history.
METHODS The authors followed up 197 patients with nonfunctioning PAs that had not been treated (including surgery and radiation therapy) at the time of detection, in a single center, between March 2000 and February 2017. They conducted a hormone test, visual field test, and MRI at the time of diagnosis and yearly thereafter.
RESULTS The overall median follow-up duration was 37 months. Microadenomas (n = 38) did not cause visual disturbance, pituitary apoplexy, or endocrine dysfunction. The incidence of patients with tumor volume growth ≥ 20% was higher for macroadenomas than microadenomas (13.8 vs 5.0 per 100 person-years [PYs], p = 0.002). The median time to any tumor growth was 4.8 years (95% CI 3.4-4.8 years) for microadenomas and 4 years (95% CI 3.3-4.2 years) for macroadenomas. The overall incidence of worsening visual function was 0.69 per 100 PYs. Patients with a tumor volume growth rate ≥ 0.88 cm3/year (n = 20) had a higher incidence of worsening visual function (4.69 vs 0.30 per 100 PYs, p < 0.001). The tumor growth rate of all microadenomas was < 0.88 cm3/year. The median time to tumor growth ≥ 20% was 3.3 years (95% CI 1.8-3.9 years) in patients with a tumor growth rate ≥ 0.88 cm3/year and 4.9 years (95% CI 4.6-7.2 years) in patients with a tumor growth rate < 0.88 cm3/year.
CONCLUSIONS The authors have devised a follow-up strategy based on the tumor volume growth rate as well as initial tumor volume. In patients with microadenomas, the next MRI study can be performed at 3 years. In patients with macroadenomas, the second MRI study should be performed between 6 months and 1 year to assess the tumor growth rate. In patients with a tumor growth rate ≥ 0.88 cm3/year, the MRI study should be performed within 2 years. In patients with a tumor growth rate < 0.88 cm3/year, the MRI study can be delayed until 4 years.
PubMed IF 3.8 내분비대사내과
28772019

제1저자 안상훈, 김원 · 교신저자 한광협

, , , , , , , , , , , , , , , , , , , , , , , , , , ,
Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection.
Clin Gastroenterol Hepatol. 2019;17(9):1850-1859.e4.

Abstract
BACKGROUND & AIMS Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea.
METHODS We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks.
RESULTS After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV-BSV and 85.7% of patients in the TDF-BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups.
CONCLUSIONS BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. ClinicalTrials.gov no: NCT01937806.
PubMed IF 16.2 소화기내과
28762019

제1저자 윤소현, 한미연 · 교신저자 오국환

, , , , , , ,
Genetic risk score raises the risk of incidence of chronic kidney disease in Korean general population-based cohort.
Clin Exp Nephrol. 2019;23(8):995-1003.

Abstract
BACKGROUND Chronic kidney disease (CKD) is a common disease, affecting about 10% of the general population. The genetic component about CKD incidence in Asian population is not well known. The aim of the study is to find the genetic loci associated with incident CKD and to figure out the effect of genetic variation on the development of CKD.
METHODS We conducted a genome-wide association (GWA) study regarding the development of CKD based on two population-based cohorts of Korean Genome Epidemiology Study. 3617 Koreans from two different cohorts, aged 40-49 years without CKD at initial visit, were included in our analysis. We used 2510 individuals in Ansan as the discovery set and another 1107 individuals from Ansung as the replication set. At baseline, members of both cohorts provided information on creatinine, and DNA samples were collected for genotyping. Single nucleotide polymorphisms that surpassed a significance threshold of P < 5 × 10^-3 were selected.
RESULTS A total of 281 among 3617 developed CKD during the follow-up period. Incident CKD group was older (P < 0.001), included more female (P < 0.001), and had more hypertension and diabetes (P < 0.001). We identified 12 SNPs that are associated with incident CKD in the GWA study and made genetic risk score using these SNPs. In multiple Cox regression analysis, genetic risk score was still a significant associated factor (HR 1.311, CI 1.201, 1.431, P < 0.001).
CONCLUSIONS We identified several loci highly associated with incident CKD. The findings suggest the need for further investigations on the genetic propensity for incident CKD.
PubMed IF 2.4 신장내과
28752019

제1저자 정민선, 김소연 · 교신저자 김태민, 전윤경

, , , , , , , , , , , , , , , , ,
Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study.
Oncologist. 2019;24(8):e740-e748.

Abstract
BACKGROUND NUT carcinoma is a rare aggressive disease caused by BRD4/3-NUT fusion, and C-MYC upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC-targeting agents against patient-derived NUT carcinoma cell lines.
MATERIALS AND METHODS Thirteen patients with NUT carcinoma were evaluated for p53, C-MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD-L1) by immunohistochemistry. The half maximal inhibitory concentration (IC₅₀) values of NUT carcinoma cell lines (SNU-2972-1, SNU-3178S, HCC2429, and Ty-82) were determined using MYC-targeting agents, including bromodomain and extraterminal (BET) inhibitors (I-BET, OTX-015, AZD5153) and histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin, panobinostat, CUDC-907).
RESULTS Primary tumor sites included head and neck (n = 9) and lung (n = 4). The patient age ranged from 8 to 73 years with the male/female ratio of 1.2:1. Nine patients died at 3-23.6 months (median, 10.6) after diagnosis. Eight patients had been misdiagnosed initially with other diseases. One patient with metastatic NUT carcinoma who received mass excision plus metastasectomy followed by chemoradiotherapy was a long-term survivor (>27 months). Although expressions of C-MYC (8/12, 73%) and p53 (12/12, 100%) were commonly observed, EGFR, HER2, and PD-L1 expressions were observed in 2 of 7 (29%), 2 of 8 (25%), and 1 of 12 (8.3%) patients, respectively. BET and HDAC inhibitors showed variable but limited in vitro efficacy. However, a dual HDAC/PI3K inhibitor, CUDC-907, was most potent against NUT carcinoma cells, with an IC₅₀ of 5.5-9.0 pmol/L. Consistent with these findings, kinome short interfering RNA screening showed a positive hit for PI3KCA in NUT carcinoma cells. Panobinostat (IC₅₀, 0.4-1.3 nmol/L) and a bivalent BET inhibitor, AZD5153 (IC₅₀, 3.7-8.2 nmol/L), also showed remarkable efficacies.
CONCLUSION East Asian patients with NUT carcinoma showed dismal survival outcomes like Western patients, and CUDC-907 might be promising in NUT carcinoma treatment.
IMPLICATIONS FOR PRACTICE NUT carcinoma (NC) is a disease caused by BRD-NUT fusion leading to C-MYC upregulation. NC is often misdiagnosed and very aggressive, requiring development of effective therapeutic strategy. This article presents the clinicopathological features of the largest series of NCs in East Asians and preclinical sensitivities to MYC-targeting agents in NC cell lines. Patients with NC had grave outcomes and poor response to treatment. Among MYC-targeting agents, including BET and HDAC inhibitors, CUDC-907 (a dual PI3K/HDAC inhibitor) was most effective against NC cells, followed by panobinostat (an HDAC inhibitor) and AZD5153 (a bivalent BET inhibitor). CUDC-907 might be promising in NC treatment.
PubMed IF 4.7 혈액종양내과
28742019

제1저자 오도연, 이근욱 · 교신저자 방영주

, , , , , , , , , ,
A First-in-Human Phase I Study of GC1118, a Novel Anti-Epidermal Growth Factor Receptor Antibody, in Patients with Advanced Solid Tumors.
Oncologist. 2019;24(8):1037-e636.

Abstract
LESSONS LEARNED GC1118 is a novel fully human anti-epidermal growth factor receptor (EGFR) antibody with unique binding epitopes and different ligand-binding inhibitory activity compared with cetuximab or panitumumab.GC1118 showed promising antitumor activity, especially in patients with colorectal cancer resistant to prior EGFR antibody. Skin toxicities were more common and diarrhea was less frequent compared with other anti-EGFR antibodies.
BACKGROUND GC1118 is a novel monoclonal antibody targeting epidermal growth factor receptor (EGFR) with more potent ligand inhibition than cetuximab or panitumumab. We conducted a first-in-human, phase I study of GC118 in patients with refractory solid tumors.
METHODS In the dose escalation part, GC1118 was administered on days 1, 8, 15, and 22, followed by a 2-week rest, during which dose-limiting toxicities (DLTs) were evaluated. In the expansion part, patients were enrolled into three cohorts (Cohort 1 [C1], patients with colorectal cancer [CRC] without prior anti-EGFR treatment; Cohort 2 [C2], patients with CRC with tumors resistant to anti-EGFR therapy; Cohort 3 [C3], EGFR-overexpressing gastric cancer).
RESULTS In the dose escalation part, 24 patients were treated at five dose levels: 0.3, 1.0, 3.0, 4.0, and 5.0 mg/kg. In the 5.0 mg/kg cohort, two patients experienced DLTs (skin toxicities). The maximum-tolerated dose (MTD) was 4.0 mg/kg. Common adverse events were skin toxicities. In the expansion part, 39 patients were enrolled. In Cohort 1, stable disease (SD) was observed in 58%; in Cohort 2, partial response (PR) 17% and SD 8%; in Cohort 3, PR 8% and SD 17%.
CONCLUSION GC1118 showed promising antitumor activity and was well tolerated. Infrequent diarrhea compared with other anti-EGFR antibodies might be advantageous for further development.
PubMed IF 4.7 혈액종양내과
28732019

제1저자 유민수 · 교신저자 백우현

, , , , , , , , , ,
Optimal Biliary Drainage for Patients With Biliary Anastomotic Strictures After Right Lobe Living Donor Liver Transplantation.
Liver Transpl. 2019;25(8):1209-1219.

Abstract
Right lobe (RL) living donor liver transplantation (LDLT) usually includes 2 bile duct anastomosis sites, namely, the right anterior and the right posterior segmental ducts. This study aimed to evaluate the optimal treatment for biliary strictures following RL LDLT with respect to unilateral or bilateral drainage techniques. From January 2005 to December 2017, 883 patients at Seoul National University Hospital underwent RL LDLT. Of these, 110 patients were enrolled who had 2 duct-to-duct anastomosis sites and who were considered at risk of developing biliary anastomotic strictures. Unilateral or bilateral biliary drainage during the follow-up period was identified by endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic biliary drainage (PTBD). The clinical success, complication, and 180-day mortality rates were compared between the unilateral and bilateral biliary drainage groups according to the initial ERCP findings. The mean age at the time of LDLT was 54.2 ± 8.2 years. The median time from LDLT to initial biliary anastomotic strictures was 177 (interquartile range, 18-1085) days. At the initial ERCP, unilateral drainage was performed in 55 (50.0%) patients, and bilateral drainage was performed in 11 (10.0%) patients. Of the patients who underwent unilateral drainage, 35 (63.6%) patients required conversion to bilateral drainage during follow-up. Overall, 71 (64.5%) patients required bilateral drainage more than once, whereas only 27 (24.5%) patients reached a resolution with unilateral biliary drainage. In this study, most patients required bilateral biliary drainage more than once during follow-up. An active attempt should be made to drain bilaterally in patients with biliary anastomotic strictures following RL LDLT.
PubMed IF 3.8 소화기내과
28722019

제1저자 안창호, 채세현 · 교신저자 조영민, 황대희

, , , ,
Dynamic Adaptive Changes of the Ileum Transposed to the Proximal Small Intestine in Rats.
Obes Surg. 2019;29(8):2399-2408.

Abstract
BACKGROUND Ileal transposition (IT) is an experimental surgery to investigate the role of the distal ileum in Roux-en-Y gastric bypass (RYGB) surgery. To systematically investigate the dynamic adaptation process of the ileum after IT, we performed transcriptome analyses of the transposed ileum compared with the ileum in situ at different postoperative time points.
METHODS Sprague-Dawley rats fed a chow diet underwent IT or sham surgery. One and 4 weeks after IT or sham surgery, total RNA was extracted from the ileal tissue and subjected to transcriptome analyses using microarray.
RESULTS Principal component analysis showed that the difference between weeks 1 and 4 was the largest, and the differences between the IT and sham groups were larger in week 4 than in week 1. We identified 1792 differentially expressed genes (DEGs) between IT and sham ileal tissues, including 659 and 1133 DEGs in weeks 1 and 4, respectively. Interestingly, only 45 and 24 DEGs were commonly up- or downregulated in weeks 1 and 4, indicating a marked transition during the adaptation process. Functional enrichment and network analyses showed that structural adaptation predominantly occurred in week 1, while metabolic and immune adaptations predominantly occurred in week 4. These analyses further revealed potential components that modulate structural adaptation (e.g., extracellular matrix) in week 1 and metabolic (e.g., glucose transporter) and immune (e.g., Th17 cells) adaptations in week 4.
CONCLUSIONS The transposed distal ileum underwent dynamic adaptation processes that may help explain the metabolic changes after RYGB.
PubMed IF 3.4 내분비대사내과
28712019

제1저자 김나영 · 교신저자 김나영

Chemoprevention of gastric cancer by Helicobacter pylori eradication and its underlying mechanism.
J Gastroenterol Hepatol. 2019;34(8):1287-1295.

Abstract
The cascade of gastric cancer, a leading cause of cancer incidence and mortality, is multifactorial. Helicobacter pylori (HP) infection plays a major role in gastric cancer (GC), and there has been an accumulation of data regarding the chemopreventive effect of HP eradication. However, it remains unclear how HP infection causes GC and how HP eradication prevents GC. To clarify this issue, the following approaches were performed in this review article. First, how HP-induced atrophic gastritis (AG) and intestinal metaplasia (IM) provoke the development of GC is shown, followed by how long HP eradication takes to induce a reversible change in AG and IM. Second, epigenetic studies of PTPN6, MOS, DCC, CRK, and VAV1 were performed in noncancerous gastric specimens in terms of HP status. Among these genes, MOS was found to be a possible surrogate marker for GC development. HP eradication decreased aberrant DNA methylation in a gene-specific manner, and MOS played a role in metachronous gastric neoplasms. Third, transforming growth factor-β1 (TGF-β1) and TGF-β1-induced epithelial-mesenchymal transition (EMT) markers were investigated in gastric mucosa. HP infection triggered the TGF-β1-induced EMT pathway and caused the emergence of GC stem cells, such as CD44v8-10. When HP was eradicated, these two pathways were inhibited. Finally, a 2222 cohort study showed that HP eradication significantly decreased the risk of noncardiac GC. Taken together, HP eradication is effective as a primary GC prevention method, and its underlying mechanism includes reversibility of AG and IM, methylation, EMT, and stem cells.
PubMed IF 3.5 소화기내과
28702019

제1저자 이현우, 박현경 · 교신저자 이연주

, , ,
Intensive care unit length of stay is reduced by protocolized family support intervention: a systematic review and meta-analysis.
Intensive Care Med. 2019;45(8):1072-1081.

Abstract
PURPOSE This study aimed to elucidate the impact of protocolized family support intervention on length of stay (LOS) in the intensive care unit (ICU) through a systematic review and meta-analysis.
METHODS Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and other web-based databases were referenced since inception until November 26, 2018. We included randomized-controlled trials wherein protocolized family support interventions were conducted for enhanced communication and shared medical decision-making. LOS (in days) and mortality were evaluated using a random-effects model, and adjusted LOS was estimated using a mixed-effects model.
RESULTS We included seven randomized-controlled trials with 3477 patients. Protocolized family support interventions were found to significantly reduce the ICU LOS {mean difference = - 0.89 [95% confidence interval (CI) = - 1.50 to - 0.27]} and hospital LOS [mean difference = - 3.78 (95% CI = - 5.26 to - 2.29)]; the results of the mixed-effect model showed that they significantly reduced ICU LOS after adjusting for the therapeutic goal [mean difference = - 1.30 (95% CI = - 2.35 to - 0.26)], methods of measurement [mean difference = - 0.89 (95% CI = - 1.55 to - 0.22)], and timing of intervention [mean difference = - 1.05 (95% CI = - 2.05 to - 0.05)]. Similar results were found after adjusting for patients' disease severity [mean difference = - 1.21 (95% CI = - 2.03 to - 0.39)] and the trim-and-fill method [mean difference = - 0.86 (95% CI = - 1.44 to - 0.28)]. There was no difference in mortality rate in ICU and hospital between the protocolized intervention and control groups.
CONCLUSIONS Protocolized family support intervention for enhanced communication and shared decision-making with the family reduced ICU LOS in critically ill patients without impacting mortality.
PubMed IF 22 호흡기내과
28692019

제1저자 이소령 · 교신저자 최의근

, , , , , , ,
Effectiveness and Safety of Contemporary Oral Anticoagulants Among Asians With Nonvalvular Atrial Fibrillation.
Stroke. 2019;50(8):2245-2249.

Abstract
Background and Purpose- Limited evidence exists on the effectiveness and safety of warfarin and all 4 available non-vitamin K antagonist oral anticoagulants (NOACs) from current clinical practice in the Asian population with nonvalvular atrial fibrillation. We aimed to evaluate the comparative effectiveness and safety of warfarin and 4 NOACs. Methods- We studied a retrospective nonrandomized observational cohort of oral anticoagulant naïve nonvalvular patients with atrial fibrillation treated with warfarin or NOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) from January 2015 to December 2017, based on the Korean Health Insurance Review and Assessment database. For the comparisons, warfarin to 4 NOACs and NOAC to NOAC comparison cohorts were balanced using the inverse probability of treatment weighting. Ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and a composite clinical outcome were evaluated. Results- A total of 116 804 patients were included (25 420 with warfarin, 35 965 with rivaroxaban, 17 745 with dabigatran, 22 177 with apixaban, and 15 496 with edoxaban). Compared with warfarin, all NOACs were associated with lower risks of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and composite outcome. Apixaban and edoxaban showed a lower rate of ischemic stroke compared with rivaroxaban and dabigatran. Apixaban, dabigatran, and edoxaban had a lower rate of gastrointestinal bleeding and major bleeding compared with rivaroxaban. The composite clinical outcome was nonsignificantly different for apixaban versus edoxaban. Conclusions- In this large contemporary nonrandomized Asian cohort, all 4 NOACs were associated with lower rates of ischemic stroke and major bleeding compared with warfarin. Differences in clinical outcomes between NOACs may give useful guidance for physicians to choose drugs to fit their particular patient clinical profile.
PubMed IF 11.1 순환기내과
28682019

제1저자 이소령 · 교신저자 최의근

, , , , ,
Efficacy of the optimal ablation index-targeted strategy for pulmonary vein isolation in patients with atrial fibrillation: the OPTIMUM study results.
J Interv Card Electrophysiol. 2019;55(2):171-181.

Abstract
PURPOSE The ablation index (AI) is a recently developed marker for ablation lesion quality that incorporates contact force (CF), time, and power in a weighted formula. There is a paucity of information on whether AI-guided pulmonary vein isolation (PVI) could improve the outcome in patients with atrial fibrillation (AF). We evaluated the optimal AI threshold for avoiding acute pulmonary vein reconnection (PVR), and to compare the efficacy of optimal AI-targeted PVI with that of conventional CF-guided PVI.
METHODS Seventy patients with AF (paroxysmal, 67%) were enrolled. In a phase 1 study, the patients underwent conventional CF-guided PVI (CON group), and the optimal AI threshold for avoiding acute PVR was identified. In phase 2, the patients underwent AI-guided PVI (OAI group). We compared the acute PVR rate between the CON group and the OAI group to demonstrate the efficacy of AI-guided PVI.
RESULTS In phase 1 (n = 38), acute PVR was observed in 57 of 532 (10.7%) segments. AI values of ≥ 450 at the anterior/roof segments and of ≥ 350 at the posterior/inferior/carina segments were identified as the optimal AI thresholds for avoiding acute PVR. In the phase 2 study targeting those AI values, the OAI group (n = 32) showed a significantly lower acute PVR rate than the CON group (4.2% vs. 10.7%, p < 0.001). The OAI group showed a higher minimum AI and smaller variations in AI values than the CON group.
CONCLUSIONS Optimal AI-targeted PVI is feasible and could improve the acute outcome in patients with AF.
TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT03389074.
PubMed IF 2.7 순환기내과
28672019

제1저자 김주혜 · 교신저자 이창훈

, , , , , , , , , ,
Acute Exacerbation According to GOLD 2017 Categories in Patients with Chronic Obstructive Pulmonary Disease.
Arch Bronconeumol (Engl Ed). 2019;55(8):414-420.

Abstract
INTRODUCTION The association between GOLD categorizations and future exacerbations has not been fully investigated. This study elucidates whether the GOLD 2017 classification is associated with different future exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) compared with the previous GOLD categorization. Another objective was to investigate the impacts of the symptoms and FEV1 on the predicted future exacerbation independently of previous exacerbation history.
METHODS We analyzed patients from three prospective COPD cohorts (SNUH, KOCOSS, and KOLD) and evaluated the risk of moderate to severe exacerbation among different models, including GOLD grade (FEV1), GOLD 2011, and GOLD 2017.
RESULTS In total, 611 COPD patients were included (36 from SNUH, 257 from KOCOSS, and 318 from KOLD). GOLD 2017 classification, excluding FEV1% for categorization criteria, showed no differences in future exacerbation risk compared with GOLD grade and GOLD 2011 based on c-statistics. Among those with no frequent exacerbation history and FEV1 ≥50%, the group with more symptoms was significantly associated with future exacerbations than the group with less symptoms. A lower FEV1 (FEV1 <50%) was not associated with a higher future exacerbation risk than a higher FEV1 (FEV1 ≥50%), regardless of prior exacerbation history and symptom group.
CONCLUSION The GOLD 2017 classification was not different from GOLD grade and GOLD 2011 regarding the association with future exacerbation risk, and there were no significant differences in exacerbation risk according to FEV1%. This suggests that FEV1 might not be an important factor in future exacerbation risk. These results partly support the GOLD 2017 assessment tool.
PubMed IF 4.214 호흡기내과
28662019

제1저자 김진동/조은주 · 교신저자 김윤준

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
A Model to Predict 1-Month Risk of Transplant or Death in Hepatitis A-Related Acute Liver Failure.
Hepatology. 2019;70(2):621-629.

Abstract
Acute liver failure (ALF) caused by hepatitis A is a rare but fatal disease. Here, we developed a model to predict outcome in patients with ALF caused by hepatitis A. The derivation set consisted of 294 patients diagnosed with hepatitis A-related ALF (ALFA) from Korea, and a validation set of 56 patients from Japan, India, and United Kingdom. Using a multivariate proportional hazard model, a risk-prediction model (ALFA score) consisting of age, international normalized ratio, bilirubin, ammonia, creatinine, and hemoglobin levels acquired on the day of ALF diagnosis was developed. The ALFA score showed the highest discrimination in the prediction of liver transplant or death at 1 month (c-statistic, 0.87; 95% confidence interval [CI], 0.84-0.92) versus King's College criteria (KCC; c-statistic, 0.56; 95% CI, 0.53-0.59), U.S. Acute Liver Failure Study Group index specific for hepatitis A virus (HAV-ALFSG; c-statistic, 0.70; 95% CI, 0.65-0.76), the new ALFSG index (c-statistic, 0.79; 95% CI, 0.74-0.84), Model for End-Stage Liver Disease (MELD; c-statistic, 0.79; 95% CI, 0.74-0.84), and MELD including sodium (MELD-Na; c-statistic, 0.78; 95% CI, 0.73-0.84) in the derivation set (all P < 0.01). In the validation set, the performance of the ALFA score (c-statistic, 0.84; 95% CI, 0.74-0.94) was significantly better than that of KCC (c-statistic, 0.65; 95% CI, 0.52-0.79), MELD (c-statistic, 0.74; 95% CI, 0.61-0.87), and MELD-Na (c-statistic, 0.72; 95% CI, 0.58-0.85) (all P < 0.05), and better, but not statistically significant, than that of the HAV-ALFSG (c-statistic, 0.76; 95% CI, 0.61-0.90; P = 0.28) and new ALFSG indices (c-statistic, 0.79; 95% CI, 0.65-0.93; P = 0.41). The model was well-calibrated in both sets. Conclusion: Our disease-specific score provides refined prediction of outcome in patients with ALF caused by hepatitis A.
PubMed IF 18 소화기내과
28652019

제1저자 김정한, 김택수 · 교신저자 박완범

, , , , , , , , , , , , , , , ,
Prospective evaluation of a rapid antimicrobial susceptibility test (QMAC-dRAST) for selecting optimal targeted antibiotics in positive blood culture.
J Antimicrob Chemother. 2019;74(8):2255-2260.

Abstract
OBJECTIVES MALDI-TOF MS has been successfully used for empirical antibiotic selection. However, limited data are available regarding the usefulness of MALDI-TOF MS in common resistant organisms compared with rapid antimicrobial susceptibility testing (AST). We prospectively evaluated the usefulness of rapid AST, compared with MALDI-TOF MS, for optimal antibiotic selection by infectious disease (ID) physicians in patients with bacteraemia including polymicrobial infection.
METHODS Three hundred and fifty-nine patients with positive blood culture were included for analysis. ID physicians prospectively decided on antibiotic regimens with consensus at each timepoint of receiving results of Gram stain, MALDI-TOF MS and rapid AST, the last of which was performed using QMAC-dRAST.
RESULTS ID physicians with MALDI-TOF MS results chose optimal targeted antibiotics in 255 (71.0%) cases, with appropriate antibiotic selection in 303 (84.4%) cases. The proportion of optimal targeted antibiotic selection and appropriate antibiotic selection was significantly lower for resistant strains than for susceptible strains [62.5% versus 79.2% (P < 0.001) and 68.2% versus 100% (P < 0.001), respectively]. QMAC-dRAST results led to optimal antibiotic treatment in 95 (91.3%) of the 104 cases receiving non-optimal targeted antibiotics. Optimal targeted treatments based on QMAC-dRAST results were possible in 322 (98.2%) of the 328 cases with monobacterial infection and in 345 (96.1%) of the 359 cases with monobacterial and polymicrobial infection.
CONCLUSIONS MALDI-TOF MS has a high chance of failure in guiding ID physicians to optimal antibiotics, especially against resistant organisms. With increasingly common resistant organisms, rapid AST is needed to identify optimal targeted antibiotics early in bacteraemia.
PubMed IF 3.6 감염내과
28642019

제1저자 박혜주 · 교신저자 윤성수

, , ,
The upregulation of Pim kinases is essential in coordinating the survival, proliferation, and migration of KIT D816V-mutated neoplastic mast cells.
Leuk Res. 2019;83:106166.

Abstract
About ˜80% of mast cell neoplasm patients harbor the c-Kit activating mutation D816 V, which is associated with c-Kit inhibitor resistance and poor prognosis. However, the molecular basis for these effects is not fully known. To address this issue, in this study we screened molecules whose expression is altered by KIT D816 V mutation and found that Pim kinases were overexpressed in D816V-mutant neoplastic mast cells. This was accompanied by upregulation of signal transducer and activator of transcription (STAT) and mammalian target of rapamycin (mTOR) and downregulation of Akt and extracellular signal-regulated kinase (ERK1/2). Activated Pim kinases promoted the survival of D816 V cells by maintaining mTOR and p70S6K activation even under nutrient starvation. Conversely, cell proliferation was suppressed by inhibiting Pim kinases. The mRNA level of C-X-C chemokine receptor type 4 (CXCR4) was about 2-fold higher in D816 V cells; this was associated with a 2-fold increase in migratory capacity, which was modulated by Pim kinases. We also confirmed that upregulation of Pim kinases is a feature specific to cells with the D816 V mutation and is not observed in cells with the c-Kit activating N822 K mutation. These data suggest Pim kinases as a promising therapeutic target for the treatment of mast cell neoplasms with KIT D816 V mutation.
PubMed IF 2.4 혈액종양내과
28632019

제1저자 문인기, 진광남 · 교신저자 김학령

, , , , , , , ,
Association of arterial stiffness with aortic calcification and tortuosity.
Medicine (Baltimore). 2019;98(33):e16802.

Abstract
Impact of arterial stiffness on aortic morphology has not been well evaluated. We sought to investigate the association of brachial-ankle pulse wave velocity (baPWV) with aortic calcification and tortuosity.A total of 181 patients (65.4 ± 10.4 years, males 59.7%) who underwent computed tomographic angiography and baPWV measurement within 1 month of study entry were retrospectively reviewed. Aortic calcification was quantified by the calcium scoring software system. Aortic tortuosity was defined as the length of the midline in the aorta divided by the length of linear line from the aortic root to the distal end of the thoraco-abdominal aorta. In simple correlation analyses, baPWV was correlated with aortic calcification (r = 0.36, P < .001) and tortuosity (r = 0.16, P = .030). However, these significances disappeared after controlling for confounders in multivariate analyses. Factors showing an independent association with aortic calcification were age (β = 0.37, P < .001), hypertension (β = 0.19, P = .003), diabetes mellitus (β = 0.12, P = .045), smoking (β = 0.17, P = .016), and estimated glomerular filtration rate (β = -0.25, P = .002). Factors showing an independent association with aortic tortuosity were age (β = 0.34, P < .001), body mass index (β = -0.19, P = .018), and diabetes mellitus (β = -0.21, P = .003).In conclusion, baPWV reflecting arterial stiffness was not associated with aortic calcification and tortuosity. Traditional cardiovascular risk factors were more influential to aortic geometry. Further studies with a larger sample size are needed to confirm our results.
PubMed IF 2 순환기내과
28622019

제1저자 박현경 · 교신저자 오도연

, , , , , ,
Prognostic implications of soluble programmed death-ligand 1 and its dynamics during chemotherapy in unresectable pancreatic cancer.
Sci Rep. 2019;9(1):11131.

Abstract
In pancreatic cancer, acquiring a sufficient amount of tumor tissue is an obstacle. The soluble form of PD-L1 (sPD-L1) may have immunosuppressive activity. Here, we evaluated the prognostic implications of sPD-L1 in unresectable pancreatic cancer. We prospectively enrolled 60 patients treated with first-line FOLFIRINOX chemotherapy. We collected blood samples at diagnosis, first response assessment and disease progression. Serum sPD-L1 levels were measured using enzyme-linked immunosorbent assays. The median sPD-L1 level was 1.7 ng/mL (range, 0.4-5.7 ng/mL). Patients with low sPD-L1 level (<4.6 ng/mL) at diagnosis showed better overall survival (OS) than those with high sPD-L1 level (P = 0.015). Multivariate analysis identified sPD-L1 and the neutrophil-to-lymphocyte ratio as independent prognostic factors for OS. During chemotherapy, more patients achieved complete response (CR)/partial response (PR) as their best response when sPD-L1 was decreased at the first response assessment (P = 0.038). In the patients who achieved CR/PR as their best response, sPD-L1 was significantly higher at the time of disease progression than at the first response assessment (P = 0.025). In conclusion, the sPD-L1 level at diagnosis exhibits a prognostic value in pancreatic cancer. Furthermore, sPD-L1 dynamics correlate with disease course and could be used to understand various changes in the tumor microenvironment during chemotherapy.
PubMed IF 4.9 혈액종양내과
28612019

제1저자 임석아, Yen-Shen Lu, Sara Hurvitz, Debu Tripathy · 교신저자 Debu Tripathy

, , , , , , , , , , , , , , , , , ,
Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer.
N Engl J Med. 2019;381(4):307-316.

Abstract
BACKGROUND An earlier analysis of this phase 3 trial showed that the addition of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided a greater benefit with regard to progression-free survival than endocrine therapy alone in premenopausal or perimenopausal patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report the results of a protocol-specified interim analysis of the key secondary end point of overall survival.
METHODS We randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen). Overall survival was evaluated with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods.
RESULTS A total of 672 patients were included in the intention-to-treat population. There were 83 deaths among 335 patients (24.8%) in the ribociclib group and 109 deaths among 337 patients (32.3%) in the placebo group. The addition of ribociclib to endocrine therapy resulted in significantly longer overall survival than endocrine therapy alone. The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5 to 76.0) in the ribociclib group and 46.0% (95% CI, 32.0 to 58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test). The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the overall intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50 to 0.98). The percentage of patients who received subsequent antineoplastic therapy was balanced between the groups (68.9% in the ribociclib group and 73.2% in the placebo group). The time from randomization to disease progression during receipt of second-line therapy or to death was also longer in the ribociclib group than in the placebo group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.55 to 0.87).
CONCLUSIONS This trial showed significantly longer overall survival with a CDK4/6 inhibitor plus endocrine therapy than with endocrine therapy alone among patients with advanced hormone-receptor-positive, HER2-negative breast cancer. No new concerns regarding toxic effects emerged with longer follow-up. (Funded by Novartis; MONALEESA-7 ClinicalTrials.gov number, NCT02278120.).
PubMed IF 84.5 혈액종양내과
28602019

제1저자 최정연 · 교신저자 송경호

, , , , , , , ,
Immunogenicity of the Varicella-Zoster Vaccine in Community-Dwelling Non-robust Elderly Individuals Compared to Robust Elderly Individuals: A Prospective Cohort Study.
J Gerontol A Biol Sci Med Sci. 2019;74(8):1225-1230.

Abstract
To determine whether immunogenicity of the herpes zoster live-attenuated vaccine (ZVL) in elderly individuals is influenced by frailty status and cytokine levels, individuals aged at least 65 years were prospectively administered ZVL after their frailty status and cytokine levels were assessed. Humoral and cellular immunogenicity were assessed using enzyme-linked immunosorbent assays for the varicella-zoster virus-specific IgG antibody and varicella-zoster virus-specific enzyme-linked immunospot assays, before and 6 weeks after vaccination. We enrolled 69 participants (mean age, 74.3 years); 31 were non-robust. Thirty-seven participants had a greater than 2 geometric mean fold rise in IgG antibodies, 22 more participants had at least 10 spot-forming cells/106 peripheral blood mononuclear cells (from 35 to 57 participants), and 42 experienced a twofold geometric mean fold rise increase of spot-forming cells 6 weeks after vaccination. The geometric mean fold rises of the antibody titers were similar in the robust and non-robust groups; moreover, the baseline enzyme-linked immunospot assay geometric mean values were not significantly different before or 6 weeks after vaccination. We observed no significant correlations between baseline cytokine levels and immunogenicity. Approximately half of the community-dwelling elderly participants in this study experienced a twofold rise in antibodies and one-third more participants showed at least 10 spot-forming cells after ZVL administration, suggesting that the ZVL can boost immunity in non-robust (especially pre-frail) and robust elderly individuals.
PubMed IF 4.6
28592019

제1저자 이연희 · 교신저자 이중엽, 오국환

, , , , , , , , ,
Incremental Peritoneal Dialysis May be Beneficial for Preserving Residual Renal Function Compared to Full-dose Peritoneal Dialysis.
Sci Rep. 2019;9(1):10105.

Abstract
Maintaining residual renal function (RRF) is a crucial issue in peritoneal dialysis (PD). Incremental dialysis is the practice of initiating PD exchanges less than four times a day in consideration of RRF, and increasing dialysis dose in a step-wise manner as the RRF decreases. We aimed to compare the outcomes of incremental PD and full-dose PD in terms of RRF preservation and other outcomes. This was a single-center, observational study. Data were extracted retrospectively from a cohort of incident PD patients over 16 years old who started PD between 2007 and 2015 in the PD Unit of Seoul National University Hospital. We used inverse probability weighting (IPW) adjustment based on propensity scores to balance covariates between the incremental and full-dose PD groups. Multivariate, time-dependent Cox analyses were performed. Among 347 incident PD patients, 176 underwent incremental PD and 171 underwent conventional full-dose PD. After IPW adjustment, the incremental PD group exhibited a lower risk of developing anuria (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.43-0.88). Patient survival, technique survival, and peritonitis-free survival were all similar between these groups (P > 0.05 by log-rank test). Incremental PD was beneficial for preserving RRF and showed similar patient survival when compared to conventional full-dose PD.
PubMed IF 4.9 신장내과
28582019

제1저자 곽낙원 · 교신저자 임재준

, , , , , , , , , , , , ,
M ycobacterium abscessus pulmonary disease: individual patient data meta-analysis.
Eur Respir J. 2019;54(1):13993003.01991-2018.

Abstract
Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense or M. abscessus subsp. bolletii, is challenging.We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment.Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36-5.10). For patients with M. abscessus subsp. abscessus, the use of azithromycin (aOR 3.29, 95% CI 1.26-8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05-1.99) or imipenem (aOR 7.96, 95% CI 1.52-41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense, the choice among these drugs was not associated with treatment outcomes.Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus.
PubMed IF 23.8 호흡기내과
28572019

제1저자 박준원 · 교신저자 이은영

, , , , , ,
Effects of tapering tumor necrosis factor inhibitor on the achievement of inactive disease in patients with axial spondyloarthritis: a nationwide cohort study.
Arthritis Res Ther. 2019;21(1):163.

Abstract
OBJECTIVES To investigate the association between the extent of tapering tumor necrosis factor inhibitor (TNFi) and the likelihood of achieving inactive disease in patients with axial spondyloarthritis (axSpA) METHODS: We analyzed 1575 1-year follow-up interval data of 776 axSpA patients treated with TNFi for more than 1 year in a nationwide observational cohort. The decision on tapering TNFi was made by patients and their physicians. We quantified TNFi used during interval as a dose quotient (DQ). The intervals were classified into the heavy-tapering (DQ < 50), mild-tapering (DQ 50-99), and control groups (DQ = 100). Outcome variables included achieving Ankylosing Spondylitis Disease Activity Score-inactive disease (ASDAS-ID) and major clinical response of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) in the follow-up visit. The effects of TNFi tapering on the outcome were analyzed using the generalized estimating equation.
RESULTS At the baseline visit, 91.1% of the patients showed a high disease activity (ASDAS-CRP ≥ 2.1). DQ of each interval was significantly influenced by the ASDAS-CRP measure in the prior follow-up (P < 0.001). ASDAS-ID was observed in 42.3% of the intervals. A multivariable analysis showed that the likelihood of outcome achievement was comparable between the control and mild-tapering groups, but significantly decreased in the heavy-tapering group (vs. the control group, adjusted OR = 0.28, [95% CI, 0.08-0.94]). In contrast, the likelihood to achieve BASDAI50 response was not different among the groups. In the subgroup of patients who reached ASDAS-ID 1 year after TNFi treatment (n = 327), ASDAS-ID was observed in 66.1% of the subsequent intervals, and only the mild-tapering group showed a likelihood of target maintenance comparable with that of the control group (adjusted OR = 1.25 [0.41-3.80]). This likelihood decreased with an increase in ASDAS-CRP.
CONCLUSION Mild tapering of TNFi has efficacy comparable with that of the standard-dose treatment for ASDAS-ID achievement in patients with axSpA.
PubMed IF 5.4 류마티스내과
28562019

제1저자 이소령, 이현정 · 교신저자 최의근

, , , , , , ,
Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Liver Disease.
J Am Coll Cardiol. 2019;73(25):3295-3308.

Abstract
BACKGROUND Advanced liver disease is known to increase the risk for bleeding and affects the hepatic clearance and metabolism of drugs. Subjects with active liver disease were excluded from pivotal clinical trials of direct oral anticoagulants (DOACs), so the evidence regarding the efficacy and safety of DOACs in patients with liver disease is lacking.
OBJECTIVES The aim of this study was to compare DOACs with warfarin in patients with nonvalvular atrial fibrillation and liver disease.
METHODS Using the Korean National Health Insurance Service database, subjects with atrial fibrillation and active liver disease treated with oral anticoagulation were included (12,778 with warfarin and 24,575 with DOACs), and analyzed ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome. Propensity score weighting was used to balance covariates between the 2 groups.
RESULTS DOACs were associated with lower risks for ischemic stroke (hazard ratio [HR]: 0.548; 95% confidence interval [CI]: 0.485 to 0.618), intracranial hemorrhage (HR: 0.479; 95% CI 0.394 to 0.581), gastrointestinal bleeding (HR: 0.819; 95% CI: 0.619 to 0.949), major bleeding (HR: 0.650; 95% CI: 0.575 to 0.736), all-cause death (HR: 0.698; 95% CI: 0.636 to 0.765), and the composite outcome (HR: 0.610; 95% CI: 0.567 to 0.656) than warfarin. Among the total study population, 13% of patients (n = 4,942) were identified as having significant active liver disease. A consistent benefit was observed in patients with significant active liver disease (HR for the composite outcome: 0.691; 95% CI: 0.577 to 0.827).
CONCLUSIONS In this large Asian population with atrial fibrillation and liver disease, DOACs showed better effectiveness and safety than warfarin, which was consistent in those with significant active liver disease.
PubMed IF 22.3 순환기내과
28552019

제1저자 강지훈 · 교신저자 박경우, 김효수

, , , , , , , , , , , , , ,
Development and Validation of an Ischemic and Bleeding Risk Evaluation Tool in East Asian Patients Receiving Percutaneous Coronary Intervention.
Thromb Haemost. 2019;119(7):1182-1193.

Abstract
BACKGROUND The ischemic/bleeding risk of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is still uncertain. We sought to develop a tool to predict ischemic and bleeding events in East Asians receiving 2nd generation drug-eluting stents (DESs) PCI.
METHODS A pooled cohort of 13,172 East Asian patients receiving PCI with 2nd generation DES (the Grand DES cohort) was analyzed to develop a scoring system. A net score was calculated by subtracting the bleeding score from the ischemic score. External validation was performed in the HOST-ASSURE and NIPPON trials.
RESULTS Among the total population, ischemic and bleeding events occurred in 195 patients (1.5%) and 166 patients (1.3%), respectively. The score to predict ischemic events included previous myocardial infarction (MI) or PCI, presentation as acute MI, anemia, stent diameter < 3 mm, and total stent length of ≥30 mm, while that for bleeding events included older age, low creatinine clearance, and anemia. C-statistics of the ischemic and bleeding model was 0.708 and 0.665, respectively. Patients with a net score of ≥1 had a higher ischemic risk compared with bleeding risk, and patients with a net score of ≤-1 had a higher bleeding risk compared with ischemic risk. The validation cohort showed a C-statistic of 0.647 for ischemic events and 0.633 for bleeding events.
CONCLUSION We developed a tool to predict ischemic and bleeding events in East Asian patients received PCI with 2nd generation DES. This system can be used to assess clinical event risks, and to determine the adequate duration of DAPT in East Asians.
PubMed IF 5.2 순환기내과
28542019

제1저자 윤연이, 김경민 · 교신저자 서정원, 윤보라

, , , , , , , , ,
Prediction of Subclinical Coronary Artery Disease With Breast Arterial Calcification and Low Bone Mass in Asymptomatic Women: Registry for the Women Health Cohort for the BBC Study.
JACC Cardiovasc Imaging. 2019;12(7 Pt 1):1202-1211.

Abstract
OBJECTIVES This study sought to determine whether evaluations of breast arterial calcification (BAC) and low bone mass (LBM) could improve the ability to predict subclinical coronary artery disease (CAD) in asymptomatic women.
BACKGROUND An improved risk stratification strategy beyond the measurement of conventional risk factors is needed to identify women at high risk of CAD.
METHODS The BBC (Women Health Registry Study for Bone, Breast, and Coronary Artery Disease) enrolled 2,100 asymptomatic women who underwent dual-energy X-ray absorptiometry, digital mammography, and coronary computed tomography angiography. We assessed the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk and evaluated the presence and severity of BAC, LBM, coronary artery calcification (CAC), and coronary atherosclerotic plaque (CAP).
RESULTS CAC and CAP were found in 11.2% and 15.6% of participants, respectively. In women with CAC or CAP, increasing trends in the presence and severity of both BAC and LBM were observed. Both BAC and LBM were found to be associated with the presence of CAC (unadjusted odds ratios [OR]: 3.54 and 2.22, respectively) and CAP (unadjusted OR: 3.02 and 1.91, respectively). However, in multivariate analysis, only the presence of BAC and BAC score remained as independent predictors. For the prediction of CAC and CAP, addition of the BAC presence to the 10-year ASCVD risk significantly increased the areas under the curve (area under the curve: 0.71 to 0.72; p = 0.016; and area under the curve: 0.66 to 0.68; p = 0.010; respectively) and resulted in net reclassification index improvements (area under the curve: 0.304; p <0.001; and area under the curve: 0.245; p <0.001; respectively).
CONCLUSIONS The presence and severity of BAC and LBM were significantly associated with the risk of subclinical CAD in asymptomatic women. BAC evaluation especially provides an independent and incremental value over conventional risk algorithms. (Women Health Cohort for Breast, Bone and Coronary Artery Disease [BBC]; NCT03235622).
PubMed IF 19 순환기내과
28532019

제1저자 김정연, 이대원 · 교신저자 이경훈

, , , , , , , , , , , , , ,
Prognostic role of body mass index is different according to menopausal status and tumor subtype in breast cancer patients.
Breast Cancer Res Treat. 2019;176(2):453-460.

Abstract
PURPOSE Although controversial, obesity and underweight may have a negative impact on breast cancer outcome. However, the relationship between body mass index (BMI) and breast cancer outcomes according to tumor subtype and menopausal status remains unclear.
METHODS This study investigated the association between BMI and breast cancer outcome in stage I-III breast cancer patients. The relationships were further evaluated according to tumor subtype and menopausal status.
RESULTS A total of 5919 patients, 3475 (58.7%) hormone receptor (HR)(+) human epidermal growth factor receptor 2 (HER2)(-), 608 (10.3%) HR(+)HER2(+), 621 (10.5%) HR(-)HER2(+), and 1079 (18.2%) HR(-)HER2(-) were included. Underweight and obesity had a negative impact on relapse-free survival but did not affect overall survival. Importantly, the prognostic role of BMI was different according to tumor subtype and menopausal status. In HR(+)HER2(-) patients, underweight was associated with poor relapse-free survival and overall survival in pre-menopausal women. In contrast, obesity had negative impact on relapse-free survival and overall survival in HR(+)HER2(-) post-menopausal patients. Underweight may have a negative prognostic role in HR(+)HER2(+) patients. However, BMI did not impact the outcome of HR(-)HER2(+) and HR(-)HER2(-) patients.
CONCLUSIONS The impact of BMI on breast cancer outcome was dependent on tumor subtype and menopausal status. In HR(+)HER2(-) patients, underweight and obesity had a negative prognostic role in pre-menopausal and post-menopausal women, respectively. These findings in Asian population should be further evaluated and compared in Western population.
PubMed IF 3.3 혈액종양내과
28522019

제1저자 최미홍 · 교신저자 김범석

, , , , , ,
Pemetrexed in the Treatment of Leptomeningeal Metastasis in Patients With EGFR-mutant Lung Cancer.
Clin Lung Cancer. 2019;20(4):e442-e451.

Abstract
INTRODUCTION Leptomeningeal metastasis (LM), still an area of unmet need, has frequently been observed in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Because the antitumor efficacy of systemic cytotoxic agents against LM is unclear, we explored the role of pemetrexed in the treatment of patients with LM from EGFR-mutant NSCLC.
PATIENTS AND METHODS We retrospectively reviewed the medical records of patients with LM from EGFR-mutant NSCLC treated between 2006 and 2016. Post-LM survival was evaluated as well as clinical factors.
RESULTS In our patient cohort with EGFR-mutant NSCLC (n = 631), 17.4% (n = 110) developed LM. Their median post-LM survival was 5.7 months (95% confidence interval, [CI], 0.0-12.0 months). Post-LM survival was significantly longer with pemetrexed use after LM (median, 13.7 months; 95% CI, 4.1-23.2 months) than without pemetrexed use after LM (median, 4.0 months; 95% CI, 2.2-5.7 months; P = .008). In the multivariate analyses, no pemetrexed use after LM (vs. use) and no EGFR tyrosine kinase inhibitor use after LM (vs. use) were independently associated with a poor post-LM survival with a hazard ratio of 3.1 (95% CI, 1.5-6.3; P = .002) and 3.0 (95% CI, 1.6-5.8; P = .001), respectively.
CONCLUSION Pemetrexed use after LM was independently associated with a longer post-LM survival in patients with EGFR-mutant NSCLC with LM. Prospective studies are warranted to validate this finding.
PubMed IF 3.9 혈액종양내과
28512019

제1저자 방영주 · 교신저자 방영주

, , , , , , , , , , , , , , , , , ,
Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study.
Gastric Cancer. 2019;22(4):828-837.

Abstract
BACKGROUND The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented.
METHODS Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m² on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m² on days 1-5 of each 3-week cycle (or capecitabine 1000 mg/m² twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy).
RESULTS In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8-24.1) and 17.5 months (range 1.7-20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3-5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7-78.9] (combination therapy) and 25.8% (95% CI 11.9-44.6) (monotherapy).
CONCLUSIONS Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma.
CLINICAL TRIAL ClinicalTrials.gov NCT02335411.
PubMed IF 6.1 혈액종양내과
28502019

제1저자 조경민 · 교신저자 김범석

, , , , , , , , , , ,
Clinical significance of rituximab infusion-related reaction in diffuse large B-cell lymphoma patients receiving R-CHOP.
Korean J Intern Med. 2019;34(4):885-893.

Abstract
BACKGROUND/AIMS This study was to evaluate the clinical significance of infusion-related reaction (IRR) of rituximab in diffuse large B-cell lymphoma (DLBCL) patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) as a first-line chemotherapy.
METHODS The medical records of 326 patients diagnosed with DLBCL were re trospectively analyzed. Both doctor's progress records and nursing records were reviewed. IRR was graded according to the National Cancer Institute Common Terminology Criteria.
RESULTS IRR was not associated with overall survival (OS) or progression-free survival (PFS) of DLBCL patients as compared to those who did not have IRR (OS: median 78.0 months vs. 69.0 months, p = 0.700; PFS: median 65.4 months vs. 64.0 months, p = 0.901). IRR grade did not affect OS or PFS. B symptoms was independently associated with IRR (hazard ratio [HR], 1.850; 95% confidence interval [CI], 1.041 to 3.290; p = 0.036). Further, bone marrow involvement was independently associated with re-IRR (HR, 4.904; 95% CI, 0.767 to 3.118; p = 0.029).
CONCLUSION Our study shows that IRR of rituximab is not associated with OS or PFS of DLBCL patients who received R-CHOP. Furthermore, our study suggests a need for more careful observation for IRR in patients with B symptoms or bone marrow involvement.
PubMed IF 2.2 혈액종양내과
28492019

제1저자 김진원 · 교신저자 김지현

, , , , , , , , , , , , , , , , , , ,
Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy.
Cancer Res Treat. 2019;51(3):1249-1256.

Abstract
PURPOSE The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy.
MATERIALS AND METHODS Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC).
RESULTS The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006).
CONCLUSION KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.
PubMed IF 4.2 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.