SCI 발표논문
2013년 272편
- 322013
제1저자 김광일 · 교신저자 진호준
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Differential white blood cell count and all-cause mortality in the Korean elderly.Exp Gerontol. 2013;48(2):103-8.
PubMed IF 5.1 신장내과Abstract
The circulating white blood cell (WBC) count has been considered a good biomarker of systemic inflammation, but the predictive value of this inexpensive and universally obtained test result has not been fully explored in the elderly. The objective of this study was to assess the independent association of WBC count and its individual components with mortality in an elderly population. We studied a total of 9996 participants (age ≥65 years) who underwent routine health examinations at the 2 healthcare centers affiliated with Seoul National University. Mortality data were obtained from the National Statistics Office of Korea. The mean age of the study population was 69.7 (SD 4.3) years, and 5491 of the subjects (54.9%) were male. The median length of follow-up was 44.9 months (range, 1.2-78.7 months). There were 118 deaths (1.2%) during the follow-up period. The leading cause of death was cancer. Compared with the survivors, the deceased subjects were older, predominantly male, had increased levels of inflammatory markers, and had poor nutritional status. A significant difference in mortality was identified among patients in different WBC and WBC subtype quartile groups. Cox proportional hazards analysis indicated that monocyte count (HR: 5.18, 95% CI: 2.44-11.02) was a strongest predictor of all-cause mortality than total WBC count (HR: 1.57, 95% CI: 0.88-2.80), granulocyte count (HR: 2.11, 95% CI: 1.15-3.88), and lymphocyte count (HR: 1.11, 95% CI: 0.66-1.86), even after adjusting for possible confounding variables. Monocyte counts were associated with an increased risk of cardiovascular and cancer-related mortality in the elderly population. In conclusion, the total WBC count is an independent predictor of mortality in older adults, but the monocyte subtype provides greater predictive ability.
- 312013
제1저자 김경임, 김지원 · 교신저자 윤성수, 오정미
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Recombinant human epidermal growth factor on oral mucositis induced by intensive chemotherapy with stem cell transplantation.Am J Hematol. 2013;88(2):107-12.
PubMed IF 9.4 혈액종양내과Abstract
Oral mucositis (OM) is one of the most common and debilitating complications in patients undergoing intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for OM induced by intensive chemotherapy followed by HSCT. Patients were randomly assigned to either the rhEGF group or placebo group. The severity of OM and self-reported quality of life (QOL) were assessed daily. A total of 58 patients were analyzed. Baseline characteristics were similar between the two groups. The incidence of NCI grade ≥ 2 OM was higher in the rhEGF group (78.6% vs. 50%, P = 0.0496). However, the duration of OM in patients with NCI grade ≥ 2 tended to be shorter in the rhEGF group (8.5 days vs. 14.5 days, P = 0.262). The QOL analysis in patients with World Health Organization (WHO) grade ≥ 3 OM showed that rhEGF significantly reduced limitations in swallowing (P = 0.039) and drinking (P = 0.042). The duration of hospitalization (P = 0.047), administration of total parenteral nutrition (P = 0.012), and the usage of opioid analgesics (P = 0.018) were significantly shorter in the rhEGF group with WHO grade ≥ 3 OM. Adverse events were mild and similar between the two groups. In conclusion, this analysis showed that rhEGF did not reduce the incidence of NCI grade ≥ 2 OM. However, the patients with WHO grade ≥ 3 OM in the rhEGF group showed better results compared to the placebo group for several secondary endpoints.
- 302013
제1저자 김도형 · 교신저자 이정표
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Early referral to a nephrologist improved patient survival: prospective cohort study for end-stage renal disease in Korea.PLoS One. 2013;8(1):e55323.
PubMed IF 2.8 신장내과Abstract
The timing of referral to a nephrologist may influence the outcome of chronic kidney disease patients, but its impact has not been evaluated thoroughly. The results of a recent study showing an association between early referral and patient survival are still being debated. A total of 1028 patients newly diagnosed as end-stage renal disease (ESRD) from July 2008 to October 2011 were enrolled. Early referral (ER) was defined as patients meeting with a nephrologist more than a year before dialysis and dialysis education were provided, and all others were considered late referral (LR). The relationship of referral pattern with mortality in ESRD patients was explored using a Cox proportional hazards regression models. Time from referral to dialysis was significantly longer in 599 ER patients than in 429 LR patients (62.3 ± 58.9 versus 2.9 ± 3.4 months, P<0.001). Emergency HD using a temporary vascular catheter was required in 485 (47.2%) out of all patients and in 262 (43.7%) of ER compared with 223 (52.0%) of LR (P = 0.009). After 2 years of follow-up, the survival rate in ER was better than that in LR (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.27-4.45, P = 0.007). In patients with diabetes nephropathy, patient survival was also significantly higher in ER than in LR (HR 4.74, 95% CI 1.73-13.00, P = 0.002). With increasing age, HR also increased. Timely referral to a nephrologist in the predialytic stage is associated with reduced mortality.
- 292013
제1저자 이하정 · 교신저자 허남주
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Potassium intake and the prevalence of metabolic syndrome: the Korean National Health and Nutrition Examination Survey 2008-2010.PLoS One. 2013;8(1):e55106.
PubMed IF 2.8 신장내과Abstract
Lower potassium intake is considered to be correlated with diabetes incidence. However, few studies have investigated the effect of potassium intake on metabolic syndrome (MetS). Data was taken from the Korean National Health and Nutritional Examination Survey (2008-2010) using weighted adjustment. MetS was defined as per the revised National Cholesterol Education Program criteria. Homeostasis model assessment indices were calculated to diagnosis insulin resistance (IR). A total of 16,637 participants (44 ± 0.25 years) were included. Women ingested lower amounts of potassium (2.71 ± 0.02 g/day) than men (3.45 ± 0.03 g/day). A curvilinear association between potassium intake and MetS prevalence was found among women. Women with less than the Adequate Intake (4.7 g/day) of potassium had an 11% risk reduction for MetS (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.82-0.96; P = 0.004) and a 10% risk reduction for IR (OR, 0.90; 95% CI, 0.82-0.99; P = 0.026) for every 1 g/day potassium increase. Compared with the reference group (3.5-4.5 g/day), potassium intake was inversely associated with an increased risk of MetS (1.5-2.5 g/day; OR, 1.29; 95% CI, 1.02-1.63; P = 0.035; <1.5 g/day; OR, 1.40; 95% CI, 1.06-1.85; P = 0.017) and IR (<1.5 g/day; OR, 1.36; 95% CI, 1.05-1.76; P = 0.021). This relationship was more prominent in postmenopausal women, but not observed among men. Higher potassium intake is significantly associated with a lower MetS prevalence in women, and IR is believed to be connected.
- 282013
제1저자 이하정 · 교신저자 진호준
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Mortality and renal outcome of primary glomerulonephritis in Korea: observation in 1,943 biopsied cases.Am J Nephrol. 2013;37(1):74-83.
PubMed IF 3.8 신장내과Abstract
BACKGROUND Previous epidemiological studies have focused on the prevalence of primary glomerulonephritis (GN), but few have explored long-term patient outcomes. This study was conducted to investigate the long-term patient and renal outcomes of primary GN.
METHODS A total of 1,943 biopsy-proven primary GN patients were included. The outcomes were mortality and end-stage renal disease (ESRD) progression. The relative mortality rate was expressed by the standardized mortality ratio (SMR) and the 95% confidence interval (CI).
RESULTS During the median follow-up of 90 months, 325 (16.7%) patients progressed to ESRD and 164 (8.4%) patients died. Patients with minimal change disease exhibited the best renal and patient outcomes, whereas those with membranoproliferative GN had the worst. IgA nephropathy patients appeared to have a good survival rate in spite of their considerable progression to ESRD, and focal segmental glomerulosclerosis patients showed poor renal and patient outcomes. Mortality was 67% higher in primary GN patients than in the age- and sex-matched general population (SMR, 1.67; 95% CI, 1.42-1.95). The difference was more prominent in women (SMR, 2.95; 95% CI, 2.27-3.77) than in men (SMR, 1.31; 95% CI, 1.07-1.60). Renal risk factors, e.g. hypertension, proteinuria and initial renal dysfunction, were all associated with higher mortality, and the relative mortality rate increased with the number of risk factors.
CONCLUSIONS In patients with primary GN, mortality is significantly higher than in the age-/sex-matched general population, especially in women. Moreover, the presence of renal risk factors is positively associated with both relative mortality and progression to ESRD.
- 272013
제1저자 명선정 · 교신저자 박완범
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Effect of enhanced analytic reasoning on diagnostic accuracy: a randomized controlled study.Med Teach. 2013;35(3):248-50.
PubMed IF 4 소화기내과Abstract
BACKGROUND Diagnostic error can be caused by several types of cognitive bias, which may be reversed by enhancing analytic reasoning.
AIMS To evaluate whether enhancing analytic reasoning can increase diagnostic accuracy in objective structured clinical examination (OSCE) in medical students.
METHODS All fourth-year medical students, randomly assigned to the analytic reasoning or control groups, undertook the OSCE with four cases using standardized patients. The analytic reasoning group was requested to list differential diagnoses and findings compatible or not compatible with each diagnosis prior to providing a diagnosis, while the control group provided a diagnosis without these processes. Mean diagnostic accuracy scores (perfect score, 4.0) from four cases of OSCE were compared between the two groups.
RESULTS One hundred forty-five students were randomly assigned to the analytic reasoning group (n = 65) or the control group (n = 80). The baseline characteristics, including grade point average and the scores from each patient encounter, were comparable between groups. Mean diagnostic accuracy scores were significantly higher in the analytic reasoning group than in the control group (3.40 ± 0.66 versus 3.05 ± 0.98; p = 0.011).
CONCLUSION Enhancement of analytic reasoning may improve diagnostic accuracy in novice doctors.
- 262013
제1저자 김정목 · 교신저자 김주성
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The guggulsterone derivative GG-52 inhibits NF-κB signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice.Am J Physiol Gastrointest Liver Physiol. 2013;304(2):G193-202.
PubMed IF 3 소화기내과Abstract
Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.
- 252013
제1저자 김학령, 임문순 · 교신저자 조주희
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The association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population.Cardiovasc Ultrasound. 2013;11(1):2.
PubMed IF 2 순환기내과Abstract
BACKGROUND The aim of this study is to investigate the association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population.
METHODS A total of 115 healthy subjects without known cardiovascular risk factors or overt heart disease who underwent both transthoracic echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement at the same day during their routine check-ups were analyzed.
RESULTS The mean age of study subjects was 52.8 ± 8.4 years, and 78 (67.8%) were men. The mean baPWV value was 1,325 ± 185 cm/s. Study subjects were divided into 3 groups according to E/E' value: subjects with E/E' < 8, 8-12.9 and E/E' ≥ 13. As E/E' increased, baPWV value increased gradually: baPWV in subjects with E/E' < 8, E/E' 8-12.9 and E/E' ≥ 13, were 1,261 ± 163, 1,345 ± 169, 1,569 ± 232 cm/s, respectively (p < 0.001). In multiple linear regression analyses, baPWV was significantly associated with E/E' (β = 0.371, p < 0.001) after controlling confounders including age, sex and body mass index. In receiver-operating characteristic (ROC) curve analysis, the sensitivity and specificity for detection of E/E' ≥ 10 were 78.6% and 59.8%, respectively with mean baPWV of 1,282 cm/s as the cut off value. The discriminatory capacity for predicting E/E' ≥ 10 was improved from an area under the ROC curve of 0.646 with age alone to 0.734 when baPWV was added (p < 0.001).
CONCLUSIONS There is a significant association between baPWV and E/E' in an apparently healthy Korean population. BaPWV is useful as a simple and non-invasive method for early detection of increased LV filling pressure among these people.
- 242013
제1저자 조소영 · 교신저자 김나영
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Comparison of gastroesophageal reflux disease symptoms and proton pump inhibitor response using gastroesophageal reflux disease impact scale questionnaire.J Neurogastroenterol Motil. 2013;19(1):61-9.
PubMed IF 3.7 소화기내과Abstract
BACKGROUND/AIMS To compare gastroesophageal reflux disease (GERD) symptoms and response to proton pump inhibitor (PPI) in patients with erosive esophagitis (EE), non-erosive reflux disease (NERD) or functional heartburn (FH) using GERD impact scale (GIS) questionnaire.
METHODS Total 126 patients with GERD symptoms were diagnosed as EE (n = 62), NERD (n = 34) and FH (n = 30) by endoscopy, 24-hour esophageal pH testing and Bernstein test, prospectively. Analysis of risk factors and GIS questionnaire for GERD symptoms and quality of life were performed before and 8 weeks after PPI treatment.
RESULTS EE group had a higher proportion of men, frequent alcohol consumption, smoking, hiatal hernia, body mass index ≥ 25 kg/m(2) and triglyceride levels (≥ 150 mg/dL) than the other groups (all P < 0.05). On the other hand, both psychiatric treatment and psychopharmacotherapy were more frequent in patients with FH than in those with EE and NERD (both P < 0.05). Among GERD symptoms, chest pain was more frequent in FH group than in EE and NERD groups (P < 0.05). Eating problems and limitation of productive daily activities occurred frequently in FH group and NERD group, respectively. GIS after 8 week PPI treatment showed improvement in all of the GERD symptoms in EE (all P < 0.05) and in acid regurgitation, epigastric pain and hoarseness in NERD group (all P < 0.05). In terms of quality of life, PPI treatment improved sleep disturbance in EE (P = 0.031) and limitation of productive activity in the NERD group (P = 0.001).
CONCLUSIONS GIS questionnaire showed that different characteristics and symptoms improved after PPI therapy among patients with EE, NERD and FH, demonstrating the usefulness of the GIS questionnaire.
- 232013
제1저자 정고은 · 교신저자 박민정
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Helicobacter pylori seropositivity in diabetic patients is associated with microalbuminuria.World J Gastroenterol. 2013;19(1):97-102.
PubMed IF 7.7 소화기내과Abstract
AIM To investigate the relationship between Helicobacter pylori (H. pylori) seropositivity and the presence of microalbuminuria.
METHODS Between December 2003 and February 2010, asymptomatic individuals who visited the Seoul National University Healthcare System Gangnam Center for a routine check-up and underwent tests for H. pylori immunoglobulin G antibodies and urinary albumin to creatinine ratio (UACR) were included. All study subjects completed a structured questionnaire, anthropometric measurements and laboratory tests. Anti-H. pylori immunoglobulin G was identified using an enzyme-linked immunosorbent assay kit. A random single-void urine sample, collected using a clean-catch technique, was obtained to determine the UACR. The presence of microalbuminuria was defined as a UACR from 30 to 300 μg/mg. The presence of diabetes mellitus (DM) was defined as either a fasting serum glucose level greater than or equal to 126 mg/dL or taking anti-diabetic medication. Multiple logistic regression analysis was performed to identify the risk factors. The dependent variable was microalbuminuria, and the independent variables were the other study variables.
RESULTS A total of 2716 subjects (male, 71.8%; mean age, 54.9 years) were included. Among them, 224 subjects (8.2%) had microalbuminuria and 324 subjects (11.9%) had been diagnosed with DM. Subjects with microalbuminuria had a significantly higher H. pylori seropositivity rate than subjects without microalbuminuria (60.7% vs 52.8%, P = 0.024). Multivariate analysis after adjustment for age, body mass index (BMI), waist circumference, and glucose and triglyceride levels showed that H. pylori seropositivity was significantly associated with microalbuminuria [odds ratio (OR), 1.40, 95% CI, 1.05-1.89, P = 0.024]. After the data were stratified into cohorts by glucose levels (≤ 100 mg/dL, 100 mg/dL < glucose < 126 mg/dL, and ≥ 126 mg/dL or history of DM), H. pylori seropositivity was found to be significantly associated with microalbuminuria in diabetic subjects after adjusting for age, BMI and serum creatinine level (OR, 2.21, 95% CI, 1.20-4.08, P = 0.011). In addition, the subjects were divided into five groups. Those without microalbuminuria (an UACR of < 30 μg/mg) were divided into four groups in accordance with their UACR values, and subjects with microalbuminuria comprised their own group. Notably, H. pylori seropositivity gradually increased with an increase in UACR (P = 0.001) and was highest in subjects with microalbuminuria (OR, 2.41, 95% CI, 1.14-5.11). This suggests that H. pylori seropositivity is positively associated with microalbuminuria in diabetic subjects.
CONCLUSION H. pylori seropositivity was independently associated with microalbuminuria, and the prevalence of H. pylori seropositivity was associated with the severity of UACR in diabetic subjects.
- 222013
제1저자 김수정 · 교신저자 이근욱
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Safety, compliance, and predictive parameters for dosage modification in adjuvant S-1 chemotherapy for gastric cancer.Cancer Sci. 2013;104(1):116-23.
PubMed IF 4.9 혈액종양내과Abstract
This study was performed to investigate the compliance, safety, dosage modifications (dose reduction and/or schedule change [including permanent S-1 withdrawal]), and clinical parameters that predict S-1 dosage modification in gastric cancer patients receiving adjuvant S-1 chemotherapy. One hundred and forty-nine patients who underwent curative D2 surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m(2) twice daily on days 1-28 every 6 weeks) for 1 year. For patients unable to tolerate S-1, the dosage was reduced or the schedule was changed to a 3-weekly schedule of 2 weeks on treatment followed by 1 week off treatment. The planned 1-year treatment was completed in 73.8% of patients; 69 patients required dosage modification because of toxicity. The most frequent cause of dosage modification was enterocolitis (37 patients; defined as ≥ grade 2 abdominal pain and/or ≥ grade 2 diarrhea). Most dosage modification occurred during the early cycles of treatment (within the first 3 months). Severe toxicities (≥ grade 3) included neutropenia (13.4%), abdominal pain (8.1%) and diarrhea (8.1%). In multivariate analyses, decreased relative dose intensity was related to poor disease-free survival independent of stage, and only low creatinine clearance predicted S-1 dosage modification. In conclusion, although adjuvant S-1 therapy has a high compliance rate, meticulous monitoring of adverse events is required in the early period of treatment. Decreased creatinine clearance was the only factor that predicted dosage modification. In patients with creatinine clearance <50 mL/min, dosage reduction should be considered from the initiation of S-1 treatment.
- 212013
제1저자 남현진 · 교신저자 오도연
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Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer.Mol Cancer Ther. 2013;12(1):16-26.
PubMed IF 6.9 혈액종양내과Abstract
Src is a nonreceptor tyrosine kinase involved in the cross-talk and mediation of many signaling pathways that promote cell proliferation, adhesion, invasion, migration, and tumorigenesis. Increased Src activity has been reported in many types of human cancer, including gastric cancer. Therefore, this factor has been identified as a promising therapeutic target for cancer treatments, and targeting Src in gastric cancer is predicted to have potent effects. We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways, and it induced G(1) arrest and apoptosis in SNU216 and NCI-N87 cells. Apoptosis required induction of the proapoptotic BCL2 family member Bim. Knockdown of Bim using siRNA decreased apoptosis induced by treatment with saracatinib, suggesting that Bim has an important role in saracatinib-induced apoptosis. Saracatinib enhanced the effects of lapatinib, an EGFR/HER2 dual inhibitor, in SNU216 and NCI-N87 cells. Furthermore, combined treatment with saracatinib and 5-fluorouracil (5-FU) or cisplatin exerted synergistic effects in both saracatinib-sensitive and saracatinib-resistant cells. Consistent with our in vitro findings, cotreatment with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These data indicate that the inhibition of Src kinase activity by saracatinib alone or in combination with other agents can be a strategy to target gastric cancer.
- 202013
제1저자 임수 · 교신저자 Liguori Gary
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Changes in metabolic syndrome in American and Korean youth, 1997-2008.Pediatrics. 2013;131(1):e214-22.
PubMed IF 6.1 내분비대사내과Abstract
BACKGROUND Metabolic syndrome (MetSyn) in children and adolescence is increasing worldwide; however, its pattern may be different between Asians and Americans. We compare the prevalence and patterns of MetSyn between American and Korean children and adolescents between roughly 1998 and 2007.
METHODS Data from the American and Korean versions of the NHANES (NHANES and KNHANES) were used for this study. The main outcome is prevalence and pattern of MetSyn among participants separately in each country. In each survey, stratified multistage probability sampling designs and weighting adjustments were conducted to represent the entire population. The revised National Cholesterol Education Program criteria were used to define MetSyn.
RESULTS Totals of 934, 1781, and 1690 Americans aged 12 to 19 participated in NHANES 1988-1994, NHANES 1999-2002, and NHANES 2003-2006, respectively; and 1225, 976, 705, and 456 Koreans aged 12 to 19 have participated in KNHANES 1998, 2001, 2005, and 2007. The age-adjusted prevalence of MetSyn in American NHANES decreased from 7.3% to 6.7% and 6.5%, whereas in Korean NHANES there was an increase from 4.0% to 5.9%, 6.6%, and 7.8% in each country's respective study. Increases in dyslipidemia and abdominal obesity contributed to the increased prevalence in Korea, whereas in the United States, decreases in low high-density lipoprotein cholesterolemia and high blood pressure contributed to a decreased prevalence.
CONCLUSIONS Considering different phenotype changes, different approaches should be conducted at the national level to reduce the burden and consequences of MetSyn between Korea and the United States.
- 192013
제1저자 박미영 · 교신저자 이춘택
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Genetic blockade of insulin-like growth factor-1 receptor via recombinant adenovirus in lung cancer can be enhanced by the histone deacetylase inhibitor, vorinostat.J Gene Med. 2013;15(3-4):115-22.
PubMed IF 3 호흡기내과Abstract
BACKGROUND Many approaches have been suggested as anti-tumor therapy for targeting insulin-like growth factor 1 receptor (IGF-1R), such as monoclonal antibodies and tyrosine kinase inhibitor. We introduced recombinant adenoviruses expressing antisense, dominant negative or short hairpin RNA to IGF-1R. Moreover, we demonstrated that histone deacetylase inhibitor (vorinostat) can increase the transduction efficiency of adenoviruses by increasing CAR-induced transduction and by enhancing the transcription of the adenoviral transgene. In the present study, we showed that the combination of ad-sh (short hairpin) IGF-1R with vorinostat leads to a synergistic enhancement of IGF-1R blockade.
METHODS We measured the change in IGF-1R upon cotreatment with vorinostat and ad-shIGF-1R. Changes in transduction efficiency of ad-shIGF-1R were measured by fluorescent microscopy. Changes in apoptotic proportion and cell survival after the cotreatment were measured by the sub-G1 assay and cell counts. The effect of nuclear factor (NF)-κB activation was also measured by NF-κB p65 activation enzyme-linked immunosorbent assay. Drug interactions were analyzed upon cotreatment with ad-shIGF-1R, vorinostat and cisplatin.
RESULTS Combined treatment of ad-shIGF-1R and vorinostat synergistically suppressed the IGF-1R expression in lung cancer cell lines and also increased the transduction efficiency of ad-shIGF-1R. Ad-shIGF-1R and vorinostat cotreatment increased apoptotic cell death and synergistically suppressed cell growth compared to ad-shIGF-1R or vorinostat treatment alone. Vorinostat suppressed NF-κB activation, which was activated by ad-shIGF-1R. Moreover, triple combination of ad-shIGF-1R, vorinostat and cisplatin demonstrated synergistic cytotoxicity on lung cancer cells.
CONCLUSIONS Vorinostat enhanced the blocking capability of ad-shIGF-1R. The combined treatment of vorinostat and ad-sh-IGF-1R appears to have promising potential as a new therapeutic approach for lung cancer.
- 182013
제1저자 Maruja Lira/김태민 · 교신저자 김동완/Mao Mao
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Multiplexed gene expression and fusion transcript analysis to detect ALK fusions in lung cancer.J Mol Diagn. 2013;15(1):51-61.
PubMed IF 3.9 혈액종양내과Abstract
Anaplastic lymphoma kinase gene (ALK) fusions have been identified in approximately 5% of non-small-cell lung carcinomas (NSCLCs) and define a distinct subpopulation of patients with lung cancer who are highly responsive to ALK kinase inhibitors, such as crizotinib. Because of this profound therapeutic implication, the latest National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend upfront ALK screening for all patients with NSCLC. The Food and Drug Administration-approved companion diagnostic test (ie, fluorescence in situ hybridization) for identification of ALK-positive patients, however, is complex and has considerable limitations in terms of cost and throughput, making it difficult to screen many patients. To explore alternative screening modalities for detecting ALK fusions, we designed a combination of two transcript-based assays to detect for presence or absence of ALK fusions using NanoString's nCounter technology. By using this combined gene expression and ALK fusion detection strategy, we developed a multiplexed assay with a quantitative scoring modality that is highly sensitive, reproducible, and capable of detecting low-abundant ALK fusion transcripts, even in samples with a low tumor cell content. In 66 archival NSCLC samples, our results were highly concordant to prior results obtained by fluorescence in situ hybridization and IHC. Our assay offers a cost-effective, easy-to-perform, high-throughput, and FFPE-compatible screening alternative for detection of ALK fusions.
- 172013
제1저자 음영욱, 김용태 · 교신저자 이상협
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Stent patency using competing risk model in unresectable pancreatic cancers inserted with biliary self-expandable metallic stent.Dig Endosc. 2013;25(1):67-75.
PubMed IF 3.6 소화기내과Abstract
BACKGROUND AND AIM Biliary self-expandable metallic stents (SEMS) play an important role in the quality of life and palliative treatment in unresectable pancreatic cancer patients. We aimed to determine the factors affecting the patency of biliary SEMS and the survival in unresectable pancreatic cancer with obstructive jaundice.
METHODS Considering the competing risk and survival, we retrospectively evaluated the patency in 107 unresectable pancreatic cancer patients with obstructive jaundice who were successfully treated with biliary SEMS from January 2000 to April 2010.
RESULTS There were 107 incidents of biliary drainage that were clinically successful and the overall survival period was a median of 133 days. Stent occlusion before death was observed in 36 (33.6%) of 107 patients. Cumulative stent obstruction rates were 4.7%, 16.8%, and 24.4% at 1, 3, and 6 months, respectively. Lower cancer stage (<5 month's hazard ratio [HR] = 2.327, >5 month's HR = 0.108) was only associated with the longer patency of the stents in a multivariable analysis using a Fine and Gray model that considered competing risk. In multivariable analysis, lower cancer stage, uncovered stent and normalized serum bilirubin level were associated with a longer survival period (HR = 2.335, 1.906 and 1.795 respectively, P < 0.05).
CONCLUSION The patency of biliary SEMS in unresectable pancreatic cancers might be affected by the stage. Lower cancer stage and normalized bilirubin are associated with longer survival.
- 162013
제1저자 김지연 · 교신저자 김상균
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Comparison of treatment outcomes of endoscopic stenting for colonic and extracolonic malignant obstruction.Surg Endosc. 2013;27(1):272-7.
PubMed IF 3.3 소화기내과Abstract
BACKGROUND Self-expandable metal stents (SEMS) have been used as a bridging or palliative treatment for malignant colorectal obstruction. Colonic obstruction also may arise from advanced extracolonic malignancy, but the clinical outcomes of stent placement for extracolonic malignancy are unclear. This study compared the clinical outcomes of SEMS between patients with colorectal cancer and those with extracolonic malignancy.
METHODS Patients who underwent endoscopic SEMS placement for a malignant colorectal obstruction were enrolled at Seoul National University Hospital from April 2005 and August 2011. Their medical records were retrospectively reviewed in terms of success rate, complications, and duration of stent patency.
RESULTS Endoscopic SEMS placements were performed for colorectal cancer in 149 patients and for extracolonic malignancy in 60 patients. The causes of obstruction in extracolonic malignancy were advanced gastric cancer in 39 patients (65%), pancreatic cancer in nine patients (15%), ovarian cancer in three patients (5%) and other causes in nine patients (15%). The clinical success rates were similar between the two groups (92.6 vs 86.7%; p = 0.688), and multivariate analysis showed no significant risk factor for unsuccessful endoscopic SEMS placement. Reobstruction in palliative endoscopic SEMS placement occurred for 16 patients with colorectal cancer (21.9%) and 18 patients with extracolonic malignancy (30%) during a median follow-up period of 90 days (p = 0.288). The rates did not differ significantly between the two groups (4.1 vs 8.3%; p = 0.467). The median duration of stent patency was 193 ± 42 days for the patients with colorectal cancer and 186 ± 31 days for the patients with extracolonic malignancy (p = 0.253). The duration of stent patency was not affected by underlying malignancy, previous surgery, or palliative chemotherapy.
CONCLUSIONS Endoscopic SEMS placement is highly effective and comparable for palliation of obstruction in extracolonic malignancy and colorectal cancer in terms of clinical success, complications, and duration of patency.
- 152013
제1저자 김보현 · 교신저자 정숙향
, , , , , , , , , , , , , , , , , , , , , , , ,
Clinical features of autoimmune hepatitis and comparison of two diagnostic criteria in Korea: a nationwide, multicenter study.J Gastroenterol Hepatol. 2013;28(1):128-34.
PubMed IF 3.5 소화기내과Abstract
BACKGROUND AND AIM As a rare liver disease, little is known about autoimmune hepatitis (AIH). This study investigated the clinical features and compared two diagnostic criteria of AIH in Korea.
METHODS A nationwide, multicenter, retrospective analysis was done of data of adult patients diagnosed with AIH from January 2005 to December 2009.
RESULTS The enrolled patients (n = 343; mean age, 52.8 years; range, 19-87 years; 12% male, 88% female) met diagnostic criteria of AIH according to the revised original criteria (n = 311) or the simplified criteria (n = 250). At diagnosis, 30.6% were asymptomatic, 22.7% were cirrhotic, and 4.3% displayed hepatic decompensation. The positive results for anti-nuclear antibody, smooth muscle antibody, and anti-liver/kidney microsomal antibody were 94.2%, 23.0%, and 2.9%, respectively. Definite AIH and probable AIH according to the revised original criteria were 24.8% and 65.3%, respectively, while those according to the simplified criteria were 34.4% and 38.5%, respectively. The diagnostic sensitivity and positive predictive value of simplified criteria in comparison with the revised original criteria were 69.9% and 86.4%, respectively. As an initial therapy, corticosteroid (37.7%) or corticosteroid with azathioprine (36.8%) was administered. Remission, incomplete response, and treatment failure were noted with 85.7%, 10.5%, and 3.9% of patients, respectively.
CONCLUSIONS Autoimmune hepatitis in Korea is mostly type I, showing a mean age of 53 years with comparable clinical features to other countries. The concordant rate of the two diagnostic criteria was rather low with modest sensitivity of the simplified criteria. Further studies on the validation of the diagnostic criteria are warranted.
- 142013
제1저자 김진주 · 교신저자 김나영
, , , , , , ,
Relationship of interleukin-1β levels and gastroesophageal reflux disease in Korea.J Gastroenterol Hepatol. 2013;28(1):90-8.
PubMed IF 3.5 소화기내과Abstract
BACKGROUND AND AIM Gastric mucosal expression of interleukin (IL)-1β may alter acid secretion and influence the development of gastroesophageal reflux disease (GERD). The relationship of gastric mucosal IL-1β level and GERD was evaluated in the Korean population.
METHODS Genotypes of IL-1B-511 and IL-1RN VNTR polymorphism and clinical characteristics were analyzed in 44 patients with erosive esophagitis (EE), 32 patients with minimal change lesions (MCL), 54 patients with non-erosive reflux disease (NERD) and 113 controls. Gastric mucosal IL-1β levels were measured by enzyme linked immunosorbent assay.
RESULTS Significant differences were found between the EE and the control group with respect to sex, body mass index, and Helicobacter pylori infection. On the other hand, the MCL and the NERD group showed similar characteristics to that of the control group. IL-1B-511 genetic polymorphism showed relationship with gastric mucosal IL-1β levels. That is, T/T group (112.4 ± 14.3 pg/mg) had higher IL-1β level than C/C group (59.5 ± 11.6, P = 0.011). T carriers (92.8 ± 7.6 pg/mg) showed higher level than T non-carrier group (P = 0.050). In addition, mucosal IL-1β level of the EE group (52.3 ± 9.9 pg/mg) was lower than that of the control (107.8 ± 12.6 pg/mg, P = 0.001), the MCL (103.1 ± 13.5 pg/mg, P = 0.004), and the NERD group (83.8 ± 14.5 pg/mg, P = 0.079). However, genetic polymorphisms of IL-1B-511 and IL-1RN VNTR did not reach statistical significance among four groups.
CONCLUSION Gastric mucosal IL-1β level might be one factor in the development of GERD.
- 132013
제1저자 이준구 · 교신저자 허대석
, , , , , ,
Surrogate decision-making in Korean patients with advanced cancer: a longitudinal study.Support Care Cancer. 2013;21(1):183-90.
PubMed IF 3.4 혈액종양내과Abstract
PURPOSE Although surrogate decision-making in cancer patients is well-known, few studies investigating the prevalence of surrogate decision-making over time have been reported. The objectives of this study were to investigate the level of surrogate decision-making in advanced cancer patients over time and the impact of demographic and clinical variables on surrogate decision-making.
METHODS The level of surrogate decision-making was measured in 572 consecutive cancer patients who died between January 1 and December 31, 2009. We reviewed 8,639 informed consent forms of these patients, calculated the proportion of decisions made by a surrogate (PDS) for each patient, and analyzed the association of PDS with demographic and clinical variables.
RESULTS Surrogates completed 40.3 % of all consent forms. The prevalence of surrogate decision-making was higher in the end-of-life period (death <7 days, OR = 29.05; reference, >365 days). Surrogates signed consent forms more frequently for do-not-resuscitate directives, intensive care unit admission, emergency hemodialysis, surgery and invasive interventions compared with chemotherapy, radiotherapy, and diagnostic tests (OR = 3.88, P < 0.001). Patients of older age (P = 0.036) and those with a shorter duration of management (P < 0.001) were independently associated with greater PDS.
CONCLUSIONS Surrogate decision-making was frequently observed among Korean cancer patients in this study, especially when the patient's death was imminent, and for decisions related to end-of-life care. Surrogates were also frequently involved in decisions for elderly or rapidly deteriorating patients. Healthcare professionals should consider the significant role of familial surrogates in the end-of-life period; comprehensive approaches are needed to preserve the best interest of the patients.
- 122013
제1저자 이경희 · 교신저자 유철규
, ,
Positive feedback regulation of heat shock protein 70 (Hsp70) is mediated through Toll-like receptor 4-PI3K/Akt-glycogen synthase kinase-3β pathway.Exp Cell Res. 2013;319(1):88-95.
PubMed IF 3.5 호흡기내과Abstract
Alarmins, the endogenous molecules that recruit and activate innate immune cells, are considered as subgroups of damage-associated molecular patterns. Heat shock protein 70 (Hsp70) is one of putative alarmins together with high mobility group box 1, S100s, interleukin-1α, and annexins. It has cytokine-like functions as well as molecular chaperone functions. However, the cytokine function of Hsp70 has not been clear. Here, we demonstrated that there exists the positive feedback regulation of Hsp70 induction in innate immune cells. Heat stress (HS) increased intracellular Hsp70 (iHsp70) and it was actively released into extracellular space through the Golgi complex. Human recombinant Hsp70 (rhHsp70) up-regulated iHsp70 expression and induced pro-inflammatory cytokine secretion via Toll-like receptor 4 (TLR4). rhHsp70 rapidly activated Akt, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Moreover, glycogen synthase kinase-3β (GSK-3β) was inactivated by rhHsp70-induced Akt activation. Knockdown of TLR4 and overexpression of dominant negative TLR4 (DN-TLR4) suppressed the above effects of rhHsp70. The effects of rhHsp70 were not due to endotoxin contamination. Akt-dependent GSK-3β inactivation was responsible for iHsp70 induction by rhHsp70. Overexpression of DN-Akt or constitutively active GSK-3β or pretreatment of LY294002 inhibited rhHsp70-induced iHsp70 up-regulation, which was similar to the mechanism of HS-mediated induction of Hsp70. Thus, these data suggest the positive feedback regulatory mechanism of iHsp70 induction.
- 112013
제1저자 조현재, 이호재 · 교신저자 김효수
, , , , , , , , , ,
Generation of human secondary cardiospheres as a potent cell processing strategy for cell-based cardiac repair.Biomaterials. 2013;34(3):651-61.
PubMed IF 13.6 순환기내과Abstract
Cell therapy is a promising approach for repairing damaged heart. However, there are large rooms to be improved in therapeutic efficacy. We cultured a small quantity (5-10 mg) of heart biopsy tissues from 16 patients who received heart transplantation. We produced primary and secondary cardiospheres (CSs) using repeated three-dimensional culture strategy and characterized the cells. Approximately 5000 secondary CSs were acquired after 45 days. Genetic analysis confirmed that the progenitor cells in the secondary CSs originated from the innate heart, but not from extra-cardiac organs. The expressions of Oct4 and Nanog were significantly induced in secondary CSs compared with adherent cells derived from primary CSs. Those expressions in secondary CSs were higher in a cytokine-deprived medium than in a cytokine-supplemented one, suggesting that formation of the three-dimensional structure was important to enhance stemness whereas supplementation with various cytokines was not essential. Signal blocking experiments showed that the ERK and VEGF pathways are indispensable for sphere formation. To optimize cell processing, we compared four different methods of generating spheres. Method based on the hanging-drop or AggreWell™ was superior to that based on the poly-d-lysine-coated dish or Petri dish with respect to homogeneity of the product, cellular potency and overall simplicity of the process. When transplanted into the ischemic myocardium of immunocompromised mice, human secondary CSs differentiated into cardiomyocytes and endothelial cells. These results demonstrate that generation of secondary CSs from a small quantity of adult human cardiac tissue is a feasible and effective cell processing strategy to improve the therapeutic efficacy of cell therapy.
- 102013
제1저자 박준빈, 구본권 · 교신저자 김효수
, , , , , , ,
Comparison of antiplatelet efficacy and tolerability of clopidogrel napadisilate with clopidogrel bisulfate in coronary artery disease patients after percutaneous coronary intervention: a prospective, multicenter, randomized, open-label, phase IV, noninferiority trial.Clin Ther. 2013;35(1):28-37.e4.
PubMed IF 3.7 순환기내과Abstract
BACKGROUND Clopidogrel bisulfate, a potent antiplatelet agent, has a pivotal role in the prevention and treatment of atherothrombotic disease. Clopidogrel napadisilate, a different salt preparation of clopidogrel, has been developed and approved in Korea and several European countries. Recent studies have suggested that clopidogrel napadisilate might have improved stability and comparable bioequivalence to clopidogrel bisulfate. However, these 2 clopidogrel preparations have not been compared in terms of efficacy and tolerability in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI).
OBJECTIVE We sought to investigate the antiplatelet efficacy and safety profile of clopidogrel napadisilate compared with clopidogrel bisulfate in CAD patients after PCI.
METHODS This was a randomized, multicenter, open-label, Phase IV, noninferiority clinical trial. We prospectively recruited CAD patient in 6 institutions in Korea between October 2010 and November 2011. Patients who underwent PCI were randomly assigned to the test group (clopidogrel napadisilate plus aspirin) or control group (clopidogrel bisulfate plus aspirin). Antiplatelet efficacy and safety profile were assessed after 4 weeks of maintenance treatment. The primary end point was noninferiority of the percentage of P2Y(12) inhibition, measured by point-of-care assay. The rate of major adverse cardiovascular events (MACE), as a secondary end point, was compared between the 2 clopidogrel preparations. To assess tolerability, we evaluated the incidence, severity, and causal relation of adverse events (AEs) of 2 groups.
RESULTS A total of 169 patients were screened, and 127 patients completed the study (64 in the test group and 63 in the control group; P = 0.296). The baseline characteristics of patients did not differ significantly between the treatment groups. The between-group difference in percentage of P2Y(12) inhibition did not exceed the prespecified limit for noninferiority (P for noninferiority = 0.032; 95% CI, -8.33 to 5.53). With respect to the risk of MACE, no significant difference was found in the incidence of myocardial infarction or stroke between the groups (1 in the test group and 2 in the control group; P > 0.99); no mortality was reported in either group. The tolerability of clopidogrel napadisilate was comparable with that of clopidogrel bisulfate in terms of all AEs, drug-related AEs, and serious AEs (all AEs: test group, 33.3%; control group, 32.9% [P > 0.99]; drug-related AEs: test group, 4.17%; control group, 0% [P = 0.113]; serious AEs: test group, 1.39%; control group, 5.26% [P=0.367]).
CONCLUSIONS In this study of CAD Korean patients who have undergone PCI, the antiplatelet efficacy of clopidogrel napadisilate was noninferior to that of clopidogrel bisulfate after 4 weeks of maintenance treatment. No statistically significant difference was found in tolerability between the 2 treatment groups.
- 92013
제1저자 김상현, 서명기 · 교신저자 김효수
, , , , ,
Assessment of the efficacy and tolerability of 2 formulations of atorvastatin in Korean adults with hypercholesterolemia: a multicenter, prospective, open-label, randomized trial.Clin Ther. 2013;35(1):77-86.
PubMed IF 3.7 순환기내과Abstract
BACKGROUND A manufacturer of atorvastatin is seeking marketing approval in Korea of a generic product for adult patients with primary hypercholesterolemia.
OBJECTIVE The objective of this study was to compare the efficacy and tolerability of a new generic formulation of atorvastatin (test) with those of an original formulation of atorvastatin (reference) to satisfy regulatory requirements for marketing of the generic product in Korea.
METHODS Patients enrolled were aged 20 to 79 years with documented primary hypercholesterolemia who did not respond adequately to therapeutic lifestyle changes and with a LDL-C level >100 mg/dL from a high-risk group of coronary artery disease patients. Eligible patients were randomized to receive 1 of the 2 formulations of atorvastatin 20 mg per day for 8 weeks. The primary end point was the percent change in LDL-C level from baseline to week 8. Secondary end points included the percent change in total cholesterol, triglycerides, HDL-C level, apolipoprotein B:apolipoprotein A-I ratio, LDL:HDL ratio, LDL-C particle size, high-sensitivity C-reactive protein from baseline to week 8, and achievement rate of the LDL-C goal.
RESULTS A total of 298 patients (141 men and 157 women; 149 patients in each group; mean [SD] age, 62.4 [9.2] in the test group vs 60.3 [8.9] years in the reference group) were included. LDL-C levels were significantly decreased from baseline to week 8 in both groups, and there was no significant difference in the percent change in LDL-C level between groups (-44.0% [17.2%] in the test group, -45.4% [16.9%] in the reference group; P = 0.49). The between-group differences in the percent changes in total cholesterol and triglyceride levels were not statistically significant. In addition, there was no significant difference between the 2 groups in percent changes in HDL-C, apolipoprotein B:apolipoprotein A-I ratio, LDL-C:HDL-C ratio, LDL-C particle size, high-sensitivity C-reactive protein, and the achievement rate of the LDL-C goal. Two (1.3%) patients in the reference group (N = 150) experienced treatment-related serious adverse events (AEs): toxic hepatitis and aggravation of chest pain. Common AEs were cough (4.1%), myalgia (2.1%), and indigestion (1.4%) in the test formulation group and cough (5.3%), creatine kinase elevation (2.7%), and edema (0.7%) in the reference formulation group; however, the differences in overall prevalence of AEs between the 2 treatment groups was not significant (P = 0.88).
CONCLUSIONS There were no significant differences observed in the efficacy and tolerability between the test and reference formulations of atorvastatin in these Korean adult patients with primary hypercholesterolemia.
- 82013
제1저자 황인창 · 교신저자 김용진
, , , , , , ,
Prognostic value of B-type natriuretic peptide in patients with chronic mitral regurgitation undergoing surgery: mid-term follow-up results.Eur J Cardiothorac Surg. 2013;43(1):e1-6.
PubMed IF 3.3 순환기내과Abstract
OBJECTIVES The prognostic value of B-type natriuretic peptide (BNP) for surgical outcome in patients with mitral regurgitation (MR) has not been studied. The purpose of this study was to determine the prognostic value of BNP in patients with chronic severe MR, undergoing mitral valve surgery.
METHODS In total, 117 patients with chronic severe MR undergoing surgery were evaluated from the MR registry of Seoul National University Hospital. Patients were excluded if they had acute MR or acutely decompensated heart failure, and significant renal, pulmonary, coronary or other significant valvular heart disease. The plasma BNP level assay and echocardiographic studies were done before surgery. Study endpoint was a composite of cardiac death and cardiac hospitalization during follow-up.
RESULTS The median duration of the follow-up was 4.5 years, and the study endpoint was reached in 11 (9.4%) patients. Receiver-operating characteristic curve analysis yielded an optimal cut-off point of 125 pg/ml for BNP that distinguished patients with poor prognosis. Kaplan-Meier survival analysis with the log-rank test and multivariate Cox proportional hazards model showed that patients with BNP ≥125 pg/ml had a worse clinical outcome after surgery (log rank 7.606, P = 0.006; adjusted hazard ratio = 5.536 [95% confidence interval 1.189-25.788], P = 0.029).
CONCLUSIONS Among patients with chronic severe MR undergoing mitral valve surgery, BNP independently predicts the poor clinical outcome. The BNP measurement should be considered in the risk stratification of these patients.
- 72013
제1저자 이창현, 고성준 · 교신저자 김병관
, , , , , , , ,
Incidental colonic 18F-fluorodeoxyglucose uptake: do we need colonoscopy for patients with focal uptake confined to the left-sided colon?Dig Dis Sci. 2013;58(1):229-35.
PubMed IF 2.8 소화기내과Abstract
BACKGROUND/AIMS Although access to [18F]2-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography and computed axial tomography (PET/CT) for patients with malignancy has increased, little information is available on the suitability of PET/CT for diagnosis of advanced colonic neoplasms in oncology patients and on the clinical significance of incidental 18F-FDG focal uptake confined to the left-sided colon.
METHODS Patients who underwent 18F-FDG PET/CT followed, within 90 days, by colonoscopy were identified. Case-control analysis was undertaken to determine whether focal 18F-FDG uptake confined to the left-sided colon was associated with advanced neoplasms in the right-sided colon.
RESULTS One hundred ninety-five patients with colonic 18F-FDG uptake and 561 without colonic (18)F-FDG uptake were identified. Of the 195 patients with focal colonic 18F-FDG activity, 103 patients (52.8%) had 145 advanced colonic neoplasms, including 58 colon cancers and 11 metastatic cancers. In the detection of advanced colonic neoplasms, the sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT were 54.4, 82.4, 46.9, and 86.3%, respectively. Overall accuracy was 76.2%. Ten (8.0%) of the 125 patients with focal 18F-FDG uptake confined to the left-sided colon had three colon cancers and seven advanced adenomas in the right-sided colon. Case-control analysis revealed that focal 18F-FDG uptake confined to the left-sided colon was associated with an advanced neoplasms in the right-sided colon (OR, 3.02; 95% CI, 1.12-8.13; P = 0.023).
CONCLUSIONS Colonic focal (18)F-FDG uptake by oncology patients warrants endoscopic verification. Complete colon evaluation by colonoscopy is required, even for patients with focal 18F-FDG uptake confined to the left-sided colon.
- 62013
제1저자 김충종 · 교신저자 박완범
, , , , , , , , , ,
Differentiating rapid- and slow-growing mycobacteria by difference in time to growth detection in liquid media.Diagn Microbiol Infect Dis. 2013;75(1):73-6.
PubMed IF 1.8 감염내과Abstract
Nontuberculous mycobacteria (NTM) are classified into 2 categories: slow-growing mycobacteria (SGM) and rapid-growing mycobacteria (RGM), based on interval to colony formation by subculture on solid media. However, little is known about the growth rate of NTM in liquid broth media. We evaluated the differences in time to growth detection (TGD) of RGM and SGM in liquid broth media according to acid-fast stain. Among the 696 NTM isolates, 201 were RGM and 495 were SGM. In acid-fast bacilli (AFB)-negative specimens, the mean TGD was 133 h for RGM and 269 h for SGM (P < 0.001). In AFB-positive specimens, the mean TGD was 112 ± 37 h for RGM and 155 ± 125 h for SGM (P = 0.063). In the AFB-negative group, a cut-off value of 6 days was most effective for distinguishing SGM from RGM; however, in the AFB-positive group, an appropriate cut-off value was hard to define with TGD only.
- 52013
제1저자 방수미, 이정옥 · 교신저자 김기웅
, , , , , , , , , ,
Anemia and activities of daily living in the Korean urban elderly population: results from the Korean Longitudinal Study on Health and Aging (KLoSHA).Ann Hematol. 2013;92(1):59-65.
PubMed IF 2.3 혈액종양내과Abstract
This study was planned to investigate the prevalence and risk factors of anemia and its impact on health-related quality of life and activities of daily living (ADL) in elderly Koreans. Of the 1,118 randomly sampled elderly Koreans aged 65 years or older living in Seongnam, Korea, on Aug. 1, 2005, we estimated the prevalence of anemia from 695 responders. We investigated the risk factors of anemia using a merged sample of this random sample and 270 volunteers enrolled from Seongnam residents aged 85 years or older. We diagnosed anemia according to the World Health Organization criteria. The estimated age- and gender-standardized prevalence of anemia was 8.33 % for the overall random sample (95 % confidence intervals (CI) 6.28-10.39), 10.58 % in men (95 % CI 7.09-14.07), and 6.85 % in women (95 % CI 4.37-9.34). The identified risk factors were age ≥80 years, male, iron deficiency, history of stroke, renal dysfunction, and metabolic syndrome. Anemia was associated with impairment in physical functioning (p = 0.031) and instrumental ADL (p < 0.001). This is the first report about anemia's prevalence in community-dwelling Korean elders, adjusted and standardized according to the city's and nation's population. Timely diagnosis of anemia and correction of its treatable cause may improve QOL and ADL in elderly individuals.
- 42013
제1저자 이해영, 윤석원 · 교신저자 김효수
, , , , , , , ,
FOXO1 impairs whereas statin protects endothelial function in diabetes through reciprocal regulation of Kruppel-like factor 2.Cardiovasc Res. 2013;97(1):143-52.
PubMed IF 12.5 순환기내과Abstract
AIMS Krüppel-like factor 2 (KLF2) is implicated as a key molecule maintaining endothelial function. This study was designed to evaluate the reciprocal regulation of KLF2 by the forkhead transcription factor FOXO1, and the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin, in hyperglycaemic conditions.
METHODS AND RESULTS Exposure of human umbilical vein endothelial cells to 30 mM glucose activated FOXO1 and suppressed KLF2. These effects were reversed by FOXO1 small interfering RNA. Adenoviral transfection of constitutively active FOXO1 suppressed KLF2 expression. Interestingly, atorvastatin inhibited FOXO1 by increasing phosphorylation and also by inhibiting nuclear localization and replenished KLF2 in high-glucose conditions. This effect of atorvastatin was attenuated by mevalonate. Chromatin immunoprecipitation analysis demonstrated that glucose increased whereas atorvastatin decreased FOXO1 binding to the promoter region of the KLF2 gene. In the vessels of Otsuka Long-Evans Tokushima Fatty rats, animal models of type 2 diabetes, FOXO1 was activated and KLF2 was suppressed, and this was reversed by atorvastatin treatment. The arteries from Otsuka Long-Evans Tokushima Fatty rats showed impairment of endothelium-dependent vasodilatation, and both atorvastatin and KLF2 gene therapies restored it.
CONCLUSIONS Suppression of KLF2 by FOXO1 may be a plausible mechanism of diabetic endothelial dysfunction. High-glucose-induced, FOXO1-mediated KLF2 suppression was reversed by atorvastatin, suggesting that intensive statin treatment could be a therapeutic option in diabetic vascular dysfunction.
- 32013
제1저자 이승표 · 교신저자 김형관
, , , , , , ,
Prevalence of significant tricuspid regurgitation in patients with successful percutaneous mitral valvuloplasty for mitral stenosis: results from 12 years' follow-up of one centre prospective registry.Heart. 2013;99(2):91-7.
PubMed IF 4.4 순환기내과Abstract
BACKGROUND Percutaneous mitral valvuloplasty (PMV) is an attractive therapeutic option for mitral stenosis (MS).
OBJECTIVE To investigate the incidence and development of tricuspid regurgitation (TR) long after successful PMV. DESIGN, PATIENTS AND INTERVENTIONS: A prospective cohort of 299 patients with symptomatic MS who underwent successful PMV as first-line treatment between 1988 and 2010.
SETTING One tertiary university hospital.
MAIN OUTCOME MEASURES Significant TR, defined as a grade ≥3 on echocardiographic analysis.
RESULTS Although most TR regressed in these patients immediately after the procedure, 56 patients developed significant TR during follow-up (median 12 years, IQR 8.0-18.0 years). The cumulative incidence of significant TR increased time-dependently (9.4%, 19.8% and 35.2% at 8, 12 and 18 years of follow-up, respectively). Atrial fibrillation (AF) and TR grade ≥2 before PMV were found to be independent predictors of significant TR (HR (95% CI) 3.049 (1.169 to 7.949) and 3.016 (1.303 to 6.982), p=0.023 and 0.010 for pre-PMV AF and pre-PMV TR grade ≥2, respectively). Even after, exclusion of patients with significant TR at baseline, pre-PMV TR grade ≥2 and AF remained important factors of de novo TR development. Mitral valve restenosis was also associated with late significant TR development.
CONCLUSIONS Significant TR after successful PMV in patients with MS is not uncommon long after PMV. TR development is closely associated with mitral valve restenosis. More attention should be paid during long-term follow-up to TR development in patients with MS who have significant pre-PMV TR and/or AF.
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