SCI 발표논문

2017년 269편

892017

제1저자 이준구 · 교신저자 김태민, 주영석

, , , , , , , , , , , , ,
Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma.
Ann Oncol. 2017;28(4):890-897.

Abstract
BACKGROUND Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored.
PATIENTS AND METHODS We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes.
RESULTS Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%-75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells.
CONCLUSION Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.
PubMed IF 80.4 혈액종양내과
882017

제1저자 홍아람 · 교신저자 김정희

, , , , , , , , , ,
Long-term effect of aromatase inhibitors on bone microarchitecture and macroarchitecture in non-osteoporotic postmenopausal women with breast cancer.
Osteoporos Int. 2017;28(4):1413-1422.

Abstract
UNLABELLED In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index.
INTRODUCTION AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer.
METHODS We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >-2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry.
RESULTS BMD significantly decreased from baseline to 5 years at the lumbar spine (-6.15%), femur neck (-7.12%), and total hip (-6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (-2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD.
CONCLUSIONS Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs.
PubMed IF 5.4 내분비대사내과
872017

제1저자 이연주 · 교신저자 박상헌

, , , , , , , , , , , , , ,
Differences in the Clinical Characteristics of Rapid Response System Activation in Patients Admitted to Medical or Surgical Services.
J Korean Med Sci. 2017;32(4):688-694.

Abstract
Variability in rapid response system (RRS) characteristics based on the admitted wards is unknown. We aimed to compare differences in the clinical characteristics of RRS activation between patients admitted to medical versus surgical services. We reviewed patients admitted to the hospital who were detected by the RRS from October 2012 to February 2014 at a tertiary care academic hospital. We compared the triggers for RRS activation, interventions performed, and outcomes of the 2 patient groups. The RRS was activated for 460 patients, and the activation rate was almost 2.3 times higher for surgical services than that for medical services (70% vs. 30%). The triggers for RRS activation significantly differed between patient groups (P = 0.001). They included abnormal values for the respiratory rate (23.2%) and blood gas analysis (20.3%), and low blood pressure (18.8%) in the medical group; and low blood pressure (32.0%), low oxygen saturation (20.8%), and an abnormal heart rate (17.7%) in the surgical group. Patients were more likely classified as do not resuscitate or required intensive care unit admission in the medical group compared to those in the surgical group (65.3% vs. 54.7%, P = 0.045). In multivariate analysis, whether the patient belongs to medical services was found to be an independent predictor of mortality after adjusting for the modified early warning score, Charlson comorbidity index, and intervention performed by the RRS team. Our data suggest that RRS triggers, interventions, and outcomes greatly differ between patient groups. Further research is needed to evaluate the efficacy of an RRS approach tailored to specific patient groups.
PubMed IF 3.2 호흡기내과
862017

제1저자 김원, 김병관 · 교신저자 김윤준

, , , , , , , , , , , , ,
Randomised clinical trial: the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease.
Aliment Pharmacol Ther. 2017;45(8):1073-1083.

Abstract
BACKGROUND Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model.
AIM To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD).
METHODS We performed a multicentre, double-blind, placebo-controlled, phase II study. Subjects with a liver fat >20% and hypertransaminasemia were randomised to the three groups: placebo (n = 22), 30 mg of oltipraz (n = 22) or 60 mg of oltipraz (n = 24) twice daily for 24 weeks. Changes in the liver fat from baseline to 24 weeks quantified using magnetic resonance spectroscopy were the primary outcome.
RESULTS Compared with the placebo group (-3.2 ± 11.1%), absolute changes in the liver fat content increased in a dose-dependent manner: -7.7 ± 7.0% and -13.9 ± 10.7% for the low-dose and high-dose groups (P = 0.13 and P < 0.01). Per cent reduction in the liver fat content was also significantly greater in the high-dose group than in the placebo group (-34.6 ± 29.4% vs. -0.6 ± 62.9%, P = 0.046). Body mass indices (-1.0 ± 0.9% vs. -0.5 ± 1.4%, P = 0.04) significantly decreased in the high-dose group compared to the placebo group. However, absolute changes in insulin resistance, liver enzymes, lipids and cytokines were not significantly different among groups. The incidence of adverse events was comparable among groups.
CONCLUSIONS Twenty-four-week oltipraz treatment significantly reduced the liver fat content in patients with NAFLD. Clinicaltrials.gov (NCT01373554).
PubMed IF 6.8 소화기내과
852017

제1저자 오태정,임수 · 교신저자 장학철, 조남한

, , , , , , , ,
One-hour postload plasma glucose concentration in people with normal glucose homeostasis predicts future diabetes mellitus: a 12-year community-based cohort study.
Clin Endocrinol (Oxf). 2017;86(4):513-519.

Abstract
OBJECTIVE In Caucasians, plasma glucose concentration at 1 h during an oral glucose tolerance test (OGTT) may be a better predictor of future diabetes mellitus than the fasting or 2-h postload glucose concentration. We investigated whether the 1-h glucose concentration could be used to predict future diabetes mellitus in Asian ethnicity.
MEASUREMENTS A total of 5703 Koreans with normal glucose tolerance were enrolled from the Korean Genome and Epidemiology Study. Indices of insulin sensitivity and β-cell function estimated from standard 75-g OGTTs performed every 2 years for 12 years were used to identify whether the 1-h glucose concentration could predict future diabetes mellitus.
RESULTS The mean age and body mass index at baseline were 51·3 ± 8·7 years and 24·2 ± 3·0 kg/m² , respectively. During the 12-year follow-up, 593 subjects (10·3%) developed diabetes mellitus. The area under the receiver-operating characteristic curve for incident diabetes mellitus was higher for the 1-h postload glucose concentration than for the fasting or postload 2-h glucose concentration (0·74 vs 0·61 or 0·63). The cut-off value of ≥8·0 mmol/l identified incident diabetes mellitus with 70% sensitivity and 68% specificity. After adjusting for typical risk factors, subjects with a 1-h postload glucose concentration ≥8·0 mmol/l had lower β-cell function and a 2·84-fold increased risk of incident diabetes mellitus compared with their counterparts.
CONCLUSIONS In this community-based 12-year prospective cohort study, 1-h postload plasma glucose concentration was an independent predictor of future diabetes mellitus and 8·0 mmol/l was suggested as a cut-off value.
PubMed IF 2.8 내분비대사내과
842017

제1저자 정숙향,박병주 · 교신저자 조인수

, , , , , ,
Isolation of hepatitis E virus genotype 4 from patients with acute cryptogenic hepatitis in Korea.
J Clin Virol. 2017;89:10-13.

Abstract
BACKGROUND Autochthonous hepatitis E occurs sporadically in developed countries. The consumption of undercooked pork containing hepatitis E virus genotype 3 (HEV-3) or 4 (HEV-4) is the major risk factor for infection. The serological diagnostic kits currently used in hospitals sometimes produce false-negative or -positive results. Therefore, detection of both HEV RNA and antibodies to the virus is required for confirmative diagnosis of hepatitis E.
OBJECTIVES We aimed to detect HEV in serum samples from patients with cryptogenic hepatitis and to determine the origin of HEV.
STUDY DESIGN A nested polymerase chain reaction (PCR) method was developed for detection of HEV-3 and HEV-4 in patients with hepatitis. A total of 23 serum samples, deposited in 2006-2012, from patients with acute cryptogenic hepatitis who were serologically negative for hepatitis A, B, C, and E were examined using this method. The amplified PCR products were genetically analyzed.
RESULTS Four HEV-4 isolates were detected from the 23 serum samples. Phylogenetic analysis indicated that three of the four isolates were closely related to HEV-4 isolates found in pigs in Korea and in patients with hepatitis E in Japan.
CONCLUSIONS The newly developed nested PCR method was useful for detection of HEV in patients with cryptogenic hepatitis. The close relationship between the human HEV-4 isolates identified in this study and swine isolates implied that zoonotic transmission of HEV might be a source of infection in patients with hepatitis.
PubMed IF 3.7 소화기내과
832017

제1저자 류신혜 · 교신저자 김인호

, , , , , , , , , , , , , , , , , ,
Salvage therapy for acute chemorefractory leukemia by allogeneic stem cell transplantation: the Korean experience.
Ann Hematol. 2017;96(4):605-615.

Abstract
Little is known about the characteristics that make patients with acute leukemia suitable for undergoing salvage therapy by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we analyzed the clinical outcomes of 223 patients with acute leukemia who underwent allo-HSCT while not in complete remission (CR). The primary end points were overall survival (OS) and CR rate. CR was achieved in 79.8% of patients after allo-HSCT. Acute graft-versus-host disease (GVHD) was significantly associated with CR (P = 0.045). During a median follow-up of 30.1 months, the median OS was 6.1 months. OS was significantly longer in patients with good or standard risk cytogenetic characteristics than in those with poor risk cytogenetic characteristics (P = 0.029, P = 0.030, respectively). Patients who received allo-HSCT from a matched sibling donor had better survival than those with unrelated donors (P = 0.015). Primary chemorefractoriness was not associated with poor survival (P = 0.071). The number of chemotherapies before allo-HSCT was significantly correlated with outcome (P = 0.006). Chronic GVHD was a strong predictor of a longer OS (P = 0.025). In conclusion, survival of patients with primary chemorefractory acute leukemia is not lower when treated upfront with allo-HSCT. Hence, allo-HSCT should be actively considered in such patients. Acute and chronic GVHD is associated with better outcomes patients with acute leukemia who have undergone allo-HSCT and not achieved CR.
PubMed IF 2.3 혈액종양내과
822017

제1저자 이민종 · 교신저자 김윤준

, , , , , , , , , , , ,
3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells.
PLoS One. 2017;12(3):e0174271.

Abstract
BACKGROUND & AIMS Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells.
METHODS We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells. Expression of hexokinase II, gamma-glutamylcysteine synthetase (rGCS), and epithelial-mesenchymal transition (EMT) markers in AR cells was assessed. Anti-tumor effects of a combination treatment of 3-BP and BSO were evaluated in AR cells and an HCC xenograft mouse model.
RESULTS AR HCC cells showed significantly higher chemoresistance, glycolysis and lower ROS production than attached cells. Expression of hexokinase II, rGCS, and EMT markers was higher in AR HCC cells than attached cells. A combination treatment of 3-BP/BSO effectively suppressed proliferation of AR HCC cells through apoptosis by blocking glycolysis and enhancing ROS levels. In xenograft mouse models, tumor growth derived from AR HCC cells was significantly suppressed in the group treated with 3-BP/BSO compared to the group treated with 3-BP or sorafenib.
CONCLUSIONS These results demonstrated that a combination treatment of 3-BP/BSO had a synergistic anti-tumor effect in an AR HCC model. This strategy may be an effective adjuvant therapy for patients with sorafenib-resistant HCC.
PubMed IF 2.8 소화기내과
812017

제1저자 허혁 · 교신저자 임춘수

, , , , , , ,
Factors affecting the long-term outcomes of idiopathic membranous nephropathy.
BMC Nephrol. 2017;18(1):104.

Abstract
BACKGROUND We attempted to describe the clinical features and determine the factors associated with renal survival in idiopathic membranous nephropathy (iMN) patients with nephrotic syndrome (NS) and to determine the factors associated with spontaneous complete remission (sCR) and progression to NS in iMN patients with subnephrotic proteinuria.
METHODS This retrospective study involved 166 iMN patients with NS and 65 patients with subnephrotic proteinuria. The primary end point was a doubling of serum creatinine or initiation of dialysis. In patients with subnephrotic proteinuria, we determined the factors associated with sCR and factors associated with progression to NS.
RESULTS Remission of NS was achieved in 125 out of 166 patients (75.3%). Of those who reached remission, 26 patients (20.8%) experienced relapse that was followed by second remission. The relapse or persistence of proteinuria was associated with the primary end points (hazard ratio [HR] = 12.40, P = 0.037, HR = 173, P < 0.001, respectively). In patients with subnephrotic proteinuria, sCR occurred in 35.4% of the patients. The patients with sCR had lower proteinuria and serum creatinine levels and higher serum albumin concentrations at baseline. The serum albumin level at diagnosis was a prognostic factor for progression to NS (Odds ratio [OR] = 0.015, P < 0.001).
CONCLUSIONS The occurrence of relapse or persistence of proteinuria had negative effects on renal survival in iMN patients with NS, and low serum albumin levels at baseline were associated with non-achievement of sCR and progression to NS.
PubMed IF 2.9 신장내과
802017

제1저자 차명진 · 교신저자 조구영

, , , ,
Prognostic power of global 2D strain according to left ventricular ejection fraction in patients with ST elevation myocardial infarction.
PLoS One. 2017;12(3):e0174160.

Abstract
BACKGROUNDS We aimed to evaluate the predictive power of longitudinal and circumferential fibers according to left ventricular ejection fraction (LVEF) in successfully reperfused acute ST elevation myocardial infarction (STEMI) patients.
METHODS Total 691 patients (age 59±13, 20% female) underwent clinical evaluation and conventional and strain echocardiography (Global longitudinal strain (GLS), global circumferential strain (GCS)). The clinical outcome was defined as the composite of death, hospitalization for heart failure, non-fatal myocardial infarction, and ventricular arrhythmia.
RESULTS During a follow-up of 39±19 months, there were 47 (6.8%) clinical events. In multivariate Cox models adjusted clinical risk factors, age (HR 1.08, p = 0.001) and GLS (HR 1.37, p = 0.001) were independent predictors. The addition of GLS resulted in significant incremental improvement in the predictive value on LVEF (χ2 = 31.8→45.8, p<0.001), although GCS offers no additional benefit. In the subgroup analysis according to LVEF, adjusted with clinical factors, GLS was significant predictive for outcome for the patients with mildly depressed (LVEF 40-50%, HR 2.25, p<0.001) and significantly depressed (LVEF<40%, HR 1.28, p = 0.016) systolic function, although GCS and LVEF lost their power with LVEF<40%. For the patients with preserved LVEF (>50%), GLS, GCS and LVEF did not show significant predictive power.
CONCLUSIONS GLS is a most powerful predictor of outcome in successfully reperfused STEMI patients, especially with depressed LV dysfunction, although GCS and LVEF lost their predictive power for the patients with significantly depressed LV function. However, GLS did not predict outcome for the patients with preserved LVEF (>50%).
PubMed IF 2.8 순환기내과
792017

제1저자 김형우 · 교신저자 황진혁

, , , , ,
Early versus delayed initiation of adjuvant treatment for pancreatic cancer.
PLoS One. 2017;12(3):e0173960.

Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC.
METHODS We retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20-83 days]).
RESULTS Patient baseline characteristics were comparable in both groups, except for grade III or IV postoperative complications (5.4% in the early group vs. 22.8% in the delayed group). With a median 20.3-month follow-up, the overall survival (OS) and disease-free survival (DFS) times were 29.5 and 14.7 months, respectively. The early group had significantly prolonged OS (39.1 vs. 21.1 months, p = 0.018) and DFS (18.8 vs. 10.0 months, p = 0.034), compared to the delayed group. Among 71 patients who completed planned adjuvant treatment, patients in the early group tended to have longer, though not statistically significant, OS and DFS times than those in the delayed group. In 67 patients without postoperative complications, patients in the early group had longer OS (42.8 vs. 20.5 months, p = 0.002) and DFS (19.6 vs. 9.1 months, p = 0.005) than those in the delayed group. By multivariate analysis, incompletion of treatment (hazard ratio [HR]: 4.039, 95% confidence interval [CI]: 2.334-6.992), delayed treatment initiation (HR: 1.822, 95% CI: 1.081-3.070), and positive angiolymphatic invasion (HR: 2.116, 95% CI: 1.160-3.862) were significantly associated with shorter OS.
CONCLUSIONS Adjuvant treatment should be delivered earlier and completed for better outcomes in resected PDAC patients, especially without postoperative complications.
PubMed IF 2.8 소화기내과
782017

제1저자 임주현 · 교신저자 김상균

, , , , , , , , , , , , , , , , , ,
Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of Helicobacter pylori in Peptic Ulcer Disease.
Gut Liver. 2017;11(2):226-231.

Abstract
BACKGROUND/AIMS The resistance rate of Helicobacter pylori is gradually increasing. We aimed to evaluate the efficacy of levofloxacin-based third-line H. pylori eradication in peptic ulcer disease.
METHODS Between 2002 and 2014, 110 patients in 14 medical centers received levofloxacin-based third-line H. pylori eradication therapy for peptic ulcer disease. Of these, 88 were included in the study; 21 were excluded because of lack of follow-up and one was excluded for poor compliance. Their eradication rates, treatment regimens and durations, and types of peptic ulcers were analyzed.
RESULTS The overall eradiation rate was 71.6%. The adherence rate was 80.0%. All except one received a proton-pump inhibitor, amoxicillin, and levofloxacin. One received a proton-pump inhibitor, amoxicillin, levofloxacin, and clarithromycin, and the eradication was successful. Thirty-one were administered the therapy for 7 days, 25 for 10 days, and 32 for 14 days. No significant differences were observed in the eradication rates between the three groups (7-days, 80.6% vs 10-days, 64.0% vs 14-days, 68.8%, p=0.353). Additionally, no differences were found in the eradiation rates according to the type of peptic ulcer (gastric ulcer, 73.2% vs duodenal/gastroduodenal ulcer, 68.8%, p=0.655).
CONCLUSIONS Levofloxacin-based third-line H. pylori eradication showed efficacy similar to that of previously reported first/second-line therapies.
PubMed IF 4.1 소화기내과
772017

제1저자 윤기철 · 교신저자 김나영

, , , , , , , , , , , , , , ,
Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery.
Gut Liver. 2017;11(2):209-215.

Abstract
BACKGROUND/AIMS Helicobacter pylori eradication is recommended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for "retesting" postoperative H. pylori status.
METHODS Patients who underwent curative gastrectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were assessed pre- and postoperatively.
RESULTS One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently positive for H. pylori, and 60 (42.9%) showed spontaneous negative conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group.
CONCLUSIONS A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individuals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori.
PubMed IF 4.1 소화기내과
762017

제1저자 최윤진, 최윤정 · 교신저자 김나영

, , , , , , , ,
Açaí Berries Inhibit Colon Tumorigenesis in Azoxymethane/Dextran Sulfate Sodium-Treated Mice.
Gut Liver. 2017;11(2):243-252.

Abstract
BACKGROUND/AIMS The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development.
METHODS The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting.
RESULTS Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells.
CONCLUSIONS Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer.
PubMed IF 4.1 소화기내과
752017

제1저자 정광현 · 교신저자 류지곤

, , , , , ,
Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy.
Gut Liver. 2017;11(2):298-305.

Abstract
BACKGROUND/AIMS Second-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) that progresses following gemcitabine-based treatment has not been established. This study aimed to investigate the efficacy and safety of second-line combination chemotherapy with capecitabine and oxaliplatin (XELOX) in these patients.
METHODS Between August 2011 and May 2014, all patients who received at least one cycle of XELOX (capecitabine, 1,000 mg/m² twice daily for 14 days; oxaliplatin, 130 mg/m² on day 1 of a 3-week cycle) combination chemotherapy for unresectable or recurrent PDAC were retrospectively recruited. The response was evaluated every 9 weeks, and the tumor response rate, progression-free survival and overall survival, and adverse events were assessed.
RESULTS Sixty-two patients were included; seven patients (11.3%) had a partial tumor response, and 20 patients (32.3%) had stable disease. The median progression-free and overall survival were 88 days (range, 35.1 to 140.9 days) and 158 days (range, 118.1 to 197.9 days), respectively. Patients who remained stable longer with frontline therapy (≥120 days) exhibited significantly longer progression-free and overall survival. The most common grade 3 to 4 adverse events in patients were vomiting (8.1%) and anorexia (6.5%). There was one treatment-related mortality caused by severe neutropenia and typhlitis.
CONCLUSIONS Second-line XELOX combination chemotherapy demonstrated an acceptable response and survival rate in patients with advanced PDAC who had failed gemcitabine-based chemotherapy.
PubMed IF 4.1 소화기내과
742017

제1저자 이선화 · 교신저자 이하정

, , , , , , , , , , , ,
Lower serum potassium associated with increased mortality in dialysis patients: A nationwide prospective observational cohort study in Korea.
PLoS One. 2017;12(3):e0171842.

Abstract
BACKGROUND Abnormal serum potassium concentration has been suggested as a risk factor for mortality in patients undergoing dialysis patients. We investigated the impact of serum potassium levels on survival according to dialysis modality.
METHODS A nationwide, prospective, observational cohort study for end stage renal disease patients has been ongoing in Korea since August 2008. Our analysis included patients whose records contained data regarding serum potassium levels. The relationship between serum potassium and mortality was analyzed using competing risk regression.
RESULTS A total of 3,230 patients undergoing hemodialysis (HD, 64.3%) or peritoneal dialysis (PD, 35.7%) were included. The serum potassium level was significantly lower (P < 0.001) in PD (median, 4.5 mmol/L; interquartile range, 4.0-4.9 mmol/L) than in HD patients (median, 4.9 mmol/L; interquartile range, 4.5-5.4 mmol/L). During 4.4 ± 1.7 years of follow-up, 751 patients (23.3%) died, mainly from cardiovascular events (n = 179) and infection (n = 120). In overall, lower serum potassium level less than 4.5 mmol/L was an independent risk factor for mortality after adjusting for age, comorbidities, and nutritional status (sub-distribution hazard ratio, 1.30; 95% confidence interval 1.10-1.53; P = 0.002). HD patients showed a U-shaped survival pattern, suggesting that both lower and higher potassium levels were deleterious, although insignificant. However, in PD patients, only lower serum potassium level (<4.5 mmol/L) was an independent predictor of mortality (sub-distribution hazard ratio, 1.35; 95% confidence interval 1.00-1.80; P = 0.048).
CONCLUSION Lower serum potassium levels (<4.5 mmol/L) occur more commonly in PD than in HD patients. It represents an independent predictor of survival in overall dialysis, especially in PD patients. Therefore, management of dialysis patients should focus especially on reducing the risk of hypokalemia, not only that of hyperkalemia.
PubMed IF 2.8 신장내과
732017

제1저자 유수종, 김현수 · 교신저자 윤정환, 김영수

, , , , , , , , , , , , , ,
Targeted Proteomics Predicts a Sustained Complete-Response after Transarterial Chemoembolization and Clinical Outcomes in Patients with Hepatocellular Carcinoma: A Prospective Cohort Study.
J Proteome Res. 2017;16(3):1239-1248.

Abstract
This study was aimed to identify blood-based biomarkers to predict a sustained complete response (CR) after transarterial chemoembolization (TACE) using targeted proteomics. Consecutive patients with HCC who had undergone TACE were prospectively enrolled (training (n = 100) and validation set (n = 80)). Serum samples were obtained before and 6 months after TACE. Treatment responses were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). In the training set, the MRM-MS assay identified five marker candidate proteins (LRG1, APCS, BCHE, C7, and FCN3). When this five-marker panel was combined with the best-performing clinical variables (tumor number, baseline PIVKA, and baseline AFP), the resulting ensemble model had the highest area under the receiver operating curve (AUROC) value in predicting a sustained CR after TACE in the training and validation sets (0.881 and 0.813, respectively). Furthermore, the ensemble model was an independent predictor of rapid progression (hazard ratio (HR), 2.889; 95% confidence interval (CI), 1.612-5.178; P value < 0.001) and overall an unfavorable survival rate (HR, 1.985; 95% CI, 1.024-3.848; P value = 0.042) in the entire population by multivariate analysis. Targeted proteomics-based ensemble model can predict clinical outcomes after TACE. Therefore, this model can aid in determining the best candidates for TACE and the need for adjuvant therapy.
PubMed IF 3.8 소화기내과
722017

제1저자 신중곤 · 교신저자 김윤준

, , , , , , , , , , , , ,
Identification of novel OCT4 genetic variant associated with the risk of chronic hepatitis B in a Korean population.
Liver Int. 2017;37(3):354-361.

Abstract
BACKGROUND & AIMS Hepatitis B viral infection is a serious risk factor for chronic hepatitis B (CHB), cirrhosis and hepatocellular carcinoma. Recently, several genome-wide association studies (GWASs) have been conducted to identify important genetic variant associated with the risk of CHB. In our previous GWAS, TCF19 was identified as one of the susceptibility genes for CHB risk (P=4.2×10^-9 at rs1419881). In order to discover possible additional causal variants around TCF19, we performed an association study by genotyping single nucleotide polymorphisms (SNPs) in OCT4, a nearby gene to TCF19.
METHODS Nineteen OCT4 genetic variants were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 population controls).
RESULTS Logistic regression analysis revealed that OCT4 rs1265163 showed the most significant association signal for the risk of CHB (OR=1.46, P=4.78×10^-12 ). Linkage disequilibrium and conditional analysis confirmed rs1265163 in OCT4 as a novel genetic marker for CHB susceptibility. The genetic risk scores (GRSs) were calculated to visualize the combined genetic effects of all known CHB-associated loci, including OCT4 rs1265163, which had been identified in this study. Individuals with higher cumulative GRSs showed significantly increased ORs. The luciferase activity of rs885952, a tagging SNP of rs1265163, showed that OCT4 promoter activity was significantly different between the wild-type and SNP mutant form (P<.05).
CONCLUSIONS This follow-up study to our previous GWAS identified a possible causal genetic variant associated with the risk of CHB, and findings from this study may prove useful in the understanding of genetic susceptibility to CHB.
PubMed IF 6.2 소화기내과
712017

제1저자 박경선 · 교신저자 정혜승

, , , , , ,
Vildagliptin reduces plasma stromal cell-derived factor-1α in patients with type 2 diabetes compared with glimepiride.
J Diabetes Investig. 2017;8(2):218-226.

Abstract
AIMS/INTRODUCTION Dipeptidyl peptidase-4 inhibitors might have pleiotropic protective effects on cardiovascular disease (CVD), in contrast to sulfonylureas. Therefore, we compared various CVD risk factors between vildagliptin and glimepiride.
MATERIALS AND METHODS We carried out a randomized, prospective and crossover trial. A total of 16 patients with type 2 diabetes whose glycated hemoglobin was >7% were randomized to add vildagliptin or glimepiride. After 12-week treatment, each drug was replaced with the other for another 12 weeks. Before and after each treatment, glucose homeostasis and CVD risk factors were assessed, and the continuous glucose monitoring system was applied to calculate glycemic variability.
RESULTS The mean age of the participants was 60 years, 31% were men, body mass index 25.5 kg/m² and HbA1c 8.41%. Both vildagliptin and glimepiride significantly decreased glycated hemoglobin and glycemic variability indices. Despite the improved glucose homeostasis, favorable change of CVD markers was not prominent in both the arms, along with significant weight gain. Only plasma stromal cell-derived factor (SDF)-1α decreased by 30% in the vildagliptin arm. According to regression analyses, the reduction of SDF-1α was independently associated with vildagliptin usage and serum interleukin-6 changes, but white blood cells were not related with the SDF-1α changes.
CONCLUSION Compared with glimepiride, vildagliptin arrestingly decreased plasma SDF-1α, and its clinical implications should be further investigated.
PubMed IF 3.6 내분비대사내과
702017

제1저자 이서희, 김병관 · 교신저자 고성준

, , , , , , , ,
Obstructive sleep apnea is associated with an increased risk of colorectal neoplasia.
Gastrointest Endosc. 2017;85(3):568-573.e1.

Abstract
BACKGROUND AND AIMS A recent meta-analysis showed that obstructive sleep apnea (OSA) is associated with a higher prevalence of cancer and cancer-related mortality; however, little information is available on the association between OSA and colorectal neoplasia.
METHODS We identified consecutive patients who underwent overnight polysomnography (PSG) and subsequent colonoscopy. We compared the prevalence of colorectal neoplasia between patients with or without OSA according to the results of PSG. For each patient with OSA, 1 or 2 controls matched for age (±5 years), sex, body mass index (BMI), and smoking who had undergone first-time screening colonoscopy were selected.
RESULTS Of the 163 patients, 111 patients were diagnosed with OSA and 52 patients were within the normal range of the Apnea-Hypopnea Index. Of the 111 patients with OSA, 18 patients (16.2%) had advanced colorectal neoplasia, including 4 (3.6%) colorectal cancers. In the multivariate analyses, OSA was associated with an increased risk of advanced colorectal neoplasia after adjusting for factors including age and sex (mild: odds ratio [OR], 14.09; 95% confidence interval [CI], 1.55-127.83; P = .019; moderate or severe: OR, 14.12; 95% CI, 1.52-131.25; P = .020). Our case-control study revealed that the odds of detecting advanced colorectal neoplasia among patients with OSA were approximately 3.03 times greater than in the controls matched for age, sex, BMI, and smoking (OR, 3.03; 95% CI, 1.44-6.34; P = .002).
CONCLUSION Physicians should be aware of the association between OSA and the development of colorectal neoplasia and explain the need for colonoscopy to patients with OSA.
PubMed IF 8 소화기내과
692017

제1저자 이서영 · 교신저자 강혜련

, , , , , ,
Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients.
Ann Allergy Asthma Immunol. 2017;118(3):339-344.e1.

Abstract
BACKGROUND Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified.
OBJECTIVE To assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media.
METHODS Our premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded.
RESULTS Among a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001).
CONCLUSION In a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions.
PubMed IF 7.1 알레르기내과
682017

제1저자 신정훈 · 교신저자 김범석

, , , , , , ,
Prognostic Impact of Newly Proposed M Descriptors in TNM Classification of Non-Small Cell Lung Cancer.
J Thorac Oncol. 2017;12(3):520-528.

Abstract
INTRODUCTION The International Association for the Study of Lung Cancer recently proposed new M descriptors for the next edition of the TNM classification for NSCLC, subdividing the current M1b category into two subcategories: M1b, which indicates a solitary extrathoracic metastasis in a single organ, and M1c, which indicates multiple extrathoracic metastasis. The purpose of this study was to validate the prognostic value of the newly proposed M descriptors in an independent cohort with multivariate and subgroup analysis.
METHODS A total of 1024 patients in a consecutive lung cancer database who had stage IV NSCLC treated between 2011 and 2014 were analyzed. Newly proposed M staging was used for classification and comparison of survival. Adjustment for other clinical covariates and subgroup analysis was conducted.
RESULTS According to the newly proposed M descriptors, 262 patients (25.6%), 152 patients (14.8%), and 610 patients (59.6%) were classified into the subgroups M1a, M1b, and M1c, respectively. The median overall survival times were 22.5, 17.8, and 13.6 months for the M1a, M1b, and M1c groups, respectively (p < 0.001). After adjustment for other covariates, Cox proportional hazards regression revealed statistically significantly shorter overall survival for the M1b group than for the M1a group (hazard ratio = 1.30; 95% confidence interval: 1.03-1.65, p = 0.03) and for the M1c than the M1b group (hazard ratio = 1.57; 95% confidence interval: 1.28-1.93, p < 0.001). These differences showed a consistent tendency regardless of pathologic and molecular subtypes.
CONCLUSIONS The newly proposed M descriptors have prognostic value in patients with stage IV NSCLC.
PubMed IF 23.3 혈액종양내과
672017

제1저자 김범석, 김민경 · 교신저자 박완범

, , , , , , , , , , , , , ,
Optimal timing of influenza vaccination during 3-week cytotoxic chemotherapy cycles.
Cancer. 2017;123(5):841-848.

Abstract
BACKGROUND Cytopenia occurs frequently during cytotoxic chemotherapy. Little is known about the optimal timing of influenza vaccination for patients receiving chemotherapy. This study compared the immunogenicity of an influenza vaccine administered concurrently with chemotherapy (day 1) and within the cytopenic period (day 11) during 3-week cytotoxic chemotherapy cycles.
METHODS Adult patients with solid cancer undergoing scheduled 3-week cytotoxic chemotherapy were randomly assigned to receive the 2014-2015 seasonal influenza vaccine on day 1 or 11 during the chemotherapy cycle. Patients were stratified by their age (<60 and ≥60 years) and previous influenza vaccination status. Antibody responses to influenza vaccine strains H1N1, H3N2, and B were measured before and 21 to 28 days after vaccination with a hemagglutination inhibition antibody assay.
RESULTS Ninety-seven patients were randomized into a day 1 group (n = 43) or a day 11 group (n = 54). Eighty-three patients were included in the final analysis. The mean age was 54 (± 11) years. Cancer types included breast (61%) and lung cancer (30%). Baseline characteristics were not significantly different between the groups. Seroprotection rates after vaccination were also not significantly different for the day 1 and 11 groups (strain H1N1, 67% vs 75% [P = .403]; strain H3N2, 77% vs 80% [P = .772]; strain B, 21% vs 27% [P = .472]). Seroconversion rates and postvaccination geometric mean titers were also similar for the groups. Vaccine-related adverse events were more common in the day 11 group (13% vs. 32%; P = .040).
CONCLUSIONS The antibody responses to influenza vaccination on days 1 and 11 during a 3-week cytotoxic chemotherapy cycle were comparable. Influenza vaccination can be performed concurrently with cytotoxic chemotherapy or during the cytopenic period. Cancer 2017;123:841-48. © 2016 American Cancer Society.
PubMed IF 5.6 감염내과
662017

제1저자 이희선, 구본권 · 교신저자 김효수

, , , , , , , , , , , , , , ,
A randomized clinical trial comparing long-term clopidogrel vs aspirin monotherapy beyond dual antiplatelet therapy after drug-eluting coronary stent implantation: Design and rationale of the Harmonizing Optimal Strategy for Treatment of coronary artery stenosis-Extended Antiplatelet Monotherapy (HOST-EXAM) trial.
Am Heart J. 2017;185:17-25.

Abstract
UNLABELLED Percutaneous coronary intervention (PCI) has been developed by drug-eluting stent (DES), but stent implantation has brought the issue of stent thrombosis and optimal antiplatelet therapy. Guidelines recommend at least 6- to 12 months of dual antiplatelet therapy (DAPT) with aspirin and a P2Y₁₂ receptor inhibitor such as clopidogrel. Beyond DAPT after PCI with DES, however, there has been still a debate for antiplatelet regimen. Therefore, we report on the upcoming HOST-EXAM trial (NCT02044250), which will evaluate the efficacy and safety of aspirin and clopidogrel monotherapies beyond DAPT after DES implantation.
TRIAL DESIGN The HOST-EXAM is a prospective, randomized, open-label, multicenter, comparative effectiveness trial, to compare between clopidogrel (75 mg once daily) and aspirin (100 mg once daily) as long-term antiplatelet agents. A total of 5,530 patients with no clinical events during combined antiplatelet therapy for 12±6 months after index PCI will be screened, enrolled, and randomized to either group (1:1 ratio) receiving antiplatelet monotherapy for 2 years. The primary endpoint will be the rate of clinical events defined as a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, or major bleeding at 24 months after randomization.
CONCLUSIONS The HOST-EXAM will be the first large-scale randomized controlled study to directly compare the efficacy and safety of long-term antiplatelet monotherapy beyond DAPT after DES implantation. This study will provide clinical evidence to establish optimal regimen for long-term antiplatelet therapy after DES implantation.
PubMed IF 3.4 순환기내과
652017

제1저자 안창호 · 교신저자 조영민

, , , ,
Effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on lipid metabolism and endotoxemia after a high-fat meal in patients with type 2 diabetes.
Diabetes Obes Metab. 2017;19(3):457-462.

Abstract
We aimed to investigate the effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on postprandial lipoprotein levels and endotoxemia in a randomized, double-blind, placebo-controlled, crossover study. Ten people with type 2 diabetes mellitus (T2DM), inadequately controlled with oral antidiabetic medications and/or lifestyle modification, were randomized to gemigliptin or placebo for 4 weeks. At the end of each treatment phase, the study participants underwent a high-fat meal tolerance test and needle aspiration of abdominal subcutaneous adipose tissue. The median (range) fasting and total area under the curve of apolipoprotein B48 (ApoB48) were significantly lower with gemigliptin than with placebo (2.9 [1.5-15.8] µg/mL vs 4.2 [1.3-23.4] µg/mL; P = .020; 35.3 [14.4-87.4] µg/mL × hour vs 42.2 [17.5-109.0] µg/mL × hour; P = .020, respectively), whereas apolipoprotein B100 showed no significant difference. Serum endotoxin levels were undetectable in 70% of the samples, so we were not able to evaluate the effect of gemigliptin on endotoxemia. The gene expression of inflammatory cytokines in subcutaneous adipose tissue was not affected by gemigliptin. Gemigliptin reduced ApoB48 levels after a high-fat meal in participants with T2DM. Whether systemic endotoxin levels can be reduced by gemigliptin requires further investigation.
PubMed IF 6.1 내분비대사내과
642017

제1저자 김지원, 이근욱 · 교신저자 김지현, 김태원

, , , , , , , , , , , , , , , , , , , , , , ,
Efficacy and Safety of FOLFIRI Regimen in Elderly Versus Nonelderly Patients with Metastatic Colorectal or Gastric Cancer.
Oncologist. 2017;22(3):293-303.

Abstract
BACKGROUND Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients.
PATIENTS AND METHODS Using the patient cohort (n = 1,545) from the UGT1A1 genotype study, we compared the efficacy and safety between elderly and nonelderly patients with metastatic CRC (n = 934) or GC (n = 611) who received first- or second-line FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy.
RESULTS Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (<70 years) patients in the CRC cohort (hazard ratio [HR], 1.117; 95% confidence interval [CI], 0.927-1.345; p = .244, and HR, 0.989; 95% CI, 0.774-1.264; p = .931, respectively) and the GC cohort (HR, 1.093; 95% CI, 0.854-1.400; p = .479, and HR, 1.188; 95% CI, 0.891-1.585; p = .241, respectively). In both cohorts, febrile neutropenia (22.1% vs. 14.6% in CRC cohort and 35.2% vs. 22.5% in GC cohort) and asthenia (grade 3: 8.4% vs. 1.7% in CRC cohort and 5.5% vs. 2.9% in GC cohort) were more frequent in elderly patients. In the CRC cohort, mucositis and anorexia were more frequent in elderly patients. In the GC cohort, nausea and vomiting were less frequent in elderly patients.
CONCLUSION The efficacy of the FOLFIRI regimen was similar between elderly and nonelderly patients in both the CRC and the GC cohorts. However, special attention should be paid to elderly patients because of increased risk for febrile neutropenia and asthenia. The Oncologist 2017;22:293-303 IMPLICATIONS FOR PRACTICE: The efficacy of FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy in elderly patients with metastatic colorectal cancer or gastric cancer was similar to that in nonelderly patients. However, special attention should be paid to elderly patients because of the increased risk for febrile neutropenia and asthenia. These data suggest that the FOLFIRI regimen could be considered as a standard backbone of therapy in elderly patients with metastatic colorectal cancer or gastric cancer and that the clinical decision between doublet and singlet chemotherapy may not be based solely on age. However, the data require further assessment of frailty and performance status.
PubMed IF 4.7 혈액종양내과
632017

제1저자 김경진, 김학령 · 교신저자 조주희

, , , , , , , , ,
Gender Difference in the Association between Aortic Pulse Pressure and Left Ventricular Filling Pressure in the Elderly: An Invasive Hemodynamic Study.
J Card Fail. 2017;23(3):224-230.

Abstract
BACKGROUND This study was conducted to determine the association between aortic pulse pressure (APP) and left ventricular (LV) filling pressure in the elderly of both genders.
METHODS A total of 211 stable elderly subjects (age ≥65 years, mean age 72.1 ± 5.2 years, 53.6% women) who underwent invasive coronary angiography (ICA) for the evaluation of coronary artery disease (CAD) were prospectively investigated. APP was measured in the ascending aorta using a pigtail catheter immediately before ICA. E/e', reflecting LV filling pressure, was assessed by transthoracic echocardiography.
RESULTS There were positive linear correlations between APP and E/e' in both genders, but the correlation power was stronger in women than in men (r = 0.402, P <.001 vs r = 0.208, P = .040). The significance of this association between APP and E/e' remained after controlling for potential confounders in multiple linear regression analysis in women (β = 0.359, P <.001), but not in men (r = 0.139, P = .108).
CONCLUSIONS Invasively measured APP is independently associated with E/e' in elderly women, but not in elderly men undergoing ICA. Aortic stiffness may be a potential mechanism for more prevalent LV diastolic dysfunction and heart failure with preserved ejection fraction in elderly women.
PubMed IF 9.9 순환기내과
622017

제1저자 이주명 · 교신저자 김효수

, , , , , , , , , , , , , , , , ,
Comparison of outcomes after treatment of in-stent restenosis using newer generation drug-eluting stents versus drug-eluting balloon: Patient-level pooled analysis of Korean Multicenter in-Stent Restenosis Registry.
Int J Cardiol. 2017;230:181-190.

Abstract
BACKGROUND Studies comparing the drug-eluting balloon (DEB) with contemporary drug-eluting stent (DES) in the treatment of in-stent restenosis (ISR) have been scarce. We compared that the efficacy and safety of contemporary DES versus DEB in unselected, real world patients of ISR occurred in bare-metal stent or DES.
METHODS Patient-level pooled analysis from nationwide multicenter registries was performed with 628 consecutive patients who underwent ISR treatment using 2nd or 3rd generation DES or DEB. Target lesion failure (TLF) and patient-oriented composite outcomes (POCO, composite of all-cause mortality, all-cause myocardial infarction, or any revascularization) at 1-year follow-up were compared between the DES and DEB groups.
RESULTS A total of 628 patients with 697 ISR lesions were treated using newer generation DES (n=409) or DEB (n=219). About 55.1% presented with acute coronary syndrome, and 15.1% showed left ventricular dysfunction. The risks of TLF and POCO were significantly lower in the DES group, even after being adjusted by an inverse probability weighted model (TLF, 9.2% vs. 17.9%, HR_adjust 0.22, 95% CI 0.11-0.47; POCO, 12.4% vs. 24.1%, HR_adjust 0.25, 95% CI 0.13-0.48, all p-values<0.001), mainly driven by the significantly lower risk of target lesion revascularization (TLR) (7.6% vs. 13.0%, HR_adjust 0.21, 95% CI 0.09-0.49, p<0.001). Treatment of ISR with DEB independently predicted TLF (HR 1.87, 95% CI 1.05-3.02, p=0.034) along with multi-vessel disease, chronic kidney disease, type B2 or C lesion, and number of treated lesion>1.
CONCLUSIONS In unselected patients of ISR, clinical outcome at one year was mainly dependent on difference in TLR and found to be better with contemporary DES than DEB.
PubMed IF 3.3 순환기내과
612017

제1저자 김학령,이정표 · 교신저자 김상현

, , , , , , , , , , , ,
Soluble Tumor Necrosis Factor Receptors and Arterial Stiffness in Patients With Coronary Atherosclerosis.
Am J Hypertens. 2017;30(3):313-318.

Abstract
BACKGROUND Soluble forms of tumor necrosis factor receptors (sTNFRs) are emerging target molecules of inflammatory disease. However, their role in vascular biology is not well known. This study was performed to investigate the association between serum concentrations of sTNFRs and arterial stiffness.
METHODS A total of 117 consecutive patients with suspected coronary artery disease (CAD) (63.6 ± 11.0 years; men, 65%) who were referred for invasive coronary angiography (ICA) were prospectively enrolled. Arterial blood sTNFR1 and sTNFR2 were measured using commercially available ELISA kits. Brachial-ankle pulse wave velocity (baPWV) measurements were made within 24 hours of blood sampling for sTNFRs measurement.
RESULTS Most of the patients (86.3%) had significant CAD (stenosis ≥ 50%) in ICA. In simple linear regression analyses, there were significant positive correlations of baPWV with sTNFR1 (r = 0.483, P < 0.001) and sTNFR2 (r = 0.366, P < 0.001). In multiple linear regression analyses, sTNFR1 (β = 0.316, P < 0.001) and sTNFR2 (β = 0.235, P = 0.005) had independent association with baPWV even after controlling for potential confounders.
CONCLUSION sTNFR1 and sTNFR2 were independently associated with baPWV in patients undergoing ICA. This result may extend previous knowledge on close interactions between inflammation and arterial stiffening.
PubMed IF 2.9 순환기내과
602017

제1저자 오수연 · 교신저자 김상균

, , , , , , ,
Ablation of residual gastric tumor by argon plasma coagulation after endoscopic resection.
Surg Endosc. 2017;31(3):1093-1100.

Abstract
BACKGROUND For residual gastric tumors (RT) found at the treated sites after endoscopic resections (ER), additional treatment options are additional ER, surgery or argon plasma coagulation (APC). Long-term efficacy of APC as the curative modality for RT has not been fully elucidated. This study aimed to investigate the efficacy and long-term outcome of APC for RT with relevant tumor factors.
METHODS Eighty-two patients who received ER for gastric adenocarcinoma or adenoma and were subsequently treated with APC for RT were reviewed retrospectively. Characteristics of the tumors curatively ablated with single-session of APC and the non-curatively ablated were compared by multiple logistic regression analysis. Overall rate of curative ablation and follow-up duration was calculated.
RESULTS Initial tumor size <20 mm [odds ratio for second residual recurrence (OR) 0.16; 95 % confidence interval (CI) 0.039-0.63], en-bloc resection (OR 0.16; 95 % CI 0.039-0.72), histologic complete resection (OR 0.14; 95 % CI 0.028-0.66) and RT with flat or depressed type (OR 0.20; 95 % CI 0.051-0.77) were significantly associated with curative ablation of RT by single-session of APC. Anterior wall or lesser curvature location showed a tendency toward curative APC, but not reached statistical significance (OR 0.36; 95 % CI 0.11-1.16). A total of 60 patients (73.2 %) achieved curative ablation after single-session of APC. Eleven among the patients (n = 22) with second or more residual recurrence achieved curative ablation with one or two more additional sessions of APC. Overall rate of curative ablation was 86.6 % (71/82). From the last APC, the final curative ablation group (n = 71) has been followed up for 49.7 ± 37.4 months.
CONCLUSIONS En-bloc resection, histologic complete resection, RT with flat or depressed type and initial tumor size less than 2 cm can be predictors of favorable clinical outcome of APC as an additional treatment for RT. For selected patients with RT, APC and close monitoring could be a reasonable alternative to immediate resection.
PubMed IF 3.3 소화기내과

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